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Dengue has become a worldwide affliction despite incessant efforts to search for a cure for this long-lived disease. Optimistic consequences for dengue vaccine are implausible as the efficiency is tied to previous dengue virus (DENV) exposure and a very high cost is required for large-scale production of vaccine. Medicinal plants are idyllic substitutes to fight DENV infection since they constitute important components of traditional medicine and show antiviral properties, although the mechanism behind the action of bioactive compounds to obstruct viral replication is less explored and yet to be discovered. This review includes the existing traditional knowledge on how DENV infects and multiplies in the host cells, conscripting different medicinal plants that obtained bioactive compounds with anti-dengue properties, and the probable mechanism on how bioactive compounds modulate the host immune system during DENV infection. Moreover, different plant species having such bioactive compounds reported for anti-DENV efficiency should be validated scientifically via different in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Background: IgG4-related disease is an autoimmune process that presents with tumefactive lesions characterized by storiform fibrosis, a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, obliterative phlebitis, and often elevated serum IgG4 levels. Central nervous system IgG4-related disease is very rare and usually occurs in the form of hypertrophic pachymeningitis or hypophysitis. Presentation as a large solitary meningioma-like mass with overlying hyperostosis in a young adult has not been reported before. Case summary: A 16-year-old male presented with focal seizures for 5 months. Imaging showed a large, extra-axial, and contrast-enhancing mass lesion in the left frontoparietal region with focal calvarial thickening. Histopathology revealed a fibrosclerotic lesion involving dura with a polymorphic infiltrate of plasma cells, mature lymphocytes, histiocytes, and occasional eosinophils. Immunohistochemical workup excluded the possibilities of meningioma, lymphoproliferative neoplasms, and histiocytic lesions. Majority of plasma cells were IgG4+ rendering a diagnosis of IgG4-related disease. Further serological and imaging workup did not reveal any evidence of systemic involvement. His serum IgG4 levels were normal. Considering a gross total resection of the lesion, no further treatment was given and the patient has been asymptomatic since. Conclusion: IgG4-related lesions of the CNS are under-recognized and accurate diagnosis, especially in those with isolated CNS disease and normal serum IgG4 levels, necessitates robust histopathological and laboratory workup to exclude mimics. They may occur as large dural masses with hyperostosis and differentiation from lymphoplasmacyte-rich meningiomas, in particular, can be challenging. While steroids are the mainstay of treatment in IgG4-related disease, surgical resection may be curative in solitary lesions presenting with compressive symptoms. [ABSTRACT FROM AUTHOR]

Infection of human immunodeficiency virus (HIV) is determined through the decay of healthy CD4+ T-cells in a well-mixed compartment, such as a bloodstream. A mathematical model is considered to illustrate the effects of combined drug therapy, i.e. reverse transcription plus protease inhibitor, on viral growth and T-cell population dynamics. This model is used to explain the existence and stability of infected and uninfected steady states in HIV growth. An analytical technique, called variational iteration method (VIM), is used to solve the mathematical model. This method is modified to obtain the rapidly convergent successive approximations of the exact solution. These approximations are obtained without any restrictions or the transformations that may change the physical behavior of the problem. Numerical simulations are computed and exhibited to illustrate the effects of proposed drug therapy on the growth or decay of infection. [ABSTRACT FROM AUTHOR]

