جستجوی مقالات مرتبط با کلیدواژه "inhibitors" در نشریات گروه "پزشکی"

The high-level antimicrobial resistance, particularly carbapenem resistance, in Pseudomonas aeruginosa is a global health challenge. The combination of antibiotics and synergy effects is beneficial in control of drug-resistant P. aeruginosa. The synergic interaction of antimicrobial agents is af-fected by the mechanisms of antimicrobial resistance. The aim of the current study was to evaluate the effect of efflux pump inhibition on the synergy of antibiotics against carbapenem-resistant P. aeruginosa.

The antibiotics’ minimum inhibitory concentration (MIC) was determined by the microbroth dilu-tion method. The synergy effect of antibiotics was determined using the checkerboard assay with-out and with Resistance-Nodulation- Division (RND) efflux pump inhibitor phenylalanine-arginine beta-naphthylamide (PAβN).

The highest levels of synergistic effects were found between cefepime/tobramycin and meropenem/tobramycin combinations in 35.3% of isolates. After adding PAβN, the most frequent synergistic effects were observed between the meropenem/ciprofloxacin and cefepime/ciprofloxacin combinations, found in 64.7% of isolates. The adding PAβN led to an increase in the synergy of all combinations except tobramycin/colistin. The highest effect of PAβN on the synergy effects of antibiotics combination was observed in meropenem/ciprofloxacin, cefepime/ciprofloxacin, and ciprofloxacin/colistin (an increase of 41.2%). 

RND efflux pump inhibition has a noticeable effect on the results of synergy tests of some antimi-crobial agent combinations. Given the drug- and strain-dependent effects of PAβN on synergy re-sults, the effects of efflux pump inhibitors should be studied on different combinations of drugs and a large population of bacterial strains.

High levels of adherence to treatment among HIV patients as one of the sexually transmitted diseases (STD) are essential for promoting viral suppression and preventing drug resistance, but little is known about the factors that contribute to antiretroviral adherence. This study aimed to evaluate adherence to therapy and its related factors among HIV-infected patients.

This mixed-methods study was carried out at the Behavioural Diseases Center in Tabriz, Iran in 2021. In a cross-sectional study phase, 137 HIV-infected patients were selected through census sampling method. Then, 21 in-depth interviews were conducted during the qualitative phase using a content analysis approach. Quantitative and qualitative data analysis was performed by SPSS (version 24) and MAXQDA (Version 10), respectively.  

The mean score of Adherence was 8.96±2.36 and the majority of participants had moderate to high adherence to treatment. The analyses of regression, predictors of adherence included marital status (β= 0.219, SE= 0.090, P=0.016), income level (β= 0.206, SE= 0.201, P=0.030), and education (β= 0.226, SE= 0.063, P=0.021). Also, two themes of “perceived barriers” and “perceived facilitators” emerged which included six main categories at the individual, socio-environmental and organizational as well as drug and treatment levels.

Despite moderate to high adherence, antiretroviral treatment is a challenging issue. Based on the results, various factors play a role as obstacles and facilitators factors of adherence to treatment among HIV patients. So, intervention programs can be aimed at removing barriers and strengthening facilitators based on based on the factors involved.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are the most recent pharmaceutical group for type 2 diabetes (T2D) treatment. Evidence indicates contradictory relationships between sodium-glucose cotransporter-2 inhibitors and bladder cancer (BC). Hence, this study aims to investigate the relationship between SGLT2 inhibitors and BC in patients with T2D.

This study is a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). International databases including Cochrane, Web of Science, Scopus, PubMed, and Google Scholar were conducted for searching with keywords and without time and language limitations. The reference searching stage continued upgrading until November, 2022. Data analysis was performed with STATA 14 software. The tests with P values lower than 0.05 were considered statistically significant.

