Increased Stool Weight Research Articles

Therapeutic effect of Novalac-IT in infants with constipation

Objective Infant constipation is a frequent condition in formula-fed infants. Methods A prospective randomized clinical trial was performed in infants who had constipation with Novalac-IT (IT group) versus a 20% strengthened formula (S group). Enrolled subjects had difficulties in defecating, hard stools, or low frequency of defecation (≤3 times/wk). Results Ninety-three infants (47 boys, mean age 3.8 ± 1.7 mo) were included because of hard consistency of (50.5%), low frequency in (44.1%), or painful (33.3%) defecation. A statistically significant improvement was observed after 4 and 8 wk of intervention in the IT group ( P = 0.014 and P < 0.001, respectively). In the IT group, significantly more infants were symptom free at 4 wk (82.9% versus 50%, P = 0.029) and at 8 wk (89.1% versus 54.1%, P < 0.001). Increased stool weight was significant in the IT group after 4 and 8 wk ( P = 0.048 and 0.029). Conclusion Novalac-IT decreases constipation in formula-fed infants.

Mitemcinal (GM‐611), an orally active motilin agonist, facilitates defecation in rabbits and dogs without causing loose stools

The effects of mitemcinal (GM-611), an orally active motilin agonist, on defecation were investigated in rabbits and dogs. In normal rabbits, within 0-3 h of dosing, orally administered mitemcinal (2.5-10 mg kg(-1)) increased stool weight in a dose-dependent manner without causing loose stools. Sennoside (12-48 mg kg(-1)) also facilitated defecation within 2-9 h of oral administration, but the stools were significantly loosened. In the morphine-induced constipation model, the stool weight of morphine-treated rabbits (1 mg kg(-1)) was only 37.5% of that of untreated animals. Mitemcinal (0.5-20 mg kg(-1)) dose-dependently increased stool weight without increasing stool water content. At the highest dose of mitemcinal, stool weight recovered to 83.9% of that of untreated animals. In normal dogs, mitemcinal (0.3-3 mg kg(-1)) reduced the time to first bowel movement after oral administration without inducing diarrhoea at any dose. These results indicate that mitemcinal facilitates defecation without inducing severe diarrhoea. It is suggested that mitemcinal may be a novel therapeutic agent for constipation that enables easier control of the timing of defecation because of the early onset and short duration of its action, compared with sennoside.

Causes of Chronic Diarrhea

Diarrhea can be classified in several ways. It is both a symptom and a sign. As a symptom, it is whatever the patient says it is: a decrease in consistency, an increase in the number or volume of bowel movements, or any combination thereof. As a sign, diarrhea is an increase in stool weight (or volume) of more than 200 g (or ml) per 24 hours in a person on a Western diet. The distinction between chronic and acute diarrhea is arbitrary: it is determined by duration. Diarrhea is generally considered acute when it lasts less than two or three . . .

Bile acids and post-vagotomy diarrhoea.

Abstract Cholecystectomy increases the risk of post-vagotomy diarrhoea and bile acid binding agents may relieve it, suggesting a role for bile acids in its pathogenesis. The faecal bile acid loss in 15 patients with episodic diarrhoea after vagotomy and drainage was not raised when compared with 12 normal subjects, except on days when diarrhoea occurred. This elevation was caused by an increase in stool weight rather than bile acid concentration, suggesting that the increased bile acid loss during attacks was not causally related. Asymptomatic vagotomy patients excreted normal amounts of bile acids. Seven patients with episodic diarrhoea after vagotomy and drainage with cholecystectomy continuously excreted excessive amounts of bile acids when compared with normal subjects and asymptomatic patients. The concentration of bile acid in their stools was higher than that observed in symptomatic patients after vagotomy and drainage alone. The continuous presence of excess bile acid may prime the colon to react more readily to stimuli caused by disturbed gastric emptying and rapid small bowel transit, without being the main factor in causing the condition. These findings may explain the increased risk of diarrhoea when cholecystectomy is combined with vagotomy.

Dietary fibre and gastrointestinal disease.

This review examines the evidence linking dietary fibre to gastrointestinal disease. Fibre increases stool weight, decreases whole gut transit time and lowers colonic intraluminal pressure. While it may be of benefit in the treatment of constipation, the irritable bowel syndrome and diverticular disease, its role in the prevention or treatment of other gastrointestinal disease has yet to be established.

