Novel report of Bipolaris heliconiae causing frog-eye-like leaf spot on Dypsis lutescens in Indian Sub-Continent.

Dypsis lutescens, commonly known as areca palm, is a highly valued ornamental species due to its aesthetic value. However, the foliage is vulnerable to various pathogens, particularly those responsible for fungal leaf spot diseases. In October 2023, a severe incidence (93 %) of destructive leaf spots was recorded on Dypsis lutescens at the University of Agricultural Sciences, GKVK, Bangalore, and surrounding areas. The leaf spot symptoms manifested as frog-eye-like lesions, leading to complete leaf desiccation and significantly reducing the palms ornamental value. The pathogen exhibited the highest radial growth (90.00 mm) and prominent sporulation on oat meal agar, whereas Richard's synthetic agar resulted in the lowest radial growth (38.00 mm) with no sporulation. Morphological and multilocus phylogenetic analyses confirmed the pathogen as Bipolaris heliconiae. Pathogenicity tests fulfilled Koch's postulates, confirming that Bipolaris heliconiae is the causative agent of leaf spot disease in Dypsis lutescens in India. This novel finding underscores the emergence of a new disease and highlights the urgent need for effective management strategies.

Unleashing the potential of vanillic acid: A new twist on nature's recipe to fight inflammation and circumvent azole-resistant fungal infections.

Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.

Clerodane Furanoditerpenoids from Tinospora bakis (A.Rich.) Miers (Menispermaceae).

Tinospora bakis (A.Rich.) Miers (Menispermaceae) has traditionally been used to alleviate headaches, rheumatism, mycetoma, and diabetes, among others. Despite its extensive use, the active components of the plant have never been investigated. In this work, a series of furanoditerpenoids (1-18) and five compounds from other classes (19-23) were isolated from T. bakis. Notably, two new compounds were discovered and named: tinobakisin (1) and tinobakiside (10). Their molecular structures were elucidated with NMR, MS, UV, IR, and ECD spectra. Additionally, known compounds (2-9 and 11-23) were corroboratively identified through spectral comparisons with previously reported data, while highlighting and addressing some inaccuracies in the prior literature. Remarkably, compounds 6, 7, 13, and 17 exhibited a superior anti-glycation effect, outperforming established agents like rutin and quercetin in a lab model of protein glycation with glucose. The overall findings suggest that furanoditerpenoids play a crucial role in the antidiabetic properties of T. bakis. This research marks the first comprehensive phytochemical investigation of T. bakis, opening the door for further investigation into furanoditerpenoids and their biological mechanisms.

New anti-inflammatory and non-cytotoxic metabolites of methylstenbolone obtained by microbial transformation.

A synthetic anabolic-androgenic steroid, methylstenbolone (1), was structurally transformed into a series of nine analogues, 2,17α-dimethyl-7α,17ß-dihydroxy-5α-androst-1-en-3-one (2), 2,17α-dimethyl-15ß,17ß-dihydroxy-5α-androst-1-en-3-one (3), 2,17α-dimethyl-6α,9α,17ß-trihydroxy-5α-androst-1-en-3-one (4), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (5), 2-methyl-11ß,17ß-dihydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (6), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3,6-dione (7), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5ß-androst-1-en-3,6-dione (8), 2,17α-dimethyl-7ß,17ß-dihydroxy-5α-androst-1-en-3-one (9), and 2,17α-dimethyl-12ß,17ß-hydroxy-5α-androst-1-en-3,7-dione (10) by fungal cell suspension cultures, Macrophomina phaseolina and Cunninghamella blakesleeana for the first time. Among those, compounds 2-4 and 6-10 were identified as new. Herein, spectral data of metabolite 5 was reported for the first time. Their structures were elucidated by NMR, MS, UV, and IR spectroscopic methods. Substrate 1 (IC50 10.1 ± 0.3 µg/mL) was identified as a potent anti-inflammatory agent against nitric oxide (NO) production. Its transformed products 3 (IC50 as 27.8 ± 1.1 µg/mL) and 9 (26.9 ± 0.4 µg/mL) displayed good inhibition. Compounds 2 (IC50 = 45.9 ± 0.8 µg/mL) and 6 (IC50 = 36.6 ± 1.2 µg/mL) were also active moderately against NO production, in comparison to standard LNMMA (IC50 = 24.2 ± 0.8 µg/mL). Cytotoxicity assay showed 1 was active to cancer cell line MCF7 (IC50 = 12.26 ± 0.35 µg/mL), compared to the standard Doxorubicin having IC50 as 1.25 ± 0.11 µg/mL. However, it is also toxic to human normal cell line (BJ) with IC50 as 8.69 ± 0.02 µg/mL. More importantly, all transformed products are non-cytotoxic on BJ. Therefore, biotransformation can be an efficient approach to reduce the toxicity of methylstenbolone.

