Asian Journal of Pharmaceutical and Clinical Research

INSIGHTS INTO THE MOLECULAR AND BIOCHEMICAL ROLE OF QUINIC ACID IN ALLEVIATING ETHANOL-INDUCED LIVER TOXICITY IN A RAT MODEL: EXPLORING OXIDATIVE STRESS, INFLAMMATION, AND APOPTOSIS SIGNALING PATHWAYS

2024-10-03T21:43:14+0530

Objective: The study aimed to evaluate the effects of quinic acid, a natural bioactive compound, on tissue and circulatory antioxidant status, lipid peroxidation, and its anti-apoptotic and anti-inflammatory mechanisms in ethanol-induced hepatotoxicity in rats.

Methods: The rats were divided into four groups. Groups 1 and 4 were administered isocaloric glucose. Groups 2 and 3 received 30% ethanol at a dose of 5 g/kg body weight daily. In addition, Groups 3 and 4 were treated with quinic acid (50 mg/kg body weight) dissolved in 2% dimethyl sulfoxide.

Results: The results demonstrated significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxides (LOOH), along with significantly reduced enzymatic and non-enzymatic antioxidant activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), as well as reduced levels of glutathione (GSH), Vitamin C, and Vitamin E in ethanol-treated rats compared to the control group. Administration of quinic acid to rats with ethanol-induced liver injury significantly reduced the levels of TBARS, LOOH, and CD while markedly increasing the activity of SOD, CAT, GPx, GR, GST, and levels of GSH, Vitamin C, and Vitamin E in liver tissues compared to untreated ethanol-exposed rats. In addition, ethanol-treated rats showed increased mast cell accumulation, which was reduced by quinic acid treatment, along with elevated expressions of inflammatory and apoptotic markers, including Bax, Caspase-9, tumor necrosis factor-alpha, Nuclear factor kappa B, and interleukin-6, and a decreased expression of Bcl2 in the liver. Quinic acid supplementation in ethanol-fed rats reversed these ethanol-induced changes. Immunohistochemical studies further supported these findings.

Conclusion: Quinic acid, with its antioxidant, anti-inflammatory, and anti-apoptotic properties, may offer a therapeutic option for protecting against ethanol-induced hepatotoxicity

A COMPARATIVE STUDY ON EFFICACY AND SAFETY OF STREPTOKINASE AND RETEPLASE IN PATIENTS WITH MYOCARDIAL INFARCTION IN A TERTIARY CARE TEACHING HOSPITAL

2024-10-10T12:15:47+0530

Objectives: This study compares the efficacy, safety, and cost-effectiveness of streptokinase and reteplase in treating patients with acute myocardial infarction (AMI) at SRM Hospital. A total of 86 patients were divided into two groups, each receiving either streptokinase or reteplase, with outcomes tracked over a 3-month period.

Methods: Over the course of 3 months, the results of 86 patients who were split into two groups and given either reteplase or streptokinase were monitored.

Results: The duration of hospital stays (6.05 days vs. 9.79 days) and the time it took to relieve symptoms (4.58 h vs. 8.74 h for streptokinase) were both significantly shortened by reteplase, according to the results. However, streptokinase was found to be more cost-effective. Both treatments showed similar increases in creatine phosphokinase (CPK) and CPK-MB biomarkers post-thrombolysis, but reteplase demonstrated superior efficacy. While reteplase was associated with a higher incidence of bleeding, streptokinase had more cases of hypotension and hypersensitivity. No significant mortality or morbidity was observed during the study period.

Conclusion: This study highlights the clinical advantages of reteplase over streptokinase, despite its higher cost.

ROLE OF TEXTURE ANALYSIS IN PREDICTING HISTOPATHOLOGICAL OUTCOME IN PATIENTS WITH BRAIN MASSES USING CT AND MRI IMAGING

2024-10-26T11:12:53+0530

Objectives: Brain tumors, particularly gliomas, are difficult to differentiate radiologically, whether they are benign or malignant, which usually requires histopathological examination. Texture analysis (TA), a method for quantification of heterogeneity of the tumor, can be used as a tool for this differentiation. This study aims to elucidate possible associations between computed tomography (CT) scan or magnetic resonance imaging TA (MRI TA) of brain tumors and their histopathological diagnosis.

Methods: A total of 20 patients with brain tumor were retrospectively studied. A detailed history was taken so that only pre-treatment CT/MRI scans were included to avoid heterogeneity of the sample. Patients from all age groups and sexes were included. Postcontrast images with the largest cross-section of the tumor were processed for TA (using texRAD software).

