Computational study of the potential molecular target for antibreast cancer activity of limonoid derivatives from chisocheton sp

Limonoid is a class of natural compounds that are originated from lemon and other citrus fruits. However, derivativesof limonoids are also produced in other plants, such as Chisocheton sp. Limonoids from Chisocheton sp. showedvarious biological activities, including anticancer. Nevertheless, the molecular target for anticancer activity of thesecompounds is still unclear. Many studies suggested nuclear receptors (NR) as the protein target for limonoids. In thisstudy, we investigated the possible NR as a molecular target for limonoids from Chisocheton sp. using moleculardocking and molecular dynamics (MD) simulation. The docking study was done on AutoDock Vina. Two out of 11NR expressed in breast tissue, i.e., progesterone receptor (PR) and glucocorticoid receptor, was used as the mostpotential target for limonoids. The docking pose was further observed by MD simulation. Both receptors showedstable molecular interactions with limonoids, indicated with a low deviation of binding site residues. Interestingly,simulations of PR showed the alteration of Helix-12, which is one of the key factors to the antagonist action of theligand. It is hoped that the findings could shed insight into the further molecular assay development of anticanceragents based on limonoids.

Potential biomarkers in NASH-induced liver cirrhosis with hepatocellular carcinoma: A preliminary work on roles of exosomal miR-182, miR-301a, and miR-373

@#Introduction: Recent studies have published the roles of exosomal miRNAs in the pathogenesis of various type of malignancies and can be developed as potential biomarkers for diagnostic, prognostic and therapeutic purposes. The aim of this study was to identify the expression level of selected miRNAs (miR-182, miR-301a, and miR-373) in exosomes of the serum and ascitic fluid in patients with non-alcoholic steatohepatitis (NASH)-related liver cirrhosis with or without hepatocellular carcinoma (HCC). Materials and Methods: A literature search was performed to identify potential miRNAs involved in the pathogenesis of HCC. Unpaired serum and ascitic fluid were obtained from 52 patients with NASH related liver cirrhosis (n=26 for each group of with and without HCC). Exosomal miRNA was isolated from all samples. Expression levels of miR-182, miR-301a and miR373 were determined using quantitative real-time PCR. Results: Serum-derived exosomal mir-182, miR-301a and miR-373 were significantly up-regulated with fold change of 1.77, 2.52, and 1.67 (p< 0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC. We identified the expression levels of ascitic fluid-derived exosomal mir-182, miR-301a, and miR-373 were significantly up-regulated with fold change of 1.6, 1.94 and 2.13 respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC (p <0.05). There was poor correlation expression of all the selected exosomal miRNA between serum- and ascitic fluid-derived in HCC group. Conclusions: This preliminary data showed significant increase in the expression levels of exosomal miR-182, miR-301a and miR373 in both serum and ascetic fluid suggesting the possible roles of these miRNAs as circulating biomarkers for NASH-induced liver cirrhosis with hepatocellular carcinoma

Lung computed tomography patterns of a cluster of asymptomatic young males with COVID-19 admitted to a teaching hospital in Kuala Lumpur

@#Background and objective: Coronavirus Disease 2019 (COVID19) was first reported in Malaysia in March 2020. We describe here the clinical characteristics and computed tomography (CT) patterns in asymptomatic young patients who had laboratory-confirmed COVID-19. Methods: This is a retrospective observational study where 25 male in-patients with laboratory-confirmed COVID-19 in Hospital Canselor Tuanku Muhriz. Demographics, clinical data and CT images of these patients were reviewed by 2 senior radiologists. Results: In total there were 25 patients (all males; mean age [±SD], 21.64±2.40 years; range, 18-27 years). Patients with abnormal chest CT showed a relatively low normal absolute lymphocytes count (median: 2.2 x 109/L) and absolute monocyte count (median: 0.5 x 109/L). Lactate dehydrogenase was elevated in 5 (20%) of the patients. The procalcitonin level was normal while elevated levels of alanine aminotransferase, total bilirubin, platelet and C-reactive protein were common. Baseline chest CT showed abnormalities in 6 patients. The distribution of the lesions were; upper lobe 3 (12%) lower lobe 3 (12%) with peripheral distribution 4 (16%). Of the 25 patients included, 4 (16%) had ground glass opacification (GGO), 1 (4%) had a small peripheral subpleural nodule, and 1 (4%) had a dense solitary granuloma. Four patients had typical CT features of COVID-19. Conclusion: We found that the CT imaging showed peripheral GGO in our patients. They remained clinically stable with no deterioration of their respiratory symptoms suggesting stability in lung involvement. We postulate that rapid changes in CT imaging may not be present in young, asymptomatic, non-smoking COVID-19 patients. Thus the use of CT thorax for early diagnosis may be reserved for patients in the older age groups, and not in younger patients.

