Preparation and In vitro Evaluation of Intelligent Blood Glucose Regulating Nanonetwork Based on PLGA and Chitosan Nanoparticles

Introduction: Intelligent systems which release insulin in response to glucose level have been investigated thoroughly and many researches work in this area. In this work we present preparation and characterization of a novel Nano system composed of chitosan and PLGA nanoparticles, incorporating insulin, glucose oxidase and catalase. Methods and Results: Chitosan nanoparticles were prepared through ionic gelation method. First chitosan solution (2 mg/ml) in acetic acid 1% (v/v) was prepared. 2 mg insulin was dissolved in 5 ml of this solution. TPP solution was added dropwise. Stirring the solution was continued for 1 hour. Chitosan nanoparticles were separated by ultracentrifugation. Size of these nanoparticles was found to be 180-200 nm. Preparation of PLGA nanoparticles containing glucose oxidase (GOx) and catalase (CAT) was done by double emulsification technique.  PLGA was dissolved in ethyl acetate then aqueous solution of GOx and CAT were added to this organic phase. Sonication was performed to prepare w1/o emulsion. Deionized water was added and by second sonication w1/o/w2 emulsion was formed. Theorganic phase was removed by vacuum rotary evaporator and nanoparticles were separated through filtration, in size range of 130-150 nm. Chitosan NPs were added to PLGA NPs and the Nano system was formed through an electrostatic attraction between two oppositely charged particles. In vitro insulin release from this Nano system was investigated through radiolabeling method at two different glucose concentrations of 70 and 400 mg/dl. Conclusions: At high glucose concentration after glucose entrance into PLGA NPs it was converted to gluconic acid. Lowering of the Nano system microenvironment pH caused protonation and swelling of chitosan NPs and hence insulin release

Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT1) and L-type calcium channels were investigated on isolated rat aorta. Materials and MethodsAortic rings were pre-contracted with 1 µM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution.ResultsThe results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100,000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. ConclusionFinally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents

Contrastive Learning of Temporal Distinctiveness for Survival Analysis in Electronic Health Records

Survival analysis plays a crucial role in many healthcare decisions, where the risk prediction for the events of interest can support an informative outlook for a patient's medical journey. Given the existence of data censoring, an effective way of survival analysis is to enforce the pairwise temporal concordance between censored and observed data, aiming to utilize the time interval before censoring as partially observed time-to-event labels for supervised learning. Although existing studies mostly employed ranking methods to pursue an ordering objective, contrastive methods which learn a discriminative embedding by having data contrast against each other, have not been explored thoroughly for survival analysis. Therefore, in this paper, we propose a novel Ontology-aware Temporality-based Contrastive Survival (OTCSurv) analysis framework that utilizes survival durations from both censored and observed data to define temporal distinctiveness and construct negative sample pairs with adjustable hardness for contrastive learning. Specifically, we first use an ontological encoder and a sequential self-attention encoder to represent the longitudinal EHR data with rich contexts. Second, we design a temporal contrastive loss to capture varying survival durations in a supervised setting through a hardness-aware negative sampling mechanism. Last, we incorporate the contrastive task into the time-to-event predictive task with multiple loss components. We conduct extensive experiments using a large EHR dataset to forecast the risk of hospitalized patients who are in danger of developing acute kidney injury (AKI), a critical and urgent medical condition. The effectiveness and explainability of the proposed model are validated through comprehensive quantitative and qualitative studies.Comment: This paper has been accepted for publication at the CIKM 2023 conferenc

Prevalence of qnr, intI, and intII genes in extendedspectrum beta-lactamase (ESBL)-producing Escherichia coli isolated from clinical samples in Iran

Purpose: To investigate the prevalence of qnr, intI, and intII genes in extended spectrum betalactamase (ESBL)-producing Escherichia coli isolated from clinical samples in Kerman, Iran.Methods: A total of 127 E. coli were collected from clinical samples in Kerman hospitals. The antibiotic susceptibility test was performed using disc diffusion method, while the presence of ESBL-producing E. coli was determined by phenotypic confirmatory test. Furthermore, the presence of qnrA, qnrB, qnrS, intI, intII, and β-lactamase-encoding genes was detected by polymerase chain reaction (PCR). Finally, the data were analyzed and associations between different genes and antibiotic resistance were evaluated.Results: The highest and lowest rates of resistance were observed against ampicillin (72.4 %) and imipenem (2.3 %), respectively. Also, 41.7 % of the isolates produced ESBL-enzymes. The qnrS and genes were detected in 6.3 and 0.78 %, respectively, of the isolates, while qnrA gene was not detected in the current study. The results revealed that 64.5 and 10.2 % of isolates carried intI and intII genes, respectively. Data analysis showed a significant association between ESBL production and class I integrin gene in E. coli isolates.Conclusions: Due to the variation in the resistance patterns of E. coli against antibiotics in different geographical regions, antimicrobial treatments should be based on local experience. Also, the coexistence of ESBL and intI gene in the majority of E. coli isolates suggests that care should be taken in choosing antibiotic therapy.Keywords: Extended-spectrum β-lactamase, E. coli, Integrin, Imipenem, Bacterial genes, Antibiotic resistanc