Effects of lactulose and polyethylene glycol on colonic transit

The effects of lactulose and polyethylene glycol on colonic transit are poorly established. To assess the effects of these laxatives on colonic transit in normal subjects. Colonic transit (mean residence time, cumulative counts in stool, counts remaining in the proximal or distal colon) was measured scintigraphically in normal subjects on the second and third day of a 3-day ingestion of 67-134 g/day lactulose, or 59 g/day polyethylene glycol. At similar stool weight (lactulose: 653 +/- 120 g/day; polyethylene glycol: 522 +/- 66 g/day), transit was significantly slower during 99 g/day lactulose when compared with 59 g/day polyethylene glycol; this was most pronounced in the distal colon (mean residence time: lactulose - 403 +/- 55 min; polyethylene glycol - 160 +/- 41.9 min). Short chain fatty acid concentration in 24-h stool correlated significantly with counts remaining in the distal colon at 12 h (r = 0.79, P = 0.001). Increasing lactulose doses were significantly associated with increasing stool weight (r = 0.79) and shorter mean residence time in the total (r = -0.56) and distal colon (r = -0.64). The sum of faecal carbohydrates plus short chain fatty acids was associated with stool weight (r = 0.95, P < 0.001). Lactulose accelerates colonic transit. However, compared with polyethylene glycol, transit during lactulose is prolonged.

A tube-fed liquid formula diet containing dietary fiber increased stool weight in bed-ridden elderly patients

Objective The number of bedridden elderly patients who need a liquid diet has been increasing. We evaluated the usefulness of a tube-fed liquid diet containing cellulose and oligosaccharide for elderly bedridden patients. Methods Twenty-two elderly bedridden patients were given a liquid diet containing cellulose and lafinose for 4 wk. Parameters associated with blood and stool weight were measured during this period. Results Stool weight increased by 32.0 g in men and 8.8 g in women at 2 wk and remained at these weights up to 4 wk ( P < 0.05 before and after 2 wk, 3 wk, and 4 wk in men, and P < 0.05 before and after 3 wk in women). Body weight increased in men (0.5 kg) and women (0.7 kg) 15 d after starting the diet and then remained at these values up to 29 d thereafter, and statistically significant differences were not seen. There were no changes in nutritional parameters such as total protein. Conclusion No significant changes were observed in the general condition of elderly patients, with the exception of a positive increase in fecal weight, by 30-d supplementation of a liquid diet containing cellulose and lafinose.

Fibre effects on intestinal functions (diarrhoea, constipation and irritable bowel syndrome)

Summary The effects of fibre on intestinal functions and diseases have been the area of a large body of research conducted over the past decades. In this presentation, some aspects of its effects on diarrhoea, constipation and its use in the irritable bowel syndrome (IBS) are discussed. Dietary fibre is difficult to define and difficult to analyse. Some studies on bowel function and intestinal disease have used high-fibre diets, while most have used fibre concentrates such as wheat bran or preparations of isolated non-digestible carbohydrates. Different fibre sources in the diet do not have the same qualitative or quantitative effects on intestinal functions, making general recommendations on fibre type and amount extremely difficult. Increased fibre intake will generally increase stool weight. The magnitude of the increase varies with the fibre source. The contributions of this increase from an elevated bacterial mass, faecal water and undigested fibre also vary markedly with the type of fibre. Data on the use of fibre are most convincing regarding constipation. Fibre increase bowel movement frequency modestly in constipation and improves symptoms. However, there is too little evidence to determine if one treatment is better than another, and to determine the best treatment for different types of patients, or what fibre source which is most effective. The use of fibre for the treatment of diarrhoea is poorly documented outside the area of enteral nutrition. Though effects have been shown, especially on the duration of diarrhoea in children, further research is needed for recommendations to be made. Fibre and bulking agents are commonly used in the treatment of IBS, but the benefits seem to remain unproven despite a large number of trials. Some IBS patients may benefit from fibre supplementation, but there are problems of tolerance in many patients. Some fibre products may be better tolerated than others, but data are too sparse for definite recommendations to be made.