Results: In this study, it was found that for World Health Organisation (WHO) grade I and II brain tumors, mean and mean of positive pixel (MPP) are high and Kurtosis is low when compared with WHO grade III and IV. The strongest differences on unfiltered images were found for mean and MPP (p=0.049) and on medium-level filter for Kurtosis (p=0.049).

Conclusion: TA has a great potential to improve the diagnosis and stratification of patients of brain tumors. It can also give information regarding the underlying growth patterns, and hormonal/tumor markers, may add inputs in decisions regarding therapeutic efficacy, follow-up before and after treatment and prognosis, thus helping in the management of the patient.

DEVELOPMENT AND EVALUATION OF CONTROLLED POROSITY OSMOTIC TABLETS OF CANDESARTAN CILEXETIL USING INCLUSION COMPLEX SYSTEM

2024-11-15T12:19:50+0530

Objective: This study aims to enhance the solubility of BCS Class-II drug candesartan cilexetil (CC) by forming inclusion complexation with hydroxypropyl β-cyclodextrin (CDs) and develop a controlled-release osmotic tablet for 24-h release.

Methods: Solubility of Candesartan was enhanced using hydroxypropyl β-CDs at a molar ratio1:1 and analyzed for drug content and drug release profile. Fourier transform infrared interaction studies were conducted in drug complex and excipients. Core tablets were prepared with various ratios of osmogens (mannitol: Lactose monohydrate). Pre-compression studies were performed, and cellulose acetate solution containing sorbitol as pore-forming agent was used to coat the tablet cores, achieving 3% and 5% weight gain. The core tablets were subjected to post-compression tests assessing parameters such as thickness, weight variation, hardness, friability, and drug content, while the coated tablets underwent in vitro dissolution studies. Data obtained were subjected to drug release kinetics and formulation F6 was subjected to stability studies.

Results: Characterization confirmed good flow properties, mechanical stability, and uniform drug content. Formulation F6 coated with cellulose acetate, showed 97.33% drug release at 24 h, following zero-order kinetics. Stability studies indicated that F6 remained stable for 3 months, with no notable changes in attributes such as appearance, drug content, and dissolution profile.

Conclusion: This study successfully formulated a controlled drug delivery system for CC using controlled porosity osmotic delivery suggesting its potential for further development and clinical evaluation to enhance patient compliance and therapeutic efficacy.

IMPACT MONITORING OF LOW AND HIGH DEXAMETHASONE DOSES ON COVID-19 OUTCOMES IN HODEIDAH, YEMEN: A PHARMACOEPIDEMIOLOGICAL STUDY

2024-11-19T11:48:55+0530

Objectives: The study aimed to describe the pharmacoepidemiological properties of high and low dexamethasone doses on patients from COVID-19 in Hodeidah, Yemen.

Methodology: A randomized clinical trial included 192/323 patients with COVID-19 (28/49 cases in the first wave 2020 and 164/274 cases in the second wave 2021), aged from 3 to 80 years old, confirmed by real time-polymerase chain reaction. All patients were admitted in the isolation department, Center of Tropical Medicine and Infectious Diseases, AL Thawara Public Hospital Authority, Hodeidah, Yemen. 28 patients received high dose of dexamethasone (20–10 mg daily for 10 days) with standard care in the first wave and 164 patients received low dose of dexamethasone (6–8 mg daily for 10 days) in the second wave with standard care.

Results: The results showed non-significant differences between the impact of dexamethasone in both waves with different doses of dexamethasone (X2: 1.70; p=0.91). On the other mean, the case fatality rate (CFR) in the first wave with high dose was 10.71% and CFR of the second wave with low dose was 22.29%. While the results showed significant differences between high dose and low dose group with mechanical ventilator “mechanical ventilation (MV)” (X2: 7.10; p=0.0076), the CFR of patients with MV and high dose was 37% and CFR of the second wave with low dose was 77% In addition, all admitted cases had acute respiratory distress syndrome and the onset date of symptom was 2 weeks before hospitalization. Old age, chronic diseases, and co-infection may be contributing factors to effect on dexamethasone efficacy and excess mortality among COVID-19 patients.

Conclusion: The study assessed the effectiveness of dexamethasone in high and low dose in treating patients hospitalized with COVID-19 in Hodeidah, Yemen and found difference between mortality and recovery outcomes with high and low dose where the high doses of dexamethasone had good outcome for critical cases with MV.

