Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

IMPROVEMENT OF INTESTINAL PERMEABILITY WITH ALANYL-GLUTAMINE IN HIV PATIENTS: a randomized, double blinded, placebo-controlled clinical trial

Context Glutamine is the main source of energy of the enterocyte and diarrhea and weight loss are frequent in HIV infected patients. Objective To determine the effect of alanyl-glutamine supplementation on intestinal permeability and absorption in these patients. Methods Randomized double-blinded, placebo-controlled study using isonitrogenous doses of alanyl-glutamine (24 g/day) and placebo (glycine, 25 g/day) during 10 days. Before and after this nutritional supplementation lactulose and mannitol urinary excretion were determined by high performance liquid chromatography. Results Forty six patients with HIV/AIDS, 36 of whom were male, with 37.28 ± 3 (mean ± standard error) years were enrolled. Twenty two and 24 subjects were treated with alanyl-glutamine and with glycine respectively. In nine patients among all in the study protocol that reported diarrhea in the 14 days preceding the beginning of the study, mannitol urinary excretion was significantly lower than patients who did not report this symptom [median (range): 10.51 (3.01–19.75) vs. 15.37 (3.93–46.73); P = 0.0281] and lactulose/mannitol ratio was significantly higher [median (range): 0.04 (0.00–2.89) vs. 0.02 (0.00–0.19); P = 0.0317]. There was also a significant increase in mannitol urinary excretion in the group treated with alanyl-glutamine [median (range): 14.38 (8.25–23.98) before vs 21.24 (6.27–32.99) after treatment; n = 14, P = 0.0382]. Conclusion Our results suggest that the integrity and intestinal absorption are more intensely affected in patients with HIV/AIDS who recently have had diarrhea. Additionally, nutritional supplementation with alanyl-glutamine was associated with an improvement in intestinal absorption. .

Contexto A glutamina é a principal fonte de energia do enterócito e diarreia e perda de peso são frequentes em pacientes infectados pelo HIV. Objetivo Determinar o efeito da alanil-glutamina sobre a permeabilidade e a absorção intestinais nesses pacientes. Métodos Estudo duplo-cego, randomizado, controlado por placebo, utilizando doses isonitrogênicas de alanil-glutamina (24 g/dia) e de placebo (glicina, 25 g/dia) durante 10 dias. Antes e depois dessa suplementação nutricional a excreção urinária de lactulose e manitol foi determinada por cromatografia líquida de alta performance. Resultados Quarenta e seis pacientes com HIV/AIDS, sendo 36 do sexo masculino, com 37,28 ± 3 anos (média ± erro padrão) foram incluídos. Vinte e dois e 24 indivíduos foram tratados com alanil-glutamina e com glicina, respectivamente. Nos nove pacientes que relataram ter apresentado diarreia nos 14 dias anteriores ao início do estudo, a excreção urinária de manitol foi significativamente menor do que nos pacientes que não referiram essa queixa [mediana (intervalo): 10,51 (3,01-19,75) vs 15,37 (3,93-46,73), P = 0,0281] e a razão lactulose/manitol foi significativamente mais elevada [mediana (intervalo): 0,04 (0,00-2,89) vs 0,02 (0,00-0,19), P = 0,0317]. Constatou-se também aumento significativo na excreção urinária de manitol no grupo tratado com alanil-glutamina [mediana (intervalo): 14,38 (8,25-23,98), antes vs 21,24 (6,27-32,99) após o tratamento, n = 14, P = 0,0382]. Conclusão Os resultados do presente estudo sugerem que a integridade e a absorção intestinais são mais intensamente afetadas em pacientes com HIV/AIDS que tiveram diarreia recentemente. Adicionalmente, a suplementação ...

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-forheight z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. RESULTS: Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9 percent. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. CONCLUSIONS: During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to benefit immediate nutritional status, which can translate into better long-term cognitive outcomes.

