Wound Infection in Surgical Ward of a Tertiary Care Hospital in Dhaka City: The Identification of Organisms and Their Sensitivity Pattern.

Wound infection is one of the most important causes of morbidity and mortality worldwide. The aim of this study was to identify the organisms and their sensitivity pattern from wound infection patients attending in a tertiary care hospital in Dhaka city. This cross-sectional study was carried out in a total of 240 aseptically collected wound swab samples from wound infection suspected patients visiting Bangladesh Medical College Hospital, Dhaka, Bangladesh were analyzed from July 2017 to June 2019. Bacteriological culture of the samples, colony morphology, Gram's staining, and biochemical tests were done following standard microbiological techniques. The antimicrobial susceptibility testing was performed by modified Kirby-Bauer disc diffusion technique following clinical and laboratory standards institute guidelines. Out of 240 wound swab samples from suspected patients of wound infection, 126(52.5%) showed bacterial growth whereas 114(47.5%) were culture negative. No sample yielded more than one organism. Among 126 culture positive cases 75(59.52%) were male and 51(40.48%) were female. The higher rate of bacterial infections 26.19% was noted in the age group of 21-30 years, followed by the age group of 31-40 years, 41-50 years, 51-60 years. Among 126 culture positive cases, 74.6% were Gram negative and 25.4% were Gram positive bacteria. Out of total 126 isolates, E. coli was the most prevalent pathogen 31(24.60%) followed by Staphylococcus aureus 29(23.01%); Pseudomonas 27(21.43%); Klebsiella 18(14.29%); Enterobacter 12(9.52%); Acinetobacter 4(3.17%), while Coagulase negative Staphylococcus 3(2.38%) and Proteus 2(1.59%) were least detected isolates in wound swab. Highly effective antibiotics against Staph aureus were vancomycin 100.0%; imipenem 100.0%; linezolid 100.0% and meropenem 89.65%. Amikacin; gentamicin; netilmicin; imipenem and meropenem showed higher sensitivity in E coli, Klebsiella and Enterobacter species. Colistin was 88.88% effective against Pseudominas spp. followed by imipenem 81.48%, piperacillin-tazobactam 77.78%, meropenem 70.37% and amikacin 51.85%. Acinetobacter spp. showed 75.0% and 50.0% sensitivity to netilmicin and colistin respectively. Injectable and reserve drugs were sensitive to bacterial populations among patients of wound infections in our hospital. It is a wake-up call for clinician to treat wound infections. To prevent the increase resistance to antibiotics, it is necessary to avoid the administration of uncontrolled and unnecessary antibiotics available.

Dysfunction of Thyroid Hormones Following Acute Coronary Syndrome in a Tertiary Care Hospital in Dhaka City.

In cardiovascular homeostasis thyroid hormone plays an important role. We planned to study the changes in thyroid hormone profile in acute coronary syndrome patients admitted in the coronary care unit and compare them between two groups: unstable angina/non-ST elevated Myocardial infarction (UA/NSTEMI) and ST elevated Myocardial infarction (STEMI). This study was a hospital based descriptive cross sectional study which was conducted from 01 March 2018 to 01 February 2019 in Coronary Care Unit of Bangladesh Medical College Hospital and laboratory tests were done in Microbiology Department of Bangladesh Medical College, Dhaka, Bangladesh. Eighty three cases of acute coronary syndromes were taken for the study. Troponin-I was measured as cardiac marker, Electrocardiogram, Complete blood count, blood glucose level, Blood urea, serum creatinine, serum electrolytes, Fasting lipid profile, Thyroid profile, Echocardiography 2D were done. Most of the respondents were distributed in age group 46-60 years where 34(64.15%) male and 19(35.85%) female. Out of 83 Acute Coronary Syndrome (ACS) patients, 27(32.53%) hypertensive, 22(26.50%) diabetic and 16(19.27%) were Chronic kidney disease (CKD). Abnormal lipid profile was present in 30(43.47%) patients. Among total 52 male and 31 female 9(17.30%) male and 6(19.35%) female had abnormal thyroid function. We further elaborated abnormal thyroid function tests in STEMI group and UA/Non STEMI group of ACS patients. We found 10 patients in STEMI group and 5 patients in UA/Non STEMI group with abnormal thyroid function 29.41% and 10.20% respectively which was not statistically significant (p=0.025). This study depicts abnormality in thyroid hormone profile in 18.07% patients of ACS. Abnormal thyroid function increases risk of coronary artery disease. TSH level of ACS patients on hospital admission could be helpful to evaluate further prognosis of the disease.

