Heart transplantation for Chagas cardiomyopathy in the United States.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Investigating the effect of CoCl2 administration on diabetic nephropathy and associated aortic dysfunction.

AIM: Endothelial dysfunction appears to be a consistent finding in diabetic nephropathy. The study aimed to investigate the effect of cobalt chloride in the amelioration of endothelial dysfunction in uninephrectomized diabetic rats. METHODS: We examined the effect of CoCl(2) (10 mg/kg, i.p., OD = once a day) treatment on contractile responses to angiotensin II (10(-10) to 10(-6)M) in an aortic preparation of control rats and uninephrectomized diabetic control rats. Blood glucose, plasma urea, creatinine, uric acid, aortic endothelial nitric oxide synthase (eNOS), nitrate/nitrite (NOx), superoxide dismutase, catalase and reduced glutathione levels were checked in the different groups. RESULTS: A significant attenuation of the augmented responses to angiotensin II was observed in CoCl(2)-treated animals along with a fall in plasma urea, creatinine and uric acid levels. A significant reduction in blood glucose and an increase in aortic eNOS and NOx levels along with antioxidants levels were observed. CONCLUSION: Chronic hypoxia augments angiotensin II responses in the thoracic aorta of uninephrectomized diabetic control rats. CoCl(2) attenuates these enhanced vascular responses with a significant decrease in blood glucose signifying stabilization of the hypoxia-inducible factor in the alleviation of endothelial dysfunction in diabetic nephropathy.

Biodegradable anionic acrylic resin based hollow microspheres of moderately water soluble drug rosiglitazone maleate: preparation and in vitro characterization.

BACKGROUND: Most of floating systems have an inbuilt limitation of high variability in the gastric retention time, invariably affecting the bioavailability of drug. An oral sustained release system is formulated to increase gastric residence time by a different way like floating. AIM: The objective of present investigation was to prepare hollow microspheres of Rosiglitazone Maleate in order to increase its bioavailability and reduce the dose frequency. METHOD: Hollow microspheres of Rosiglitazone Maleate were prepared by O/W emulsion-solvent diffusion technique using biodegradable anionic acrylic resin as a polymer. A mixture of dichloromethane and ethanol (1:1) used as solvent system for drug and polymer with water containing polyvinyl alcohol and salt as external aqueous phase. RESULT: Entrapment efficiency of drug was increased upto 89.71% as a result of salting out effect. The morphology of Eudragit S100 based microspheres in comparison to Ethyl cellulose and hydroxy propyl methyl cellulose (HPMC) was found to be hollow, spherical, and porous which was analysed by scanning electron microscopy. Microspheres were evaluated for micromeritic profile and found satisfactory. The FT-IR spectra confirmed the absence of drug-polymer interaction. The Eudragit S100 based formulation demonstrated favorable in vitro floating and sustained release profile for longer period of time with increased bioavailability. The anionic acrylic resin based microspheres confirmed to have high floating ability >12 h. CONCLUSION: Entrapment efficiency and bioavailability of Rosiglitazone Maleate loaded microspheres were increased significantly after modification of method. The release mechanism for formulation was diffusion controlled and had followed first order kinetics, as well as physically and chemically stable as per ICH guidelines.

A new record of Asia II 5 genetic group of Bemisia tabaci (Gennadius) in the major potato growing areas of India and its relationship with tomato leaf curl New Delhi virus infecting potato.

The whitefly, Bemisia tabaci (Gennadius), is responsible for significant yield losses in many crops, including potato, by sucking the phloem sap and transmitting a number of plant viruses. B. tabaci is a complex of cryptic species which is commonly designated as genetic groups. The B. tabaci genetic groups differ biologically with respect to host plant preference, insecticidal resistance, reproduction capacity, and ability to transmit begomoviruses. Therefore, understanding genetic variation among populations is important for establishing crop-specific distribution profile and management. We sequenced the mitochondrial cytochrome oxidase I (mtCOI) gene of B. tabaci collected from major potato growing areas of India. BLAST analysis of the 24 mtCOI sequences with reference Gene Bank sequences revealed four B. tabaci genetic groups prevailing in this region. mtCOI analysis exhibited the presence of Asia II 1, Asia II 5, Asia 1, and MEAM1 B. tabaci genetic groups. Our study highlighted that a new genetic group Asia II 5 has been detected in Indo-Gangetic Plains. Further virus-vector relationship study of ToLCNDV with Asia II 5 B. tabaci revealed that females are efficient vector of this virus as compared to males. This behavior of females might be due to their ability to acquire more virus titer than males. This study will help in better understanding of whitefly genetic group mediated virus diseases.

