Razvoj i biofarmaceutsko vrednovanje pripravka za povećano oslobađanje tramadol hidroklorida na principu osmotske tehnologije

Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve the same. Formulation variables like level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect the drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with performance of two commercial tablets of TRH. The developed formulation provided more prolonged and controlled TRH release as compared to marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable during 6 months of accelerated stability testing.U radu je opisana priprava i evaluacija pripravaka tramadol hidroklorida (TRH) na principu osmotske tehnologije. Da bi se postigao željeni profil oslobađanja mijenjane su različite varijable. Pokazalo se da najveći utjacaj na oslobađanje ljekovite tvari imaju udjeli polimera koji bubri, plastifikatora i debljina ovojnice polupropusne membrane (SPM). TRH oslobađanje bilo je proporcionalno udjelu plastifikatora, a obrnuto proporcionalno udjelu polimera i vrijednosti SPM. Oslobađanje ljekovite tvari bilo je neovisno o pH i intenzitetu miješanja, a ovisno o osmotskom talku medija. U in vivo studiji provedenoj na šest zdravih volontera određeni su farmakokinetički parametri (cmax, tmax, AUC0-24, MRT) i izračunata relativna bioraspoloživost. Rezultati dobiveni u pokusima in vitro i in vivo uspoređeni su s dvije vrste komercijalno dostupnih tableta TRH: oslobađanje ljekovite tvari iz pripravka razvijenog u ovom radu bilo je dulje i više kontrolirano. In vitro-in vivo korelacija (IVIVC) je analizirana prema Wagner-Nelsonovoj metodi. Optimizirani pripravak (IVB) pokazao je dobru IVIV korelaciju (R = 0,9750). Proizvodni proces je bio reproducibilan i pripravci su bili stabilni tijekom 6 mjeseci u uvjetima ubrzanog starenja

The role of the intensive care unit environment and health-care workers in the transmission of bacteria associated with hospital acquired infections

The goal of this study was to attempt to determine the rate of contamination of health-care workers' (HCWs) hands and environmental surfaces in intensive care units (ICU) by the main bacteria associated with hospital acquired infections (HAIs) in Tehran, Iran. A total of 605 and 762 swab samples were obtained from six ICU environments and HCWs' hands. Identification of the bacterial isolates was performed according to standard biochemical methods, and their antimicrobial susceptibility was determined based on the guidelines recommended by clinical and laboratory standards institute (CLSI). The homology of the resistance patterns was assessed by the NTSYSsp software. The most frequent bacteria on the HCWs' hands and in the environmental samples were Acinetobacter baumannii (1.4 and 16.5, respectively), Staphylococcus aureus (5.9 and 8.1, respectively), S. epidermidis (20.9 and 18.7, respectively), and Enterococcus spp. (1 and 1.3, respectively). Patients' oxygen masks, ventilators, and bed linens were the most contaminated sites. Nurses' aides and housekeepers were the most contaminated staff. Imipenem resistant A. baumannii (94 and 54.5), methicillin-resistant S. aureus (MRSAs, 59.6 and 67.3), and vancomycin resistant Enterococci (VREs, 0 and 25) were detected on the hands of ICU staff and the environmental samples, respectively. Different isolates of S. aureus and Enterococcus spp. showed significant homology in these samples. These results showed contamination of the ICU environments and HCWs with important bacterial pathogens that are the main risk factors for HAIs in the studied hospitals. © 2015 King Saud Bin Abdulaziz University for Health Sciences

Nanopore native RNA sequencing of a human poly(A) transcriptome

High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes

Effect of date on blood sugar in patients with type 1 diabetes mellitus

Background: The importance of feed controlling has been proved in metabolic control of diabetic patients. An appropriate metabolic control prevents later complications. Patients with diabetes mellitus are deprived from eating sweat foods. Considering the effect of different carbohydrates on blood sugar, physicians and patients confront a lot of questions about eating these foods. The aim of this study was to compare the effect of sugar cube and Date consumption on blood sugar in patients with type 1 diabetes. Methods: As a clinical-trial, we selected 20 patients with type I diabetes mellitus sequentially. They were divided into two groups with 10 subjects in each group. The patient's blood sugar was measured in 2 days with one week interval, before and after eating a Date (10gr) and a sugar cube (5gr). We measured blood sugar at 30, 60, 90 and 120 minutes after consumption. Data analysis was performed by SPSS software version 11, and the results were compared by paired t test. Results: There was no significant difference between the blood sugar after eating Date and sugar cube. We also compared the surface under the curve of blood sugar after eating date and sugar cube in 2 hours, which was 1619.4 ± 614 mg.min/dL and 1572 ± 967 mg.min/dL for sugar cube and Date respectively, which the difference was not significant. Conclusion: Rising in blood sugar after Date consumption has not significant difference in comparison with sugar cube consumption in patients with type I diabetes. So, eating Date in diabetic patients is not preferable to eating sugar cube

