ABSTRACT
Assessments of respiratory response and animal activity are useful endpoints in drug pharmacology and safety research. We investigated whether continuous, direct monitoring of breathing rate and body motion in animals in the home cage using the Vum Digital Smart House can complement standard measurements in enabling more granular detection of the onset and severity of physiologic events related to lung injury in a well-established rodent model of paraquat (PQ) toxicity. In rats administered PQ, breathing rate was significantly elevated while body motion was significantly reduced following dosing and extending throughout the 14-day study duration for breathing rate and at least 5 days for both nighttime and daytime body motion. Time course differences in these endpoints in response to the potential ameliorative test article bardoxolone were also readily detected. More complete than standard in-life measurements, breathing rate and body motion tracked injury progression continuously over the full study time period and aligned with, and informed on interval changes in clinical pathology. In addition, breathing rates correlated with terminal pathology measurements, such as normalized lung weights and histologic alveolar damage and edema. This study is a preliminary evaluation of the technology; our results demonstrate that continuously measured breathing rate and body motion served as physiologically relevant readouts to assess lung injury progression and drug response in a respiratory injury animal model.
ABSTRACT
BACKGROUND: An unceasing threat of resistance of malarial parasites to available antimalarial drugs makes the development of new drugs imperative. Natural plant-based products are an alternative source for discovering new antimalarial drugs. AIM: To determine the prophylactic efficacy of a traditionally used plant-based drug on prevention of malaria in endemic villages of Odisha, India. METHODS: A total of 267 healthy human volunteers of both sexes, aged 18-60 years were enrolled in Odisha, India, to receive either minimum 20 doses of aqueous extract of Traditional Plant-based Malaria Prophylactic drug 74, twice a week (experimental group), or no drug (control group) for 14 weeks. The primary criterion was the occurrence of malaria positive cases confirmed through expert microscopy during the study period. Analyses were by per-protocol (PP) and modified intention-to-treat (mITT). RESULTS: A significant (P < 0.01) reduction (64%) of malaria incidence was observed in the experimental group compared to control group, 12.3% and 26.6%, respectively, as PP analysis. However, the reduction was nonsignificant as per mITT analysis (P = 0.22). The experimental group showed a relative risk of 0.36 compared to control group. CONCLUSION: This preliminary study constitutes a potential "proof of concept" for the development of malaria prophylactic drug and provide a scientific basis for the use of traditional remedy as a malaria preventive by tribal populations in India.
ABSTRACT
Reported lack of efficacy of Ayurvedic treatments in clinical trials is often not due to inefficacy of the treatment itself, but arises from inadequacies of trial design. This paper argues that trials of Ayurvedic interventions should exclusively use its multi-component, individualized and inherently holistic approach, and that general guidelines for rigorously reporting such clinical trials should be developed. Holistic Ayurvedic clinical trials, rigorously conducted and with high standards of reporting should translate into good clinical science, and may be expected to generate higher credibility for clinical studies of the Ayurvedic knowledge system.
