Biomedical subjects
Publications and source records attributed to Mona Patel.
A series of indole-O-glucosides and C-glucosides was synthesized and evaluated in SGLT1 and SGLT2 cell-based functional assays. Compounds 2a and 2o were identified as potent SGLT2 inhibitors and screened in ZDF rats.
A series of benzo-fused heteroaryl-O-glucosides was synthesized and evaluated in SGLT1 and 2 cell-based functional assays. Indole-O-glucoside 10a and benzimidazole-O-glucoside 18 exhibited potent in vitro SGLT2 inhibitory activity.
BACKGROUND: Until recently, minority and poor men have been characterized as "an invisible population," overlooked by public and private efforts to improve the health status of women, children, and the elderly. OBJECTIVE: This study compares the health care experiences of racial and ethnic minority men with that of white men, and low socioeconomic status with those of higher status. MEASURES/SUBJECTS: Quality-of-care measures in multiple clinical domains are evaluated. The authors use data from several databases, including the National Health Interview Survey, Medical Expenditure Panel Survey, and Health Care Cost and Utilization Project State Inpatient Database. The relative difference between each racial/ethnic and socioeconomic group and a fixed reference group is used to assess differences in use of services. Statistical significance is assessed using z tests. RESULTS: Hispanic men were much less likely to receive colorectal cancer screening (relative risk [RR] range, 0.61-0.69), cardiovascular risk factor screening and management (RR, 0.84-0.88), and vaccinations (RR, 0.47-0.94). Black and Asian men were significantly less likely to have received selected preventive services (adult immunization and colorectal cancer screening). The differences in end-stage renal disease care that black and white men received were statistically significant (RR, 0.39-0.97), with black men consistently receiving worse care. For some measures of management of end-stage renal disease, Asian men received care that was similar to or better than that received by non-Hispanic whites. CONCLUSION: Minority men are at a markedly elevated risk for the receipt of poor health care quality. However, generalizations about "minority" men are likely to be misleading and incomplete. There is a considerable variation in the magnitude, direction, and significance of these risks.
This review describes the role of nuclear receptors in the regulation of genes involved in cholesterol transport and synthetic modulators of these receptors. Increasing the efflux of cholesterol from peripheral cells, such as lipid-laden macrophages, through a process called reverse cholesterol transport (RCT) requires HDL. Increasing the circulating levels of HDL, as well as the efficiency of the RCT process, could result in a reduction in the development of coronary artery disease and atherosclerosis. Nuclear receptors of the RXR heterodimer family have recently been shown to regulate key genes involved in HDL metabolism and reverse cholesterol transport. These include the PPARs (peroxisome proliferator activated receptors), the LXR (liver X receptor) and the farnesoid X receptor (FXR). The synthesis of specific and potent ligands for these receptors has aided in ascertaining the physiological role of these receptors as lipid sensors and the potential therapeutic utility of modulators of these receptors in dyslipidemias and cardiovascular disease.
A series of substituted spirobenzazepines was prepared and evaluated as V(1a) and V(2) dual vasopressin receptor antagonists. Compounds 7p and 7q have been shown to be not only potent inhibitors of vasopressin receptors, but also have exhibited an excellent overall pharmaceutical suitability profile.
A novel series of spirobenzazepines was synthesized and evaluated for V1a and V2 receptor antagonist activity. Compounds 8b, 8i, and 8k have shown selective V1a receptor antagonist activity. Compounds 8p and 8q were shown to be dual V1a/V2 receptor antagonists.
A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and pharmacokinetics are described.
The practical and highly diastereoselective syntheses of CF(3)-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2). In addition, the scope of the new diastereoselective 1,4-addition chemistry is investigated. The first preparation of DPC 961 (1) described in this paper is a derivatization fractional crystallization protocol.
Diabetes mellitus has been declared to be at an epidemic level by the World Health Organization. The syndrome is characterised as either Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. Impaired glucose tolerance for extended periods of time results in serious complications such as kidney damage and impaired blood circulation and is the main cause for blindness and amputations in patients with diabetes. A combination of life-style change, dietary change and oral medications can treat Type II diabetes mellitus effectively and prevent long-term complications. Combination therapy appears to be the most effective approach in controlling blood glucose levels. This review updates the progress made in medicinal chemistry towards promising biological targets, with the development of a new generation of small molecules having improved efficacy and safety profiles.
The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions, such as motor or learning disabilities, cerebral palsy, epilepsy or even death. No effective treatment is currently available and this study is the first to use hyperbaric oxygen (HBO) as a treatment for neonatal HI. Herein, we sought out to determine if HBO is able to offer neuroprotectivity against an HI insult. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O(2) at 37 degrees C). HBO treatment was administered by placing pups in a chamber (3 ATA for 1 h) 1 h after hypoxia exposure. Brain injury was assessed based on ipsilateral hemispheric weight divided by contralateral hemispheric weight, light microscopy, and EM. Sensorimotor functional tests were administered at 5 weeks after hypoxia exposure. After HI, the ipsilateral hemisphere was 52.65 and 57.64% (P<0.001) of the contralateral hemisphere at 2 and 6 weeks, respectively. In HBO treated groups, the ipsilateral hemisphere was 77.77 and 84.19% (P<0.001) at 2 and 6 weeks. There was much less atrophy and apoptosis in HBO treated animals under light or electron microscopy. Sensorimotor function was also improved by HBO at 5 weeks after hypoxia exposure (Chi-square, P<0.050). The results suggest that HBO is able to attenuate the effects of HI on the neonatal brain by reducing the progression of neuronal injury and increasing sensorimotor function.