300,000 IU or 600,000 IU of oral vitamin D3 for treatment of nutritional rickets: a randomized controlled trial.

OBJECTIVE: To evaluate the non-inferiority of a lower therapeutic dose (300,000 IU) in comparison to standard dose (600,000) IU of Vitamin D for increasing serum 25(OH) D levels and achieving radiological recovery in nutritional rickets. DESIGN: Randomized, open-labeled, controlled trial. SETTING: Tertiary care hospital. PARTICIPANTS: 76 children (median age 12 mo) with clinical and radiologically confirmed rickets. INTERVENTION: Oral vitamin D3 as 300,000 IU (Group 1; n=38) or 600,000 IU (Group 2; n=38) in a single day. OUTCOME VARIABLES: Primary: Serum 25(OH)D, 12 weeks after administration of vitamin D3; Secondary: Radiological healing and serum parathormone at 12 weeks; and clinical and biochemical adverse effects. RESULTS: Serum 25(OH)D levels [geometric mean (95% CI)] increased significantly from baseline to 12 weeks after therapy in both the groups [Group 1: 7.58 (5.50­10.44) to 16.06 (12.71­ 20.29) ng/mL, P<0.001]; Group 2: 6.57 (4.66­9.25) to 17.60 (13.71­22.60, P<0.001]. The adjusted ratio of geometric mean serum 25(OH)D levels at 12 weeks between the groups (taking baseline value as co-variate) was 0.91 (95% CI: 0.65­1.29). Radiological healing occurred in all children by 12 weeks. Both groups demonstrated significant (P<0.05) and comparable fall in the serum parathormone and alkaline phosphatase levels at 12 weeks. Relative change [ratio of geometric mean (95% CI)] in serum PTH and alkaline phosphatase, 12 weeks after therapy, were 0.98 (0.7­1.47) and 0.92 (0.72­1.19), respectively. The serum 25(OH)D levels were deficient (<20 ng/mL) in 63% (38/60) children after 12 weeks of intervention [Group 1: 20/32 (62.5%); Group 2: 18/28 (64.3%)]. No major clinical adverse effects were noticed in any of the children. Hypercalcemia was documented in 2 children at 4 weeks (1 in each Group) and 3 children at 12 weeks (1 in Group 1 and 2 in Group 2). None of the participants had hypercalciuria or hypervitaminosis D. CONCLUSION: A dose of 300,000 IU of vitamin D3 is comparable to 600,000 IU, administered orally, over a single day, for treating rickets in under-five children although there is an unacceptably high risk of hypercalcemia in both groups. None of the regime is effective in normalization of vitamin D status in majority of patients, 3 months after administering the therapeutic dose.

Neuroprotective effect of Azadirachta indica on cerebral post-ischemic reperfusion and hypoperfusion in rats.

We assessed the effect of Azadirachta indica (A. indica), a plant that has been reported to possess antioxidant, anti-inflammatory and anxiolytic properties, on cerebral reperfusion injury and long term cerebral hypoperfusion. When blood flow to brain region that has undergone critical period of ischemia is re-established, additional injury is to be expected from the reperfusion. In the present study, bilateral common carotid artery (BCCA) occlusion for 30 min followed by 45 min reperfusion resulted in increase in lipid peroxidation, superoxide dismutase (SOD) activity and fall in total tissue sulfhydryl (T-SH) groups. A. indica pretreatment (500 mg/kg/day x 7 days) attenuated the reperfusion induced enhanced lipid peroxidation, SOD activity and prevented fall in T-SH groups. Moreover, A.indica per se increased brain ascorbic acid level, which was unchanged during reperfusion insult. Long-term cerebral hypoperfusion induced by permanent BCCA occlusion has been reported to cause behavioral and histopathological abnormalities. In the present study, as tested by open field paradigm and Morris' water maze, a propensity towards anxiety and disturbances of learning/memory were observed in animals subjected to hypoperfusion for 2 weeks. A. indica (500 mg/kg/day x 15 days) significantly reduced these hypoperfusion induced functional disturbances. Reactive changes in brain histology like gliosis, perivascular lymphocytic infiltration, recruitment of macrophages and cellular edema following long term hypoperfusion were also attenuated effectively by A. indica. We conclude that our study provides an experimental evidence for possible neuroprotective potentiality of A. indica.

Evaluation of antioxidant and neuroprotective effect of Ocimum sanctum on transient cerebral ischemia and long-term cerebral hypoperfusion.

Free radicals are implicated in causation of cerebral reperfusion injury and chronic cerebral hypoperfusion in rats is associated with functional and histopathological disturbances. Ocimum sanctum (OS), a plant widely used in Ayurveda, has been shown to possess anti-inflammatory, antioxidant and cognition-enhancing properties. In the present study, we investigated the effect of methanolic extract of OS leaves in cerebral reperfusion injury as well as long-term hypoperfusion. Occlusion of bilateral common carotid arteries (BCCA) for 30 min followed by 45 min reperfusion caused increase in lipid peroxidation and up-regulation of superoxide dismutase (SOD) activity accompanied by fall in tissue total sulfhydryl groups (TSH) in rat forebrains. Ascorbic acid levels were unchanged, however. OS pretreatment (200 mg/kg/day for 7 days) prevented this reperfusion-induced rise in lipid peroxidation and SOD activity. OS pretreatment also stabilized the levels of TSH during reperfusion. Long-term cerebral hypoperfusion (a model of cerebrovascular insufficiency and dementia) induced by permanent occlusion of BCCA for 15 days demonstrated altered exploratory behavior in open-field testing and memory deficits as tested by Morris' water maze. Histopathological examination of hypoperfused animals revealed reactive changes, like cellular edema, gliosis and perivascular inflammatory infiltrate. OS treatment (200 mg/kg/day for 15 days) significantly prevented these hypoperfusion-induced functional and structural disturbances. The results suggest that OS may be useful in treatment of cerebral reperfusion injury and cerebrovascular insufficiency states.