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Biomedical subjects

S Bustamante

Publications and source records attributed to S Bustamante.

At least 19 recordsLinked to original sources

A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission.

1. The present study was designed to characterize the adenosine receptors involved in the relaxation of the pig intravesical ureter, and to investigate the action of adenosine on the non adrenergic non cholinergic (NANC) excitatory ureteral neurotransmission. 2. In U46619 (10(-7) M)-contracted strips treated with the adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI, 10(-6) M), adenosine and related analogues induced relaxations with the following potency order: 5'-N-ethylcarboxamidoadenosine (NECA) = 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA) = 2-chloroadenosine (2-CA) > adenosine > cyclopentyladenosine (CPA) = N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) = 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoaden os ine (CGS21680). 3. Epithelium removal or incubation with indomethacin (3 x 10(-6) M) and L-N(G)-nitroarginine (L-NOARG, 3 x 10(-5) M), inhibitors of prostanoids and nitric oxide (NO) synthase, respectively, failed to modify the relaxations to adenosine. 4. 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10(-8) M) and 4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 3 x 10(-8) M and 10(-7) M), A1 and A2A receptor selective antagonists, respectively, did not modify the relaxations to adenosine or NECA. 8-phenyltheophylline (8-PT, 10(-5) M) and DPCPX (10(-6) M), which block A1/A2-receptors, reduced such relaxations. 5. In strips treated with guanethidine (10(-5) M), atropine (10(-7) M), L-NOARG (3 x 10(-5) M) and indomethacin (3 x 10(-6) M), both electrical field stimulation (EFS, 5 Hz) and exogenous ATP (10(-4) M) induced contractions of preparations. 8-PT (10(-5) M) increased both contractions. DPCPX (10(-8) M), NECA (10(-4) M), CPCA, (10(-4) M) and 2-CA (10(-4) M) did not alter the contractions to EFS. 6. The present results suggest that adenosine relaxes the pig intravesical ureter, independently of prostanoids or NO, through activation of A2B-receptors located in the smooth muscle. This relaxation may modulate the ureteral NANC excitatory neurotransmission through a postsynaptic mechanism.

Adenosine

Vasorelaxant effect of the analgesic clonixin on rat aorta.

1. A novel vasorelaxant effect of clonixinate of L-lysine (Clx), analgesic and anti-inflammatory, was studied in rat aortic rings. 2. Clx completely relaxed aortic rings contracted by KCl 70 mM and together with its analog flunixin exhibited lesser potency but equal efficacy than verapamil. In comparison, indomethacin, which is a more potent cyclo-oxygenase inhibitor relaxed only about 40% of the maximal contraction of aortic rings. 3. Furthermore, Clx antagonized Ca2+ dependent aortic contraction and BAY K-8644 induced aortic contraction suggesting its calcium antagonist character. 4. From these results it can be concluded that the hypotensive effect seen in rats in vivo after Clx i.v. injection arises because of vasodilatory effect of Clx and gives further support to the proposal that the pharmacological mechanism of action of Clx should be calcium antagonism.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

[Depression in the early course of schizophrenia].

Depressive syndromes in schizophrenia are reported in the prodromal stage of the early course, during the first or later psychotic episodes, but also after the fading out of an acute episode and as a precursor of relapse. According to these multiple conditions several explanations also exist as to how to understand depression in schizophrenia. Some authors interpret it as an elementary part of the schizophrenic symptomatology, which is only masked by positive symptoms (revealed depression). However, it can also be understood as a reactive depression or as caused by neuroleptic treatment, as part of the negative syndrome or as co-morbidity. In the ABC-Schizophrenia-Study, depression in the early course was analysed for patients in their first psychotic episode at index admission and an ICD-9 diagnosis of schizophrenia (ICD 295). In 81% of this sample depression was observed, beginning on average 4.3 years prior to index admission. In 42% of the patients depression began in the prepsychotic phase. In 18% the positive and the depressive syndrome developed within one month, and in 21% depression started after the first positive symptom occurred. We could only observe a clear sequence of depressive, negative and positive symptoms in the subgroup characterised by prepsychotic depression. A clear order of negative and positive symptoms was not observed in the other groups. Patients without depression in the early course have lower symptom levels at index admission. They present less positive symptoms (CATEGO-subscore DAH), fewer behavioural disturbances (subscore BSO) and also lower scores of non-specific symptoms (subscores SNR and NSN). More than 80% of the patients with depression in the early course also had a simple depression (as defined by the CATEGO-syndrome SD). Contrary to this, only 20% of the patient group without depression in the early course have positive SD values. Comparable percentages of males and females have depression in the early course, but in females depression begins more frequently in the prepsychotic phase, whereas in the male subgroup it more often starts postpsychotically, i.e. after the onset of the first psychotic symptom.