Phytochemical Characterizations of Maranthes polyandra (Benth.) Prance.

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.

Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains.

The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16-24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.

Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid.

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5-6 and 8a-8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.

Safety and efficacy of Holmium laser enucleation of the prostate (HoLEP) in patients with previous transperineal biopsy (TPB): outcomes from a dual-centre case-control study.

BACKGROUND: We investigated the surgical feasibility, safety and effectiveness of 50 W (low power) Holmium Laser enucleation of the prostate (HoLEP) in patients who have undergone previous template biopsy of the prostate (TPB). METHODS: Data encompassing pre-operative baseline characteristics, intra-operative measures and post-operative outcomes was collected for 109 patients undergoing HoLEP across two UK centres. Patients were stratified into two groups; group 1 (n = 24) had undergone previous TPB were compared with 'controls' (no previous TPB) in group 2 (n = 85). The primary outcome was successful HoLEP. RESULTS: There were no statistically significant differences in either key baseline characteristics or mass of prostate enucleated between groups 1 and 2. There was no statistically significant difference in enucleation or morcellation times parameters between the two groups other than enucleation efficiency in favour of group 1 (p = 0.024). Functional outcomes improved, without any statistically significant difference, in both groups. CONCLUSIONS: In patients with a previous TPB, HoLEP is surgically feasible, safe and effective. TPB should not be considered a contraindication to HoLEP. Our work provides a strong foundation for further research in this area.

Impact of Fibroblast Growth Factors 19 and 21 in Bariatric Metabolism.

BACKGROUND: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine. Synthesis of FGF21 is upregulated predominately in the fasting state through peroxisome proliferator-activated receptor pathways and to a lesser extent by FGF15/19. Key Messages: The biological functions of FGF15/19 and FGF21 are diverse and complicated. The tissue targeted effects of FGF15/19 and FGF21 of importance after bariatric surgery include the regulation of hepatic bile acid biosynthesis and ketogenesis as well as thermogenesis in adipose tissue, respectively. Furthermore, FGF15/19 and FGF21 function to regulate carbohydrate and lipid metabolism. CONCLUSION: The long-term effects of bariatric surgery on weight loss are undisputable. However, the mechanism for improvements in glucose and lipid homeostasis observed shortly after bariatric surgery is less understood. This review article attempts to describe the known metabolic effects of FGF15/19 and FGF21 that may potentiate these improvements after bariatric surgery.

Evaluation of vascular endothelial growth factors A, C and D as indicators of lymphangiogenesis and angiogenesis in invasive and non-invasive urothelial carcinoma bladder.

