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In this study, we evaluated sheep sperm quality after using Tris-citrate-fructose-based extender with and without egg yolk, a Tris-citrate without fructose and with egg yolk and the commercial extender Biladyl®, preserving diluted semen at 15 and 23°C for different times (4, 24, 48 and 72 h). The results showed that the diluents with fructose and egg yolk gave the best results of seminal quality. Moreover, the production of ROS was higher for the temperature of 23°C compared to the temperature of 15°C (control). In addition, VCL and the percentage of spermatozoa with intact acrosome decreased with temperatures of 23°C. Finally, a drastic decrease in sperm quality was observed after 24 hours of preservation for most of the parameters evaluated., (© 2024 The Author(s). Reproduction in Domestic Animals published by Wiley‐VCH GmbH.)

To assist in the conservation of collared peccary, it is important to strengthen semen processing protocols. The aim of this study was to compare the effects of different commercial extenders (BTS; NUTRIXcell+ and PRIMXcell Ultra) and TRIS + egg yolk on the functional and morphological aspects of collared peccary semen stored at 17 °C for 48 hours. Ten ejaculates obtained by electroejaculation were divided into 4 aliquots and diluted in the respective extenders, then stored in a biological incubator at 17 °C for 12, 24, 36, and 48 hours. The samples were evaluated for kinetic parameters, membrane functionality, membrane integrity, mitochondrial activity, morphology, and sperm-binding capacity. At the end of storage (48 h), promising results were found for motility parameters, with TRIS + egg yolk (71.0 ± 4.6%) being more efficient than NUTRIXcell+ (38.9 ± 10.9%) (P < 0.05) and similar to BTS (42.9 ± 11.9%) and PRIMXcell Ultra (46.8 ± 10.8%). The results for membrane integrity and mitochondrial activity were around ∼30-50%, with TRIS being the only extender to preserve both parameters (58.9 ± 5.3 and 59.2 ± 5.6%) for up to 48 hours, respectively (P < 0.05). Finally, the extenders could guarantee 60% membrane functionality and ∼ 60-70% normal sperm morphology, as well as similar binding capacity among the groups. In conclusion, TRIS + egg yolk is effective in preserving the sperm parameters of collared peccary semen at 17 °C for 48 hours, while PRIMXcell Ultra and BTS are viable alternatives for this purpose., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We further confirm that any aspect of the work covered in this manuscript that has involved experimental animals has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from legio2000@yahoo.com or alexrs@ufersa.edu.br, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To determine the effect of 0.0005% chlorhexidine and tris-EDTA solution on the strength of three commonly used suture types for closure of equine ventral midline celiotomy., Study Design: Controlled laboratory study., Sample Population: Knotted loops (n = 10/group, 150 knot constructs total)., Methods: Strands of 2 polyglactin 910, 3 polyglactin 910, and 2 polydioxanone were tied to form knotted loops. All knotted loops were mounted on a tabletop force measurement machine system and loaded at 100 mm/min until the breaking force (N) was determined. The breaking force (N) of knotted loops using dry suture was recorded at study start, then of knotted loops soaked in either 0.0005% chlorhexidine and tris-EDTA for 20 min followed by incubation in equine serum (treatment) or serum alone (control) for 14 and 21 days. Analysis of variance (ANOVA) compared the breaking force between the treatment and control groups at each time point., Results: There was no significant difference in the breaking force of 2 USP polyglactin 910 (p = .35, confidence interval [CI] = -0.21-0.59), 3 USP polyglactin 910 (p = .61, CI = -0.41-0.24), or 2 USP polydioxanone (p = .76, CI = -0.63-0.46) soaked in 0.0005% chlorhexidine and tris-EDTA solution followed by equine serum when compared to each respective suture soaked in equine serum only., Conclusion/clinical Significance: Since 0.0005% chlorhexidine and tris-EDTA solution did not exhibit a significant effect on the breaking force of the absorbable sutures studied, the solution may be used for incisional lavage in the clinical setting., (© 2023 American College of Veterinary Surgeons.)

The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency, international guidelines recommend reducing administration of fluoroquinolones, in the context of growing resistance and the long-lasting and potentially disabling side effects of these drugs. The favoured drug to replace fluoroquinolones is fosfomycin trometamol (FT), a well-known derivate of phosphonic acid with broad-spectrum activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant (MDR) strains. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently reduced the susceptibility breakpoint for E. coli from 32 mg/L to 8 mg/L regarding FT used for uUTIs. This might lead to increased appropriate use of oral fosfomycin target therapy against E. coli and other microorganisms, and may be associated with a high likelihood of success. For species such as Klebsiella spp, particularly MDR strains, the absence of clinical breakpoints might lead to reduced use of oral fosfomycin, particularly if minimum inhibitory concentration is not available. To address this issue, this review presents an overview of the preclinical evidence on the activity of FT, and a systematic review of the clinical activity of FT in uUTIs in women, and in the prevention of infectious complications after prostate biopsy. The findings indicate that the safety and microbiological and clinical effectiveness of a single oral dose of FT are similar to that for comparator regimens with longer treatment schedules in women with uUTI, and FT can be considered a viable alternative to fluoroquinolones for antimicrobial prophylaxis in prostate biopsy. These observations and a broad clinical experience support the empirical use of FT for treating uUTI and indicate that FT is a promising candidate to effectively counteract antibiotic-resistant uUTIs throughout Europe., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

Aim: Epilepsy is one of the most common neurological diseases. Dexketoprofen (DEX) is a nonselective nonsteroidal anti-inflammatory drug that is used as an analgesic. The present study aimed to assess the efficiency of DEX on WAG/Rij rats by electrophysiologically and behaviorally., Material and Methods: Twenty-eight male WAG/Rij rats were used. The effects of acute treatment with DEX (5, 25, and 50 mg/kg, i.p) on absence-like seizures, and related psychiatric comorbidity were assessed. The ECoG recording was taken for 180 min before and after drug injection. After drug injection and EcoG recording, anxiety-depression-like behavior was tested with the open field test for 5 min., Results: The 5 mg/kg DEX significantly reduced the number and duration of SWDs percentage (p < 0.05) between 120 and 180 min, but 25 and 50 mg/kg DEX significantly increased the number and duration of SWDs percentage between 0 and 30 min (p < 0.05), and after 30 min the increase stopped (p > 0.05). And also, the 5 mg/kg DEX decreased the number and duration of SWDs percentage (p < 0.05) for 180 min (p < 0.05), but 25 and 50 mg/kg DEX administration did not alter (p > 0.05). The 5, 25, and 50 mg/kg doses of DEX significantly increased the duration of grooming (p < 0.05) but did not change the number of squares crossed (p > 0.05)., Conclusion: Low dose DEX reduced absence-like seizures, but care should be taken when using high doses in absence epilepsy. Also, it may be beneficial for painful diseases accompanied by anxiety-depression.

Aim of this study was to compare different combinations of penetrating intracellular CPAs, i.e., glycerol (G), ethylene glycol (EG), propylene glycol (PG), dimethyl formamide (DM), and methyl acetamide (MA) and extracellular [egg yolk (EY), egg yolk plasma (EYP), low-density lipoproteins (LDL), and coconut water (CW)] in Tris-citric acid-fructose buffer (T) for Labrador dog semen cryopreservation. The study was conducted in two parts, first trial was conducted to assess optimum glycerol concentration (5-7%) in TEY and equilibration time (ET, 2-4 hrs) for Labrador dog semen cryopreservation. Secondly, compatibility of 15% TEY, 15% TEYP, 13% TLDL, and 25% TCW with G, DMF, MA, D + M, EG, and PG was evaluated for in vitro sperm function tests. Decline in sperm attributes, i.e., motility, viability, plasma membrane integrity (PMI), and acrosome integrity (AI)) was significantly ( p  < 0.05) less in 7% TEY-G and 4 h compared to other concentrations and ET at post-thaw. There was significantly ( p  < 0.05) less decline in sperm attributes in TEY-G, TEYP-G, TLDL-G, TLDL-D, TLDL-EG, and TCW-D extenders compared to other combinations at post-thaw. However, these parameters were significantly ( p  < 0.05) high in TEY-G and TEYP-G compared to TEYP-D, TLDL-G, TLDL-D, TLDL-EG, and TCW-D extenders at post-thaw. However, decline in motility, viability, PMI, and AI was identical in these seven extenders. This study concluded that glycerol at a concentration of 7% in TEY and 4 h ET were optimum for successful cryopreservation and besides TEY-G, other combinations of protectants may be an alternative for canine semen cryopreservation.

