Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP.     

IL-10 elicits IFNγ-dependent tumor immune surveillance

Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8(+) T?cells. Intratumoral CD8(+) T?cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8(+) T?cells, expression of the Th1 cytokine interferon-γ (IFNγ) and granzymes in CD8(+) T?cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8(+) T?cell function and controls tumor growth.     

Oral lesions of 500 habitual psychoactive substance users in Chennai, India

The aim of this study was to ascertain the prevalence of oral lesions among 500 psychoactive substance users in a hospital-based population. The study group consisted of 500 consecutive patients attending TTK Hospital, a non-governmental organisation involved in rehabilitation of substance users. Patient history was recorded in a pre-determined format and clinical findings were recorded by a trained physician and dental surgeons. Psychoactive substances used by the patients were alcohol (97%), tobacco (72%), arecanut (57.2%), narcotics (6.8%), cannabis (3.2%) and benzodiazipines (1.8%). Ninety-one percent of patients had one or more oral lesions: dental caries (39%), gingivitis (37.6%), extrinsic stains (24%), oral submucous fibrosis (OSF) (8%), periodontitis (7.4%), leukoplakia (6.6%), melanosis (5.2%), nicotina palatini (2.2%) and erythroplakia (0.6%). For OSF, those using arecanut and alcohol had an odds ratio (OR) of 2.4 [95% confidence intervals (CI) 1.23-4.69, P=0.009], smokers using arecanut products and alcohol had an OR of 3.07 (95% CI 1.59-5.91, P=0.000), and smokers who chewed arecanut products and used drugs had an OR of 23.1 (95% CI 2.05-260, P=0.001) compared with the general population. Those who smoked and used alcohol, arecanut and drugs had a 20.67-fold higher risk of developing leukoplakia compared with those who did not engage in these habits. In conclusion, 91% of patients had one or more oral lesions that needed dental treatment, and most patients were not aware of their oral lesions. The high prevalence of OSF and leukoplakia in substance abusers compared with the general population emphasises the need for regular dental assessments in these patients.     

Diagnostic ability of computed tomography using DentaScan software in endodontics: case reports

Radiographic examination is essential in diagnosis and treatment planning in endodontics. Conventional radiographs depict structures in two dimensions only. The ability to assess the area of interest in three dimensions is advantageous. Computed tomography is an imaging technique which produces three-dimensional images of an object by taking a series of two-dimensional sectional X-ray images. DentaScan is a computed tomography software program that allows the mandible and maxilla to be imaged in three planes: axial, panoramic, and cross-sectional. As computed tomography is used in endodontics, DentaScan can play a wider role in endodontic diagnosis. It provides valuable information in the assessment of the morphology of the root canal, diagnosis of root fractures, internal and external resorptions, pre-operative assessment of anatomic structures etc. The aim of this article is to explore the clinical usefulness of computed tomography and DentaScan in endodontic diagnosis, through a series of four cases of different endodontic problems.