Resveratrol-induced depression of the mechanical and electrical activities of the rat heart is reversed by glyburide: evidence for possible K<Subscript>ATP</Subscript> channels activation

Resveratrol, a natural phytoalexin found in wine, has been suggested to have benefits in preventing cardiovascular diseases. However, the direct effects of resveratrol on the activity of cardiac tissues and its mechanism of action have not been determined. This study examined the effects of resveratrol on the right and left atrium and left papillary muscle isolated from the rat heart. The contractile responses of the right atrium and papillary muscle and the action potential from the left atrium were recorded and the effects of resveratrol on these responses were observed. The resting force of the isolated right atrium and the peak developed force of the left papillary muscle were depressed by resveratrol (0.1 nM - 0.1 mM). Exposure to the K(ATP) channel blocker glyburide (3 microM) prevented significantly the resveratrol-induced decrease. Resveratrol (0.1 mM) shortened the repolarization phase of action potential recorded from the left atrium and this effect of resveratrol was reversed by glyburide (3 microM). These results indicated that resveratrol depressed cardiac muscle contraction and shortened action potential duration probably due to the activation of K(ATP) channels in the rat heart.     

The effects of cyclooxygenase-2 expression in prostate cancer cells: modulation of response to cytotoxic agents

Cyclooxygenase (COX)-2 has emerged as an exciting target for therapeutic intervention in the management of cancer. Immunohistochemistry studies have indicated higher expression of COX-2 in cancerous versus benign prostatic tissue. We have explored the role of COX-2 in prostate cancer in terms of attenuation of apoptosis and sensitivity to pharmacological agents, including COX-2 inhibitors. The human prostate cancer cell line LNCaP was stably transfected with COX-2 (LNCaPCOX-2) and compared with the empty vector control line (LNCaPneo). Chemosensitivity testing indicated no change in sensitivity to the cytotoxic effects of COX-2 inhibitors celecoxib or sulindac or VP16. However, LNCaPCOX-2 cells showed 3-fold resistance to carboplatin, which was partially reversed by coincubation with the phosphatidylinositol 3-kinase inhibitor wortmannin. Concomitant with reduced apoptotic response to cytotoxic agents, LNCaPCOX-2 cells expressed increased levels of survivin and Bcl-2 with enhanced activation of AKT. We also investigated the effects of celecoxib on expression levels of genes relevant to prostate cancer and drug resistance in our model system using quantitative polymerase chain reaction analysis. Celecoxib treatment resulted in highly significant increases in the mRNA expression of the smooth muscle component desmin, the detoxification enzyme glutathione S-transferase pi (GSTpi), and nonsteroidal anti-inflammatory response gene (NAG-1) in the LNCaPCOX-2 cell line compared with LNCaPneo cells. Significant decreases in survivin levels and increases in GSTpi and NAG-1 appeared to be COX-2-dependent effects because they were more pronounced in LNCaPCOX-2 cells. Our findings indicate both COX-2-dependent and -independent mechanisms attributable to celecoxib and support its utility in the management of prostate cancer.     

The protective role of zinc and calcium in Vicia faba seedlings subjected to cadmium stress

The aim of the present study was to evidence the possible antagonistic effect of Zinc (Zn(2+)) and Calcium (Ca(2+)) against cadmium (Cd(2+))-induced DNA damage by using random amplification of polymorphic DNA (RAPD) and metabolic activities in Vicia faba. The results showed that all doses of Cd(2+) (10( -3) M, 10(-5) M) caused an increase in polymorphism value and a decrease in genomic template stability (GTS %). In addition, when 10( -4)-10(-6) M Ca(2+), 10(-6) M Zn(2+) were added together with 10(-3) M, 10(-4) M, 10(-5) M of Cd(2+), polymorphism value decreased besides GTS, total protein and chlorophyll content increased. Results suggested that Zn(2+) and Ca(2+) have an antagonistic effect against Cd(2+). The order of the antagonisms of Ca(2+), Zn(2+) against Cd(2+) toxicity was Ca(2+) > Zn(2+). Especially, the degree of antagonistic effect of Zn(2+) against Cd(2+) is probably related to its concentration ratio.     