Itraconazole nanosuspension for oral delivery: Formulation, characterization and in vitro comparison with marketed formulation.

BACKGROUND AND THE PURPOSE OF THE STUDY: Itraconazole is a poorly water soluble drug which results in its insufficient bioavailability. The purpose of the present study was to formulate Itraconazole in a nanosuspension to increase the aqueous solubility and to improve its formulation related parameters, dissolution and hence oral bioavailability. METHODS: Itraconazole nanosuspension was prepared by pearl milling technique using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and glycerol as a wetting agent. Effects of various process parameters like, stirring time and the ratio of the beads were optimized by keeping drug:surfactant:milling media (1:3.0:50) as a constant initially and then optimized process parameters were used to optimize formulation parameters by 32 factorial designs. The optimized nanosuspension was lyophilized using mannitol (1:1 ratio) as a cryoprotectant. Nanosuspension was characterized by particle size and size distribution, drug content, scanning electron microscopy, differential scanning colorimetry and X-ray diffraction techniques. RESULTS: Optimized nanosuspension showed spherical shape with surface oriented surfactant molecules and a mean particle diameter of 294 nm. There was no significant change in crystalline nature after formulation and it was found to be chemically stable with high drug content. CONCLUSION: The in vitro dissolution profile of the optimized formulation compared to the pure drug and marketed formulation (Canditral Capsule) by using 0.1N Hydrochloric acid as release medium showed higher drug release.

Physicochemical characterization and evaluation of buccal adhesive patches containing propranolol hydrochloride.

Buccal adhesive patches containing 20 mg of propranolol hydrochloride were prepared using solvent casting method. Chitosan was used as a natural bioadhesive polymer. Patches were prepared at different ratios of PVP K-30 and evaluated for various physicochemical characteristics such as weight variation, drug content uniformity, folding endurance, surface pH, ex-vivo mucoadhesive strength, ex-vivo residence time, in vitro drug release and in vitro buccal permeation study. Patches exhibited sustained release over a period of 7 hours. The mechanism of drug release was found to be Non-Fickian diffusion. Addition of PVP K-30 generally enhanced the releasing rate. The ex-vivo mucoadhesive strength was performed using sheep buccal mucosa on modified physical balance. Optimized patches (batch F4) showed satisfactory bioadhesive strength (9.6 degrees 2.0 gram) and ex vivo residence time (272 degrees 0.25 minutes). Swelling index was proportional to PVP K-30. The surface pH of all batches was within satisfactory limit (7.0+/-1.5) and hence patches would not cause irritation in the buccal cavity. Good correlation was observed between in vitro drug release and in vitro drug permeation with correlation coefficient of 0.9364. Stability of optimized patches was performed in natural human saliva showed that both drug and dosage forms were stable in human saliva.

Clozapine in the treatment of refractory psychotic mania.