The Use of Complementary and Alternative Medicine among Malaysian Chronic Kidney Disease Patients

@#Many of our chronic kidney disease (CKD) patients venture into complementary and alternative medicine (CAM) to seek a cure for the disease beyond conventional management. The objective of this study was to determine the prevalence and pattern of CAM usage; and its association with the progression of CKD in our population. This was a cross-sectional survey recruited CKD patients from Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Data was collected via interview using questionnaires which explore the demographics, type and pattern of CAM use. Patients’ comorbidities and serum creatinine were extracted from the medical notes to assess the association between progression of CKD and usage of CAM. Chi-square, Independent Samples t-test, Mann-Whitney U test and logistic regression were used to evaluate for an association. Three hundred and seventy two eligible patients were recruited. The prevalence of CAM use was 29% in the past year. Younger age, higher education and higher income level were associated with significantly more usage of CAM. Natural products were the commonest type of CAM used (86.1%). The belief in the effectiveness of CAM was the main reason for its uptake and about 57.8% revealed their practice to their physician. We found that the use of CAM in Malaysian CKD patients did not influence the progression of the disease.

Frequency of prolonged corrected QT interval in child pugh class in patients of cirrhosis of liver

Objective: To determine the frequency of prolonged corrected QT interval [QTc] in Child Pugh Class in patients of liver cirrhosis presenting to Combined Military Hospital Peshawar. Study Design: Cross sectional study. Place and Duration of Study: Department of Medicine, Combined Military Hospital Peshawar, from Dec 2013 to Jun 2014

Material and Methods: One hundred and thirty three patients with liver cirrhosis fulfilling the inclusion criteria were included in the study using non-probability consecutive sampling after taking informed consent. All patients were assigned their Child's Class either A, B or C. Electrocardiogram [ECG] was done and QTc was calculated using Bazett's formula. QTc of more than 0.44 seconds was taken as prolonged

Results: Out of 133 patients, QTc was prolonged in 78 patients yielding frequency of QTc prolongation in cirrhosis of 58.64%. Frequency of QTc prolongation was 61.18% in males and 54.17% in females. QTc prolongation was 15% in Child Pugh grade A, 54.76% in Child Pugh grade B and 73.24% in Child Pugh grade C. There was a statistically significant association between QTc prolongation and the severity of cirrhosis [p<0.001]

Conclusion: This study concludes that there was a statistically significant increase in frequency of QTc prolongation with worsening of Child Pugh Class thereby indicating an association between QTc prolongation and the severity of cirrhosis

Surgical outcome of pancreaticoduodenectomy in pancreatic and periampullary neoplasms

Objective: To report the results in the surgical treatment of pancreatic and periampullary neoplasms with emphasis on surgical technique, short-term postoperative outcome and the lessons learnt

Study Design: Case series

Place and Duration of Study: This study was carried out at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, from October 2014 to May 2016

Methodology: Patients undergoing surgical treatment of pancreatic and periampullary neoplasms were selected. Patients' characteristics including demographics, surgical technique, and 30-day morbidity and mortality were recorded. International Study Group of Pancreatic Fistula [ISGPF] classification was used to define postoperative pancreatic fistula and Clavien-Dindo classification to grade complications

Results: A total number of 65 patients underwent the trial of dissection; 50 had pancreaticoduodenectomy and 15 patients underwent palliative bypass and were excluded from analysis. Sixty-four percent were males and 36% were females. The most common tumor was periampullary [n=29, 58%] followed by pancreatic head [14, 28%] and duodenal tumors [n=07, 14%]. Mean age was 52.92 +/- 13.27 years; mean operating time was 470 +/- 358.28 minutes and median blood loss was 400 [287-500] ml. Pancreaticogastrostomy [PG] was the preferred reconstruction technique in 37 [74%] verses pancreaticojejunostomy [PJ] in 13 [26%] patients. Four [08%] patients needed portal vein reconstruction and two [04%] replaced right hepatic artery resection and reconstruction due to tumor involvement. There were seven Grade A, and one Grade B and C pancreatic fistulae each. Three patients [06%] needed endoscopic therapy for gastrointestinal hemorrhage from pancreatic stump. There was one death in postoperative period