The four reviewed studies with a sample size comprising 497 755 individuals indicated the impact of SGLT2 inhibitors on BC of patients with T2D (OR: 0.68; 95% CI: 0.37, 1.2). The effect of dapagliflozin, canagliflozin and empagliflozin administration on the incidence of BC among the T2D patients were (OR: 0.72; 95% CI: 0.39, 1.30), (OR: 0.53; 95% CI: 0.23, 1.20), and (OR: 0.51; 95% CI: 0.20, 1.28), respectively.

The general conclusion of this study revealed that SGLT2 inhibitors did not increase the risk of BC in T2D patients. The analysis of subgroups also indicated that the administration of dapagliflozin, canagliflozin, and empagliflozin also did not increase the risk of BC in T2D patients.

Depression is a prevalent psychiatric disorder. Treatment of depression is still a challenge due to the lack of response of some patients to a variety of available medications and side effects. Isatin is an interesting molecule with diversified biological effects. It also participates in many synthetic reactions, as a precursor molecule. In this study, a new series of N-alkyl and N-benzyl isatin derivatives bearing Schiff bases were synthesized and screened for antidepressant activities in mice.

The synthesis was initiated by N-alkylation and N-benzylation of isatin by an alkylation reaction to give N-substituted isatins. 2-(Benzyloxy) benzohydrazide derivatives were synthesized by treating methyl2-hydroxybenzoate with benzyl bromide or 4-chlorobenzyl bromide which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. The final compounds were obtained by condensation of N-substituted isatins with 2-(benzyloxy) benzohydrazide derivatives as Shiff-base products. Compounds were evaluated for antidepressant activities in mice by the locomotor activity, marble burying test, and forced swimming test. Monoamine oxidase–A (MAO–A) enzyme has been used for molecular docking studies.

Compounds 8b and 8e in both doses, and 8 c in the lower dose, reduced immobility time during the forced swimming test relative to the control group. All preparations reduced the number of marbles buried compared with the control group. The highest docking score was -11.01 kcal/mol for compound 8e.

N-Benzylated-isatin (8b, 8e) and N- acetic acid ethyl ester -isatin derivatives (8c) showed more effective antidepressant activity compared with N-phenyl acetamide isatin derivatives. Docking results relatively confirm the pharmacological results.

Isoprenoids and their derivatives are building blocks for the synthesis of biomolecules with important biological functions such as cholesterol in eukaryotes and lipid carrier undecaprenol, which is involved in cell wall biosynthesis in bacteria. With the global threat of multidrug‑resistant bacteria, there is a need for finding new metabolic targets for killing bacteria. In the present study, we examined the impact of eukaryotic sterol biosynthesis inhibitors on the growth of four pathogenic bacteria.

Antibacterial effect of HMG CoA reductase inhibitor (simvastatin), farnesyl pyrophosphate synthase inhibitor (alendronate), squalene epoxidase inhibitor (terbinafine), and lanosterol demethylase inhibitor (ketoconazole) were studied against four pathogenic bacteria: two gram‑positive bacteria, Staphylococcus aureus and Enterococcus faecalis and two gram‑negative bacteria, Escherichia coli and Pseudomonas aeruginosa. Broth microdilution method was used for assessing the antibacterial susceptibility of the components using 96 well plats. MIC and MBC were determined visibly.

MIC of Ketoconazole for Staphylococcus aureus and Enterococcus faecalis were 0.166 and 1 mg/mL, respectively. Terbinafine had a weak inhibitory effect on Staphylococcus aureus (MIC: 8 mg/mL). Ketoconazole and terbinafine had no inhibitory effect on gram‑negative bacteria. MBC of Simvastatin for both Staphylococcus aureus and Enterococcus faecalis was 0.5 mg/mL and of Alendronate for Pseudomonas aeruginosa was 6.6 mg/mL.