Background SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These three HDAC classes are highly expressed in castration resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We designed a phase II study of SB939 in men with metastatic CRPC. Methods Patients received SB939 60 mg on alternate days three times per week for 3 weeks on a 4-week cycle. Primary endpoints were PSA response rate (RR) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating tumor cell (CTC) enumeration and safety. Exploratory correlative studies of the TMPRSS2-ERG fusion and PTEN biomarkers were also performed. Results Thirty-two patients were enrolled of whom 88 % had received no prior chemotherapy. The median number of SB939 cycles administered was three (range 1-8). Adverse events were generally grade 1-2, with five pts experiencing one or more grade three event. One patient died due to myocardial infarction. A confirmed PSA response was noted in two pts (6 %), lasting 3.0 and 21.6 months. In patients with measurable disease there were no objective responses. Six patients had stable disease lasting 1.7 to 8.0 months. CTC response (from ≥5 at baseline to <5 at 6 or 12 weeks) occurred in 9/14 evaluable patients (64 %). Conclusion Although SB939 was tolerable at the dose/schedule given, and showed declines in CTC in the majority of evaluable patients, it did not show sufficient activity based on PSA RR to warrant further study as a single agent in unselected patients with CRPC. [ABSTRACT FROM AUTHOR]

Background:Rhabdomyosarcoma is a malignant mesenchymal neoplasm rarely diagnosed in the larynx. Traditionally, it has been treated by radical surgery (i.e. total laryngectomy), followed by radiation and/or chemotherapy. Recent advances suggest that it may be treated with combination therapy comprising high-dose radiation and pulse chemotherapy, with a high success rate.Case report:We report the first documented case of subglottic embryonal rhabdomyosarcoma in an adolescent female treated with chemoradiation alone, and review the literature reflecting a move towards organ preservation.Conclusion:While surgery has been successfully used to treat this neoplasm, combination therapy, as described in our study, also seems effective and has the added advantage of preserving laryngeal function. [ABSTRACT FROM PUBLISHER]

Introduction: Preexisting malnutrition in surgical patients has been conclusively correlated with complications such as wound infection, anastomotic leakage, chest infection and myriad of other adverse outcomes during and after hospitalization. So, it is imperative to recognize and manage this status preoperatively in an effort to improve outcome. The aim of the study was to compare the Subjective Global Assessment (SGA) and Nutritional Risk Index (NRI) with outcome after abdominal surgery. Methods: This is a prospective study conducted at the Department of Surgery, Tribhuvan University Teaching Hospital, Nepal, for the period of one year. The study included a total of fifty patients undergoing abdominal surgery. Patients were assessed with two types of nutritional assessment techniques, namely, SGA and NRI. The outcome parameters included were wound infection, chest infection, and length of hospital stay. Results: No complications occurred in 24 of the 50 patients; 13 patients had more than one complication. The frequency of malnutrition was found to be 74% and 80% as assessed by SGA and NRI respectively. Morbidity rate was significantly higher in malnourished patients assessed by SGA group. Wound infection rate was significantly higher and length of hospital stay was also longer in malnourished patients when assessed by SGA. The area under the receiver operating characteristic curve for SGA and NRI revealed that SGA was better for predicting overall morbidity as well as specific complications than the NRI. Three patients died during treatment period. Conclusions: Malnutrition is a marker of poor postoperative outcome. Subjective Global Assessment is better than Nutritional Risk Index to predict postoperative complications in patients undergoing abdominal surgery. [ABSTRACT FROM AUTHOR]

The role of quantitative hepatitis B surface antigen ( HBs Ag) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBs Ag response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBs Ag decline of ≥1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBe Ag-positive and HBe Ag-negative patients, respectively. Early decline in HBs Ag levels at week 4 was predictive of subsequent significant HBs Ag level decline. HBe Ag seroconversion occurred in 29.9% of HBe Ag-positive patients. On multinomial logistic regression, HBs Ag level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBe Ag seroconversion and HBV DNA level decline from baseline at week 4 and week 12 ( OR = 3.704; 95% CI = 1.511-9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032-2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV-infected patients treated with tenofovir exhibit a significant (≥1.0 log) decline in HBs Ag levels. Early decline in HBs Ag levels at week 4 was predictive of subsequent and significant HBs Ag level decline. The HBs Ag decline did not correlate with HBe Ag seroconversion in HBe Ag-positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion. [ABSTRACT FROM AUTHOR]

