Mild Laxative Effect Research Articles

Antibacterial Activity of Hibiscus Flower Extracts

In Ayurveda and the traditional Chinese medicine system, it is well documented that the use of herbal extracts and nutritional supplements for the treatment of various diseases. The Hibiscus plant has been used as a diuretic, mild laxative, and treatment for cardiac and nerve diseases. This plant is used for mild laxative effect, the ability to increase urination, relief during hot weather, and treatment of cracks in the feet, bilious, sores, and wounds. The purpose of this study was to examine the evolution of antimicrobial activity of flower extract of Hibiscus against human pathogens. Fresh flowers and dried flower powder were used for extract production. Two types of extracts were prepared, viz. aqueous and solvent extracts. Their antibacterial activity was studied against different human pathogens. Well agar diffusion assay was used for antibacterial investigation.

Bidirectional regulation effect of rhubarb as laxative and astringent by metabolomics studies

Ethnopharmacological relevanceRhubarb, a prominent traditional Chinese medicine, has been employed as a potent laxative for centuries and garnered particular popularity among the youth owing to its notable efficacy in weight management. Historical records indicated that rhubarb initially exhibited robust laxative properties, but extended and consistent usage may lead to an astringent response in the later stage of long-term use. In contrast, steamed pieces of rhubarb (SR), preparing through the process of steaming with wine, have demonstrated a gentle laxative effect with no reported adverse effects. Aim of the studyOur study was designed to explore the intricate mechanisms underlying laxative and astringent properties of rhubarb through metabolomics research. Materials and methodsIn this investigation, we employed a serum metabolomics approach utilizing the UPLC-Q-Extractive-Orbitrap-MS method to delve into the contrasting laxative and astringent effects of rhubarb, as well as to unravel the mechanisms of underpinning its bidirectional regulatory influence. To commence, we assessed alterations in Evacuation Index (EI) values, intestinal hormone levels, and colon histopathology in mice to gauge rhubarb's laxative and astringent effects. Subsequently, metabolomics methodology was employed for cluster analysis through Principal Component Analysis (PCA) and biomarker identification via Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). Then, we delved into the distinctions in characteristic biomarkers, metabolic pathways, their association with pathological changes, and correlation heatmap for biomarkers between raw pieces of rhubarb (RR) and SR to gain insights into the potential mechanisms behind rhubarb's bidirectional regulatory effects. ResultsOur findings revealed that RR exhibited a laxative effect in the early stage and transitioned to an astringent effect in the later stage, as indicated by the EI values. In contrast, SR consistently demonstrated a mild laxative effect. Biochemical indexes and histopathological assessments unveiled that RR triggered its astringent effect by inhibiting secretion of motilin (MTL), promoting secretion of vasoactive intestinal peptide (VIP) and epinephrine (EPI), and inducing onset of inflammation. Furthermore, serum metabolomics analysis identified 59 discriminative biomarkers modulated by RR and SR. Through comprehensive analysis, we elucidated the in vivo transformation relationships among multiple endogenous metabolites. Notably, our results underscored the down-regulation of certain phosphatidylcholines (PCs), amino acids, acylcarnitines, and up-regulation of lysophosphatidylcholines (LysoPCs) played pivotal roles in the onset of gut dysfunction, intestinal inflammation, gut barrier damage, and gastrointestinal motility disorder upon prolonging RR administration, ultimately contributing to its astringent effect. Additionally, our correlation analysis elucidated that anthraquinones, stilbenes, and phenylbutanones were the pharmacodynamic material basis responsible for inducing the astringent effect of RR. ConclusionThis study provides valuable insights into the bidirectional regulatory effects of rhubarb and sheds light on its underlying mechanisms through a comprehensive metabolomics approach.

