Characterization of Human Genes Modulated by Porphyromonas gingivalis Highlights the Ribosome, Hypothalamus, and Cholinergic Neurons.

Porphyromonas gingivalis, a bacterium associated with periodontal disease, is a suspected cause of Alzheimer's disease. This bacterium is reliant on gingipain proteases, which cleave host proteins after arginine and lysine residues. To characterize gingipain susceptibility, we performed enrichment analyses of arginine and lysine proportion proteome-wide. Genes differentially expressed in brain samples with detected P. gingivalis reads were also examined. Genes from these analyses were tested for functional enrichment and specific neuroanatomical expression patterns. Proteins in the SRP-dependent cotranslational protein targeting to membrane pathway were enriched for these residues and previously associated with periodontal and Alzheimer's disease. These ribosomal genes are up-regulated in prefrontal cortex samples with detected P. gingivalis sequences. Other differentially expressed genes have been previously associated with dementia (ITM2B, MAPT, ZNF267, and DHX37). For an anatomical perspective, we characterized the expression of the P. gingivalis associated genes in the mouse and human brain. This analysis highlighted the hypothalamus, cholinergic neurons, and the basal forebrain. Our results suggest markers of neural P. gingivalis infection and link the cholinergic and gingipain hypotheses of Alzheimer's disease.

Physician perspectives on education, training, and implementation of complementary and alternative medicine.

Over recent decades, the demand for complementary and alternative medicine (CAM) has continued to rise in the US. Like the practice of traditional Western medicine, CAM is associated with not only significant health benefits but also significant risks. Unlike traditional Western medicine, however, much of CAM use is less regulated and often occurs unbeknownst to a patient's medical doctor. The use of herbals, dietary supplements, and over-the-counter (OTC) medications can result in adverse effects, and many significant interactions can occur when their use is combined with allopathic medications. Even the more peripheral CAM practices (eg, acupuncture, massage, yoga, and Reiki) have associated risk (eg, adverse effects or worsening of physical injury and conditions). There is, however, impetus for change: both patients and physicians favor increasing physician knowledge of CAM and the synergistic implementation of CAM into routine clinical practice. Although improvement has been achieved from contemporary physician educational efforts, recently published results from patient and physician surveys strongly indicate that additional effort to increase physician knowledge of CAM is needed. Utilizing a 37-item survey and convenience-sampling methodology, we collected detailed information from 114 physicians, fellows, and residents from the Ohio State University Medical Center regarding impediments to increasing physician knowledge of CAM and its implementation in routine clinical practice. The aggregate results of our survey data showed that most physicians 1) desired to increase their knowledge of CAM, 2) believed that less than half of their patients were spontaneously reporting their use of CAM therapies, 3) were not aware of available evidence-based resources on CAM, 4) preferred case-based lectures for learning about CAM, and 5) reported insufficient time during patient encounters as the primary barrier for increasing the implementation of CAM in routine clinical practice.

Online education about herbs and dietary supplements: margin or mission?

BACKGROUND: Online education is increasingly used to train health professionals, but little is known about how variations in cost affect use of elective training. We assessed whether offering registration for free increased the number of modules consumed in both absolute terms (# modules consumed per person, pp) and relative terms (# modules consumed per # modules registered). METHODS: We analyzed results of the 'natural experiment' on learner's use of the OSU Center for Integrative Health and Wellness online elective curriculum, Introduction Herbs and Dietary Supplements Across the Lifespan, in which costs varied based on monthly discounts for students, faculty, staff, alumni, and members of selected professional associations. RESULTS: Over 7 months there were a total of 905 registrants for 8553 modules. Most (847/905, 94%) registered for free; they completed 1505 (18%) of 8344 modules for which they registered. Fewer (58/905, 6%) people paid for registration; they completed a significantly higher percentage 90/209 (43%, P < 0.001) of modules for which they registered; those who paid full, non-discount rates had the highest completion rates (62%, P < 0.001). Free and paid registrants completed about the same average number of modules per person, pp, (1.8 pp free vs.1.6 pp paid). CONCLUSION: Although it may not contribute to financial margins, offering free online elective training addresses the institutional mission of increasing the number health professionals trained and the number of modules consumed compared with charging for training. Additional research is needed to determine the impact of pricing on educational outcomes and ultimately on patient care.

Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats.