The present study examines the effect of psychotherapy on pathological gamblers. Ninety five (95) treated and 95 non-treated pathological gamblers were evaluated at SIMPHS Varanasi (India). The two groups were matched with respect to age (ranging from 23 to 61 years with a mean age of 41.2 years and mean length of uncontrollable gambling of 10.3 years). Indian adaptation of T.A.T. (Seven cards: 1, 3B, 4, 6BM, 7BM, 13MF, and 16) and Middlesex Hospital Questionnaire were administered to ascertain personality and mental health characteristics on ten selected dimensions viz: need, press, interpersonal relations, outcome, anxiety, obsession, phobia, somatization, depression, and hysteria. Mean scores obtained on different variables were analyzed using t-test of significance. Results indicated that the characteristics associated with treated pathological gamblers were cognizance, dominance, autonomy, achievement, counteraction, affiliation, sex capacity, interpersonal relations and outcome whereas the characteristics associated with non-treated pathological gamblers were aggression, rejection, passivity, acquisition, anxiety, obsession, somatization, depression, and press [ABSTRACT FROM AUTHOR]

Aims: Obstetric anesthesia presents a challenge to the anesthesiologist. The effective pain management allows the parturient adequate degree of comfort and promotes physical recovery and a sense of well being. Methods: This randomized controlled study was designed to assess the analgesic efficacy and side effects of single dose direct epidural morphine (Group 1) versus intermittent 12 hourly epidural morphine with bupivacaine (Group2) for postoperative analgesia in lower segment caesarean section cases. Results: Each group consisted of 36 patients. Demographic characteristics of two groups were comparable and differences among them were not statistically significant. Mean duration of analgesia was significantly longer in group one patients (16.5 ± 2.5) in comparison to group two patients (11.5 ± 1.5). Mean highest visual analogue scales (VAS scale) was significantly lower (3.2± 0.9) in group one patients in comparison of group two (6.7±0.8) patients. Only 43% patient in group one required supplementary analgesic (Inj Paracetamole/ Diclofenac) and 71% required Inj epidural Morphine / Inj bupivacaine in group two. Mean number of supplementary analgesic required in group one was 0.7 and it was 1.8 in group two. There was no significant difference in nausea, vomiting, itching and pruritis in two groups of patients. Conclusions: our study showed that the use of single dose epidural morphine was associated with lower pain scores at rest and movement when compared to intermittent epidural morphine with bupivacaine in post-caesarean section analgesia. Single dose epidural morphine was found more convenient, less cumbersome and less costly as compared to intermittent epidural morphine for post-caesarean section analgesia. [ABSTRACT FROM AUTHOR]

Statins are the most effective and widely used drugs for treating dyslipidemia, a major risk factor for coronary heart disease. These are one of the safest hypolipidemic drugs but many patients are bound to discontinue statins due to their side effects. Hepatotoxicity, myotoxicity and peripheral neuropathy are important out of them. Discontinuation of statins leads to dylipidemia and its grave consequences. Hence, there should be enough strategies for statin intolerant patients, so that they can be saved from these consequences. These side effects can be avoided by the awareness of certain factors viz. potential drug interactions and dose adjustment according to patho-physiology of the patient. Baseline investigations for liver function and muscle toxicity should be done before initiating statin therapy. Here, we are discussing various options for statin intolerant hyperlipidemic patients such as lower and intermittent dosing of statins, alternate hypolipidemic drugs, red yeast rice, supplementation with coenzyme Q10 and vitamin D. A number of hypolipidemic drugs are in trial phases and hold promise for statin intolerant patients. [ABSTRACT FROM AUTHOR]

