Recombinant glycoprotein based vaccine for Chandipura virus infection

Chandipura virus (CHPV) has emerged as an important pediatric encephalitis-causing pathogen with very high mortality in India. No specific vaccine or treatment is available till date. We attempted to prepare a candidate vaccine employing recombinant CHPV Glycoprotein (rGp). The Glycoprotein gene (G-gene) of CHPV was expressed using Baculovirus expression system. The rGp was purified by HPLC and used for mice immunization, 3 doses, and 4 weeks apart. One microgram rGp was found to be optimum. Sero-conversion was observed as early as 2nd week by detecting anti-CHPV IgG antibodies. Antibody titres were immunogen-concentration dependent. Intracerebral challenge of the immunized mice with 100 LD₅₀ of the homologous strain demonstrated 90% protection. In in vitro neutralization, antibodies from the immunized mice were able to neutralize heterologous viruses. There was 60% T cell proliferation observed against rGp in immunized mice. The study shows that rGp induces both arms of immune response and represents an ideal vaccine candidate for further evaluations.     

Influence of glucose amendment on the toxicity of two nitrophenols to Chlorella vulgaris

Glucose amendment (0.5%) to the culture medium of Chlorella vulgaris reversed the algal toxicity caused by p-nitrophenol (PNP) and m-nitrophenol (MNP), only at their algistatic levels. Algistatic and algicidal concentrations of PNP and MNP, in the absence of glucose, led to the liberation of more nitrite in the culture medium. However, addition of glucose inhibited nitrite formation.     

Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles.

Clozapine, a lipophilic antipsychotic drug, has very poor oral bioavailability (<27%) due to first pass effect. Solid lipid nanoparticle (SLN) delivery systems of clozapine have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 and charge modifier stearylamine. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. Particle size and zeta potential were measured by photon correlation spectroscopy (PCS) using Malvern Zetasizer. Process and formulation variables have been studied and optimized. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies were performed to characterize state of drug and lipid modification. In vitro release studies were performed in 0.1 N HCl, double-distilled water and phosphate buffer, pH 7.4, using modified Franz diffusion cell. Stable SLN formulations of clozapine having mean size range of 60-380 nm and zeta potential range of -23 to +33 mV were developed. More than 90% clozapine was entrapped in SLN. DSC and PXRD analysis showed that clozapine is dispersed in SLN in an amorphous state. The release pattern of drug is analyzed and found to follow Weibull and Higuchi equations.     

Lipid-based formulations of amphotericin B

Amphotericin B remains the drug of choice for the treatment of invasive fungal infections and visceral leishmaniasis. However, both the dose-dependent nephrotoxicity and the low response rates (10-80%) associated with amphotericin B limit its clinical use. The first marketed formulation of amphotericin B with deoxycholate, Fungizone, remains the "gold standard" in spite of its renal toxicity. Several investigations have been made to reduce the nephrotoxicity of amphotericin B by formulation strategies. Lipid-based formulations of amphotericin B were found to reduce toxicity and to increase tolerance and therapeutic efficacy. Three lipid formulations are now available in most countries: liposomal amphotericin B (AmBisome), amphotericin B lipid complex and amphotericin B colloidal dispersion. Amphotericin B colloidal dispersion was less nephrotoxic, but immediate reactions to this formulation were as frequent and severe as those to amphotericin B. Amphotericin B lipid complex appeared to be as effective as amphotericin B, with improved general and renal tolerability. Several comparative studies have confirmed that AmBisome has similar or superior efficacy relative to amphotericin B in various fungal infections, in visceral leishmaniasis and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. A significant drawback to the newer, less toxic, commercial lipid-based formulations is their cost. There is a need to develop more affordable lipid-based formulations of amphotericin B.     

Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study

This study was performed to determine the safety and tolerability of injecting autologous bone marrow stem cells (BMC) (CD34+) into four patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony stimulating factor (G-CSF) mobilized blood and autologous bone marrow contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated the CD34+ stem cell population from the bone marrow. The potential of the BMC to differentiate into hepatocytes and other cell lineages has already been reported. Several reports have also demonstrated the plasticity of hematopoietic stem cells to differentiate into hepatocytes. Recently Sakaida demonstrated reduction in fibrosis in chemically induced liver cirrhosis following BMC transplantation. From a therapeutic point of view, chronic liver cirrhosis is one of the targets for BMC transplantation. In this condition, there is excessive deposition of extracellular matrix and hepatocyte necrosis. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte-like elements, four patients with liver insufficiency were given G-CSF to mobilize stem cells. CD34+ cells (0.1 x 10(8)) were injected into the hepatic artery. No complications or specific side effects related to the procedure were observed; four patients showed improvements in serum albumin, bilirubin and ALT after one month from the cell infusion.     

Hydrophilic polymer vasculopathy with coinciding pseudoxanthoma elasticum‐like changes in an amputated toe

For the past decades, hydrophilic polymer gel coating have been widely used on endovascular devices to decrease friction and to aid with binding and delivering of medications in drug‐eluting stents. In the recent years, hydrophilic polymer emboli disease has been recognized as an iatrogenic adverse effect which has led to considerable morbidity and mortality of patients. This under‐recognized embolic phenomenon now has reproducible pathognomonic histologic findings. Small‐ to medium‐sized blood vessels are occluded with basophilic, amorphous, non‐refractile, non‐polarizable and whirled aggregates of foreign body material. Depending on the affected organ, the patients have variable symptomatology, from livedo racemosa, gangrene of extremities to cardiac arrhythmias, hemiparesis, stroke and death. Here, we present a unique case of hydrophilic polymer vasculopathy 6 years post‐endovascular procedure with coinciding pseudoxanthoma elasticum‐like changes. As the literature has seen increased reporting of individual cases and case series documenting the patients’ diverse symptomatology; hydrophilic polymer vasculopathy should be entertained sooner in the patient's differential diagnosis.     

Seco-sethukarailin,a novel diterpenoid from the soft coral Sinularia dissecta

Seco-sethukarailin (1), a novel diterpenoid, has been isolated along with known sesquiterpenes Delta(9(15))africanene, beta-elemene, african-1-ene, 6R,7R-6,7-epoxycaryophyll-3(15)-ene, and known diterpenoids sethukarailin and isomandapamate, from the soft coral Sinularia dissecta collected from Mandapam Coast, South India. The structure of the novel diterpenoid seco-sethukarailin (1) was characterized by interpretation of spectral data.