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The present study was aimed at isolating endophytic fungi from the Algerian medicinal plant Salicornia arabica and analyzing its antifungal and antibacterial effects. The morphological analysis allowed us to identify endophyte isolates at the genus level as belonging to 8 different genera, Aureobasidium sp., Ulocladium sp., Acremonium sp., Stemphylium sp., Penicillium sp., Aspergillus sp., Phoma sp., and Chrysosporium sp. with frequency percentages 6.7%, 13.3%, 20%, 13.3%, 13.3%, 13.3%, 6.7%, 6.7%, respectively. The antimicrobial activity was caried out using the agar plug diffusion method. The three isolates of the genus Acremonium sp. were highly active against all tested bacteria except Enterococcus faecalis. Comparison of the means of inhibition zones of the active isolates showed that the three fungal isolates of Acremonium were the most active, followed by Chrysosporium sp., Penicillium sp.1, Aureobasidium sp., Stemphylium sp.1, Penicillium sp. .2, and Ulocladium sp.2. The widest zones of inhibition were 22.33 and 20.33mm for Acremonium sp.3, 18.33 and 15.33mm for Aureobasidium sp., 19.33mm for Penicillium sp.1, and 19 and 15mm for Stemphylium sp.1 obtained against Bacillus cereus and Staphylococcus aureus bacteria, respectively. Regarding the antifungal activity, the best inhibitory activity was 80 and 64.70% obtained with the isolate Penicillium sp.2 against Fusarium oxysporum f.sp. ciccri and Fusarium oxysporum f.sp. albedinis, respectively, and of 63.29 and 58% observed against Phytophthora infestans and Fusarium oxysporum f.sp. ciccri, respectively, with the endophytic isolate Aspergillus sp.2. These results indicated the possible prospect of endophytes fungi isolated from Salicornia arabica as a promising resource of antimicrobial compounds and in the quest for the potential starting points for the development of new antibiotics.

Unilateral right-sided varicocele is a rare and warning condition that should hint at a serious retroperitoneal disease such as renal cell neoplasm. Furthermore, its thrombosis is such an unusual entity that only a few cases have been described. We review the literature and report, to our knowledge, the second case of acute scrotal pain caused by unilateral right-sided varicocele thrombosis complicating an ipsilateral epididymo-orchitis, with no underlying coagulopathy or abdominal neoplasm, to illustrate the clinical, morphologic and therapeutic features of this entity.

Iman A Basheti,1 Yara B Salhi,1 Mariam M Basheti,2 Salim A Hamadi,3 Walid Al-Qerem41Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan; 2Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmacology & Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan; 4Department of Pharmacy, Al-Zaytoonah University of Jordan, College of Pharmacy, Amman, JordanIntroduction: Pharmacists can have a valuable role in educating patients on correct inhaler technique leading to improved asthma management. Rural areas can benefit from the role of the pharmacist considering the barriers found in attending primary health-care facilities.Objectives: This study aimed to assess the impact of inhaler technique education delivered by pharmacists on patients’ inhaler technique, Asthma Control Test (ACT) score, forced expiratory volume in the first 1 second (FEV1%), and reliever use (puffs/day).Methods: A pre–post interventional study was conducted over 6 months from February 2017 to July 2017 in rural areas in Jordan. Asthma patients visiting respiratory clinics and using metered dose inhaler (MDI) or turbuhaler (TH) controlled medication were randomly recruited. Inhaler technique was assessed via published checklists. The ACT, FEV1%, and reliever use (puffs/day) were assessed. Patients were educated on inhaler technique via demonstration with return demonstration education. All assessments were repeated 3 months post education.Results: A total of 103 (TH, n=44; MDI, n=59) patients were recruited (mean age=46.5±13.5), 74% females. Patients reported an overuse of their reliever (5.1±4.2 puffs/day). Only 2 patients (1.9%) had well-controlled asthma, while the rest had either moderately (19.4%) or poorly (78.6%) controlled asthma. Patients using the MDI achieved 3.03±4.30 ACT score improvement (p

