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In this study, a novel three-dimensional ordered macroporous gelatin (3DOMG) was fabricated as a carrier for increasing the solubility of poorly water-soluble drugs, offering sustained release and a high oral bioavailability. Polymethyl methacrylate nanospheres (257 nm) were used as a colloidal plastic framework to synthesize 3DOMG. Fenofibrate (FNB) was selected as a model drug and loaded onto 3DOMG by the adsorption equilibrium method. Detailed characterization showed that the FNB absorbed onto 3DOMG was in a microcrystalline state. A fluorescence experiment and the prepared drug microcrystal network gave further information on the physical state of the drug. A degradation experiment proved that 3DOMG was readily biodegradable. In vitro release testing showed that 3DOMG increased the dissolution rate of FNB and produced a sustained release. An in vivo pharmacokinetic study confirmed that 3DOMG improved the oral bioavailability compared with that of commercial sustained-release capsules. These findings confirm that 3DOMG can be regarded as a promising carrier for an oral drug delivery system., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Although considered promising materials for assisting organ regeneration, few hydrogels meet the stringent requirements of clinical translation on the preparation, application, mechanical property, bioadhesion, and biocompatibility of the hydrogels. Herein, we describe a facile supramolecular approach for preparing gelatin hydrogels with a wide array of desirable properties. Briefly, we first prepare a supramolecular gelatin macromer via the efficient host-guest complexation between the aromatic residues of gelatin and free diffusing photo-crosslinkable acrylated β-cyclodextrin (β-CD) monomers. The subsequent crosslinking of the macromers produces highly resilient supramolecular gelatin hydrogels that are solely crosslinked by the weak host-guest interactions between the gelatinous aromatic residues and β-cyclodextrin (β-CD). The obtained hydrogels are capable of sustaining excessive compressive and tensile strain, and they are capable of quick self healing after mechanical disruption. These hydrogels can be injected in the gelation state through surgical needles and re-molded to the targeted geometries while protecting the encapsulated cells. Moreover, the weak host-guest crosslinking likely facilitate the infiltration and migration of cells into the hydrogels. The excess β-CDs in the hydrogels enable the hydrogel-tissue adhesion and enhance the loading and sustained delivery of hydrophobic drugs. The cell and animal studies show that such hydrogels support cell recruitment, differentiation, and bone regeneration, making them promising carrier biomaterials of therapeutic cells and drugs via minimally invasive procedures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β-cyclodextrin (βCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, electrospun nanofibrous scaffolds are vastly taken into consideration in the bone tissue engineering due to mimicking the natural structure of native tissue. In our study, surface features of nanofibers were modified through simultaneous electrospining of the synthetic and natural polymers using poly l-lactide (PLLA) and gelatin to fabricate the hybrid scaffold (PLLA/gelatin). Then, hydroxyapatite nanoparticles (nHA) were loaded in electrospun PLLA nanofibers (PLLA,nHA/gelatin) and also dexamethasone (DEX) was incorporated in these fibers (PLLA,nHA,DEX/gelatin) in the second experiment. Fabricated nanofibrous composite scaffolds were characterized via SEM, FTIR spectroscopy, contact angle, tensile strength measurements, DEX release profile and MTT assay. After seeding adipose derived mesenchymal stem cells, osteoinductivity and osteoconductivity of fabricated scaffolds were analyzed using common osteogenic markers such as alkaline phosphatase activity, calcium depositions and gene expression. These results confirmed that all properties of nanofibers were improved by modifications. Moreover, osteogenic differentiation of stem cells increased in PLLA,nHA/gelatin group in comparison with PLLA/gelatin. The sustained release of DEX was obtained from PLLA,nHA,DEX/gelatin which subsequently led to more osteogenic differentiation. Taken together, PLLA,nHA,DEX/gelatin showed significant potential to support the stem cell proliferation and ostogenic differentiation, and can be a good candidates for tissue engineering and regenerative medicine applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Coating of gelatin and chitosan can improve fish fillet's quality, but the mechanism is not clear. Chitosan/gelatin coatings significantly prevented deterioration of golden pomfret fillet at 4 °C. Chitosan with 7.2% gelatin group showed the best effect on preserving the length of myofibril, which remained greater than 15 μm at day 17 of storage, while for control, chitosan and chitosan combined with 3.6% gelatin group, it was 5.03, 10.04 and 9.02 μm, respectively. The MALDI-TOF MS result revealed that the coatings slowed down the protein deterioration of fillet. On days 13 and 17, the myosin light chain and myoglobin in control group degraded, while the two proteins still existed in chitosan/gelatin coated groups. Overall, the chitosan with 7.2% gelatin coating had the best effect on preserving fillet's quality during storage. The coating may exert its protective effect via inhibiting myofibril degradation within fillet., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent-free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose-dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To evaluate the feasibility and safety of transarterial embolization (TAE) using trisacryl gelatin microspheres (TGMs) for hypervascular tumors., Materials and Methods: This was a prospective multicenter clinical trial involving five institutions. TAE using TGMs was performed for hypervascular tumors in various locations. The primary endpoint was the technical success. The secondary endpoints included catheter accessibility, preservation of the feeding arteries, local tumor response based on the Response Evaluation Criteria in Cancer of the Liver (RECICL) and adverse events related to TAE based on the Common Terminology Criteria for Adverse Events, version 4.0., Results: Twenty-three patients with liver tumors (n = 9), uterine fibroids (n = 3) and other tumors (n = 11) were enrolled. The technical success rate was 95.7 % (22 of 23 patients). Catheter accessibility and preservation of the feeding arteries were obtained in all 55 target vessels (100 %). Local tumor response rates were 46.7 and 55.8 % at 4 and 12 weeks, respectively. Eighteen (78.3 %) patients developed 53 symptomatic events including grade ≧3 events: hypertension 21.7 %, pain 8.7 %, vomiting 4.3 % and anorexia 4.3 %, all related to postembolization syndromes., Conclusion: TAE using TGMs was technically feasible and safe for devascularization of hypervascular tumors.