The aim of present study was to assess the anti-inflammatory activity of polyherbal formulation of leaves of Annona Squamosa and rhizome of Curcuma longa. The mature green leaves of Annona Squamosa and Curcuma longa were collected and authenticated. Extractions of dried leaves and rhizome were carried out with ethanol in soxhlet apparatus. The polyherbal formulation showed the significant anti-inflammatory activity comparable to the standard drug Indomethacin against carrageenan induced rat paw edema method. The polyherbal formulation reduced the inflammation induced by carrageenan by 49.3% and 61.73% on oral administration at 100 mg/ kg and 200 mg/kg respectively as compared to the control treated group an analgesic activity comparable to the standard drug tramadol HCl. Antidepressant activity comparable to the standard drug Fluoxetine HCl. [ABSTRACT FROM AUTHOR]

The aim of present study was to assess the anti-inflammatory activity of polyherbal formulation of leaves of Annona squamosa, Azadiracta indica and rhizome of Curcuma longa. The mature green leaves of Annona squamosa, Azadiracta indica and rhizome of Curcuma longa were collected and authenticated. Extractions of dried leaves and rhizome were carried out with ethanol in soxhlet apparatus. The polyherbal formulation showed the significant anti-inflammatory activity comparable to the standard drug Indomethacin against carrageenan induced rat paw edema method. The polyherbal formulation reduced the inflammation induced by carrageenan by 49.3% and 61.73% on oral administration at 100 mg/ kg and 200 mg/kg respectively as compared to the control treated group an analgesic activity comparable to the standard drug tramadol HCl. [ABSTRACT FROM AUTHOR]

The aim of present study was to assess the anti-inflammatory activity of polyherbal formulation of leaves of Annona squamosa, Azadiracta indica. The mature green leaves of Annona squamosa, Azadiracta indica were collected and authenticated. Extractions of dried leaves and rhizome were carried out with ethanol in soxhlet apparatus. The polyherbal formulation showed the significant anti-inflammatory activity comparable to the standard drug Indomethacin against carrageenan induced rat paw edema method. The polyherbal formulation reduced the inflammation induced by carrageenan by 53.0% and 47.0% on oral administration at 100 mg/ kg and 200 mg/kg respectively as compared to the control treated group an analgesic activity comparable to the standard drug tramadol HCl. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim To determine the prevalence of blindness, visual impairment and the cataract surgical coverage for people aged 50 years and older in the Lumbini Zone and the Chitwan District (Narayani Zone) of Nepal. Methods A population-based cross-sectional study in 2006 selected subjects aged 50 years and older through a random multistage cluster sampling and door-to-door enumeration. Ophthalmic examination included visualacuity assessment and refraction, and anterior and posterior segment examination of the eyes carried out by a trained ophthalmologist and two ophthalmic assistants at centralised locations. Results The survey examined 5138 of 5196 persons enumerated (response rate of 86.8%). The mean age of the subjects was 61 (SD 9.2) years, and 2701 (52.6%) subjects were women. The age - sex-adjusted prevalence of blindness (best presenting vision <6/60) and visual impairment (better-eye presenting visual acuity of <6/18 to $6/60) were 4.6% (95% CI 3.4 to 5.8) and 18.9% (95% CI 16.4 to 21.4), respectively. Blindness was significantly lower in the hill (3.3%) compared with the plain (5.8%) regions (OR 0.6; 95% CI 0.4 to 0.9). The primary causes for blind eyes were cataract (n=228, 48.1%), refractive error (n=149, 31.4%), retinal disorders (n=19, 4.0%) and corneal opacity (n=18, 3.8%). The overall cataract surgical coverage was 66.6%. Cataract surgical coverage was not significantly associated with age, sex, literacy or District. Conclusion Although the prevalence of blindness and visual impairment is lower than 10 years ago, particularly among women, correctable blindness due to cataract and refractive error (79.5% of blind people) remains a significant population health problem in Lumbini Zone and Chitwan District. [ABSTRACT FROM AUTHOR]

