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Solvent-free hot-melt coating processing is a novel and cost-efficient approach to manufacturing taste-masked multiparticulate systems. However, most API powders are fine and cohesive and not processable by hot-melt coating. The aim of this study was to produce dense and abrasion-resistant granules with high drug content (>80%) via roller compaction for hot-melt coating process optimization. The selected API was ibuprofen sodium dihydrate, a salt of ibuprofen with improved bioavailability and poor intrinsic compactibility. The formulation and roller compaction process were developed for the production of granules with 94%w/w of API and low friability (∼30%), using sorbitol and isomalt as excipients. The strong bonding mechanism relied on powder jamming prior to the rollers and was investigated via scanning electron microscopy, differential scanning calorimetry and small and wide angle X-ray scattering. It was shown that sorbitol crystals are solubilized during roller compaction and recrystallize as sorbitol hydrate, acting as strong solid bridges. The robustness of the roller compaction process and the re-compaction of fines were investigated. A statistical design of experiments was conducted to evaluate the hot-melt coating process for taste masking of ibuprofen sodium granules. Taste masking required coating ratios higher than 40%w/w of granule batch, emphasizing the need for high-drug-content and abrasion-resistant granules., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The encapsulation of payloads in micro- to nano-scale capsules allows protection of the payload from the surrounding environment and control of its release profile. Herein, we program the release of hydrophilic payloads from nanocontainers by co-encapsulating simple inorganic salts for adjusting the osmotic pressure. The latter either leads to a burst release at high concentrations of co-encapsulated salts or a sustained release at lower concentrations. Osmotic pressure causes swelling of the nanocapsule's shell and therefore sustained release profiles can be adjusted by crosslinking it. The approach presented allows for programing the release of payloads by co-encapsulating inexpensive salts inside nanocontainers without the help of stimuli-responsive materials.

Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.

Background: Motivation to academic achievement is critical for students of medical sciences, particularly nursing students. It is directly related to high levels of achievement and quality of life. Accordingly, diminished motivation would result in academic decline, study and work desertion and exhaustion. Therefore, this study aimed to investigate the effect of cognitive behavioural intervention on the motivation for academic achievement of the nursing students., Materials and Methods: This study was conducted on 64 female nursing students who were recruited to study based on the inclusion criteria. After sampling, the subjects were randomly assigned to study and control groups. Then, cognitive behavioural intervention was administered in study group during 60 days. Academic motivation scale was filled before, after and one month after the intervention. Data were analyzed by descriptive and inferential statistical tests (Chi-square, t-test)., Results: After the intervention, mean scores of academic motivation were significantly increased in study group, compared to control group (P < 0.001). Comparison of the mean scores of academic motivation in two groups revealed a significant increase in mean score of academic motivation 151.50 (20.22) after cognitive behavioural intervention (P < 0.001)., Conclusions: The findings suggested that cognitive behavioural intervention was a valuable psychotherapy technique to improve academic achievement motivation among nursing students.

