Littlebranch0189
In the present review, we summarize some of the known non-genotoxic effects of PAHs, focusing primarily on those that have been also shown to be modulated by PAH metabolites. Despite the limitations of the available data, it seems evident that a more attention should be paid to the discrimination between the potential non-genotoxic effects of parental PAHs and those of their metabolites. This may provide further insight into the mechanisms of toxicity of this large and diverse group of environmental pollutants.
The variability in drug response is highly complex and can be attributed to the polymedication, genetic polymorphisms modulating drug-metabolizing enzyme activities (cytochromes P450, CYP), physiological and environmental factors.” sentence could be revised as “The variability in drug response is highly complex and can be attributed to the polymedication, genetic polymorphisms modulating drug-metabolizing enzyme activities (cytochromeP450s (CYP)), physiological and environmental factors.
The main objective of this review is to deeply discuss the role of biotransformation in the occurrence of antidepressant and anticonvulsant induced inter individual variabilities with the focus on genetic variations and drug interactions.
An extensive search of the literature has been conducted related to biotransformation of the antidepressant and anticonvulsant agents on relationships between genetic differences and drug interactions on available databases. Following keywords are used for relevant articles “metabolic otential results of the drug-drug interactions and individual genetic characteristics should always be considered to make pharmacotherapy safer and more effective, as they have major clinical implications.
The present review clearly illustrates that interindividual differences in the biotransformation (including genetic variability of the drug metabolizing enzymes, age, sex, diet) of the antidepressant and anticonvulsant drugs, which are commonly prescribed medications globally, has a crucial role in the occurrence of adverse effects and various drug responses. Therefore, the potential results of the drug-drug interactions and individual genetic characteristics should always be considered to make pharmacotherapy safer and more effective, as they have major clinical implications.
Catalpol, an iridoid glycoside, is one of the richest bioactive components present in Rehmannia glutinosa. More and more metabolites of drugs have exhibit various pharmacological effects, thus providing guidance for clinical application. However, few researches have paid attention on the metabolism of catalpol.
This study aimed to establish a rapid and effective method to identify catalpol metabolites and evaluate the biotransformation pathways of catalpol in rats.
In this study, catalpol metabolites in rat urine, plasma and faeces were analyzed by UHPLC-Q-Exactive MS for the characterization of metabolism of catalpol. Based on high-resolution extracted ion chromatograms (HREICs) and parallel reaction monitoring mode (PRM), metabolites of catalpol were identified by comparing the diagnostic product ions (DPIs), chromatographic retention times, neutral loss fragments (NLFs) and accurate mass measurement with those of catalpol reference standard.
A total of 29 catalpol metabolites were detected and idenhich phase Ⅰ and phase Ⅱ reactions occurred. However, hydrophilic chromatography-mass spectrometry still needed to further find the polar metabolites of catalpol.
CsaA is among the few chaperones which are present in both bacteria and archaea, but absent in eukaryotes. There are no reports on interactome analysis of CsaA from archaea, till date. Identification of binding partners of CsaA might be helpful in understanding CsaA-associated processes in Picrophilus torridus- an extreme thermoaci-dophilic euryarchaeon.
The present study was conducted to identify the binding partners of CsaA of P. torridus (PtCsaA).
The binding partners of PtCsaA were isolated and identified using a pull down assay and liquid chromatography-mass spectrometry (LC-MS).
The results revealed twelve potential binding partners of CsaA. These were thermosome subunits (Q6KZS2 and Q6L132), nascent polypeptide-associated complex protein (Q6L1N3), elongation factor 1-alpha (Q6L202), uncharacterized protein (Q6L0Y6), citrate synthase (Q6L0M8), asparaginyl-tRNA synthetase (Q6L0M5), succinyl-CoA synthetase beta chain (Q6L0B4), pyruvate ferredoxin oxidoreductase alpha and beta chain proteins (Q6KZAof CsaA-associated processes in archaea.Diabetes mellitus (DM) and peripheral artery disease (PAD) are two clinical entities closely associated. They share many pathophysiological pathways such as inflammation, endothelial dysfunction, oxidative stress and pro-coagulative unbalance. Emerging data focusing on agents targeting these pathways may be promising. Moreover, due to the increased cardiovascular risk, there is a growing interest in cardiovascular and "pleiotropic" effects of novel glucose lowering drugs. This review summarizes the main clinical features of PAD in patients, the diagnostic process and current medical/interventional approaches, ranging from "classical treatment" to novel agents.
Due to the rapid growth in life threatening diseases such as cancer, diabetes, chronic wound and HIV/AIDS along with rise of side effects of the current treatments, world is now focusing to utilize new treatment options. Currently, the development of green nanotechnology field seems as a potential alternate for diseases diagnosis and treatment by preparation of various sizes and shapes of nanomaterials.
This review is to present the explored biological sources in synthesis of nanomaterials particularly metal and metal oxides nanoparticles and critical review of the applications of biosynthesized nanoparticles in pharmaceutical and biomedical fields.
