INFANTILE DIARRHEA—Tolerance to Solutions of Electrolytes by Mouth

Since Darrow''s recommendation of electrolyte administration by mouth to infants with diarrhea, the constituting of a palatable liquid has been in the minds of all persons concerned with the treatment of diarrhea. Owing to the frequent association of gastric distress with oral administration of electrolyte solution, presumably because of increased osmolarity, a study was made at Kern County General Hospital to determine what osmolarity of solution was tolerated by most infants. For this purpose a commercially prepared oral electrolyte solution was used. When this new solution was given undiluted—that is, at an osmolarity of 20 times that of physiologic solution—only one of 29 patients, who were acutely ill and dehydrated, refused it or vomited it, probably due to irritation of the gastric mucosa. However, at a dilution of 1:3 with 5 per cent glucose and an osmolarity of six times physiological, only one of the 29 infants vomited and two others occasionally refused it.The length of hospital stay was not shortened by the substitution of the commercial preparation in either dilution. However, since the babies readily drank this electrolyte solution, it was possible to stop parenteral administration of electrolytes once fluid replacement had been carried out when the patient was first admitted.     

Antigastrolesive, gastric antisecretory, diarrheagenic and mucus-stimulating effects in rats following topically applied rioprostil, a synthetic prostaglandin E1 analog

Prostaglandins may have many biological actions including hypotensive and antipeptic ulcer activity. The purpose of this investigation was to determine if the primary alcohol prostaglandin E1 analog rioprostil1 prevents ethanol-induced gastric lesions (antigastrolesive activity), inhibits gastric acid secretion (antisecretory activity), or causes diarrhea in rats when administered topically, and to compare these responses to the effect of rioprostil following enteral (oral or intraduodenal) administration. Rioprostil exhibited antigastrolesive activity in rats when administered either orally or when applied topically. The topical antigastrolesive potency of rioprostil against ethanol-induced lesions [ED50 = 3.7 (0.5-12) micrograms/kg] was similar to its oral potency [ED50 = 1.9 (1.7-2.2) micrograms/kg]. In 4 hr pylorus-ligated rats, topically administered rioprostil inhibited total gastric acid output with a potency [ED50 = 5.1 (2.6-24) mg/kg] similar to intraduodenal administration [ED50 = 3.7 (2.8-5.3) mg/kg]. In addition, in these rats rioprostil increased mucin levels and did not cause dermal irritation. Finally, the incidence of diarrhea was lower when rioprostil was applied topically than when given orally with a 16-fold difference in potency between these two routes of administration. These data show that when rioprostil is applied via the skin it has antigastrolesive, gastric antisecretory and mucus stimulatory effects in rats equal to enteral administration, and a diarrheagenic potency lower than following oral administration. This profile suggests that topical administration of rioprostil may be a useful means of delivery for clinical treatment of peptic ulcer disease.     

Oral Passive Immunization Effect of Anti-Human Rotavirus IgY and Its Behavior against Proteolytic Enzymes

The neutralization titer of anti-human rotavirus (HRV) IgY was completely inactivated by pepsin at pH 2.0. However, it was not significantly affected by trypsin or chymotrypsin under certain conditions. The immunological activity of the IgY was observed in the intestine of suckling mice for 2 h after oral administration and the activity rapidly decreased thereafter. The effects of oral supply of IgY were thus estimated for HRV-induced diarrhea in suckling mice and it was found that a previous supply of the IgY, (1 h before HRV infection) completely prevented the HRV-induced diarrhea. The preventive effect was decreased as the time gap between IgY administration and HRV infection was longer. However, the oral supply of the IgY within 24h after HRV infection was still effective and decreased the incidence of HRV diarrhea in suckling mice.     

Bumetanide: Potent New “Loop” Diuretic

Bumetanide, a pharmacologically new diuretic, was evaluated in 27 subjects. Its onset of action was within 30 minutes with a peak at 90 minutes and a total duration of action of about 270 minutes. In a controlled study in oedematous patients it was equipotent with frusemide at one-fortieth the molar dosage and did not differ from frusemide with regard to its pattern of electrolyte excretion. On continuous oral administration for eight days it produced effective diuresis with minimal alteration in biochemical and haematological status. The only adverse effect was gastric discomfort in one patient.     

