Probiotic potential of Lacticaseibacillus rhamnosus VHProbi M15 on sucralfate-induced constipation in mice.

The main objective of this study was to investigate the potential probiotic properties of Lacticaseibacillus rhamnosus VHProbi®M15 (M15). This study examined the effects of M15 on sucralfate-induced constipation in a mouse model. The BALB/c mice were randomly divided into four groups: the normal group (NOR) was without any treatment, while the constipation (CON), phenolphthalein (PHE), and probiotic (PRO) treatment groups were fed with sucralfate until the appearance of constipation symptoms. Afterward, the NOR and CON groups were given 1 ml saline orally every day until the end of the experiment; the PHE and PRO groups were given phenolphthalein or M15 suspension in 1 ml orally, respectively. Compared with the CON group, the fecal water content and intestinal peristalsis improved in the PRO group. Here, intake of M15 effectively attenuated sucralfate-induced constipation, recuperated colonic epithelial integrity, and increased serum levels of gastrointestinal excitatory neurotransmitters (motilin, gastrin, substance P). Analysis of the intestinal microbiota of mice by 16S rRNA metagenomic revealed an increase in the relative abundance of Bacteroides and a decrease in Sclerotinia, Verrucosa and Proteus in the PRO group. Compared with the CON group, the constipation-induced intestinal microecological changes were partially recovered in the PHE and PRO groups. These results demonstrate that M15 enhanced gastrointestinal transit and alleviated in mice with sucralfate-induced constipation.

Therapeutic effects of Bombax ceiba flower aqueous extracts against loperamide-induced constipation in mice.

CONTEXT: Bombax ceiba Linnaeus (Bombacaceae) is known as silk cotton tree, the flowers of which are used in many medicinal applications. OBJECTIVE: To investigate the therapeutic effect of B. ceiba flower aqueous extracts (BCE) against loperamide-induced constipation and characterize the chemical composition of BCE. MATERIALS AND METHODS: Sixty male Kunming mice were divided into control (saline), model (10 mg/kg loperamide + saline), phenolphthalein (10 mg/kg loperamide + 10 mg/kg phenolphthalein) and different dosage of BCE (10 mg/kg loperamide + 40, 80 and 160 mg/kg BCE, respectively) groups, and received intragastric administrations for eight days. Faecal water content, number of faeces, first black-stool defecation time and gastrointestinal transit rates were evaluated. Various biochemical and molecular biomarkers were assessed in blood and colon. UPLC-ESI-QTOF-MS/MS was used to tentatively identify the composition of the BCE. RESULTS: BCE treatment (160 mg/kg) could increase faecal water (15.75%), faeces number (11.65%), gastrointestinal transit rate (25.37%) and decrease first black-stool defecation time (24.04%). The BCE (80 mg/kg) increased the serum level of motilin (30.62%), gastrin (54.46%) and substance P (18.99%), and decreased somatostatin (19.47%). Additionally, the BCE (160 mg/kg) reduced the mucosal damage, restored colonic goblet cell function, down-regulated the protein expression of AQP3 (33.60%) and increased c-kit protein expression (11.63%). Twelve known compounds, including protocatechuic acid, chlorogenic acid and rutin, previously reported in B. ceiba, were identified in the BCE. DISCUSSION AND CONCLUSIONS: This study suggested that BCE is a promising agent for the treatment of constipation.

Phenolphthalein-induced toxic epidermal necrolysis.

