Dominant role for osmolality in the efficacy of glucose and glycine-containing oral rehydration solutions: studies in a rat model of secretory diarrhoea.

The effect of osmolality on the efficacy of oral rehydration solutions (ORS) and the contribution of the amino acid glycine to water absorption from ORS have been studied in an animal model of secretory diarrhoea. After exposure to pure cholera toxin, rat small intestine (excluding the duodenum) was perfused in situ with seven different ORS. All ORS were derived from a "basic" solution containing Na 50, K 25, Cl 75 and glucose 50 mmol/l to which 25 or 50 mmol/l of glycine, glucose, or mannitol was added. All ORS reversed water secretion to absorption, but maximum water absorption was obtained with the "basic" solution with an osmolality of 200 mOsm/kg. When the osmolality of the "basic" solution was raised to 225 and 250 mOsm/kg by adding mannitol, water absorption decreased. At each of these osmolalities, substitution of mannitol by glycine or glucose resulted in similar increases in water absorption, but all modifications compared unfavourably with the "basic" solution. Net sodium secretion occurred with all ORS tested, despite net water absorption. These findings in a perfusion model of rat small intestine suggest that osmolality is a key factor influencing the efficacy of ORS and that addition of a second substrate, such as glycine, has no beneficial effects. Our results suggest that there is a maximal rate for water absorption from the small intestine which is inversely related to the osmolality of the perfusate.

Changes in the fetal tibial growth plate secondary to maternal zinc deficiency in the rat: a histological and histochemical study.

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. To elucidate further the effects of maternal ZD in the fetal skeleton, we performed a morphological and histochemical study of tibial growth plate (GP) in ZD rat fetuses. The histochemical study included the identification of calcium, of hydrolytic enzymes associated with the process of calcification, and of oxidative enzymes related to energy production and to the synthesis of proteoglycans. Pregnant Sprague-Dawley rats were fed (1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), (2) a zinc-deficient diet (0 micrograms/g) ad libitum (group ZD), or (3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed, the fetuses were removed, and fetal tibiae obtained. Specimens were stained with hematoxylin-eosin (H&E) and Masson Trichrome and were processed for identification of alkaline phosphatase, adenosine triphosphatase, succinic dehydrogenase, NADH dehydrogenase, and calcium. The morphologic patterns found in ZD fetal tibiae indicated defects in various cell types implicated in bone metabolism. Staining for hydrolytic enzymes revealed alterations in the size and distribution of matrix vesicles and a weaker staining for ATPase in ZD fetuses. Staining for oxidative enzymes was overall more intense in ZD fetal tibiae. ZD fetuses also presented irregular and defective calcification. These findings indicate that severe maternal ZD in the rat results in structural and functional alterations in the GP of fetal bone, leading to a defective endochondral ossification.

History of the development of oral rehydration therapy.

Humans have often used oral fluids to replace perceived losses of water, either instinctively or with a therapeutic orientation in the form of folk remedies. Replacement therapy with intravenous (IV) fluids was formally introduced in the last century for the treatment of patients with cholera. The modern implementation of oral replacement therapy was begun by pediatricians in the 1940s who used electrolyte solutions as maintenance therapy in mildly purging children with diarrhea. However, the scientific development of oral rehydration therapy (ORT) has occurred only in the last 30 years. Basic physiologic research in the 1950s demonstrated the cotransport mechanism of sodium and organic solutes (sugars and amino acids) in the intestinal cells, thereby establishing the scientific basis for ORT. The use of ORT based on scientific observations was first reported in 1964 from the Philippines by Phillips and coworkers. Research laboratories in Dhaka and Calcutta subsequently demonstrated that the mechanism of sodium and glucose cotransport remains intact in cholera patients and that oral solutions can successfully rehydrate and maintain hydration in these patients. Clinical studies carried out in Dhaka and Calcutta confirmed the efficacy of oral rehydration solutions (ORS) and showed that nearly 80% of IV fluid could be saved if patients were hydrated by the oral route. Further studies demonstrated the safety and efficacy of ORT in patients of all ages suffering from acute diarrhea of any cause. The use of ORT has substantially reduced morbidity and mortality from acute diarrhea, particularly after the World Health Organization adopted and promoted ORT on a worldwide scale. Researchers continue to search for better ORS formulations in terms of safety, efficacy, availability, and cost. Food-based ORS are a promising area of research. The use of a sound scientific method, the establishment of a close link between basic and clinical science, and the use of field studies have proved to be major assets in the development of ORT.

Sodium content of oral rehydration solutions: a reappraisal.

