Clinical and serological study of myasthenia gravis using both radioimmunoprecipitation and cell-based assays in a South Asian population.

BACKGROUND: Identification of autoantibodies has defined distinct clinico-immuno-pathological subtypes of myasthenia gravis (MG) such as AChR-antibody-positive-MG and MuSK-antibody-positive-MG. The use of more sensitive assays such as the cell-based assay (CBA) is expected to reduce the proportion of seronegative-MG. We studied the seroprevalence of AChR and MuSK antibodies using both radioimmunoprecipitation (RIA) and CBA amongst MG patients in Sri Lanka and related their antibody status to their clinical subtypes and severity. METHODS: 113 patients with MG attending Neurology units in the district of Colombo were studied. Clinical data were obtained using an interviewer-administered questionnaire and medical records. The severity of MG was assessed according to MGFA clinical grading. RIA and CBA were used to detect serum AChR and MuSK antibodies. Patients with other neurological diseases were recruited as controls. RESULTS: We detected either AChRAb (85%) or MuSKAb (6.2%) in 91.2% of MG patients. Complementing the RIA with the CBA improved the diagnostic power of detecting AChRAbs by 21% and MuSKAbs by 77%. The clinical characteristics and the occurrence of thymic pathology were similar to other populations except for a male preponderance (1.5:1). The AChRAb titer appeared to parallel the clinical severity. Seven of 11 (63.6%) patients with AChRAb-negative generalized MG had MuSK-MG. CONCLUSIONS: Clinical characteristics of MG in Sri Lanka are similar to other populations. Complementing the RIA with CBA increases the diagnostic power of detecting pathogenic autoantibodies.

Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model.

OBJECTIVES: To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats. MATERIALS AND METHODS: The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day. PHASE I: There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001). CONCLUSIONS: C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.

Brain targeted transcranial administration of diazepam and shortening of sleep latency in healthy human volunteers.

Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about ß activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted dosage design is therefore feasible.