Between November 2014 and October 2015, 12 patients with prostates measuring 80-150 cm(3) and lower urinary tract symptoms (LUTSs) were enrolled in a prospective single-center US trial to evaluate Embosphere Microspheres for use in prostatic artery embolization (PAE). At 3 months, mean improvements in International Prostate Symptom Score and quality of life score were 18.3 points (range, 5-27) and 3.6 points (range, 1-6), respectively. One-month cystoscopies and anoscopies demonstrated no ischemic injuries. There were no major complications. In this cohort, Embosphere Microspheres, when used for PAE, were safe and effective in reducing LUTSs in the early follow-up period., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Recent studies have reported that oral intake of gelatin hydrolysate has various beneficial effects, such as reduction of joint pain and lowering of blood sugar levels. In this study, we produced a novel gelatin hydrolysate using a cysteine-type ginger protease having unique substrate specificity with preferential peptide cleavage with Pro at the P2 position. Substantial amounts of X-hydroxyproline (Hyp)-Gly-type tripeptides were generated up to 2.5% (w/w) concomitantly with Gly-Pro-Y-type tripeptides (5%; w/w) using ginger powder. The in vivo absorption of the ginger-degraded gelatin hydrolysate was estimated using mice. The plasma levels of collagen-derived oligopeptides, especially X-Hyp-Gly, were significantly high (e.g., 2.3-fold for Glu-Hyp-Gly, p < 0.05) compared with those of the control gelatin hydrolysate, which was prepared using gastrointestinal proteases and did not contain detectable X-Hyp-Gly. This study demonstrated that orally administered X-Hyp-Gly was effectively absorbed into the blood, probably due to the high protease resistance of this type of tripeptide.

The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.

Introduction: Freshly isolated human hepatocytes are the best model for predicting adverse drug reactions. However, their preparation and use present the investigator with many variables that are beyond their control. These include operation continuity and timing, size and number of cut surfaces on liver tissue and the prior history of the patient. To exploit the potential of freshly isolated human hepatocytes a method is required to preserve the cells in their initial in vivo like state. This experimental pausing allows experiments to be prioritised at convenient times of the day., Methods: A novel approach for selecting viable human hepatocytes by functional attachment to a gelatin gel is described rather than relying on their physical characteristics. The cells are preserved as a monolayer on the semi-solid support at 10°C as single spherical entities., Results: The hepatocytes can be released into suspension, when required, by a temperature transition to 37°C for 20min. The cells can be used in suspension or as a monolayer. The length of preservation depends upon the source tissue. Hepatocytes from normal liver can be maintained for at least 4days and demonstrated to have the same level of CYP3A4 and the enzymes involved in glucuronidation and sulphation as freshly isolated cells. Cells from fatty liver, attached to gelatin, vary in their preservation time but it is at least 24h and so confluent monolayers, that survive at 37°C can be generated the following day., Discussion: The technique enables freshly isolated human hepatocytes to be used more effectively. They can be preserved in times of plenty so more experimentation is possible. Alternatively, with poorer fatty cells the initial attachment on gelatin enables confluent monolayers of lipid rich cells to be studied., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Absence of contrast on contrast enhanced MRI (CEMRI) and reduction in uterine volume at 6 months post-uterine artery embolisation (UAE) currently indicate the successful disruption of the fibroid blood supply by UAE. This study assesses whether (1)H MR spectroscopy ((1)H MRS) can also indicate the success of UAE., Method: 20 patients with symptomatic fibroids were randomised 1:1 to undergo UAE with either Gelfoam or Embospheres. CEMRI and spectra (1.5 T) were acquired pre-, 24-h and 6 months post-UAE. LCModel was used to detect significant levels of choline, creatine and lactate in fibroid spectra. Uterine volumes were measured and paired t tests (p < 0.05) assessed volume reduction over time. Qualitative assessments of CEMRI were performed., Results: Choline was detected in 17/18 spectra pre-UAE, 12/14 at 24-h and 6/16 at 6 months post-UAE. Choline was not detected in the 7/7 spectra available for the Embospheres group at 6 months. These fibroids were non-enhancing on CEMRI and associated with a significant reduction in mean uterine volume at 6 months (mean/min/max 396.5/84.1/997.5 cm(3), p = 0.003). Choline was detected in 6/9 fibroid spectra available for the Gelfoam group at 6 months. Of these fibroids, four demonstrated persistent enhancement on CEMRI and two were non-enhancing. This group did not demonstrate significant uterine volume reduction (mean/min/max 117.2/-230.6/382.6 cm(3), p = 0.15). The negative minimum value indicates fibroid growth., Conclusions: This study has demonstrated the potential of (1)H MRS to provide an additional marker of the success of UAE.

Background: Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD., Methods: Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining., Results: In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs., Conclusions: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.

Background: Air-saline transcranial Doppler is nowadays the first-choice examination to identify right-to-left shunt. To increase right-to-left shunt detection in echocardiography, cardiologists also use air-gelatin mixtures, which are more stable, more echogenic, and easier to be prepared., Aim: We assessed the sensitivity of air-gelatin compared with air-saline for transcranial Doppler right-to-left shunt detection., Methods: Air-saline transcranial Doppler, during unilateral middle cerebral artery monitoring at rest and after Valsalva maneuver, was performed in patients referred to our neurosonology laboratory for right-to-left shunt detection. The same transcranial Doppler protocol was repeated with air-gelatin. To consider transcranial Doppler positive for cardiac right-to-left shunt, at least one embolic signal had to be detected within 20″ from contrast injection. Later signals were interpreted of pulmonary origin. Trans-thoracic echocardiography was repeated with both air-saline and air-gelatin., Results: A total of 97 patients were enrolled; 46 had negative transcranial Doppler for cardiac right-to-left shunt with both air-saline and air-gelatin; out of these, four patients with air-saline plus two more patients with air-gelatin presented late, isolated microemboli, slightly more numerous with air-gelatin: these were interpreted as pulmonary shunts and confirmed with trans-thoracic echocardiography. In 28 patients with already early positive air-saline transcranial Doppler at rest, air-gelatin induced a marked right-to-left shunt increase, facilitating its visualization at trans-thoracic echocardiography. In 23 patients in whom air-saline transcranial Doppler was negative at rest and positive for cardiac right-to-left shunt only after Valsalva maneuver, air-gelatin was able to reveal shunt also at rest., Conclusions: Air-gelatin increases right-to-left shunt detection sensitivity with transcranial Doppler in particular at rest, even in patients in whom air-saline mixture fails to identify the shunt. The choice of air-gelatin mixture should be considered for multicentric, clinical, and research trials., (© 2016 World Stroke Organization.)

Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.

Purpose: To assess the effectiveness and safety of uterine artery embolization (UAE) using progressively larger calibrated gelatin sponge particles for symptomatic uterine fibroids., Material and Methods: Thirty patients with symptomatic uterine fibroids underwent UAE. Calibrated gelatin sponge particles were used in all patients, beginning with 355-500 μm particles, progressively increasing to 500-710 μm and finally to 710-1000 μm particles. Changes in tumor, uterine volume, and tumor infarction rate were assessed using pelvic magnetic resonance imaging (MRI). The level of complication, improvement of clinical symptoms, and Uterine Fibroid Symptom and Quality of Life (UFS-QOL) score were assessed., Results: MR imaging revealed the mean largest tumor volume reduction was 56.23 ± 16.25% at three months and 72.61 ± 14.47% at 12 months after the procedure. 100% infarction of the dominant fibroids was 91.27 ± 5.02% at three months and 96 ± 5.20% at 12 months after the procedure. Menorrhagia improved markedly in all 23 patients. Bulk-related symptoms improved in 12 (92.30%) of 13 patients. The baseline UFS-QOL score was 43.13 and improved to 11.88 (p < 0.001). No major complications were observed., Conclusion: UAE using progressively larger calibrated gelatin sponge particles is an effective and safe treatment for symptomatic uterine fibroids.

A novel surgical sealant was developed by partially modifying the amino groups of Alaska pollock-derived gelatin derivative with cholesteryl groups (Chol-apGltn), which was combined with the crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG). The burst strength of the resultant sealant was tested using fresh porcine aorta as an adherend. The Chol-apGltn/4S-PEG sealant cured within 25.4 ± 2.0 s. Burst strength increased with increasing degree of Chol modification up to a maximum value of 8.3 mol% (8.3Chol-apGltn). The highest burst strength of the 8.3Chol-apGltn/4S-PEG sealant was 341.3 ± 77.5 mmHg, which was 3.5- and 11.6-fold higher than that of the original apGltn/4S-PEG and commercial fibrin sealants, respectively. The 8.3Chol-apGltn/4S-PEG sealant swelled only slightly in solution (1.1-fold as compared to commercially prepared sealant). Furthermore, tissue migration into the 8.3Chol-apGltn/4S-PEG sealant and subsequent biodegradation was observed following implantation for 4-8 weeks. These results suggest that the 8.3Chol-apGltn/4S-PEG sealant has biomedical applications, including use in cardiovascular and thoracic surgery.

Despite all scientists efforts exerted over the past years, the ocular delivery of drugs remains a great challenge due to several barriers and hurdles faced by this kind of administration. The exploitation of gelatin that has a long history of safe use in pharmaceuticals and which is considered as a GRAS (Generally Regarded As Safe) material by the FDA was not fully achieved in this field. This review summarizes the recent studies and findings where gelatin-based micro- and nanoparticles were used for successful ocular delivery aiming at drawing the attention of researchers and scientists to this valuable biomaterial that has not been fully explored.

Gelatin sponge particles are commonly used in the conventional transarterial chemoembolization (c-TACE) as an adjuvant embolizing agent for hepatocellular carcinoma (HCC). However, there are few reports regarding the clinical applications of gelatin sponge microparticles (GSMs) as a main embolizing agent in the treatment of HCC. This retrospective study aim to evaluate the efficacy and safety of patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC treated with intra-arterial injection of 350 to 560 μm GSMs mixed with anticancer agents.Twenty-four patients with unresectable BCLC stage B HCC without any prior treatment underwent transarterial chemoembolization with gelatin sponge microparticles (GSMs-TACE) of diameter 350 to 560 μm mixed with lobaplatin. The mixture was injected into tumor-feeding arteries until the sluggish flow in selective artery. Safety was measured by assessing complication rate, and efficacy was reflected by assessing response to mRECIST therapy and overall survival. The survival rate was calculated using the Kaplan-Meier method.All 24 BCLC stage B HCC patients showed good tolerance to the procedure. The mean follow-up period was 27 months and mean number of TACE treatments per patient was 3.7 sessions (range 1-10) during the follow-up period. Postprocedure complications were mild and treated by symptomatic treatment. Six months and 1 year overall survival rates were 100% and 87.5%, respectively. Overall median survival time was 25 months (95%CI: 21.06-28.95 months).GSMs-TACE is a safe and effective method for BCLC stage B HCC patients., Competing Interests: The authors have no funding and conflicts of interest to disclose.

The present study discusses about the preparation and characterization (thermal, mechanical, and electrical) of the genipin-crosslinked gelatin emulgels. Emulgels have gained importance in recent years due to their improved stability than emulsions and ability to control the drug release. Mustard oil was used as the representative oil. A decrease in the enthalpy and entropy of the formulations was observed with the increase in the oil fraction. The mechanical studies suggested formation of softer emulgels as the oil fraction was increased. As the proportion of the oil fraction was increased in the emulgels, there was a corresponding increase in the impedance. The drug release properties from the emulgels were also studied. Ciprofloxacin was used as the model antimicrobial drug. The drug release was higher from the emulgels whose electrical conductivity was higher.