BACKGROUND: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties. OBJECTIVE: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats. MATERIALS AND METHODS: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg). Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg) along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg) treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by 'analysis of variance' test followed by post hoc Tukey's test, with significant level of P < 0.05. RESULTS AND DISCUSSION: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group. CONCLUSION: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property.

Hypothalamic injection of oxyntomodulin suppresses circulating ghrelin-like immunoreactivity.

Ghrelin is a gastric peptide that regulates appetite and GH secretion. Circulating ghrelin levels are elevated by fasting and suppressed postprandially. However, the mechanisms regulating circulating ghrelin levels are unclear. Oxyntomodulin is an anorexic peptide hormone released from L cells in the gut. We investigated the effects of intracerebroventricular (icv) administration of oxyntomodulin on circulating ghrelin levels. The icv administration of 1, 3, or 10 nmol oxyntomodulin reduced circulating acylated and total (acylated and des-acylated) ghrelin 60 min after icv injection. Administration of 1 nmol oxyntomodulin directly into the arcuate nucleus of the hypothalamus significantly reduced total and acylated ghrelin levels, and administration of 3 nmol oxyntomodulin into the lateral ventricle induced c-fos mRNA expression in arcuate nucleus neurons expressing the glucagon-like peptide-1 (GLP-1) receptor. In a final study, the reduction in total ghrelin observed after icv injection of 3 nmol oxyntomodulin was blocked by coadministration of the GLP-1 receptor antagonist exendin (9-39). These studies suggest oxyntomodulin reduces peripheral ghrelin levels via GLP-1 receptor-dependent hypothalamic pathways. Postprandial release of anorexic gut hormones may thus act centrally to contribute to the postprandial reduction in circulating ghrelin.

Peripheral and central administration of xenin and neurotensin suppress food intake in rodents.

Xenin is a 25-amino acid peptide highly homologous to neurotensin. Xenin and neurotensin are reported to have similar biological effects. Both reduce food intake when administered centrally to fasted rats. We aimed to clarify and compare the effects of these peptides on food intake and behavior. We confirm that intracerebroventricular (ICV) administration of xenin or neurotensin reduces food intake in fasted rats, and demonstrate that both reduce food intake in satiated rats during the dark phase. Xenin reduced food intake more potently than neurotensin following ICV administration. ICV injection of either peptide in the dark phase increased resting behavior. Xenin and neurotensin stimulated the release of corticotrophin-releasing hormone (CRH) from ex vivo hypothalamic explants, and administration of alpha-helical CRH attenuated their effects on food intake. Intraperitoneal (IP) administration of xenin or neurotensin acutely reduced food intake in fasted mice and ad libitum fed mice in the dark phase. However, chronic continuous or twice daily peripheral administration of xenin or neurotensin to mice had no significant effect on daily food intake or body weight. These studies confirm that ICV xenin or neurotensin can acutely reduce food intake and demonstrate that peripheral administration of xenin and neurotensin also reduces food intake. This may be partly mediated by changes in hypothalamic CRH release. The lack of chronic effects on body weight observed in our experiments suggests that xenin and neurotensin are unlikely to be useful as obesity therapies.

Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake.

Neuropeptide S (NPS) is a recently discovered peptide shown to be involved in the modulation of arousal and fear responses. It has also been shown that lateral ventricle administration of NPS causes a significant decrease in food intake. Neuropeptides involved in the modulation of arousal have been shown to be involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis and food intake. In this study, we have examined the effect of intracerebroventricular (ICV) administration of NPS on behavior, regulation of the HPA axis, and food intake. ICV NPS significantly increased plasma ACTH and corticosterone 10 and 40 min after injection, respectively. A single ICV injection of NPS caused a significant increase in rearing activity as well as ambulatory movement for up to 45 min after injection. We then studied the effect of paraventricular nucleus (PVN) administration of NPS on the regulation of the HPA axis, behavior, and food intake. There was a significant increase in plasma ACTH and corticosterone after a single NPS PVN injection. Incubation of hypothalamic explants with increasing concentrations of NPS caused a significant increase in CRH and arginine vasopressin release. In addition, PVN administration of NPS dose-dependently inhibited food intake in the first hour after injection, although no effect on food intake was seen after this time. PVN administration of NPS caused a significant increase in rearing activity. These data demonstrate a novel role for NPS in the stimulation of the HPA axis.