Frequency of Beta-Lactamase Antibiotic Resistance Genes in Escherichia Coli and Klebsiella pneumoniae

Background: This cross-sectional study was performed on isolates of Klebsiella pneumoniae, and E.coli from clinical specimens of patients admitted to Sayyad Shirazi Hospital by census sampling method in 2019. Antibiogram testing was performed using the disk diffusion method as defined by the Clinical and Laboratory Standards Organization for performing this test. Finally, the abundance of genes was evaluated by PCR using specific primers. Frequency, percentage, mean±SD were used to describe the data. Chi-square and Fisher's exact tests were used to compare the presence and absence of the studied genes alone and in the presence of each other. Result: This study was performed on 130 positive samples, isolated from 32 (24.6) males and 98 (65.4) females with a mean age of 43.78 ± 21.72. From the total number of 130 isolates, 84 (64.6) consisted of E.coli, and 46 (35.4) were Klebsiella. Most of the cultures were urine and vaginal (61.5). The highest antibiotic resistance in isolates was cephalexin and cefazolin (67.9 in E.coli & 63 in Klebsiella). Colistin was identified as the most effective antibiotic (100) in both. AMPC extendedspectrum β-lactamase genes were present in 40 (30.8) isolates. The highest frequency about the gene pattern of AMPC positive β-lactamase bacteria was correlated to DHA, FOX, and CIT genes, while none of the samples contained the MOX β-lactamase gene. E.coli and Klebsiella beta-lactamase-producing AMPC isolates were also significantly correlated with antibiotic resistance to the cephalosporin class (P <0.05). Conclusion: This study indicated a high percentage of resistance to third and fourth generation cephalosporins. Hence, careful antibiogram tests and prevention of antibiotic overuse in infections caused by AMPC-producing organisms and screening of clinical samples for the resistance mentioned above genes and providing effective strategies to help diagnose and apply appropriate treatments and change antibiotic usage strategies can partially prevent the transmission of this resistance. © 2021 Roghieh G.Ayele, et al

Comparison of pulse propagation and gain saturation characteristics among different input pulse shapes in semiconductor optical amplifiers

This paper presents the pulse propagation and gain saturation characteristics for different input optical pulse shapes with different energy levels in semiconductor optical amplifiers (SOAs). A finite-difference beam propagation method (FD-BPM) is used to solve the modified nonlinear Schrödinger equation (MNLSE) for the simulation of nonlinear optical pulse propagation and gain saturation characteristics in the SOAs. In this MNLSE, the gain spectrum dynamics, gain saturation are taken into account those are depend on the carrier depletion, carrier heating, spectral hole-burning, group velocity dispersion, self-phase modulation and two photon absorption. From this simulation, we obtained the output waveforms and spectra for different input pulse shapes considering different input energy levels. It has shown that the output pulse shape has changed due to the variation of input parameters, such as input pulse shape, input pulse width, and input pulse energy levels. It also shown clearly that the peak position of the output waveforms are shifted toward the leading edge which is due to the gain saturation of the SOA. We also compared the gain saturation characteristics in the SOA for different input pulse shapes

Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology

Nonsyndromic oral clefting (NSOC) is although one of the most common congenital disorders worldwide, its underlying molecular basis remains elusive. This process has been hindered by the overwhelmingly high level of heterogeneity observed. Given that hitherto multiple loci and genes have been associated with NSOC, and that complex diseases are usually polygenic and show a considerable level of missing heritability, we used a systems genetics approach to reconstruct the NSOC network by integrating human-based physical and regulatory interactome with whole-transcriptome microarray data. We show that the network component contains 53% (23/43) of the curated NSOC-implicated gene set and displays a highly significant propinquity (P ≺ 0.0001) between genes implicated at the genomic level and those differentially expressed at the transcriptome level. In addition, we identified bona fide candidate genes based on topological features and dysregulation (e.g. ANGPTL4), and similarly prioritised genes at GWA loci (e.g. MYC and CREBBP), thus providing further insight into the underlying heterogeneity of NSOC. Gene ontology analysis results were consistent with the NSOC network being associated with embryonic organ morphogenesis and also hinted at an aetiological overlap between NSOC and cancer. We therefore recommend this approach to be applied to other heterogeneous complex diseases to not only provide a molecular framework to unify genes which may seem as disparate entities linked to the same disease, but to also predict and prioritise candidate genes for further validation, thus addressing the missing heritability