OBJECTIVE: To report a case of phenolphthalein-induced toxic epidermal necrolysis (TEN) in a patient maintained on several other medications more commonly known to be associated with TEN. CASE SUMMARY: A 78-year-old white man presented with intractable lower back pain and constipation. On day 1 of admission, the patient exhibited a diffuse urticarial rash over his trunk and extremities. History revealed that the patient had taken a combination phenolphthalein/docusate sodium (Correctol) over-the-counter laxative 1 day prior to admission. He had a similar urticarial rash 1.5 years earlier with this product and was instructed not to use it. A biopsy was performed and evidence from light microscopic analysis of the tissue led to a diagnosis of TEN. Furosemide, spironolactone, allopurinol, and hydroxyurea were considered possible causes of the reaction and were discontinued. Despite this, the lesions worsened in severity. The patient subsequently responded well to intravenous antibiotics, intravenous corticosteroids, and local wound care. Furosemide, spironolactone, hydroxyurea, allopurinol, and docusate were all reintroduced without reactivation of the lesions. DISCUSSION: Phenolphthalein is the active ingredient in several over-the-counter laxative preparations and has only rarely been reported to cause TEN. (It is no longer contained in Correctol.) To our knowledge, this case report represents only the third description of laxative-induced TEN. Although this patient had been exposed to several other medications more commonly associated with TEN, his long-term tolerance of and uneventful rechallenge with these medications exclude them as potential catalysts to this drug reaction. The patient's previous rash and the temporal relation of this event and the ingestion of phenolphthalein, as well as the similarity of this case to other reports, point to phenolphthalein as the cause of TEN in this patient. CONCLUSIONS: TEN is a rare disorder that can be fatal in up to 30% of patients. Clinicians should include phenolphthalein in their list of possible causes of drug-induced TEN. A careful and complete medication history can help avoid unnecessary discontinuation of clinically important medications and inadvertent rechallenge with the causative agent.

Diarrea crónica por ingesta de laxantes / Chronic diarrhea due to laxatives

La constipación crónica es una condición muy frecuente en el sexo femenino. La toma habitual y muchas veces, autoprescrita de laxantes es igualmente frecuente. Los mucílagos y los lubricantes no tienen riesgos no así los irritantes drásticos que pueden producir cuadros diarreicos crónicos graves

Phenolphthalein-containing laxative use in relation to adenomatous colorectal polyps in three studies.

Phenolphthalein, the active ingredient in many laxatives, was recently found to be a carcinogen in animal models. Human data suggest a laxative-colon cancer association, but few data specifically address the effects of phenolthalein-containing laxatives. We examined use of phenolphtalein-containing laxatives in relation to occurrence of adenomatous colorectal polyps in data from three case-control studies. The study conducted in Los Angeles, California (1991-1993), and the two studies conducted in North Carolina (1988-1990 and 1992-1995) altogether included 866 cases and 1,066 controls. The prevalence of using phenolphthalein-containing laxatives at least once a week in the recent past, however, was less than 5% among these subjects. The multivariate-adjusted odds ratios associated with recent use of phenolphthalein-containing laxatives once a week or more were 1.8 -95% confidence interval (CI), 0.5-6.2] in Los Angeles, 1.0 (CI, 0.4-2.2) in North Carolina (1988-1990), and 1.1 (CI, 0.2-5.7) in North Carolina (1992-1995). For use of other types of laxatives, the corresponding odds ratios were 1.3 (CI, 0.9-1.9) in Los Angeles, 1.0 (CI, 0.5-1.7) in North Carolina (1988-1990), and 0.9 (CI, 0.4-1.8) in North Carolina (1992-1995). Although the low prevalence of frequent use made for relatively wide confidence intervals, overall these data suggest that use of phenolphthalein-containing laxatives does not increase risk of adenomatous colorectal polyps.

Therapeutic modalities for mechanical cleansing of the colon.

Mechanical cleansing of the colon is an accepted standard of practice prior to colon surgery, and endoscopic and radiographic procedures. Cleansing the bowel prior to these procedures increases the accuracy of the diagnostic procedures and decreases the morbidity and mortality following surgery, where fecal contamination is a concern. Mechanical cleansing agents are sometimes used for acute constipation, but because of the extent and harshness of the evacuation they induce, and because of their adverse effects, they are not used for long-term management of constipation. Dosages vary among products, procedures, and individuals. Manufacturer guidelines should be consulted for proper dosing and administration.

Comparative assessment of phenolphthalein and phenolphthalein glucuronide: is phenolphthalein glucuronide a better laxative?

