Evaluation of ambrein and epicoprostanol for their antioxidant properties: protection against adriamycin-induced free radical toxicity.

Ambrein and epicoprostanol were evaluated for their antioxidant potential in vitro by chemiluminescence (CL), as well as in vivo using lipid peroxides and glutathione levels as indicators in liver tissue of rats treated with adriamycin (doxorubicin) a well known free radicals producing drug. In the in vitro test, the inhibition in CL by ambrein was dose dependent. Both the high concentrations of ambrein (20-40 microg/ml) inhibited CL response significantly (P<0.05 and P<0.01, respectively) when compared to control. Similarly two low concentrations (5-20 microg/ml) of epicoprostanol inhibited CL significantly (P<0.001 and P<0.01, respectively) in comparison of DMSO control. The high concentration (40 microg/ml) of epicoprostanol behaved exceptionally and caused an increase in CL response that was more than control and significantly (P<0.001) higher than both the low concentrations. In the in vivo studies adriamycin treatment significantly (P<0.05) increased malondialdehyde (MDA) and decreased non-protein sulfhydryl (NP-SH) contents in the liver tissue of mice after 5 days treatment. Ambrein (25 and 50 mg/kg) treatment as a solo therapy at both the dose levels significantly (P<0.001) decreased MDA contents in the liver tissue. On the other hand, in the combined treatment the high dose effectively prevented any rise in MDA contents and it remained around the levels of ambrein alone. In the same experiment, adriamycin declined NP-SH contents significantly (P<0.001). Ambrein alone at both the dose levels caused a decline (P<0.01) in NP-SH contents when compared to adriamycin group. But in the combined treatment this decline in NP-SH was significantly (P<0.05) different from adriamycin alone. In the experiments dealing with epicoprostanol, adriamycin treatment increased MDA contents significantly (P<0.05) that declined significantly (P<0.001) with epicoprostanol (10- or 20mg/kg) treatment. In the same experiment co-treatment with adriamycin prevented any rise in MDA contents significantly (P<0.001) as it was observed in adriamycin alone group. Although, this treatment failed to prevent any decline in NP-SH contents either alone or in combination with adriamycin. Epicoprostanol itself had the comparative declining effect on the contents of NP-SH as seen in adriamycin group. From the results of our experiments it seems that ambrein at all concentrations behaves like antioxidant in in vitro studies but the same time it decreased NP-SH contents in vivo accompanied by a decline in MDA contents. Whereas, epicoprostanol at two low concentrations had a decline in CL indicating a possible antioxidant potential but the high concentration increased CL showing a tendency towards oxidant prospective. However, in animal studies it has shown a clear protection against adriamycin induced free radical damage.     

Pakistani urban population demonstrates a poor knowledge about cancers: A pilot survey

Background. This cross-sectional study was carried out to assess the perceptions and level of knowledge of a Pakistani urban population regarding presentations, risk factors, and screening of cancers. Methods. From 4 tertiary care hospitals, 439 subjects were recruited through convenient sampling method and interviewed using a standard questionnaire. Results. More than 90% of subjects demonstrated poor knowledge. Good knowledge was associated with female gender, being married, higher socioeconomic status, and level of education. Conclusions. Our sample demonstrates an inadequate knowledge regarding the presentations, risk factors, and screening of cancers. Efforts aiming to correct these deficiencies might result in a successful and cost-effective model for primary and secondary prevention of major cancers in Pakistan.     

Ventilatory function of healthy, urban, non smoking, Pakistani young adults aged 18-24 years.

Age may have a different contribution to normal lung function values in those aged less than 25 years, as compared to older individuals. We report regression equations predicting ventilatory parameters in this age group, as none have been reported from Pakistan. The study was conducted on students of King Edward Medical College Lahore, Pakistan. Participants had never smoked and reported no respiratory symptoms. In addition to anthropometric data, forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and forced expiratory flow at 50% of FVC (FEF50) were measured. Equations predicting normal values of these parameters were derived using SPSS (Chicago, Illinois, U.S.A.) P < or = 0.05 was treated as statistically significant. Of the students, 519 took part in the study. All four parameters correlated significantly (P < 0.001) and positively with height. FEF50 had a negative correlation with age in both sexes (P < 0.05). The correlation of other parameters with age was variable and not statistically significant. On multiple regression, height featured as an independent predictor in equations for all parameters. The contribution of age as an independent predictor of ventilatory function was, once again, variable. Independent variables were retained in the raw form as their transformation did not improve the goodness of fit of the derived equations. Only height and age emerged as independent predictors of ventilatory function. Values derived from the equations presented in this study were less than those for height and age matched white Caucasians. Such differences were greater than the 'Asian correction factors'.     