Multiparticulate dosage forms are a recent strategy to meet the special needs of children, elderly people and patients suffering from dysphagia. Our study presents a novel and cost-efficient approach for the manufacturing of a taste-masked multiparticulate system with a stable immediate release profile by applying lipid-based excipients in a solvent-free hot melt coating process. The thermosensitive N-acetylcysteine (N-ac) was used as model drug and hot-melt coated with a mixture of tripalmitin and polysorbate 65. A predictive in vitro method for the evaluation of the taste masking efficiency was developed based on the deprotonation of the carboxyl group of N-ac and the decline of pH, responsible for the unpleasant sour taste of the compound. The method was confirmed using in vivo studies. Differential scanning calorimetry and X-ray scattering experiments revealed polymorphic transformation and its dependency on transformation time, temperature and emulsifier concentration. During the process, the coating was transformed almost completely into the stable β-polymorph, leading to an unaltered dissolution profile during storage. A statistical design was conducted that revealed the critical process parameters affecting the taste masking efficiency and drug release. This study shows the successful application of solvent-free hot-melt coating in the development of a taste-masked and stable formulation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Hot-melt coating is of growing interest, because it does not require solvents, resulting in reduced process times and costs. However, excipients for this technology are mainly triacylglycerides (TAGs) or their derivatives, which exhibit polymorphism, surface disruption, and complex crystallite networks, affecting the release profile of produced microcapsules. In this work, anhydrous citric acid crystals were coated with molten tristearin using conventional inlet air temperatures (microcapsules A) and temperatures above the melting point of α-form (microcapsules B). Additionally, microcapsules A were tempered to achieve polymorphic stability (microcapsules AB). The product yield and coating efficacy were above 90% and 97%, respectively, demonstrating the feasibility and efficacy of the process. Small angle X-ray scattering analysis confirmed that the tristearin shell of microcapsules B is in the β-form with a larger average crystallite size than microcapsules A and AB. Scanning electron microscopy images revealed a nonbloomed surface of microcapsules B. We showed that blooming does not play a critical role in the drug release, but the apparent diffusion coefficient of drug is dramatically reduced by increasing TAGs crystallite size and resulting tortuosity. This work brings new insights on the micrometric properties of solid lipid dosage forms, being an important step to prevent the overuse of excipients with unknown toxicity., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Aim: To evaluate the relationship between children's perception of caries and gingivitis and their oral health behaviours., Design: Participants in this cross-sectional study were children aged 11-14 years. A questionnaire for measuring children's perceptions and behaviours was developed, validated and applied. Perceptions were analysed as predictors for behaviours using multiple logistic regression analysis., Results: A total of 434 children (57% males) participated in the study. Half of them perceived caries as a disease and believed in visiting the dentist regularly regardless of dental need. More than 60% were unaware that gum bleeding is a sign of disease and only 60.7% believed that it requires a management. Being aware that gum bleeding is a sign of disease and that it requires treatment increased the odds of brushing 2.83 (OR = 2.83, 95% CI:1.33-6.12) and 2.1 (OR = 2.1, 95% CI:1.05-5.55) times, respectively. Children aware of importance of dental visits even without dental decay were 2.9 times more likely to visit the dentist regularly (OR = 2.86, 95% CI:1.25-5.75) and were 77% more likely to never miss a dental appointment (OR = 1.77, 95% CI:1.03-3.37)., Conclusion: Being aware that bleeding gum requires treatment was a determinant of toothbrushing habit. Improved perceived need for dental check-up regardless of dental problem may promote children's preventive dental attendance., (© 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pulmonary drug delivery is characterized by short onset times of the effects and an increased therapeutic ratio compared to oral drug delivery. This delivery route can be used for local as well as for systemic absorption applying drugs as single substance or as a fixed dose combination. Drugs can be delivered as nebulized aerosols or as dry powders. A screening system able to mimic delivery by the different devices might help to assess the drug effect in the different formulations and to identify potential interference between drugs in fixed dose combinations. The present study evaluates manual devices used in animal studies for their suitability for cellular studies., Methods: Calu-3 cells were cultured submersed and in air-liquid interface culture and characterized regarding mucus production and transepithelial electrical resistance. The influence of pore size and material of the transwell membranes and of the duration of air-liquid interface culture was assessed. Compounds were applied in solution and as aerosols generated by MicroSprayer IA-1C Aerosolizer or by DP-4 Dry Powder Insufflator using fluorescein and rhodamine 123 as model compounds. Budesonide and formoterol, singly and in combination, served as examples for drugs relevant in pulmonary delivery., Results and Conclusions: Membrane material and duration of air-liquid interface culture had no marked effect on mucus production and tightness of the cell monolayer. Co-application of budesonide and formoterol, applied in solution or as aerosol, increased permeation of formoterol across cells in air-liquid interface culture. Problems with the DP-4 Dry Powder Insufflator included compound-specific delivery rates and influence on the tightness of the cell monolayer. These problems were not encountered with the MicroSprayer IA-1C Aerosolizer. The combination of Calu-3 cells and manual aerosol generation devices appears suitable to identify interactions of drugs in fixed drug combination products on permeation.

Lipid excipients are applied for numerous purposes such as taste masking, controlled release, improvement of swallowability and moisture protection. Several melting techniques have evolved in the last decades. Common examples are melt coating, melt granulation and melt extrusion. The required equipment ranges from ordinary glass beakers for lab scale up to large machines such as fluid bed coaters, spray dryers or extruders. This allows for upscaling to pilot or production scale. Solvent free melt processing provides a cost-effective, time-saving and eco-friendly method for the food and pharmaceutical industries. This review intends to give a critical overview of the published literature on experiences, formulations and challenges and to show possibilities for future developments in this promising field. Moreover, it should serve as a guide for selecting the best excipients and manufacturing techniques for the development of a product with specific properties using solvent free melt processing.