Introduction: Uncontrolled haemorrhage as a result of trauma remains a significant surgical challenge, accounting for approximately 25-40% of trauma-related mortality. A wide range of local internal haemostatic agents have been developed to help achieve intra-cavity control of bleeding, with choice of agent influenced by the circumstances and nature of the haemorrhage. Trauma patients are frequently coagulopathic, so products that incorporate pro-coagulant technology and thereby act independently of the clotting cascade may be more effective in these settings. A range of products that utilise thrombin and fibrinogen to promote local haemostasis at intra-cavity bleeding points are available or in development, including fibrin glues (e.g. Tisseel®/Tissucol® and Evicel®/Crosseal®/Quixil®), fibrin sealant patches (e.g. TachoSil®) and products based on a gelatin-thrombin haemostatic matrix (e.g. FloSeal®)., Materials and Methods: This systematic review was performed to assess all peer-reviewed evidence of product efficacy., Results: Fibrin sealant patches have shown haemostatic efficacy in a variety of surgical procedures and appear to offer practical advantages over liquid fibrin glues. Existing evidence suggests that patch products enable delivery of pro-coagulants to defined areas with less chance of dilution and/or displacement by blood flow, but they require a pressure buttress for a suitable amount of time to achieve good results after trauma., Conclusions: Our experience, supported by other reports in the literature, suggests the use of such fibrin patches may provide an effective option in helping to control haemorrhage after trauma. However, there is a general paucity of clinical data for intra-cavity haemostatic agent use, with the majority of data being based on animal models and case reports. Further clinical evidence, ideally including comparative studies between different agents, would be beneficial in helping guide surgeon choice to the most appropriate products to use in trauma settings.

The aim of this study was to evaluate commercial gelatin in the total replacement of bovine heart in feed training of "pacamã" Lophiosilurus alexandri in different water salinities. A completely randomized experimental design, in a 2 × 3 factorial arrangement, was performed using two types of moist ingredients (bovine heart and gelatin) and three water salinities (0.0; 2.0 and 4.0 g of salt L(-1)) with three replications. Juveniles (2.39 ± 0.08 cm standard length and 0.20 ± 0.03 g of weight) were conditioned to accept commercial diets by the technique of the gradual transition of ingredients. At the end of 36 days no differences were observed to weight gain, length gain and specific growth rate. The feed training efficiency was better (P < 0.05) with the gelatin use, 100.0%. There was a negative effect of salinity on the survival rate and management efficiency in the concentration of 4 g of salt L(-1), with values of 58.6 ± 12.0 % and 58.0 ± 12.0 %, respectively. Lophiosilurus alexandri juveniles could be feed-trained to accept commercial diets with gelatin in the total replacement of bovine heart in freshwater or salinity of 2 g of salt L(-1).

Unlabelled: The aim of the study was to investigate the immune-modulatory potential of commercially available PTFE and polyester vascular grafts with and without gelatine-coating. The biomaterial-cell-interaction was characterized by changes of established parameters such as PMN-related receptors/mediators, phagocytosis potential and capacity as well as the effect of an additional plasma-dependent modulation., Material and Methods: By means of a standardized experimental in vitro model, various vascular graft material (PTFE/polyester/uncoated/gelatine-coated) was used for incubation with or without plasma and co-culturing with human neutrophile granulocytes (PMN) followed by analysis of representative receptors and mediators (CD62L, CD11b, CXCR2, fMLP-R, IL-8, Elastase, LTB4). Oxidative burst assessed phagocytosis capacity., Results: Comparing the vascular grafts, un-coated PTFE induced the lowest magnitude of cell stimulation whereas in case of gelatine-coating, cell response exceeded those of the other vascular grafts. This was also found comparing the polyester-based prosthetic material. Gelatine-coated polyester led to a more pronounced release of elastase than gelatine-coated PTFE and the uncoated materials. The results of oxidative burst indicated a reduced phagocytosis capacity in case of gelatine-coated polyester. Plasma incubation did also provide an impact on the cellular response. While in case of gelatine-coating, PMN-related receptor stimulation became lower, it increased by native polyester. The latter one did also induce more mediators such as IL-8 and LTB4 than gelatine-coated material., Conclusions: There have been no extensive data on cell-cell interactions, cytokines and general histo-/hemocompatibility of human cells by the new generation of vascular grafts. It remains still open whether healing process and infectious resistance can be compromised by material-dependent over-stimulation or reduced phagocytosis potential of the immune cells of the primary unspecific immune response induced by gelatine-coated materials.

Objective: To explore the effectiveness of absorbable hemostatic fluid gelatin in preventing postoperative cerebrospinal fluid leakage., Methods: The clinical data of 17 patients with dura mater tear were retrospectively analyzed from March to September in 2003. There were 16 males and 1 female, aged from 16 to 67 years old with an average of (39.6 ± 15.4) years. The injury site was at cervical vertebrae in 1 case, thoracic vertebrae in 9 cases, thoracolumbar junction in 4 cases, lumbar vertebrae in 3 cases. There were burst fracture in 4 cases and fracture-dislocation in 13 cases. According to ASIA grade, 12 cases were grade A, 2 cases were grade B, 2 cases were grade D, 1 case were grade E. Two cases caused by traffic accident, 10 by high falling, 4 by heavy parts crash, 1 by stairs fell during the earthquake. Absorbable hemostatic fluid gelatins were used to plug the dura mater tear,in order to prevent postoperative cerebrospinal fluid leakage. Postoperative drainage were recorded every day., Results: Of 17 patients, 15 cases did not develop with cerebrospinal fluid leakage. Two cases develop with cerebrospinal fluid leakage after operation and their drainage were removed at 6 to 7 days after operation. In all cases, no complications related with cerebrospinal fluid leakage occurred, such as headache, dizzy, fever,neck resistance, rash, incision disunion, incision infection, hematoma, neurologic symptoms aggravation. No abnormal phenomena was found on incision surrounding at follow-up of 9 months., Conclusion: Using absorbable hemostatic fluid gelatin to plug the dura mater tear during operation is an effective method in preventing postoperative cerebrospinal fluid leakage.