The measurement of oil reservoirs and their performance with hydrocarbon reservoirs is used to distinguish the properties of reservoir fluids, which is significant in various reservoir studies. As a result, in the various oil industries, adopting the appropriate methods to obtain accurate property values is very important. The current paper is about a case study of the BUZURGAN Oilfield and how the PVTp software was used to predict phase activity and physical properties. To understand the properties of fluids for the reservoir and phase behavior, the black oil model and the equation of state (EoS) model are used. (Glaso) correlation is used to calculate the bubble point strain, solubility, and formation volume factor. The Beal's correlation was also used to measure viscosity, while the equation of state (EoS) model was used to determine phase behavior and density. Furthermore, the properties of PVT were discovered using the software, and the results were compared to laboratory analysis of PVT, with suitable models being displayed. According to the findings, the used model has the highest saturation pressure, which was chosen for use in reservoir management processes and the preparation of a geological model to reflect the field later. It is clear that the program is appropriate due to the accurate dependence of PVT measurements on laboratory tests in the case that tests are required during the reservoir's productive existence.

SUMMARY Eighteen cases of transposition of the male external genitalia have been reviewed. The atiology of the condition is discussed. A new case is presented and the method of its surgical correction described. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether an association exists between health care professionals’ (HCPs) asthma knowledge and inhaler technique demonstration skills. Methods: HCPs’ asthma knowledge and inhaler technique demonstration skills were assessed at baseline at an inter-professional educational workshop focusing on asthma medication use. Asthma knowledge was assessed via a published questionnaire. Correct inhaler technique for the three inhalers, the Accuhaler, Turbuhaler and pressurized Metered Dose Inhaler (pMDI) was assessed using published checklists. Results: Two hundred HCPs agreed to participate: 10 specialists (medical doctors specialized in respiratory diseases) (5%), 46 general practitioners (23%), 79 pharmacists (39%), 15 pharmacists’ assistants (8%), 40 nurses (20%) and 10 respiratory therapists (5%). Backwards stepwise multiple regression conducted to determine predictors of HCPs’ inhaler technique, showed that out of many independent variables (asthma knowledge score, profession, age, gender, place of work, years in practice and previous personal use of the study inhaler/s), asthma knowledge score was the only variable showing significant association with inhaler technique (R2=0.162, p

The authors report one case of a seminal vesicle cyst. They discuss this pathology and its relation to ureteral ectopy, as well as the therapeutic options for these entities. They present their experience in the resolution of this case. [Copyright &y& Elsevier]