Primary and secondary constipation: causes of occurrence, methods of correction

Constipation develops in up to 30% of the adult population of economically developed countries. The main reason for the occurrence of constipation are lifestyle features: inactivity and unbalanced nutrition. During constipation, motor, absorptive and secretory functions of the large intestine change. Treatment of patients with constipation begins after determining the cause of constipation and excluding lesions of the large intestine that could provoke constipation. Both soluble and insoluble dietary fibers should be increased in the diet. The main approach to treatment is the use of combined therapy, and if the effect is insufficient, laxatives administration is recommended.
 Objective — to evaluate the effectiveness and safety of using the multicomponent laxative EasyDo in the treatment of patients with functional constipation and irritable bowel syndrome (IBS) with constipation.
 Materials and methods. The study involved 28 patients with functional constipation/IBS with constipation, who met the Rome IV criteria (2016). Women prevailed in this group, 19 (68.0%). IBS with constipation was diagnosed in 15 (53.6%) cases, and functional constipation in 13 (46.4%) subjects. Patients were administered EasyDo (Prakruti Products Pvt Ltd, India), which includes a mixture of natural extracts of medicinal plants, namely: Operculina turpethum, Cassia fistula, Terminalia chebula, Glycyrrhiza glabra 2 tablets in the evening. Besides, recommendations were given to change the lifestyle, to add dietary fibers into the diet with individual selection of the dose. The dynamics of the following symptoms were evaluated: lack of regular bowel movement, difficulty in defecation, feeling of incomplete emptying, flatulence, etc. The intensity of each of these symptoms was assessed with the use of a 5‑point Likert scale.
 Results. The analysis of EasyDo effectiveness was carried out after three weeks of the drug administration. All patients noted positive changes, but the degree of positive dynamics was different. After the treatment, the number of bowel movements per week increased. Three or more stools without unproductive straining were recorded in 21 (75%) patients. The severity of complaints in most patients has significantly decreased.
 Conclusions. The obtained results demonstrated the following EasyDo effectiveness: considerable in 21 (75%) patients, moderate in 6 (21.4%) patients, no effects in one (3.6%) patient. The combination of plant components in EasyDo has a mild laxative effect, it is well tolerated and can be recommended in the complex treatment of patients with constipation.

РЕЗУЛЬТАТЫ КЛИНИЧЕСКИХ ИСПЫТАНИЙ ЭФФЕКТИВНОСТИ И ФУНКЦИОНАЛЬНОЙ НАПРАВЛЕННОСТИ НОВОГО ЭНТЕРОСОРБЕНТА НА РАСТИТЕЛЬНОЙ ОСНОВЕ «ФИТОСОРБОВИТ»

The evidence of the effectiveness and functional orientation of the new plant-based type of enterosorbent which contains “Fitosorbovit” biologically active additive (BAA), the formulation of which consists of ingredients that have a synergistic action in respect of the claimed functional properties. The dietotherapy was carried out by the inclusion of a specialized product in the diet of trial subjects who suffer from vegetative-vascular dystonia. The biochemical status with determination of sugar in liver transaminases, thymol turbidity test, and total protein of blood is studied. A favorable effect of biologically active additives on cholesterol metabolism on the basis of the content of the free level and group value of this indicator is discovered. Overall health and physical activity improvement is shown, which gives evidence of positive changes in the quality of life. Normalization of the cerebral cortex function and higher nervous activity, which is manifested in the reduction of frequency of complaints, improvement of emotional status, muscle tone, improvement of initiatives and mental alertness is pointed out. The “Fitosorbovit” BAA improves motor-evacuation function of the gastrointestinal tract (GIT) and liver function, and has a mild laxative effect. Specialized product can be recommended as a preventive measure and complex treatment of irritable bowel syndrome, as well as to prevent a biliary dyskinesia.

Polydextrose and Soluble Corn Fiber Increase Five-Day Fecal Wet Weight in Healthy Men and Women