Benzo(a)pyrene induces lung toxicity and inflammation in mice: prevention by carvacrol.

Benzo(a)pyrene (B(a)P) is an environmental pollutant which causes various lung toxicities. The present study was designed to evaluate the protective effects of carvacrol, a monoterpenic phenol against B(a)P-induced lung toxicity. In this study, Swiss albino mice were pretreated with carvacrol (25 mg/kg and 50 mg/kg) orally for 7 consecutive days before administering oral B(a)P (125 mg/kg). Preventive efficacy of carvacrol was assessed in terms of membrane oxidation, antioxidant enzyme activities, histopathological changes, and inflammatory (iNOS, NF-κB, and COX-2) markers. Carvacrol pretreatment in the two doses restored B(a)P-induced lipid peroxidation and increased the activities of antioxidant enzymes. Protein expressions of iNOS, NF-κB, and COX-2 in the lung tissue were found to be upregulated by B(a)P. Carvacrol treatment, however, downregulated their expressions by decreasing the marker of positive stained cells and restored the histopathological architecture of lung tissue. Our results suggest that carvacrol can be used as a protective agent against B(a)P-induced lung toxicity and inflammation.

Amelioration of Benzo[a]pyrene-induced oxidative stress and pulmonary toxicity by Naringenin in Wistar rats: A plausible role of COX-2 and NF-κB.

Naringenin is a naturally occurring flavanones and has been found to exhibit free radical scavenging, enzyme inhibition, antioxidants, anti-inflammatory, and anticancer activities. Present study was designed to evaluate the protective role of naringenin against benzo[a]pyrene (B[a]P)-induced oxidative stress and pulmonary toxicity. Rats were treated with naringenin at a dose of 100 mg/kg body weight (b. wt.), by oral gavage. B[a]P in a single dose of 50 mg/kg b. wt. was given intraperitoneally. Total protein, total cell counts, lactate dehydrogenase, lipid peroxidation, reduced glutathione, antioxidant enzymes activities, lung histology and expression of nuclear factor kappa B (NF-κB), and cyclo-oxygenase-2 (COX-2) was assessed to evaluate protective effects of naringenin. Histopathological and immunohistochemical studies were also carried out to observe lung toxicity and inflammation. B[a]P administration enhanced the levels of lung injury markers and reduced antioxidant enzymes activities. Naringenin treatment attenuated the levels of oxidative stress by restoring antioxidant enzymes, further improved lung histological damage and significant decrease in inflammatory responses. Naringenin also effectively decreased the expression of NF-κB, and COX-2 induced by B[a]P. These findings suggest that naringenin supplementation is beneficial in maintaining the integrity of alveoli and the epithelium that may be used as a protective agent in B[a]P-induced oxidative stress and lung damage. However, further studies are warranted to elucidate the potential mechanism of action of naringenin.

Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial.

BACKGROUND/AIM: Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients. PATIENTS AND METHODS: A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement ≥ 2 or NAS improvement ≥ 1 with fibrosis improvement ≥ 1 were considered as responders. RESULTS: Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 ± 1.66 and 1.10 ± 0.57 (P = 0.017) and fibrosis improvement was 0.65 ± 0.93 and -0.30 ± 0.48 (P = 0.001), respectively. NAS improved by ≥ 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by ≥ 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39-6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups. CONCLUSION: Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events.

Hydroxyl radical formation resulting from the interaction of nickel complexes of L-histidine, glutathione or L-cysteine and hydrogen peroxide.

L-histidine, L-cysteine, reduced glutathione (GSH) and other bioligands, which are ubiquitously present in biological systems, are recognized as antioxidants. Studies have shown that nickel (II) complexed with these ligands catalyzes the disproportionation of H2O2, leading to the generation of hydroxyl radicals (OH radical). However, none of the studies could provide information regarding effective concentrations at which these ligands act either as pro-oxidant or antioxidant. Therefore, the observed paradoxical behaviour of biological antioxidants in nickel-induced oxidative response was evaluated. Benzoic acid (BA) is hydroxylated by OH radical to form highly fluorescent dihydroxy benzoate (OH-BA). We used this model to study the effect of nickel complexes of L-histidine, GSH or L-cysteine on the hydroxylation of BA. The concentration-dependent effect of L-histidine, GSH and L-cysteine, or nickel on the hydroxylation of BA was studied. The hydroxylation of BA was significantly enhanced up to 1:0.5 molar ratio (Ni:hist or GSH). However, beyond 1:0.5 molar ratios, histidine/GSH inhibited the hydroxylation and complete inhibition was observed at 1:1 molar ratios. Sorbitol and caffeic acid, considered as scavengers of hydroxyl radicals, inhibited nickel-induced hydroxylation of BA. The present study demonstrates paradoxical behaviour of these bioligands. They act as pro-oxidant at lower ligand ratios and as antioxidant at higher ligand ratios. The redox properties of nickel complexes with histidine, GSH or cysteine reported here may be crucial for the toxicity of nickel.