OBJECTIVE: The efficacy of clozapine was examined in a group of patients with treatment-refractory bipolar disorder, manic type with psychotic features. METHOD: Twenty-two subjects with treatment-refractory bipolar disorder with active manic and psychotic symptoms participated in a 12-week open-label trial of clozapine. After a 2-10-day drug washout period, patients began treatment with clozapine at 25 mg/day; the dose was increased 25 mg/day (as tolerated) to a maximum level of 550 mg/day. Patients were evaluated longitudinally over the course of the study with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale, and the Clinical Global Impressions (CGI) scale. RESULTS: Fourteen of the 22 subjects in the study continued taking clozapine for at least 10 of the 12 weeks. Among the entire group, mean improvements of 56. 7%, 56.6%, and 39.1% were seen on the BPRS, Young Mania Rating Scale, and CGI, respectively. Seventeen of the 22 subjects (77.3%) experienced at least a 20% improvement in scores on all three scales. CONCLUSIONS: The findings from this open-label study, which are consistent with previous retrospective studies, case reports, and one other open-label prospective study, suggest that clozapine is an effective agent for patients with treatment-refractory psychotic mania.

Effects of antidepressant treatments on first-ECT seizure duration in depression.

1. Current guidelines on the practice of Electroconvulsive Therapy (ECT) suggest that antidepressant medications should be discontinued prior to the course of therapy. However, the practice of withholding potentially helpful medication is debatable because the effects of these medications on seizure duration remain unclear. In particular, there is a lack of empirical knowledge about the effects of Selective Serotonin Reuptake Inhibitors (SSRIs) on ECT treatment. 2. Therefore, we investigated and compared the effects of SSRIs and tricyclic antidepressants (TCAs) on seizure duration after the first bilateral ECT treatment. 3. The diagnosis of major depressive disorder was made using the DSM-IV criteria. Both patient groups were age- and sex-matched. ECT was indicated for acute suicidal acts or refractoriness to medications. All patients had received antidepressant treatment for at least eight weeks and were receiving at least the recommended dose of medication. All patients were ECT treatment-naïve and we measured the seizure duration after the first bilateral ECT treatment. 4. There was no significant difference between electrical charge applied to either group. Between the TCA and SSRI group the seizure duration was not significantly different: 33.2 seconds and 31.4 seconds respectively.

Weight gain from novel antipsychotic drugs: need for action.

Obesity is common in schizophrenia, and people with schizophrenia appear to be at increased risk for certain obesity-related conditions, such as type 2 diabetes and cardiovascular disease. Antipsychotic drugs, used chronically to control symptoms of schizophrenia, are associated with often-substantial weight gain, a side effect that is a special concern with the latest generation of highly effective "novel" agents. That the most effective (e.g., novel) antipsychotic medications lead to substantial weight gain presents the field with a critical public health problem. Although preliminary data have been reported regarding the beneficial use of behavior therapy programs for short-term weight control in patients with schizophrenia, the available data are quite limited, and there are no data regarding the long-term beneficial effects of these programs in this population. The obesity field recently has developed programs emphasizing "lifestyle changes" (e.g., diet, exercise, and problem-solving skills) to successfully manage weight in patients without schizophrenia. Such programs can be adapted for patients with schizophrenia through the use of highly structured and operationalized modules emphasizing medication compliance, social skills development, and participation in outpatient programs. Moreover, these programs can potentially be combined with the use of adjunctive pharmacotherapy to maximize and maintain weight loss. The field must solve the paradox that some of our most effective medications for schizophrenia produce substantial weight gain and its associated troubling health risks.

Lost time, found hope and sorrow: the search for self, connection, and purpose during "awakenings" on the new antipsychotics.

The novel antipsychotic medications clozapine and olanzapine provide well-documented clinical improvement for some patients with psychosis. We interviewed 15 patients with chronic psychosis who demonstrated significant improvement on these new medications and offer a conceptual framework to organize their narratives. In our conceptual model, our patients' descriptions are divided into three broad areas: sense of self, sense of connection, and sense of purpose. We also highlight the opportunities for psychotherapy with this population.

Cardiac transplant experience with cyclosporine.