Dietary fiber has well-established beneficial effects on laxation. Many fibers have been developed with positive sensory properties and 2 such fibers are polydextrose (PDX) and soluble corn fiber (SCF), which can be added to many commercially produced products. We conducted a randomized, double-blind, placebo-controlled, crossover study comparing the laxative effects of PDX and SCF at a dose of 20 g/d with a low fiber control (LFC) eaten daily as a muffin and cereal in 36 healthy men and women. Each treatment period was 10 d with a 2-wk washout period between. Participants collected fecal samples during the last 5 d of each treatment and completed food diaries and gastrointestinal tolerance questionnaires on d 1, 2, and 10 of each treatment period. Five-day fecal wet weight was higher after the PDX and SCF treatments than the LFC treatment (P ≤ 0.0007). The number of stools per day and daily fecal output also were significantly greater during the PDX treatment compared with the LFC treatment. The whole gut transit time did not differ among treatments. The PDX treatment resulted in a softer stool (P = 0.002) than the SCF and LFC treatments. Fecal pH was lowered by the PDX treatment (P = 0.02), whereas SCF tended to lower it compared with the LFC treatment (P = 0.07). When the participants consumed PDX and SCF, they reported significantly more flatulence and borborygmi compared with when they consumed the LFC. Consumption of PDX and SCF at a dose of 20 g/d results in a mild laxative effect with nominal gastrointestinal tolerance issues.

Prune juice has a mild laxative effect in adults with certain gastrointestinal symptoms

Prunes are believed to have a laxative effect. Our aim was to study whether prune juice affects gastrointestinal function in adults with certain gastrointestinal symptoms. The study comprised 54 volunteers (13 men, 41 women) whose mean age was 44 years (range, 24-82 years). The study began with a 1-week baseline period, followed by a 2-week prune juice period, and finally a 1-week follow-up period. During the prune juice period, the subjects drank, twice a day, 125 mL of the test prune juice, which consisted of plum juice concentrate, prune puree, water, and fructose. During the 4 study weeks the subjects kept a daily record of fecal frequency, difficulty of defecation, stool consistency, and gastrointestinal symptoms. The subjects reported fewer days with difficulty in defecation during the prune juice period (combined first and second weeks) than during the baseline week (1.3 vs 1.7 days, P = .02). This effect appeared to continue into the follow-up week. The mean frequency of days with flatulence was higher during the prune juice period than during the baseline week (2.1 vs 1.4 days, P = .02). Regularly ingested prune juice had a mild laxative effect in adults with certain gastrointestinal symptoms. However, it also increased flatulence. Prune juice may offer an alternative to laxatives, at least, in cases of mild constipation.

Advances in the Use of Milk Thistle (Silybum marianum)

Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.

Gastrointestinal responses following acute and medium term intake of retrograded resistant maltodextrins, classified as type 3 resistant starch

Study part 1 was executed as a randomized double-blind placebo-controlled crossover study and study part 2 as a longitudinal study. Forty-one healthy adult volunteers aged 18-24 years were recruited from the student population of the University of Salford. All subjects enrolled and completed study part 1 and 39 subjects enrolled and completed study part 2. In study part 1, individuals consumed, in random order 0, 20, 40, 60, 80, 100 or 120 g of a RRM containing starch product incorporated in pre-prepared foods on individual test days. Assuming a minimum content of 50% RRM in the starch product this delivered respectively 0, 10, 20, 30, 40, 50 or 60 g of RRM. All foods were prepared and coded by personnel not involved in carrying out the tests. Test days were separated by 7 day washout periods. In study part 2, consumption of RRM was increased from 3.6 g at day 1 in incremental doses up to each subject's MNED as determined in study 1, to be achieved at day 14. Subsequently, RRM intake was from day 15-21 in a way that the final intake at day 21 was at least 10 g above the individual MNED. In both parts of the study, subjects reported the prevalence and magnitude of GI symptoms. No significant change was observed in either defecation frequency and faecal consistency or the number of subjects experiencing any GI symptoms, following consumption of foods containing 0-60 g RRM. The individual MNED at which an increase in symptoms did not occur was determined as 60 g RRM for 71% of the subjects who participated in study part 1. Regression analysis showed that consumption of gradually increasing doses of RRM in food products over 21 days was associated with a significant increase in the mean symptom score for flatulence (P=1.5 x 10(-4)), total bowel movement frequency (P=0.023) and bowel movement frequency to pass watery faeces (P=0.0157). Increasing the ingested dose of RRM by 10 g above the predetermined MNED, however, did not provoke significant increases in GI symptoms. In both studies, the majority of symptom responses were classified by the subjects as 'little more than usual'. Consumption of up to 60 g RRM is tolerated well by most individuals with no evidence of any significant dose-dependent increase in the magnitude of symptoms or the occurrence of multiple GI symptoms. However, a mild laxative effect when consuming >60 g RRM is suggested. Although there was no change in GI responses following consumption of increasing doses of RRM over 21 days, generally a dose of 10 g RRM above the MNED level was tolerated well during medium term intake.