The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

This study aimed to investigate the effects of alkaline agents on reducing strong inspiratory effort. Rabbits with hypercapnia or lung injury, induced via repeated lung lavage following injurious ventilation, were treated with Saline, NaHCO 3 , or Trometamol. In the hypercapnia, minute ventilation and tidal volume were unchanged during NaHCO 3 administration; however, one hour after the end of NaHCO 3 these parameters decreased (82.1+/-7.8 %, 90.8+/-6.0 % of the baseline, respectively, p < 0.05). Trometamol reduced minute ventilation, tidal volume, and respiratory rate after infusion (59.8+/-19.0 %, 87.0+/-9.2 %, 68.2+/-18.4 % of the baseline, respectively, p < 0.05). Alkaline agents did not cause a large change in the cerebrospinal fluid acid-base balance. In the lung injury model, NaHCO 3 and Trometamol had little effect on ventilation. However, Trometamol reduced transpulmonary pressure. Trometamol exerted more inhibitory effects on ventilation than NaHCO 3 in the hypercapnia model, and Trometamol reduced the transpulmonary pressure in the lung injury model., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Fructose is considered a vital energy source for metabolic events occurring naturally in the seminal plasma of buffalo spermatozoa., Objective: To explore the effect of different concentrations of fructose and glycerol in tris citric acid extender on post thaw quality and in vivo fertility of buffalo spermatozoa., Materials and Methods: Semen was collected from three bulls through artificial vagina (42 °C). Two ejaculates were collected from each bull per collection day and were evaluated initially for consistency, volume, motility and concentration, followed by dilution in five extenders with supplements (Treatment 1: F0.1,G7 = fructose 0.1 % + glycerol 7 %; T2: F0.2,G7= fructose 0.2 % + glycerol 7 %; T3: F0.4,G6.5 = fructose 0.4 % + glycerol 6.5%; T4: F0.8,G6 = fructose 0.8 %, glycerol 6 %; T5: F1.0,G5 = fructose 1 % + glycerol 5 %). The experiment was replicated four times and the data were assessed with ANOVA., Results: The results showed that percent progressive motility, plasma membrane integrity and supra-vital plasma membrane integrity of spermatozoa was significantly higher (P < 0.05) in extender supplemented with T5 than T1 and T2. Spem hypo-resistivity, acrosome integrity and DNA integrity were significantly higher in extender supplemented with T5 than T1. Moreover, sperm in vitro quality was significantly higher in T5 than T1 during 30 and 60 min of incubation at 37 ºC. Sperm in vivo fertility was significantly higher in extenders supplemented with T5 (57.3%) as compared to T1 (41.3%)., Conclusion: It is concluded that extender supplemented with T5 improved post thaw semen quality and in vivo fertility of buffalo bull.

Angiogenesis is a fundamental process of wound healing, embryogenesis etc. but occurs in cancer and chronic inflammation pathologically. HET-CAM assay is a useful, well established and animal alternative test to screen anti-inflammatory potentials of pharmaceutical products as well as nano-formulations. Dexketoprofen trometamol (DT) belongs to the nonsteroidal anti-inflammatory drug (NSAID) group which is a rapidly acting analgesic ingredient. Because DT has a short half-life, high and frequent dosing is used in treatment. The need of design and producing a new oral prolonged-release dosage form containing DT is the major aim of the study with low dose and low side effects. Chitosan (CS) has been widely used in the pharmaceutical area because of its favorable biological properties. In this study, DT loaded CS nanoparticles (CS-NPs) were produced by spray drying method for oral drug delivery. Structures of CS-NPs were elucidated by particle size, zeta potential, SEM, DSC, FT-IR and 1 H NMR. High encapsulation efficiency was obtained (73-84%) for the prepared formulations. In vitro release was examined in pH 1.2 buffer and pH 6.8 buffer. DT-loaded CS-NPs showed prolonged release, particularly at pH 6.8. Weibull kinetic model was found to fit best to DT release from CS-NPs in both release medium. The anti-inflammatory activity of optimum formulation (M-DT) was examined using the in vivo HET-CAM assay. The anti-inflammatory activity results indicated that M-DT coded NPs formulation showed significantly good anti-inflammatory potential with closer inhibition value to the standard anti-inflammatory DT at one fifth lower dosage. According to the proposed method and results it can be successfully applicable to the NP preparation containing DT and it could be concluded that DT loaded CS-NPs seem to be a promising prolonged release drug delivery system for oral administration with low dose and high efficiency., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Due to the global decrease in jaguar population, conservation strategies are essential and the development of effective semen cryopreservation protocols would contribute to the formation of germplasm banks. Therefore, the objectives were to (1) evaluate the use of TRIS and ACP-117c extenders for jaguar semen freezing, (2) describe the ultrastructural changes in sperm after cryopreservation, and (3) evaluate the binding capacity of the thawed sperm. Eight ejaculates from five mature individuals were collected by electroejaculation, extended in TRIS or a coconut based-extender (ACP-117c), and frozen in liquid nitrogen. Samples were evaluated for sperm motility, vigor, membrane functionality, mitochondrial activity, morphology (using light microscopy, scanning electron microscopy - SEM and transmission electron microscopy - TEM), sperm kinetic parameters (by computerized analysis - CASA), and sperm binding capability using an egg yolk perivitelline membrane assay. Samples preserved in TRIS presented better post-thaw motility (46.0 ± 7.7%) and membrane functionality (60.5 ± 4.2%) and higher mitochondrial activity (21.5 ± 3.7%) than those preserved in ACP-117c (20.9 ± 5.4% motile sperm; 47.1 ± 2.5% functional membrane; 11.8 ± 1.7% mitochondrial activity). Regarding ultrastructural evaluations, SEM showed that both extenders were able to preserve the superficial membrane of the sperm, but TEM revealed the occurrence of nuclear electron lucent points, especially in samples extended in ACP-117c. Additionally, TRIS also provided a higher number of sperm bound to the perivitelline membrane (29.5 ± 3.3%) in comparison to samples diluted in ACP-117c (18.6 ± 1.5%). Overall, we suggest the use of a TRIS-based extender for cryopreservation of jaguar semen., Competing Interests: Declaration of competing interest The authors have stated that there are no competing interests. None of the authors has financial or personal relationships that may influence or distort the content of the article., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study aimed to investigate the effects of different concentrations of soybean lecithin (SL; 0.5%, 1%, and 1.5%) and egg yolk (EY) in Tris-based extenders on the semen quality parameters of post-thawed goat semen. Sixteen ejaculates were collected from eight healthy, mature Chongming White goats (3-5 years of age). Each ejaculate was divided into five equal aliquots, and then each pellet was diluted with one of the five Tris-based extenders containing 20% EY, 0.5% SL, 1% SL, 2% SL, or 3% SL. The cooled diluted semen was loaded into 0.5 mL polyvinyl French straws and cryopreserved in liquid nitrogen. Frozen semen samples were thawed at 37 °C and assessed for sperm motility, viability, plasma acrosome integrity, membrane integrity, and mitochondria integrity, and the spermatozoa were assessed for reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA). The semen extended in the 2.0% SL extract tended to have a higher sperm viability (57.44%), motility (52.14%), membrane integrity (45.31%), acrosome integrity (52.96%), and mitochondrial activity (50.21%) than the other SL-based extender concentrations (P < 0.05). The 2.0% SL treatment group was equivalent to the semen extended in 20% EY (P > 0.05). The extenders supplemented 20% EY or 2.0% SL significantly increased the SOD activity and decreased the ROS and MDA activities compared to the other groups (P < 0.05). In conclusion, the extenders supplemented with 20% EY and 2.0% SL had similar effects on spermatozoa preservation. These results indicate that a soybean lecithin-based diluent may be used as an alternative extender to egg yolk for the cryopreservation of goat semen., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2019. Published by Elsevier Inc.)

