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Biomedical subjects

E Mussini

Publications and source records attributed to E Mussini.

At least 19 recordsLinked to original sources

The effects of S(-) and R(+) sulpiride, metoclopramide, cisapride and domperidone on the small intestine suggest DA2-receptors are involved in the control of small intestinal transit time in rats.

To study the effect of intraperitoneal S(-)sulpiride (1-15 mg/kg), R(+)sulpiride (5-10 mg/kg), metoclopramide (1-15 mg/kg), cisapride (10 mg/kg) and domperidone (5-10 mg/kg) on intestinal progression, rats were given the test drug followed by oral lactulose. Their hydrogen excretion was used to calculate the small bowel transit time (SBTT) and maximum peak time (MPT). Metoclopramide (7.5 mg/kg) had the greatest effect on SBTT (-25%), followed by S(-)sulpiride and domperidone. S(-)sulpiride (10 mg/kg) had the greatest activity on the MPT (-35.2%) followed by metoclopramide. R(+)sulpiride and cisapride did not modify SBTT and MPT. In conclusion S(-)sulpiride is the isomer active on intestinal transit and DA2-receptors seem important targets in the modulation of intestinal progression, since S(-)sulpiride, metoclopramide and domperidone are DA2-receptor antagonists, and R(+)sulpiride and cisapride are not. The H2 breath test proved a valid method for measuring the effect of drugs on the small intestine in animals.

Animals

Indomethacin-induced enteropathy: effect of the drug regimen on intestinal permeability in rats.

To set up and characterize reproducible, long-standing small intestinal inflammation in rats, animals were given three different oral regimens of indomethacin (Ind): a bolus of 10 mg/kg in water and three daily doses of 2, 4, and 8 mg/kg Ind in (a) the drinking water or (b) the standard diet. The effect of Ind on the small intestine was monitored by measuring intestinal permeability (IP). The three-day regimen seemed more suitable than a bolus dose to induce long-standing inflammatory modifications in the rat small intestine and Ind administered in the drinking water gave more consistent modifications of IP and more reproducible results than Ind in food. IP seemed a suitable tool for detecting these inflammatory changes in the small-intestinal physiology. This model could be used to assess the effect of new drugs on inflammation.

Administration, Oral

High-performance liquid chromatographic determination of desmosine and isodesmosine after phenylisothiocyanate derivatization.

A new sensitive and selective high-performance liquid chromatographic method for the analysis of desmosine and isodesmosine in human and rat tissues is described. This method requires a purification step with column chromatography, followed by precolumn derivatization phenylisothiocyanate. The reaction products are then separated by isocratic chromatography on a C18 column and quantitated by ultraviolet detection at 254 nm. The recovery of standards of both compounds added to tissue samples and analysed by this method is usually greater than 90%, and the absolute detection limit is 0.5 ng for both compounds. The method is sensitive enough to measure both substances in tissue fragments of 30 mg of wet mass, which means that it can be used to study elastin in small human biopsies.

Animals

Effect of bile salts on carbonic anhydrase from rat and human gastric mucosa.

Gastric carbonic anhydrase (CA) is believed to play an important role related to cytoprotection, and duodenogastric reflux of bile salts (BS) is suspected of having a causal role in many pathologic conditions. Thus, we decided to investigate the effect of free and conjugated BS on human and rat gastric CA activity. Cholate exerted the most potent inhibitory activity on both human (I50 = 2.24 mM) and rat (I50 = 1.68 mM) gastric CA, followed by glycochenodeoxycholate and taurocholate (I50 = 6.90 mM and 13.67 mM on rat gastric CA). Human and rat whole bile produced 10-90% and 20-40% inhibition of gastric CA of the same species. Since the concentrations of free and conjugated BS tested in this study can be found in the postgastrectomized stomach, our data suggest that inhibition of gastric CA might be one mechanism contributing to the gastric mucosa damage caused by BS refluxing into the stomach after gastric surgery.