Background: Since the first liver transplantation, pretransplantation or post-transplantation renal problems are still among the main causes of mortality and morbidity. The aim of this study was to evaluate the effects of fluid replacement solutions used intraoperatively on renal functions in elective living-donor liver transplantation., Methods: After Ethics Committee approval, informed consents were obtained from patients. Patients with normal renal functions and scheduled for elective living-donor-liver transplantation were included in the study. Patients were randomly allocated to infusion with 6% hydroxyehylstarch 130/40 (HES group) and 4% Gelofusine (GEL group). Blood samples were obtained before the induction of anesthesia (baseline), at the end of the operation, and postoperative days 1 and 4. Different estimated glomerular filtration rate (eGFR) formulas using creatinine (modification of renal disease, chronic kidney disease-epidemiology collaboration and Cockraud Gault) were used to calculate the eGFR., Results: Thirty-six patients were included in the study (GEL group = 18; HES group = 18). Patient characteristics, modified end stage liver disease-Child Pugh score, American Society of anaesthesiologist scores, and intraoperative data were similar between groups. Postoperative measurements showed that creatinine was significantly higher in the GEL group compared with the baseline, which was not the case for the HES group. Similarly, postoperative eGFR levels, as measured using MDRD and CKD-EPI, were found to be significantly lower in the GEL group. Postoperative urine albumin:creatinine ratios were significantly higher in the GEL group compared with baseline. Total crystalloid amount used, colloid, blood, fresh frozen plasma values, extubation, and intensive care unit (ICU) and hospital stay were similar in both groups. Postreperfusion syndrome developed in 6 patients in each group., Conclusion: In conclusion, Gelofusine seem to cause more impairment in renal functions in elective living-donor liver transplantation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Compare the effects on inflammatory (TNF-α, IL-6, IL-8 and IL-10) and immunologic (CD3(+), CD4(+), CD8(+), CD11b(+), CD16(+)/56(+) T cells and total lymphocyte concentration) variables of hydroxyethyl starch 130/0.4, 4% modified fluid gelatin, or crystalloid when used as volume replacement fluids for acute normovolemic hemodilution (a blood conservation technique) in coronary artery bypass graft patients., Methods: Thirty patients undergoing coronary artery bypass graft surgery were randomized to receive Isolyte S® (Group ISO), 6% hydroxyethyl starch 130/0.4 (Group HES) or 4% modified gelatin solution (Group GEL) for acute normovolemic hemodilution. Blood samples were taken immediately after induction of anaesthesia (T0), and 2 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) after separation from cardiopulmonary bypass. TNF-α, IL-6, IL-8 and IL-10 levels were determined with commercially available ELISA kits. CD3(+) (mature T cells), CD4(+) (T helper cells), CD8(+) (suppressor cytotoxic T cells), CD16(+)/56(+) (natural killer lymphocytes), and CD11b(+) (Mac-1, adhesion receptor) levels were measured using flow-cytometry reagents. The CD4(+):CD8(+) ratio was calculated., Results: Between-group comparisons showed significantly higher levels of TNF-α at T1 (2 h after weaning from cardiopulmonary bypass) in Group HES compared to Group ISO (p=0.003). IL-8 was significantly lower in Group HES than Group GEL at T1 (p=0.0005). IL-10 was significantly higher in Group HES than in Group GEL at T1 (p=0.0001). The CD4(+):CD8(+) ratio in Group ISO was significantly lower than that in Group HES at T2 (p=0.003). CD11b(+) levels in Group HES were also higher than those in Group GEL and group ISO at T2, but not significantly. CD16/56(+) levels in Group HES were higher than those in Group GEL at T2 (p<0.003). No excessive hemorrhage occurred in any patient. Mediastinal drainage during the first 24 h after surgery in Group HES (347±207 mL) was not significantly different from that of Group GEL (272±177 mL) or Group ISO (247±109) (p>0.05)., Conclusion: Hydroxyethyl starch 130/0.4 reduced pro-inflammatory responses and increased anti-inflammatory responses to a greater degree than gelatin solution and isolyte S®. The use of hydroxyethyl starch, compared to gelatin solution and isolyte S®, resulted in less decrease in the CD4(+):CD8(+) ratio, suggesting less immunosuppression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The possibility to use a suspended tridimensional matrix as scaffolding for re-epithelialization of in vitro cutaneous wounds was investigated with the aid of a human in vitro wound healing model based on viable full thickness skin. Macroporous gelatin microcarriers, CultiSpher-S, were applied to in vitro wounds and cultured for 21 days. Tissue sections showed incorporation of wound edge keratinocytes into the microcarriers and thicker neoepidermis in wounds treated with microcarriers. Thickness of the neoepidermis was measured digitally, using immunohistochemical staining of keratins as epithelial demarcation. Air-lifting of wounds enhanced stratification in control wounds as well as wounds with CultiSpher-S. Immunohistochemical staining revealed expression of keratin 5, keratin 10, and laminin 5 in the neoepidermal component. We conclude that the CultiSpher-S microcarriers can function as tissue guiding scaffold for re-epithelialization of cutaneous wounds.

Articular cartilage has restricted self-regenerative capacity; therefore, treatment of cartilage lesions is a great challenge in the field of orthopedics. In the present study, we evaluate the enhancing effect of a transforming growth factor-beta 1 (TGF-β1)-immobilized scaffold, fabricated by incorporating TGF-β1-loaded gelatin microspheres into PLGA framework, on the differentiation of adipose-derived stem cells (ASCs) into chondrocytes. Significant increase in cell proliferation was observed in the TGF-β1-immobilized PLGA-gelatin scaffold, as compared with the ASC-seeded non-TGF-β1-immobilized PLGA-gelatin scaffold. When chondrogenic differentiation of ASCs was evaluated for both constructs, sulfated glycosaminoglycan (sGAG) content was significantly higher in the TGF-β1-immobilized scaffold. This study showed that ASCs containing the TGF-β1-immobilized scaffold better promoted cartilage regeneration in defective articular cartilage, which is assessed by histological observation. Based on the above results, we conclude that TGF-β1-immobilized PLGA-gelatin scaffold seeded with ASCs considerably enhances the quality of the tissue-engineered cartilage, therefore, advancing the field of cartilage tissue engineering.