Our results show that farnesyl pyrophosphate synthase and classII HMG‑CoA reductases inhibitors(ketoconazole and simvastatin) have reasonable antibacterial activity against gram‑positive bacteria. These two enzymes provide suitable targets for designing new antibiotics based on modifying the chemical structure of currently used drugs to obtain maximum activity

The severe acute respiratory syndrome coronavirus 2 (known as COVID-19), initially appeared in the Wuhan city of China in December 2019, has become a current medical issue around the world. Due to its highly contagious nature, COVID-19 has spread widely to all countries. As no effective treatment or vaccine is developed for this infectious disease, preventive measures are the only mandatory strategy to stop its human-to-human transmission. In the present spread of COVID-19, the discovery of antiviral drugs is crucially important as the development of these drugs often takes time. However, no specific drug has yet been approved for COVID-19. In this review, we focus on the available drug candidates used for the treatment of infections caused by COVID-19 to identify potential inhibitors through molecular docking.

Oral squamous cell carcinoma (OSCC) represents the most common oral cavity cancer worldwide, being among the 10 most frequent cancers of all types. Only around 50% of patients survive longer than 5 years in view of currently applied medical procedures of diagnosis and treatment. The delay in diagnosis accounts for the shortening of survival despite advances in treatment protocols. The poor prognosis as well as high occurrence rate exerts a burden on both patients and clinicians. Cancer biomarkers may possibly present cancer profiles of different patients and foreseeing each upcoming therapy response and the subsequent outcomes. Identification of the most fundamental biomarkers in OSCC may lead us to precise detection, which can give rise to earlier diagnosis, more effective treatment options, and more patient oriented prognostic decisions, alleviating the current situation regarding the failure in effectual OSCC management.  In this review, we have outlined the molecular biomarkers for early diagnosis of OSCC and suggested inhibitors through which metastasis and its molecular pathways could potentially be inhibited.

The high prevalence of skin hyperpigmentation makes it necessary to search for remedies that could hinder this process. Among such substances, tyrosinase inhibitors can be distinguished, which may be pyrimidine derivatives.

This study aimed to investigate new compounds with anti-tyrosinase activity in 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one by an in vitro analysis and investigating their molecular docking.

A molecular docking was performed using AutoDock 4.0 with the 3-dimensional structure of tyrosinase of the fungus Agaricus bisporus from the Protein Data Bank (PDB; rcsb.org) with identification number 2Y9X. A synthesis of 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one was carried out during the heterocyclization reaction of azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in glacial acetic acid with the addition of dimethyl sulfoxide. Tyrosinase activity was determined in vitro by the spectrophotometric method.

Molecular docking data suggest the feasibility of synthesizing 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one as possible tyrosinase inhibitors. Of particular interest are compounds with hydroxy groups in the radical. Next, pharmacological screening showed that the leading compound is 4g. It is likely that metal–ligand interactions are the main interactions in the active site of tyrosinase because kojic acid, hydroquinone, and lactic acid (reference compounds), as well as compounds with only hydroxy groups in phenyl substituents (4b, 4c, and 4g), have the greatest anti-tyrosinase activity.

As a result of molecular docking studies, the feasibility of synthesizing 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one as potential tyrosinase inhibitors was justified. 2-Substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one was obtained using new synthesis conditions. The leading compound is 4g containing a fragment of 2,4-dihydroxybenzene.

Fire is one of the potential dangers that threaten human activities more and more. Given that, this study will seek to introduce the factors preventing the spread of fire in hospitals to policymakers through prioritization based on applied mathematics modeling.

This study consisted of two stages. In the first stage, first through a comprehensive review of studies, factors preventing the spread of fire were identified, and then in the second stage, based on experts' opinions, the attributes affecting selection prioritization, their weights were determined and finally, based on the simple additive weighting (SAW) model the final prioritization was done for 5 types of hospital buildings.