Increased levothyroxine requirement in a woman with previously well-controlled hypothyroidism and intestinal giardiasis / Aumento da necessidade de levotiroxina em uma paciente com hipotireoidismo previamente bem-controlado e giardíase intestinal

The most common cause of apparent inefficiency or resistance to oral therapy with levothyroxine for hypothyroidism is nonadhesion. However, in some subjects in whom the control of hypothyroidism is extremely difficult, levothyroxine bioavailability defects should be considered. We report here the case of a 57-year-old woman with hypothyroidism that was well-controlled for the previous 6 years but suddenly presented with poor hormonal control and abdominal symptoms, despite repeatedly reporting good compliance to therapy. Adequate control of thyroid function was only obtained after intestinal giardiasis was diagnosed and treated.

A causa mais comum de aparente ineficácia ou resistência ao tratamento do hipotireoidismo com levotiroxina oral é a má adesão. No entanto, em alguns pacientes nos quais o controle do hipotireoidismo é extremamente difícil, defeitos na biodisponibilidade da levotiroxina devem ser considerados. Relatamos aqui o caso de uma mulher de 57 anos de idade com hipotireoidismo que vinha previamente bem controlado durante 6 anos, mas que, abruptamente, começou a apresentar mau controle hormonal, apesar de insistentemente relatar boa adesão ao tratamento. O controle adequado da função tireoidiana só foi possível depois que uma giardíase intestinal foi diagnosticada e tratada.

Effect of binary and ternary solid dispersions on the in vitro dissolution and in-situ rabbit intestinal absorption of gliclazide

Solid dispersion technique is widely used to improve the dissolution rate of drugs. Most investigators relied on the in-vitro characterization and considered the enhanced dissolution as an indication of improved bioavailability. The current study investigated the effects of binary and ternary solid dispersions of gliclazide with polyethylene glycol 6000 [PEG 6000] and/or pluronic F68 [PL F68] on the dissolution of gliclazide. The study also investigated the intestinal absorption in presence of solid dispersion components. The latter employed the in-situ rabbit intestinal perfusion technique. Preparation of binary solid dispersion with PEG 6000 or PL F68 significantly enhanced the dissolution rate compared to pure drug. The ternary solid dispersion of gliclazide with both polymers resulted in rapid drug dissolution with most drug being released in the first five minutes. The intestinal perfusion indicated the possibility of complete drug absorption from the small intestine. This, together with slow dissolution of pure drug suggested that the absorption of gliclazide is dissolution rate limited. The presence of PEG 6000 did not alter the intestinal absorption but PL F68 showed a trend of enhanced intestinal absorption of the drug. Ternary solid dispersion can thus provide rapid absorption due to rapid dissolution and potential increase in intestinal permeability

Ingestion of polydextrose increase the iron absorption in rats submitted to partial gastrectomy / A ingestão de polidextrose aumenta a absorção de ferro em ratos submetidos à gastrectomia parcial

PURPOSE: To investigate whether polydextrose stimulates iron absorption in rats submitted to partial gastrectomy and sham operated. METHODS: The rats were submitted to partial gastrectomy (Billroth II) or laparotomy (sham-operated control), in groups of 20 and 20 each respectively. The animals were fed with a control diet (AIN-93M) without polydextrose or a diet containing polydextrose (50g/Kg of diet) for eight weeks. They were divided into four subgroups: sham-operated and Billroth II gastrectomy and with or without polydextrose. Two animals died during the experiment. All rats submitted to gastrectomy received B-12 vitamin (intramuscular) each two weeks. The hematocrit and hemoglobin concentration were measured at the start and on day 30 and 56 after the beginning of the experimental period. At the end of the study, the blood was collected for determination of serum iron concentration. RESULTS: The diet with polydextrose reduced the excretion of iron. Apparent iron absorption was higher in the polydextrose fed groups than in the control group. The haematocrit and haemoglobin concentration were lower after Billroth II gastrectomy rats fed the control diet as compared to the polydextrose diet groups. CONCLUSION: Polydextrose increase iron absorption and prevents postgastrectomy anemia.