Delayed healing or non-union of skeletal fractures are common clinical complications. Ibandronate is a highly potent anti-catabolic reagent used for treatment of osteopenia and fracture prevention. We hypothesized that local application of ibandronate after fracture fixation may improve and sustain callus formation and therefore prevent delayed healing or non-union. This study tested the effect of local application of an ibandronate/gelatin sponge composite on osteotomy healing. A right-side distal-femoral osteotomy was created surgically, with fixation using a k-wire, in forty adult male rabbits. The animals were divided into four groups of ten animals and treated by: (i) intravenous injection of normal saline (Control); (ii) local implantation of absorbable gelatin sponge (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS), and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks the affected femora were harvested for X-ray photography, computed tomography (CT), biomechanical testing and histopathology. At both time-points the results showed that the calluses in both the ibandronate-treated groups, but especially in the IB+GS group, were significantly larger than in the control and GS groups. At four weeks the cross sectional area (CSA) and mechanical test results of ultimate load and energy in the IB+GS group were significantly higher than in other groups. Histological procedures showed a significant reduction in osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results indicate that local application of an ibandronate/gelatin sponge biomaterial improved early osteotomy healing after surgical fixation and suggest that such treatment may be a valuable local therapy to enhance fracture repair and potentially prevent delayed or non-union.

Background: Besides albumin, which is gained from human donors, synthetic colloids have been playing a dominant role in treating patients in shock and are standard therapy in intensive care units (ICU). Since the publication of large randomized controlled trials indicating negative effects on renal function, their use has been questioned, especially for hydroxyethyl starch products. The preliminary assumption that these side effects are only existent in first or secondary generation starch fluids was proven incorrect. In fact, the use of hydroxyethyl starch products in critically ill patients is prohibited by the European Medicines Agency., Current Discussion and Indications: Several methodological limitations exist in each of these trials that limit the evidence value of these investigations, although they served as the basis for the negative judgment of the European Medicines Agency. In addition, a large randomized controlled trial on the efficacy of gelatin is lacking. The use of colloids in ICU patients is indicated in cases where crystalloid volume therapy is inadequate., Conclusion: Especially during the first 6 h of sepsis, when aggressive volume therapy is decisive for patient outcome, colloids may be relevant to increase patient survival. The latest guideline on treatment with colloids has been published in the German S3 guideline "Intravascular volume therapy in adults."

Background: It has been suggested that perturbations in branched-chain amino acid (BCAA) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs. Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism, but there is limited evidence in humans., Objective: We hypothesize that a diet rich in BCAAs will increase BCAA catabolism, which will manifest in a reduction of fasting plasma BCAA concentrations., Methods: The metabolome of 27 obese women with metabolic syndrome before and after weight loss was investigated to identify changes in BCAA metabolism using GC-time-of-flight mass spectrometry. Subjects were enrolled in an 8-wk weight-loss study including either a 20-g/d whey (whey group, n = 16) or gelatin (gelatin group, n = 11) protein supplement. When matched for total protein by weight, whey protein has 3 times the amount of BCAAs compared with gelatin protein., Results: Postintervention plasma abundances of Ile (gelatin group: 637 ± 18, quantifier ion peak height ÷ 100; whey group: 744 ± 65), Leu (gelatin group: 1210 ± 33; whey group: 1380 ± 79), and Val (gelatin group: 2080 ± 59; whey group: 2510 ± 230) did not differ between treatment groups. BCAAs were significantly correlated with homeostasis model assessment of insulin resistance at baseline (r = 0.52, 0.43, and 0.49 for Leu, Ile, and Val, respectively; all, P < 0.05), but correlations were no longer significant at postintervention. Pro- and Cys-related pathways were found discriminant of whey protein vs. gelatin protein supplementation in multivariate statistical analyses., Conclusions: These findings suggest that BCAA metabolism is, at best, only modestly affected at a whey protein supplementation dose of 20 g/d. Furthermore, the loss of an association between postintervention BCAA and homeostasis model assessment suggests that factors associated with calorie restriction or protein intake affect how plasma BCAAs relate to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00739479., (© 2015 American Society for Nutrition.)

We herein present a case involving a 41-year-old woman in whom ultrasound examination revealed multiple liver hemangiomas more than 3 years ago. Follow-up ultrasound examination revealed that the masses had significantly increased; the largest was located in the right lobe (about 8.2 cm × 7.4 cm × 6.0 cm). Abdominal multidetector computed tomography revealed multiple well-circumscribed, heterogeneous, hypodense masses (largest, 6.4 cm × 6.3 cm × 5.0 cm) with significant contrast enhancement during the arterial and portal phases and with contrast wash-out and peripheral enhancement during the delayed phases. Magnetic resonance images demonstrated multiple well-circumscribed, heterogeneous, hypointense hepatic masses with significant contrast enhancement (largest, 6.4 cm × 6.5 cm × 5.1 cm); multiple enlarged porta lymph nodes; and multiple slightly enlarged retroperitoneal lymph nodes. Histological and immunohistochemical examination of the right mass biopsy specimen suggested a malignant neoplasm that had originated from a neuroendocrine cell type (grade 2 well-differentiated neuroendocrine carcinoma). After performing a systemic examination to exclude metastasis from an extrahepatic primary site, we considered that the masses had arisen from a primary hepatic neuroendocrine tumor with multiple liver metastases. The patient underwent transcatheter arterial chemoembolization using a combination of oxaliplatin (150 mg) mixed with one bottle of gelatin sponge particles (560-710 μm) and lipiodol (6 mL). Primary neuroendocrine tumors of the liver are extremely rare. This case is interesting because of the rarity of this neoplasm and previous misdiagnosis as multiple liver hemangiomas. Previously reported cases in the literature are also reviewed.

Objective: Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP., Method: Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected., Results: After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups., Conclusion: In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients., (© The Author(s) 2014.)