The aromatic amino acid l-tryptophan is an essential and versatile molecule, acts by transferring an electron to free radicals and protects the plasma membrane from injuries. The aim of the present study was to investigate the effects of l-tryptophan in extender on semen quality parameters, in vitro longevity and in vivo fertility rate of buffalo spermatozoa during cryopreservation. Two ejaculates were collected from each bull (n = 2 ejaculates and n = 4 bulls) with artificial vagina at 42 °C followed by initial evaluation for volume, motility, concentrations and were diluted in five extenders (C = lacking l-tryptophan, D1 = 25 μ M l-tryptophan, D2 = 50 μ M l-tryptophan, D3 = 75 μ M l-tryptophan, and D4 = 100 μ M l-tryptophan) respectively, and cryopreserved. The experiment was repeated four times (n = 4 replicates). At post-dilution, sperm plasma membrane integrity (PMI, %), supravital plasma membrane integrity (SVPMI, %), hypo-resistivity (HR, %) and acrosome integrity (ACR-I, %) were significantly higher (P < 0.05) in extender supplemented with D4 than control. At post-thawing, progressive motility (PM, %), PMI, SVPMI, HR, ACR-I, and DNA-I of buffalo bull spermatozoa were significantly higher in D4 than control. Sperm in vitro longevity (%) assessed in terms of PM, SVPMI, and ACR-1 were significantly higher in D4 than control. Sperm mitochondrial membrane potential (%) was higher in treated groups than the control. The in vivo fertility rate was significantly higher in D4 than control (60.17% vs. 44.17%, P < 0.05). It is concluded that the supplementation of l-tryptophan in tris citric acid extender improves semen quality parameters, in vitro longevity and in vivo fertility rate of buffalo spermatozoa during freezing and thawing process., Competing Interests: Declaration of competing interest The authors have no conflict of interest in the publication of this research article., (Copyright © 2019. Published by Elsevier Inc.)

This study was designed to determine the effects of the combined addition of different levels of certain sugars (trehalose, sucrose and raffinose) and antioxidants (vitamin E, C and taurine), in Tris-egg yolk extender on frozen-thawed ram semen parameters. Semen samples were collected from five healthy, mature and fertile Iranian Afshari rams, twice a week for 8 weeks. Selected samples were pooled and diluted with a Tris-egg yolk extender containing different levels of sugars and antioxidants. In Experiment 1, different levels of trehalose (0, 50 and 100 mM) were tested with different levels of taurine (0, 25 and 50 mM), vitamin E and C (0, 1 and 2 mM). In Experiment 2, different levels of sucrose (0, 60 and 80 mM) were tested with different levels of taurine (0, 25 and 50 mM), vitamin E and C (0, 1 and 2 mM). In Experiment 3, different levels of raffinose (0, 5, 10 mM) were tested with different levels of taurine (0, 25 and 50 mM), and vitamin E and C (0, 1 and 2 mM). In Experiment 4, the selected extenders of experiments 1, 2 and 3 were compared statistically with control (no selected sugar and antioxidant) extender. The results of experiments 1, 2 and 3 revealed that the highest frozen-thawed sperm parameters were recorded for the selected extenders containing 100 mM trehalose +2 mM vitamin E (T100E2), 60 mM sucrose + 2 mM vitamin E (S60E2) and 10 mM raffinose + 2 mM vitamin E (R10E2), respectively. The results of experiment 4 revealed that the post-thaw sperm total motility in T100E2 (62.41 ± 2.41%), S60E2 (59.52 ± 1.91%) and R10E2 (58.33 ± 2.00%) was higher than that of the control extender (46.00 ± 1.79%; P ≤ 0.05). Similarly, the progressive sperm motility in T100E2 (57.18 ± 1.96%), S60E2 (57.49 ± 1.94%) and R10E2 (55.03 ± 2.99%) was also higher than that of the control extender (41.20 ± 1.70%; P ≤ 0.05). Post-thaw sperm viability in selected extenders of T100E2 (65.20 ± 2.67%), S60E2 (62.00 ± 2.07%) and R10E2 (61.80 ± 2.46%) was higher than that of control extender (51.00 ± 1.88%; P ≤ 0.05). In conclusion, the addition of 100 mM trehalose, 60 mM sucrose and 10 mM raffinose combined with 2 mM vitamin E in Tris-egg yolk extender significantly improved frozen-thawed ram semen parameters., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest and this is their original research work., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The present study was undertaken in order to compare the anti-microbial efficacy, in vitro, of 5 candidate cross-linking solutions against 5 different microbial pathogens with relevance to infectious keratitis., Methods: In vitro bactericidal efficacy studies were carried out using 5 different FARs [diazolidinyl urea (DAU), 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM), sodium hydroxymethylglycinate (SMG), 2-(hydroxymethyl)-2-nitro-1,3-propanediol (NT = nitrotriol), 2-nitro-1-propanol (NP)] against 5 different microbial pathogens including two antibiotic-resistant species [methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa (PA), and Candida albicans (CA)]. Standard in vitro antimicrobial testing methods were used., Results: The results for MSSA were similar to those for MRSA. DAU, DMDM, and SMG all showed effectiveness with greater effects generally observed with longer incubation times and higher concentrations. Against MRSA, 40 mM SMG at 120 min showed a > 95% kill rate, p < 0.02. Against VRE, 40 mM DAU for 120 min showed a > 94% kill rate, p < 0.001. All FARs showed bactericidal effect against Pseudomonas aeruginosa, making PA the most susceptible of the strains tested. Candida showed relative resistance to these compounds, requiring high concentrations (100 mM) to achieve kill rates greater than 50%., Conclusion: Our results show that each FAR compound has different effects against different cultures. Our antimicrobial armamentarium could potentially be broadened by DAU, DMDM, SMG and other FARs for antibiotic-resistant keratitis. Further testing in live animal models are indicated.

Various animal models, especially rodents, are used to study pain, due to the difficulty of studying it in humans. Many drugs that produce analgesia have been studied and there is evidence among which NSAIDs deserve to be highlighted. Dexketoprofen (DEX) provides a broad antinociceptive profile in different types of pain; therefore, this study was designed to evaluate the profile of antinociceptive potency in mice. Analgesic activity was evaluated using the acetic acid abdominal constriction test (writhing test), a chemical model of visceral pain. Dose-response curves for i.p. DEX administration (1, 3, 10, 30 and 100 mg/kg), using at least six mice in each of at least five doses, was obtained before and 30 min after pre-treatment with different pharmacological agents. Pretreatment of the mice with opioid receptor antagonists was not effective; however, the serotonin receptor antagonist and nitric oxide synthase inhibitor produce a significant increase in DEX-induced antinociception. The data from the present study shows that DEX produces antinociception in the chemical twisting test of mice, which is explained with difficulty by the simple inhibition of COX. This effect appears to be mediated by other mechanisms in which the contribution of the NO and 5-HT pathways has an important effect on DEXinduced antinociception.

The aim of the present study was to determine the protective effects of pomegranate juice in tris-based extender on semen parameters, computer-assisted sperm analysis (CASA) motion characteristics and field fertility of post-thawed Nili Ravi buffalo (Bubalus bubalis) bull spermatozoa. Two consecutive ejaculates/collection from each of the five adult Nili Ravi buffalo bulls were collected with artificial vagina at 42°C for a period of 7 weeks, diluted in extender containing different concentrations of pomegranate juice (0.0%, 2.5%, 5%, 7.5% and 10%). Diluted samples were packed and frozen in 0.54 ml French straws. The addition of 10% pomegranate juice in extender significantly improved post-thaw sperm morphology (%), motilities (CASA total motility, progressive motility (%) as well as VAP, VSL, VCL, STR, DAP, DSL) compared to the control group (p < 0.05). Plasma membrane, acrosome membrane and DNA integrity were significantly higher in extender with 10% pomegranate juice than the control group (p < 0.05). Field fertility rate (60.39% vs. 46.53%) was higher (p < 0.05) in extender with 10% pomegranate juice as compared to the control. It is therefore concluded that the addition of 10% pomegranate juice in tris-based extender improves post-thaw semen parameters, CASA motion dynamics and field fertility in Nili Ravi buffaloes., (© 2019 Blackwell Verlag GmbH.)