18-ß Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: Role in hyperproliferation, inflammation and oxidative stress.

2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-ß Glycyrrhetinic acid (18ß-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18ß-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18ß-GA at two different doses (45 and 75 mg kg(-1) b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18ß-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18ß-GA. Our findings suggest that pretreatment with 18ß-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation.

Green tea polyphenols and tannic acid act as potent inhibitors of phorbol ester-induced nitric oxide generation in rat hepatocytes independent of their antioxidant properties.

The deleterious effects of excessive release of nitric oxide (NO) have been implicated in the tissue damage and inflammation. In this study, the effect of various flavonoids and other oxidant scavenging chemical agents have been studied for their ability to inhibit 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced NO generation in rat hepatocyte. Hepatocytes activated with TPA (25-200 nM) released NO in a concentration- and time-dependent manner. Green tea polyphenols (GTP) and tannic acid (TA) were most effective in inhibiting TPA-induced NO generation (90%). These agents were also effective in inhibiting NO formation when added 2 h following TPA addition. The other oxidant scavengers, such as L-histidine, sodium azide, vitamin E and sodium benzoate, were not found to be effective even up to 1.0 mM concentration. These results suggest that TA and GTP are potent inhibitors of NOS activity and the inhibition of TPA-induced NO generation by these polyphenols is independent of their antioxidant activity. It is tempting to speculate that these agents could be utilized in the pharmacological manipulations of NO-dependent pathophysiological responses.

The distribution of manganese-54 in fetal, young and adult rats.

The distribution of 54Mn in various organs of pregnant rats and of their 19-day-old fetuses and in non-pregnant female rats of various ages has been studied 18 h after an i.v. injection of 54MnCl2. The results indicate that early neonates are more susceptible to manganese (Mn) than the growing rats. The localization of 54Mn in liver and brain of the embryo was highly significant.

Evaluation of the oral hypoglycaemic effect of Trigonella foenum-graecum L. (methi) in normal mice.

Trigonella foenum-graecum (Fenugreek) (Leguminosae) is employed as a herbal medicine. Its seeds are known for their carminative, tonic and antidiabetic effects. A curative dose of Trigonella foenum-graecum also produces antiulcer action. In this study we have investigated the hypoglycaemic activities of the aqueous extract of the seeds Trigonella foenum-graecum in normal mice using oral route of adminstration. The methanolic extract administered through the same route produced hypoglycaemic effect only at the dose of 1 g/kg body weight. The aqueous extract is under further investigation to determine the chemical structure of the active component. The presence of hypoglycaemic activity in aqueous and methanolic extract indicates that the active compounds are polar in nature.

Scavenging action of zinc and green tea polyphenol on cisplatin and nickel induced nitric oxide generation and lipid peroxidation in rats.

OBJECTIVE: Toxic metal ions have been implicated in the generation of reactive oxygen species (ROS) and nitric oxide (NO). Metallothionines (MT) and plant flavonoids have been reported in the intervention against oxidative damage. We investigated the effect of zinc induced MT and green tea polyphenol (GTP) in reducing the oxidative responses induced by nickel and platinum. METHODS: Zinc (10 mg/kg b. wt, sc) was administered to rats twice at a gap of 24 hrs and GTP (10 mg/100 mL in drinking water) was fed ad libitum for 8 days. Nickel chloride (150 umol/kgb.wt, ip) and cisplatin (50 mumol/kg b.wt, sc) was administered to rats 24 h after Zn or GTP pre-treatment. Animals of all the groups were sacrificed 16 hrs after treatment and biochemical markers for toxicity were monitored. RESULTS: Zinc or GTP pre-treatment caused significant protection against nickel or cisplatin enhanced mortality in rats, and reduction in lipid peroxidation and NO. CONCLUSION: It is proposed that inhibition of ROS and NO by GTP and zinc may prove useful as a selective pharmacological agent in the amelioration of metal toxicity.

