Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3)-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall. Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT) and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis. The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.

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Objective : Hemoglobin F augmentation is another approach to treat sickle cell disease (SCD). This study evaluates the efficacy and impact of Hydroxyurea (HU) on fetal hemoglobin (HbF) and other hematological parameters, which result in decreasing the painful crisis and lower hospital admissions. Materials and Methods : A prospective study was carried out in the Department of Medicine, Government Medical College, Jagdalpur. Twenty-seven patients with SCD received HU at a mean dose of 22 mg/kg/d. The baseline results were analyzed and compared with the post treatment result, at the end of one year. Statistics : Student's t-test was used to determine the level of significance. Results : Twenty-four patients completed a one-year period successfully; a significant increase was noted in the mean HbF%, from 12.83 to 19.17, and the mean corpuscular volume (MCV) from 82.57 to 89.87 Fl. The mean hospital admission (numbers) in the last one year decreased from 4.75 to 2.25 and the mean number of SCD crisis for the last one year decreased significantly from 3.63 to1.67. Conclusion : We found a significant reduction in hospital admissions, a reduction in the overall sickle cell crisis and an associated improvement in HbF% without any significant side effects in the patients with SCD, treated with HU.

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Objective : To investigate the immunosuppressive potential of Pluchea lanceolata 50% ethanolic extract (PL) and its bioactive chloroform fraction (PLC). Materials and Methods : Preliminary screening of the Pluchea lanceolata 50% ethanolic extract (PL) was carried out with basic models of immunomodulation, such as, the humoral antibody response (hemagglutination antibody titers), cell-mediated immune response (delayed-type hypersensitivity), skin allograft rejection test, in vitro (C. albicans method), and in vivo phagocytosis (carbon clearance test). The extract was then fractionated with chloroform, n-butanol, and water to receive the respective fractions by partitioning. These fractions were employed for flow cytometry to study the T-cell specific immunosuppressive potential of these fractions. Results : Oral administration of PL at doses of 50 to 800 mg/kg in mice, with sheep red blood cells (SRBC) as an antigen, inhibited both humoral and cell-mediated immune responses, as evidenced by the production of the circulating antibody titer and delayed-type hypersensitiviy reaction results, respectively, and the immune suppression was statistically significant (P < 0.01) in Balb/C mice. PL also decreased the process of phagocytosis both in vitro (31.23%) and ex vivo (32.81%) and delayed the graft rejection time (30.76%). To study the T-cell-specific activities, chloroform, n-butanol, and water fractions from P. lanceolata were tested for T-cell specific immunosuppressive evaluation, wherein only the chloroform fraction (PLC) showed significant (P < 0.01) suppression of CD8+ / CD4+ T-cell surface markers and intracellular Th1 (IL-2 and IFN- _Y ) cytokines at 25 - 200 mg/kg p.o. doses. PLC, however, did not show significant suppression of the Th2 (IL-4) cytokine. Conclusion : The findings from the present investigation reveal that P. lanceolata causes immunosuppression by inhibiting Th1 cytokines.

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Aims : This prospective study was designed to monitor and analyze the pattern of occurrence of adverse drug reactions (ADRs) to cisplatin-based chemotherapy regimen in the cancer ward of a tertiary care hospital. Materials and Methods : Cancer patients who received cisplatin-based cancer chemotherapy were monitored for adverse reactions. The collected reports were analyzed for demographic and drug details, causality, preventability and severity of adverse effects. Causality was assessed by the World Health Organization (WHO) causality assessment scale and Naranjo's Algorithm. Preventability and severity of ADRs were assessed by modified Schumock and Thornton scale, modified Hartwig and Siegel scale respectively. Results : Among 51 patients, 48 developed ADRs to cisplatin chemotherapy. The reactions observed were nausea, alopecia, anorexia, vomiting, taste alteration, diarrhea, constipation, tinnitus, and hypocalcaemia. The WHO causality assessment scale indicated 69% "possible" and 31% "probable" but no "certain" reactions. Naranjo's Algorithm showed 62% "probable" and 38% "possible" reactions. Most of the reactions belonged to the category of "not preventable". Reactions like nausea and vomiting belonged to the category of "definitely preventable". Modified Hartwig and Siegel scale of severity assessment showed that most of the reactions were of "mild level 1" severity except for vomiting, diarrhea and hypocalcaemia, which were of "moderate level 3" severity. Conclusion : Cisplatin-based chemotherapy has a high potential to cause adverse effects. Most of the reactions were of milder nature but not preventable. The common adverse effects such as nausea and vomiting were preventable, but reactions like hypersensitivity reactions and anaphylaxis were not predictable.

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Background : The repercussion of the heated dispute on cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) led to the national and international withdrawal of several of the recently introduced coxibs. Further debate and research have highlighted risks of the classical NSAIDs too. There is much controversy about the cardiovascular safety of a nonselective NSAID naproxen (NAP) and its possible cardioprotective effect. Objectives : The study was undertaken to determine the cardiovascular effects of NAP on doxorubicin-induced cardiomyopathy in rats. Materials and Methods : Male albino rats received a single i.p. injection of normal saline (normal control group) and doxorubicin (DOX) 15 mg/kg (toxic control group). Naproxen was administered alone (50 mg/kg/day, p.o.) and in combination with DOX and DOX + trimetazidine (TMZ) (10 mg/kg/day, p.o.) for 5 days after 24 h of DOX treatment. DOX-induced cardiomyopathy was assessed in terms of increased activities of serum lactate dehydrogenase (LDH), tissue thiobarbituric acid reactive substances (TBARS) and decreased activities of myocardial glutathione, superoxide dismutase and catalase, followed by transmission electron microscopy of the cardiac tissue. Results : Doxorubicin significantly increased oxidative stress as evidenced by increased levels of LDH and TBARS and decreased antioxidant enzymes levels. Both biochemical and electron microscopic studies revealed that NAP itself was cardiotoxic and aggravated DOX-induced cardiomyopathy and abolished the protective effect of TMZ in rats. Conclusions : This study indicates that NAP has the potential to worsen the situation in patients with cardiovascular disease. Therefore, it should be used cautiously in patients with compromised cardiac function.