OBJETIVO: Investigar se a polidextrose estimula a absorção de ferro em ratos submetidos à gastrectomia parcial e sham operados. MÉTODOS: Os ratos foram submetidos à gastrectomia parcial (Billroth II) e à laparotomia (controle sham-operados) em grupos de 20 e 20 cada, respectivamente. Os animais foram alimentados com uma dieta controle (AIN-93M), sem polidextrose ou uma dieta contendo polidextrose (50g/kg de dieta) durante oito semanas. Foram divididos em quatro grupos: sham-operados e com gastrectomia BII e com ou sem polidextrose. Dois animais morreram durante o experimento. Todos os ratos com gastrectomia receberam vitamina B-12 (intramuscular) a cada duas semanas. O hematócrito e a hemoglobina foram dosados no início e nos dias 30 e 56 após o início do período experimental. No final do estudo, o sangue foi coletado para determinação da concentração de ferro sérico. RESULTADOS: A dieta com polidextrose reduziu a excreção de ferro e a absorção de ferro aparente foi maior nos grupos alimentados com polidextrose do que no grupo controle. As dosagens de hematócrito e hemoglobina foram menores em ratos com gastrectomia alimentados com a dieta controle em relação aos grupos de dieta com polidextrose. CONCLUSÃO: A polidextrose aumenta a absorção do ferro e previne a anemia pós-gastrectomia.

Intestinal permeability assessed by 51Cr-EDTA in rats with CCl4 - induced cirrhosis / Permeabilidade intestinal ao 51-Cr-EDTA em ratos com cirrose induzida por CCl4

CONTEXT: The straight relationship between cirrhosis and impaired intestinal barrier has not been elucidated yet. OBJECTIVES: To verify 51Cr-EDTA-intestinal permeability in rats with CCl4-induced cirrhosis and controls. METHOD: Fifty male Wistar rats weighing 150-180 g were separated in three groups: 25 animals received CCl4 0.25 mL/kg with olive oil by gavage with 12 g/rat/day food restriction for 10 weeks (CCl4-induced cirrhosis); 12 received the same food restriction for 10 weeks (CCl4-non exposed). Other 13 rats received indomethacin 15 mg/kg by gavage as positive control of intestinal inflammation. RESULTS: The median (25-75 interquartile range) 51Cr-EDTA-IP values of cirrhotic and CCl4-non exposed rats were 0.90 percent (0.63-1.79) and 0.90 percent (0.60-1.52) respectively, without significant difference (P = 0.65). Animals from indomethacin group showed 51Cr-EDTA-IP, median 7.3 percent (5.1-14.7), significantly higher than cirrhotic and CCl4-non exposed rats (P<0.001). CONCLUSION: This study showed the lack of difference between 51Cr-EDTA-intestinal permeability in rats with and without cirrhosis. Further studies are necessary to better clarify the relationship between intestinal permeability and cirrhosis.

CONTEXTO: A relação direta entre cirrose e alterações na barreira intestinal ainda não foi devidamente esclarecida. OBJETIVO: Verificar a permeabilidade intestinal ao 51Cr-EDTA em ratos com cirrose induzida por tetracloreto de carbono (CCl4) e controles. MÉTODO: Cinquenta ratos Wistar machos pesando 150-180 g foram separados em três grupos: 25 animais receberam CCl4 0,25 mL/kg diluído em óleo de oliva por gavagem com restrição dietética de 12 g/rato/dia por 10 semanas (grupo cirrose induzida por CCl4); 12 receberam a mesma restrição dietética por 10 semanas (grupo não exposto ao CCl4). Outros 13 ratos receberam indometacina 15 mg/kg por gavagem como controle positivo de inflamação intestinal. RESULTADOS: A mediana (intervalo interquartil 25-75) dos valores de permeabilidade intestinal ao 51Cr-EDTA dos grupos cirrose induzida por CCl4 e não exposto ao CCl4 foram 0,90 por cento (0,63-1,79) e 0,90 por cento (0,60-1,52), respectivamente, sem significância estatística (P = 0,65). Os animais do grupo indometacina apresentaram uma mediana de permeabilidade intestinal ao 51Cr-EDTA de 7,3 por cento (5,1-14,7), sendo significativamente maior do que os grupos cirrose induzida por CCl4 e não exposto ao CCl4 (P<0,001). CONCLUSÃO: Este estudo não demonstrou diferenças entre a permeabilidade intestinal ao 51Cr-EDTA em ratos com e sem cirrose. Mais estudos são necessários para melhor esclarecer a relação entre a permeabilidade intestinal e cirrose.