It is well known that amyloid beta (Aβ) peptides are generated in blood vessels, released into the brain during thrombosis, and temporarily accumulate in this organ after injury. Here we demonstrate that 24 h after transient middle cerebral artery occlusion (tMCAO), one of the standard models of focal ischemic stroke, Aβ peptide accumulates in the brain, concentrating on the blood vessel walls. Because Aβ oligomers are known to induce significant damage to brain cells, they act as an additional damaging factor during ischemic stroke. Considering that they have been shown to form ion channels in cells, affecting osmotic balance, we used an Aβ peptide channel blocker, tromethamine (2-amino-2-(hydroxymethyl) propane-1,3-diol), to prevent this additional injury. Tromethamine injected 0.1 g/100 g body weight intraperitoneally at 5 min before tMCAO decreased water content in the damaged hemisphere, as measured by dry brain weight. Congo red staining, which binds only to Aβ oligomer plaques (amyloid), showed that there was no significant presence of plaques. Therefore, we suggest that Aβ peptide oligomers are responsible for some of the brain damage during stroke and that blockage of the ion channels that they form could be beneficial in treating this complex neurological syndrome.

The main challenges in treating cancer using chemotherapeutics are insufficient dose at the target site and the development of drug resistance, while higher doses can induce side effects by damaging nontarget tissues. Combinatorial drug therapy may overcome these limitations by permitting lower doses and more specific targeting, thereby mitigating drug resistance and nontarget side effects. Recent reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer potential and can be used together with conventional chemotherapeutics to improve efficacy and safety. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as model drugs to develop targeted surface-modified liposome and nanocochleate formulations for fibrosarcoma treatment. The physicochemical properties and in vitro efficacy of various formulations were evaluated by measurement of particle size distribution, polydispersity index, zeta potential, encapsulation efficiency, diffusion through Caco-2 cells, and toxicity in culture. Selected formulations were then evaluated in fibrosarcoma-bearing model mice by histopathological observations and tyrosine kinase receptor inhibition assays. The most effective formulation on the fibrosarcoma model was a PEGylated nanocochleate formulation. These findings provide a foundation for developing more effective formulations and chemotherapeutic strategies for the treatment of fibrosarcoma and other types of cancer., (© 2019 Wiley Periodicals, Inc.)

Objective: To evaluate the efficacy of dexketoprofene trometamol solution following the administration of contrast agent for Endoscopic Retrograde Cholangiopancreatography (ERCP) in decreasing the rate of pancreatitis, in experimental rat model., Study Design: Experimental study., Place and Duration of Study: Faculty of Medicine, Research and Animal Laboratory of Bezmialem University, Istanbul, Turkey in January 2018., Methodology: Forty Wistar-Albino® male rats of 250-300g were divided into 4 equal groups. Group I underwent cannulation; group II had cannulation with saline; group III had cannulation and contrast agent; group IV had cannulation with contrast agent and dexketoprofene trometamol intra-muscular (IM). Twenty four hours following the procedure, the rats were sacrified and pancreatic tissues were examined histopathologically, with evaluation of blood levels of leukocyte, glucose, SGOT, LDH, amylase, and C-reactive protein (CRP) level. Histopathological grading of acute pancreatitis was performed using haematoxylin and eosin staining., Results: Mean levels of amylase and leukocyte were found to be significantly higher in groups II, III, IV when compared to group I (p=0.001). CRP level was found to be highest in group III (p=0.001). Histopathological grade of pancreatitis was found to be significantly higher in groups II, III, IV than group I (p: 0.001, 0.001, 0.028, and 0.001, respectively). Scores of edema, acinar necrosis, inflammation and perivascular infiltration of group III were higher than in group IV (p=0.001)., Conclusion: Intra-muscular administration of dexketoprofen trometamol during ERCP procedure may be beneficial in decreasing the rate of post-ERCP pancreatitis, as shown by histopathological and laboratory profile.

This study was conducted to examine the effect of supplementation of Tris-egg yolk extender with lyophilized royal jelly (RJ) on chilled and frozen-thawed ram semen parameters. Ejaculates were collected by artificial vagina from 4 mature rams, twice a week for 4 weeks. Only samples with motility of ≥70% were included, pooled and divided into four equal parts and then diluted in extenders with various concentrations of RJ (0, 1, 3 and 5%, vol/vol) to a final concentration of 200 × 10 6 sperm/mL and was incubated at 37 °C for 30 min and were subsequently evaluated. After equilibration of extended semen for 2 h at 4 °C, some semen samples were packed in 0.25 mL plastic straws. Then, the straws were frozen in the liquid nitrogen vapor phase for 15 min and stored at -196 °C in liquid nitrogen. The frozen straws were thawed in warm water (37 °C) for 30 s and evaluated; whereas, other semen samples were stored in the refrigerator (4 °C) up to 7 days. The chilled samples were kept in water bath (37 °C) for 5 min and then were evaluated. After dilution, the lowest and highest sperm total abnormality was recorded in 3 and 5% RJ supplemented groups, respectively (P < 0.05). The chilled sperm total motility and membrane integrity were significantly (P < 0.05) higher in 3% than those in 0% and 5% RJ supplemented groups. The chilled sperm progressive motility and viability was significantly (P < 0.05) higher in 1 and 3% than those in 0 and 5% RJ supplemented groups. The frozen-thawed sperm total motility, progressive motility, membrane integrity and viability were significantly higher in 3% RJ supplemented group (P < 0.05). In conclusion, supplementation of Tris-egg yolk extender with 3% lyophilized RJ had a protective effect on chilled and cryopreserved ram spermatozoa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Arsenic acts as a human carcinogen and contributes to skin cancer via mechanisms that remain largely unknown. Recent evidence implicates the perturbation of Wnt, Shh and BMP signals as a potential mechanism. We initiated studies to examine gene expression changes in these signaling pathways. Meanwhile, the antagonistic effect of retinoic acid was explored. In this study, HaCaT and NHEK cells were treated with arsenic trioxide (As2O3) alone or in combination with arotinoid trometamol (retinoic acid receptor agonist). Flow cytometric analysis, PCR array and Western blot were used to determine the potential mechanism and signaling pathways associated with arsenic carcinogenesis. The results showed that low concentration As2O3 could stimulate keratinocyte proliferation, and arotinoid trometamol inhibited the process via regulating the expression of about 20 genes. These genes included components of Wnt signaling (CSNK1A1L, CTNNB1, SFRP1, Wnt10B, Wnt11, Wnt16, Wnt5A, Wnt8A), Shh signaling (C6orf138, HHIP, PTCHD1) and BMP signaling pathway (BMP2, BMP7). The changes of some differentially expressed genes of these signaling pathways in As2O3 treatment group were counteracted by the subsequent arotinoid trometamol treatment. Our data suggest that dysregulation and cross-talk of Wnt, Shh and BMP signals play great roles in the process of arsenic-induced carcinogenesis, which could be antagonized by arotinoid trometamol., (Copyright 2019 Biolife Sas www.biolifesas.org.)

