Expression of Cyclin D1 in Urothelial Carcinoma of Urinary Bladder and its Association with Tumour Grade.

Urothelial carcinoma (UC) is the most common malignancy of urinary bladder. It is the 9th leading cause of death worldwide and second most common genitourinary malignancy among male. Incidence is increasing in developing countries like Bangladesh. About 80% of patients are found between 50 to 80 years of age. It is 3-4 times more common in male than in female. Determination of therapeutic strategy and prediction of progression of urothelial carcinoma is a major clinical challenge. Treatment of urothelial carcinoma still now mostly depends on pathological stages. Amplification or genomic alteration of Cyclin D1 (a proto-oncogene) may cause protein overexpression which is frequently realized as a clonal pathology in various human neoplasms including bladder cancer. Evaluation of Cyclin D1 expression is promising for guiding therapeutic strategies, risk stratification and prediction of tumor progression. The aim of the study was to determine the expression of Cyclin D1 in urothelial carcinoma of urinary bladder and its association with tumour grade. This cross-sectional observational study was conducted in Department of Pathology, Dhaka Medical College, Dhaka, Bangladesh from July 2019 to June 2021. Histomorphologically diagnosed 51 urothelial carcinomas were included. Sections were stained with hematoxylin and eosin. Immunostaining with Cyclin D1 antibody was also done. Relevant information was collected and recorded in a predesigned data sheet. Statistical analysis was carried out as required. Mean age ±SD was 57.8±10.55 years. Male female ratio was 4.6:1. In this study 39(76.5%) patients were smoker. Regarding clinical presentations 36(70.6%) patients presented with painless hematuria alone. Lateral wall (64.7%) was the most frequent tumor location. Among 51 cases, 38(74.5%) cases were high grade urothelial carcinoma (HGUC) and 13(25.5%) cases were low grade urothelial carcinoma (LGUC). Considering Cyclin D1 expression, most of the LGUC cases showed high level of expression by both percentage (84.6%) and intensity (84.6%). Most of the HGUC cases showed low level of expression by both percentage (63.2%) and intensity (60.5%). Cyclin D1 showed significant inverse association with HGUC (p<0.05). In urothelial carcinoma of urinary bladder, Cyclin D1 expression was decreased with increasing grade of the tumor. Cyclin D1 expression was inversely associated with tumour grade.

Antibacterial Activities of Methanolic Seeds Extract of Black pepper (Piper nigrum L.) against Gram Positive Staphylococcus aureus & Gram-Negative Escherichia coli.

Evaluation of the in vitro antibacterial activity of Methanolic extracts isolated from Black pepper seeds (Piper nigrum L.) against two infection causing pathogens, Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Between July 2022 and June 2023, this experimental study was conducted at the Mymensingh Medical College's Department of Pharmacology and Therapeutics in conjunction with the Department of Microbiology. Using the disc diffusion and broth dilution methods, the antibacterial activity of methanolic extract of black pepper seeds (MBPE) was evaluated at various doses. The solvents Methanol and 10.0% Di Methyl Sulfoxide (DMSO) were used to make the extract. Using the broth dilution procedure, the conventional antibiotic Ciprofloxacin was utilized and the outcome was contrasted with that of Methanol extracts. Methanolic extract of black pepper seeds (MBPE) at seven distinct concentrations (100, 80, 60, 40, 20, 10 and 5 mg/ml) were utilized, then later in chosen concentrations as needed to confirm the extracts' more precise margin of antimicrobial sensitivity. At 80 mg/ml and above doses of the MBPE, it had an inhibitory impact against the aforementioned microorganisms. For Staphylococcus aureus and Escherichia coli the MIC were 60 and 75 mg/ml in MBPE respectively. As of the MIC of Ciprofloxacin was 1µg/ml against Staphylococcus aureus and Escherichia coli. In comparison to MICs of MBPE for the test organisms, the MIC of Ciprofloxacin was the lowest. This study clearly shows that Staphylococcus aureus and Escherichia coli are sensitive to the methanolic extract of black pepper seeds' antibacterial properties.

Antibacterial Effects of Chloroform Henna (Lawsonia inermis) Leaf Extracts against Two Nosocomial Infection Causing Pathogens: Gram-positive Staphylococcus aureus and Gram-negative Klebsiella pneumoniae: A Comparative Study.