Therapeutic drug monitoring is used to ensure that medications are prescribed and administered according to safe doseage advice and for the purpose of achieving the desired therapeutic effects in patients. Several methods are used to perform therapeutic drug monitoring. However, there is insufficient evidence to currently support therapeutic drug monitoring of Valproic acid using salivary samples. The aim of this paper is to determine the feasibility of using salivary samples as a substitute for plasma samples for therapeutic drug monitoring of Valproic acid. In this study a total of 23 patients participated, with the mean age of 33.39. Salivary and plasma samples were collected and analysed to determine the peak and trough concentrations of Valproic acid for comparison between the two methods. Calibrated LC- MS/ MS was used to measure Valproic acid levels. Statistical analyses were performed using ANOVA test and ethical approval was obtained prior to sample collection. The results showed that saliva Valproic acid levels were less than that of plasma levels. There was no significant correlation between saliva and plasma level of Valproic acid (P>0.05). However, there was a significant correlation between the area under the curve for both saliva and plasma Valproic acid (P<0.05). Creatinine clearance was significantly correlated with peak plasma levels of Valproic acid (P<0.05). Albumin was significantly correlated with plasma levels of Valproic acid. There was also a significantly positive and moderate relationship between Log Saliva Cmax and Log plasma free Valproic acid concentration (r=0.76, p<0.018). In conclusion, saliva samples can be used as a substitute for plasma samples in the therapeutic drug monitoring of Valproic acid., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: There is a scarcity of evidence regarding the real-world effectiveness of coronavirus disease 2019 (COVID-19) vaccines. This was the first study to evaluate the effectiveness of four types of vaccines against asymptomatic and symptomatic infection, and COVID-19 outcomes among the general population., Methods: This was a matched comparison group quasi-experimental study conducted in Jordan between 1 January and 29 August 2021. In the first part of the study, 1200 fully vaccinated individuals were matched with 1200 unvaccinated control participants. In order to measure vaccine effectiveness, the infection rates of both vaccinated and unvaccinated groups were calculated. The second part of the study included measuring specific anti-SARS CoV-2 immune cells and antibodies., Results: BNT162b2 (Pfizer, New York, NY, USA) showed a significantly higher effectiveness against asymptomatic COVID-19 infection (91.7%) and hospitalization (99.5%) than BBIBP-CorV (Sinopharm, Beijing, China) (88.4% and 98.7%, respectively) and ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) (84.3%, and 98.9%, respectively). The effectiveness rates of the Sputnik V (Gamaleya Research Institute, Moscow, Russia) vaccine against asymptomatic, symptomatic, and hospitalization were 100%, 100%, and 66.7%, respectively. The highest median anti-spike (S) IgG values were seen in individuals who received BNT162b2 (2.9 AU/mL) and ChAdOx1 nCoV-19 (2.8 AU/mL) vaccines. The levels of anti-S IgG were significantly decreased after 7 months of vaccination with BNT162b2 and BBIBP-CorV. There were significant decreases in the median number of neutralizing antibodies one month and seven months after receiving BNT162b2 (from 88.5 to 75.2 4 Bioequivalent Allergen Unit per milliliter/mL), BBIBP-CorV (from 69.5 to 51.5 BAU/mL), and ChAdOx1 nCoV-19 (from 69.2 to 58.BAU/mL) vaccines. The highest percentage of T cells specific to COVID-19 vaccine was found in individuals who received BNT162b2 (88.5%)., Conclusion: All four vaccines evaluated in this study showed effectiveness against asymptomatic COVID-19 infection, symptomatic infection, hospitalization, and death. Furthermore, BNT162b2, BBIBP-CorV, and ChAdOx1 nCoV-19 induced high levels of immunology markers within one month of vaccination.

Tailor-made and designed micro- and nanocarriers can bring significant benefits over their traditional macroscopic counterparts in drug delivery applications. For the successful loading and subsequent release of bioactive compounds, carriers should present a high loading capacity, trigger release mechanisms, biodegradability and biocompatibility. Hydrophobic drug molecules can accumulate in fat tissues, resulting in drawbacks for the patient's recovery. To address these issues, we propose to combine the advantageous features of both host molecules (cyclodextrin) and calcium carbonate (CaCO 3 ) particles in order to load hydrophobic chemicals. Herein, hybrid cyclodextrin-CaCO 3 micro- to nano-particles have been fabricated by combining Na 2 CO 3 solution and CaCl 2 solution in the presence of an additive, namely poly (vinylsulfonic acid) (PVSA) or glycerol (gly). By investigating experimental parameters and keeping the Na 2 CO 3 and CaCl 2 concentrations constant (0.33 M), we have evidenced that the PVSA or gly concentration and mixing time have a direct impact on the final cyclodextrine-CaCO 3 particle size. Indeed, by increasing the concentration of PVSA (5 mM to 30 mM) or gly (0.7 mM to 4 mM) or the reaction time (from 10 min to 4 h), particles with a size of 200 nm could be reached. Interestingly, the vaterite or calcite form could also be selected, according to the experimental conditions. We hypothesised that the incorporation of PVSA or gly into the precipitation reaction might reduce the nucleation rate by sequestering Ca 2+ . The obtained particles have been found to keep their crystal structure and surface charge after storage in aqueous media for at least 6 months. In the context of improving the therapeutic benefit of hydrophobic drugs, the developed particles were used to load the hydrophobic drug tocopherol acetate. The resulting particles are biocompatible and highly stable in a physiological environment (pH 7.4, 0.15 M NaCl). A selective release of the cargo is observed in acidic media (pH lower than 5).

