Genomics and natural products: role of bioinformatics and recent patents.

The post genomic era has promised major breakthroughs in personalized medicine which will improve a patient's health by selecting treatments including diet based on the patient's unique DNA sequence. The post genomic era is allowing scientists and clinicians to examine an individuals' DNA and then recommend the best diet in order to remain healthy and attenuate disease processes which the individual might be predisposed to because of their genetic make-up, e.g., cardiovascular disease. Nutrigenomics and nutrigenetics are related terms to pharmacogenomics and pharmacogenetics with an emphasis on diet or nutrition. There has been an increasing interest in consumers on natural medicines or Nutraceuticals in order to remain healthy. The post genomic era will allow a patient to visit their physician who will screen the patients DNA on a silicon chip. This will indicate which of the patient's genes have polymorphisms, e.g., a single nucleotide polymorphism (SNP) that might lead the patient to be more susceptible to certain diseases and then the physician could prescribe the appropriate dietary supplements to prevent or diminish these potential diseases. Several recently published patents are discussed in the article covering recent developments in the field.

ENGAGING THE COMMUNITY IN HEALTH RESEARCH IN INDIA.

Community-engaged research approaches involve members of the community in various aspects of a research endeavor to improve the health of populations. Engaging the community in research is important in the development, dissemination, and evaluation of new interventions, technologies, and other medical advancements to improve population health globally. A review of published community-engaged research studies conducted in India was performed. Fifteen published studies were identified and reviewed to evaluate the state of community-engaged research in India. The review indicated that community-engaged research in India is limited. Most published community-engaged research focused on health promotion, especially in the prevention or management of HIV/AIDS and other STIs. Community members were involved in a variety of aspects of the research, but there was not one published article indicating that community members had defined the disease of focus. Community-engaged research often led to valuable insights into the views, experiences, and behaviors of community members and also led to increased community participation in health initiatives. It is anticipated that future community-engaged research will lead to improvements in global health through increased empowerment of communities and a better ability to implement new and innovative medical advances, technologies, and interventions.

Medullary monoamines and NMDA-receptor regulation of cardiovascular responses during peripheral nociceptive stimuli.

We have previously reported that AMPA-receptor blockade within the rostral ventrolateral medulla (RVLM) attenuates cardiovascular responses and extracellular concentrations of glutamate during mechanical, but not during thermal stimulation [Gray, T., Lewis III, E., Maher, T.J., Ally, A., 2001. AMPA-receptor blockade within the RVLM modulates cardiovascular responses via glutamate during peripheral stimuli. Pharmacol. Res. 43, 47-54]. In this study, we examined the role of NMDA-receptor blockade within the RVLM on cardiovascular responses and release of biogenic monoamines (serotonin [5HT], dopamine [DA], and norepinephrine [NE]) during both mechanical and thermal nociception using anesthetized Sprague-Dawley rats. Both mechanical and thermal stimulation have been shown to activate peripheral Adelta and C-fiber polymodal nociceptors. Noxious mechanical stimuli were induced by applying a pinch to alternate hindpaw for 5s while the noxious thermal stimuli involved immersion of the metatarsus of alternate hindpaw in a water bath at a temperature of 52 degrees C for 5 s. Mechanical stimulation increased mean arterial pressure (MAP), heart rate (HR), extracellular fluid 5HT, and DA concentrations (n=10). However, extracellular levels of NE were decreased within the RVLM. Furthermore, NMDA-receptor blockade with a competitive antagonist, AP-7 (200 nM), within the RVLM attenuated the cardiovascular responses and changes in 5HT and DA, but had no effect on NE levels. The thermal stimulation elicited similar increases in MAP and HR, however, extracellular levels of 5HT or DA did not change. Concentrations of NE were decreased during a thermal stimulation similar to the levels observed following mechanical stimuli. In contrast to mechanical stimuli, bilateral administration of AP-7 (200-1 mM) into the RVLM had no effect on cardiovascular responses, 5HT, DA or NE concentrations during a thermal stimulation. These results show that NMDA receptors within the RVLM most likely play a role in modulating cardiovascular responses by altering 5HT and DA concentrations within the RVLM during mechanical but not thermal nociception. Overall, the present study delineates the NMDA-receptor mediated central integrative mechanisms within the RVLM that coordinate processing of sensory impulses arising from peripheral noxious stimulation.

Neurochemistry within ventrolateral medulla and cardiovascular effects during static exercise following eNOS antagonism.

Nitric oxide synthase (NOS), necessary for the production of nitric oxide from l-arginine, exists in three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). We have previously demonstrated that blockade of nNOS within the rostral (RVLM) and caudal ventrolateral medulla (CVLM) differentially modulated cardiovascular responses to static exercise [Ishide, T., Nauli, S.M., Maher, T.J., Ally, A., 2003. Cardiovascular responses and neurotransmitter changes following blockade of nNOS within the ventrolateral medulla during static muscle contraction. Brain Res. 977, 80-89]. In this study, we have examined the effects of bilaterally microdialyzing a specific eNOS antagonist into the RVLM and CVLM on cardiovascular responses and glutamatergic/GABAergic neurotransmission during the exercise pressor reflex in anesthetized rats. Bilateral microdialysis of a selective eNOS antagonist, l-N(5)-(1-iminoethyl)ornithine (l-NIO; 10.0 microM) into the RVLM potentiated cardiovascular responses and increased extracellular fluid glutamate levels during a static muscle contraction. At the same time, levels of GABA within the RVLM were decreased. The cardiovascular responses and neurochemical changes to muscle contraction recovered after discontinuation of the drug. In contrast, bilateral application of the eNOS antagonist into the CVLM attenuated cardiovascular responses and glutamate concentrations during a static muscle contraction, but augmented levels of GABA. These results demonstrate that eNOS within the ventrolateral medulla plays an important role in modulating glutamate/GABAergic neurotransmission, that in turn regulates the exercise pressor reflex. The present study provides further evidence of simultaneous sympathoexcitatory and sympathoinhibitory effects of nitric oxide within the RVLM and CVLM involved in the neural control of circulation during static exercise.