Osmotic stress on dilution of acid injured Escherichia coli O157:H7

To determine surviving numbers of Escherichia coli from cultures or food systems, dilution with 0.1% peptone is regularly used. Higher numbers of survivors could be obtained from an acid-treated culture if 0.5 mol l-1 sucrose was added to the 0.1% peptone. Sorbitol, glucose or sodium chloride, but not glycerol, could be used in place of sucrose. Using electron microscopy distinct differences could be seen between acid-treated and untreated cells. The osmolarity of the diluents ranged from 5 to 500 mosmol kg-1 H2O for the 0.5 mol l-1 sugar or glycerol solutions, to about 1000 mosmol kg-1 H2O for the salt solution. Maximum recovery diluent has an osmolarity of about 300 mosmol kg-1 H2O and resulted in recovery of similar numbers of injured cells as a 0.5 mol l-1 solution of sugar in 0.1% peptone. Taking into account the observed damage to acid-treated cells and the differences in osmolarity of the diluents, it is likely that dilution in 0.1% peptone imposed additional stress on the acid-injured cells which caused further cell damage. Dilution in a more osmotically stable solution alleviated this osmotic stress.     

Estimation of serum zinc and copper in children with acute diarrhea

Diarrhea is, in reality, as much a nutritional disease as one of fluid and electrolyte loss. Children who die from diarrhea, despite good management of dehydration, are usually malnourished and often severely so. In this study, we determined the serum levels of zinc and copper before and after standard oral rehydration solution (ORS) therapy in children with acute diarrhea and correlated it with diarrheal duration and severity. One hundred ten children suffering from acute diarrhea were included. Serum zinc and copper levels of these children were estimated at the time of enrollment and after treatment with standard ORS therapy. This study shows that children suffering from acute diarrhea show a statistically significant decrease of 13.1% and 12.8% in serum zinc and copper concentrations, respectively, compared to normal. These levels further decrease by 22.6% and 22.4%, respectively, after treatment with standard ORS therapy. Our study shows that children with the lower plasma zinc and copper levels suffered with more severe and longer duration of diarrhea. Zinc and copper supplementation could be added to standard ORS therapy for the reduction in morbidity and mortality associated with acute diarrhea in children.     

Effectiveness of oral immunization of white mice with a complex S. typhimurium antigen]

The protective properties of hydroxylamine preparation obtained from a virulent strain of S. typhimurium were studied in experiments with natural infection after a single oral immunization. The new data obtained in these experiments suggest that the treatment of bacteria with hydroxylamine allows to produce the preparation which, when administered orally, has the immunizing dose only 20 times as great as its immunizing dose for subcutaneous administration. The action of gastric juice on hydroxylamine preparation, as well as the duration and specificity of immunity induced by the oral administration of this preparation were studied. The oral administration of some adjuvants was found to make it possible to considerably decrease the effective dose of the vaccine.     

IgY Antibodies Protect against Human Rotavirus Induced Diarrhea in the Neonatal Gnotobiotic Piglet Disease Model

Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV) diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab) to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV). Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA) and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization –VN- titer = 256) for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC) responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV–specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV). Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea.     

Honey in the treatment of infantile gastroenteritis.

A clinical study was undertaken using honey in oral rehydration solution in infants and children with gastroenteritis. The aim was to evaluate the influence of honey on the duration of acute diarrhoea and its value as a glucose substitute in oral rehydration. The results showed that honey shortens the duration of bacterial diarrhoea, does not prolong the duration of non-bacterial diarrhoea, and may safely be used as a substitute for glucose in an oral rehydration solution containing electrolytes. The correct dilution of honey, as well as the presence of electrolytes in the oral rehydration solution, however, must be maintained.     