OBJECTIVE: To study the immunohistochemical expression of vascular endothelial growth factors in urothelial tumours of bladder and its possible association with tumour characteristics and microvessel density. METHODS: The cross-sectional descriptive study was conducted at the Histopathology Department of the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 2011 to December 2012, and comprised cases of non-invasive and invasive urothelial tumours of the bladder. The microvessel density and expression of vascular endothelial growth factors A, C, D were evaluated by immunohistochemistry. Specimens of transurethral bladder biopsies and surgical resection were examined. The cases were classified into non-invasive (stage pTa ) and invasive groups as well as low-grade and high-grade groups. The presence of in-situ component was evaluated in each category. To assess the microvessel density, highly vascularised foci ('hot spots') after immuno-staining with CD34 were quantified for number of vessels per square millimetre and for vascular surface area density. No distinction was made between lymphatic and blood vessels. Vascular endothelial growth factor staining was scored semi-quantitatively. RESULTS: The study examined 100 histopathology specimens, including 90(90%) transurethral bladder biopsies and 10(10%) surgical resection specimens of bladder. There were 45(45%) non-invasive (stage pTa) cases and 55(55%) invasive (stage pT1-4) cases. Besides, there were 43(43%) low-grade (grades 1 and 2) cases, and 57(57%) high-grade (grade 3) cases. Vascular endothelial growth factors A, C and D staining scores showed positive association with stage (p=0.02;p<0.01; p<0.01)and grade (p=0.007;p=0.004; p=0.002) of the tumour. Tumours with in-situ component showed association with number of vessels per square millimetre (p<0.01) and vascular surface area density (p=0.02). CONCLUSIONS: Parameters like vascular endothelial growth factor and microvessel density need to be studied further for selection of cases with potential for targeted therapy.

Association between serum total testosterone and Body Mass Index in middle aged healthy men.

OBJECTIVE: To determine correlation of serum total testosterone with body mass index (BMI) and waist hip ratio (WHR) in healthy adult males. METHODS: A cross sectional study was conducted on 200 nonsmoker healthy males (aged 30-50 years) university employees. They were selected by convenience sampling technique after a detailed medical history and clinical examination including BMI and Waist Hip Ratio (WHR) calculation. Blood sampling was carried out to measure serum total testosterone (TT) using facilities of Chemiluminescence assay (CLIA) technique in Dow Chemical Laboratory. Independent sample T test was used for mean comparisons of BMI and WHR in between low and normal testosterone groups. (Subjects having < 9.7 nmol/L of total testosterone in blood were placed in low testosterone group and subjects having ≥ 9.7 nmol/L of total testosterone in blood were placed in normal testosterone group). Correlation of testosterone with BMI and WHR was analyzed by Pearson Correlation. RESULTS: Mean (± SD) age of the subjects included in this study was 38.7 (± 6.563) years mean (± SD) total testosterone was 15.92 (±6.322)nmol/L. The mean (± SD) BMI, and WHR were 24.95 (±3.828) kg/m(2) and 0.946 (±0.0474) respectively. Statistically significant differences were observed in the mean values of BMI and WHR for the two groups of testosterone. Significant inverse correlation of serum total testosterone with BMI(r = -0.311, p = 0.000) was recorded in this study. However testosterone was not significantly correlated with waist/hip ratio.(r = -0.126, p = 0.076). CONCLUSION: Middle age men working at DUHS who have low level of serum total testosterone are more obese than individuals with normal total testosterone level.

Synthesis of Second-Generation Analogs of Temporin-SHa Peptide Having Broad-Spectrum Antibacterial and Anticancer Effects.

Antimicrobial peptides (AMPs) are a promising class of therapeutic alternatives with broad-spectrum activity against resistant pathogens. Small AMPs like temporin-SHa (1) and its first-generation analog [G10a]-SHa (2) possess notable efficacy against Gram-positive and Gram-negative bacteria. In an effort to further improve this antimicrobial activity, second-generation analogs of 1 were synthesised by replacing the natural glycine residue at position-10 of the parent molecule with atypical amino acids, such as D-Phenylalanine, D-Tyrosine and (2-Naphthyl)-D-alanine, to study the effect of hydrophobicity on antimicrobial efficacy. The resultant analogs (3-6) emerged as broad-spectrum antibacterial agents. Notably, the [G10K]-SHa analog (4), having a lysine substitution, demonstrated a 4-fold increase in activity against Gram-negative (Enterobacter cloacae DSM 30054) and Gram-positive (Enterococcus faecalis DSM 2570) bacteria relative to the parent peptide (1). Among all analogs, [G10f]-SHa peptide (3), featuring a D-Phe substitution, showed the most potent anticancer activity against lung cancer (A549), skin cancer (MNT-1), prostate cancer (PC-3), pancreatic cancer (MiaPaCa-2) and breast cancer (MCF-7) cells, achieving an IC50 value in the range of 3.6-6.8 µM; however, it was also found to be cytotoxic against normal cell lines as compared to [G10K]-SHa (4). Peptide 4 also possessed good anticancer activity but was found to be less cytotoxic against normal cell lines as compared to 1 and 3. These findings underscore the potential of second-generation temporin-SHa analogs, especially analog 4, as promising leads to develop new broad-spectrum antibacterial and anticancer agents.