Synthesis and Effects of 4,5-Diaryl-2-(2-alkylthio-5-imidazolyl) Imidazoles as Selective Cyclooxygenase Inhibitors

Objective(s)In recent years highly selective COX-2inhibitors were withdrawn from the market because of an increased risk of cardiovascular complications. In this study we were looking for potent compounds with moderate selectivity for cox-2. So, four analogues of 4, 5-diaryl-2-(2-alkylthio-5-imidazolyl) imidazole derivatives were synthesized and their anti-inflammatory and anti-nociceptive activities were evaluated on male BALB/c mice (25-30 g). Molecular modeling and in vitro COX-1 and COX-2 isozyme inhibition studies were also performed. Materials and Methods2-(2-Alkylthio-5-imidazolyl)-4,5-diphenylimidazole compounds were obtained by the reaction of benzyl with 2-alkylthio-1-benzylimidazole-5-carbaldehyde, in the presence of ammonium acetate. Spectroscopic data and elemental analysis of compounds were obtained and their structures elucidated. Anti-nociception effects were examined using writhing test in mice. The effect of the analogues (7.5, 30, 52.5 and 75 mg/kg) against acute inflammation were studied using xylene-induced ear edema test in mice. Celecoxib (75 mg/kg) was used as positive control.ResultsAll four analogues exhibited anti-nociceptive activity against acetic acid induced writhing, but did not show significant analgesic effect (P< 0.05) compared with celecoxib. It was shown that analogues injected 30 min before xylene application reduced the weight of edematic ears. All analogues were found to have less selectivity for COX-2 in comparison to celecoxib. ConclusionInjected doses of synthesised analogues possesses favorite anti-nociceptive effect and also has anti-inflammatory effects, but comparing with celecoxib this effect is not significantly different. On the other hand selectivity index for analogues is less than celecoxib and so we expect less cardiovascular side effects for these compounds

Diagnostic Performance of Ultrasonography for Identification of Small Bowel Obstruction: A Systematic Review and Meta-analysis

Introduction: Small bowel obstruction (SBO) is known as a common cause of acute abdominal complaints in the emergency department (ED). The modality of choice for the diagnosis of SBO has not yet been established. This systematic review and meta-analysis aimed to investigate the accuracy of ultrasonography for the diagnosis of SBO. Methods: Systematic search was performed on five electronic databases including Medline, Scopus, Web of Sciences, Embase, and Cochrane Library, and the retrieval period was from the inception of each database to November 2023. The quality of the included studies were investigated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The pooled values of diagnostic characteristics for ultrasonography were estimated using meta-Disc and Stata statistical software. Results: Twenty-one studies with a total of 1977 patients were included in the meta-analysis. The pooled estimate for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary ROC curve of ultrasonography for diagnosing SBO were 0.93 (95% CI: 0.91–0.95), 0.8 (95% CI: 0.77–0.83), 5.69 (95% CI: 3.64–8.89), 0.1 (95% CI: 0.07–0.16), 83.51 (95% CI: 18.12–182.91) and 0.96, respectively. Conclusion: The findings of this meta-analysis showed that the utilization of ultrasonography holds promise as a diagnostic imaging for SBO with high accuracy. However, additional worldwide studies are essential to get more evidence on the value of ultrasonography for the diagnosis of SBO

Synergistic Cytotoxic Effect of Gold Nanoparticles and 5-Aminolevulinic Acid-Mediated Photodynamic Therapy against Skin Cancer Cells

Background: Photodynamic therapy (PDT) is a promising therapeutic modality for the treatment of cancer and other diseases. In this study, the epidermoid carcinoma cell line A431 and the normal fibroblasts were used to investigate whether gold nanoparticles (GNPs) can induce an increase in cell death during PDT using 5-aminolevulinic acid (5-ALA) as a photosensitizer. Methods: Human fibroblast and A431 cells were grown in 96-well plates. The effect of GNPs on the efficacy of 5-ALA-mediated PDT (5-ALA-PDT) was evaluated by comparing the effect of 5-ALA with GNPs to the effect of 5-ALA alone. Cell viability was determined by the methyl- tetrazolium assay. Results: Dark toxicity experiments showed that 5-ALA at concentrations 0.5, 1 and 2 mM had no significant effect on cell viability of both cell lines. However, treatment of cells with 5-ALA (0.5 to 2 mM) and light dose of 25 Jcm-2 led to 5-10% and 31-42% decrease in cell viability of fibroblast and A431 cells respectively. The data also shows that GNPs in both the absence and the presence of light, results in a dose-dependent decrease in cell viability of both cell lines. However, the sensitivity of cancer cells to GNPs at concentrations more than 24 μg/ml was approximately 2.5- to 4-fold greater than healthy cells. Furthermore, data indicates that 5-ALA in combination with GNPs results in a synergistic reduction in viability of A431 cells. Conclusion: In summary, the findings of this study suggest that concomitant treatment with 5-ALA and GNPs may be useful in enhancing the effect of 5-ALA-PDT