BACKGROUND: Phenolphthalein is widely used as a safe and effective laxative. After oral administration, phenolphthalein is absorbed in the small bowel and is conjugated in the liver to phenolphthalein glucuronide which passes into the colon where it is deconjugated and the active compound, phenolphthalein, is released. Since phenolphthalein glucuronide does not undergo enterohepatic circulation it should theoretically have a more rapid onset of action and a lower threshold dose for laxation. The present study was designed to examine this issue. METHODS: Ten normal healthy subjects volunteered for the study. All subjects were administered placebo, phenolphthalein (at doses of 15, 30, 45, 60, 75 and 90 mg) or phenolphthalein glucuronide (at equivalent doses of 24, 48, 72, 96, 120 and 144 mg) in a random order. Stool weight, the frequency and consistency of stools, and the development of symptoms were recorded at 12-h intervals for 84 h. RESULTS: There was a significant increase in the mean stool weight obtained within the first 24 h of administration of a 30 mg dose of phenolphthalein and its glucuronide equivalent compared to the values obtained with placebo. A further increase in the dose did not improve the therapeutic response. There was no difference between phenolphthalein and phenolphthalein glucuronide with respect to the rapidity of action, the threshold dose, effectiveness of laxation, or the frequency of adverse effects. CONCLUSIONS: The therapeutic response and side effect profile of the different doses favoured 30 mg phenolphthalein as the optimum laxative dose. Although theoretically superior, phenolphthalein glucuronide was not found to be a more effective laxative compared to phenolphthalein in normal subjects.

Renal failure associated with laxative abuse.

Eating disorder patients often abuse laxatives in an attempt to purge excess food. Laxative abuse can cause hypokalemia and volume depletion. Hypokalemia, in turn, can lead to rhabdomyolysis. Laxative-induced hypokalemia and volume depletion have been previously reported to cause renal insufficiency, but not severe enough to require hemodialysis. A 27-year-old woman with a long history of laxative abuse presented with severe renal failure associated with hypokalemia and volume depletion. She required acute hemodialysis for worsening acidosis (pH 7.05) despite assisted ventilation. A prior episode of hypokalemic rhabdomyolysis at age 23 had resulted in only mild renal insufficiency. Her later episode of severe renal failure was linked to profound volume depletion (blood urea nitrogen 135 mg/dl). This patient calls attention to a potentially life-threatening complication of laxative abuse and indicates that volume depletion can exacerbate laxative-associated renal failure.

Laxative use not a risk for colorectal cancer: data from the Melbourne Colorectal Cancer Study.

Commercial laxative use as a risk factor in colorectal cancer was investigated as one part of a large population based epidemiological study of colorectal cancer incidence, aetiology and survival "The Melbourne Colorectal Cancer Study", conducted in Melbourne, Australia. Commercial laxative use was similar in 685 colorectal cancer patients and 723 age/sex matched community based controls. Also, when laxatives were subdivided into various groups containing anthraquinones, phenolphthalein, mineral salts and others, previous laxative intake was similar between cases and controls. Previous use of anthraquinone laxatives and of phenolphthalein containing laxatives was not associated with the risk of colorectal cancer.

Laxative abuse as a cause for ammonium urate renal calculi.

Nine women with laxative abuse and predominantly ammonium urate renal calculi underwent metabolic studies to identify common chemical abnormalities and determine pathophysiology. The 24-hour urine studies demonstrated marked decreases in volume (902 cm.3), sodium (28 mEq.), citrate (116 mg.) and potassium (21 mEq.). A significant elevation in ammonium urate supersaturation was found compared to control subjects when studied by the computer model EQUIL 2. Of the patients 7 had 1 or more urine specimens positive for phenolphthalein. Gastrointestinal loss of fluid and electrolytes allowed for chronic extracellular volume depletion. Intracellular acidosis was present as judged by low urinary citrate and potassium. The fact that the ion product for ammonium urate is increased significantly compared to controls reflects the stated pathophysiological changes. Laxative abuse should be suspected whenever a woman has an ammonium urate renal calculus in sterile urine.

Fixed drug eruptions. A study of 20 occurrences in Singapore.

Twenty occurrences of fixed drug eruptions (FDE) were studied. Of these, 12 were due to tetracyclines and 4 were due to analgesics (3 from pyrazolone derivatives and 1 from acetylsalicylic acid). Sixteen of the patients had less than 10 lesions each. The lips were affected in eight instances, and therefore seem preferentially involved. At presentation, seven patients were unaware of a drug relationship to their condition. A comparison of six reported series (including this one) revealed that the causative drugs varied over the years 1956-1983 as well as by region.

Acute pancreatitis complicating excessive intake of phenolphthalein.

A case is described in which a patient presented with acute pancreatitis following inadvertent ingestion of large quantities of phenolphthalein for the treatment of his chronic constipation. There was complete recovery and no sequelae from the acute attack of pancreatitis.