In a prospective, randomised trial, 100 pregnant women with ≥ one prior spontaneous pre-term birth were randomised into two groups. Group 1 women received 100 mg natural micronised progesterone intravaginally once daily from 20-24 weeks' gestation until 36 weeks. Group 2 women did not receive progesterone. Both groups were regularly supervised until delivery. Pre-term birth (<37 and <34 weeks) and other maternal, neonatal outcomes were primary and secondary outcomes, respectively. Chi-square test and Fisher exact test were used to compare categorical variables. Independent sample t-test and one-way ANOVA were used to compare continuous variables and multiple comparisons, respectively. Pre-term births <37 weeks were significantly lower in Group 1 (12% vs 38%, p = 0.002), but pre-term births <34 weeks were similar. The mean birth weight of neonates born to women in Group 1 was significantly higher (2800 vs 2,500 g, p = 0.023). We concluded intravaginal administration of 100 mg of natural micronised progesterone significantly reduced the incidence of pre-term birth <37 weeks in women with ≥ one prior pre-term birth. Future research is warranted to assess the long-term safety and efficacy of progesterone. [ABSTRACT FROM AUTHOR]

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Daptomycin is bactericidal against Staphylococcus aureus, with susceptibility defined as a minimal inhibitory concentration (MIC) ≤1 μg/ml. Higher MIC developed in a few cases during therapy. The frequency of MIC rise in persistent bacteremia is unknown. We evaluated all patients with S. aureus bacteremia (SAB) treated with daptomycin (≥2 days) from 1 April 2004 to 30 October 2006. All patients with post-daptomycin-exposure saved isolates were studied. Daptomycin susceptibility was determined (in duplicate) on all pre- and post-daptomycin-exposure isolates by the broth (Mueller-Hinton) microdilution method. Among 74 treatment courses in 67 patients, 18 were for SAB. Ten had persistent bacteremia (median = 11 days; range = 1–21) and post-daptomycin-exposure saved isolates. The patient age was 29–84 years (median = 57.5 years). Intravascular catheter was the most common source (50%). Most patients (90%) failed therapy prior to starting daptomycin. The initial daptomycin dose was 4 mg/kg in four (40%) cases. The pre-exposure MIC was 0.125–0.5 μg/ml. The post-exposure MIC increased in four cases and was elevated in two cases (60%), to 2 μg/ml in five and 4 μg/ml in one. MIC rise was noted within 5–15 days of exposure and persisted up to 247 days after stopping daptomycin. Pulse-field gel electrophoresis (PFGE) band pattern of isolates with increased MIC revealed 1–3-band differences, implying genetic relatedness. All patients with non-susceptible isolates relapsed or failed therapy. These findings illustrate that daptomycin susceptibility often decreases during the treatment of persistent SAB. Therefore, susceptibility should be closely monitored during therapy. [ABSTRACT FROM AUTHOR]

The aims of our randomized, single-blind trial involving 49 patients were to study the efficacy, side effects, and tolerance of metronidazole and satranidazole in patients of amebic liver abscess. Twenty-five patients received metronidazole (800 mg TID) and 24 received satranidazole (300 mg TID with placebo at mealtime). Patients recorded side effects and tolerability through a performa. The time taken for resolution of fever and pain and the fall in abscess size was not significant. However, tolerance of satranidazole as reported by the patients was significantly better than metronidazole (P < .005). The incidence of adverse effects was significantly lower in the group given satranidazole (P < .005). The incidence of nausea and metallic taste was significantly lower in the patients given satranidazole (P < .005). Thus, despite having a similar efficacy, satranidazole showed a far lower incidence of side effects and had a significantly better tolerance than Metronidazole. [ABSTRACT FROM AUTHOR]