Purpose: Previously, we reported that the prepared resveratrol (RSV) loaded gelatin nanoparticles (GNPs) possessed enhanced anticancer effect than free RSV in non-small cell lung carcinoma cells and Swiss albino mice. The present study aims to explore the relevant mechanism of cell death induced by the combination of RSV-GNPs in NCI-H460 cells., Methods and Results: To increase its bioavailability and anticancer efficacy, we have encapsulated RSV-GNPs by Coacervation method. The detailed methods of preparation and characterization of RSV-GNPs were reported in our earlier publication. RSV-GNPs treated cells showed a further increased level of lipid peroxidative markers, i.e. TBARS and LHP in NCI-H460 cells. Activities of antioxidant enzymes SOD, CAT, GPx and GSH levels were decreased upon the treatment with RSV-GNPs in NCI-H460 cells. The nuclear fragmentation was evaluated by DAPI staining and data showed condensed apoptotic bodies upon treatment with the combination of RSV-GNPs compared to RSV alone treatment group. In addition, cell death induced by RSV-GNPs was mainly due to apoptosis which was characterized by a nuclear DNA fragmentation in a ladder-pattern was obtained from the genomic DNA analysis. Moreover, Western blotting analysis showed that apoptosis induced by RSV-GNPs is associated with the increased Bax, p53, p21, caspase-3 protein levels, and decreased Bcl-2 and NF-κB proteins expression, which indicates the involvement of mitochondria-dependent apoptosis in the anticancer efficacy of RSV-GNPs in NCI-H460 cells. It was also found that this enhanced anticancer efficacy of RSV-GNPs induced cell arrest in the G0/G1 phase of cell cycle., Conclusions: Taken together, the results of our study clearly suggested that the cell death induced by the combination of RSV-GNPs would involve alteration in expression of p53, p21, caspase-3, Bax, Bcl-2 and NF-κB, indicating oxidative mechanism in NCI-H460 cells. Based on these results, it is concluded that GNPs is an ideal way to deliver RSV because of its high loading efficiency and superior efficacy in NCI-H460 cells., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aims: In the critically ill patient, fluid loading is commonly done to stabilise hemodynamics and increase diuresis, whereas the absence of diuresis may predispose to harmful overloading. The goal of the current study was to evaluate the diuretic response and determinants thereof upon crystalloid and colloid fluid loading., Subjects and Methods: This is a substudy on 42 clinically hypovolemic, septic or non-septic patients without acute kidney injury, who were randomly assigned, after stratification for sepsis, to a 90-min fluid loading protocol with either 0.9% saline or a colloid solution (gelatin, hydroxyethyl starch 200/0.5 or albumin). Hemodynamics, biochemical parameters and diuresis were recorded. A response was defined by an increase in diuresis of >10% during fluid loading., Results: Diuresis increased more during saline than colloid infusion, together with a decline in colloid osmotic pressure (COP) of plasma and less increase in plasma volume and global hemodynamics with saline, at similar fluid balance. Nine patients (82%) receiving saline had a diuretic response, compared to 13 patients (42%) receiving colloids (P = 0.04), and the response was not predicted by underlying condition, global hemodynamics, volume of fluid infused and COP., Conclusion: In critically ill patients with clinical hypovolemia, diuresis increases more during saline than colloid fluid loading, only partly dependent of a fall in plasma COP.

The purpose of this study was to determine the effects of age, sex, body mass index (BMI), viscosity, and volume on esophageal motility using high-resolution manometry (HRM). Manometric studies were performed on 60 asymptomatic volunteers (27 men and 33 women, age: 19-56 years) while in a supine position. Manometric protocol included 10 water swallows (5 cc), 10 jelly swallows (5 cc), and 1 water swallow (20 cc). Evaluation of HRM parameters including length of proximal pressure trough (PPT length), distal latency (DL), contractile front velocity (CFV), distal contractile integral (DCI), and 4-second integrated relaxation pressure (IRP) was performed using MATLAB. Significant differences were noted in median IRP between water 5 cc (median 7.2 mmHg [range 5.5-9.6]), jelly 5 cc (median 6.0 mmHg [range 3.8-8.0]), and water 20 cc {(Median 4.8 mmHg [range 3.3-7.4]), P < 0.01}. DL were significantly different between water 5 cc, jelly 5 cc, and water 20 cc (P < 0.01), and in terms of PPT, proportions of small (2 cm ≤ < 5 cm) and large (5 cm≤) break for jelly 5 cc were significantly higher than those for the water 5 cc swallow (P < 0.05). Furthermore, DCI increased with age for water 5 cc, and a significant negative correlation was noticed between proportions of small break and BMI for water 5 cc. Manometric measurements vary depending on age, BMI, viscosity, and volume. These findings need to be taken into account in the interpretation of manometry results., (© 2014 International Society for Diseases of the Esophagus.)

Recent studies in zebrafish have shown that exposure to ethanol in tank water affects various behaviors, including locomotion, anxiety and aggression, and produces changes in brain neurotransmitters, such as serotonin and dopamine. Building on these investigations, the present study had two goals: first, to develop a method for inducing voluntary ethanol intake in individual zebrafish, which can be used as a model in future studies to examine how this behavior is affected by various manipulations, and second, to characterize the effects of this ethanol intake on different behaviors and the expression of hypothalamic orexigenic peptides, galanin (GAL) and orexin (OX), which are known in rodents to stimulate consumption of ethanol and alter behaviors associated with alcohol abuse. Thus, we first developed a new model of voluntary intake of ethanol in fish by presenting this ethanol mixed with gelatin, which they readily consume. Using this model, we found that individual zebrafish can be trained in a short period to consume stable levels of 10% or 20% ethanol (v/v) mixed with gelatin and that their intake of this ethanol-gelatin mixture leads to pharmacologically relevant blood ethanol concentrations which are strongly, positively correlated with the amount ingested. Intake of this ethanol-gelatin mixture increased locomotion, reduced anxiety, and stimulated aggressive behavior, while increasing expression of GAL and OX in specific hypothalamic areas. These findings, confirming results in rats, provide a method in zebrafish for investigating with forward genetics and pharmacological techniques the role of different brain mechanisms in controlling ethanol intake., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer-Peppas kinetic model with an R (2) of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).

Collagen and gelatin have been widely used in the food, pharmaceutical, and cosmetic industries due to their excellent biocompatibility, easy biodegradability, and weak antigenicity. Fish collagen and gelatin are of renewed interest, owing to the safety and religious concerns of their mammalian counterparts. The structure of collagen has been studied using various modern technologies, and interpretation of the raw data should be done with caution. The structure of collagen may vary with sources and seasons, which may affect its applications and optimal extraction conditions. Numerous studies have investigated the bioactivities and biological effects of collagen, gelatin, and their hydrolysis peptides, using both in vitro and in vivo assay models. In addition to their established nutritional value as a protein source, collagen and collagen-derived products may exert various potential biological activities on cells in the extracellular matrix through the corresponding food-derived peptides after ingestion, and this might justify their applications in dietary supplements and pharmaceutical preparations. Moreover, an increasing number of novel applications have been found for collagen and gelatin. Therefore, this review covers the current understanding of the structure, bioactivities, and biological effects of collagen, gelatin, and gelatin hydrolysates as well as their most recent applications.