Injudicious use of laboratory facilities in tertiary care hospitals at Rawalpindi, Pakistan: a cross-sectional descriptive study.

BACKGROUND: In recent years inappropriate and excessive use of clinical laboratory facilities has become a cause of concern and has led to concurrent rise in the laboratory errors and the health care costs. The aim of the study was to find out the frequency of incomplete laboratory request forms, inappropriate test requests at various professional levels and the financial impact of uncollected reports at Armed Forces Institute of Pathology (AFIP) and Combined Military Hospital (CMH) Laboratory Rawalpindi. METHODS: The cross-sectional descriptive study was conducted during a three month period from April to June 2012 at AFIP and CMH Laboratory Rawalpindi. A total of 1000 laboratory request forms were collected and scrutinized for completion from AFIP (n=500) and CMH Rawalpindi laboratory (n=500). 536 request forms of costly/specialized tests from different departments of AFIP were studied to find out the professional level of test request. The total number of tests performed at AFIP during the study period and number of uncollected reports were noted. The financial impact of these uncollected reports was also calculated. Collection of data and sorting were done manually. Patient confidentiality was maintained. Microsoft excel software and SPSS-17 were used for analysis. The study was approved by the Institutional Ethical Review Committee. RESULTS: Out of a total of 1000 forms studied none was completely filled with clinical notes being present in only 2.4% and 13% of forms sent to CMH and AFIP respectively. 62% of the expensive investigations were requested by specialists while 38% were ordered by residents and general practitioners but the percentage of avoidable expensive tests ordered by the general practitioners and residents was significantly higher than the specialists(p<0.001). A total of 9026 (40%) and 5046 (22%) diagnostic test reports were not collected from the Chemical pathology and Hematology departments respectively. Financial impact of uncollected reports from all the departments at AFIP collectively amounted to Pakistani Rupees (PKR) 3338201. CONCLUSION: Processing incomplete laboratory request forms and injudicious use of laboratory facilities leads to incorrect interpretation of laboratory test results affecting outcome of the overall treatment.

Toxic effects of chromium on tannery workers at Sialkot (Pakistan).

Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.

Serum leptin values in the healthy obese and non-obese subjects of Rawalpindi.

OBJECTIVE: To determine serum leptin concentrations from a sample of Rawalpindi population in relation to body mass index, age and gender. METHODS: The observational, comparative study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, and Benazir Bhutto Hospital, Rawalpindi from August 2008 to December 2008. Subjects were 100 including healthy obese, overweight and non-obese of both genders aged between 20-50 years. Sampling was done by non-probability convenience method. Body Mass Index was calculated by formula BMI = weight in kg/height in m2: non-obese subjects were defined as 18.5-23.0 kg/m2; overweight 23.1-27.4 kg/m2; and obese 27.5-40 kg/m2. Serum glucose was measured using Glucose oxidase-phenol amino phenazone (GOD-PAP) method and serum leptin by sandwich enzyme-linked immunosorbent assay method. RESULTS: Serum leptin concentrations were higher in obese subjects (mean 52.8 +/- 24.6 ng/mL; range 28.2-77.4 ng/mL; P < 0.001) than in non-obese subjects (mean 12.7 +/- 6.1 ng/mL, range 6.6-18.8ng/mL). Mean Body Mass Index in obese group was 31.7 +/- 3.1 kg/m2 (range 28.6-34.8 kg/m2) while it was 21.2 +/- 1.5 kg/m2 (range 19.7-22.7 kg/m2) in the nonobese group. Body Mass Index was strongly positively correlated with serum leptin concentration (r = 0.59, p < 0.001) in the obese group. The mean serum leptin concentration was much higher in the healthy obese and non-obese women (64.4 ng/mL and 8.7 ng/mL respectively) than in men of both categories (40.4 ng/mL and 5.5 ng/mL respectively). Age had no significant relation with serum leptin level (p = 0.416). CONCLUSIONS: In the study sample, serum leptin concentration was positively correlated with Body Mass Index in healthy obese and non-obese subjects of both genders. The levels were higher in women than in men. Age had no significant relation with serum leptin level in this age group.