Effects of Isomalto-Oligosaccharides on Bowel Functions and Indicators of Nutritional Status in Constipated Elderly Men

Objectives: To evaluate effects of isomalto-oligosaccharides (IO) on the bowel function and nutritional status of elderly men.Methods: Seven older male subjects participated in this study that consisted of a 30-day control low fiber period followed by a 30-day IO-supplemented (10 g active components) experimental period. Bowel functions such as defecation, enema use and bloating were monitored daily. Fecal characteristics such as wet and dry stool weights, stool moisture, pH and short-chain fatty acid contents were determined on five-day fecal composites collected in each period. Feces were further fractionated into plant, bacterial and soluble fractions to determine the bases for the increase in stool weight. Nutritional status of subjects was assessed with anthropometric parameters, nutrient intake and biochemical measurements.Results: Incorporation of IO significantly increased the defecation frequency, wet stool output and dry stool weight by twofold, 70% and 55%, respectively. Fecal acetate and propionate concentrations significantly increased by nearly two and a half fold with IO supplement. The increase in stool bulk was mainly attributed by increased bacterial mass. Mean serum sodium concentration decreased in the experimental period while other blood characteristics did not change significantly. Anthropometric parameters and nutrient intake remained constant throughout the study.Conclusions: Consumption of IO effectively improved bowel movement, stool output and microbial fermentation in the colon without any adverse effect observed in this study. Therefore, supplementation of IO into ordinary low fiber diets may be practical in relieving constipation in the elderly population.

Effects of fructooligosaccharide on bowel function and indicators of nutritional status in constipated elderly men

Five subjects completed the study consisting of a 30-d low fiber control period and another 30-d experimental period in which 10 g of FO was supplemented to a 3-d cycle menus. Status of large bowel function was monitored daily. Feces were completely collected on last 5 d of each period to determine the fecal characteristics and fecal short-chain fatty acid (SCFA) contents. Nutrient intake, body weight, arm anthropometric parameters, serum albumin, total protein, triglyceride, cholesterol, and electrolytes were measured as indices of nutritional status. Incorporation of FO significantly increased the defecation frequency, daily stool weight, weight per stool and decreased the use of enema. Concentrations of fecal acetate, propionate, i-butyrate, n-butyrate, i-valerate and n-valerate increased by 3–18 fold in the experimental period. Nutrient intake and anthropometric indices remained constant throughout the study. Serum concentrations of Na and K were decreased and concentrations of Ca and P were increased in the experimental period. Other blood biochemical parameters were not affected by the treatment. Therefore, we conclude that supplementation of FO was able to alleviate constipation, increase stool weight and fecal SCFA concentrations without affecting plasma lipid concentrations in the normolipidemic, constipated elderly men.

An unfermented gel component of psyllium seed husk promotes laxation as a lubricant in humans

In addition to increasing stool weight, supplements of psyllium seed husk produce stools that are slick and gelatinous. Our purpose was to test the hypothesis that a gel-forming fraction of psyllium escapes microbial fermentation and is responsible for the characteristics that enhance laxation. Fifteen healthy adults consumed controlled diets for two 7-d periods, one of which included 8.8 g dietary fiber provided by 15 g/d of a psyllium seed husk preparation. All stools were collected and evaluated and diet was monitored throughout. Psyllium significantly increased the apparent viscosity of an aqueous stool extract, stool moisture, and wet and dry stool weights. A very viscous fraction, not present in low-fiber stool and containing predominantly 2 sugars that are also found in abundance in psyllium husk, was isolated from psyllium stool. In contrast with other viscous fibers that are fermented completely in the colon, a component of psyllium is not fermented. This gel provided lubrication that facilitated propulsion of colon contents and produced a stool that was bulkier and more moist than were stools resulting with use of comparable amounts of other bowel-regulating fiber sources.

