Vascular Calcification in Rat Cultured Smooth Muscle Cells: a Role for Nitric Oxide

The underlying inflammatory storm in renal or diabetic disease may induce expression of inducible nitric oxide synthase (iNOS). Similarly, expression of iNOS or nitric oxide (NO) production in vascular smooth muscle cells (VSMCs) in a calcifying environment, may promote vascular calcification (VC) (Zaragoza et al., 2006). However, emerging data suggests that NO generated by either endothelial nitric oxide synthase (eNOS) or iNOS may protect VSMCs from VC (Kanno et al., 2008). Thus, the role of NO and its associated enzymes in the development of VC is unclear. The aim of this study was to identify whether NO produced by iNOS regulates calcification in VSMCs, and to further understanding of potential mechanisms that may mediate the actions of NO/iNOS. A significant and sustained production of NO by iNOS, which peaked at day 3 and declined thereafter was found in rat aortic smooth muscle cells (RASMCs) that were preactivated with lipopolysaccharide (LPS; 100μg ml-1) and interferon gamma (IFN-γ;100U ml-1) in the presence of calcification buffer (CB) containing calcium chloride (CaCl2; 7mM) and β-glycerophosphate (β-GP; 7mM). This was associated with formation of hydroxyapatite crystals (HA) or calcification plaques, observed via alizarin red staining (ARS) and/or fourier transform infrared (FT-IR) analysis. However, when RASMCs were incubated with the iNOS inhibitor GW274150 at 10 μM, together with LPS + IFN-γ + CB, HA crystal formation was abolished. When RASMCs were pretreated with diethylenetriamine/nitric oxide adduct (NOC 18) at either 30 or 50 μM for an hour prior to addition of CB, to generate NO; calcium levels were elevated leading to form HA crystals. However, the elevation of calcium caused by the presence of NO generated via iNOS, did not result in phosphorylation of mitogen activated protein kinases (p38 MAPK), extracellular signal-regulated kinases (Erks), and protein kinase B. Furthermore, there was a reduction of Runx2 levels (pro-calcific factor) which could be another pro-calcific factor involved in this mechanism. These findings suggest that NO may indeed play a fundamental role in calcification, enhancing mineralisation of smooth muscle cells. Furthermore, the expression of iNOS/ NO appears to be enhanced under conditions that favour calcification and these together may contribute to enhanced calcification with potential detrimental consequences in vivo

Pathogenic and Non-Pathogenic Microbial Presence in Ventilator Associated Pneumonia Patients in Intensive Care Unit and Safety Protocols Under Surveillance of Healthcare Provider: A Research Study

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection that is associated with longer stays in intensive care units (ICUs) and under mechanical ventilation for more than 48 hours. This article explores the prevalence and impact of VAP on mortality and morbidity, emphasizing the microbial associations involved in hospital-acquired infections. Various infections, including Lung infections, surgical site infections, sepsis, and urinary tract infections, are discussed, along with their associated microorganisms. Diagnostic criteria for VAP and related infections are outlined, highlighting the importance of microbiological testing for accurate diagnosis. The underlying factors for VAP acquisition in ICU patients are identified, and prompt antibiotic initiation is emphasized as a critical first-line defense against VAP. In this study, we have populated data from 100 ICU patients, among which 45 were suffering from VAP. It was found that female patients (57.40%) were more affected than male patients (30.43%). The decreasing PaO2 level was seen to be the early sign of infection. It was found that the time of ventilation was the major factor influencing the VAP. The most common organism causing infection in our study was found to be Staphylococcus Aureus (45.1%). The prognosis of early-onset VAP was 35.55% while compared to Late-onset VAP 64.44%. When compared to VAP and Non-VAP patients there was not very huge difference with 55% and 45% respectively. The other factor was age and position. Implementation of Prevention strategies, such as protective environments and HEPA filtration systems, is proposed to reduce VAP incidence. Proper diagnosis, treatment, and prevention are crucial to combatting VAP and enhancing patient outcomes in hospital settings

Acute Kidney Injury Caused Due to Colistin Therapy: A Case Report Study Analysis

An abrupt bout of kidney damage or failure that lasts a few hours to a few days is referred to as acute renal failure (ARF) or acute kidney injury (AKI). Nephrotoxicity is classified into the following categories: R-risk, I-injury, F-failure, L-loss of function, and E-end stage renal failure. It is inherited, brought on by medications, and associated with diabetes, liver diseases, and heart issues. Typically, a drug's dose-dependent nephrotoxicity affects its severity. Multi-medication resistant (MDR) infections have led to an unprecedented increase in the use of Colistin medicine. Pseudomonas aeruginosa, Klebsiella pneumoniae, and other gram-negative bacteria are to blame. One type of bacteria is Acinetobacter baumannii. This paper will provide the case of a 62-year-old male patient who was admitted to the hospital after receiving a diagnosis of venous thromboembolism and anemia. Human-acquired pneumonia results from Acinetobacter baumannii's multidrug resistance, which makes the bacteria only responsive to the antibiotics colistin and azithromycin meropenem. Two days after commencing the (Oliguria-500) medicine, there was a decrease in urine production. The renal parenchyma showed changes, and the levels of creatinine were elevated to 3.18 mg/dL. USG has been seen. Laboratory results indicate that he suffered from AKI Colistin and demonstrates strong (Naranjo score: 8) usually connected to AKI. Drug dosages were not changed. It was routine practice to monitor BUN and creatinine levels. The amount of urine produced increased to 2450 mL 15 days following treatment. Respiratory failure is one of the neurological side effects of collistin was ignored. On discharge day, the patient was stable and doing well. It seems from this that if the medication is beneficial and the risk is manageable, there is no reason to stop taking it; however, careful observation is needed. Diminish the quantity of adverse reactions