VIRTUAL SCREENING OF THE ZIMBABWE NATURAL PRODUCT DATABASE FOR GLUCOKINASE ACTIVATORS

2024-11-23T12:00:29+0530

Objective: This study aimed to identify potential glucokinase activators within Zimbabwean natural products using virtual screening techniques.

Methods: Twenty-one compounds filtered from ChEMBL ID 3820 (pEC50 ≥ 8) were used to generate a pharmacophore model, validated with DUD-E data. The model screened the 6220 compounds in the Zimbabwe Natural Products Database (ZiNaPoD) using LigandScout. Hit compounds were docked with glucokinase (protein ID 4NO7) using AutoDock Vina and AutoDock 4 in PyRx, followed by adsorption, distribution, metabolism, and excretion (ADME) screening by SwissADME. Molecular dynamics simulations were conducted on the resulting complexes using the CHARMM36m force field on GROMACS.

Results: The validated pharmacophore model (80% accuracy, 95% sensitivity, 80% specificity) produced 149 hits, 16 of which had binding energies ≤ −8 kcal/mol after the two rounds of molecular docking. The ADME analysis narrowed the selection to four compounds, with binding energies ranging from −8.35 to −9.82 kcal/mol. All four demonstrated stability in molecular dynamic simulations, with average root mean square deviation (RMSD) values ranging from 1.491 to 3.835 Å. The Sphenostylisin I and Dihydroxymethyl dihydroxybenzyl chromanone (DMDBC) complexes exhibited the highest stability with average RMSD values of 1.491±2.794 Å and 2.875±1.452 Å, respectively. They also exhibited low-binding free energies of −30.30±0.38 and −30.20±0.49 kcal/mol, making them promising targets.

Conclusion: Four potential glucokinase activators were identified, with Sphenostylisin I and DMDBC showing promise as candidates for developing new diabetes treatments due to their stability, favorable binding, and absence of liver-toxic groups.

PHYTOCHEMICAL CHARACTERIZATION, IN VITRO AND IN SILICO STUDIES ON THERAPEUTIC POTENTIAL OF EDIBLE AND WILD MUSHROOMS

2024-12-06T15:08:40+0530

Objective: The present study evaluates the in vitro and in silico analyses of mushrooms such as Agaricus bisporus, Pleurotus ostreatus, Ganoderma wiiroense, and Pleurotus tuber-regium.

Methods: The quantitative and qualitative analysis of the mushrooms was analyzed and their antioxidant, antimicrobial, and anti-inflammatory assays were done. In addition, molecular docking of their bioactive compounds was docked against the targeted proteins.

Results: The study found that the ethanolic extract of P. ostreatus contained high amounts of carbohydrates, phenolics, and flavonoids. The hot water extract of A. bisporus showed antioxidant activity in phosphomolybdenum assay, while G. wiiroense showed the highest antioxidant activity in superoxide radical scavenging assay. The ethanol extract of the latter also showed maximum 2,2-Diphenyl-picrylhydrazyl radical scavenging and ferric-reducing antioxidant power (reducing activity). A. bisporus hot water extract showed the highest inhibitory activity against Escherichia coli, while G. wiiroense showed the highest anti-inflammatory activity. In silico analysis revealed that chlorogenic and ganodermic acids had high binding affinity toward protein targets.

Conclusion: The study compared the biological activities of commercial edible and wild mushrooms extracts, finding that active compounds from both mushrooms were effective against diseases such as cancer, tuberculosis, and rheumatoid arthritis through computational approaches

A COMPARATIVE STUDY OF FEMORAL NERVE BLOCK (WITH AND WITHOUT DEXAMETHASONE) VERSUS INTRAVENOUS FENTANYL FOR POSITIONING AND DURATION OF POSTOPERATIVE ANALGESIA IN FRACTURE FEMUR PATIENT UNDER SPINAL ANESTHESIA

2024-12-15T18:34:04+0530

Objectives: The preferred technique for fracture femur operation is spinal anesthesia (SA). During position for SA, femoral nerve block (FNB) and intravenous (IV) fentanyl are used to decrease the pain. The analgesia provided by FNB with dexamethasone (FNBD), FNB only, and intra-venous fentanyl (FENT) was compared before positioning in patients undergoing femur fracture surgery.