Plant Residue and Bacteria as Bases for Increased Stool Weight Accompanying Consumption of Higher Dietary Fiber Diets

Objective: Stool diluting effects of relatively inert material, such as unfermentable dietary fiber, has been proposed as an effect of fiber beneficial to the colon. Stool dilution by increasing bacterial mass may be beneficial or deleterious, depending on bacterial metabolic products. The purpose of this study was to determine the basis for stool weight when two stepwise increases of fiber from all classes of fiber-containing foods were consumed.Methods: Stool from five men consuming three constant diets containing 15, 30 and 42 g/d of dietary fiber were fractionated into plant material and bacteria and analyzed for neutral and amino sugar content. Fecal nitrogen, fat and ash were measured.Results: Daily gravimetric yield and sugar content of the plant fraction from stool increased with each fiber addition. Compared to the low fiber diet, the medium fiber diet decreased the concentration of the bacterial mass in wet stool by 11% and the high fiber diet by an additional 32%. The high fiber diet decreased stool fat concentration; the medium and high fiber diets decreased stool nitrogen concentration to the same extent. Apparent digestibility of plant-derived neutral sugars decreased with each fiber addition.Conclusions: Inherently less fermentable plant material modulates the colon environment in three beneficial ways: it is a relatively unreactive diluent of lumenal contents; it adds mass to promote distal movement of waste; it does not promote a large bacterial mass.

Extract from Clinical Evidence: Diarrhoea

Interventions Trade off between benefits and harms Empirical antibiotic treatment in travellers' diarrhoea Empirical antibiotic treatment in community acquired diarrhoea Summary points RCTs have found that empirically treating travellers' diarrhoea with antibiotics reduces the length of illness by one to two days. In community acquired diarrhoea, RCTs have found that ciprofloxacin reduces the duration of diarrhoea by one to two days. Trials of other antibiotics have found no evidence of benefit or have not reported on time to cure. Some RCTs found that treatment prolonged excretion of organisms and was associated with the development of resistant organisms. ### Definition Diarrhoea is defined as watery or liquid stools, usually with an increase in stool weight above 200 g per day and an increase in daily stool frequency. Incidence/prevalence An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths.1 In developing countries, diarrhoea is reported to cause more deaths in children aged under five years than any other condition.1 In the United States, which has a low incidence, the estimated incidence for infectious intestinal disease is 0.44 episodes per person per year, or one episode per person every 2.3 years, resulting in about one consultation with a doctor per person every 28 years.2 The epidemiology of travellers' diarrhoea (people who have crossed a national boundary) is not well known. Incidence is higher in travellers going to developing countries but varies widely by location and season of travel. 3 ### Aetiology The cause depends on geographic location, standards of food hygiene, sanitation, water supply, and …

Mechanisms by which wheat bran and oat bran increase stool weight in humans

Generally, stool weight is significantly increased by adding sources of insoluble fiber to the diet. Comparable amounts of fiber provided by wheat and oat brans have the same effect on daily stool output, even though > 90% of wheat bran fiber but only 50-60% of oat bran fiber is insoluble. To determine the bases for these increases in stool weight, stool samples collected from 5 men in 2 constant diet studies that determined the effects of wheat and oat brans on large-bowel physiology were fractionated by using a physicochemical procedure into plant, bacterial, and soluble fractions, which were weighed and analyzed for sugar content and composition. Nitrogen, crude fat, and ash outputs were also determined. Wheat bran increased the fecal concentration of sugars and mass of plant material more than did oat bran, whereas oat bran increased fecal bacterial mass more. Each fiber source increased nitrogen, ash, and fat excretion, but excretion of fat was greater with oat bran. The apparent digestibility of plant-derived neutral sugars decreased significantly when wheat but not oat bran was consumed. The apparent digestibility of neutral sugars provided by wheat bran was 56%; the apparent digestibility of those provided by oat bran was 96%. We conclude that bacteria and lipids are major contributors to the increase in stool weight with oat bran consumption, whereas undigested plant fiber is responsible for much of the increase in stool weight with wheat bran consumption. Results are consistent with the hypothesis that oat bran increases stool weight by providing rapidly fermented soluble fiber in the proximal colon for bacterial growth, which is sustained until excretion by fermentation of the insoluble fiber.

