Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.

BACKGROUND: Gut-liver axis (GLA) dysfunction appears to play a role in obesity and obesity-related hepatic complications. OBJECTIVES: This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease. METHODS: Thirty-two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST-), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/-]). Subjects were characterized by using auxologic, ultrasonographic and laboratory parameters. A glucose hydrogen breath test was performed to test for small intestinal bacterial overgrowth, a urinary lactulose/mannitol ratio (LMR) was obtained to assess intestinal permeability, and tests for transaminases, blood endogenous ethanol, endotoxin and faecal calprotectin were also conducted. RESULTS: Eleven out of 23 patients OB(+) (p < 0.05) exhibited pathological (>90th percentile of the control group values) LMR, with values paralleling the grade of liver involvement (normal weight < OB[+] < OB[+]ST[+]ALT[-] < OB[+)]ST[+]ALT[+] [p < 0.05]). LMR significantly correlated with ethanolaemia (r = 0.38, p = 0.05) and endotoxaemia (r = 0.48, p = 0.015) concentrations. Increased permeability was a risk factor for the development of steatosis (p < 0.002). SIBO was present only in patients with obesity. Faecal calprotectin concentrations were within normal limits in all subjects. CONCLUSIONS: Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.

Development of the hamster submandibular gland. II. The ductal system.

The major secretory duct is differentiated from the SMG anlage in early embryogenesis and undergoes minor morphologic changes from its inception until full maturation. Structurally, the ducts appear to be suited for a conduit function. At birth, the extralobular and intralobular ducts arise directly from the major duct or indirectly from the primary and secondary branches, respectively. They are distinguishable from each other by their topography only. However, developmentally, intralobular ducts give rise to 'terminal tubule' complexes but no such function is performed by the extralobular ducts. Both duct types first show distinct evidence of striation of their cells at one week after birth. Their lateral and basal infoldings, interdigitations and close association with mitochondria provide them with increased surface area and a source of energy for exchange of ions and fluids. The differentiation of convoluted granular ducts begins at 2 weeks of age with the appearance of membrane-bound and dense secretory granules in the apical cytoplasm of the luminal cells. The changes start in the proximal segment of the intralobular striated duct, and extend to occupy a large part of it in a mature 6-week old animal. These ducts comprise the bulk of the ductal system. The distribution of the granules is size-gradient dependent, the small granules being near the lumen and the large ones being close to the nucleus. The morphologic features of CGD are in keeping with absorptive and secretory functions.

Development of the hamster submandibular gland. I. The acinar-intercalated duct complex.

On the basis of light and electronmicroscopic observations of the prenatal and postnatal development of the hamster submandibular gland, several stages of cyto-morphodifferentiation were identified. The initial critical period was between the 13th and 14th day of gestation. An anlage of 'undifferentiated' pluripotential stem cells was transformed into terminal tubules which consisted of secretory cells, myoepithelial cell precursors and stem cells. From the periphery of the terminal tubules originated terminal buds which were the forerunners of the acini. The intercalated ducts, terminal tubules and terminal buds constituted the 'terminal tubule complex'. Several morphological similarities were noted between the hamster and the rat developing SMG and between the hamster developing SMG and the rat parotid. It seemed that various human salivary gland tumors recapitulated different stages of their normal cytomorphogenesis.

Conformational analysis of the ergot alkaloids ergotamine and ergotaminine.

Conformational analyses by 1H NMR and potential-energy calculations are reported for the ergot alkaloids ergotamine and ergotaminine, both as free bases and as the protonated species. In the neutral forms in CDCl3. two strong intramolecular hydrogen bonds fix the molecules in folded conformations, but the protonated species adopt a more extended conformation, with a single intramolecular hydrogen bond. Of the 24 alternative conformations available to ergotamine, the most likely biologically active species in environments with low dielectric constants, e.g., the presumed ergotamine binding site, is the folded, hydrogen-bonded conformation observed for the neutral molecule in CDCl3 solution.

Quantitation of hepatitis B viral markers in a dental school population.

Ample evidence exists that dentists and dental personnel are vulnerable to hepatitis B disease. Epidemiologic studies, which provide a further understanding of the prevalence, infectious nature, and risks of transmission of the hepatitis B virus, are particularly significant in a dental school environment because of the insidious nature of the virus. Screening should be done for anti-HBs because it is the most reliable marker for hepatitis B infection and is generally believed to confer immunity. However, because no experimental data are available concerning the amount of antibody needed for protection, quantitation of anti-HBs levels in human serum or gingival crevicular fluid would be the first step in ultimately correlating antibody titers to the immune process. In this study, we present quantitative data on the relative antibody titers in a dental school population. Our findings may be of importance for monitoring the effectiveness of vaccination, for improving safety guidelines in dental clinics, and for developing new and rapid oral diagnostic screening methods. Recently, a new method using gingival crevicular fluid has been developed; it permits identification of not only antibody, but also of hepatitis B surface and e antigens (L. Andors, and associates, unpublished data).