Sicilian Manna: A Sweet Gift of Nature

An Unusual Ingredient – Manna Manna, a gift from nature, comes from a kind of ash called “Fraxinus angustifolia” or “Fraxinus ornus” found in the surrounding areas of the towns of Castelbuono, Pollina and Cefalù (Italy). In the past, it was grown extensively in the Mediterranean basin though all traces of it seem to be lost. The history is pieced together with historical references from the Bible, health manuals from ancient civilizations, and references to the implements used to harvest it. Its mysterious or miraculous properties are presented; two kinds of manna were thought to exist, one from Heaven, and the other from a tree. The ideal conditions for growing the trees and harvest are described with plentiful folklore, local customs, special vocabulary and tools mentioned. Manna is harvested in summertime when the plant is “in love”, from June to September or until the first rains, which would dissolve it, start to fall. The people of Pollina romantically call manna, “a sweet gift of nature”. It tastes like honey mixed with carob. The sap flows through a gash made with a special technique, using a curved cutter called a “mannarolo,” on the vein of the trunk of the tree, and it is left to drip for several days. The sap crystallizes and forms long clumps similar to stalactites, which are called “cannolo” in the manna-world vocabulary. The juice is violet and very bitter when it drips, but the contact with the air and the strong Sicilian sun dries and sweetens it. “Cannoli” are harvested with an “archetto.” There is a second and third grade of sap, which doesn’t crystallize or form cannoli. Prickly-pear leaves act as a sort of spout to catch the manna. Its medicinal qualities include its mild laxative effect, its natural sweetness for dietary purposes, and its use in digestive alcoholic drinks and cosmetics is noted. It is sold at pharmacies and tobacco stores.

Chemical Composition and Potential Health Effects of Prunes: A Functional Food?

Referee: Paul La Chance, Dept. of Food Science, Rutgers University, New Brunswick, NJSupported in part by an educational grant from California Dried Plum Board.Prunes are dried plums, fruits of Prunus domestica L., cultivated and propagated since ancient times. Most dried prunes are produced from cultivar d'Agen, especially in California and France, where the cultivar originated. After harvest, prune-making plums are dehydrated in hot air at 85 to 90°C for 18 h, then further processed into prune juice, puree, or other prune products. This extensive literature review summarizes the current knowledge of chemical composition of prunes and their biological effects on human health. Because of their sweet flavor and well-known mild laxative effect, prunes are considered to be an epitome of functional foods, but the understanding of their mode of action is still unclear. Dried prunes contain ∼6.1 g of dietary fiber per 100 g, while prune juice is devoid of fiber due to filtration before bottling. The laxative action of both prune and prune juice could be explained by their high sorbitol content (14.7 and 6.1 g/100 g, respectively). Prunes are good source of energy in the form of simple sugars, but do not mediate a rapid rise in blood sugar concentration, possibly because of high fiber, fructose, and sorbitol content. Prunes contain large amounts of phenolic compounds (184 mg/100 g), mainly as neochlorogenic and chlorogenic acids, which may aid in the laxative action and delay glucose absorption. Phenolic compounds in prunes had been found to inhibit human LDL oxidation in vitro, and thus might serve as preventive agents against chronic diseases, such as heart disease and cancer. Additionally, high potassium content of prunes (745 mg/100 g) might be beneficial for cardiovascular health. Dried prunes are an important source of boron, which is postulated to play a role in prevention of osteoporosis. A serving of prunes (100 g) fulfills the daily requirement for boron (2 to 3 mg). More research is needed to assess the levels of carotenoids and other phytochemicals present in prunes to ensure correct labeling and accuracy of food composition tables in order to support dietary recommendations or health claims.

Silymarin: a review of its clinical properties in the management of hepatic disorders.