Study of Alcohol Extract of Sesame on Wound Healing of Diabetic Male Wistar Rats

Introduction and Aims Diabetes is a metabolic disorder, which is characterized by hyperglycemia resulting from defects in insulin secretion and impaired pancreatic function. Regarding to the medicinal properties of amaranth, this study was conducted to investigate the effects of amaranth on skin histomorphological changes in diabetic rats. Materials and Methods In this study, 48 male Wistar rats were divided into four groups (control group, sham group, first experimental group, and second experimental group). In these rats, an injured area of 3cm2 was created on the left spine. Wound healing was evaluated macroscopically. Results Wound healing in group that became diabetes using streptozocin, showed late recovery compared to normal wound healing in normal groups and wound healing in experimental groups treated with alcohol extract of sesame was accelerated compared to control group. Conclusion Results of this study showed that alcohol extract of sesame causes accelerated skin wound healing in normal and diabetic samples. * Corresponding Author: Islamic Azad University, Shahrood Branch, School of Medical Sciences. Email: [email protected]

A Yearlong Epidemiologic Study on Unintentional Acute Carbon Monoxide Poisoning in Fars Province, Southwest Iran

Background: Knowing the pattern of carbon monoxide (CO) poisoning in each region is vital for enhanced health planning. This study was designed to evaluate the epidemiologic pattern of unintentional acute CO poisoning in major cities of Fars province, southwest of Iran.  Methods: This one-year cross-sectional study was carried out on unintentional CO poisoning incidents in Fars province, Iran, during the year 2011. The target population was people living in 7 major cities under supervision of Shiraz University of Medical Sciences including Shiraz, Eghlid, Neyriz, Khorambid, Marvdasht, Darab and Bavanat. Results: During 2011, 111 CO poisoning events occurred in the catchment area. These events involved 420 individuals (50.2% men) who were present during the poisoning event, of which 281 individuals with mean age of 27.8 ± 14.8 years were poisoned (46.5% men). The majority of CO poisoning events (77.3%) occurred in colder months of the year. Most events happened in urban areas (61.3%). The most common source of CO was water heater (27.5%) closely followed by gas stove (24.8%). The majority of poisoned patients were asleep during the event (150/281: 53.3%). The main causes of CO generation were inbound gas return (62.2%) and inappropriate ventilation (28.8%). The fatality rate of CO poisoning was significantly higher in men compared to women both in involved individuals and poisoned patients (P = 0.035, < 0.001; respectively). Moreover, poisoned victims who were asleep during the accident were more likely to die than those who were awake (14.3 vs. 3.7%, P < 0.001). Conclusion: Generally, the incidence and fatality rate of CO poisoning in the current study were comparable to those of the world statistics, but higher than in developed counties. Attention and emphasis on the safety of gas heaters, stoves, and other gas-powered appliances in residential places should be enforced

Evaluation of new cases of HCV infection in thalassaemia patients for source of infection

Background: Screening tests on blood bags is important step for blood safety. In Iran, screening for HCV started from 1996. We decided to determine the new cases of hepatitis C in our thalassemic patients, after screening of blood bags was initiated and trace backing from recipients to find their donors. Materials and Methods: The study was done on patients with complete files for HCVAb test results. Only cases that had a positive HCVAb result following a negative result were considered as new cases. For trace backing, we recorded the blood transfusions&#x2032; date and the blood bags&#x2032; number from last negative test results (HCVAb) to the first positive test result. These data were sent to the transfusion center. The suspected donors were contacted and asked to be tested again in the transfusion center. Results: A total of 395 patients were studied; 229 (58&#x0025;) males and 166 (42&#x0025;) females. Mean age was 27.5 years. We had 109 HCV (27.5&#x0025;) positive cases of whom 21 were infected after 1996. We traced the last five cases contaminated during 2003 and 2004. These five patients had 13, 10, 13, 12, and 6 donors, respectively (totally 54 donors were found). We proved the healthy state in 68.5&#x0025; (37 of 54) of our donors population. Of them, 81&#x0025; were repeated donors and 17 of 54 donors (31.5&#x0025;) could not be traced (because of change in addresses). We did not have any HCV new cases after 2004. Conclusion: We could not prove HCV transmission from donors as the source of infection. Although parenteral transmission is always on top of the list in HCV infection, the possibility of hospital and/or nursing personnel transmission and/or patient-to-patient transmission such as use of common instruments like subcutaneous Desferal&#174; infusion pumps; which the patients used for iron chelation therapy, should also be kept in mind