ANG II applied to the interstitial space influences carbohydrate and lipid metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic effect on tissue metabolism that could be reversed with ANG II type 1 (AT1) receptor blockade, particularly during adrenergic stimulation. We studied 14 obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan or with placebo in a double-blind and crossover fashion. At the end of each treatment period, we assessed skeletal muscle and adipose tissue metabolism using the microdialysis technique. The ethanol dilution technique was applied to follow changes in tissue blood flow. Measurements were obtained at baseline and during application of incremental isoproterenol concentrations through the microdialysis catheter. Blood pressure decreased from 133 ± 3/84 ± 3 to 128 ± 3/79 ± 2 mmHg for systolic and diastolic blood, respectively (P = 0.02 and 0.006, respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose-dependent increase in dialysate glycerol in adipose tissue and in skeletal muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response in adipose tissue (P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose supply, and lactate production in adipose tissue and skeletal muscle were similar with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men does not reveal a major tonic ANG II effect on interstitial glucose supply, lipolysis, or glycolysis in skeletal muscle, either at rest or during β-adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue lipolysis. The mechanism may promote the redistribution of triglycerides from adipose tissue toward other organs. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the comparative effect of yogic and conventional treatment in diarrhea-predominant irritable bowel syndrome (IBS) in a randomized control design. The patients were 22 males, aged 20–50 years, with confirmed diagnosis of diarrhea-predominant IBS. The conventional group (n =12, 1 dropout) was given symptomatic treatment with loperamide 2–6 mg/day for 2 months, and the yogic intervention group (n =9) consisted of a set of 12 asanas (yogic poses, i.e., Vajrasana, Shashankasana, Ushtrasana, Marjariasana, Padhastasana, Dhanurasana, Trikonasana in two variations, Pawanmuktasana, and Paschimottanasana) along with Surya Nadi pranayama (right-nostril breathing) two times a day for 2 months. All participants were tested at three regular intervals, at the start of study—0 month, 1 month, and 2 months of receiving the intervention—and were investigated for bowel symptoms, autonomic symptoms, autonomic reactivity (battery of five standard tests), surface electrogastrography, anxiety profile by Spielberger's Self Evaluation Questionnaire, which evaluated trait and state anxiety. Two months of both conventional and yogic intervention showed a significant decrease of bowel symptoms and state anxiety. This was accompanied by an increase in electrophysiologically recorded gastric activity in the conventional intervention group and enhanced parasympathetic reactivity, as measured by heart rate parameters, in yogic intervention group. The study indicates a beneficial effect of yogic intervention over conventional treatment in diarrhea-predominant IBS. [ABSTRACT FROM AUTHOR]

A prospective randomized controlled study was designed to evaluate differences in efficacy and complication rate between the two most commonly used sclerosing agents, sodium tetradecyl sulfate (STD) and polidocanol. Of 52 patients with esophageal variceal bleeding, 26 were randomized to receive sclerotherapy with 1.5% STD and 26 to receive 1% polidocanol at weekly intervals. Eradication of varices was achieved in 88% patients each of the STD and polidocanol group. There was no significant difference between patients injected with STD and polidocanol with regard to rebleeding (27% vs. 15%) and mortality (11.5% in both). The use of STD, in contrast to polidocanol, was associated with a higher incidence of complications in terms of severe retrosternal pain (27% vs. 4%), deep ulceration (53% vs. 23%), dysphagia (88% vs. 46%), and stricture formation (27% vs. 8%). It was concluded that these two agents were similar in efficacy. However, polidocanol was superior due to a lower incidence of complications. [ABSTRACT FROM AUTHOR]

Objectives: Lansoprazole, a newer benzimidazole, is more potent than omeprazole in its anti-Helicobacter pylori effect in vitro. The present study was aimed at assessing its efficacy in a developing country. Methods: Fifty patients were randomized to receive either lansoprazole or omeprazole. with norfloxacin for 2 wk; the ulcer healing rates, H. pylori eradication rates, and recurrence rates were compared over a 6-month period. Results: Both lansoprazole and omeprazole were equally effective in inducing healing of ulcer (96.1 vs 95.5%, p > 0.05) and eradicating H. pylori (76.9 vs 63.9%, p > 0.05), with very low recurrence rates over a 6-month follow-up period. Conclusions: Either lansoprazole or omeprazole combined with norfloxacin is effective in eradicating H. pylori in a high percentage of cases of duodenal ulcer, with little difference between the two proton pump inhibitors. [ABSTRACT FROM AUTHOR]