Adult

Population study of horizontal cells in live carp retinas using microinjections of horseradish peroxidase.

In order to randomly sample horizontal cells (HCs) of carp retina, horseradish peroxidase (HRP) was delivered into axon terminals by means of vitreally inserted micropipettes in live fish. Survival time was extended to several hours to permit label diffusion into HC somata. A function measuring the relative complexity of cell contours was defined in order to help classify HCs according to their morphological types. The histogram of measurement from 313 HCs showed three modes fitting normal distributions. The numbers of cells in each group were 267, 36 and 10, respectively, representing a relative population of 85.3% H1s, 11.5% H2s and 3.2% H3s. It is suggested that cone HC somata are extended in a monolayer constituted by predominant type-H1 with interspersed groups of both type-H2 and type-H3 cells.

Animals

Fast activity and oscillatory potential of carp retina in the frequency domain.

There are two kinds of fast activity in the ERG: fast retinal potentials (FRP), an irregular series of spiky wavelets and oscillatory potentials (OP), a rhythmic sequence of events. Corneal ERG from nine intact young carps, evoked by extended pulses of diffuse white light under mesopic adaptation, displayed two different groups of wavelets related to ON and OFF, respectively. Stimulation and recording conditions were established to permit separate Fourier analysis of both groups of wavelets. Power distributions of normalized ON spectra showed both a wide dispersion and a high inter-subject variability. All normalized OFF spectra showed, instead, components within a narrow band from 52 to 56 Hz, most of them maximum relative power peaks. It is concluded that FRP originating in highly labile sources dominate ON fast activity, while the predominant OFF fast activity are OP originating in a stable discrete source.

Animals

Response of activity of jejunal disaccharidases and pancreatic amylase in young and middle-aged rats to a high carbohydrate diet.

Sprague-Dawley rats fed a nonpurified diet from weaning to 3 mo (young) or 12 mo (middle aged) of age were fed a low (5 cal%) starch (LST) purified diet for 2 wk. They were then fed a high (70 cal%) starch (HST) purified diet for up to 4 wk. Body weights of both age groups were greater in rats fed the LST than in those fed nonpurified diet throughout. The young, but not the middle-aged, group continued this gain while consuming HST. The levels of activity of intestinal disaccharidases of upper (proximal one-third) and lower (middle one-third) jejunum, and pancreatic alpha-amylase were lower in rats fed LST diet in both age groups than in rats fed HST. Similar increases of specific (per protein or DNA) activity were observed in both age groups throughout the first three (disaccharidase) to four (pancreatic alpha-amylase) days of feeding HST. Values of specific activity of the middle-aged group returned to initial levels with continued feeding of HST. In contrast, values in the young group tended to plateau (disaccharidases) or continued to increase (alpha-amylase). Differences in adaptability over 1 mo were most dramatic for alpha-amylase and sucrase, but negligible for lactase.

Aging

Chronic effects of an alpha-glucosidase inhibitor (Bay o 1248) on intestinal disaccharidase activity in normal and diabetic mice.

Bay o 1248 is a potent alpha-glycosidase inhibitor that reduces postprandial hyperglycemia when administered p.o. with sucrose or maltose. The compound binds to and competitively inhibits the alpha-disaccharidases and is also readily absorbed across the intestinal mucosa. To evaluate its effect on the activity of disaccharidases and on metabolic control, groups of obese diabetic mice (C57BLKsJ db/db) were given the drug for periods of 3, 7 and 84 days as a drug food mixture (5 or 10 mg/100 g of food). Nondiabetic mice of the same strain were dosed for 3 and 7 days. The drug did not influence body growth, food intake or fasting blood glucose. However, urine glucose excretion was significantly decreased at the higher dose in the diabetic mice. The drug had no effect on the protein content of jejunum (proximal and middle thirds) or ileum (distal third) of the small intestine. The activity of sucrase and maltase was significantly decreased in practically all segments of the small intestine in both diabetic and nondiabetic mice. These changes were evident after 3 days of drug administration. Lactase was not affected by the drug. The mechanism underlying these changes, although unclear, is of significant interest and deserves further investigation.

1-Deoxynojirimycin

Effect of a high-dextrose diet on sucrase and lactase activity in jejunum of obese mice (C57BL/6J obob).

