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Objectives: Doxycycline hyclate is a controlled-release doxycycline polymer which can locally be applied. This study aimed to assess the effects of the prophylactic application of doxycycline hyclate at the implant-abutment interface on the shortterm outcomes of implant therapy. Method and materials: The present split-mouth randomized clinical trial included 20 subjects who received two mandibular implants bilaterally (40 implants in total). In the test side (n = 20), doxycycline hyclate was injected at the implant-abutment interface at the time of delivery of final prosthesis. No intervention was performed for the control side (n = 20). The marginal bone level on mesial and distal implant surfaces, bleeding on probing, pocket probing depth, and incidence of peri-implant mucositis were recorded at baseline and after 3, 6, and 12 months. Results: Significant differences were found between the test and control sites, all favoring the test group, for marginal bone level changes at mesial and distal implant surfaces as well as for changes in pocket probing depth after 6 and 12 months. Furthermore, the numbers of implants with bleeding on probing and risk of developing peri-implant mucositis were significantly greater in the control group compared to the test group at 3-months, 6-months, and 12-months following baseline. Conclusions: Within the limitations of this study, it can be concluded that prophylactic application of doxycycline hyclate at the implant-abutment interface results in reduced crestal bone resorption and pocket probing depth levels. In addition, it reduces the risk of developing peri-implant mucositis. [ABSTRACT FROM AUTHOR]

Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ transplantation, has a narrow therapeutic range with considerable inter-individual and intra-individual pharmacokinetic variability. To date, there is no information on the pharmacokinetics of tacrolimus in Iranian liver transplant recipients. This study was designed to determine pharmacokinetic properties of orally administered tacrolimus in Iranian adult liver transplant recipients. Tacrolimus doses and steady state whole blood trough concentrations as well as patient demographic and clinical data were obtained retrospectively using the 30 included patients' medical records. Pharmacokinetic parameters were estimated by using a nonlinear mixed effect model program (Monolix version 3.1). Absorption rate constant was fixed at two hours-1. Drug apparent clearance (CL/F), apparent volume of distribution (Vd/F), and elimination half life (t1/2β) were calculated. The administered dose of tacrolimus to the patients ranged from 0.02 to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t1/2β were found to be 9.3 ± 0.96 L/h, 101 ± 29 L, and 7.5 hours, respectively. The pharmacokinetics of tacrolimus was highly variable among our patients. CL/F, Vd/F, and t1/2β of tacrolimus in this study were comparable to reported values from Italian heart transplant patients but somewhat different from reported ones from other solid organ transplant populations. [ABSTRACT FROM AUTHOR]

Clavulanic acid (CA) production by Streptomyces clavuligerus was compared in fermentation media containing various nitrogen sources, including soybean meal, peptone, corn steep powder, cotton seed meal, ammonium sulfate, and ammonium nitrate, respectively. The basal fermentation medium was also supplemented with various concentrations of peanut derivatives. The highest CA concentration was obtained in medium containing soybean meal supplemented with peanut protein. The production of N-(2-carboxyethyl)- L-arginine (CEA) by a wild-type and a mutant strain of Streptomyces clavuligerus [in which the gene encoding β-lactam synthetase ( orf3 ) was inactivated] in fermentation broth was compared. The assay of CA and CEA in the peanut protein-containing fermentation broth of the orf3 blocked mutant of S. clavuligerus and the analysis of amino acids and fatty acids of peanut seed flour showed that peanut protein can provide the aspartate amino acids family, arginine, and glycerol for the production of CA. Based on these results, we conclude that peanut seed flour and its derivatives can be used for CA production on an industrial scale as a supplementary nitrogen and carbon source. [ABSTRACT FROM AUTHOR]