O efeito do consumo crônico de etanol na absorção duodenal de ferro em camundongos / The effect of chronic ethanol consumption on duodenal absorption of iron in mice

CONTEXTO: Os indivíduos alcoolistas apresentam aumento da concentração hepática de ferro e os mecanismos responsáveis por essa deposição são ainda desconhecidos. Apesar da extensa literatura existente sobre a absorção de ferro nos diferentes estados patológicos, os efeitos do consumo prolongado do etanol não estão totalmente esclarecidos. OBJETIVOS: Determinar a absorção de ferro no duodeno de camundongos após consumo prolongado de etanol, com relação ao controle de camundongos normais. MÉTODOS: Foram utilizados 10 camundongos machos da raça Swiss, distribuídos em dois grupos: grupo 1 (n = 5) - controle e grupo 2 (n = 5) - consumo de água com etanol, como única fonte de água ofertada. Os animais foram acompanhados durante 120 dias. Decorrido esse período, isolou-se o duodeno e pela parte oral de cada alça, infundiu-se solução salina contendo ascorbato de ferro II na concentração de 0,016 mg de ferro elemento. O efluente foi coletado nos tempos 20, 40, 60, 80, 100 e 120 minutos. Os resultados foram analisados pelo teste Mann-Whitney e Kruskal-Wallis, com significância para P<0,05. RESULTADOS: Não houve diferença entre a absorção duodenal de ferro dos grupos 1 e 2, assim como na curva de absorção. CONCLUSÕES: Conclui-se que, nas condições deste experimento, o consumo prolongado de etanol não alterou a absorção de ferro.

CONTEXT: Alcoholists present an increase of iron hepatic concentration, although the responsible mechanisms for this deposition are still unknown. Despite the extensive literature related on the iron absorption in different pathological conditions, the effect of chronic ethanol consumption are still not conclusive and not completely understood. OBJECTIVE: To verify the effect of chronic ethanol ingestion on duodenal absorption of iron. METHODS: Ten male Swiss mice were divided into two groups: group 1 (n = 5) - control, and group 2 (n = 5) - water consumption with ethanol, as only water source. The animals were followed during 120 days. After this period, the duodenum was isolated and saline solution containing ascorbate of iron II in the 0,016 concentration of mg of iron element was infused. The effluent was collected in times 20, 40, 60, 80, 100 and 120 minutes. The results were analyzed by Mann-Whitney and Kruskal-Wallis tests. The significance was set for P<0.05. RESULTS: No difference was found between iron absorption as well as iron absorption curves in groups 1 and 2. CONCLUSION: The chronic consumption of ethanol did not alter iron absorption.

Impact of zinc deficiency on vibrio cholerae enterotoxin-stimulated water and electrolyte transport in animal model.