Limited effect of consumption of uncooked (RS2) or retrograded (RS3) resistant starch on putative risk factors for colon cancer in healthy men

To investigate whether resistant starch (RS) affects putative risk factors for colon cancer, 24 healthy men consumed a daily RS supplement for 4 wk in addition to their habitual diet in a single-blind, randomized, balanced multiple crossover trial. During the first week, all subjects consumed the control supplement containing glucose. Subsequently, each subject consumed, in random order, a supplement with RS2 (uncooked high-amylose cornstarch), RS3 (extruded and retrograded high-amylose cornstarch), and glucose, each for 1 wk. The RS2 and RS3 supplements provided 32 g RS/d. Lithium was added to the supplements to measure compliance. Feces, 24-h urine, and breath samples, as well as a 24-h food-consumption recall were obtained weekly from each subject. Compliance as measured by urinary lithium recovery was satisfactory. The mean composition of the background diet did not differ between the various supplementation periods. Breath-hydrogen excretion, stool weight, and fecal starch excretion were significantly higher during RS than during glucose supplementation, but did not differ during RS2 and RS3 supplementation. There were no significant differences in fecal dry weight, pH, or short-chain fatty acid concentrations, nor in the pH, bile acid concentrations, cytotoxicity, or osmolality of fecal water. It is concluded that in healthy men, supplementing the habitual diet for 1 wk with 32 g RS2 or RS3/d compared with glucose had no effect on putative risk factors for colon cancer, except for increasing stool weight and colonic fermentative activity. There were no significant differences between the effects of RS2 and RS3 on the indexes studied.

Effect of dietary oat and soy fiber on bowel function and clinical tolerance in a tube feeding dependent population.

The role of fiber in tube feeding products has not clearly been defined. While some studies suggest that fiber can increase stool weight and bowel transit time in acutely ill patients, there is less information in stable patients receiving chronic enteral nutritional support. Using a crossover study design, we investigated the effect of 28.8 g/day of a 50% soy and 50% oat fiber combination in 10 medically stable residents of a chronic care facility. Subjects were randomized to initially receive 10 days of either Isocal HN or Ultracal, which are identical in composition except Ultracal contains 14.4 g/L of fiber. After the first 10-day study, subjects underwent a washout followed by a second 10-day study using the other product. Fecal dye markers were used to identify appropriate collection times. Fiber significantly increased the number of bowel movements per day (0.9 +/- 0.4 vs 0.5 +/- 0.2, p < 0.05) and fecal weights (57 +/- 31 vs 32 +/- 25 g/day, p < 0.05). Fiber also caused a significant increase in fecal nitrogen output (110 +/- 65 vs 75 +/- 74 mg/day, p < 0.05) and fecal energy (141 +/- 73 vs 76 +/- 62 kcal/day, p < 0.05). Fiber did not affect fecal moisture, gastric emptying, or intestinal transit time. We conclude that the addition of a combination of soy and oat fiber to tube feeding material is well tolerated, and promotes regular bowel movements without altering the rate of gastric emptying or intestinal transit time.

Carbohydrates: Significance for Energy Balance and Gastrointestinal Function

The 10th edition of the RDA discusses carbohydrates in the context of dietary fiber and digestible carbohydrates, which provide energy, and recommends that more than half the energy requirement beyond infancy be provided by carbohydrates and that a desirable intake of fiber be achieved by consumption of fruits, vegetables, legumes, and whole-grain cereals. The recommendations on digestible carbohydrates are primarily based on the desirability of limiting the intake of fat. An additional consideration is the suggestion that excess calories from carbohydrate vs. fat are metabolized and stored with different efficiencies. The scientific basis for recommending an appropriate intake of dietary fiber is not clearly evident in the current RDA. The association between a high plant food, and thus fiber intake, and lower incidence of cardiovascular disease, colon cancer, and diabetes is of interest but difficult to use to form the basis of specific recommendations for an appropriate amount of fiber to include in the diet. The importance of fiber for normal gastrointestinal function provides the best scientific basis for developing recommended intake levels. Dietary fiber, as well as non-digested starch, are the only known dietary components that increase stool weight and are the primary substrates for the microflora in the large intestine. Metabolism of this microflora, including production of short chain fatty acids that are used by epithelial cells, appears to be important for intestinal health. However, the challenge we still face is to define the parameters of gastrointestinal function that are compatible with health.

How effective is nonlaxative treatment of constipation?

In almost any textbook of medicine so-called simple measures are proposed for treating constipation, such as increasing physical activity, drinking more fluid, triggering the gastrocolonic response by, e.g., drinking a glass of water or a cup of coffee, and bowel training. All of these have not been formally evaluated in constipated patients. Biofeedback training is useful for paradoxical puborectal contraction ('anismus'). Dietary fibre, e.g. in the form of wheat bran, increases stool weight and decreases colonic transit time. So every patient should have an empiric treatment with an adequate amount of fibre. Some patients, especially those with slow transit constipation and those with stasis in the right hemicolon, are not likely to respond to a therapy with bran, however.