A new sesquiterpene, prosoterpene, from Prosopis africana (Guill. & Perr.) Taub.

A new sesquiterpene (Prosoterpene, 1) and eleven reported compounds (2-12) of several classes, such as flavonoids, alkaloids, phenolic acids, and long-chain alcohols, were isolated from the BuOH extract of Prosopis africana (Guill. & Perr.) Taub. Compounds 2-10 were reported for the first time from this plant. Isomers 11 and 12 were separated for the first time. Extensive spectroscopic techniques and literature comparisons were used to characterise their structures. Furthermore, compounds 3, 5-8, and 10-12 were performed for anti-glycation and cytotoxicity activities. Compound 3 (quercetin-3-O-α-L-rhamnoside) exhibited moderate anti-glycation activity. All tested compounds were non-cytotoxic against MCF-7 (breast cancer), NCI-H460 (lung cancer), Hela (cervical cancer), and BJ (normal human fibroblast) cell lines.

Exploring the diversity of virulence genes in the Magnaporthe population infecting millets and rice in India.

Blast pathogen, Magnaporthe spp., that infects ancient millet crops such pearl millet, finger millet, foxtail millet, barnyard millet, and rice was isolated from different locations of blast hotspots in India using single spore isolation technique and 136 pure isolates were established. Numerous growth characteristics were captured via morphogenesis analysis. Among the 10 investigated virulent genes, we could amplify MPS1 (TTK Protein Kinase) and Mlc (Myosin Regulatory Light Chain edc4) in majority of tested isolates, regardless of the crop and region where they were collected, indicating that these may be crucial for their virulence. Additionally, among the four avirulence (Avr) genes studied, Avr-Pizt had the highest frequency of occurrence, followed by Avr-Pia. It is noteworthy to mention that Avr-Pik was present in the least number of isolates (9) and was completely absent from the blast isolates from finger millet, foxtail millet, and barnyard millet. A comparison at the molecular level between virulent and avirulent isolates indicated observably large variation both across (44%) and within (56%) them. The 136 Magnaporthe spp isolates were divided into four groups using molecular markers. Regardless of their geographic distribution, host plants, or tissues affected, the data indicate that the prevalence of numerous pathotypes and virulence factors at the field level, which may lead to a high degree of pathogenic variation. This research could be used for the strategic deployment of resistant genes to develop blast disease-resistant cultivars in rice, pearl millet, finger millet, foxtail millet, and barnyard millet.

Persistent high on-treatment platelet reactivity in acute coronary syndrome.

Persistent high on-treatment platelet reactivity in acute coronary syndrome (ACS) patients managed with appropriate antiplatelet therapy has been correlated with increased risk of cardiovascular events; however, the evolution of this phenomenon overtime is not well known. We investigated platelet activity at a three month follow-up after initial presentation with an ACS. We enrolled a total of 124 patients in the study, 65 were diagnosed with ACS and 59 controls who presented with non-cardiac chest pain for baseline comparisons. Of the enrolled patients, we had 25 ACS patients return, in stable condition, three months after their initial presentation for repeat platelet functional testing. Epinephrine (EPI), adenosine diphosphate (ADP), and arachidonic acid induced platelet aggregation were monitored at baseline with repeat measurement of EPI- and ADP-stimulated aggregation at follow-up. In addition, P-selectin and PAC-1 expression were monitored at presentation and at a three month follow-up period. ACS patients were maintained on aspirin therapy during the intervening period. At the three month follow-up visit, ACS patients initiated on aspirin had no significant percentage change in aggregation to submaximal concentrations of EPI and ADP. They also had no significant percentage change in PAC-1 or P-selectin expression. This study demonstrates persistent high on-treatment platelet reactivity in ACS patients at a three month follow-up, which may place these patients at increased risk of recurrent cardiovascular events.