PIP: Proper choice of oral rehydration solution, with regard to sodium content, is a conflicting issue to general practitioners and pediatricians. World Health Organization (WHO) recommendations of oral rehydration solution containing 90mmol/1 sodium, have been effective throughout developing countries worldwide. In developed countries, however, such as England, this recommendation seems inappropriate; a recommendation of 50 - 60 mmol/1 sodium with 90 -111mmol/1 glucose is preferred. This combination will eliminate the need for free water recommended by the WHO maintenance therapy. Normonatraemia is maintained, and hyponatraemia and hypernatraemia can both be corrected. Sodium content is adequate in replacing stool loss resulting from viral and bacterial diarrheas. Iatrogenic hyponatraemia and hypernatraemia do not occur as they would with oral rehydration solutions with low (30-35) or high (90mmol/1) sodium concentration. Solutions containing 50-60 mmol/1 sodium is safer in neonates and young infants with immature renal functions, incapable of properly distributing increased sodium leads. Glucose concentration necessary to make oral rehydration with 50 - 60 mmol/1 isotonic, or hypotonic, resembles WHO - ORS, but is half that in 30-35 mmol/1 sodium solutions. In controlled clinical trials, oral rehydration solutions with 50-60 mmol/1 sodium have proven safe, and performance was compatible with WHO-ORS. For both rehydration and correction of acidosis, the solution proved effective. When oral rehydration solution sodium, concentrate is below 90 mmol/1, errors in reconstituting may be common, but offers less risk resulting in dangerous hypernatraemia. An "all purpose" physiological oral rehydration solution would make oral rehydration therapy, more economical, simpler, and safe in developed countries worldwide.^ieng

Evaluation of three oral rehydration solutions designed for use in developed communities.

One hundred and sixteen children (less than 2 years old) admitted to a London hospital with acute gastroenteritis were randomized to receive either an oral rehydration solution (ORS) with low sodium and high glucose concentration (Na+ 35, glucose 200 mmol/L), an ORS with a high sodium but low glucose concentration (Na+ 60, glucose 111 mmol/L), or an ORS containing glycine and a glucose polymer (Na+ 50, glucose 50, glycine 50 mmol/L). Clinical, biochemical and haematological features of the three groups were similar on admission. Rotavirus was common (31%); the majority of children had minimal dehydration or acid-base disturbance. The clinical outcome, including ORS intake, prevention of dehydration, rehydration, and duration of hospital stay was similar in the three treatment groups. All initial electrolyte abnormalities were corrected; no child developed hypernatraemia or hyponatraemia. At 24 h, the mean serum urea was higher in those who received the ORS containing glycine than in other groups, and it had not fallen significantly since admission. Eighteen per cent of children had carbohydrate intolerance: four children with greater than or equal to 2% reducing substances in their stool had all received ORS with a high glucose content and had numerous watery green stools containing rotavirus. All ORS solutions were safe and effective for rehydration and correction of biochemical abnormalities, however carbohydrate intolerance was more prevalent in children who received the ORS with a high glucose content.

Teratogenicity of zinc deficiency in the rat: study of the fetal skeleton.

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. This study identifies fetal skeletal malformations that affect calcified and non-calcified bone tissue as a result of gestational zinc deficiency in rats, and it assesses the effect of maternal ZD in fetal bone calcification. Pregnant Sprague-Dawley rats (180-250 g) were fed 1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), 2) a zinc-deficient diet (0 microgram/g) ad libitum (group ZD), or 3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed. Fetuses were weighed, examined for external malformations, and stained in toto with a double-staining technique for the study of skeletal malformations. Maternal and fetal tissues were used for Zn, Mg, Ca, and P determinations. Gross external malformations were present in 97% of the ZD fetuses. No external malformations were found in fetuses from groups C and PF. Ninety-one percent of cleared ZD fetuses had multiple skeletal malformations, whereas only 3% of the fetuses of group PF had skeletal defects; no skeletal malformations were found in fetuses from group C. Some of the skeletal malformations described in the ZD fetuses, mainly affecting non-calcified bone, were not mentioned in previous reports, thus stressing the importance of using double-staining techniques. Examination of stained fetuses and counting of ossification centers revealed important calcification defects in ZD fetuses. These effects were confirmed by lower Ca and P concentrations in fetal bone with alteration of the Ca:P ratio.

Optimising oral rehydration solution composition for the children of Europe: clinical trials.

Clinical trials testing different oral rehydration solutions (ORS) are reviewed. The effects of individual components and their concentrations are analysed in order to establish margins of safety for the composition of the ideal ORS for children in Europe. Glucose is the solute of choice for ORS and concentrations of 70-140 mmol/l are adequate. Glucose may be replaced by sucrose or glucose polymers. "Low" sodium concentrations (35-60 mmol/l) are advised for rehydration and maintenance in acute non-cholera diarrhoea, for children of all ages, including neonates, and for any degree of dehydration except shock. Although intended for children who are not malnourished, the European ORS should have an adequate potassium concentration (20-30 mmol/l), namely the same concentration as found in WHO-ORS. Chloride concentration depends upon other constituents of ORS, namely sodium and potassium, but the range of 30-90 mmol/l is considered to be adequate. Base or base precursors are not required for correction of acidosis except in the severe cases that always need intravenous replacement. A relatively low osmolality seems advisable.

[Thrombosis of the pulmonary artery associated with maternal deficiency of antithrombin III]. / Trombosis de la arteria pulmonar asociada a déficit materno de antitrombina III.

Authors report a case of newborn with thrombosis of the pulmonary artery, probably caused by a maternal deficit of antithrombin III. Deficit of antithrombin III (AT III) as the possible cause of thrombosis is discussed.