Intravenous rehydration for diarrheal dehydration of eutrophic children: survey of protocols provided at Colombian medical schools

Introduction. In all cases of severe dehydration from diarrhea, WHO recommends rapid rehydration. If oral rehydration in children is contraindicated, intravenous rehydration is recommended for immediate administration. However, methods of intravenous rehydration appear to be inadequately addressed in the medical schools of Colombia. Objective. Current approaches to oral rehydration were summarized, and instructors were informed concerning current WHO recommendations. Materials and methods. A survey was designed for pediatric instructors in Colombian medical schools. Direct questions about rehydration methods were included as well as presentation of theoretical clinical situations with dehydrated children. The survey also asked for the conditions necessary for intravenous rehydration and method of administration (volume, solution, concentration and speed of infusion). Results. Forty-one surveys were included (82% of medical schools in Colombia). Inadequate contraindications for oral rehydration therapy were made in 41%. Rapid and slow intravenous rehydration was recommended in 71% and 29%, respectively; 57% recommended fluid bolus to rehydrate. Adequate volumes were recommended by less than half of the respondents and adequate sodium concentration was recommended by 85%. In 56% of medical schools, glucose was not included in solutions and 66% use Ringer lactate. Normal saline solution, dextrose solution with electrolytes and polyelectrolytes solutions are also used. Conclusions. Misconceptions are common concerning the contraindications to oral rehydration therapy. One-third of medical schools promote a slow therapy despite the superiority of the rapid therapy. Uniformity for rapid therapy schemes is lacking. Bolus rehydration is commonly advocated despite the fact that this method is unsupported by the literature. Concepts about rehydration must be updated in medical schools and a national guide for intravenous rehydration is recommended.     

Central nervous system action of calcitonin gene-related peptide to inhibit gastric emptying in the conscious rat

The central nervous system action of rat alpha-calcitonin gene-related peptide (alpha-CGRP) on gastric emptying of a liquid, noncaloric, methylcellulose solution was assessed in 24-hr fasted, conscious rats using phenol red method as a marker. Intracisternal injection of alpha-CGRP (0.75-250 pmol) dose-dependently inhibited gastric emptying by 27-94% as measured 20 min after oral administration of the solution. The ED50 was 6.2 pmol. alpha-CGRP injected intravenously at 250 pmol delayed gastric emptying by 71% whereas a lower dose (75 pmol) was inactive. Intracisternal alpha-CGRP-induced inhibition of gastric emptying was completely abolished by bilateral adrenalectomy and partially suppressed by subdiaphragmatic vagotomy or coeliac/superior mesenteric ganglionectomy. Adrenalectomy or vagotomy in saline-treated animals did not significantly modify the rate of gastric emptying whereas coeliac/superior mesenteric ganglionectomy caused a significant 29% inhibition as compared to the nonoperated group. These results demonstrate that alpha-CGRP is a potent centrally acting inhibitor of gastric emptying of a nonnutrient liquid. The inhibitory effect of intracisternal injection of CGRP appears to be mediated by the adrenal gland and in part by the sympathetic and parasympathetic nervous system.     

MDL-646, a new synthetic E1-prostaglandin with local protective effects on the gastric mucosa

The gastric protection, diarrheogenic and arterial hypotensive effects of MDL-646, a PGE1 derivative, have been studied in rats. The compound administered p.o. or i.v. was able to inhibit the macroscopic damage to gastric mucosa produced by noxious stimuli (ethanol and indomethacin). In the stomach perfusion test with the anesthetized rat, intravenously administered MDL-646 reduced histamine- or pentagastrin-stimulated gastric secretion. After intraduodenal administration (i.d.) doses at least 40-50 times greater were necessary for an antisecretory effect. In conscious rats with chronic gastric fistulas, intragastrically administered (i.g.) MDL-646 affected both acid concentration and volume of unstimulated gastric secretion. In experimental models for gastric lesions, MDL-646 was much more potent after oral (p.o.) (15-30 times) than after i.v. administration. (ED50 micrograms/kg: vs. alcohol lesions, 0.05 p.o. and 0.7 i.v.; vs. indomethacin ulcers, 7.0 p.o. and 195 i.v.). Our data would fit the hypothesis that it was a local effect on the gastric mucosa. The mechanism of this effect is not known. The supposed local activity coupled with the antisecretory effects and the good tolerability make it interesting to test MDL-646 as an anti-ulcer agent in man.     