The mechanisms of action of silymarin involve different biochemical events, such as the stimulation of the synthetic rate of ribosomal RNA (rRNA) species through stimulation of polymerase I and rRNA transcription, protecting the cell membrane from radical-induced damage and blockage of the uptake of toxins such as alpha-amanitin. Studies in patients with liver disease have shown that silymarin increases superoxide dismutase (SOD) activity of lymphocytes and erythrocytes, as well as the expression of SOD in lymphocytes. Silymarin has also been shown to increase patient serum levels of glutathione and glutathione peroxidase. Silybin 20 to 48 mg/kg/day has shown promise as a clinical antidote to acute Amanita (deathcap mushroom) poisoning. Primary efficacy data from 3 trials which examined the therapeutic potential of silymarin in patients with cirrhosis, and included patient survival as an end-point, demonstrated that silymarin had no significant beneficial effect on patient mortality. However, upon subanalysis, silymarin 420 mg/day had a significantly beneficial effect on patient survival rate (compared with patients receiving placebo) in 1 randomised, double-blind trial in patients with alcoholic cirrhosis. Silymarin 420 mg/day was also shown to improve indices of liver function [AST, ALT, gamma-glutamyl transferase and bilirubin] in patients with liver disease of various aetiology, including those exposed to toxic levels of toluene or xylene; however, it was largely ineffective in patients with viral hepatitis. Reports of adverse events while receiving silymarin therapy are rare. However, there have been accounts of nausea, epigastric discomfort, arthralgia, pruritus, headache and urticaria. Silymarin has also been reported to have possibly caused a mild laxative effect. The antioxidant properties of silymarin (a mixture of at least 4 closely related flavonolignans, 60 to 70% of which is a mixture of 2 diastereomers of silybin) have been demonstrated in vitro and in animal and human studies. However, studies evaluating relevant health outcomes associated with these properties are lacking. Although silymarin has low oral absorption, oral dosages of 420 mg/day have shown some therapeutic potential, with good tolerability, in the treatment of alcoholic cirrhosis. Moreover, silybin 20 to 48 mg/kg/day has shown promise as an antidote for acute mushroom poisoning by Amanita phalloides; however, further studies paying attention to the amount of ingested mushroom and time elapsed before administration of treatment are needed to clarify its role in this indication. Studies in patients with the early onset of liver disease may demonstrate the liver regeneration properties that silymarin is promoted as possessing.

Pharmacological investigations of sticky viscome extract (Cleome viscosa L.) in rats, mice and guinea‐pigs

AbstractThe aqueous extract of seeds of Cleome viscosa L. has been studied for its pharmacological activities. It was found to be nontoxic when dosed orally and intraperitoneally to rats and mice. The extract showed significant analgesic activity in mice and local anaesthetic activity in guinea‐pigs. It potentiated the barbiturate sleeping time in rats and had a mild laxative effect, increasing the passage of soft faeces. It failed to protect against convulsions induced by picrotoxin in rats. The results are discussed in terms of the alleged uses of the plant in folklore medicine.

Effects of Ricinoleic and Oleic Acids on the DigestiveContractile Activity of the Canine Small and Large Bowel

Oleic and ricinoleic acids or their trans isomers, elaidic and ricinelaidic acids, were administered intraduodenally and evaluated for their effects on the digestive motor activity of the canine small and large bowel. Four dogs of mixed breed were implanted with duodenal cannulas and extraluminal strain gage transducers along the circular axis of the proximal and mid-jejunum, terminal ileum, and proximal colon. After feeding 200 g of canned dog food to induce continuous contractile activil of isotonic saline was given into the duodenum as a single bolus infusion and recordings were made for a 1-hr period. A 30-ml volume of saline served as control. Administration of each cis fatty acid produced an initial stimulation in jejunal areas of about a 2-min duration followed by a post-stimulatory inhibition. Both the initial stimulation and post-stimulatory inhibition were greater for ricinoleic acid than for oleic acid. Minimal or no effects were produced in ileal or colonic areas. In contrast, the trans isomers produced little or no effect on either the small or large bowel. Alterations in the digestive contractile patterns produced by oral administration of 10 ml of oleic, ricinoleic acid or their respective triglycerides were also tested. Triolein had no effects. Ricinoleic acid and castor oil poduced a brief initial stimulation followed by polonged inhibition of small bowel motor activity. Both cathartics had a mild laxative effect. Digestive motor patterns returned to control approximately 45 min after oleic acid. There was no indication at any time of an initiation of continuous contractile activity after ricinoleic acid or castor oil which could justify the use of the terms irritant of stimulant to describe their actions.