In this review, the various biological sources including bacteria, fungi, algae and plants used in synthesis of nanomaterials and mechanism involved in preparation are elaborated. In addition, biosynthesized nanomaterials applied as drug delivery system for anticancer, antibiotic, antidiabetic agent and functioned as potential diagnostic, antimicrobial, antiinimize the potential side effects.Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases which are characterized by chronic inflammation and an increase in mucus production, and are highly prevalent conditions. Despite recent advances and multiple available therapies, there remains a significant unmet medical need. Selleck NBQX Over the past 40 years, the introduction of new classes of safe and effective therapy is scanty. In spite of the high burden of asthma and COPD among patients, there are fewer new approved therapies in comparison to cardiovascular, metabolic and neurological diseases due to few drug candidates and a higher failure rate in the development of respiratory medicine. Lung diseases are amongst the leading causes of death globally with asthma being one of the most prevalent respiratory diseases, which affects people of all ages but, despite effective therapies available, many patients are poorly controlled and have a low quality of life. COPD is currently ranked the fourth cause of death worldwide and predicted to become the third leading cause of death in 2030. The development of more effective treatments is urgently needed in order to reduce the high mortality rate and the enormous suffering from asthma and COPD. Various inhalation devices with different classes of medications are the foundation as therapies in both asthma and COPD. This article gives a comprehensive review of the promising inhaled therapies in the treatment of asthma and COPD. However, the lack of disease control in asthma and COPD patients may be due to numerous reasons. The association between non-adherence to guidelines on the part of the health care provider and poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patients is common. It is therefore essential to discuss the different delivery systems and the methods used in asthma and COPD patients.Paclitaxel (PTX) is a first-line drug for late-stage non-small cell lung cancer (NSCLC) patients who do not benefit from targeted therapy or immunotherapy. However, patients invariably develop resistance to PTX upon prolonged treatments. Although diverse mechanisms leading to PTX resistance have been well-documented in the literature, strategies to overcome PTX resistance in NSCLC based on these mechanisms are still challenging. In this article, we reviewed recent advancements elucidating major mechanisms of PTX resistance in NSCLC, including the overexpression of ABC transporters, alternations to tubulin structures, and the involvement of cytokines, miRNAs, kinase signaling pathways, and epithelial-mesenchymal transition. Potential markers of PTX resistance or PTX response that could help to direct treatment decisions and restore cellular sensitivity to PTX were also discussed. Finally, we summarized the corresponding strategies to overcome PTX resistance in NSCLC cells, which might provide new insights into clinical trials and benefit lung cancer patients in the future.
The impact of magnetic resonance imaging-detected extramural vascular invasion (mrEMVI) in distant metastasis is well known but its correlation with prevalence of lymph node metastasis is less studied. The aim of this systematic review and meta-analysis was to assess the prevalence of nodal disease in mrEMVI-positive and negative cases in rectal cancer.
Following guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic literature search in PubMed, Web of Science, Cochrane Library, and EMBase was carried out to identify relevant studies published up to May 2019.
Our literature search generated 10 studies (863 and 1212 mrEMVI-positive and negative patients, respectively). The two groups (mrEMVI-positive and negative) were significantly different in terms of nodal disease status (odds ratio [OR] 3.15; 95% confidence interval [CI] 2.12-4.67;
< 0.001). The prevalence of nodal disease was 75.90% vs 52.56% in the positive mrEMVI vs negative mrEMVI group, respectively (
< 0.001). The prevalence of positive lymph node in positive mrEMVI patients treated with neoadjuvant/adjuvant chemoradiotherapy (nCRT/CRT) (OR 2.47; 95% CI 1.65-3.69;
< 0.001) was less compared with the patients who underwent surgery alone (OR 6.25; 95% CI 3.74-10.44;
< 0.001).
The probability of positive lymph nodes in cases of positive mrEMVI is distinctly greater compared with negative cases in rectal cancer. Positive mrEMVI indicates risk of nodal disease prevalence increased by threefold in rectal cancer.
The probability of positive lymph nodes in cases of positive mrEMVI is distinctly greater compared with negative cases in rectal cancer. Positive mrEMVI indicates risk of nodal disease prevalence increased by threefold in rectal cancer.Acinetobacter baumannii, notorious for causing nosocomial infections especially in patients admitted to intensive care unit (ICU) and burn units, is best at displaying resistance to all existing antibiotic classes. Consequences of high potential for antibiotic resistance has resulted in extensive drug or even pan drug resistant A. baumannii. Carbapenems, mainly imipenem and meropenem, the last resort for the treatment of A. baumannii infections have fallen short due to the emergence of carbapenem resistant A. baumannii (CRAB). Though enzymatic degradation by production of class D β-lactamases (Oxacillinases) and class B β-lactamases (Metallo β-lactamases) is the core mechanism of carbapenem resistance in A. baumannii; however over-expression of efflux pumps such as resistance-nodulation cell division (RND) family and variant form of porin proteins such as CarO have been implicated for CRAB inception. Transduction and outer membrane vesicles-mediated transfer play a role in carbapenemase determinants spread. Colistin, considered as the most promising antibacterial agent, nevertheless faces adverse effects flaws.