The effect of zinc deficiency on the function of the intestine to absorb water and electrolytes was studied in animal models, stimulated by Vibrio cholerae enterotoxin. Sprague-Dawley rats, used in the study, were divided into four groups: Zinc-deficient, ad libitum zinc-fed control, zinc weight-matched control, and zinc-deficient acutely-repleted. 14C-labelled polyethylene glycol solution was used for measuring the absorption capacity of the small intestine. Significantly lower absorption of water and sodium per cm of the intestine was observed in the zinc-deficient animals compared to the ad libitum zinc-fed control animals (p < 0.01). An improved absorption capacity was equally observed in the zinc-deficient acutely-repleted animals and ad libitum zinc-fed control group. The zinc-deficient animals showed four times greater cholera toxin-induced net secretions of water and sodium compared to the ad libitum zinc-fed group (p < 0.01), while a 40% reduction was observed in the zinc-deficient acutely-repleted group. The results suggest that zinc deficiency is associated with reduced absorption of water and electrolytes and increased secretion of the same stimulated by cholera toxin.

Efeitos da desnervação intrínseca do jejuno após enterectomia extensa na síndrome do intestino curto em ratos / Effects of intrinsic denervation of the jejunum after extensive enterectomy in the rat bowel syndrome

OBJETIVO: Investigar em ratos Wistar as respostas adaptativas da mucosa em conseqüência da desnervação intrínseca do jejuno após ressecção intestinal extensa. MÉTODOS: Utilizaram-se 30 ratos distribuídos em três grupos segundo o procedimento realizado: C (controle), R (ressecção intestinal) e D (ressecção intestinal e desnervação intrínseca do jejuno). Posteriormente foi avaliado o ganho de peso e realizado estudos morfométrico da mucosa intestinal. RESULTADOS: Os animais do grupo D apresentaram ganho ponderal consideravelmente maior do que os do grupo R (D=312,2±21g e R=196,7±36,2g). A contagem neuronal mostrou diminuição na população de neurônios mientéricos no grupo D (344,8±34,8 neurônios/mm de jejuno) em relação aos outros grupos (R=909,0±55,5 e C=898,5±73,3). A área do epitélio da mucosa jejunal foi maior no grupo D (10,8±4,3mm²) em comparação aos grupos R (7,3±3,9mm²) e C (5,8±3,0mm²). O índice de proliferação celular epitelial da mucosa foi maior no grupo D (48,7 por cento), em relação aos grupos R (31,9 por cento) e C (23,6 por cento). CONCLUSÕES: O modelo experimental mostrou-se eficaz em melhorar o ganho ponderal dos animais submetidos à ressecção intestinal extensa, provocando intensificação da resposta hiperplásica da mucosa, a qual provavelmente levou a aumento da superfície de absorção de nutrientes. Abrem-se boas perspectivas para novas abordagens cirúrgicas para a síndrome do intestino curto.

Absorption and metabolism of paracetamol in rats drinking high concentration of arsenic.

The effect of chronic intake of arsenic on the plasma concentration of paracetamol in rat was investigated. Rats received saline water with or without arsenic trioxide (10 mg/kg body weight/day) by gastric gavage on every alternate day for 29 days. A single dose of paracetamol (range 10 infinity 40 mg/kg body weight) was administered by gastric gavage to both arsenic-untreated and -treated rats on 30(th) day. Rats were sacrificed after 30 min and the amounts of free paracetamol and its metabolites in plasma were estimated using isocratic reverse-phase High Performance Liquid Chromatography (HPLC). Arsenic toxicity reduced the plasma concentration of paracetamol to 53 - 65% when compared with the rats received no added arsenic. There were maximum 67.4 and 76.9% inhibitions of sulfate and cysteine conjugations of paracetamol respectively. But arsenic had no effect on glucuronide and mercapturate conjugations. Both liver and small intestine showed increased accumulation of arsenic and decreased amount of glutathione in arsenic-treated rats. This study suggests that chronic ingestion of arsenic inhibit the absorption and metabolism of paracetamol.

Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil.