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Angiogenesis is a fundamental biological process that is regulated by a fine balance between pro- and antiangiogenic molecules, and is deranged in various diseases. Historically, angiogenesis was only implicated in few diseases, such as, cancer, arthritis, and psoriasis. However, in recent years, it has been increasingly evident that excessive, insufficient or abnormal angiogenesis contributes to the pathogenesis of many more disorders. Research in angiogenesis offers a potential to cure a variety of diseases such as Alzheimer's and AIDS. Modulation of angiogenesis may have an impact on diseases in the twenty-first century similar to that which the discovery of antibiotics had in the twentieth century.

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Background : Treatment of chronic idiopathic urticaria (CIU) is challenging because of its unpredictable course and negative influence on the quality of life. New treatments are being developed, but antihistaminics remain the cornerstone of the therapeutic approach. Newer generation antihistaminics such as loratadine and levocetirizine have already proved to be safe and efficacious for CIU. Objective : To choose the better drug between loratadine and levocetirizine for CIU, by comparing their efficacy and safety. Methods : A randomized, open, outdoor-based clinical study was conducted on 60 patients of CIU, to compare the two drugs. After initial clinical assessment and baseline investigations, loratadine was prescribed to 30 patients and levocetirizine to another 30 patients for four weeks. At follow-up, the patients were re-evaluated and then compared using different statistical tools. Result : The comparative study showed that the changes in differential eosinophil count (P = 0.006) and absolute eosinophil count (P = 0.003) in the levocetirizine group was statistically significant. The results of the Total Symptom Score showed better symptomatic improvement of CIU with levocetirizine as compared to loratadine. The overall incidence of adverse drug reactions was also found to be less in the levocetirizine group. Conclusion : An analysis of the results of all the parameters of safety and efficacy proves the superiority of levocetirizine over loratadine for CIU.

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Objectives : To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM). Materials and Methods : In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes) and on the peripheral pain or the late phase (15 to 30 minutes). To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation. Results : DRDE-07 (81.7%) and DRDE-30 (79.4%) showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%), DRDE-30 (82%), and DRDE-35 (61.3%) showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60%) including amifostine (43.9%) showed significant reduction of paw edema in the carrageenan-induced paw edema in mice. Conclusion : The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin.

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Drug-induced pancreatitis is a rare but serious complication of many drugs, some of which have been well documented. Here we present a case of a middle-aged man with chronic myeloid leukemia who developed acute pancreatitis after being initiated on imatinib mesylate. The case history, the pharmacodynamics, uses, and adverse effects of imatinib mesylate are discussed in detail.

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Objectives : Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. Materials and Methods : One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Results : Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P < 0.05). No cases of hypotension were observed with the use of d-ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P < 0.05). Three patients (10%; 0 to 20.7) on d-ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P < 0.05). Conclusions : The phosphonate group in p-ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea.

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Objective : To study the effect of pantoprazole on neuromuscular transmission and its interactions with vecuronium at the neuromuscular junction (NMJ). Materials and Methods : Effect of pantoprazole on neuromuscular transmission (2 µM - 16 mM) and reversal of neuromuscular blockade by pantoprazole and vecuronium with neostigmine (3.3 µM), 3,4-diaminopyridine (0.25 mM), KCl (6 mM), and CaCl ₂ (10 mM) were studied by the indirect and direct stimulated preparation of rat phrenic nerve hemidiaphragm. Cumulative reponse curves (CRC) of vecuronium (1 µM to 32 µM) were studied in the absence and presence of 32 µM, 64 µM, and 128 µM pantoprazole. Time for head drop by vecuronium infusion was recorded in the absence and presence of acute and chronic administration of pantoprazole (1.9 mg/kg) in rabbits. Results : Pantoprazole potentiated the basal contractile twitch responses at a lower concentration followed by neuromuscular blockade at a higher concentration. The neuromuscular blockade was not reversed by neostigmine (3.3 µM), 3,4-diaminopyridine (0.25 mM), KCl (6 mM), and CaCl ₂ (10 mM). Pantoprazole potentiated the vecuronium-induced neuromuscular blockade. It decreased the total time for complete blockade in rat phrenic nerve hemidiaphragm preparation (P < 0.05) and decreased the time for the head drop in rabbits with vecuronium infusion (P < 0.0001). Conclusion : Pantoprazole has a direct neuromuscular blocking action. It has the potential to interact with vecuronium.

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Torsades de pointes (TdP) or polymorphic ventricular tachycardia owing to drug-induced QT prolongation is a common cause of withdrawal of marketed drugs and has caused increasing concern in the recent past. Carbimazole, the common antithyroid drug, is not a very well-known offender to cause QT prolongation and TdP. Only a few cases of carbimazole-induced TdP have been reported so far. We report a 53-year-old woman who was on tab. carbimazole (10 mg) twice daily for one month and who presented with respiratory distress, palpitation and syncope attack. Her surface electrocardiogram (ECG) was showing the evidence of TdP and subsequently hypokalemia was also detected. She received conservative management including potassium supplementation. However, QT prolongation persisted even after normalization of serum potassium level. Carbimazole was withdrawn and the patient was discharged as she remained stable and symptom free. This study highlights a possible association between carbimazole and TdP.

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