Vancomycin is a commonly used antibiotic for multi-drug resistant gram-positive infections treatment, especially methicillin-resistant Staphylococcus aureus (MRSA). Despite that, it has wide individual pharmacokinetic variability and nephrotoxic effect. Vancomycin trough concentrations for 57 Jordanian patients were measured in plasma and saliva through immunoassay and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. Plasma levels were within accepted normal range, with exception of 6 patients who showed trough levels of more than 20 μg/ml and vancomycin was discontinued. Bayesian dose-optimizing software was used for patient-specific pharmacokinetics prediction and AUC/MIC calculation. Physiological-based pharmacokinetic (PBPK) vancomycin model was built and validated through GastroPlus™ 9.8 using in-house plasma data. A weak correlation coefficient of 0.2478 (P=0.1049) was found between plasma and saliva concentrations. The suggested normal saliva trough range of vancomycin is 0.01906 to 0.028589 (μg/ml). Analysis of variance showed significant statistical effects of creatinine clearance and albumin concentration on dose-normalized Cmin plasma and saliva levels respectively, which is in agreement with PBPKmodeling. It can be concluded that saliva is not a suitable matrix for TDM of vancomycin. Trough levels in plasma matrix should always be monitored for the safety of patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Tissue damage caused by COVID-19 could be detected by several clinical indicators including hematological, immunological, biochemical, and inflammatory markers. This study was to detect these clinical parameters to reveal the correlation between the factors and their roles in the development of COVID-19, to explore the hazard factors in severe cases., Materials and Methods: A total of 200 participants of both sexes were included in the study, with an age range of (25-72) years, categorized into three main groups: 50 healthy individuals, 62 mild infected patients, and 88 severe infected patients with pneumonia. Different hematological and clinical parameters were included in the analysis (Basrah city, Iraq). Serum levels of interleukin-6 (IL-6), ferritin, and high-sensitivity C -reactive protein (hs-CRP) were assessed for all participants using an enzyme-linked immunosorbent assay (ELISA). The liver, renal, and cardiac functions were assessed by clinical chemistry testing., Results: COVID-19 patients had leukocytosis, with an increased number of neutrophils and a decreased lymphocyte count, according to our findings. In regard to inflammatory parameters, both ESR and hs-CRP showed significant differences between the two groups, whereas IL-6 was significantly higher in the total severe group compared to the other two groups. Biochemical results revealed that each lactate dehydrogenase (LDH), ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) had significant changes in the total severe group. Among pneumonic with an O2 requirement and pneumonic without an O2 requirement, there were significant differences in immunological and inflammatory markers ( p > 0.05). The neutrophils-lymphocytes ratio (NLR) was highly elevated in severe who required O2. Moreover, IL-6, lymphocytes, and neutrophils were possible risk factors for COVID-19 infection, with the strongest influence of IL-6 with a high odds ratio (OR: 24.138, 95% CI: 8.437-30.65, p < 0.01). Furthermore, there were significant correlations among the indicators., Conclusion: Each of IL-6, lymphocytes, and neutrophils might represent major factors in the severity of COVID-19 and IL-6 plays the main role in inducing the inflammatory and pathophysiology process that is known as the cytokine storm., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Eman T. Ali et al.)