Influence of senna, fibre, and fibre + senna on colonic transit in loperamide-induced constipation.

Retarded colonic transit and disturbed defecation are the most prominent pathophysiological mechanisms in constipation. Both may be influenced by bulking agents and by laxatives such as senna. Direct measurements of the influence of such substances on colonic transit are rare mainly because of technical problems. We measured gastric emptying, small and large intestinal transit in 24 healthy volunteers by a newly developed method employing a metal detector. Twelve persons taking a normal diet received loperamide in a dose sufficient to double the individual transit time. All subjects measured gastrointestinal transit time under normal conditions and with Sennatin containing purified sennosides 20 mg, Agiocur (30 g) as a fibre product containing 20 g Plantago ovata seeds/husks, or Agiolax (10 g) as a combination of 5.4 g P. ovata seeds/husks + 1.2 g senna pod with a sennoside content of 30 mg. Colonic transit was reduced by Sennatin and by Agiolax from 39 +/- 4 h to 17 +/- 3 h (p < 0.005). Agiocur did not influence colonic transit (39 +/- 3 h). Loperamide prolonged colonic transit from 27 +/- 0.7 to 72 +/- 12 h. This effect was abolished by Sennatin (30 +/- 5 h) and Agiolax (27 +/- 1 h) (p < 0.005), but not by Agiocur (64 +/- 13 h). The same effects were seen when right and left colonic transit were analyzed separately. Neither gastric emptying nor small intestinal transit were affected by either substance. All of the three study drugs increased stool weight significantly (p < 0.05). When stool frequency and consistency were compared, the effects were less clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of CCK in regulation of pancreaticobiliary functions and GI motility in humans: effects of loxiglumide

To evaluate the physiological role of cholecystokinin (CCK) in humans, we studied the influence of the specific CCK receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output, plasma CCK concentrations, mouth-to-cecum transit time (MCTT), stool weight, and fecal fat excretion. Infusion of CCK-8, producing CCK plasma levels of 10-12 pmol/l, decreased gallbladder volume to 21% of the initial volume (P less than 0.01) and increased bilirubin output 8- to 10-fold and pancreatic enzyme secretion 2- to 4-fold. Infusion of loxiglumide (10 mg.kg-1.h-1 iv) abolished CCK-8-stimulated enzyme and bilirubin output. Basal gallbladder volume increased 68% during loxiglumide infusion (P less than 0.001) and 137% (P less than 0.001) after 7 days of oral loxiglumide treatment (3 x 1.6 g/day). Gallbladder contraction and bilirubin output in response to the intraduodenal instillation of a liquid meal (382 kcal) was completely inhibited by loxiglumide; gallbladder volume even increased 45% postprandially during loxiglumide infusion (P less than 0.02) and 145% after long-term loxiglumide treatment (P less than 0.001). Meal-stimulated pancreatic enzyme output was diminished 46-53% after acute and 25-29% after chronic administration of loxiglumide. Meal-stimulated integrated plasma CCK-immunoreactive (CCK-ir) concentrations, determined by RIA, were 3.2-fold higher during loxiglumide infusion (P less than 0.02); plateau CCK levels were markedly elevated (10.1 +/- 1.4 vs. 3.7 +/- 0.5 pM). Plasma CCK-like bioactivity, measured by a sensitive bioassay, was identical to CCK-ir levels in the absence of loxiglumide; in the presence of loxiglumide, no circulating CCK-like bioactivity was detectable, indicating complete inhibition of plasma CCK. MCTT was augmented 24% (P less than 0.05). Oral treatment with loxiglumide increased stool weight 72% (P less than 0.01) and fecal fat excretion 186% (P less than 0.001). In conclusion, 1) meal-induced gallbladder contraction and fasting tone are primarily controlled by CCK; 2) the contribution of CCK to the intestinal phase of postprandial pancreatic enzyme secretion is 40-50%; 3) GI motility and absorption are partially controlled by CCK; and 4) postprandial CCK secretion is substantially augmented by loxiglumide via an unknown mechanism.