酪酸梭菌活菌散与抗菌药间隔序贯应用预防抗生素相关性腹泻疗效观察

目的观察和评价酪酸梭菌活菌散（商品名：宝乐安）与抗菌药间隔序贯应用治疗小儿肺炎预防抗生素相关性腹泻的临床疗效。方法将203例肺炎患儿随机分为预防组和对照组,预防组103例,对照组100例,2组均给予抗菌药及对症支持治疗。其中预防组在治疗的同时间隔2～3 h序贯使用酪酸梭菌活菌散,0.5 g/次,3次/d,出现腹泻继续服用;对照组不用酪酸梭菌活菌散预防,出现腹泻用酪酸梭菌活菌散治疗,0.5 g/次,3次/d。对2组继发腹泻的发生率、腹泻持续天数、肺炎治疗的总疗程、腹痛和脱水等症状和体征进行统计分析。结果预防组继发腹泻12例,发生率为11.7%,对照组继发腹泻57例,发生率为57.0%,2组相比差异具有非常显著性（P〈0.01）;预防组腹泻持续时间和治疗疗程显著短于对照组（P〈0.01）;预防组患儿腹痛和脱水等症状和体征发生率均少于对照组（P〈0.01）。结论酪酸梭菌活菌散与抗菌药间隔序贯应用治疗肺炎,能显著降低小儿抗生素相关性腹泻的发生率,预防性应用具有积极的临床意义。     

MDL-646, a new synthetic E1-prostaglandin with local protective effects on the gastric mucosa

The gastric protection, diarrheogenic and arterial hypotensive effects of MDL-646, a PGE₁ derivative, have been studied in rats. The compound administered p.o. or i.v. was able to inhibit the maroscopic damage to gastric mucosa produced by noxious stimuli (ethanol and indomethacin). In the stomach perfusion test with the anesthetized rat, intravenously administered MDL-646 reduced histamine- or pentagastrin-stimulated gastric secretion. After intraduodenal administration (i.d.) doses at least 40–50 times greater were necessary for an antisecretory effect. In conscious rats with chronic gastric fistulas, intragastrically administered (i.g.) MDL-646 affected both acid concentration and volume of unstimulated gastric secretion. In experimental models for gastric lesions, DML-646 was much more potent after oral (p.o.) (15–30 times) than after i.v. administration. (ED₅₀ μg/kg: vs. alcohol lesions, 0.05 p.o. and 0.7 i.v.; vs. indomethacin ulcers, 7.0 p.o. and 195 i.v.). Our data would fit the hypothesis that it was a local effect on the gastric mucosa. The mechanism of this effect is not known. The supposed local activity coupled with the antisecretory effects and the good tolerability make it interesting to test MDL-646 as an anti-ulcer agent in man.     

酪酸梭菌活菌散与蒙脱石散间隔应用治疗小儿迁延性腹泻62例临床研究

目的观察酪酸梭菌活菌散与蒙脱石散间隔应用治疗小儿迁延性腹泻的临床疗效。方法将124例迁延性腹泻患儿随机分为观察组和对照组,观察组在服用蒙脱石散2 h后服用酪酸梭菌活菌散,对照组在服用蒙脱石散2 h后服用复方胃蛋白酶散。结果观察组总有效率为100%,对照组总有效率为72.58%,2组间差异具有显著统计学意义(P0.01)。结论酪酸梭菌活菌散与蒙脱石散间隔应用治疗小儿迁延性腹泻疗效显著,值得临床推广应用。     

The Effect of O,O-DIMETHYL-O-(2,4,5-Trichlorophenyl) Phosphorothioate (Fe Nc H Lor Phos) On Cholinesterases in the Blue Fox (Alopex Lagopus)

Four blue fox bitches were used in the experiments. Two foxes were given fenchlorphos in the feed, one 100 mg/kg body weight and the other 200 mg/kg daily for 30 days. The maximum inhibition of plasma Cholinesterase was 65 and 69 %, respectively. The corresponding values of the erythrocyte acetylcholinesterase were 43 and 63 %. For the third bitch given 0.4 mg/kg as a single dose i.v. the effect was only measurable as a small transient decrease of the plasma Cholinesterase level. Eighty % of the plasma Cholinesterase of the fourth fox, given 500 mg/kg as a single oral dose, was inhibited on the third day. The erythrocyte acetylcholinesterase activity level only showed a slight decline. This fox vomited during feeding the day after administration. Symptoms as salivation, tremors, diarrhea, pinpoint pupils and respiratory distress were never seen in any of the foxes. It was concluded that fenchlorphos administration in the feed in doses recommended to dogs is well tolerated by healthy foxes as far as Cholinesterase inhibition is concerned.     