Nanoparticles (NPs) are increasingly being used in different branches of science and in industrial applications; however, their rapid detection and characterization at low concentration levels have remained a challenge; more specifically, there is no single technique that can characterize the physicochemical properties of NPs (e.g. composition and size). In this work we have developed a colorimetric sensor array for defining the physicochemical properties of NPs in aqueous solution with ultra-low concentrations (e.g. 10(-7) g ml(-1) for gold NPs). Various NPs were readily identified using a standard chemometric approach (i.e. hierarchical clustering analysis), with no misclassifications over 400 trials.

Background: Various strategies have been applied to improve the response to hepatitis B virus (HBV) vaccination in hemodialysis patients., Objectives: The present study was under taken to compare the seroconversion rate of hemodialysis patients who had not respond to 3 intramuscular (IM) doses (40 μg each) of HBV vaccine , after a fourth IM dose (40 μg) of HBV vaccine that was administered alone or with subcutaneous granulocyte-colony stimulating factor (G-CSF) (5 μg/kg)., Patients and Methods: Twenty six hemodialysis patients who had not responded to 3 IM injections of HBV vaccine were randomized into 2 groups: Group 1 received a booster dose of 40 μg HBV vaccine IM, group 2 received a booster dose of 40 μg HBV vaccine IM plus 5 μg/kg subcutaneous G-CSF. Antibody to hepatitis B surface antigen was measured 1 month after the booster dose., Results: Seroconversion rate in group 1 was 40%. There was a trend towards a higher seroconversion rate at 60% in group 2 patients; however, because of the small number of patients it did not reach statistical significance., Conclusions: Larger number of patients and other innovative strategies should be applied for vaccination of this group of patients. More prolonged follow up of the patients is needed to evaluate the duration of protection induced by each method of vaccination.

The emergence of nanocarrier systems in drug delivery applications has ushered in rapid development of new classes of therapeutic agents which can provide an essential breakthrough in the fight against refractory diseases. However, successful clinical application of nano-drug delivery devices has been limited mainly due to the lack of control on sustained release of therapeutics from the carriers. A wide range of sophisticated approaches employs the formation of crosslinkable, non-crosslinkable, stimuli-responsive polymer nanocarriers in order to enhance their delivery efficiency. Despite the extensive research conducted on the development of various nanocarriers, the effect of the biological milieu on the drug release profile of these constructs is not yet fully investigated. In particular, the formation of a protein corona on the surface of nanocarriers, when they interact with living organisms in vivo is largely decisive for their biological function. Using a number of synthetized (i.e., superparamagnetic iron oxide nanoparticles and polymeric nanocapsules) and commercialized nanocarriers (i.e., Abraxane®, albumin-bound paclitaxel drug), this study demonstrates that the protein corona can shield the nanocarriers and, consequently, alters the release profile of the drugs from the nanocarriers. More specifically, the protein corona could significantly reduce the burst effect of either protein conjugated nanocarriers or carriers with surface loaded drug (i.e., SPIONs). However, the corona shell only slightly changed the release profile of polymeric nanocapsules. Therefore, the intermediary, buffer effect of the protein shells on the surface of nanoscale carriers plays a crucial role in their successful high-yield applications in vivo., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Bearing in mind that many promising drug candidates have the problem of reaching their target site, the concept of advanced drug delivery can play a significant complementary role in shaping modern medicine. Among other nanoscale drug carriers, superparamagnetic iron oxide nanoparticles (SPIONs) have shown great potential in nanomedicine. The intrinsic properties of SPIONs, such as inherent magnetism, broad safety margin and the availability of methods for fabrication and surface engineering, pave the way for diverse biomedical applications. SPIONs can achieve the highest drug targeting efficiency among carriers, since an external magnetic field locally applied to the target organ enhances the accumulation of magnetic nanoparticles in the drug site of action. Moreover, theranostic multifunctional SPIONs make simultaneous delivery and imaging possible. In spite of these favorable qualities, there are some toxicological concerns, such as oxidative stress, unpredictable cellular responses and induction of signaling pathways, alteration in gene expression profiles and potential disturbance in iron homeostasis, that need to be carefully considered. Besides, the protein corona at the surface of the SPIONs may induce few shortcomings such as reduction of SPIONs targeting efficacy., Areas Covered: In this review, we will present recent developments of SPIONs as theranostic agents. The article will further address some barriers on drug delivery using SPIONs., Expert Opinion: One of the major success determinants in targeted in vivo drug delivery using SPIONs is the adequacy of magnetic gradient. This can be partially achieved by using superconducting magnets, local implantation of magnets and application of magnetic stents. Other issues that must be considered include the pharmacokinetics and in vivo fate of SPIONs, their biodegradability, biocompatibility, potential side effects and the crucial impact of protein corona on either drug release profile or mistargeting. Surface modification of SPIONs can open up the possibility of drug delivery to intracellular organelles, drug delivery across the blood-brain barrier, modifying metabolic diseases and a variety of other multimodal and/or theranostic applications.