Studies on Single Oral Doses of a High Gel Point Methylcellulose

A high gel point methylcellulose (Methocel HG) was given in single doses to normal healthy young adults. Only minor symptoms were reported, e. g., mild laxative effect, mild constipating effect, and a few instances of commonplace symptoms such as cramping, flatus, headache, and tenesmus which apparently were not related to the ingestion of Methocel HG. Essentially all of the ingested Methocel HG was eliminated in the feces within ninety‐six hours following administration.

Wood Sugar Molasses as a Feedstuff for Laying Hens

CANE and beet molasses have been accepted and used as feedstuffs in live-stock rations for a number of years. Their basic nutritive value appears to be in their carbohydrate content. These products, however, are also reasonably good sources of such vitamins as biotin, pantothenic acid, pyridoxine, and niacin. Cane and beet molasses are comparatively high in mineral elements varying from 6 to 10 percent of the total weight. (Ewing, 1947; Morrison, 1948; Titus, 1949).Acceptance and use of molasses as a feed stuff for poultry have in general been slow. Winter (1929) reported results from feeding cane molasses to pullet and laying hens at 5, 10, and 15 percent levels. The product produced a mild laxative effect while feed intake and egg production were only slightly less than that obtained from the control birds. Mortality was reported to have been less in the lots fed molasses than in the controls. .

Note on Cholecystography with Priodax: Dosage and Gastro-Intestinal Effects

It is a new cholecystographic medium, β-(4-hydroxy -3,5 -di -iodophenyl) -α - phenylpropionic acid (Priodax), is superior to the tetraiodophenolphthalein preparations. Its diagnostic reliability is unchallenged, its yields better roentgenograms, it is comparatively easy to take, and it produces fewer and less severe side-effects than does tetraiodophenolphthalein. The recorded figures for the frequency of gastro-intestinal side-effects vary considerably. Vomiting is reported in different series as having occurred in 0.08 to 3 per cent, nausea in 8 to 26 per cent, and diarrhea in 3 to 23 per cent and “less than one-third” of the cases (1, 2, 3, 4, 5, 6). These variations might be due to differences in patients at various geographical locations, in the dose administered and method of preparation, and—in the case of nausea and diarrhea—to differences of definition. This paper deals with the frequency of gastro-intestinal effects as observed in two series of 100 cases each, and with the correlation of gastro-intestinal effects and dosage of the contrast medium. The first series includes 100 consecutive cases referred for gallbladder examination. The patients were prepared as recommended by the manufacturers of Priodax. The dose administered was 6 tablets for patients up to 150 lb., 9 tablets from 150 to 200 lb., and 12 tablets above 200 lb. If the gallbladder was not visualized, a reexamination was done with 12 tablets for patients up to, and 18 tablets for patients above, 150 lb. In every case, we recorded weight and number of tablets taken, also the number of bowel movements between taking the tablets and examination and the occurrence of vomiting and of persistent nausea. Transitory slight nausea of a few minutes' duration was not recorded. The results of this investigation are shown in Table I (Series I). Seventeen patients in this series reported nausea, but none of them vomited. Forty-four registered a mild laxative effect with two to four bowel movements, and 20 had from five to twelve bowel movements. The average number of bowel movements was 2.8. The patients were divided into classes according to the number of tablets received per pound. In all classes with from 0.03 to 0.06 tablets per pound (or up to one tablet per 17 lb.) the average number of bowel movements was about the same. A total of 56 patients fell into this range (Series IA in the table); they produced an average of 1.9 bowel movements, and 6 (or 11 per cent) registered nausea. The remaining 44 patients (series IB in the table) had received from 0.061 to 0.104 tablets per pound; they produced an average of 4.0 bowel movements, and 11 (or 25 per cent) experienced nausea. These figures indicate that there is a definite relation between dose administered and gastro-intestinal effects. There seems to be a borderline near the dose of one tablet per 17 lb.