Frequency of conversion to overt hypothyroidism in patients with and without subclinical hypothyroidism.

BACKGROUND: Sub-clinical hypothyroidism (SCO) poses diagnostic and management difficulties for pathologists and clinicians. Cases of SCO are now diagnosed with increasing frequencies worldwide mainly because of availability of more sensitive methods for serum TSH, total T3 and free T4 assays. The rate of progression of SCO to overt hypothyroidism varies in different populations. Sub-clinical hypothyroidism has been suggested as a risk factor for hypothyroid complications. There is a need to identify and treat patients with SCO before they convert to overt hypothyroidism and develop complications. Objective was to compare the development of overt hypothyroidism in a cohort of patients of sub-clinical hypothyroidism and in subjects with normal thyroid function tests. METHODS: It was Cohort study conducted at Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi. Hundred patients of SCO and almost equal number of age and sex-matched subjects with normal Thyroid function test (TFT) were enrolled as healthy controls. Subclinical hypothyroid patients and controls were followed for a period of one year on six monthly bases. The patients were examined for signs and symptoms of hypothyroidism and serum TSH, total T3 and free T4 were estimated. The clinical history, physical examination and thyroid function tests were recorded on the pre-designed Performa. RESULTS: Fourteen (14%) out of 100 cases of the SCO patients developed overt hypothyroidism, SCO had 2.8 times more risk for conversion to overt hypothyroidism as compared to healthy controls. Moreover female gender and initial levels of serum TSH were the most important predictors for conversion of SCO to overt hypothyroidism. CONCLUSION: The frequency of conversion to overt hypothyroidism in SCO patients approaches 14% and was more commonly observed in female patients.

Role of serum-ascites albumin gradient in differential diagnosis of ascites.

BACKGROUND: The classification of ascites as 'exudative' and 'transudative' based on ascitic fluid total protein (AFTP) has been challenged in many clinical conditions like cardiac ascites, patients on prolonged diuretic therapy and malignant ascites because it had poor diagnostic efficacy. These drawbacks have led to the development of another approach to classify ascites, which is based on Serum-Ascites Albumin Gradient (SAAG) to differentiate ascitic fluid into two categories: SAAG > or = 11 g/L in ascites due to portal hypertension and SAAG < 11 g/L in ascites unrelated to portal hypertension. Objective of this study was to compare the diagnostic efficacy of serum/ascites fluid albumin gradient and ascitic fluid total protein in patients having ascites. METHODS: This Cross-sectional comparative study was conducted in the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from 1st Jun 2007 to 30th May 2008. Ninety-three patients were included in the study by non probability convenience sampling. The patient grouped as: (Group I) 73 cases of liver cirrhosis, (Group II) 14 cases of hepatoma and 6 cases of tuberculous ascites. Ascitic fluid specimen and 3 ml blood were obtained for ascitic fluid estimation of ascitic fluid albumin, total proteins and serum albumin. Diagnostic efficacy of SAAG and AFTP was calculated by comparing the results with clinical, ultrasonographic, histopathological findings, ascitic fluid cell count/acid fast bacilli culture and other relevant investigations. RESULTS: Seventy-three cases had liver cirrhosis (group I), 14 cases had hepatoma and 6 cases had tubercular ascites (group II). Age ranged 25-80 years with mean age 56 years. Diagnostic accuracy, Sensitivity, Specificity, Positive predictive value (PPV) and Negative predictive value (NPV) of SAAG were 96%, 97%, 95%, 98.6%, and 90% respectively, whereas those of AFTP were 56%, 53%,70%, 86%, and 29% respectively. CONCLUSION: Differential diagnosis of ascites should be based on SAAG because diagnostic efficacy of SAAG was significantly higher than AFTP in work-up of ascites.