Leprosy and hepatitis B surface antigen

An ELISA technique has been developed to detect HBsAg in the sera of leprosy patients. Out of ninety-two serum samples taken from untreated leprosy patients, 10 samples were positive for HBsAg. The ELISA used in the present investigation is a low cost, reliable and sensitive marker of HBsAg. It is better than lesser sensitive (haemagglutination and counterimmunoelectrophoresis), costly and hazardous (radioimmunoassay) techniques and is therefore recommended for routine use.     

Structural Stability of Recombinant Human Growth Hormone (r-hGH) as a Function of Polymer Surface Properties

Purpose

Despite the fact that r-hGH was first approved for use by FDA in 1995 and the conventional dosage form in the market has a limitation of daily subcutaneous injections, there remains a lack of sustained delivery system in the market. Nutropin depot, a long-acting dosage form of r-hGH was approved for marketing by FDA in 1999, however, it was discontinued in 2004. Since then, unabating efforts have been made to develop biodegradable polymer based formulations for r-hGH delivery. However, grey area is the comprehension of structural stability of r-hGH at an interface with the polymer and it is of utmost important to attain safe and efficacious sustained delivery system. The purpose of this study was to evaluate the changes in structure of r-hGH upon adsorption at biodegradable PLGA nanoparticles of different hydrophobicity as a function of pH.

Methods

DLS, fluorescence spectroscopy, and CD were collectively employed to evaluate structural changes in r-hGH.

Results

The studies revealed that r-hGH is most stable with low to high hydrophobicity PLGA grades under pH 7.2 followed by 5.3.

Conclusion

Overall, the nature and magnitude of structural changes observed has a strong dependence on the pH and differences and degree of hydrophobicity of PLGA.

     

Integrative Pharmacology: Advancing Development of Effective Immunotherapies

With the recent advances in cancer immunotherapy, it is now evident that the antigen-specific activation of the patients’ immune responses can be utilized for achieving significant therapeutic benefits. Novel molecules have been developed and promising advances have been achieved in cancer therapy. The recent success of cancer immunotherapy clearly reflects the novelty of the approach and importance of this class of therapeutics. Due to the nature of immunotherapy, i.e., harnessing the patient’s immune system, it becomes critical to evaluate the important variables that can guide preclinical development, translational strategies, patient selection, and effective clinical dosing paradigms following single and combination therapies. To further boost the durability and efficacy profiles of IO (immuno-oncology) drugs following single agent therapy, novel combination therapies are being sought. Combination strategies have become critical for enhancing the anti-tumor immunity in broader cancer indications. Comprehensive methods are being developed to quantify the synergistic combination effect profiles at various development phases. Further evaluation of the signaling and pathway components can potentially establish a unique “signature” characteristic for specific combination therapies following modulation of various immunomodulatory pathways. In this article, critical topics related to preclinical, translational, and clinical development of IO agents are discussed.     

Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo

Aims—To investigate the efficacy of dailymaintenance treatment with omeprazole 10 mg in reducing the relapserate of healed erosive oesophagitis.
Methods—Three hundred patients with erosiveoesophagitis (grade 2 or greater) received omeprazole 20 mg daily for12 weeks, followed by 40 mg daily for a further 12 weeks if required.After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse thetreatment cycle was repeated.
Results—The cumulative healing rate at 12 weeksin the initial healing period was 95%, and 96% and 98% on rehealingcourses after relapse in the first and second maintenance periodsrespectively. After 12 weeks of treatment, 98% of patients were freefrom heartburn and 97% were free of all reflux related symptoms.Relapse in the subgroup of patients who relapsed in both maintenanceperiods was infrequent on omeprazole 20 mg daily: only 9% at twoyears. Gastrin concentrations rose above normal in one third ofpatients. One patient had linear hyperplasia of endocrine cells andanother had micronodular hyperplasia. There were no side effectsdefinitely attributable to omeprazole.
Conclusion—Maintenance treatment with omeprazole10 mg daily keeps about 60% of patients with erosive oesophagitis inprolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20mg daily.

Keywords:erosive oesophagitis; long term maintenancetreatment; omeprazole

     

Fecal microbiota transplantation for management of Clostridium difficile infection

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.     

Is Campylobacter involved in antibiotic associated diarrhoea?

Campylobacter jejuni is an important cause of acute bacterial diarrhoea. In developing countries like India, children gain immunity early during infancy. However, the incidence is higher in non-immune hosts. Antibiotic use destabilizes the gut flora and can inhibit the local immune responses, thereby compromising resistance to a variety of infections. It is not yet known whether antibiotic intake can also precipitate C. jejuni enteritis as the infectious dose is low and attack rates are high. We made a preliminary study to determine the prevalence of C. jejuni in hospitalized patients receiving antibiotics for various ailments. One hundred and thirty eight stool samples submitted for Clostridium difficile toxin assay were additionally cultured for C. jejuni in blood-free campylobacter selectivity agar. All suspected colonies were subjected to Gram staining, oxidase, catalase and nalidixic acid sensitivity tests. Confirmation of C. jejuni was done by the hippurate hydrolysis test. Of the 138 faecal samples investigated, 14 (10.1%) grew C. jejuni and 11 of them belonged to adults. Two of these 14 samples were also positive for C. difficile toxin. Though not as yet reported, C. jejuni may also be involved in antibiotic associated diarrhoea due to lowered immunity in the host. It may cause enteritis either by itself or in synergy with C. difficile infection.