Oxadiazolyl thiazolidinedione as a non-adipogenic PPAR-γ partial agonist and its effect on glucose homeostasis in type 2 diabetes.

The familiar glitazone anti-diabetics are thiazolidinedione derivatives, known to elicit action through full agonistic activity on PPAR-γ receptors. Full agonists are known for the side effect of weight gain, while partial agonists are weak to non-adipogenic compounds possessing anti-diabetic property. This work identified a new synthetic oxadiazolyl thiazolidinedione (OXTZD) as a ligand for PPAR-γ receptor with partial agonist activity and less transactivation potential compared to rosiglitazone through in-vitro PPAR-γ competitive binding assay and PPAR-γ transactivation-based luciferase reporter assay, respectively. OXTZD did not induce significant lipid accumulation when compared to differentiation control which contained insulin in PPAR-γ-dependent adipogenesis assay. In-vivo studies have proved that OXTZD effectively reduced blood glucose level in type 2 diabetic rats and also improved glucose tolerance and insulin sensitivity. After 15 days of oral treatment with OXTZD, rats did not gain weight, suggesting that OXTZD was effective in suppressing the weight gain. Molecular docking of OXTZD to PPAR-γ, predicted hydrogen bonds with SER342, ARG288, and CYS285 residues in arm III of the ligand binding domain which are unique to the partial agonists. Results of in-vitro, in-vivo, and docking studies were in good correlation to the fact that OXTZD is a PPAR-γ partial agonist having glucose-lowering property and lacks the side effect of weight gain. In conclusion, OXTZD could be developed as a therapeutic agent for diabetes and/or serve as a lead compound for further drug design studies targeting PPAR-γ for effective management of type 2 diabetes without inducing weight gain.

Status of multi bacillary patients "lost to follow up".

Completeness of coverage with MDT is essential if one were to hope for a reduction in the incidence of leprosy in an endemic area. Patients who are lost to follow up are generally declared as "Permanently left" (PL) and deleted from the known case register. A special effort was made to study the true status of multibacillary patients who had been declared "PL" in the leprosy control programme area of the Christian Medical College, Vellore. 38% of the 40 patients followed up were found to be still residing in the same area. 40% of them were BI Positive. The reasons for these erroneous deletions varied. The study shows that declaration of "PL" need to be verified carefully. Further, it was found that the present system of reporting may exaggerate the actual number of patients who have been lost to follow up.

Medical care delivery through leprosy clinics--consumer's perception, experiences and suggestions.

Randomly selected 500 adult leprosy patients, registered for treatment with six Sectors of a Leprosy Control Unit in Chingleput District of Tamil Nadu (India) were interviewed to study their perception, and experiences with medical care being delivered to them through leprosy clinic(s), and their suggestions to improve the system. About 14% patients did not perceive their disease as leprosy. And 8% of the total patients were taking treatment outside their sector leprosy clinics. The services like physiotherapy, rehabilitation, health education etc. were known to only 3-8% patients, perhaps on account of their non-availability and or non-practice. On an average, a patient had to cover a distance of 2.1 +/- 2.5 KMs (one side) in 24 +/- 49 minutes to reach clinic spot, mostly by walk (83.2%), and spent 58.9 +/- 32.2 minutes at clinic, of which two third in waiting for service(s). Each patient had consulted 1.23 +/- 0.55 medical agencies for treatment of leprosy. The average man-day and wage losses to a patient, due to monthly clinic attendance, were estimated to be 0.48 +/- 0.49 days and Rs. 2.28 +/- 3.06, respectively. Only 10.6% of the 500 patients got admitted 1.55 +/- 0.89 times in leprosy hospital for a duration of 63 +/- 69.30 days and lost wages of Rs. 126.4 +/- 85.64 per month of stay in hospital. Availability and efficient delivery of comprehensive medical care through well organized and regularly conducted leprosy clinic, by considerate and sympathetic staff was much emphasised by patients. Various factors influencing medical care delivery and its utilization by patients, are discussed in this communication.

Community leaders involvement in leprosy health education.

As an alternative approach, 310 community leaders consisting of village political leaders, school teachers, Govt. staff, members of socio-welfare and religious agencies, graduate students and traders from 21 villages of Chingleput district of Tamilnadu (India) were interviewed to explore the possibilities of their involvement in leprosy health education community. Though majority (76%) of respondents were not fully aware about various aspects of leprosy and showed negative reactions (51%) towards leprosy patients; almost all realised the importance of educating community about leprosy for its early control, for which a large majority (88%) of them had expressed their willingness to participate in leprosy health education and control programme by devoting an average of 4.4 +/- 5.4 hours per week. A good number (54%) of them had also been educating people about leprosy in one or the other way. The leaders who had been exposed to leprosy health education especially in recent past, were significantly better equipped with knowledge about leprosy and its control and were much more willing to participate in NLCP, than others. Study concluded that if the community leaders are approached, educate and motivated properly, they would certainly involve themselves to provide a valuable strength to our leprosy health education and control programme.

Utilization of medical agencies and treatment compliance by urban (Madras) leprosy patients.

The utilization of medical agencies and treatment compliance by 3880 leprosy patients registered with Govt. Leprosy Control Unit, Saidapet, Madras were studied. It was observed that 39% patients waited for 1.32 (+/- 1.75) years before medical consultation, for their negligence and unawareness of disease. About 16% and 4% patients consulted Gen. Hospitals and Private Practitioners, respectively. The leprosy clinics were most popular, 35% patients changed medical agencies. On an average, one patient had consulted 1.47 (+/- 0.51) medical agencies and 1.23 (+/- 0.52) leprosy clinics, for treatment of leprosy. Only 45% patient attended clinic regularly, others attended irregularly (22.5%) or discontinued (32.4%). The unsuitable clinic timing (morning) was an important factor for defaulting the clinics. Of the 2625 (67.66%) patients who attended last clinic, one patient had missed an average of 5.5 (+/- 8.3) DDS tablets in a month. The implications of findings and suggestions to improve the service utilization with good compliance by patients, are discussed in this communication.