Prostaglandins in human milk.

Human milk contains many different components which interact locally in the gastrointestinal tract and stimulate some systemic functions. Among these substances are prostaglandins. We obtained samples of foremilk and hindmilk in 8 lactating women by manual expression before and after 9 a.m. and 9 p.m. on the 3rd day post partum. The following values were found for prostaglandin E2: foremilk, 162 +/- 135 pg/ml; hindmilk, 198 +/- 148 pg/ml. The values for 6-ketoprostaglandin F1 alpha were: foremilk, 818 +/- 386 pg/ml, and hindmilk, 795 +/- 487 pg/ml. The values for thromboxane B2 were: foremilk, 3,557 +/- 2,770 pg/ml and hindmilk, 4,476 +/- 4,053 pg/ml. The results showed a great variability without statistical differences between paired values of the four groups. This dispersion may be produced by the procedure for extraction and by individual basal levels.

Zinc concentration in amniotic fluid of zinc-deficient rats and its relation to fetal weight.

Zinc concentration in amniotic fluid and its relation to fetal weight were investigated in three groups of pregnant rats: group A received a zinc-adequate diet, and the rats of groups B and C were fed a zinc-deficient diet. Group C also received zinc supplementation in water. The daily food consumption, weight and plasma zinc levels on days 1, 10 and 20, zinc concentration in amniotic fluid, the number of implantation sites, the number of resorptions, the number of live fetuses and fetal weight were determined. Plasma zinc concentrations were significantly different at the end of gestation between group B (Zn = 167.6 +/- 26.6 micrograms/dl) and the other two groups (group A = 199 +/- 18.6 micrograms/dl; group C = 204 +/- 13.7 micrograms/dl). The number of resorptions was significantly higher in group B and the number of live fetuses was significantly lower in this same group (p less than 0.025). Fetal weight was significantly lower in group B (p less than 0.001). The zinc concentrations of the amniotic fluid were significantly lower in group B (14 +/- 4.7 micrograms/dl) as compared to group A (83 +/- 11.4 micrograms/dl) and C (82 +/- 21 micrograms/dl; p less than 0.001). There was a positive linear correlation between zinc concentrations in amniotic fluid and fetal weight, being r: 0.7379 (p less than 0.001).

Zinc, pregnancy and parturition.

The role of zinc in the nutrition of pregnant women and its relations to prenatal growth and parturition are reviewed. Zinc deficiency (ZD) affects fetal growth and development both in experimental animals and in man. The teratogenicity of zinc deficiency was widely demonstrated in animals and is also evident in humans. Alcohol intoxication potentiates the effects of ZD in animals. Plasma zinc levels decrease during pregnancy and apparently an adequate and continuous intake of zinc is required for a normal embryonic development. The zinc content of amniotic fluid seems to be related with fetal growth but its value as an indicator of embryonic development is controversial. Zinc deficiency also affects adversely parturition. Mild zinc deficiency may affect a large number of pregnant women, being potentially harmful to the mother and the fetus. This situation requires the screening of high-risk groups, the definition of adequate dietary intakes for each population, and the supplementation with zinc when deficits are detected.

Effect of zinc nutrition on parturition and postpartum in the rat.

The effects of zinc deficiency on parturition were studied in three groups of Wistar rats. Group A received a zinc-adequate control diet (Zn = 33 ppm), group B received a zinc-deficient diet (Zn = 2.6 ppm), and group C received the zinc-deficient diet plus a supplement of zinc in the drinking water (100 micrograms/ml). The results showed a prolonged parturition (p less than 0.05) in group B (149 +/- 42 min) as compared to group A (78.6 +/- 23.7 min) and group C (82.4 +/- 20.8 min). No significant difference was found in regard to uterine bleeding. A different pattern of maternal behavior was found in the animals of group B who did not retrieve or lactate the pups. The importance of an adequate zinc status for normal parturition is stressed.

Zinc concentration of amniotic fluid in the course of pregnancy and its relationship to fetal weight and length.

The interest of the zinc content of amniotic fluid and its relationship to different maternal and fetal parameters is recent. It was reported that the zinc content of amniotic fluid increases in the course of pregnancy probably as an indirect indicator of an increased rate of protein synthesis. These considerations and the known important metabolic role of zinc led us to study the zinc content of amniotic fluid and its importance in the growth and development of the fetus. Amniotic fluid samples of 24 women with normal pregnancies and normal term deliveries were studied. The samples were obtained between weeks 29 and 42 of gestation by transabdominal amniocentesis and the zinc content was determined by means of atomic absorption spectrophotometry. The zinc content of amniotic fluid increases significantly during the third trimester. A positive linear correlation was found between the zinc concentration of amniotic fluid and fetal weight and length. Fetal growth and development would depend on the zinc available due to its biological functions and thus the increase of zinc concentration of amniotic fluid in the last weeks of gestation and its correlation with fetal weight and length. These results suggest that the determination of zinc content of amniotic fluid can be useful in the assessment of fetal development and well-being, and of course of pregnancy.