Knowledge of One Health Approach Policy and Antimicrobial Resistance Among the General Public: KAP Survey

Background: The combination of patients\u27 unsustainable use of antibiotics and doctors\u27 inappropriate prescribing practices has resulted in challenges for disease control in the community and inadequate delivery of healthcare services. Methods: The General Public\u27s understanding and awareness of AMR and the One Health Approach policy were evaluated through the use of a cross-sectional study questionnaire. Results were analysed statistically using SPSS software Study participants\u27 knowledge, attitude, and perspective scores were predicted using ordinal logistic regression analysis. Results: Participants who were self-employed have good knowledge (41.8%) about AMR and One Health Approach policy and also had higher KAP scores (CI = 4.885). Factors like age and gender were observed to have no impact on aggregate KAP scores. Conclusion: In light of the knowledge gaps identified in our survey, development and implementation of health education and campaign will help to improve awareness among General Public.   DOI: https://doi.org/10.52783/jchr.v13.i4.133

Exploring the molecular mechanisms of MSC-derived exosomes in Alzheimer's disease : Autophagy, insulin and the PI3K/Akt/mTOR signaling pathway

The authors thank you for acknowledging technical and financial support from the Ministry of Education and the University of Hafr Al Batin, Saudi Arabia. The authors gratefully acknowledge all mothers’ volunteers in the community around the Faculty of Agriculture, Benha University, for their cooperationPeer reviewe

Recent Advances Towards Treatment of HIV: Synthesis and SAR Studies

In the present study, authors want to encourage the research exertions through structureactivity relationship for the identification of effective molecules for the treatment of Human immunodeficiency virus because nowadays AIDS is considered as one of the main causes of death in human beings. A diversity of biological resources has been searched and developed for the treatment of HIV but unfortunately, until now, no medicine is found to be fully effective and safe for the cure of patients. Human immunodeficiency virus is a type of lentivirus which causes the infection of HIV and once it enters the human body, it stays for a longer period of time triggering immunodeficiency syndrome. For searching and developing new potent and effective anti-HIV molecules, medicinal chemists have engaged in countless targets with the structure-activity relationship (SAR) of molecules and on this basis, many antiretroviral therapies have been developed to cure HIV infection. Most of these new searched molecules have been found to be clinically active against various types of AIDS patient and auxiliary research in this area may lead to better treatment in the near future. This article encompasses and highlights the recent advancement of innumerable inhibitors laterally through synthetic, semi-synthetic and structure-activity relationship approaches. </jats:sec

Hydrogen Sulfide and Nitric Oxide Improve Renal Function and &alpha;-Adrenergic Responsiveness in Rats with Left Ventricular Hypertrophy

In left ventricular hypertrophy (LVH), the combined external administration of hydrogen sulfide (H2S) and nitric oxide (NO) has been shown to reverse LVH by activating the endothelial nitric oxide synthase pathway (eNOS/NO), independent of the cystathionine &gamma;-lyase (CSE/H2S) pathway. Individually, both H2S and NO have also been reported to significantly improve RCBP, restore renal excretory performance, and enhance &alpha;-adrenergic receptor responsiveness in rats. The induction of LVH was performed over a period of two weeks using drinking water with caffeine and isoprenaline. Five weeks later, the rats were fed with L-arginine (1.25 g/L) as a nitrogen oxide donor. Vascular reactions to methoxamine, phenylephrine, and noradrenaline were assessed in presences and absence of 5-methylurapidil (5-MeU), BMY7378, and chloroethylclonidine (CeC) and &alpha;1-adrenoceptor antagonists. In both the Control WKY and LVH-WKY groups, combined H2S+NO therapy significantly (p &lt; 0.05) upregulated the renal mRNA of CSE and eNOS when compared with untreated LVH rats. The treatment also markedly increased RCBP in LVH-H2S+NO rats relative to LVH controls. Furthermore, H2S+NO administration enhanced the activity of &alpha;1A, &alpha;1B, and &alpha;1D adrenergic receptors in mediating renal vasoconstriction. Even under receptor blockade with high doses (HDs) of 5-MeU, CeC, and BMY 7378, renal vasoconstriction responses to adrenergic agonists like NA, PE, and ME in the LVH-H2S+NO group remained comparable to those observed in the counterpart Control-H2S+NO group. The findings of current study suggest that simultaneous exogenous administration of H2S and NO donors improve renal cortical blood flow, support renal function, and augment &alpha;1A, &alpha;1B, and &alpha;1D adrenergic receptor responsiveness to adrenergic agonists like NA, PE, and ME in LVH rats. This effect appears to rely primarily on the eNOS/NO pathway, with partial contribution from the CSE/H2S pathway