Animals

ATPase activity defects in alloxan-induced diabetic sciatic nerve recovered by ganglioside treatment.

ATPase activities were measured in sciatic nerves from rats with alloxan-induced diabetes (ALX-D) of various duration (2 wk, 5 wk, 9 wk, and 6 mo). Our data confirm that sciatic nerve Na+-K+-ATPase abnormalities are present very early in ALX-D rats, similar to results previously described in streptozocin-induced diabetic rats, spontaneously diabetic BB Wistar rats, and ALX-D rabbits. Na+-K+-ATPase activity decreased by 26-47% in ALX-D rats compared with age-matched controls. Ganglioside treatment (10 mg/kg i.p. for 10 or 30 days starting 1 wk after ALX injection) completely impeded the enzyme reduction. The effect observed at the end of either 10 or 30 days of treatment lasted greater than or equal to 1 mo. Chronic diabetic groups treated for 30 days before killing also presented normal ATPase activity at the end of treatment. Therefore, gangliosides are effective on Na+-K+-ATPase even in animals with a longer duration of diabetes. The maintenance of fairly normal ATPase activity by ganglioside treatment could mirror a more general recovery from early metabolic dysfunction and/or late structural abnormalities in diabetic nerve fibers.

Alloxan

Investigation on the fate of orally administered DEAE-dextran in rats.

The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of digestive enzymes and colonic bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, was investigated in rats. DEAE-dextran appeared to be unaffected by either enzyme activity in the small intestine or bacterial flora in the large intestine. This may be important when dealing with the pharmacological activity of DEAE-dextran and estimating its side effects. Small intestinal transit rate appeared to be accelerated by oral DEAE-dextran in rats.

Administration, Oral

Evidence of a lack of enteric side-effects induced by DEAE-dextran in man.

The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of human bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, similar to cholestyramine, was investigated in man. Colonic bacterial flora did not appear to break down DEAE-dextran, as assessed by hydrogen respiratory excretion measured in healthy volunteers. Furthermore, the blood levels of vitamin A, E and D (as 25-OH and 1,25-OH derivatives) were measured in patients treated with the DEAE-dextran in order to study the interference of DEAE-dextran on the absorption of liposoluble vitamins. With the exception of slightly depressed vitamin A levels in 3 patients out of 16, the blood values of the vitamins A, E and D were within the normal ranges, indicating that DEAE-dextran does not interfere with liposoluble vitamin absorption by the gut.

Adult

Effects of ibopamine on systemic, pulmonary and regional hemodynamics. Experimental investigations in anesthetized dogs.

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After beta-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine's cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.

Anesthesia

Effect of swimming on protein degradation: 3-methylhistidine and creatinine excretion.

The effect of 5-km noncompetitive swimming (moderate exercise) and 2-km competitive speed swimming (intensive exercise) on protein breakdown was studied in a group of young male volunteers (16-20 years old) who followed a 3-MH-free diet throughout the study. Urinary 3-MH and creatinine were determined over a period of 24 and 48 hr as an index of protein degradation. Basal 3-MH levels in the two groups of swimmers were 2.85 and 3.07 mumole X kg-1 X day-1. Mean rates of 3-MH excretion were, respectively, 1.54 and 1.94 mumole X kg-1 X day-1 for the 48 hr after moderate exercise and the 24 hr after intensive exercise. The decrease in 3-MH urinary excretion was still evident when calculated as the urinary 3-MH-to-creatinine ratio.

Adolescent

Decrease in N-acetyl-L-aspartic acid in brain of myodystrophic mice.

Brain tissue from myodystrophic mice (male 129/ReJ-dy and female 129 B6F1/J-dy) was examined to determine whether CNS abnormalities accompany the known muscular defects. Brain N-acetyl-L-aspartate, aspartate, and glutamate were significantly lower than in brain from control mice. These amino acids are only slightly reduced in brains of female dystrophic mice.