Methods: 90 patients of fracture femurs were randomized into three Groups A (FNBD), B (FNB), and C (FENT). The FNBD and FNB group patients received drug using ultrasound-guided method 5 min before positioning. In FNB, 10 mL of 2% lidocaine with adrenaline (1:200,000) with 10 mL of bupivacaine was injected, 8 mg of dexamethasone was added in FNDB group, and in the FNET group, received IV fentanyl 1 μg/kg 5 min before positioning. Spinal was given and pain score at baseline, 5, 15, and 30 min recorded.

Results: The mean VAS was lowest for Group A and highest for Group C. The Quality of patient positioning is best in Group A and lowest in Group C and p value between Group A and C is <0.0001. The sample size came to be 30 per group by taking alpha as 5%, power of study as 95% and standard deviation as 3.

Conclusion: Patient satisfaction, positioning during spinal, and analgesia were better with FNB with or without dexamethasone than IV fentanyl

PREVALENCE OF HYPOCALCEMIA DUE TO PHOTOTHERAPY IN NEWBORNS WITH NEONATAL JAUNDICE IN A TERTIARY CARE CENTER OF SOUTHERN RAJASTHAN

2024-12-16T21:56:32+0530

Objective: Neonatal jaundice is a prevalent condition affecting approximately 60–80% of newborns, with phototherapy being a widely utilized treatment. While double surface phototherapy (DSPT) offers enhanced efficacy, it has been associated with adverse effects, notably hypocalcemia. This study aims to determine the prevalence of hypocalcemia induced by DSPT in neonates with jaundice, identify risk factors, and evaluate clinical outcomes.

Methods: This prospective observational study enrolled 200 neonates with jaundice undergoing DSPT in a tertiary neonatal intensive care unit. Baseline data, including gestational age, birth weight, and bilirubin levels, were recorded. Serum calcium levels were measured before initiating DSPT and at 24 and 48-h post-initiation. Statistical analysis was performed to identify risk factors associated with hypocalcemia.

Results: Among 200 neonates, hypocalcemia prevalence increased from 6% at baseline to 38% at 24 h and 52% at 48 h post-DSPT. Symptomatic hypocalcemia occurred in 22% of affected neonates, with 0.9% experiencing seizures. Prematurity (<37 weeks), low birth weight (<2.5 kg), and high bilirubin levels (≥20 mg/dL) were identified as significant risk factors (p<0.05). Calcium supplementation normalized serum levels in all cases within 48 h, with no long-term complications observed during follow-up.

Conclusion: DSPT is effective for treating neonatal jaundice but significantly increases hypocalcemia risk. Routine calcium monitoring and preventive supplementation protocols should be considered to minimize adverse outcomes.

ASSESSMENT OF IRON PROFILE AND ITS CORRELATION WITH MICRO R% AND OTHER RED CELL PARAMETERS IN PATIENTS WITH CHRONIC RENAL FAILURE ON DIALYSIS AND RECEIVING ERYTHROPOIETIN INJECTION

2024-12-20T14:15:15+0530

Objectives: The objectives of the study are to correlate Micro R% with red cell indices and to assess their efficiency in detecting iron deficiency in chronic kidney disease (CKD) patients receiving erythropoietin (EPO).

Methods: Red cell indices such as mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration, and red cell distribution width generated from automated analyzers frequently help in the diagnosis of iron deficiency. Micro R% is a research-only parameter in an automated analyzer while doing a complete blood count. This study is done to correlate and compare hemoglobin and biochemical parameters in healthy controls and CKD patients and to correlate the Micro R% with MCV and serum iron in detecting iron deficiency in CKD patients receiving EPO.

Results: Red cell indices showed a good correlation with serum iron studies. Micro R% is a reliable parameter for the identification of iron deficiency anemia and it correlates with other red cell indices and with serum iron studies.

Conclusion: Identification of iron deficiency in patients with chronic renal failure on dialysis helps us to start the treatment earlier. Anemia-related complications can be prevented and we can give a better quality of life in these patients.

COMPARE THE ANALGESIC EFFICACY OF 0.25% BUPIVACAINE AND 0.25% BUPIVACAINE WITH 0.9 μG/KG DEXMEDETOMIDINE IN TAP BLOCK

2024-11-23T16:05:10+0530

Objectives: The transversus abdominis plane (TAP) block is a relatively new regional anesthesia technique that provides analgesia to the parietal peritoneum as well as the skin and muscles of the anterior abdominal wall. Despite a relatively low risk of complications and a high success rate using modern techniques, TAP blocks remain overwhelmingly underutilized. The objective is to compare the analgesic efficacy of 0.25% bupivacaine and 0.25% bupivacaine with 0.9 μg/kg dexmedetomidine in TAP block as a part of a multimodal analgesia regimen for post-cesarean delivery pain management.