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Clinical pharmacists have a vital role in intercepting prescribing errors (PEs) but their impact within a Jordanian hospital emergency department (ED) has never been studied. Objective: To evaluate the impact of clinical pharmacy services on PEs and assess predictors of physicians' acceptance of clinical pharmacists' interventions. Setting: This study was conducted in the ED of the largest governmental hospital in Jordan. Method: This was a pre-post study conducted in October and November 2019 using a disguised observational method. There were 2 phases: control phase (P0) with no clinical interventions, and active phase (P1) where clinical pharmacists prospectively intervened upon errors. The clinical significance of errors was determined by a multidisciplinary committee. The SPSS software version 24 was used for data analysis. Main Outcome Measure: PEs incidence, type, severity, and predictors for physicians' acceptance. Results: Of 18003 patients, 8732 were included in P0 and 9271 in P1. PEs incidence decreased from 24.6% to 5.4%. Contraindication, drug selection, and dosage form error types were significantly reduced from 32.6%, 9.1%, and 3.7% (P0) to 12.6%, 0.0%, and 0.0% (P1), respectively. Albeit not statistically significant, drug-drug interaction, drug frequency, and allergy error types were reduced from 4.9%, 3.1%, and 0.1% to 4.5%, 2.5%, and 0.0%, respectively. Significant and serious errors were significantly reduced from 68.7% and 3.0% (P0) to 8.9% and 1.8% (P1), respectively. During P1, most errors were minor (89.3%, 1574/1763), and lethal errors ceased. Predictors for physicians' acceptance were: significant errors (OR 3.1; 95% CI 2.6-4.3; P = 0.03) and non-busy physicians (OR 2.1; 95% CI 1.6-2.7; P = 0.04). Conclusion: Clinical pharmacists significantly reduced PEs in the ED by 76%; most of interventions were significant. Policymakers are advised to implement active clinical pharmacy in the ED., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: To describe pharmacy students' attitude towards providing pharmaceutical care (PC) to patients with anxiety and their knowledge of psychotropic medicines (PM)., Methods: A cross-sectional emailed survey was sent to all 200 pharmacy students (fourth and fifth year) in one Jordanian university. Statistical analysis included descriptive statistics and chi-square test., Key Findings: A total of 134 responses were received (response rate 67%). About two-thirds of students (87, 64.9%) would like to give enough time to patients with anxiety to discuss their medications. Only half of students knew correctly that alprazolam (53.7%) and diazepam (50.0%) are categorized as anxiolytics. Undertaking a course in psychiatry was significantly associated with better students' knowledge in PM (P < 0.05)., Conclusion: Despite positive attitudes towards providing PC to patients with anxiety, policy makers should include courses on psychiatric pharmacotherapy in pharmacy curricula to improve pharmacy students' knowledge of PM., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Medication dispensing is a core function of community pharmacies, and errors that occur during the dispensing process are a major concern for pharmacy profession. However, to date there has been no national study of medication dispensing errors in Jordan. Objective The study aimed to investigate the incidence, nature, severity, causes and predictors of medication dispensing errors. Setting The study was conducted in randomly selected community pharmacies across Jordan. Method A mixed method approach was taken, incorporating prospective disguised observation of dispensing errors and interviews with pharmacists regarding the causes of errors. A multidisciplinary committee evaluated the severity of errors. Proportionate random sampling was used to include 350 pharmacies from across all regions of Jordan. SPSS (Version 24) was used for data analysis. Main outcome measure Incidence, nature, severity, causes and predictors of medication dispensing errors. Results The overall rate of medication dispensing errors was 24.6% (n = 37,009/150,442), of which 11.5% (n = 17,352/150,442) were prescription related errors and 13.1% (n = 19,657/150,442) pharmacist counselling errors. The most common type of prescription-related errors were wrong quantity (37.9%, n = 6584/17,352), whereas the most common pharmacist counselling error was wrong drug (41.9%, n = 8241/19,657). The majority of errors were caused by poor handwriting (30.7%, n = 75,651/37,009), followed by high workload (17.3%, n = 22,964/37,009). More than half of errors (52.6%) were moderate in severity, followed by minor errors (38.8%), and 8.6% of errors were rated as serious. Predictors of medication dispensing errors were: Sundays (OR 2.7; 95% CI 2.15-3.94; p = 0.02), grade A pharmacies (dispensing ≥ 60 prescriptions a day (OR 3.6; 95% CI 2.89-4.78; p = 0.04)), and prescriptions containing ≥ 4 medication orders (OR 4.1; 95% CI 2.9-6.4; p = 0.001). Conclusion Medication dispensing errors are common in Jordan and our findings can be generalised and considered as a reference to launch training programmes on safe medication dispensing and independent prescribing for pharmacists.

Gentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5-7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

Background: Mycophenolic acid (MPA) is used widely to prevent graft rejection in kidney-transplant patients. Therapeutic drug monitoring (TDM) in plasma requires an invasive procedure that is inconvenient, especially in pediatric patients. TDM in saliva is a more convenient non-invasive alternative compared with plasma., Methods: A population physiologically based pharmacokinetic (Pop-PBPK) model of mycophenolate mofetil (MMF) and MPA with enterohepatic recycling was built and verified using previously published plasma, saliva, and kidney biopsy data in healthy and kidney-transplant adult patients. The verified model was then used to predict experimentally observed plasma and saliva MMF and MPA TDM data in Jordanian pediatric kidney transplant patients measured using LC-MS/MS. A correlation was established between plasma and saliva exposures in pediatrics., Results: The developed LCMS was sensitive to both MMF and MPA in plasma and saliva. The developed Pop-PBPK model predicted well the previously reported MMF and MPA levels in plasma, saliva, and kidney tissue and those observed in the current study (more than 75% of observed data points were within 90% predictive interval of population simulations). A statistically significant correlation was found between plasma and saliva exposures for both MMF (Pop-PBPK predicted and observed) and MPA (Pop-PBPK predicted)., Conclusion: Both MPA and MMF can be classified as class III compounds in the Salivary Excretion Classification System. Saliva is an alternative body fluid to plasma that can be used for TDM of MPA and MMF in kidney-transplant patients in pediatrics. Exposure to MPA and MMF in plasma, saliva, and kidney tissue was reliably predicted using the developed Pop-PBPK model., (© 2019 John Wiley & Sons, Ltd.)

There is an urgent demand worldwide for the development of highly selective adsorbents and sensors of heavy metal ions and other organic pollutants. Within these environmental and public health frameworks, we are combining the salient features of clays and chelatant polymers to design selective metal ion adsorbents. Towards this end, the ion imprinting approach has been used to develop a novel nanohybrid material for the selective separation of Cu 2+ ions in an aqueous solution. The Cu 2+ -imprinted polymer/montmorillonite (IIP/Mt) and non-imprinted polymer/montmorillonite (NIP/Mt) nanocomposites were prepared by a radical photopolymerization process in visible light. The ion imprinting step was indeed important as the recognition of copper ions by IIP/Mt was significantly superior to that of NIP/Mt, i.e., the reference nanocomposite synthesized in the same way but in the absence of Cu 2+ ions. The adsorption process as batch study was investigated under the experimental condition affecting same parameters such as contact time, concentration of metal ions, and pH. The adsorption capacity of Cu 2+ ions is maximized at pH 5. Removal of Cu 2+ ion achieved equilibrium within 15 min; the results obtained were found to be fitted by the pseudo-second-order kinetics model. The equilibrium process was well described by the Langmuir isothermal model and the maximum adsorption capacity was found to be 23.6 mg/g. This is the first report on the design of imprinted polymer nanocomposites using Type II radical initiators under visible light in the presence of clay intercalated with hydrogen donor diazonium. The method is original, simple and efficient; it opens up new horizons in the general domain of clay/polymer nanocomposites.