The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs.

Background: Magnetic resonance imaging (MRI) is important in the early diagnosis of novel or relapsing multiple sclerosis (MS). In addition, the optimal MRI protocol plays an important role in detecting MS plaques., Purpose: To find the best time to detect MS plaques on MRI after Gadobutrol injection., Material and Methods: Sixty-two relapsing-remitting type MS patients, (56 women, 6 men) with the mean age of 31 ± 7 years were enrolled into this study. The patients underwent T1-weighted MRI scan without contrast agents. Subsequently, Gadobutrol was injected (0.1 mmol/kg) and MRI scanning was repeated after 30 s, 5, 10, 15, and 30 min of Gadobutrol injection. The size, signal intensity, and enhancement pattern were determined for each plaque by contrast-enhanced T1-weighted images., Results: Enhancing plaques were seen in 42 out of 62 patients. The mean number of enhancing plaques was 4 ± 8 plaques after 30 s of contrast injection. This figure increased to 7 ± 13 plaques after 15 min and 6 ± 10 plaques after 30 min. The signal intensity and size of plaques increased progressively, and the maximum signal intensity and plaque size were seen after 30 min (P < 0.001)., Conclusion: The maximum number of enhancing plaques in MS patients was detected 15 min after contrast agent administration and the size and signal intensity of the lesions also increased remarkably at this time.

Upon incorporation of nanoparticles (NPs) into the body, they are exposed to biological fluids, and their interaction with the dissolved biomolecules leads to the formation of the so-called protein corona on the surface of the NPs. The composition of the corona plays a crucial role in the biological fate of the NPs. While the effects of various physicochemical parameters on the composition of the corona have been explored in depth, the role of temperature upon its formation has received much less attention. In this work, we have probed the effect of temperature on the protein composition on the surface of a set of NPs with various surface chemistries and electric charges. Our results indicate that the degree of protein coverage and the composition of the adsorbed proteins on the NPs' surface depend on the temperature at which the protein corona is formed. Also, the uptake of NPs is affected by the temperature. Temperature is, thus, an important parameter that needs to be carefully controlled in quantitative studies of bionano interactions.

It is known that what the cell actually "sees" at the nanoscale is an outer shell formed of 'protein corona' on the surface of nanoparticles (NPs). The amount and composition of various proteins on the corona are strongly dependent on the biophysicochemical properties of NPs, which have been extensively studied. However, the effect of a small variation in temperature, due to the human circadian rhythm, on the composition of the protein corona and the affinity of various proteins to the surface of NPs, was ignored. Here, the effect of temperature on the composition of protein corona and the affinity of various proteins to the surface of NPs and, subsequently, cell responses to the protein coated NPs are probed. The results confirmed that cellular entrance, dispersion, and toxicity of NPs are strongly diverse with slight body temperature changes. This new finding can help scientists to maximise NP entrance to specific cells/organs with lower toxicity by adjusting the cellular/organ temperature.

Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity (286 references).

Nanoparticles for biomedical use must be cytocompatible with the biological environment that they are exposed to. Current research has focused on the surface functionalization of nanoparticles by using proteins, polymers, thiols and other organic compounds. Here we show that inorganic nanoparticles such as titanium oxide can be coated by pyrolytic carbon (PyC) and that the coating has cytocompatible properties. Pyrolization and condensation of methane formed a thin layer of pyrolytic carbon on the titanium oxide core. The formation of the PyC shell retards coalescence and sintering of the ceramic phase. Our MTT assay shows that the PyC-coated particles are cytocompatible at employed doses.