The activities of intestinal disaccharidases are known to be responsive to changes in the dietary intake of carbohydrates in the adult rat. Little is known, however, regarding the activities of these enzymes in obese subjects and how they are affected by differing carbohydrate intakes. To evaluate the effect of carbohydrate intake on the activity of intestinal disaccharidases in obesity, we used the genetically obese mouse C57BL/6J obob as an experimental model. Representing an example of early-onset obesity and mature-onset diabetes, this animal is characteristically hyperinsulinemic and hyperglycemic. Groups of obese mice and lean littermates were fed for 7 weeks equal amounts of either high-dextrose or low-dextrose isoenergetic diets. Sucrase, maltase, and lactase activities were measured on intestinal homogenates from the proximal and middle portions of the jejunoileum (upper and lower jejunum). Results were expressed as activity per tissue protein as well as total activity. Obese mice were found to have consistently greater total activity of both sucrase and maltase than their lean littermates, mostly as a result of increased intestinal size. Total lactase activity, however, was similar in the upper jejunum in both obese and lean mice, largely related to a decreased specific activity in obese mice. All mice fed the high-dextrose diet had significantly increased total activity of all disaccharidases studied when compared to the low-dextrose-fed animals, except for the lactase activity in the lower jejunum, where no differences were found in either group. Increases in activity related to high carbohydrate intake were a result of increases in specific activity.

Animals

Precocious increase of sucrase activity by carbohydrates in the small intestine of suckling rats. I. Significance of the stress effect of sugar-induced diarrhea.

In this paper, we analyze the factors involved in the precocious increase of sucrase activity evoked by the early feeding of sucrose in suckling rats, and particularly, the role of diarrhea and stress in this phenomenon. Ten-day-old rats were removed from their mothers and gavage fed for 4 days at 3-h intervals either a basic low carbohydrate milk formula (10.8% fat, 8% protein, 1.4% carbohydrate; all by weight/volume) or basic low carbohydrate milk with: lactose (13%), fructose (13%), or Polycose (2%, 6%, or 13%); all formulas were isocaloric. Feeding the formula containing fructose or high (13%) Polycose led to diarrhea and evoked a concurrent increase of small intestinal sucrase activity. In further experiments, 11-day-old rats were fed the basic formula, the lactose (13%), the fructose (13%), and a sucrose (13%) formula for 8 h between 2 a.m. and 10 a.m. Also, 10-day-old rats were fed 0.5 ml of a solution of 5% mannitol in water while nursing with their mothers. The serum corticosterone levels were substantially increased within 8 h after the initiation of feedings with sucrose and fructose milks and the mannitol solution. The mannitol-fed rats also developed diarrhea within a day in association with a marked increase in sucrase activity. We conclude that a precocious increase of sucrase activity in the small intestine of suckling rats by dietary sugars is not caused by substrate induction, but is mainly due to the effect of stress. The stress is caused by diarrhea which is evoked by the feeding of indigestible and/or unabsorbable amounts of sugar.

Age Factors

Precocious increase of sucrase activity by carbohydrates in the small intestine of suckling rats. II. Role of digestibility of sugars, osmolality, and stomach evacuation in producing diarrhea.

The mechanisms of carbohydrate-induced diarrhea in suckling rats were investigated with respect to osmolality and type of sugar in the milk. Groups of 12-day-old rats were gavage fed either a basic low carbohydrate milk formula [10.8% fat; 8% protein; 1.4% carbohydrate (weight/volume)] or basic formula with added sucrose, fructose, lactose, or glucose polymers, all as 13% (weight/ volume). All formulas were isocaloric. Their corresponding osmolalities were 278, 645, 1,130, 617, and 349 mOsmol/kg, respectively. Gastric evacuation of water-soluble materials from formulas containing sucrose, fructose, or glucose polymers was significantly slower than the gastric evacuation of the basic formula and the formula that contained lactose. The net fluid absorption from the small intestine was significantly greater from the basic and lactose-containing formulas when compared with sucrose, fructose, or glucose polymer-containing formulas. When the synthetic milk formulas were placed directly into the isolated jejunoileum in vivo, the formulas of higher osmolality (fructose, sucrose, and lactose) caused water flux into the intestine at 60 min, while digestion of the lactose formula reversed the water flux within 120 min. We conclude that the type of added sugar is a decisive factor in gastric evacuation, and that water flux into and out of the intestine is significantly affected by the osmolality and rate of digestion and absorption of the carbohydrate in the formula; these differences among sugars may play a significant role in the etiology of diarrhea.

Animals

Dietary regulation of intestinal lactase and sucrase in adult rats: quantitative comparison of effect of lactose and sucrose.