Value of the "gastric chamber", new technic performed ex vivo, for the study of the gastric mucosa of the rat]

The "gastric chamber" technique, performed in the anaesthetised rat, enables the study of gastric mucosal fragility induced by doses of phenylbutazone, which do not themselves cause ulceration or exulceration. The perfusion of buffered solution at pH 2-8 into the gastric chamber shows that prior oral administration of phenylbutazone 50 mg/kg increases the fragility of the mucosa. The optimal delay separating this administration from the time of experimentation is 6 hours. The effects seen are essentially vascular disorders.     

再水合溶液能有效改善急性脱水女举重运动员的运动表现

本研究旨在探讨女子举重运动员急性脱水后口服4种不同组成的溶液,对液体存留率、胃肠道舒适度、血液值和无氧动力的影响。本研究以12位大学生女子举重运动员为对象,采交叉、平衡次序设计;研究参与者于脱水2%体重后分别补充相当于1.5倍脱水量的低渗透压电解质液(HES)、等渗透压电解质液(IES)、运动饮料(SB)或纯水(W),补充时间为脱水后立即、再水合期的30 min、60 min及90 min。再水合期间记录胃肠舒适分数、测量体重(计算液体存留率),并采集静脉血以测量血液渗透压、葡萄糖及钠、钾与氯离子,于脱水前与再水合期120 min时进行Wingate无氧动力测验。研究结果显示:补充HES、IES及运动饮料(SB)于再水合期90 min时的胃肠道舒适分数显著低于补充纯水(W)、而补充3种溶液于再水合期60 min时的血糖值则显著高于补充纯水(W),补充HES于再水合期120 min时的血钾值显著高于补充运动饮料(SB)及纯水(W);但补充4种溶液后的无氧动力与液体存留率并无显著差异。本研究证实举重运动员急性脱水后补充4种不同口服再水合溶液并不会影响再水合后的无氧动力,但补充含有糖类及电解质的溶液能有较佳的胃肠道舒适度,并血糖与血液电解质有维持的效果。     

Application of the Convection–Dispersion Equation to Modelling Oral Drug Absorption

Models of systemic drug absorption after oral administration are frequently based on a direct or a delayed first-order rate process. In practice, the use of the first-order approach to predict drug concentrations in blood plasma frequently yields a considerable mismatch between predicted and measured concentration profiles. This is particularly true for the upswing of the plasma concentration after oral administration. The current investigation explores an alternative model to describe the absorption rate based on the convection–dispersion equation describing the transport of chemicals through the GI tract. This equation is governed by two parameters, transport velocity and dispersion coefficient. One solution of this equation for a specific set of initial and boundary conditions was used to model absorption of paracetamol in a 22-year-old man after oral administration. The GI-tract passage rate in this subject was influenced by co-administration of drugs that stimulate or delay gastric emptying. The transport-limited absorption function is more accurate in describing the plasma concentration versus time curve after oral administration than the first-order model. Additionally, it provides a mechanistic explanation for the observed curve through the differences in GI-tract passage rate.     

History of parenteral nutrition in pediatrics with emphasis on amino acids

Central venous total parenteral nutrition (TPN) has proved to be a valuable and often life-saving measure in selected newborn infants with surgically repairable, major anomalies of the gastrointestinal tract and infants with chronic intractable diarrhea. However, in infants of low--and especially very low--birth weight, the TPN regimen that was so successful in older infants was frequently associated with severe risks of hyperglycemia. An alternative approach that has proved to be the most satisfactory relies on the fact that the energy expenditure of a premature infant, nursing in a thermally neutral environment, rarely exceeds 50 kcal/kg, a level that can be safely and effectively maintained. With respect to the development of parenteral amino acid solutions, three generations of such mixtures can now be identified. The first of these was represented by the protein hydrolysates. With the advent of technology for the production of pure L-amino acids, a second generation of crystalline mixtures was developed. Evaluation of these revealed that extrapolation from data on oral nutrition was often unsatisfactory for the adequate formulation of such mixtures. The direct study of the parenterally nourished patient led to the third generation of special purpose amino acid solutions such as those targeted for patients with renal failure, liver failure, or trauma or for the promotion of anabolism. It seems likely that development of other solutions will follow the trend of relying on accurate definition of a given metabolic disorder and the perfection of a specific solution to correct it.