Exacerbation of nickel induced oxidative response by vitamin E.

Vitamin E (alpha-tocopherol), a well known naturally occurring chain breaking antioxidant and a free radical scavenger was found to exacerbate nickel (Ni) toxicity in mice. Vitamin E (Vit. E) mediated enhancement of nickel toxicity was demonstrated by (i) enhanced mortality in mice treated with Ni and Vit. E (ii) increased hepatic lipid peroxidation, (iii) increased rate of benzoate hydroxylation, and (iv) liposomal membrane damage.

Comparative molecular analysis of therapy-related and de novo acute promyelocytic leukemia.

Therapy-related acute promyelocytic leukemia (t-APL) has been reported as a late complication of exposure to radiotherapy and/or chemotherapeutic agents targeting DNA topoisomerase II. We have analyzed in t-APL novel gene mutations recently associated with myeloid disorders. Unlike previous reports in acute myeloid leukemia (AML), our results showed neither IDHs nor TET2 mutations in t-APL. However we found an R882H mutation in the DNMT3A gene in a patient with t-APL suggesting a possible role of this alteration in the pathogenesis of t-APL.

Risk of acute promyelocytic leukemia in multiple sclerosis: coding variants of DNA repair genes.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ). METHODS: Using MassARRAY high-throughput DNA analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we genotyped patients with sAPL (n=20) developed after treatment of MS (18 out 20 treated with MTZ) for the presence of 210 SNPs of 22 genes mostly involved in DNA repair and drug detoxification. Patients with MS who did not develop sAPL including 41 treated with MTZ (n=253 and 41, respectively) and healthy blood donors (n=310) were also genotyped as controls. RESULTS: We observed risk allele frequency between MS and sAPL for BRCA2 (rs1801406): 6% and 26%, p=0.007; XRCC5 (rs207906): 2.5% and 15%, p=0.016; CYP3A4 (rs2740574): 4.5% and 25%, p=0.0035. The association of homozygous variants of BRCA2 and XRCC5 yielded higher risk of sAPL (MS vs sAPL: 0.4% and 18%, p=0.001). We also observed a significant association between a SNP in the promoter region (rs2740574) of CYP3A4, an enzyme involved in the metabolism of chemotherapeutic agents and development of sAPL. CONCLUSIONS: Increased susceptibility to develop sAPL in patients with MS receiving MTZ may be linked to genetic variants in DNA repair and drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage.

Molecular pathogenesis of secondary acute promyelocytic leukemia.

Balanced chromosomal translocations that generate chimeric oncoproteins are considered to be initiating lesions in the pathogenesis of acute myeloid leukemia. The most frequent is the t(15;17)(q22;q21), which fuses the PML and RARA genes, giving rise to acute promyelocytic leukemia (APL). An increasing proportion of APL cases are therapy-related (t-APL), which develop following exposure to radiotherapy and/or chemotherapeutic agents that target DNA topoisomerase II (topoII), particularly mitoxantrone and epirubicin. To gain insights into molecular mechanisms underlying the formation of the t(15;17) we mapped the translocation breakpoints in a series of t-APLs, which revealed significant clustering according to the nature of the drug exposure. Remarkably, in approximately half of t-APL cases arising following mitoxantrone treatment for breast cancer or multiple sclerosis, the chromosome 15 breakpoint fell within an 8-bp "hotspot" region in PML intron 6, which was confirmed to be a preferential site of topoII-mediated DNA cleavage induced by mitoxantrone. Chromosome 15 breakpoints falling outside the "hotspot", and the corresponding RARA breakpoints were also shown to be functional topoII cleavage sites. The observation that particular regions of the PML and RARA loci are susceptible to topoII-mediated DNA damage induced by epirubicin and mitoxantrone may underlie the propensity of these agents to cause APL.

Evidence for the involvement of hydroxyl radicals in nickel mediated enhancement of lipid peroxidation: implications for nickel carcinogenesis.

The administration of nickel to rats resulted in enhanced hepatic lipid peroxidation, levels of glutathione and iron with a concomitant decrease in glutathione peroxidase activity. These effects were dose dependent. Enhanced lipid peroxidation was found to be inhibited by the exogenous addition of ethylenediamine tetraacetic acid (EDTA), benzoate and ethanol while catalase and superoxide dismutase were ineffective in this regard. Our data strongly suggest the involvement of hydroxyl radicals in the nickel mediated enhancement of lipid peroxidation which may have their implications in the carcinogenicity of nickel compounds.