The aim of the present study was to analyse morphological variations in ovine spermatozoa subjected to different cryopreservation protocols using high resolution imaging techniques. Ejaculates were pooled and diluted in Tris-based extender. Aliquots containing 300 × 10 6 spz/ml were prepared and evaluated a) after the semen collection and pooling, b) after conventional freezing, c) after vitrification of samples maintained at room temperature (22 °C) prior to vitrification, and d) after vitrification of samples maintained at 5 °C prior to vitrification. Sperm motility, acrosome integrity, DNA fragmentation and morphology were assessed. Subcellular sperm changes were assessed and described by light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The maintenance of spermatozoa at 5 °C prior to vitrification and the use of 0.4 M sucrose pointed out lower dimensions of area, length and width than fresh, frozen and sperm maintained at 22 °C prior to vitrification. It was observed that the head width and length are significantly higher (P < 0.0001) in fresh spermatozoa than in the vitrified sperm samples. It could be hypothesized that greater intracellular fluid loss during vitrification could prevent damages in the spermatozoon throughout the reduced ice crystals formation, but mainly by the reduction of extracellular ice crystals due to the physical properties modification obtained when high concentrations of sugars are added. This is the first ultramicroscopic study carried out in ovine vitrified spermatozoa, which confirms the functional sperm alterations previously detected., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tris (hydroxymethyl) aminomethane (Tris) has been used as a pH regulator for buffering the pH of dilution extenders for boar semen, such as the Modena extender. The purpose of the present study was to assess the effects of Tris supplementation at different concentrations (0, 8, 24 and 72 μM) into the freezing extender on the quality and fertilising capacity of frozen-thawed boar spermatozoa. The results showed that the supplementation of 24 μM of Tris gave significantly higher percentages of sperm viability and plasma membrane integrity than those of the control group at any time point of assessment (0 h and 3 h post-thawing) (P < 0.05). However, there were no significant differences in the acrosome integrity parameter among the groups. Higher percentages of sperm motility were observed in the spermatozoa cryopreserved with 24 μM of Tris compared to the control groups when the samples were analysed 0 h after thawing (P < 0.05). However, an increase of the Tris concentration to 72 μM did not enhance the sperm motility parameters. The total numbers of fertilised oocytes and blastocysts obtained with spermatozoa frozen with 24 μM Tris were significantly higher than those of the control group without Tris (P < 0.05). In conclusion, the supplementation of 24 μM Tris into the freezing extender contributes to a better boar sperm quality and fertilising capacity after the process of freezing and thawing.

Motherwort (YiMuCao), a traditional Chinese herb, has been shown beneficial effects for women's diseases. This meta-analysis aimed to evaluate the efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang from their inception to December 2017. Randomized controlled trials that determined the add-on effects of motherwort injection to carboprost for prevention of post-partum blood loss were eligible. Pooled risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used to summarize the effect sizes. Eight trials including 1276 pregnant women fulfilled the inclusion criteria. Prophylactic use of motherwort injection add-on therapy significantly reduced the post-partum 2 h (MD -127.5 mL; 95% CI -149.13 to -105.88) and 24 h (MD -146.85 mL; 95% CI -179.77 to -113.94) blood loss and incidence of post-partum hemorrhage (RR 0.28; 95% CI 0.17-0.45) than carboprost. Moreover, adjunctive treatment with motherwort injection significantly decreased the length of the third stage of labor (MD -3.41 min; 95% CI -4.33 to -2.49) and duration of lochia (MD -7.13 days; 95% CI -8.49 to -5.76). There was no statistical significant difference in the incidence of adverse events (RR 0.76; 95% CI 0.50-1.16). Prophylactic use of motherwort injection add-on therapy to carboprost tromethamine could reduce post-partum blood loss. However, more well-designed trials are necessary to confirm the findings of this study due to the methodological flaws of the included trials., (© 2018 Japan Society of Obstetrics and Gynecology.)

One reason for reduced longevity of chilled dog semen is oxidative stress. The antioxidant glutathione (GSH) improves viability of frozen-thawed dog sperm, but its effect on chilled dog semen has not been investigated. An experiment consisting of two parts was performed: Sperm rich fractions, SRF, were split, diluted with a Tris-egg yolk (TEY) extender containing 0, 5 or 10 mM GSH and stored at 4 °C for 10 days (Part 1; n = 19) or 4 days (Part 2; n = 11), respectively. For Part 1 of the study, percentage (%) of motile, viable, morphologically abnormal spermatozoa and % acrosomal deviations were assessed on days 0, 1, 2, 4 and 10 after dilution. For % sperm motility, samples from all three aliquots of each SRF (0/5/10 mM GSH) were pipetted simultaneously and analysed in a randomised order (time point of analysis, TPA). In Part 2 of the study, motility analysis was performed during 4 days storage and samples were analysed immediately after pipetting (part 2). Most investigated parameters were affected by storage time. For motility variables, there was an effect of GSH identified for circular, CM (ANOVA, Part 1: P =  0.05, Part 2: P < 0.0001) and local motility, LM (ANOVA, Part 2: P =  0.004). Furthermore, there was a trend for an interaction between time and sperm treatment for CM (Part 2: P =  0.077). In conclusion, in the present study there was not an overall positive effect of GSH addition (5/10 mM) on sperm motility in chilled dog semen samples that were characterised to be of good quality during 4- and 10-days of storage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To evaluate and compare the analgesic efficacy and adverse effects of dexketoprofen and methadone using a noninferiority trial, during the first 24 postoperative hours in dogs undergoing orthopaedic surgery., Study Design: Randomized, blinded clinical study., Animals: A total of 38 healthy dogs undergoing orthopaedic surgery., Methods: Dogs were premedicated with dexmedetomidine [1 μg kg -1 intravenously (IV)] followed by dexketoprofen (1 mg kg -1 IV; group DK) or methadone (0.2 mg kg -1 IV; group M). Anaesthesia was induced with propofol and maintained with isoflurane in 60% oxygen. Postoperatively, dexketoprofen was administered every 8 hours (group DK) and methadone every 4 hours (group M). Analgesia was assessed at baseline and at 1, 2, 4, 6, 18 and 24 hours after extubation using a dynamic and interactive visual analogue scale (DIVAS), the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF), mechanical wound thresholds (MWTs) and plasma cortisol levels. If CMPS-SF score was ≥5, rescue analgesia was administered. Data were analysed using a general linear mixed model, Mann-Whitney U test and chi-squared test as appropriate; a p value <0.05 was considered significant., Results: The CMPS-SF and DIVAS scores were significantly higher in group M compared with group DK and remained higher for a longer period in group M, although the differences were not clinically significant. No significant differences were found in MWT assessment between groups. Plasma cortisol level significantly increased 2 hours after extubation, without significant differences between treatments. Rescue analgesia was administered to three animals (one in group DK; two in group M)., Conclusion and Clinical Relevance: We conclude that 1 mg kg -1 IV dexketoprofen administered every 8 hours during the first 24 hours postoperatively is noninferior to methadone in controlling pain after orthopaedic surgery in dog, although frequent pain assessments are recommended to adjust the analgesia plan., (Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

SummaryThe aim of this study was to establish a functional freezing-thawing protocol for epididymal sperm of collared peccaries (Pecari tajacu L., 1758) by comparing different extenders. The epididymal sperm from 12 sexually mature males was recovered by retrograde flushing using Tris-based or coconut water-based (ACP®-116c) extenders. After initial evaluation, samples were diluted and frozen with the same extenders to which 20% egg yolk and 6% glycerol were added. After 2 weeks, thawing was performed at 37°C/60 s and sperm motility, vigour, morphology, functional membrane integrity, sperm viability, sperm plasma membrane integrity, and a computer-assisted semen analysis (CASA) were assessed. In addition, to evaluate the survival of frozen-thawed sperm, a thermal resistance test (TRT) was executed. Samples preserved using Tris were in better condition compared with those preserved using ACP®, showing higher values for most assessments performed, including CASA and the TRT (P<0.05). After determining Tris to be the better of the two extenders, additional samples were thawed using different thawing rates (37°C/60 s, 55°C/7 s, 70°C/8 s). Sperm thawed at 37°C/60 s had the greatest preservation (P<0.05) of viability (54.1 ± 5.9%) and functional membrane integrity (43.2 ± 5.4%), and had higher values for various CASA parameters. In conclusion, we suggest the use of a Tris-based extender added to egg yolk and glycerol for the cryopreservation of epididymal sperm obtained from collared peccaries. In order to achieve better post-thawing sperm quality, we suggest that samples should be thawed at 37°C/60 s.