To examine the association of intestinal barrier function with vitamin A deficiency and whether supplementation of micronutrients improves intestinal function and/or linear growth, height-for-age z-score (HAZ), concentrations of serum retinol and zinc, and intestinal permeability were determined in a cross-sectional sample of 75 children in northeastern Brazil. Effects of vitamin A and supplementation of zinc on intestinal permeability and growth were also determined comparing results before and after treatment in 20 children and age-matched controls. Lactulose:mannitol (L/M) permeability ratios inversely correlated with serum retinol concentrations (r = -0.55, p < 0.0005). Increased L/M permeability ratios with reduced concentrations of serum retinol were predominantly attributable to lower absorption of mannitol (r = 0.28, p = 0.02). L/M permeability ratios (p = 0.001) and HAZ scores (p = 0.007) improved with supplementation. It is concluded that impaired intestinal barrier function and linear growth shortfalls improve following supplementation of vitamin A and zinc in this setting.

The use of protein hydrolysate improves the protein intestinal absorption in undernourished mice infected with Schistosoma mansoni

Patients residing in endemic areas for schistosomiasis in Brazil are usually undernourished and when they develop the hepatosplenic clinical form of the disease should usually receive hospital care, many of them being in need of nutritional rehabilitation before specific treatment can be undertaken. In the mouse model, investigations carried out in our laboratory detected a reduced aminoacid uptake in undernourished animals which is aggravated by a superimposed infection with Schistosoma mansoni. However, in well-nourished infected mice no dysfunction occurs. In this study, we tried to improve the absorptive intestinal performance of undernourished mice infected with S. mansoni by feeding them with hydrolysed casein instead of whole casein. The values obtained for the coefficient of protein intestinal absorption (cpia) among well-nourished mice were above 90 percent (either hydrolysed or whole protein). In undernourished infected mice, however, the cpia improved significantly after feeding them with hydrolysed casein, animals reaching values close to those obtained in well-nourished infected mice

Effect of omeprazole on plasma zinc levels after oral zinc administration.

BACKGROUND: The intestines are the major site of zinc absorption and excretion. Reduced gastric acid secretion and elevated gastric pH is an important factor affecting intestinal mineral absorption. METHODS: Gastric pH and volume, and basal and maximal acid outputs were measured in 14 healthy volunteers. Plasma zinc levels were then measured at baseline and 1, 2, 3 and 4 hours after oral administration of 300 mg zinc sulfate. The experiment was repeated after omeprazole administration (60 mg/day orally) for 7 days. RESULTS: Omeprazole administration significantly increased fasting gastric pH (5.5 versus 2.4; p < 0.001). Mean basal gastric acid output (1.6 vs 8.0 mEq/h; p < 0.001) and maximal acid output (20.6 vs 106.6 mEq/h; p < 0.001) decreased after omeprazole administration. Zinc absorption decreased after omeprazole administration (141 [34] mg/dL/h) compared with pre-omeprazole values (245 [35]; p < 0.01). CONCLUSION: Suppression of gastric acid secretion by omeprazole reduces intestinal absorption of zinc.

Effect of Salmonella typhimurium toxin on the expression of rabbit intestinal functions.

BACKGROUND & OBJECTIVES: Infection by Salmonella Typhimurium is one of the leading causes of intestinal dysfunction, however the underlying mechanism of this effect is largely unknown. Hence the effect of enterotoxin secreted by Salmonella Typhimurium-(S-LT) was studied on D-glucose absorption and brush border enzymes in rabbit ileum. mRNA levels encoding these proteins were also analysed. METHODS: Adult male New Zealand white rabbits were used. The polymyxine B extract of enterotoxin obtained from Salmonella Typhimurium was tested for the presence of enterotoxicity by rabbit ileal loop test. D-glucose uptake by ileal tissue was measured by the tissue accumulation method. Intestinal brush border membranes were isolated and the effect of S-LT on various brush border enzymes studied. RESULTS: S-LT significantly inhibited (P < 0.01) the absorption of Na+ dependent D-glucose uptake but had no effect on Na+ independent sugar uptake in rabbit ileum. The activities of brush border sucrase (72% P < 0.001) and lactase (47% P < 0.01) and alkaline phosphatase (43% P < 0.01) were also significantly reduced in infected animals as compared to the controls. Northern blot analysis revealed that mRNA levels encoding Na+ glucose co-transporter (SGLT1), brush border lactase and sucrase activities were unaffected in Salmonella infected rabbit ileal loops. INTERPRETATION & CONCLUSION: The findings suggest that the intestinal dysfunctions observed in Salmonella infection are unrelated to mRNA expression encoding Na+ glucose co-transporter and brush border enzyme proteins in rabbit ileum.