To characterize the mechanisms leading to dietary evoked increases of lactase and sucrase activities by carbohydrates, we performed a quantitative comparison of the effects of lactose and sucrose on the corresponding disaccharidases in the jejunum of 2-month-old rats. For 7-10 days the rats were fed a low-starch (5 cal%), high-fat (73 cal%) diet, and for various periods of time (3-72 h) were given an isocaloric sucrose or lactose (20, 40, or 70 cal%) diet. Lactase and sucrase activities in jejunal homogenates were significantly increased within 3 h after the initial feeding of the sucrose (40 cal%) diet. After 3 h of feeding the sucrose diet, sucrase activity gradually increased and reached its maximum at 24 h, whereas lactase activity did not exhibit further change. Increased intake of sucrose led to an increase of lactase and sucrase activity. Within a range of doses of digestible amounts of lactose, the effect of diet containing lactose on these disaccharidase activities was similar to the effect of the diet containing sucrose. This similarity suggests the important role of the common constituent sugar, i.e., glucose. Further, analyses of response to these disaccharides along the villus-crypt axis revealed that the increase of lactase activity occurs at a more apical and broader locus of cohort of epithelial cells along the height of the villus than that of sucrase, suggesting that different mechanisms are involved in dietary regulation of lactase and sucrase.

Animals

Relation between dietary-induced increase of intestinal lactase activity and lactose digestion and absorption in adult rats.

To study the relation between dietary-induced increase of intestinal lactase activity and lactose absorption, 11-wk-old rats were fed either a high-starch (70 cal%), low-fat (7 cal%) diet or a low-starch (5 cal%), high-fat (73 cal%) diet for 7 days. Food intake and body weight changes were similar in the two dietary groups. In the first experiment, lactose absorption was studied in vivo after oral administration of 600 mg lactose (10% solution in water with added [3H]PEG) to rats fasted for 16 h. Groups of rats were killed at time 0 and at 1-h intervals for the next 3 h. Lactase activity and lactose absorption were significantly higher (P less than 0.01) in the high-starch group than in the low-starch group. In the subsequent experiment, 9-wk-old rats were fed the two isocaloric diets for 3 days. By use of the everted sac technique, we have demonstrated a significantly higher absorption of monosaccharides from lactose in the high-starch diet group; also, glucose transport was higher in the high-starch diet-fed animals. When Tris, an inhibitor of lactase, was added into the mucosal fluid, absorption of lactose was abolished and no effect was seen on glucose absorption (in vivo and in vitro). In both experiments, significant linear regression was established between lactase activity and lactose absorption. Our results thus show that the increase in lactase activity, induced by feeding a high-starch diet to adult rats, is accompanied by an increased capacity to hydrolyze lactose and absorb the constituent monosaccharides.

Absorption

Different effect of starvation on activity of sucrase and lactase in rat jejunoileum.

Activities of lactase and sucrase were determined in proximal, middle, and distal thirds of the jejunoileum of 15-wk-old male rats starved for 1, 2, and 3 days and in rats fed a high-sucrose diet for 24 h after 3 days of starvation. Sucrase activity (expressed per tissue protein or DNA as well as per intestinal segment) showed a progressive decrease during starvation in proximal and middle segments but not in the distal segment. Lactase activity expressed per tissue protein or DNA in all segments increased significantly. This was obviously due to the loss of tissue protein and DNA because total lactase activity per segment did not change. Refeeding the sucrose diet produced an increase of sucrase activity without influencing lactase activity. In serial tissue homogenate of jejunal villus-crypt columns prepared using cryostat sectioning, it was shown that, during starvation, activity of lactase (specific and total) increased in the upper and middle villus. Sucrase activity (specific and total) during starvation decreased and after refeeding increased in the lower and middle villus.

Animals

Dietary-induced rapid decrease of microvillar carbohydrase activity in rat jejunoileum.

Activities of several carbohydrases and peptidases were determined in proximal, middle, and distal thirds of the jejunoileum of female 16-wk-old rats that were fed a high-starch (70 cal%), low-fat (7 cal%) diet for 2 wk and also in rats that (after this introductory period) were fed an isocaloric low-starch (5 cal%), high-fat (73 cal%) diet for 1, 2, and 3 days. The body weight changes, food intake, amount of protein per intestinal segment, and rate of enterocyte migration were practically the same in all groups during these experimental periods. The decreased intake of starch was followed by a rapid decrease (40-80%) of carbohydrases (lactase, sucrase, maltase, and glucoamylase) within the first 24 h in total intestinal homogenates--and as studied in cryostat serial sections--in all regions of the jejunal villus-crypt columns, and mainly in proximal and middle segments. In contrast, the activities of leucylnaphthylamidase and L-phenylalanylglycine hydrolase exhibited little change except for a slight temporary decrease of activity on the 1st day in the proximal segment only (25-30%). Thus these data show that a decrease of starch content in an isocaloric diet evokes a rapid decrease in the activity of microvillar carbohydrases and that activity of these enzymes both in mature and immature enterocytes is capable of reacting to a change (decrease) of dietary carbohydrate content.

Animals