Background: In a previous study, we found a rebound of arterial carbon dioxide tension (PaCO 2 ) after stopping THAM buffer administration. We hypothesized that this was due to reduced pulmonary CO 2 elimination during THAM administration. The aim of this study was to investigate this hypothesis in an experimental porcine hypercapnic model., Methods: In seven, initially normoventilated, anesthetized pigs (22-27 kg) minute ventilation was reduced by 66% for 7 h. Two hours after commencing hypoventilation, THAM was infused IV for 3 h in a dose targeting a pH of 7.35 followed by a 2 h observation period. Acid-base status, blood-gas content and exhaled CO 2 were measured., Results: THAM raised pH (7.07 ± 0.04 to 7.41 ± 0.04, P < 0.05) and lowered PaCO 2 (15.2 ± 1.4 to 12.2 ± 1.1 kPa, P < 0.05). After the infusion, pH decreased and PaCO 2 increased again. At the end of the observation period, pH and PaCO 2 were 7.24 ± 0.03 and 16.6 ± 1.2 kPa, respectively (P < 0.05). Pulmonary CO 2 excretion decreased from 109 ± 12 to 74 ± 12 ml/min (P < 0.05) during the THAM infusion but returned at the end of the observation period to 111 ± 15 ml/min (P < 0.05). The estimated reduction of pulmonary CO2 elimination during the infusion was 5800 ml., Conclusions: In this respiratory acidosis model, THAM reduced PaCO 2 , but seemed not to increase the total CO 2 elimination due to decreased pulmonary CO 2 excretion , suggesting only cautious use of THAM in hypercapnic acidosis., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

To explore the mechanism of lysozyme stabilization in buffer system, we have investigated the interactions between lysozyme and the biological buffers (TRIS, TAPS, and TES) using spectroscopic techniques, including ultraviolet-visible (UV-Vis), fluorescence, thermal fluorescence, dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) spectroscopy. From the series of spectroscopic studies, it is found that the native structure of the protein remains intact in the different concentrations (0.05, 0.1, 0.25, 0.5, and 1.0M) of the biological buffer aqueous solutions at pH7.0. Moreover, all these three investigated buffers are able to protect lysozyme against thermal denaturation, particularly in high concentration (1.0M) of the buffer aqueous solutions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The left ventricular working, crystalloid-perfused heart is used extensively to evaluate basic cardiac function, pathophysiology, and pharmacology. Crystalloid-perfused hearts may be limited by oxygen delivery, as adding oxygen carriers increases myoglobin oxygenation and improves myocardial function. However, whether decreased myoglobin oxygen saturation impacts oxidative phosphorylation (OxPhos) is unresolved, since myoglobin has a much lower affinity for oxygen than cytochrome c oxidase (COX). In the present study, a laboratory-based synthesis of an affordable perfluorocarbon (PFC) emulsion was developed to increase perfusate oxygen carrying capacity without impeding optical absorbance assessments. In left ventricular working hearts, along with conventional measurements of cardiac function and metabolic rate, myoglobin oxygenation and cytochrome redox state were monitored using a novel transmural illumination approach. Hearts were perfused with Krebs-Henseleit (KH) or KH supplemented with PFC, increasing perfusate oxygen carrying capacity by 3.6-fold. In KH-perfused hearts, myoglobin was deoxygenated, consistent with cytoplasmic hypoxia, and the mitochondrial cytochromes, including COX, exhibited a high reduction state, consistent with OxPhos hypoxia. PFC perfusate increased aortic output from 76 ± 6 to 142 ± 4 ml/min and increased oxygen consumption while also increasing myoglobin oxygenation and oxidizing the mitochondrial cytochromes. These results are consistent with limited delivery of oxygen to OxPhos resulting in an adapted lower cardiac performance with KH. Consistent with this, PFCs increased myocardial oxygenation, and cardiac work was higher over a wider range of perfusate Po 2 . In summary, heart mitochondria are limited by oxygen delivery with KH; supplementation of KH with PFC reverses mitochondrial hypoxia and improves cardiac performance, creating a more physiological tissue oxygen delivery. NEW & NOTEWORTHY Optical absorbance spectroscopy of intrinsic chromophores reveals that the commonly used crystalloid-perfused working heart is oxygen limited for oxidative phosphorylation and associated cardiac work. Oxygen-carrying perfluorocarbons increase myocardial oxygen delivery and improve cardiac function, providing a more physiological mitochondrial redox state and emphasizing cardiac work is modulated by myocardial oxygen delivery.

The fear of postoperative pain is often mentioned by patients as one of the factors that is most frequently associated with dental implants. To reduce this factor, a single oral dose of 25 mg dexketoprofen trometamol (DKT) or placebo was administered 15 minutes before implant surgery. One hundred patients who required single-implant treatments were randomly assigned to 1 of 2 blinded groups. The patients in the test group were given 25 mg DKT (DKT group), and those in the control group were given 500 mg vitamin C as a placebo (PLACEBO group). A subjective visual analogue scale of 100 mm in length was used to evaluate pain. Inflammation and complications were assessed using a 5-point Likert scale. An analysis of variance, t-tests, and a Mann-Whitney U test were performed. Among the 100 patients, 83 completed the study (there were 8 dropouts in the PLACEBO group and 9 in the DKT group). The patients who received DKT reported a lower pain intensity during the immediate postoperative period. The inflammatory response was weaker in the DKT group than the control group at 48 hours, but bleeding was greater. There were no other complications in either of the groups. In conclusion, the preemptive use of 25 mg soluble DKT administered orally 15 minutes before implant surgery can reduce the severity of immediate postoperative pain.

In order to protect sperm chromosomes against degradation when they are being stored for relatively high temperatures, we investigated the optimal pH of the freeze-drying solution, EGTA/Tris-HCl buffered solution alkalinized by NaOH (Na-ETBS) or KOH (K-ETBS). Mouse spermatozoa suspended in Na-ETBS or K-ETBS were freeze-dried at pH 5.0-8.4 and stored at 4 °C or 50 °C for 3 days. Some freeze-dried samples were stored at 25 °C for 3 days or 1 month. After storage, samples injected into oocytes using intracytoplasmic sperm injection were assessed for chromosome damage in resulting zygotes. Irrespective of freeze-drying solutions and storage temperatures, almost all the zygotes (97-100%) produced using the spermatozoa freeze-dried at pH 5.0 had structural chromosome aberrations of sperm origin. When freeze-drying was conducted at pH 8.0-8.4 using Na-ETBS, the incidence of chromosome damage decreased to 14-17% in 4 °C storage and 24-26% in 50 °C storage. When freeze-dried in K-ETBS, the lowest level of chromosome damage occurred at pH levels of 7.7-8.4 at 4 °C storage (13-15%) and at pH 7.7-8.0 at 50 °C storage (16-23%). Spermatozoa freeze-dried in Na-ETBS at pH 8.2 and K-ETBS at pH 7.7 showed no significant increase in chromosome damage during 25 °C storage from 3 days to 1 month (11%-20% in Na-ETBS; 13%-18% in K-ETBS). Thus, use of the solutions optimized for short-term storage at high temperature (50 °C, 3 days) permits prolonged storage (1 month) of freeze-dried spermatozoa at room temperature., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Neutralizing tumor external acidity with oral buffers has proven effective for the prevention and inhibition of metastasis in several cancer mouse models. Solid tumors are highly acidic as a result of high glycolysis combined with an inadequate blood supply. Our prior work has shown that sodium bicarbonate, imidazole, and free-base (but not protonated) lysine are effective in reducing tumor progression and metastasis. However, a concern in translating these results to clinic has been the presence of counter ions and their potential undesirable side effects (e.g., hypernatremia). In this work, we investigate tris(hydroxymethyl)aminomethane, (THAM or Tris), a primary amine with no counter ion, for its effects on metastasis and progression in prostate and pancreatic cancer in vivo models using MRI and bioluminescence imaging. At an ad lib concentration of 200 mmol/L, Tris effectively inhibited metastasis in both models and furthermore led to a decrease in the expression of the major glucose transporter, GLUT-1. Our results also showed that Tris-base buffer (pH 8.4) had no overt toxicity to C3H mice even at higher doses (400 mmol/L). In conclusion, we have developed a novel therapeutic approach to manipulate tumor extracellular pH (pHe) that could be readily adapted to a clinical trial., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This work examines the effectiveness of a TCG (Tris, citric acid, glucose, 6% egg yolk and 5% glycerol) and a TEST (TES, Tris, glucose, 6% egg yolk and 5% glycerol) sperm extender in the freezing of mouflon spermatozoa at slow cooling rates, using different pre-freezing equilibration times (2-3 hr). It also examines the tolerance of mouflon spermatozoa to different concentrations of cryoprotectants (5, 10, 20% glycerol; 5%, 10%, 20% dimethyl sulfoxide; 6% polyvinylpyrrolidone) and/or sucrose (100, 300, 500 mm). The highest quality (p < .01) thawed spermatozoa were obtained when using the TEST extender and an equilibration time of 3 hr. Sperm motility and membrane integrity were strongly reduced when using rapid freezing rates (60-85°C min -1 ), independent of the concentration of cryoprotectants. The lowest sucrose concentration (100 mm) provided the highest (p < .05) percentage of motile spermatozoa and live spermatozoa with an intact acrosome. Vitrified-warmed sperm variables were at their best when the spermatozoa was diluted in TCG-6% egg yolk + 100 mm sucrose and warmed at 60°C. Slow warming at 37°C strongly reduced (p < .05) sperm motility and viability. However, sperm vitrification returned lower fertility, sperm motility and sperm viability values than conventional sperm freezing., (© 2016 Blackwell Verlag GmbH.)