Effects of endosulfan on intestinal functions in protein-malnourished rats.

In rats fed 18% protein diet, administration of endosulfan (2mg/kg body weight daily for 7 days) significantly decreased the brush border sialic acid and increased the hexoses contents. The intestinal uptake of glucose was increased while that of glycine and calcium was reduced. Brush border enzymes and lipids were not affected. However, in protein malnourished rats (fed 8% protein) exposed to endosulfan, brush border sucrase and peptidase activities were enhanced, while alkaline phosphatase activity was decreased compared to untreated malnourished animals. Membrane sialic acid content was low while fucose and cholesterol levels were augmented in endosulfan fed malnourished animals. The uptake of glucose and glycine was elevated under these conditions. These results Suggest that the nutritional status of the animals has an important bearing on thc susceptibility of intestinal tissue to endosulfan toxicity in rats.

Effects of depot medroxyprogesterone acetate on the calcium metabolism of adult ovariectomized rats

This paper describes experiments designed to test the effect of depot medroxyprogesterone acetate (DMPA) on calcium metabolism of adult ovariectomized rats. The 24 animals were randomly assigned to control or treated groups. Treated rats received 15 mg of DMPA i.m. per week, during four or twelve weeks. Controls received solvent alone. The variables characterizing the metabolism of Ca (daily rates of intestinal absorption and excretion, bone accretion and resorption and the sizes of the exchangeable pools and their rate constants) were measured with the aid of 45Ca according to Aubert and Milhaud. No effects were observed at four weeks of treatment. After twelve weeks, treatment produced serum levels of 46.5 ñ 5.6 nmoles of medroxyprogesterone/L, reduction of bone turnover (Ca accretion and resorption rates) and of the size of the slow exchanging Ca compartment. The increase in true Ca intestinal absorption was compensated by the increased endogenous fecal Ca excretion. The mass of body Ca was not affected by treatment.

Enhancement of sodium in relation to absorption in malnourished rats: hyperosmolar challenge

Two experimental models were tried in young molnourished rats in order to study effect of an hyperosmolar challenge in the small intestine on the bi-diretcional fluxes of sodium. Wealning rats were with emergy restricted diets. In model I 1mL of NaCl900 mOsm/kg was introduced in the smal intestine of the rats left from 5 up to 70 min, in order to determine the moment of higher net Na secretion, which occurred at 10 min. In model II, the bi-directional fluxes of Na and Cl- were studied using Na Cl or mannitol 900 mOsm/kg under the effect of mecholil, atropine or 2-4 dinitrophenol, for 10 min. Mecholil decreased the Na absorption enhancing the net secretion. Control rats were used as reference. In the restricted diets animals occurred an increase of the net secretion stimulated by NaCl 900 mOsm/kg, and this effect was enhanced by mecholil. It is suggested that in malnutrition there is an impairment in Na- intestinal absorption.

Practical issues in geriatric psychopharmacology.

In summary, clinicians must consider multiple changes in the absorption, distribution, metabolism, and elimination of psychotropic drugs among older patients. Lower starting doses (often one-quarter to one-half the usual adult dose) is advisable, with slow dosing adjustments (no sooner than every 5 to 7 days) as needed. The time required to see steady-state therapeutic levels, or for elimination of most medications, are substantially longer in the elderly. One must consider the potential for drug-drug interactions, as well as anti-cholinergic or other side-effects, when prescribing a regimen. Changes should be made slowly, changing only one variable at a time, in order to achieve best results.