Francisco Roque Carrazza

The effects of glutamine-supplemented diet on the intestinal mucosa of the malnourished growing rat

UNLABELLED Glutamine is the most abundant amino acid in the blood and plays a key role in the response of the small intestine to systemic injuries. Mucosal atrophy is an important phenomenon that occurs in some types of clinical injury, such as states of severe undernutrition. Glutamine has been shown to exert powerful trophic effects on the gastrointestinal mucosa after small bowel resection or transplant, radiation injury, surgical trauma, ischemic injury and administration of cytotoxic drugs. Since no study has been performed on the malnourished animal, we examined whether glutamine exerts a trophic effect on the intestinal mucosa of the malnourished growing rat. Thirty-five growing female rats (aged 21 days) were divided into 4 groups: control - chow diet; malnutrition diet; malnutrition+chow diet; and malnutrition+glutamine-enriched chow diet (2%). For the first 15 days of the experiment, animals in the test groups received a malnutrition diet, which was a lactose-enriched diet designed to induce diarrhea and malnutrition. For the next 15 days, these animals received either the lactose-enriched diet, a regular chow diet or a glutamine-enriched chow diet. After 30 days, the animals were weighed, sacrificed, and a section of the jejunum was taken and prepared for histological examination. All the animals had similar weights on day 1 of experiment, and feeding with the lactose-enriched diet promoted a significant decrease in body weight in comparison to the control group. Feeding with both experimental chow-based diets promoted significant body weight gains, although the glutamine-enriched diet was more effective. RESULTS The morphological and morphometric analyses demonstrated that small intestinal villous height was significantly decreased in the malnourished group, and this change was partially corrected by the two types of chow-based diet. Crypt depth was significantly increased by malnutrition, and this parameter was partially corrected by the two types of chow-based diet. The glutamine-enriched diet resulted in the greatest reduction of crypt depth, and this reduction was also statistically significant when compared with control animals. CONCLUSIONS Enteral glutamine has some positive effects on body weight gain and trophism of the jejunal mucosa in the malnourished growing rat.

Mosaic expression of brush-border enzymes in infants with chronic diarrhea and malnutrition

The chronic diarrhea observed in young malnourished infants that is sensitive to dietary glucose and other carbohydrates is associated with variable degrees of patchy mucosal villous atrophy. To explore intrinsic mucosal function in the pathogenesis of this alimentary intolerance, we have conducted an immunohistologic investigation of brush-border enzyme proteins of clinically obtained, mucosal biopsy samples. We used a group of monoclonal antibodies against human brush-border aminopeptidase, sucrase/isomaltase (SI), maltase, and lacase enzyme proteins. SI was strongly and uniformly exssed in crypts and villi of 11 of the 14 subjects; in 3 ects, however, SI was expressed in a mosaic pattern. Maltase and lactase were occasionally absent, but more commonly were expressed in a mosaic distribution. The mosaic expression of brush-border enzyme proteins has been reported in congenital enzyme deficiencies associated with normal intestinal histology. We report the mosaic expression of brush-border enzyme proteins as a functional alteration associated with a pathological lesion of the mucosa in infants with chronic diarrhea. Our observation challenges the existing concept of ontogenic regulation of brush-border enzyme activity.

A Carbon-13 Breath Test to Characterize Glucose Absorption and Utilization in Children

After the administration of a 5% glucose-water solution that contained tracer amounts of the stable nonradioactive isotope 13C, breath samples were collected from five children with congenital glucose-galactose malabsorption and five with severe small bowel villous atrophy and chronic diarrhea. The 13CO2 breath test curves of the children with the congenital malabsorption and chronic diarrhea were compared with each other and with those from three healthy children and four infants with severe malnutrition but no diarrhea. The breath test curves from the children with glucose-galactose malabsorption and from those with diarrhea were significantly different from those of the other two groups, a finding consistent with impairment of glucose absorption. The [13C]glucose breath test clearly identified the children with severe glucose malabsorption. Further studies are required to determine whether less severe cases of carbohydrate malabsorption also can be identified using the parameters described in our study.

Contribution of villous atrophy to reduced intestinal maltase in infants with malnutrition.