Animals

Small-bowel involvement in dermatitis herpetiformis and in linear-IgA bullous dermatosis.

In 23 patients with dermatitis herpetiformis (DH) and five patients with linear-IgA bullous dermatosis (BD), we evaluated the occurrence of histologic jejunal changes and small-bowel function abnormalities. None of the patients showed clinical signs or symptoms of malabsorption. Morphological jejunal changes consistent with gluten-sensitive enteropathy were found in 82% of DH patients and in 60% of BD patients. However, BD patients showed only mild jejunal histologic abnormalities, whereas more severe jejunal lesions were found in most patients with DH. Functional tests showed a rough correlation with the severity of the jejunal lesions, being almost completely normal in BD patients and DH patients with mild intestinal damage, whereas most of DH patients with subtotal or total villous atrophy showed abnormal d-xylose tests and folic acid assays. Lactose tolerance tests (H2 breath test and blood glucose after oral lactose load) showed no correlation with the degree of jejunal damage.

Adult

Respiratory excretion of hydrogen and methane in Italian subjects after ingestion of lactose and milk.

Lactose malabsorption, by the breath hydrogen test, and lactose intolerance (presence of symptoms) were studied in twenty healthy Italian subjects after intake of 12.5, 25 and 50 g lactose, whole milk and low-lactose milk. A rise in respiratory concentration of hydrogen (greater than 20 ppm) (malabsorption) was found in fifteen subjects after 50 g lactose, in thirteen after 25 g and in seven after 12.5 g. Symptoms generally occurred in subjects presenting a rise in respiratory hydrogen excretion, but such a rise was often observed without symptoms. Thirteen subjects presented symptoms after 50 g lactose, but only three after 25 g and one after 12.5 g. Whole milk (500 ml) gave a lower incidence of lactose malabsorption than 25 g lactose (7/20 versus 13/20, P less than 0.05) and more subjects developed symptoms (7/20 versus 3/20, NS). Low-lactose milk produced no malabsorbers and one intolerant. Breath methane was detected constantly in seven subjects and in three on some of the days of observation. Respiratory methane excretion generally appeared to be unrelated to lactose ingestion.

Adult

Phosphodiesterase activity in muscles of control and dystrophic mice.

Cyclic AMP and cyclic GMP phosphodiesterase activity was determined in the heart and in nine skeletal muscles of control and dystrophic Re 129/J male and female mice. Phosphodiesterase activity in the presence of 0.5 mM cyclic AMP of cyclic GMP was increased in all the muscle but the heart of dystrophic mice.

Animals

Blood levels of ditazole and inhibition of platelet aggregation in man.

5 healthy volunteers (3 males, 2 females, aged 22-35 years) were given 600 mg ditazole (Ageroplas) every 12 h (9.00 a.m. and 9.00 p.m.) for 10 days. Venous blood was collected from all volunteers at 9.00 and 11.00 a.m. on days 0, 3, 5, 7 and 10. The threshold concentrations of adrenaline inducing two distinct waves of platelet aggregation (Born's method) within 3 min were determined each time. Blood levels of ditazole were measured by a gas-chromatographic technique using a nitrogen-phosphorus selective detector. The average blood levels of the drug ranged between 0.84 and 1.30 microgram/ml at 9.00 a.m., and between 1.93 and 2.85 microgram/ml at 11.00 a.m. Inhibition of platelet aggregation (expressed by a grading system in arbitrary units) ranged between 1.6 and 2.0 at 9.00 a.m. and between 2.0 and 2.4 at 11.00 a.m. The fluctuations of blood levels and platelet aggregation inhibitory activity of ditazole observed during the study period were virtually the same. It is suggested that the treatment schedule used in the present study results in blood levels of ditazole sufficient to reveal any consistent alteration of platelet function in normal subjects.

Adult