Methods: Patients more than 18 years old posted for elective/emergency caesarean section in ABVGMC, Vidisha, Madhya Pradesh. After approval from the institutional ethical committee and written informed patients consent, 20 each pregnant women were included in the both study group. Group A: TAP block with 0.25% bupivacaine 20 mL each side Group B: TAP block with 0.25% bupivacaine with 0.9 μg/kg dexmedetomidine 20 mL each side. We studied TAP block in patients posted for elective caesarean section.

Results: The women received 0.25% bupivacaine or 0.25% bupivacaine with 0.9 μg/kg dexmedetomidine. The median visual analogue scale (VAS) for pain was significantly higher in the bupivacaine Group A at 12 h with compare to Group B. Overall, there was no difference in VAS score at 0.5, 2, 4, 6, and 24 h demands between the two groups. The mean time to first rescue analgesia in Group A was 14.6±5.5 h and in Group B was 16.8±4.2 h.

Conclusion: We conclude that the using dexmedetomidine as an additive to bupivacaine in ultrasound-guided TAP block for elective/emergency caesarean section provides prolonged duration of post-operative analgesia, and lowered VAS pain scores. The addition of dexmedetomidine to bupivacaine also reduced the total dose of opioid requirement in the first 24 h after caesarean section.

REEVALUATING MEAN ARTERIAL PRESSURE TARGETS IN SEPSIS AND SEPTIC SHOCK: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSISREEVALUATING MEAN ARTERIAL PRESSURE TARGETS IN SEPSIS AND SEPTIC SHOCK: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS

2024-11-20T12:46:52+0530

The conflicting evidence on the clinical impact of higher versus lower mean arterial pressure (MAP) targets in sepsis and septic shock underscores the urgent need to redefine optimal MAP thresholds to improve outcomes in these critical illnesses. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A data search was conducted on July 1, 2024, for randomized controlled trials and observational studies published from January 2004 to December 2023, assessing patient outcomes based on MAP goal parameters. The primary outcomes were all-cause mortality and overall adverse events. Patients with elevated MAP targets exhibited significantly higher odds of all-cause mortality (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.00–1.22), atrial fibrillation (OR: 2.52, 95% CI: 1.25–5.07), and supraventricular arrhythmia (OR: 1.81, 95% CI: 1.07–3.04) compared to those with lower MAP targets (all p≤0.05). In contrast, higher MAP patients with chronic hypertension and sepsis had significantly lower odds of requiring renal replacement therapy (RRT) (OR: 0.77, 95% CI: 0.62–0.97; p=0.03). No significant differences were observed in overall adverse events, acute myocardial infarction, intensive care unit length of stay, major bleeding, mesenteric ischemia, RRT, 28-day survival, or ventricular tachycardia between the groups. This study highlights that targeting higher MAP in sepsis patients may elevate the risk of cardiac complications, such as atrial fibrillation and supraventricular arrhythmia, without having substantial benefits in reducing mortality or adverse events.

DECODING THE RISK PROFILE OF NON-ALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

2024-11-19T17:13:04+0530

Objective: This is a systematic review and meta-analysis that aims to evaluate the prevalence of non-alcoholic fatty liver disease (NAFLD) and the risk factors such as type 2 diabetes mellitus (T2DM), hypertension, obesity, PCOS, and sleep apnea associated with it. NAFLD is one of the most prevalent diseases that affect approximately 40% of diabetic, hypertensive, dyslipidemic obese individuals. Its asymptomatic nature often leads to under diagnosis and progress to severe liver cirrhosis and hepatocellular carcinoma.

Methods: A total of 1819 studies from database from 2019 to 2024 were identified, finally 10 studies were selected, the Statistical Package for the Social Sciences software was used for data analysis.

Results: The analyses across different geographic regions with 620,3969 patients with NAFLD, T2DM prevalence came out to be 15% among males, whereas 22.2% in females. A prevalence of 52.55% was noted in the obese population and 26.74% in lean individuals, with PCOS 43%, metabolic syndrome 75.3%, and sleep apnea 40% and various risk factors were also identified.

Conclusion: This review throws light on the nature of NAFLD, focusing on the need for increased awareness and screening among people at risk, strategies could help avert liver disease progression.