Hospital do Rim e Hipertensão

Fundado em 1998 e dirigido pela Fundação Oswaldo Ramos, é orgão suplementar da Universidade Federal de São Paulo/Escola Paulista de Medicina. Oferece serviços em diagnóstico e tratamentos para pacientes com hipertensão arterial, diabetes, nefrite, insuficiência renal aguda e crônica, problemas cardiológicos, entre outros. Fornece notícias e informações sobre os estudos desenvolvidos no hospital, organização e equipamentos e aborda a questão da obesidade, um problema de saúde pública nos últimos anos.

Intestinal absorption of 25-hydroxyvitamin D3 in unanesthetized rat.

We investigated the mechanism and characteristics of 25-hydroxyvitamin D3 (25-OH-D3) absorption in the unanesthetized rat by using a single-pass intestinal perfusion technique. The rate of 25-OH-D3 absorption remained linear for a wide range of concentrations (2-900 nM). Absorption rate of 25-OH-D3 increased as the pH, the bile acid concentration, and thickness of the unstirred water layer were decreased. Absorption did not change after the additions of fatty acids of varied chain lengths and degrees of saturation. In rats with lymph and bile fistulas, 18.5% and 16.3% of the infused radio-activity appeared in the lymph and bile drainage, respectively. These experiments indicate that 25-OH-D3 is absorbed by a passive diffusion mechanism that is influenced by the intestinal pH, bile acid concentration, and thickness of the unstirred water layer, but not by the presence of fatty acids. Approximately equal fractions of the infused hydroxylated vitamin are recovered from the lymphatic and biliary fluids.

Diurnal rhythmicity of absorption of a lipid compound (vitamin K-1) in vivo in the rat.

The possibility of rhythmicity in the intestinal absorption of lipids was explored by assessing the absorption of vitamin K-1 by the unanesthetized rat at 6 PM, 12 and 6 AM, and 12 PM. A marked variability in the absorption rate of vitamin K-1 was found throughout the 18-hr period. The highest rates of absorption occurred at midnight (139.8 +/- .22 and 134.4 +/- 9.1 pmol/min/10 cm of jejunum and ileum, respectively). The lowest rates of absorption occurred at 6 AM (54.5 +/- 1 and 81.4 +/- 7.4 pmol/min/10 cm of jejunum and ileum, respectively). Absorption rates at noon were not different from absorption at 6 AM but an initial increase in absorption was noted at 6 PM. Synchronization of the absorptive rate with time is most likely related to the time of feeding and not to changes in the pattern of illumination. The possibility of marked diurnal variability in the absorption rate should be considered in the design and execution of intestinal absorption experiments.

Effect of luminal constituents on vitamin K1 absorption into thoracic duct lymph.

Lymphatic appearance rate of [3H] phylloquinone was studied in unanesthetized rats with cannulated bile and lymph ducts. A linear relationship (y= -44.9 + 10.2x, r=0.99) was found between the rate of the compound's infusion into the duodenum and its appearance rate in the lymph. Increasing the taurocholate infusate concentrations from 5 to 15 mM increased phylloquinone appearance rate in the lymph from 6.47 +/- 1.82 to 24.14 +/- 1.20 pmol/min (P less than .01). Varying the infusate pH from 4.35 to 8.0 did not change lymphatic appearance rate of vitamin K1 or lymphatic flow rate. Addition of short-chain fatty acid (butyrate) to the infusate enhanced the total absorption of vitamin K1 into the bile and lymph, whereas the addition of polyunsaturated fatty acids inhibited the total absorption of the vitamin. These experiments delineate some factors that modify the extrusion rate of vitamin K1 out of the enterocyte into the lymphatic circulation and add information regarding this phase of the absorptive pathway of lipids.

Vitamin K2 colonic and ileal in vivo absorption: bile, fatty acids, and pH effects on transport.

Colonic and ileal absorption of vitamin K2 ([2-methyl-3H]menaquinone-9) was investigated in the conscious rat. When the absorption rate was plotted against the perfusate concentration, a linear relationship was found between these two parameters in the ileum and colon. The absorption rate of menaquinone by the ileum was increased as the bile salt concentration, degree of unsaturation of the added long-chain fatty acids, hydrogen ion concentration, and perfusate flow rates were increased. Colonic menaquinone absorption decreased as the bile salt concentration was increased. Menaquinone colonic absoprtion increased as the pH decreased, but no change was noted as the perfusion rate was increased. The present experimental observations in vivo, coupled with prior observations in vitro, indicate that absorption of menaquinone by the ileum and colon occurs by a passive diffusion process that is modified by variations in the perfusate bile salt concentration, the presence of unsaturated fatty acids, and the perfusate pH. The present observations indicate that the mammalian colon and terminal ileum can provide a constant source of vitamin K to aid hemostasis despite episodic lack of dietary vitamin K.

Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport.

Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate.

Vitamin K2 absorption by rat everted small intestinal sacs.

Small intestinal absorption of vitamin K2 was investigated in vitro. Experiments with increasing concentrations of the vitamin up to 900 nM revealed linerity between the concentration and the rate of absorption (r = 0.99). Addition of metabolic uncouplers and inhibitors such as 2,4-dinitrophenol, sodium azide, and potassium cyanide did not decrease the rate of absorption of the vitamin (P less than 0.05). Absorption rate of the vitamin increased when taurocholate was replaced by a nonionic detergent, Pluronic F-68. The addition of butyric and octanoic acids to the incubation solution caused an increase in the absorption rate of vitamin K2. No change in the absorption of the vitamin occurred in the presence of oleic and linoleic acid. Addition to vitamins K1 and K3 to the incubation solution did not change the rate of vitamin K2 absorption. These findings suggest that vitamin K2 is absorbed by the small bowel by a passive noncarrier-mediated diffusion process. The rate of diffusion varied when the lipid and bile salt composition of the incubation solution was modified. Distal intestinal absorption of vitamin K from bacterial sources coupled with colonic absorption of the vitamin may be the major constant source of vitamin K in mammals.

Factors affecting the absorption of vitamin K-1 in vitro.

Factors which might affect the absorption of vitamin K of dietary origin were investigated using everted small bowel sacs. Increasing the bile salt concentration to 20 mM or the addition of long chain fatty acids, monoolein, or lecithin all resulted in significant (P less than 0-05) decrease in the absorption rate of the vitamin. The addition of 2-5 mM short and medium chain fatty acids did not change the absorption rate of vitamin K-1 (P greater than 0-05). The absorption rate of vitamin K-1 appears to be modified by the presence of compounds in the incubation medium which either alter the partition of the vitamin between the micelle and the cell membrane or which change the permeation characteristics of the compound through the unstirred water layer or modify the physical characteristics of the cell membrane itself. It is possible that some of the above factors modify the absorption of lipid soluble compounds in general.

Colonic absorption of bacterially synthesized vitamin K2 in the rat.

Colonic absorption of bacterially synthesized vitamin K2 ([3H]menaquinone-9) was studied with everted rat colonic sacs in vitro. The mean +/- SE rate of absorption of the vitamin by the colon was 20 +/- 1.45 pmol/min per 100 mg tissue at 300 nM mucosal concentration of the vitamin. The rate of absorption did not change (P greater than 0.10) with the addition of 2,4-dinitrophenol, Na azide, or KCN to the mucosal incubation medium. No evidence for transmural transport of the vitamin was detectable. When the concentration of the vitamin was increased in a stepwise fashion up to 900 nM, the absorption rate remained linear with respect to the mucosal fluid concentration (r = 0.98). Autoradiography indicated that the vitamin accumulated in the mucosal and submucosal layers of the large bowel. Absorption of the vitamin by the large bowel takes place via a passive, nonsaturable process that shows no evidence of energy dependence or carrier mediation. It was concluded that vitamin K2 (bacterial origin) is absorbable by the rat colon in amounts sufficient to meet the daily requirement of the animal and may explain the lack of bleeding problems in the face of episodic lack of dietary vitamin K.

Mechanism and site of small intestinal absorption of alpha-tocopherol in the rat.

The site and mechanism of alpha-[5-methyl-3-H]tocopherol absorption was investigated using everted rat small bowel sacs incubated in a micellar medium. Mean plus or minus SE absorption rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 2.2 plus or minus 0.17, 3.4 plus or minus 0.21, and 2.0 plus or minus 0.04 nmoles per min per 100 mg, respectively. Addition of 2,4-dinitrophenol, sodium azide, or potassium cyanide to the incubation medium in separate experiments did not change the rate of absorption (P greater than 0.10). Stepwise increase in incubation solution tocopherol concentration up to 1200 muM resulted in a linear increase in the absorption rate. In all of the above described experiments the rate of absorption of the vitamin by the medial portion of the small bowel was significantly (P smaller than 0.01) higher than the rate of absorption of the vitamin by the proximal and distal small bowel segments. No transmural transport of the vitamin into the serosal compartment took place. Autoradiographic examination of the tissue after incubation disclosed accumulation of the vitamin in the submucosal lymphatic spaces. Alpha-Tocopherol absorption by the rat small bowel appears to be a passive diffusion process taking place at the highest rate in the medial portion of the small bowel.