The advent of cyclosporine 20 years ago was a major advance in the field of solid organ transplantation. Its use enabled directed immunosuppression with a consequent decrease in the incidence of graft failure, acute rejection, and systemic infection. The early oil-based preparation, however, was difficult to administer and had limited bioavailability and unpredictable pharmacokinetics. The drug also has a fairly narrow therapeutic window with major long-term side effects, which include nephrotoxicity, malignancy, hyperlipidemia, and hypertension. The introduction of a microemulsion preparation (Neoral) with improved bioavailability has been associated with lower rates of rejection and comparable tolerability, therefore allowing the use of lower doses. Traditionally cyclosporine toxicity has been minimized by monitoring trough levels. Monitoring of levels 2 hours after dosing may provide a more accurate determination of cyclosporine exposure. The next phase in cardiac transplantation immunosuppression will most likely see a significantly diminished role for cyclosporine with the introduction of newer, more potent immunosuppressive agents with more favorable side-effect profiles. These agents, which include mycophenolate mofetil, sirolimus, and everolimus, also hold the promise of having a major impact on the development of transplant vasculopathy, which up to now has been an important determinant of limiting long-term allograft survival.

Anti-bacterial activity of Galega officinalis L. (Goat's Rue).

Alcoholic extracts of Goat's Rue (Galega officinalis L.; Papilionaceae) were tested on Gram +ve and Gram -ve bacteria as the plant was claimed to hasten skin healing after surgery. Ethanolic (60%) extract exhibited significant inhibition on growth of both Gram +ve and Gram -ve bacteria.

Correlation of fragile sites and bleomycin induced chromosome break points.

Bleomycin (Blm) induced break points in human chromosome preparations were compared with the known fragile sites. A total of 136 breaks were observed from 100 well spread G-banded plates (1.3 bps/cell). These correspond to a total of 57 break prone sites. Of these 57 sites, 24 correspond to the known fragile sites, 5 to sites of protooncogenes and neoplasia, 26 sites correspond to more than one known site of fragility, protooncogene, neoplasia or reciprocal translocation sites, and 2 unknown sites. The findings suggest that fragile sites, either commonly expressed or induced, might be a predisposing factor for chromosome aberrations in human. The expression of fragile sites induced by Blm and their correlation with the known cancer chromosome break points, oncogenes and reciprocal translocation, suggest that the fragile sites are prone to mutagenic action.

Nucleolar organizer region heteromorphism associated with trisomy-21: a risk factor for non-disjunction?

An unusual nucleolar organizer region (double NOR) on chromosome 13 was observed in a Down syndrome child [47, XY, +21, dNOR(13)]. The variant chromosome was inherited from the mother [46, XX, dNOR(13)]. The extra chromosome 21 in the proband was maternal origin. The frequency of NOR chromosome association showed relatively high frequency in the mother and proband as compared to the controls. The result suggest that chromosome variants involving extra copies of NOR may indeed be involved in the meiotic nondisjunction of chromosome-21.

Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate.

Tamoxifen Citrate (TC) is an estrogen receptor antagonist and drug of choice for hormone sensitive breast cancer. Solid Lipid Nanoparticles loaded with TC were prepared by High Shear Homogenization followed by Ultrasonication. The aim of the present work is to study the effect of four different Solid Lipids and three Surfactants on Formulation and Stability of SLN. They were characterized for Particle size, Polydispersity Index and Zeta Potential by Zetasizer Nano. SLN prepared by Solid Lipid Compritol 888 (Glyceryldibehenate) and Tween 80 (1%) showed desired Particle Size of 206.9 nm, PDI of 0.046 and Zeta Potential of 9.32 mV.

Formulation and evaluation of mouth dissolving tablets of cinnarizine.

The purpose of this research was to develop mouth dissolve tablets of cinnarizine by effervescent, superdisintegrant addition and sublimation methods. All the three formulations were evaluated for disintegration time, hardness and friability, among these superdisintegrant addition method showed lowest disintegration time; hence it was selected for further studies. Further nine batches (B1-B9) were prepared by using crospovidone, croscarmellose sodium and L-HPC in different concentrations such as 5, 7.5 and 10%. All the formulations were evaluated for weight variation, hardness, friability, drug content, in vitro disintegration time, wetting time, in vitro dissolution. Formulation with 10% L-HPC showed the less disintegration time (25.3 s) and less wetting time (29.1 s). In vitro dissolution studies showed total drug release at the end of 6 min.