Background: L-tryptophan is used widespread in the pharmaceutical industry. The majority of L-Trp production depends on microbial processes that produce L-tryptophan from indole and L-serine. These processes are very costly due to the costs of precursors, especially L-serine. Use of inexpensive substitutions as the L-serine source of Ltryptophan production enables us to reach a cost-effective process. In this paper, effect of Triton X-100 on L-Trp production and the ability to use Iranian cane molasses as inexpensive L-serine source was investigated. Methods: Escherichia coli (E. coli) ATCC 11303 cells were grown in 10-L fermenter containing minimal medium supplemented with beet molasses as an inexpensive carbon source and indole as tryptophan synthase inducer. Whole cells of stationary phase were used as biocatalyst for L-Trp production. Triton X-100 addition to the production medium as indole reservoir was investigated. Then, cane molasses was used as LSer source in L-Trp production medium. Amount of L-Tryptophan and theoretical yield of L-Trp production was determined by HPLC and by a colorimetrically method on the basis of remaining indole assay, respectively. Results: As a result, triton X-100 increased L-Trp production three times. Also, the result showed that 0.68 mM L-Tryptophan was produced in the presence of cane molasses at 37 °C for 8 hr. Conclusion: This result showed that cane molasses of Qazvin sugar factory includes significant amounts of L-Ser that makes it a suitable substitution for L-Ser in L-Trp production. Therefore, it has the potential to be used for cost-effective L-Trp production in industrial scale. [ABSTRACT FROM AUTHOR]

Background: Worldwide, type 2 diabetes mellitus (T2DM) is one of the most pervasive and fastgrowing disorders, bringing long-term adverse effects. T2DM arises from pancreatic β-cells deficiency to produce enough insulin or when the body cannot effectively use the insulin produced by such cells. Accordingly, early diagnosis will decrease the long-term effects and high-healthcare costs of diabetes., Objective: The objective is developing an integrated mathematical model of the insulin signaling network based on Brännmark's model, which can simulate the signaling events more comprehensively with the added key components., Methods: In this study, a thorough mathematical model of the insulin signaling network was developed by expanding the previously validated model and incorporating the glycogen synthesis module. Parameters (69 parameters) of the integrated model were evaluated by a genetic algorithm by fitting the model predictions to eighty percent of experimental data from the literature. Twenty percent of the experimental data were used to evaluate the final optimized model., Results: The time-response curves indicate that the GS phosphorylation reaches its maximum in response to 10 -7 M insulin after 4 min, while the maximum phosphorylated GSK3 is attained within ~50 min. The doseresponse curves for the GSP and GSK3 of the insulin signaling intermediaries in response to the increased concentration of insulin, after 10 min, in the input from 0-100 nM exhibits a decreasing trend, whereas an increasing trend was observed for the GS and GSK3P. The GSK and GS phosphorylation sensitivity was enhanced by increasing the initial insulin concentration level from 0.001 to 100 nM. However, the sensitivity of GSK3 to insulin concentration changes (from 0.001 to 100 nM) was 3-fold higher than GS sensitivity., Conclusion: Considerably, the trends of all signaling components simulated by the expanded model shows high compatibility with experimental data (R2 ≥ 0.9), which approves the accuracy of the proposed model. The proposed mathematical model can be used in many biological systems and combined with the whole-body model of the blood glucose regulation system for a better understanding of the causes and potential treatment of type 2 diabetes. Although, this model is not a complete description of insulin signaling, yet it can make profound contributions to improvements regarding other important components and signaling branches such as epidermal growth factor (EGF) signaling, as well as signaling in other cell types in the model structure of future works., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI)., Methods: This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures. For all the patients, phenytoin serum concentration was determined in three scheduled time points. Phenytoin serum concentration and pharmacokinetic parameters were compared between patients with TBI and cerebrovascular accident (CVA)., Findings: The V max and K m were significantly higher in head trauma (HT) patients than the CVA group. The phenytoin concentration (C p ) and the C p /dose ratio were significantly higher in the CVA group patients during the first sampling ( P < 0.05). The Acute Physiology and Chronic Health Evaluation П (APACHE П) score was significantly lower than the baseline at the end of the study in each group of patients ( P < 0.05). In addition, no significant correlation was observed between V max , K m , C p , C p /dose ratio, and APACHE II scores at the time of sampling., Conclusion: Due to significant differences in phenytoin plasma concentration and pharmacokinetic parameters between HT and CVA patients, close attention must be paid to the pharmacokinetic behavior of phenytoin in the efforts to improve the patient's outcome after a severe HT., Competing Interests: There are no conflicts of interest.