Application of Spinal Cord Stimulation for the Treatment of Abdominal Visceral Pain Syndromes: Case Reports

Spinal cord stimulation (SCS) has traditionally been applied to the treatment of neuropathic pain with good to excellent outcomes. Visceral pain syndromes can be just as debilitating and disabling as somatic and neuropathic pain, however, there seems to be a general lack of consensus on appropriate treatment strategies for these disorders. We present here several case studies to demonstrate the viscerotomal distribution of abdominal visceral pain pathways and the application of traditional SCS techniques for its management. Nine patients, experiencing abdominal visceral pain due to various conditions including chronic nonalcoholic pancreatitis, post‐traumatic splenectomy, and generalized abdominal pain secondary to laparotomies, were treated with SCS. Efficacy of treatment was evaluated using the Visual Analog Scale (VAS) for pain intensity and a reduction, if any, in opioid intake. There was an overall mean reduction of 4.9 points in the VAS score for pain intensity and a substantial (> 50%) decrease in narcotic use. All patients were followed for more than one year with excellent outcomes and minimal complications. We conclude, based on these case reports, that SCS might be an effective, nondestructive, and reversible treatment modality for abdominal visceral pain disorders.     

Pharmacological stress agents for evaluation of ischemic heart disease.

Ischemic heart disease is the leading cause of death in the developed countries for those older than 65 years of age. In patients suspected to have coronary artery disease a stress test should be performed to identify the vulnerability of the myocardium to ischemia. As a rule of thumb, the evaluation of coronary artery disease is best done by exercise stress test. In patients who are not able to exercise adequately, pharmacological stress agents are used. The commonly used agents are the coronary vasodilators, adenosine and dipyridamole and the catecholamines, dobutamine and arbutamine. These agents are combined with imaging techniques to increase the sensitivity and specificity of the test. These agents have been widely used and have an excellent safety profile. Another advantage in using pharmacological stress agents is that they do not affect the image quality, especially with echocardiography and magnetic resonance imaging. Ongoing developments hold promise for safer and more reliable pharmacological stress agents in the future.     

Biological Significance of Proliferation, Apoptosis, Cytokines, and Monocyte/Macrophage Cells in Bone Marrow Biopsies of 145 Patients With Myelodysplastic Syndrome

Labeling index (LI), apoptosis, levels of 2 pro-apoptotic cytokines tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(TGF-beta), and the number of monocyte/macrophage cells that are the likely source of the cytokines were simultaneously measured in plastic-embedded bone marrow (BM) biopsy sections of 145 patients with myelodysplastic syndromes (MDS). TNF-alpha was correlated with TGF-beta (P = .001) and with monocyte/macrophage cells (P = .003). Patients with excess blasts in their marrows had a higher TGF-beta level (P = .01) and monocyte/macrophage number (P = .05). In a linear regression model,TGF-beta emerged as the most significant biological difference between patients who have excess of blasts and those who do not (P = .01). We conclude that in addition to TNF-alpha, TGF-beta also plays a significant role in the initiation and pathogenesis of MDS, and that a more precise definition of its role will likely identify better preventive and therapeutic strategies.     

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.     

Rosuvastatin: A Highly Effective New HMG‐CoA Reductase Inhibitor

Rosuvastatin, a new statin, has been shown to possess a number of advantageous pharmacological properties, including enhanced HMG‐CoA reductase binding characteristics, relative hydrophilicity, and selective uptake into/activity in hepatic cells. Cytochrome P450 (CYP) metabolism of rosuvastatin appears to be minimal and is principally mediated by the 2C9 enzyme, with little involvement of 3A4; this finding is consistent with the absence of clinically significant pharmacokinetic drug‐drug interactions between rosuvastatin and other drugs known to inhibit CYP enzymes. Dose‐ranging studies in hypercholesterolemic patients demonstrated dose‐dependent effects in reducing low‐density lipoprotein cholesterol (LDL‐C) (up to 63%), total cholesterol, and apolipoprotein (apo) B across a 1‐ to 40‐mg dose range and a significant 8.4% additional reduction in LDL‐C, compared with atorvastatin, across the dose ranges of the two agents. Rosuvastatin has also been shown to be highly effective in reducing LDL‐C, increasing high‐density lipo‐protein cholesterol (HDL‐C), and producing favorable modifications of other elements of the atherogenic lipid profile in a wide range of dyslipidemic patients. In patients with mild to moderate hypercholesterolemia, rosuvastatin has been shown to produce large decreases in LDL‐C at starting doses, thus reducing the need for subsequent dose titration, and to allow greater percentages of patients to attain lipid goals, compared with available statins. The substantial LDL‐C reductions and improvements in other lipid measures with rosuvastatin treatment should facilitate achievement of lipid goals and reduce the requirement for combination therapy in patients with severe hypercholesterolemia. In addition, rosuvastatin's effects in reducing triglycerides, triglyceride‐containing lipoproteins, non‐HDL‐C, and LDL‐C and increasing HDL‐C in patients with mixed dyslipidemia or elevated triglycerides should be of considerable value in enabling achievement of LDL‐C and non‐HDL‐C goals in the numerous patients with combined dyslipidemias or metabolic syndrome who require lipid‐lowering therapy. Rosuvastatin is well tolerated alone, and in combination with fenofibrate, extended‐release niacin, and cholestyramine, and has a safety profile similar to that of currently marketed statins. A large, long‐term clinical trials program is under way to investigate the effects of rosuvastatin on atherosclerosis and cardiovascular morbidity and mortality.