Background: Magnetic resonance imaging (MRI) is the standard method for observing brain plaques and contrast material injection is necessary for demonstrating the active plaque.This study compared the rate of enhancement of plaques with Gadovist and Magnevist in relapse phase of MS., Methods: In this double blind study, after neurological examination of 62 patients in the attack phase of MS, two consecutive MRIs were performed with Gadovist and Magnevist with 48 hours interval. The two contrast materials were injected in first and second imaging randomly and the reporting radiologist was blind about the contrast material., Results: With both contrast materials, the probability of enhancement of supratentorial plaques was higher than the infratentorial ones. The probability of observing a symptomatic infratentorial enhanced plaque was higher than the supratentorial region and when the symptoms were due to supratentorial lesions, the corresponding enhanced plaque was more probable. It was detected that the number of enhanced plaques was the highest if the imaging was performed in the second week after the relapse, although there was no statistically significant difference when the imaging was done within the first month after the beginning of the symptoms., Conclusion: It seems that both Magnevist and Gadovist could be used as the contrast material to detect enhancing plaques in relapse phase of multiple sclerosis.

Background: Renal dysfunction (RD) is a common complication following liver transplantation. Postoperative renal function after split liver transplant (SLT) and (partial living related liver transplant) (LRLT) has not been well studied yet., Material/methods: Renal function immediately after surgery was analyzed retrospectively in 32 patients that received SLT and LRLT. Serum creatinine (SCr) was measured before surgery, and, after transplantation daily during the first week and at 14, 21, and 28 days after transplantation. Patient's medical records were reviewed to find clinical data;Model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh score (CTP) class, the length of surgery, length of anhepatic phase, hospital and ICU admission, incidence of acute rejection, renal dysfunction, and sepsis. These data compared between groups., Results: Length of surgery and anhepatic phase was longer in SLT and LRLT group (P<0.05). The incidence of acute rejection, reoperation, and complication such as sepsis was higher in SLT and LRLT group than FSLT group (P<0.05). There were no significant difference between groups with respect to MELD, CTP score, the need for transfusions, the length of admission to the hospital and ICU. Immunosuppression regimens were similar in both groups. RD developed in 25.8% of SLT and LRLT patients, but in only 9.5% of FSLT patients (p=0.063). The requirement for RRT in SLT and LRLT group (12.5%) was greater than that in the FSLT group (2.3%); P=0.20., Conclusions: Although the number of patients studied was small, our data suggests a higher incidence of RD in patients receiving SLT and LRLT.

In this study, we assessed the stability provided by different formulations to aerial conidia or biomasses (conidia, blastospores, and mycelia) of Beauveria brongniartii and Metarhizium anisopliae subjected to lyophilization. First, the impact of the freezing and drying processes on spore survival was evaluated. Whereas unprotected B. brongniartii spores showed high cryosensitivity, those of M. anisopliae were markedly harmed by the drying process. Then, the protective efficiency of 14 excipients was systematically evaluated and optimized regarding required concentrations. Fructose, glucose, and saccharose significantly enhanced viabilities for B. brongniartii and M. anisopliae spores following lyophilization, especially as a result of their cryoprotective effects. In addition, the effect of various bulking agents on spore survival was studied and dextran 4 was selected to enhance the physical properties of the lyophilized products. The combination of fructose and dextran 4 was further applied to prepare lyophilized biomasses of both fungi. In comparison to freshly harvested biomasses, the lyophilized products showed similar growth rates and a comparable production of virulent secondary metabolites such as destruxin A, destruxin B, or oosporein, suggesting their applicability as biological control agents., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Patients with panel reactive antibodies (PRA) have many difficulties to find a crossmatch-negative kidney for transplantation and are at a higher risk of post-transplantation rejection., Objective: To evaluate the effect of simvastatin on PRA and post-transplant outcome of these sensitized patients., Methods: 82 patients with end-stage renal disease (ESRD) with a PRA ≥25% were evaluated. In a one-year follow-up, the patients were treated with simvastatin. These patients were compared with 82 matched controls receiving placebo tablets. At the end of the second and 12(th) month, PRA was rechecked in all patients. Those patients who underwent transplantation continued to take simvastatin six months after transplantation. Serum creatinine levels were checked at monthly intervals post-operation., Results: The mean±SD PRA level at the end of the second month was 36.63%±31.14% and 45.34%±24.36% in cases and controls, respectively (P=0.012). Seven patients in the case group and 10 in the control group were lost to follow-up. The remaining patients continued to take simvastatin for 12 month. The mean±SD PRA level at the end of the 12(th) month was 24.02%±31.04% in cases and 43.15%±26.56% in controls (P=0.001). 25 patients underwent renal transplantation and continued to receive simvastatin 6 months after transplantation. These patients were matched with 25 controls treating with placebo. The mean±SD creatinine level 6 months after kidney transplantation was 2.05±1.14 mg/dL and 3.15±1.09 mg/dL in cases and controls consecutively (P=0.02)., Conclusion: Simvastatin can be safely used to lower PRA and improve post-transplantation outcomes.