The objective is using saliva instead of plasma for pregabalin therapeutic drug monitoring (TDM) since saliva reflects the free non-protein bound drug concentration, simple and noninvasive sampling, cheaper and does not require the expertise of drawing blood. Forty four patients participated in this study, two samples of saliva and another two of blood were taken from each patient; first sample of both saliva and blood is the trough sample and was taken just before the first dose of the day and second sample is the peak sample and was taken 1 h after taking the first dose of the day. Descriptive statistics and t-testing after log transformation were done using Excel, p-value=0.05 was adopted for significant difference. Optimized effective intestinal permeability of pregabalin was estimated by PK-Sim program version 7. This study for the first time revealed that pregabalin is excreted in saliva and classified as class 1 based on Salivary Excretion Classification System (SECS). A good correlation of 0.71-0.83 between Cmin and Cmax of plasma and saliva pregabalin was observed respectively which indicate that saliva sampling is a good alternative matrix for pregabalin TDM. C/D-ratios were calculated to demonstrate pharmacokinetic variability of Pregabalin; the results showed that C/D-ratio was higher in women, elderly and in those patients who had Scr.≥0.9 mg/dl. Proposed pregabalin therapeutic ranges are 0.7 to 1.84 µg/ml in plasma and 0.055 to 0.145 µg/ml in saliva, for neuropathic pain, diabetic neuropathy and disc prolapse patients., Competing Interests: The authors declare no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as an alternative to antivirals to treat human infectious diseases, especially influenza virus infections where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of an influenza virus infection of lung epithelial cells, that AgNPs down-regulated influenza induced CCL-5 and -IFN-β release (two cytokines important in antiviral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses. AgNPs activity was independent of coating and was not observed with gold nanoparticles. Down-stream analysis indicated that AgNPs disorganized the mitochondrial network and prevented the antiviral IRF-7 transcription factor influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF-7 pathway was concomitant with inhibition of either classical or alternative autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial cell type used. Altogether, this demonstration of a AgNPs-mediated functional dichotomy (down-regulation of IFN-dependent antiviral responses and up-regulation of IL-8-dependent antibacterial responses) may have practical implications for their use in the clinic.

Aim: The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS)., Methods: A pilot, open-label, two-way crossover bioequivalence study was done, and involved a single 500-mg oral dose of azithromycin given to eight healthy subjects under fasting conditions, followed by a 3-week washout period. Blood and unstimulated saliva samples were collected over 72 h and deep frozen until analysis by a validated liquid chromatography with mass spectroscopy method. The pharmacokinetic parameters and bioequivalence metrics of azithromycin were calculated by non-compartment analysis using WinNonlin V5.2. Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel. PK-Sim V5.6 was used to estimate the effective intestinal permeability of azithromycin., Results and Discussion: No statistical differences were shown in area under the concentration curves to 72 h (AUC 0-72 ), maximum measured concentration (C max ) and time to maximum concentration (T max ) between test and reference azithromycin products (P > 0.05) in the saliva matrix and in the plasma matrix. Due to the high intra-subject variability and low sample size of this pilot study, the 90% confidence intervals of AUC 0-72 and C max did not fall within the acceptance range (80-125%). However, saliva levels were higher than that of plasma, with a longer salivary T max . The mean saliva/plasma concentration of test and reference were 2.29 and 2.33, respectively. The mean ± standard deviation ratios of saliva/plasma of AUC 0-72 , C max and T max for test were 2.65 ± 1.59, 1.51 ± 0.49 and 1.85 ± 1.4, while for the reference product they were 3.37 ± 2.20, 1.57 ± 0.77 and 2.6 ± 1.27, respectively. A good correlation of R = 0.87 between plasma and saliva concentrations for both test and reference products was also observed. Azithromycin is considered a class I drug based on the SECS, since it has a high permeability and high fraction unbound, and saliva sampling could be used as an alternative to plasma sampling to characterize its pharmacokinetics and bioequivalence in humans when adequate sample size is used.

Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-γ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plasma membrane when MCs are activated. We determined the nucleotide sequences of the Prss31 gene in different mouse strains and then used a Cre/loxP homologous recombination approach to create a novel Prss31(-/-) C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)