High levels of reactive oxygen species are associated with spermatozoa cryopreservation, which bring damage to functional spermatozoa. The aim of the present study was to investigate whether and how the freezing extenders supplemented with trehalose was beneficial for the survival of rabbit spermatozoa. semen was diluted with Tris-citrate-glucose extender addition of different concentrations of trehalose. Addition of 100 mM trehaose significantly improved post-thaw rabbit sperm parameters, such as motility, acrosome integriy, membrane integrity and mitochondrial membrane potential. Moreover, when freezing extenders supplemented with trehalose, activities of catalase (CAT), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) of post-thaw spermatozoa were enhanced, meanwhile, reactive oxygen species (ROS) level and Malondialdehyde (MDA) content were decreased. The results suggest that freezing extenders supplemented with 100 mM trehalose resulted in less ROS level and MDA content, higher motility and mitochondrial membrane potential as well as the integrity of acrosome and plasma membrane. Supplementation of trehalose with freezing extenders is beneficial to the rabbit breeding industry., (Copyright © 2017 Elsevier Inc. All rights reserved.)

An increase of total glucagon-like peptide-1 (GLP-1) concentration in the plasma in rats was revealed 5 min after oral, but not intraperitoneal administration of NaCl or Trizma HCl solutions. The increase in GLP-1 level was similar to that after oral glucose administration. After intraperitoneal administration of 2.5% NaCl, GLP-1 mimetic exenatide accelerated natriuresis and urinary chloride excretion. Under conditions of normonatriemia and hyperchloremia induced by injection of 6.7% Trizma HCl, exenatide stimulated chloride excretion and reabsorption of sodium ions in the kidneys. These findings suggest that GLP-1 participates in selective regulation of the balance of sodium and chloride ions.

An isolated perfused kidney model was used to evaluate the effect of hyperglycemia on renal tubular epithelial cell morphology. Ten Sprague-Dawley rat kidneys were perfused with Krebs-Henseleit buffer containing 70 mmol/L of glucose (five for 1 h and five for 2 h). Two control groups consisted of 10 kidneys perfused with Krebs-Henseleit buffer without hyperglycemia (five for 1 h and five for 2 h), and 10 nonperfused contralateral kidneys placed in the same environment for the same duration. The hyperglycemia group had significantly increased renal tubular vacuolization (p < 0.001) compared to both control groups at 1 and 2 h. The isolated perfused kidney model recapitulates the renal tubular vacuolization phenotype found in hyperglycemia and may be a potential tool for the investigation into causal factors in renal histology. The full pattern of the Armanni-Ebstein phenomenon was not, however, reproduced, suggesting that this change requires more time or involves more complex factors., (© 2016 American Academy of Forensic Sciences.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) may act through others mechanisms, in addition to inhibition of prostaglandin synthesis. These includes cholinergic, NO, serotonergic and opioids pathways., Methods: The aim of this work was to evaluate the effect of systemic action of (S)-+-ketoprofen (dexketoprofen, DEX) on pain behaviors using the orofacial formalin test in mice and the potential involvement of cholinergic, NO, serotonergic and opioids pathways., Results: The pretreatment of the mice with 1mg/kg ip of atropine or opoid antagonists: 1mg/kg, ip of NTX or 1mg/kg ip of NTI or 1mg/kg of NOR-BNI ip, did not produce significant change in the ED 50 values of the antinociception to orofacial test induced by DEX. The pretreatment of the mice with 0.5mg/kg ip tropisetron, increased in a significant fashion the values of ED 50 of DEX. When the mice were treated with 5mg/kg ip of L-NAME or 25mg/kg ip of aminoguanidine or 50mg/kg ip of 7-nitroindazole reversed the antinociception of DEX., Conclusion: The findings of this study demonstrate activation of NO and 5-HTpathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain., (Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.)

2-[Tris(oleoyloxymethyl)methylamino]-1-ethane sulfonic acid (TES trioleate) is an inhibitor of phospholipase A 2 (PLA2), which hydrolyzes cell membrane phospholipids to produce arachidonic acid (AA) and lysophospholipids (LysoPLs). Here, we investigated the protective effects of TES trioleate on cell damage caused by ultraviolet A (UVA) light and reactive oxygen species (ROS). Pre-incubation with 250-1000μM TES trioleate resulted in concentration-dependent protection from UVA-induced damage in HaCaT cells. Additionally, 25-1000μM TES trioleate provided protection against H 2 O 2 in a concentration-dependent manner. In human erythrocytes treated with 1 O 2 , 10-100μM TES trioleate showed concentration-dependent protective effects, similar to but stronger than the controls, 4-BPB and lipophilic antioxidant (+)-α-tocopherol at 100μM. TES trioleate did not have detectable radical scavenging activity. Moreover, compared with (+)-α-tocopherol and rutin, TES trioleate showed low ROS scavenging activity. Thus, although TES trioleate showed cell protective effects against UVA, H 2 O 2 , and 1 O 2 -induced damages, these effects were not caused by the scavenging ability of the radical or ROS. Finally, pretreatment of HaCaT cells and human erythrocytes with l-α-lysophosphatidylcholine produced by PLA2 promoted increased cell damage at low concentrations. Thus, the protective effects of TES trioleate on cellular damage by UVA and ROS may be associated with inhibition of PLA2-dependent cell damage rather than ROS scavenging., (Copyright © 2016. Published by Elsevier B.V.)

Background: Topical therapy is an important alternative to systemic antibacterial therapy for treatment of canine superficial pyoderma in light of the emergence of multidrug-resistant staphylococci. Chlorhexidine is widely used in shampoo products alone or in combination with miconazole or tromethamine-ethylenediaminetetraacetic acid (trisEDTA). Comparisons of these combinations have not been made., Hypothesis/objectives: To determine minimum inhibitory concentrations (MICs) of combinations of chlorhexidine/miconazole and chlorhexidine/trisEDTA in vitro in a collection of Staphylococcus pseudintermedius (SP) from northern (NUK) and southeastern (SEUK) United Kingdom (UK) sources., Methods: MICs of chlorhexidine, miconazole, trisEDTA and combinations of chlorhexidine/miconazole (1:1) or chlorhexidine/trisEDTA (80:16:1 and 80:5:1) were determined for 196 canine SP isolates from NUK [49 meticillin-resistant (MRSP), 50 meticillin-susceptible (MSSP)] and fom SEUK (48 MRSP, 49 MSSP) using agar dilution., Results: TrisEDTA alone did not inhibit growth. Chlorhexidine/miconazole MICs (median = 0.5 mg/L) were lower than those of either drug alone (P < 0.05) and lower than chlorhexidine/trisEDTA MICs (median = 1 mg/L; P < 0.0005) in each bacterial type and from both regions, except for miconazole in NUK MSSP. An additive interaction was noted between chlorhexidine and miconazole or trisEDTA (80:16:1 ratio) in 79 and 43 isolates, respectively, whereas antagonism between chlorhexidine and trisEDTA was noted for three isolates. NUK isolates were more susceptible than SEUK isolates (P < 0.05), except MRSP exposed to chlorhexidine and the chlorhexidine/trisEDTA (80:16:1) combination., Conclusions and Clinical Importance: These low MICs are likely to be exceeded by topical therapy. Evaluation of the mechanisms by which chlorhexidine combinations interact to reduce MICs is warranted, in view of increasing concerns of biocide tolerance in staphylococci., (© 2016 ESVD and ACVD.)