On the base of literature review and expert opinions, 7 factors and 4 attributes were identified. The most important factors were following as; "use of safety architecture and equipping appropriate emergency exit accesses according to the standard" in high-rise hospitals; "continuous training of firefighters" in wide hospitals; "use of fire extinguishing systems (automatic and manual)" in subsurface hospitals; "the use of fire extinguishing systems (automatic and manual)" in combined hospitals, and "continuous training of personnel firefighters" in portable hospitals.

Fire safety is not limited to the installation of a manual fire extinguisher, but for fire safety, especially in hospitals, all aspects should be considered, including the architectural form of the building, how the materials and equipment in the building caught fire, fire behavior in terms of heat transfer methods, the amount of firefighting training of the personnel, recognition and application of modern and ready-made equipment for smoke ventilation systems and fire products, automatic and manual fire alarm and extinguishing systems to prevent the spread of fire.

A major complication in treating hemophilia A is the development of neutralizing antibodies (inhibitors) against therapeutic administered factor VIII (FVIII), which occurs in approximately 20-30% of patients with severe disease. These inhibitors render FVIII replacement therapy ineffective and increase the morbidity and mortality risk. The currently accepted method to eradicate inhibitors is immune tolerance induction (ITI), and frequent intensive administration of FVIII until inhibitor titers drop. Current ITI protocols are extremely costly and not effective in all patients. During the last decade, many types of research have been accomplished to clarify the mechanisms that mediate immune tolerance induction. Novel experimental therapies including monoclonal antibodies, viral vector-mediated gene therapy, regulatory T cell induction using immunosuppressive drugs, and nanoparticle-based immune modulation show promising results in hemophilia A clinical trials. This review focuses on treatment options towards the anti-FVIII immune responses and current novel therapies in clinical trials.

Cyclic nucleotide phosphodiesterases (PDEs) are known as a super‑family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic‑3’,5’‑adenosine monophosphate (cAMP), and cyclic‑3’,5’‑guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution. The PDE4 family has been the focus of vast research efforts over recent years because this family is considered as a prime target for therapeutic intervention in a number of inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, and it should be used and researched by pharmacists. This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP‑specific PDE, PDE4. This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

The purpose of this study is to study the factors affecting the development of higher education in Guilan province with the approach of Islamic management.

The present study is descriptive and the statistical population of the present study includes 3663 experts, professors and managers of higher centers in Guilan province. Using Morgan table, 331 people were determined as the sample size and their selection was done in a stratified-random manner. Also, the opinions of 15 experts were used to evaluate the criteria in TOPSIS and AHP models.

Library data collection method and data collection tool Researcher-made questionnaire consisting of 11 criteria and 37 sub-criteria in the form of internal and external organizational drivers and 12 criteria and 36 sub-criteria in the form of internal and external inhibitory factors The deterrent has been linked to indicators of higher education development. Analysis of pairwise comparisons of the findings showed that among the internal factors of propulsion, "factors related to finance and fair payment" with a weight ratio of 0.384 has the highest priority and "factor controlling religious-cultural teachings" with a weight ratio of 0.048 has priority Is the last. Also, among the extra-organizational criteria of the driving factors, the factor of "interaction with stakeholders" with a weight ratio of 0.419 has the highest priority and "weak physical resources" with a weight ratio of 0.026 has the highest priority. Also, among the internal criteria, the deterrents of "weak independence of universities" with a weight ratio of 0.223 have the highest priority and the factor of "competition" with a weight ratio of 0.051 is in the last priority. Finally, the analysis of external criteria of deterrents showed that the factor of "external interaction" with a weight ratio of 0.630 has the highest priority and "distance from the competitive environment" with a weight ratio of 0.218 in the second priority and finally "weak transnational interaction" with a weight ratio. 0.151 is in the last priority.

What became clear from the results of this study, in general in the areas of factors related to finance, process, accountability factor, physical factor, human factors, cultural factor, interaction with stakeholders, national quality assurance system, external interaction, It is a factor of technology and a factor of competition that should be considered by managers and stakeholders.