A novel continuous reactor process has been developed for the production of biodiesel from fats and oils. The key feature of the process is its ability to operate continuously with a high reaction rate, potentially requiring less post reaction cleaning and product/reactant separation than currently established processes. This was achieved by atomising the heated oil/fat and then spraying it into a reaction chamber filled with methanol vapor in a counter current flow arrangement. This allows the continuous separation of product and the excess methanol stream in the reactor. The overall conversion based on a single cycle of this process has been between 50% and 96% of the feed stock materials. Conversions of 94-96% were achieved while operating with 5-7 g of sodium methoxide/L of methanol at methanol flow rate of 17.2 L/h and oil flow rate of 10 L/h. Additional variations in the reactant stoichiometry (i.e. reactant flow rates), catalyst type/concentration, and reaction temperature on the overall product conversion were investigated.

Introduction: Zinc deficiency is known to occur in widely diverse areas of world. It has now been recognized in many disease states, such as ESRD patients on maintenance hemodialysis (HD). The purpose of this research was to study the effects of zinc supplementation on the concentration of serum zinc, total cholesterol, triglyceride, and cholesterol fractions (HDL, LDL) in HD patients., Patients and Methods: In a double blind trial, the effects of oral zinc supplementation on the serum concentration of zinc, total cholesterol, HDL and LDL cholesterol, and triglyceride in HD patients were evaluated., Results: After 42 days, the mean serum zinc concentration among participants in the zinc-supplemented group increased. There was a significant elevation in the serum total cholesterol and also in mean the serum LDL and HDL cholesterol and serum triglyceride for the subjects in the zinc-supplemented group., Discussion: A suboptimal level of the serum total cholesterol concentration is a factor associated with malnutrition and morbidity in the HD patients. Maintenance HD patients with both low serum zinc and low serum total cholesterol concentrations may benefit from zinc supplementation. Therefore, it is advisable to obtain baseline measurement of the serum zinc and total cholesterol concentrations in maintenance HD patients.

Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of end-stage renal disease and a common indication for renal transplantation. Patients with ADPKD show some differences in graft outcome and complications following renal transplantation. This study was undertaken to evaluate the demographics, outcome and complications of renal transplantation in patients with ADPKD. In a retrospective case-control design, 51 patients with ADPKD were recognized amongst a total of 1200 renal transplant patients. For each case, a matched control based on sex, age (+/- 5 years) and type of kidney donor, was selected. All relevant data were gathered using patients' records and PNOT software. There were 34 males (66.7%) and 17 females (33.3%) with ADPKD. Mean age at transplantation was 42.6 +/- 14.3 years and source of donor organ was predominantly live unrelated (72.5%). Forty patients (78.4%) had extra-renal manifestations of ADPKD, the most common of which were cardiac valvular disease (24 cases, 47.1%), and liver cysts (10 cases, 19.6%). Rejection occurred in 12 patients in the case-group (23.5%) in comparison to nine patients (17.6%) in the control group (p > 0.05). Twenty-nine cases (56.9%) did not develop any complications. The common complications noted after transplantation included infections (15.7% in cases vs 19.6% in controls), and cerebrovascular accidents (13.7% in cases vs 16.6% in controls). Patient outcome after short- and long-term follow-up was slightly better in the ADPKD population than the control group; however, it was not statistically significant. Also, no complication was found to occur more frequently in ADPKD patients.