Evaluation of the in vitro antibacterial activity of Chloroform extracts isolated from Henna (Lawsonia inermis) leaf against two nosocomial infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae. This interventional study was carried out for the period of January 2021 to December 2021 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Bangladesh. The antibacterial activity was tested at different concentrations of Chloroform Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents chloroform and 0.1% Dimethyl sulfoxide (DMSO). The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Chloroform extracts. Chloroform Henna Extracts (CHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000 mg/ml). Among different concentrations of the CHE, 100mg/ml and above concentrations showed inhibitory effect against Staphylococcus aureus and Klebsiella pneumoniae. The MIC for Staphylococcus aureus and Klebsiella pneumoniae were 100 and 200mg/ml in CHE respectively. The MIC of Ciprofloxacin was 1µg/ml against Staphylococcus aureus and 1.5µg/ml against Klebsiella pneumoniae. The MIC of Ciprofloxacin was the lowest in comparison to MICs of CHE for the test organisms. This study showed that Chloroform Henna extracts demonstrated antibacterial effects against food borne pathogens. It is clearly observed that there is definite antibacterial effect of the Chloroform extract of Henna leaves (Lawsonia inermis) against Staphylococcus aureus and Klebsiella pneumoniae.

Pattern of Prescribing Drugs in Chronic Obstructive Pulmonary Disease in a Tertiary Care Hospital of Bangladesh.

Chronic obstructive pulmonary disease (COPD) is a chronic obstructive disease of the airways. It is one of the most common and important chronic respiratory conditions in terms of years lived with disability. Incidence is increasing in Bangladesh like other developing countries. To evaluate drug prescription pattern for COPD, this cross-sectional, observational study was conducted from January to December in 2020 at the Department of Pharmacology in collaboration with the Department of Medicine in Mymensingh Medical College, Bangladesh. A total of 168 patients were selected for the study by non-random purposive sampling technique. Age distribution indicates that 31.5% of patients were in the 50-59 years age group and males were 93.5%. The majority (82.1%) of the participants were smokers. In this study, majority (34.12%) of the drugs were used as oral form and second most common dosage form was nebulization (26.75%). Bronchodilators were mostly prescribed 652(57.19%), followed by corticosteroids 222(19.47%) and antibiotics 165(14.47%) among drugs used for COPD. Beta sympathomimetics 322(45.49%) were mostly prescribed, followed by anticholinergics 186(28.52%) and methylxanthines 144(22.08%) as bronchodilators. Out of 1140 drugs for COPD, 53.06% and 34.12% were delivered as inhalation and oral forms, respectively. Inhalation route was the most (60.37%) preferred one over oral route (37.63%) for steroid use. The most of the patients [152 (90.48%)] were treated with combination therapy. Mostly (39.6%) used Fixed Dose Combination (FDC) therapy was salbutamol and ipratropium bromide followed by salmeteroal and Fluticasone (30.83%). Both FDC were prescribed in 57.7% of study population. Considering nomenclature, trade name was used in 24.4% of prescription.

Antibacterial Activities of Mint (Mentha piperita) Leaf Extracts (Aqueous) Against Two Food Borne infection causing pathogens: Staphylococcus aureus and Escherichia coli.

Evaluation of the in vitro antibacterial activity of Aqueous extracts isolated from Mint (Mentha piperita) leaf against two food born infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Escherichia coli. This interventional study was carried out in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Bangladesh from January 2021 to December 2021. The antibacterial activity was tested at different concentrations of Aqueous Mint leaf extracts by using disc diffusion & broth dilution method. The extract was prepared by using solvents Aqueous. The test microorganisms were also tested for their activity against a standard antibiotic Gentamicin by broth dilution method and the result was compared with that of Aqueous extracts. Aqueous extract of Mint leaves (AMLE) were used initially in eight different concentrations (25, 50, 100, 200, 400, 600, 800 and 1000µg/ml) and later in selected concentrations as needed to confirm the more precise margin of antimicrobial sensitivity of the extracts. Among different concentrations of the AMLE, 200µg/ml and above concentrations showed inhibitory effect against Staphylococcus aureus and 400µg/ml and above concentrations showed inhibitory effect against Escherichia coli. Minimum inhibitory concentration (MIC) for Staphylococcus aureus and Escherichia coli were 200 and 400µg/ml in AMLE respectively. The MIC of Gentamicin was 1µg/ml against Staphylococcus aureus and 1.5µg/ml against Escherichia coli. The MIC of Gentamicin was the lowest in comparison to MICs of AMLE for the test organisms. This study showed that Aqueous Mint extracts demonstrated antibacterial effects against food borne pathogens. It is clearly observed that there is definite antibacterial effect of the aqueous extract of Mint leaves against Staphylococcus aureus and Escherichia coli.

Antibacterial Effect of Moringa (Moringa oleifera) Leaf Ethanolic Extract Against Staphylococcus aureus and Escherichia coli.