BACKGROUND It has been known for many years that small intestinal maltase activities are reduced in malnourished infants and in other patients with villous atrophy. The recent availability of human maltase-glucoamylase cDNA provides the opportunity to test the hypothesis that villous atrophy accounts for the reduced maltase enzyme activity in malnourished infants. METHODS Mucosal biopsy specimens obtained for clinical evaluation of malnourished infants with poor responses to refeeding were examined by quantitative methods for enzyme activity and mRNA levels. RESULTS Maltase activity and maltase-glucoamylase mRNA were reduced (approximately 45% of normal). When maltase-glucoamylase message was normalized to villin message, a structural protein expressed only in enterocytes, a preservation of maltase messages in surviving enterocytes was documented. The luminal glucose transporter-villin message was also preserved. CONCLUSIONS The loss of maltase-glucoamylase message paralleled the reduction in villin message and degree of villous atrophy. The reduced maltase-glucoamylase message also paralleled sucrase-isomaltase message, previously found to be decreased in proportion to villous atrophy of malnourished infants. The data directly demonstrate, for the first time, that the terminal steps of starch 1-4 starch digestion and sucrase-isomaltase 1-6 starch digestion are decreased in malnourished infants, secondary to villous atrophy. These data in prior and present reports suggest that mechanisms underlying the chronic villous atrophy of malnutrition should be a priority for investigations in malnourished infants with slower than expected weight gain during refeeding.

Clinical and laboratory parameters in dapsone acute intoxication

OBJECTIVE To determine the severity of dapsone (DDS) acute intoxication - an uncommon medical event - using clinical and laboratory parameters. METHODS Two hundred and seventy four patients with acute DDS intoxication, aged 1 month to 50 years old, were studied and classified into four age groups. Clinical evaluation was assessed through a protocol and correlated with laboratory parameters. Spectrophotometric methods were used to analyze methemoglobinemia (MHbp) and dapsonemia (DDSp). RESULTS The most prevalent clinical sign of intoxication was cyanosis, seen in 65.7% of the patients and in 100% of children less than 5 years of age. According to laboratory criteria, MHbp-related severe clinical intoxication was seen in 56.2% and DDSp-related occurred in 58% of the patients. Regarding DDSp, intoxication was considered severe when 20 tablets (100 mg each) were ingested, a median of 29 microg/ml. Regarding MHbp, intoxication was severe when 7.5 tablets were ingested, a median of 38% of the total Hb. The correlation between MHbp and DDSp was statistically significant (n=144, r=0.32, p<0.05). Negative correlation was observed between MHbp and the time elapsed since DDS intake (n=124, r=-0.34, p<0.001). There was also a negative correlation between DDSp and the time elapsed since DDS intake (n=63, r=-0.35, p<0.0001). CONCLUSIONS Longitudinal analysis showed a significant association between methemoglobinemia and the time elapsed after the intake (t), according to the equation: Dapsonemia = 12.9256 - 0.0682t + 0.234 methemoglobinemia

Nutritional follow-up of critically ill infants receiving short term parenteral nutrition

Few studies have tried to characterize the efficacy of parenteral support of critically ill infants during short period of intensive care. We studied seventeen infants during five days of total parenteral hyperalimentation. Subsequently, according to the clinical conditions, the patients received nutritional support by parenteral, enteral route or both up to the 10th day. Evaluations were performed on the 1st, 5th, and 10th days. These included: clinical data (food intake and anthropometric measurements), haematological data (lymphocyte count), biochemical tests (albumin, transferrin, fibronectin, prealbumin, retinol-binding protein) and hormone assays (cortisol, insulin, glucagon). Anthropometric measurements revealed no significant difference between the first and second evaluations. Serum albumin and transferrin did not change significantly, but mean values of fibronectin (8.9 to 16 mg/dL), prealbumin (7.7 to 18 mg/dL), and retinol-binding protein (2.4 to 3. 7 mg/dL) increased significantly (p < 0.05) from the 1st to the 10th day. The hormonal study showed no difference for insulin, glucagon, and cortisol when the three evaluations were compared. The mean value of the glucose/insulin ratio was of 25.7 in the 1st day and 15. 5 in the 5th day, revealing a transitory supression of this hormone. Cortisol showed values above normal in the beginning of the study. We conclude that the anthropometric parameters were not useful due to the short time of the study; serum proteins, fibronectin, prealbumin, and retinol-binding protein were very sensitive indicators of nutritional status, and an elevated glucose/insulin ratio, associated with a slight tendency for increased cortisol levels suggest hypercatabolic state. The critically ill patient can benefit from an early metabolic support.