Histological grading patterns in patients of cutaneous leishmaniasis

Objective: To determine the histological grading patterns in a cohort of hospitalized patients of cutaneous leishmaniasis. Design: Case series. Place and Duration of Study: The study was conducted at PNS Shifa Hospital, Karachi, from May 2004 to June 2006. Patients and Methods: One hundred patients of Cutaneous Leishmaniasis (CL), admitted in dermatology wards at PNS Shifa Hospital, Karachi, were examined. Only admitted patients of all ages and both sexes were included in the study. Patients of CL, who had received or were receiving systemic treatment were excluded. The lesions having marked secondary bacterial infection were also excluded. Initial diagnosis was clinical. History of being to an endemic area supported the diagnosis. The lesions were divided in two groups. Early, with duration less than 03 months and late, with duration between 3 and 12 months. The clinical lesions were noted as nodules, plaques, ulcers, crusted ulcers, lupoid lesions and plaques with scarring. Three types of skin smears (slit skin smear, saline aspirate smear and dab smear) were taken and examined with Giemsa stain. Cultures were performed on Nicolle-Novy-MacNeal (NNN) culture medium from Defense Scientific and Technology Organization (DESTO) Lab., Pakistan. Incisional skin biopsies were done. The biopsy specimens were examined by hemotoxylin and eosin stain (H & E stain). The number of Leishmania Tropica (LT) bodies was graded according to modified Ridley's parasitic index 1983. Clinical features were correlated with the histological patterns. Results: Five histological patterns were identified in current study: 1) diffuse dermal infiltration without necrosis, 2) patchy dermal infiltration, 3) diffuse dermal infiltration with necrosis, 4) early reactive granuloma formation and 5) established epithelioid granuloma formation. LT bodies were identified in 75% of cases. Epidermal features were non-specific. The early lesions presented with diffuse infiltrate and late lesions showed granuloma formation. Conclusion: Five distinct types of histological patterns of CL have been recognized in this study. The early lesions presented with diffuse infiltrate and late lesions showed granuloma formation but the mixed patterns were also seen. The yield of LT bodies is much higher with histopathology as compared to skin smears and hence is most diagnostic.     

Anti-inflammatory role of methotrexate in adjuvant arthritis: effect on substance p and calcitonin gene-related Peptide in thymus and spleen

Objective: To investigate the anti-inflammatory effect of methotrexate (MTX) in rats with adjuvant arthritis through its influence on the expression of proinflammatory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in immune organs, thymus and spleen. Design: Phase-I pre-clinical trial. Place and Duration of Study: The Aga Khan University, Karachi, from July to December 2003. Materials and Method: Adjuvant arthritis was induced in rats by inoculation with heat-killed mycobacteria. One group of arthritic rats (n=6) was treated with MTX (0.2 mg/kg body weight, subcutaneously) on every 4th day for a period of 18 weeks, while another group of arthritic rats (n=6) was treated with physiological saline served as control. At the end of experiment, animals were sacrificed and thymus and spleen were dissected and prepared for immunohistochemical analysis. The neuronal density of SP and CGRP immunoreactivity in thymus and spleen was assessed by semi-quantitative analysis. Results: There was a marked reduction in hind paw swelling and inflammation in the MTX-treated rats after 18 weeks of treatment. Restoration of joint spaces (tibiotalar and subtalar) was seen after 9 weeks of MTX treatment. CGRP-positive nerve fibres were significantly reduced (p=0.0001) in thymus of rats treated with MTX compared to control rats. SP-positive nerve fibers were also found to be decreased in thymus of rats treated with MTX compared to controls, however, the decrease was not statistically significant. The neuronal density of SP and CGRP-immunoreactivity in spleen was not significantly different in MTX-treated and placebo-treated rats. Conclusion: In arthritic rats, MTX significantly reduced CGRP expression in thymus. Suppression of pro-inflammatory neuropeptides, such as CGRP and probably SP could be another mechanism by which MTX produces its anti-inflammatory effect in adjuvant arthritis.     

Structural,electronic, magnetic and elastic properties of xenon-based fluoroperovskites XeMF3 (M = Ti,V, Zr,Nb) via DFT studies

In this work, the structural, electronic, magnetic and elastic properties of the xenon-based fluoroperovskites XeMF₃ (M = Ti, V, Zr, Nb) have been studied using density functional theory. The structural study reveals that all the perovskites have stable structures. A half-metallic nature is observed due to the presence of a band gap in only the spin-down channel. The result indicates that the considered compounds are ferromagnetic materials with integer magnetic moments. The elastic parameters were studied to obtain their elastic properties. It is noted that all compounds have an anisotropic nature and show ductility. The optical characteristics show that these compounds are good optical absorbers at high energy. Furthermore, we suggest that these compounds could be good candidates for spintronic and optoelectronic devices.

In this work, the structural, electronic, magnetic and elastic properties of the xenon-based fluoroperovskites XeMF₃ (M = Ti, V, Zr, Nb) have been studied using density functional theory.