Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I

BACKGROUND: Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine) were studied in rats with ascitic cirrhosis. METHODS: Advanced cirrhosis was induced by CCl(4 )inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using (14)C or (35)S-labelled subtracts in the three experimental groups. RESULTS: Intestinal active Na(+)-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased V(max )and a reduced affinity for sugar and four amino acids transporters (expressed as an increased K(t)) in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy. CONCLUSIONS: The initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids) are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I

Vitamin status and cognitive function in a long-term care population

BACKGROUND: Ageing can be associated with poor dietary intake, reduced nutrient absorption, and less efficient utilization of nutrients. Loss of memory and related cognitive function are also common among older persons. This study aimed to measure the prevalence of inadequate vitamin status among long-term care patients and determine if an association exists between vitamin status and each of three variables; cognitive function, vitamin supplementation, and medications which alter gastric acid levels. METHODS: Seventy-five patients in a long-term care hospital in Guelph, Ontario were recruited to a cross-sectional study. 47 were female and the mean age was 80.7 (+/-11.5) years, ranging from 48 to 100 years. Blood was used to measure levels of vitamins B12 (cobalamin), B6 (pyridoxal-5'-phosphate/PLP), erythrocyte folate, vitamin B3 (niacin) and homocysteine (Hcy). The Standardized Mini-Mental State Examination (SMMSE) was administered to measure cognitive function. A list of medications and vitamin supplementation for each patient was provided by the pharmacy. RESULTS: The prevalence of low vitamin (B12, B6, erythrocyte folate, niacin) or high metabolite (homocysteine) levels among 75 patients were as follows: B12 <148 pmol/L in 5/75 (6.7%); B12 between 148 and 221 pmol/L in 26/75 (34.7%); B6 ≤30 nmol/L in 4/75 (5.3%); erythrocyte folate <370 nmol/L in 1/75 (1.3%); niacin ratio ≤1 in 20/75 (26.7%); homocysteine >13.3 μmol/L in 31/75 (41.3%). There was no significant difference among residents grouped into marked (n = 44), mild (n = 14), or normal (n = 9) cognitive function when evaluating the effect of vitamin status. There were no significant differences in mean B12 and homocysteine levels between users and non-users of drug therapy (Losec, Zantac, or Axid). Compared to vitamin supplement non-users, supplemented residents had significantly higher mean B12 (p < 0.0001) and erythrocyte folate (p < 0.05) concentrations and significantly lower mean homocysteine (p < 0.01) levels; 229.1 versus 423.6 pmol/L for B12, 882.9 versus 1043.6 nmol/L for erythrocyte folate and 14.4 versus 12.0 μmol/L for homocysteine. CONCLUSION: Given the prevalence data on vitamin status in this sample population, the possible benefits of vitamin supplementation should be considered in clinical intervention studies using these populations of elderly

Intestinal spirochetosis and acquired immunodeficiency syndrome: Ultrastructural studies of two cases

Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. In case 1, a 48-year-old homosexual black man presented with a 1-month history of alternating watery diarrhea and constipation, which dissipated following the removal of two colonic hyperplastic polyps containing IS. In case 2, a 26-year-old homosexual black man presented with a 3-month history of persistent bloody diarrhea and was found to have chronic shigellosis and IS. Pathologic findings of IS were similar in both cases. Basophilic fringes typical of IS covered the surfacing colonic epithelium and consisted of dense growths of spirochetes adherent to and oriented perpendicular to the plasma membranes of the surfacing epithelium. The spirochetes measured 3 to 5 μm in length and 0.2 μm in width, contained four to eight axial fibrils, and closely resembled Brachyspira aalborgi ultrastructurally. These cases are notable because the histopathologic changes of IS were more extensive than generally described. There was involvement of both the right colon and rectum by IS in case 2, and in both cases there was extension of the IS down into the crypts of Lieberkuhn, spirochetal invasion of the colonic mucosa, and a conspicuous inflammatory response by macrophages in the underlying lamina propria

Insulin-like growth factor I receptors in the arteries of the rabbit: Autoradiographic mapping and receptor characterization

Insulin-like growth factor I (IGF-I) is a polypeptide hormone structurally related to insulin with insulin-like metabolic effects. It is a potent mitogen, eliciting cell multiplication in tissue culture by increasing deoxyribonucleic acid and protein synthesis. IGF-I was found to promote the growth of cultured arterial smooth muscle cells. We studied the in situ distribution of IGF-I receptors in different arteries of the rabbit by autoradiography and examined their binding characteristics in the wall of the thoracic aorta. The thoracic and abdominal aortas and carotid, superior mesenteric, renal, and iliac arteries of three adult New Zealand rabbits were harvested and stored at -70°C. Autoradiographic analysis of 125I-labeled IGF-I binding to frozen arterial sections showed that silver-grain density was consistently located in the arterial wall. Binding studies in the thoracic aorta demonstrated high-affinity IGF-I receptors with a dissociation constant of 2 nmol/L and maximum IGF-I binding capacity of 4.17 pmol/mg protein. Inhibition studies with insulin, IGF-I, and IGF-II showed that these binding sites were more specific for IGF-I than for IGF-II or insulin, with a concentration of peptide that inhibits 50% of maximum binding of 1.75 nmol/L, 5 nmol/L, and \u3e100 μmol/L, respectively. The presence of high-affinity, specific IGF-I receptor binding in rabbit arteries suggests that IGF-I plays an important role in regulating the multiplication of arterial smooth muscle cells; a role that may prove important in different pathologic processes