Nutritional evaluation of children with cholestatic diseases

OBJECTIVE To characterize the type of malnutrition and to determine the usefulness of anthropometric indices in children with chronic liver disease (CLD). METHODS 11 children (aged 5 - 105 mo) with CLD underwent anthropometric evaluation when they were clinically stable. The nutritional evaluation was made by the determination of Weight/Age (W/A), Height/Age (H/A) and Weight/Height (W/E) Z scores. The nutritional evaluation by Waterlows method was also made. The fat and protein body deposits were estimated by triceps skinfold and midarm muscular circumference measurements. The analysis of the 24-hour recall was used to evaluate the quality and pattern of the feeding. RESULTS The mean weight / age (W/A = -1.18) and height / age (H/A = - 1.26) Z scores were depressed under 1 SD, whereas mean weight / height (W/H) Z score was normal. The interpretation of the nutritional evaluation by Waterlows method shows normal mean of the weight and almost normal mean of the height. Only three patients had normal triceps skinfold thickness (TSF) Z score, and the same occurred with five of them with the midarm muscular circumference. The quality and pattern of the feeding was adequate in only 4 patients. CONCLUSIONS We conclude that chronic malnutrition is common in childhood CLD and that weight/height values underestimate the degree of acute malnutrition compared with TSF thickness, most likely because of the inflated patient weight caused by organomegaly. The reduction of the triceps skinfold thickness best reflected the nutritional impairment of the patients. The quality of feeding of the patients was mostly inadequate.

In vivo study of colonic fermentation of carbohydrate in infants

Dietary carbohydrate in the colon is fermented and converted into short-chain fatty acids. We studied the fate of carbohydrate that arrives in the colon under circumstances similar to those that occur during an episode of diarrhea and determined whether a quantitative correlation exists among certain indicators of colonic fermentation of carbohydrate arriving in the large bowel. A stable-isotope method was used to estimate carbon scavenging by the colon. Fourteen infants with severe malnutrition and history of watery stools and/or increased numbers of stools in the preceding 20 days were studied. Infants underwent nasocecal intubation and a 60-min infusion of 0.5 g/kg glucose containing 5 mg/kg of 13C-glucose. Stools were assessed for carbohydrate-fermenting bacteria, acetate, glucose, and 13C abundance; blood was assessed for acetate; and breath was assessed for hydrogen. Some of the infants eliminated the infusate per anus within 30 min of the infusion (group I; n = 5), while others did so 120 min or more after the infusion (Group II; n = 9). The volume of fecal output after the intracecal infusion differed significantly between group I and group II (57 +/- 13 vs. 24 +/- 4 ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium metabolism in chronic primary hypomagnesemia

OBJECTIVES: To report three cases of primary hypomagnesemia (PH) with secondary hypocalcemia in symptomatic infants, born to consanguineous parents, and to present Mg metabolic studies.METHODS: Classic metabolic balances of Mg were performed during three consecutive days, using carmin as fecal marker, with and without Mg supplementation.RESULTS: The patients (one male) presented, between 15 and 28 days old, with convulsions and persistent hypocalcemias, which could not be controlled with anticonvulsivants and/or intravenous calcium gluconate. After diagnostic was established the above symptoms and hypomagnesemia were controlled with Mg supplementation. Without supplements, mean daily balances were negative or below daily needs, showing final magnesemias lesser than 0.7 mEq/L and hypocalcemias about 3 mEq/L. The renal conservation test performed for six days after Mg repletion showed at the beginning of the study normal magnesemias (1.4 to 1.5 mEq/L) decreasing to 0.7 or 0.8 mEq/L in the first 24 hours, indicating absence of response from the body stores. Mg total renal excretion was smaller than 1 mEq, during six consecutive days, indicating adequate renal Mg reabsorption. Intestinal absorption of Mg varied from 6 to 15% of intake. With Mg supplementation, daily balances were positive, correcting progressively the serum Ca and Mg. The intestinal absorption was greater than 22% of intake in this situation.In pacient LPCJ, urinary excretion was 35% of the administered dosis, confirming Mg depletion.CONCLUSIONS: Besides confirming specific intestinal malabsorption of Mg, adequate renal conservation and an homeostatic extracellular defect of Mg were observed, probably caused by an incapacity of mobilization of Mg from tissue reserves.

Dietary origin of retained H+ in infants with acquired monosaccharide intolerance.

Net external acid balance was studied in 12 malnourished infants with chronic diarrhea (some of whom had acquired monosaccharide intolerance). When the infants achieved an adequate energy intake from a formula that contained either glucose or glucose polymers, seven developed metabolic acidosis and Five remained free of acidosis. During the study, the acidotic infants produced a significant excess of acid (3.7 ± 2 vs. 0.5 ± 2 mEq/kg/day, p < 0.005). The amount they excreted in urine (2.9 ± 2 mEq/kg/day), however, was similar to that excreted by nonacidotic infants (2.7 ± 2 mEq/kg/day) and indicated renal inability to reduce the excess acid load. The net effect was hydrogen ion (H + ) retention ( + 0.8 ± 0.8 vs. −2.2 ± 0.8 mEq/kg/day, p < 0.001). Good correlation existed between the net acid balance and the acid-base measurement in the blood. We speculate that (a) the increased acid load was a consequence of colonic bacterial production of volatile fatty acids from carbohydrate malabsorbed from the small bowel and (b) the renal incapacity to excrete H + probably was secondary to potassium and phosphate depletion.