Background: Pseudomonas aeruginosa (PA) may cause suppurative otitis externa with severe inflammation and ulceration in dogs. Multidrug resistance is commonly reported for this organism, creating a difficult therapeutic challenge., Objective: The aim of this study was to evaluate the in vitro antimicrobial activity of a gel containing 0.5 μg/mL of antimicrobial peptide AMP2041, 0.07% chlorhexidine digluconate (CLX), 0.4% Tris and 0.1% EDTA on 30 clinical isolates of PA from canine otitis externa., Materials and Methods: Antimicrobial activity was evaluated through minimal bactericidal concentration (MBC). Standardized bacterial suspensions were incubated with different concentrations of the gel at 37°C for 30 min and plated for colony forming unit (CFU) counts. Time-to-kill kinetics were evaluated with the undiluted product and at MBC for each PA strain at 30 s, 1, 5, 10, 15, 30 min, 24 and 48 h., Results: The MBC was 1:64 for two of 30 strains, 1:128 for 15 of 30 strains and 1:256 for 13 of 30 strains. The geometric mean was 1:165, equivalent to a concentration of 0.003 μg/mL AMP2041 + 0.0004% CLX + 0.0024%Tris + 0.0006% EDTA. Time-to-kill assays with the undiluted product showed complete bactericidal effect within 30 s for all isolates, whereas at the MBC this effect was reached within 5 min for 20 of 30 isolates and within 30 min for all isolates. Bactericidal activity was maintained after 48 h for all isolates., Conclusion: This gel has shown rapid, complete and long-lasting activity against a panel of 30 PA isolates from cases of canine otitis externa., (© 2016 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.)

One of the buffers namely Tris (Tris-(hydroxymethyl)-amino methane) was used to increase the growth of microalgae by stabilizing the pH value in microalgae cultures. The objective of this research is to determine the growth rate and biomass productivity of Chlorella sp. with and without Tris addition. Both conditions function at various N:P ratios cultured in photobioreactors (carbon dioxide of 5%(v/v), light intensity of 3.3 Klux). Daily variations in nutrient removal (nitrogen and phosphorus), cell concentration, DO, temperature and pH were measured for data analysis. The results show that the largest yield of biomass was achieved at the N:P ratio of 15:1 with and without Tris. After cultivation lasting 92 h, the algae concentration at this ratio was 1250 mg L(-1) and 3568 mg L(-1) with and without Tris, respectively. This indicates that adding Tris to the photobioreactor greatly reduces algae biomass due to bacterial competition., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this study, we used a bench-top cold-cathode ultra-soft X-ray (USX) generator to expose aqueous DNA plasmid solutions to low-LET radiation under various scavenging conditions. Single- and double-strand breaks were assessed using classic gel electrophoresis quantification of linear, circular and supercoiled plasmid DNA topologies. With their very low penetration range in water, USX can only interact with matter up to short distances, of the order of 50 μm. We validated a stirring procedure which makes it possible to expose 100 µL of aqueous samples (2 mm thick). The scavenging of OH radicals by Tris buffer was studied at ambient temperature under aerobic conditions and compared to data gathered in the literature. A very good agreement was found with the rare data dealing with DNA plasmid exposed to Al Kα photons at low temperature (T ≤ 277 K), which therefore validated the experimental procedure. The yields for DNA single-strand breaks determined during this study enabled the ratio of indirect to direct effects to be determined at 96.2%, in good agreement with the value of 97.7% stemming from a study based on γ-ray irradiation of frozen solutions of plasmid DNA. Then, arginine was used both to create a "biological-like" chemical environment around the DNA plasmids and as an OH radical scavenger, in vitro. Although arginine has a greater scavenging (protecting) power than Tris, surprisingly, it led to higher rates of strand breakage. Based on the specific binding modes of arginine to DNA, we suggest that the side effects observed are due to the presence of arginine near to, but also inside, the DNA double helix.

This study was undertaken to investigate the influence of adding combinations of vitamin C to Tris extender with either catalase or reduced glutathione on post-cryopreserved semen characteristics of Holstein bulls for different preservation periods (cooling at 5°C, 48 h, 1, 2 and 3 months post cryopreservation, PC). Seven Holstein bulls of 2.5-3 years of age were used in this experiment. Semen was collected via artificial vagina in one ejaculate per bull per week for the 7 week experimental period. Pooled semen was equally divided into three treatments using Tris extender. Combinations of vitamin C (2.5mM) were added with either catalase (100 IU/ml, T2) or reduced glutathione (2mM, T3) to Tris extender and comparisons in response were made with the control group (Tris extender, T1). Individual sperm motility (IM), viability (V), plasma membrane integrity (PMI), and acrosome integrity (AI) were assessed during all periods of the study along with Malondialdehyde (MDA) concentrations and freezing ability. The IM was greater (P ≤ 0.01) in the T2 as compared with the T1 group at all periods of the study. Furthermore, the IM were greater (P ≤ 0.01) in the T3 as compared with the T1 group at the 48 h time period and at 3 months PC. The V, PMI and AI were greater (P ≤ 0.01) in T2 and T3 as compared with the T1 group at all the experimental periods. The MDA was greater (P ≤ 0.01) in the T2 as compared with the T1 group at 3 months PC. In conclusion, there was improved semen quality if semen of Holstein bulls was collected and stored in combinations of vitamin C with either catalase (T2) or reduced glutathione (T3) being added to Tris extender., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC)., Methods: Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen., Results: At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration., Conclusion: In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.

Due to its high antioxidant content, the argan oil could play a beneficial role in liquid storage of ram semen. The aim of this study was to investigate effects of different concentration of argan oil (ARO) on spermatologic parameters, lipid peroxidation and DNA fragmentation during liquid storage of ram semen until 48 h. Also effects of extenders and temperature on same parameters were assessed. For these aims, semen samples were collected from Boujaâd rams, extended with Tris egg yolk or skim milk extenders without (control) or supplemented with different concentrations of ARO (1%, 2%, 5% and 10% v/v) at a final concentration of 0.8 × 10(9) sperm/mL and stored until 48 h at 5 °C or 15 °C. The sperm quality assessments were performed at different intervals during storage (0, 8, 24 and 48 h). Sperm progressive motility started to decrease after 8h of storage in all temperatures--extenders combinations and dropped steadily during the 8-48 h interval. However, sperm viability, progressive motility and membrane integrity were markedly higher in ARO groups (especially in 1% in Tris and 5% in skim milk) until 24h and 48 h storage at both temperatures compared to controls. The argan oil also decreased the level of spontaneous and induced malondialdehyde (MDA) and the sperm DNA fragmentation until 48 h storage. In conclusion, it was determined that addition of argan oil to conventional extenders may improve the quality of ram semen during liquid storage in different temperatures., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability., (Copyright © 2014 John Wiley & Sons, Ltd.)

This study was conducted to investigate possible histopathological effects and biochemical reflections of intra-articular dexketoprofen trometamol. A total of 24 New Zealand rabbits were included in the study. Blood sampling was carried out from all animals on the first day, then they were randomly allocated either to the control group (Group C, n = 9) or the dexketoprofen trometamol group (Group D, n = 15). Group C underwent each two intra-articular injections of saline, 0.25 mL into right and 0.50 mL into left knee. Group D was injected 0.25 mL (6.25 mg) dexketoprofen trometamol into the right knee and 0.50 mL (12.5 mg) into the left. The groups were divided randomly into three. Tissue and blood samples were collected from Groups C1 and D1 on the first day, C2 and D2 on the second day and C3 and D3 on the 10th day of the study. Interleukin-1 (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) levels were studied. The histopathological examination of C and D groups did not present any deterioration. IL-6 basal levels were significantly higher in Group D2 compared with C2 and C3 compared with D3. Basal TNF-α levels were higher compared with day 1 in Group C1, and IL-6 and CRP levels were higher in Group D3. Also, none of the increases in these values are supported by histopathological evaluation results. Consequently, we suppose that dexketoprofen trometamol does not cause histopathological deterioration in articular cartilage of rabbits, and the increases in biochemical parameters exclusively are not clinically significant., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)