Conclusion: Pancreaticoduodenectomy is a safe procedure with excellent postoperative outcome, if carried out in a specialized hepato-pancreato-biliary unit. A PG reconstruction can be a safer alternative to PJ

Cefadroxil potency as cancer co-therapy candidate by glutathione s-transferase mechanism

Background: Glutathione S-transferases (GSTs) have an important role in the detoxification of electrophiles, such as some anticancer drugs. Compounds with phenolic and/or α,b-unsaturated carbonyl group have been known as GSTs inhibitor in vitro. Cefadroxil in vitro decreased GST-Pi activity but not GSTs in rat kidney cytosol. GST inhibitor in a specific organ and of a specific class is needed for safety in cancer chemotherapy. The study aims to observe the effect of cefadroxil on GSTs in vivo in rat kidney cytosol and then compare it to those seen for liver, lung, and spleen in vivo. Methods: Cefadroxil was given twice a day by forcefeeding for five days. Rat kidney cytosol was then prepared and its protein concentration was determined. Cytosolic total GST, GST-Mu and GST-Pi activities were monitored by a continuous spectrophotometric method using the following substrates: 1-chloro, 2,4-dinitrobenzene (CDNB) (non-specific substrate), 1,2-dichloro-4-nitrobenzene (DCNB) for GST-Mu, and ethacrynic acid (EA) for GST-Pi. Results: The data showed that cefadroxil significantly increased the activity of GSTs, GST-Mu, and GSTPi in rat kidney cytosol (8.75%, 47.81%, and 6.67% respectively). Conclusion: Cefadroxil did not inhibit GSTs, GST-Mu, and GST-Pi in rat kidney in vivo indicating that it does not inhibit chemotherapy detoxification by GSTs, GSTMu, and GST-Pi in normal kidney cells.

Multi-resistant gram negative bacterial infections in a surgical intensive care unit at Rawalpindi

Hospital-acquired infections encompass almost all clinically evident infections that do not originate from a patient's original admitting diagnosis. Nosocomial infections are one of the major causes of morbidity and mortality in Pakistan. This study was conducted to determine the frequency of hospital-acquired infections and its causative organisms in patients admitted to a surgical intensive care unit. A prospective observational study was carried out at Holy Family Hospital, Rawalpindi from July 2007 to April 2008. Clinical samples of tracheal aspirates, sputum, urine, blood, body fluids, pus and others were collected from patients admitted to intensive care unit and cultured. Bacterial isolates were identified along with their antimicrobial susceptibility. A total of 156 samples were collected. Bacteria or candida species were isolated in 89[57.1%] samples. Highest infection was seen in respiratory tract followed by surgical sites. Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and candida spp. were the commonest organisms. The isolation rate of gram-positive bacteria was relatively low. Resistance pattern of gram-negative isolates was: ampicillin, 67[90.5%]; co-trimoxazole, 67[90.5%]; cefaclor, 66[89.2%]; co-amoxyclav, 64[86.5%]; tetracycline, 61[82.4%]; rifampicin, 59[79.7%] cephradine, 58[78.4%]; ceftriaxone, 58[78.4%], ceftazidime, 57[77.0%], lincomicin, 53[71.6%]; ofloxacin, 50[67.6%]; ciprofloxacin, 50[67.6%]; cefotaxime, 49[66.2%]; gentamicin, 47[63.5%]; chloramphenicol, 45[60.8%]; levofloxacin, 41[55.4%]; fosfomycin, 37[50%];sparfloxacin, 35[47.3%]; enoxacin, 29[39.2%]; imipenem, 27[36.5%]; moxifloxacin, 21[28.4%], amikacin, 21[28.4%]; and aztreonam, 14[18.9%]. The high frequency of hospital acquired infections suggests that infection control practices are not strictly observed along with indiscriminate prescription of antibiotics that are causing emergence of antimicrobial resistant organisms. Guide lines to control facility based transmission of infections should be strictly followed