Background: A renewed interest in the usage of polymyxins has been observed, as they are the only treatment option left for multidrug resistant (MDR) and pan-drug resistant (PDR) pathogens like Acinetobacter baumannii. However, knowledge of the pharmacokinetics (PK) and pharmacodynamics (PD) of polymyxins is limited, resulting in inappropriate dosing, potential toxicity and development of resistance. We planned to conduct this prospective PK-PD study of intravenously administered colistin in Indian patients with MDR Gram-negative infections to estimate the levels of both total and free colistin. Methods & Materials: This was a prospective PK-PD study of intravenously administered colistin in ten patients with MDR Gram-negative infections. The recommended systemic dose of prodrug, colistin methanesulfonate (CMS) was given as 4-6 mg/kg per day as a short-term infusion (for 1 hour) or 1-2 million IU/day in three divided doses (12,500 IU/1mg of CMS). Highly sensitive UHPLC-MS/SRM method was developed and validated to quantify free and total colistin from human sera. Correlation between the predictor variables like AUC/MIC ratio was performed using Graph- PadInstat ver. 6 for Mac version 10.10.1 (GraphPad Software, San Diego CA: www.graphpad.com). Results: The area under the plasma concentration-versus-time curve over 8 hrs (AUC0 - 8) for free and total colistin ranged after 5th dose from28.2 to 126mg*Y? h/liter and25.8 to 404.9mg*Y? h/l respectively. All the follow up blood cultures were sterile and majority of the patients survived. Conclusion: This is the first Indian study where free colistin levels were also estimated. The desired colistin levels to be effective without giving the loading dose were achieved in these Indian patients. This study challenges the pharmacokinetic rationale for a loading dose similar to a study byGregoire N, et al (2014). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which reports a case of a patient with rare and aggressive midline vermian mesenchymal chondrosarcoma or tumor of the central nervous system (CNS) that underwent craniospinal irradiation as per Primitive Neuroectodermal Tumor (PNET) protocol.

Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson’s disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer’s disease. Here we demonstrate the neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20 mg/kg i.p.) for 7 days, and drugs were injected once-daily for 14 days i.p. When comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Success of modern transplantation is in large part due to the successful development of effective immunosuppressive agents. The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus (Pan Graf, Panacea Biotec Ltd, India) has only been available in India for the last 2 years. This study was conducted to assess the safety and efficacy of tacrolimus in live related kidney transplantation. We report an initial experience of tacrolimus as de novo therapy in a live related renal transplantation program. Materials and Methods: One hundred one consecutive recipients of a live renal allograft were commenced on triple immunosuppression consisting of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10–12 ng/mL in the first 3 months, 8–10 ng/mL in the next 3 months, and 5–8 ng/mL thereafter. All patients were followed up for a period ranging from 4 weeks to 24 months. The effect of this regimen on the incidence of graft rejection, graft survival, patient survival, and new-onset diabetes mellitus was evaluated. Any evidence of graft dysfunction was evaluated using a graft biopsy. Results: There were 89 male and 12 female patients with mean age of 32.08 years. The incidence of acute rejection was 3.96%; 21.05% developed new-onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV)–positive; 77.7% of HCV-positive patients and 15.1% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival rate at the current follow-up was 92.07%. No graft was lost due to rejection. Conclusion: Tacrolimus is a safe and effective immunosuppressant in live related renal transplantation. [Copyright &y& Elsevier]

Brain abscesses in neonates are extremely rare and usually occur in patients with certain risk factors. A 26 days child presented to the emergency with fever, irritability and not sucking well. CT revealed a large left frontal lobe abscess which was managed with burr hole and a drainage tube with concurrent intravenous antibiotics. [ABSTRACT FROM AUTHOR]