Increasing resistance of pathogenic microorganisms to synthetic antibiotics has lead to the search for alternative drug sources. In this regard, one of the reputed Medicinal plant, Moringa (Moringa oleifera) was investigated for potential antimicrobial effect against some commonly encountered bacteria such as Staphylococcus aureus, Escherichia coli. This experimental study was conducted from July 2019 to June 2020 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Bangladesh to determine the antibacterial effect of Ethanolic extract of Moringa oleifera leaf (EMLE) against aforementioned bacteria. The antibacterial activity was tested at different concentrations (100, 200, 400, 600, 800 and 1000µg/ml) of Ethanolic extract by using disc diffusion and broth dilution method. Dose dependent inhibitory effect was seen against the test organisms using disc diffusion method. The maximum zone of inhibition was 19 mm against S. aureus and 20mm against E. coli at 100.0% (1000µg/ml) concentration. The minimum inhibitory concentrations (MICs) of EMLE were 400µg/ml and 500µg/ml against Staphylococcus aureus and Escherichia coli respectively. The present study showed that Ethanolic extract of Moringa leaf demonstrated antibacterial effects against food borne pathogens. Further studies are required to detect and isolate the active ingredients present in the Moringa leaves extract responsible for its antibacterial effect.

Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis.

BACKGROUND: Endothelin-1 (ET-1) has been reported to evoke histamine-independent pruritus in mammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin inflammation of AD. METHODS: To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and patients with AD and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line. RESULTS: We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and patients with AD. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by an endothelin A receptor antagonist, ERK1/2 inhibitor, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor. CONCLUSION: These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis of AD, which may be a future target for antipruritic agents.

A prospective 10 year audit of a single Irish centre's experience of retroperitoneal lymph node dissection for metastatic testis cancer.

BACKGROUND: Retro-peritoneal lymph node dissection (RPLND) following chemotherapy is critical in advanced germ cell tumours with residual retro-peritoneal masses. Post-chemotherapy RPLND is more extensive, may require adjacent organ resection and has higher morbidity. The study aim was to analyse patient demographics, clinical stage, surgical procedures and cure rates following RPLND. METHODS: An RPLND database (1994-2005) was analysed prospectively for demographics, pre/post-RPLND staging, chemotherapy regimen, cure, follow-up and early/late morbidity and mortality. RESULTS: 73 patients were identified (range 17-49 median 25.7). The mean hospital stay was 14.3 days (range 6-50). Clinical stage at presentation was; IV (16), III (19), II (27), I (11) and prior to RPLND was IV (12), III (6), II (55), I (0). Eleven patients with stage I disease progressed prior to RPLND. Seventy-one patients received cisplatin-based chemotherapy with partial response (49), minimal response (14), no response (7), disease progression (3) and 13 patients required salvage chemotherapy. RPLND was bilateral (26), unilateral (36) and suprahilar (11) with nerve sparing in 10. Other major procedures included nephrectomy (22), aortic graft (1), ureterectomy (1) and caval dissection (1). RPLND histology was mature teratoma (MT) (37), fibrosis/necrosis (26), NSGCT (6), seminoma (1), mixed NSGCT/teratoma (1), sarcoma (1) and mixed seminoma/teratoma (1). Early (n = 26) and late (n = 13) morbidity was significant but expected. There was no mortality. Ninety-five per cent had complete remission following RPLND (mean follow-up 30 months). One patient is deceased following relapse. CONCLUSIONS: The decision to perform post-chemotherapy RPLND depends on the possibility of viable tumour or teratoma and surgical morbidity. Appropriate case selection and timely intervention in an experienced centre permits optimum outcome.

Ferrous ion autoxidation and its chelation in iron-loaded human liver HepG2 cells.

Ferrous ion (Fe(2+)) is long thought to be the most likely active species, producing oxidants through interaction of Fe(2+) with oxygen (O(2)). Because current iron overload therapy uses only Fe(3+) chelators, such as desferrioxamine (DFO), we have tested a hypothesis that addition of a Fe(2+) chelator, 2,2'-dipyridyl (DP), may be more efficient and effective in preventing iron-induced oxidative damage in human liver HepG2 cells than DFO alone. Using ferrozine as an assay for iron measurement, levels of cellular iron in HepG2 cells treated with iron compounds correlated well with the extent of lipid peroxidation (r = 0.99 after log transformation). DP or DFO alone decreased levels of iron and lipid peroxidation in cells treated with iron. DFO + DP together had the most significant effect in preventing cells from lipid peroxidation but not as effective in decreasing overall iron levels in the cells. Using ESR spin trapping technique, we further tested factors that can affect oxidant-producing activity of Fe(2+) with dissolved O(2) in a cell-free system. Oxidant formation enhanced with increasing Fe(2+) concentrations and reached a maximum at 5 mM of Fe(2+). When the concentration of Fe(2+) was increased to 50 mM, the oxidant-producing activity of Fe(2+) sharply decreased to zero. The initial ratio of Fe(3+):Fe(2+) did not affect the oxidant producing activity of Fe(2+). However, an acidic pH (< 3.5) significantly slowed down the rate of the reaction. Our results suggest that reaction of Fe(2+) with O(2) is an important one for oxidant formation in biological system, and therefore, drugs capable of inhibiting redox activity of Fe(2+) should be considered in combination with a Fe(3+) chelator for iron overload chelation therapy.