Postoperative acute renal failure is a frequent and serious medical complication following orthotopic liver transplant. Here, we report our experiences with liver transplant recipients who developed acute renal failure in the early period following orthotopic liver transplant. Among 100 liver transplants performed between April 1993 and January 2004, we retrospectively analyzed 91 patients (mean age, 29.9 +/- 14.0 years) who had undergone orthotopic liver transplant. The underlying causes of liver failure were cryptogenic liver cirrhosis (n=27), viral hepatitis (n= 21) (hepatitis-B-related liver cirrhosis [n=13], hepatitis-C-related liver cirrhosis [n=7], and hepatitis-B- and C-related liver cirrhosis [n=1]), autoimmune hepatitis (n=18), Wilson's disease (n=10), primary sclerosing cholangitis (n=8), biliary atresia (n=3), Budd-Chiari syndrome (n=2), and primary biliary cirrhosis (n=2). The immunosuppressive regimen included mycophenolate mofetil (azathioprine for 10 patients), cyclosporine, and steroids. Six patients received a combination of tacrolimus and steroids. Ten patients (10.9%) experienced acute renal failure, 7 (70%) were men, and none of them required renal replacement therapy and/or died. Four patients were diagnosed as having cryptogenic liver cirrhosis; 2 with hepatitis-C-related liver cirrhosis, 2 with autoimmune liver cirrhosis; 1 with primary biliary cirrhosis; and 1 hepatitis-B-related liver cirrhosis. Six patients were Child-Pugh's classification C, and the others were B. The rate of postoperative acute renal failure in our patients was relatively low when compared with other series, and our outcomes were good.

Objective: Acute rejection remains an important cause of graft loss after renal transplantation, and cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. However, the influence of gene polymorphisms on the functional immune response of transplant recipient outcomes remains controversial., Materials and Methods: The amplification refractory mutation system polymerase chain reaction was used to detect the interleukin-10 (IL-10) (-1082 G/A), tumor necrosis factor-alpha (TNF-alpha) (-308 G/A), and interferon-gamma (IFN-gamma) (+874 T/A) single nucleotide polymorphisms in 100 of the first adult kidney recipients at our institution who were receiving cyclosporine-based immunosuppressive therapy. The diagnosis of acute rejection was based on clinical and histologic findings according to the Banff criteria., Results: The results of multivariate analyses showed no significant association between episodes of acute rejection and single nucleotide polymorphisms in IL- 10, TNF-alpha genes, or dinucleotide repeat polymorphisms in the IFN-gamma gene., Conclusions: Our results demonstrate that cytokine gene polymorphisms did not influence the early outcome of kidney transplantation.

Objectives: Cyclosporine (CsA) has a narrow therapeutic range, and its pharmacokinetic characteristics vary among individuals. It also is a substrate for cytochrome P450 (CYP) 3A and P-glycoprotein, the product of the multidrug resistance 1 (MDR1) and CYP3A5 genes. Some of the single nucleotide polymorphisms (SNPs) in these genes are associated with deficient protein expression and reduced in vivo activity. We postulated that in renal transplant recipients, these SNPs should be associated with interindividual variations in CsA pharmacokinetics., Materials and Methods: In 88 Iranian renal transplant patients receiving CsA, CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Whole blood trough CsA concentrations were measured by radioactive immunosorbent assay. The dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 day (+/-2 days), 7 days, and 1 month after transplantation., Results: The MDR-1 wild-type genotype (3435CC) was observed in 17 patients (19%), whereas 45 patients (51%) were heterozygous (3435CT), and 26 patients (30%) were homozygous (3435 TT) for the mutation. In the days immediately after transplantation, we found a correlation between the concentration/dose ratio and the exon 26 MDR single nucleotide polymorphisms (33.3+/-15.24 microg mg/L/kg in the CT group vs 44.1+/-28.4 microg mg/L/kg in the TT group, P=.019). This ratio was significantly higher in subjects homozygous for the mutation (3435TT). This significant difference was not seen 1 week or 1 month after transplantation. All patients had the CYP3A5*3/*3 genotype, so no differences among the CYP3A5*1/*3 genotypes were found., Conclusions: MDR-1 (3435CC) polymorphisms are associated with CsA pharmacokinetics and dose requirements in the first few days after renal transplantation. Pharmacogenetic methods could be used to help select the initial dosage and individualize immunosuppressive therapy. According to our results, the major genotype of our recipients is CYP3A5*3/*3. According to the literature, the recommended starting dosage of CsA is 9-14 mg/kg/day; however, the Iranian population has a good response with lower dosages (3-5 mg/kg/day), which may be explained by genetic differences.