Objective: Gut barrier is a functional unit organized as a multi-layer system and its multiple functions are crucial for maintaining gut homeostasis. Numerous scientific evidences showed a significant association between gut barrier leaking and gastro-intestinal/extra-intestinal diseases., Materials and Methods: In this review we focus on the relationship between gut barrier leaking and human health. At the same time we speculate on the possible new role of gut barrier protectors in enhancing and restoring gut barrier physiology with the final goal of promoting gut health., Results: The alteration of the equilibrium in gut barrier leads to the passage of the luminal contents to the underlying tissues and thus into the bloodstream, resulting in the activation of the immune response and in the induction of gut inflammation. This permeability alteration is the basis for the pathogenesis of many diseases, including infectious enterocolitis, inflammatory bowel diseases, irritable bowel syndrome, small intestinal bacterial overgrowth, celiac disease, hepatic fibrosis, food intolerances and also atopic manifestations. Many drugs or compounds used in the treatment of gastrointestinal disease are able to alter the permeability of the intestinal barrier. Recent data highlighted and introduced the possibility of using gelatin tannate, a mucosal barrier protector, for an innovative approach in the management of intestinal diseases, allowing an original therapeutic orientation with the aim of enhancing mucus barrier activity and restoring gut barrier., Conclusions: These results suggest how the mucus layer recovering, beside the gut microbiota modulation, exerted by gut barrier protectors could be a useful weapon to re-establish the physiological intestinal homeostasis after an acute and chronic injury.

Oral administration of perioperative analgesia to laboratory mice is beneficial compared with administration by injection. The mice become less stressed when allowed to voluntarily ingest the drug in a palatable feed item and it results in high and long-lasting serum concentrations of the drug. We have previously demonstrated sticky nut and chocolate paste to be well-liked by mice and readily ingested in most cases. However, a disadvantage with nut and chocolate paste is its high content of fat and sugar, which may have undesirable effects in some experimental models. Alternatively, a delivery system using an aqueous gel may serve as a supplementary source of fluid post-operatively and as a vehicle for analgesic drugs. In the present study, we investigated the willingness of the mice to ingest a commercially available gel, by measuring the duration from introduction of the gel to first ingestion, as well as the amount ingested overnight. Furthermore, buprenorphine in two different concentrations (5 and 15 µg/mL) was mixed in the gel and the resulting serum concentrations of buprenorphine were investigated. The aqueous gel was ingested by the mice, but their willingness was low and did not increase over time. The serum concentrations of buprenorphine were similar to, or higher than, those following a subcutaneous injection (0.1 mg/kg body weight), but the variation was considerably higher. In conclusion, aqueous gel may serve as a relevant vehicle for the voluntary ingestion of buprenorphine in mice, but the willingness of the mice to ingest the gel needs to be improved., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

The aim of this research was to prepare and characterize alginate-chitosan mucoadhesive microparticles containing puerarin. The microparticles were prepared by an emulsification-internal gelatin method using a combination of chitosan and Ca2+ as cationic components and alginate as anions. Surface morphology, particle size, drug loading, encapsulation efficiency and swelling ratio, in vitro drug released, in vitro evaluation of mucoadhesiveness and Fluorescence imaging of the gastrointestinal tract were determined. After optimization of the formulation, the encapsulation efficiency was dramatically increased from 70.3% to 99.2%, and a highly swelling ratio was achieved with a change in particle size from 50.3 ± 11.2 μm to 124.7 ± 25.6 μm. In ethanol induced gastric ulcers, administration of puerarin mucoadhesive microparticles at doses of 150 mg/kg, 300 mg/kg, 450 mg/kg and 600 mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration. Consequently, significant changes were observed in inflammatory cytokines, such as prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and interleukin1β (IL-1β), in stomach tissues compared with the ethanol control group. In conclusion, core-shell type pH-sensitive mucoadhesive microparticles loaded with puerarin could enhance puerarin bioavailability and have the potential to alleviate ethanol-mediated gastric ulcers.

This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Sutures, hemoclips, and electrocautery are the primary mechanisms used to achieve hemostasis during gynecologic surgery, but in situations in which these are inadequate or not feasible, an array of hemostatic agents are available to help achieve hemostasis. These agents include physical agents such as cellulose, collagen, or gelatin products as well as biologic agents such as thrombin and fibrin products. Limited data are available on many of these agents, although their use is increasing, sometimes at high costs. In gynecologic surgery, hemostatic agents are likely most effective when used in areas of oozing or slow bleeding and as an adjunct to conventional surgical methods of hemostasis.

Chondroprogenitor cells encapsulated in a chondrogenically supportive, three-dimensional hydrogel scaffold represents a promising, regenerative approach to articular cartilage repair. In this study, we have developed an injectable, biodegradable methacrylated gelatin (mGL)-based hydrogel capable of rapid gelation via visible light (VL)-activated crosslinking in air or aqueous solution. The mild photocrosslinking conditions permitted the incorporation of cells during the gelation process. Encapsulated human-bone-marrow-derived mesenchymal stem cells (hBMSCs) showed high, long-term viability (up to 90 days) throughout the scaffold. To assess the applicability of the mGL hydrogel for cartilage tissue engineering, we have evaluated the efficacy of chondrogenesis of the encapsulated hBMSCs, using hBMSCs seeded in agarose as control. The ability of hBMSC-laden mGL constructs to integrate with host tissues after implantation was further investigated utilizing an in vitro cartilage repair model. The results showed that the mGL hydrogel, which could be photopolymerized in air and aqueous solution, supports hBMSC growth and TGF-β3-induced chondrogenesis. Compared with agarose, mGL constructs laden with hBMSCs are mechanically stronger with time, and integrate well with native cartilage tissue upon implantation based on push-out mechanical testing. VL-photocrosslinked mGL scaffold thus represents a promising scaffold for cell-based repair and resurfacing of articular cartilage defects.