To evaluate the antisecretory activity of berberine sulfate (BS), we studied 165 adult patients with acute diarrhea due to enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in randomized controlled trials. In patients with ETEC diarrhea who received 400 mg of BS in a single oral dose, the mean stool volumes were significantly less than those of the controls during three consecutive 8-hr periods after treatment (P < .05). At 24 hr after treatment, significantly more patients who were treated with BS and had ETEC diarrhea stopped having diarrhea as compared with the controls (42^0 vs 20970, PK .05). In patients with cholera who received 400 mg of BS, the mean 8-hr stool volume during the second 8-hr period after treatment declined to 2.22 liters, which was significantly less than the 2.79 liters found in the controls (P < .05). However, patients with cholera who received 1200 mg of BS plus tetracycline did not have significant reduction in stool output compared with patients who received tetracycline alone. No side effects of BS were noted. These results indicated that BS is an effective and safe antisecretory drug for ETEC diarrhea, whereas the activity against cholera is slight and not additive with tetracycline. The plant alkaloid berberine, derived from the root and bark of the deciduous shrub Berberis aristata, has been used as an antidiarrheal medication by traditional practitioners in India and China for the

Randomized Controlled Trial of Berberine Sulfate Therapy for Diarrhea Due to Enterotoxigenic Escherichia coli and Vibrio cholerae

This chapter reviews the pathophysiology of cholera, focusing on the most common and important complication, dehydration; describes the clinical features of patients with cholera; and outlines treatment for patients with this disease. The major effects of V. cholerae O1 infection are to increase active chloride and bicarbonate secretion into the intestinal lumen by crypt cells and to decrease villous absorption of sodium chloride. The majority of children with cholera and hypoglycemia have neither frank marasmus nor kwashiorkor and resemble other cholera patients in their general clinical features. Severe dehydration produces such distinctive and pronounced features that cholera is one of the few diseases in adults that can be accurately diagnosed at first sight. The major laboratory abnormalities in patients with cholera are alterations in the concentration of serum electrolytes and creatinine and the effects of hemoconcentration on other blood constituents. Although replacement of fluid lost in cholera stool remains the crucial element of treatment of cholera patients, antimicrobial therapy is an important adjunctive therapy, especially in patients with high purging rates. Antimicrobial therapy of cholera is complicated by the marked increase in multiply antibiotic-resistant strains during the last 20 years. Currently in Bangladesh, more than 90% of V. cholerae O1 isolates are resistant to tetracycline, ampicillin, and trimethoprim-sulfamethoxazole. When epidemics occur in rural areas, it is often necessary to establish temporary cholera treatment centers. The supplies required for such temporary facilities are quite straightforward, and the costs not great.

Cholera: Pathophysiology, Clinical Features, and Treatment

provide a complete document that would be applicable to the case management of diarrhea. However, some explanation and amplification is necessary to clarify the terms and phrases that have been used, as well as to explain the basis for certain decision pathways in the algorithm. Adult: The definition of ‘adult’ varies from one country to another. As applied in this guideline, the term ‘adult’ refers to someone who is of age 12 years or above. Acute diarrhea: This is defined as the passage of three or more than three loose or watery stool in 24 h, or passage of one or more bloody stool. Acute diarrhea refers to illness not lasting longer than 14 days. Other conditions that may present as acute diarrhea: ‘Acute diarrhea’ is a clinical syndrome that is commonly understood to refer to infective gastroenteritis. However, as defined, acute diarrhea may be a symptom of other intra-abdominal or systemic illnesses. These other clinical conditions may require particular investigations and management, and will need to be recognized and excluded at the outset. Careful history and physical examination is necessary to exclude these conditions from the commonly understood ‘acute diarrhea’. Special attention should be paid to exclude signs of peritonism or peritonitis, which will indicate serious illnesses that might require surgical care. Examples of these diverse clinical conditions are presented in Table 1. Specific conditions of acute diarrhea that require special consideration: Although the term ‘acute diarrhea’ commonly refers to infectious, toxin-induced and drug-induced diarrhea, there are specific acute diarrhea syndromes that may need a specifically tailored approach and management, and where the general algorithm may need to be modified. For example, during epidemic acute diarrhea such as cholera, it is important to quickly identify the organism in the first patients presenting with illness, and to initiate public health meaINTRODUCTION

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1440-1746.17.s1.11.x

Guideline for the management of acute diarrhea in adults.

The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. We report the 1.8 {angstrom} crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 familymore » not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.« less

/pdf/crystal-structure-of-an-integron-gene-cassette-associated-4xn14fn6le.pdf

Crystal structure of an integron gene cassette-associated protein from Vibrio cholerae identifies a cationic drug-binding module.

SUMMARY
Anti-diarrhoeal drugs reduce the symptoms of diarrhoea (loose stool consistency, frequency of defecation and excessive stool weight) by effects on intestinal transit, mucosal transport or luminal contents. Opiates and opioids are the most useful anti-diarrhoeal agents. Opiates have major effects on intestinal transit; pro-absorptive and anti-secretory effects are less well documented, but may be important for some of these drugs. Alpha-adrenergic agonists, somatostatin analogues and several other agents have had limited clinical use; these drugs may modify mucosal transport in addition to slowing transit. Adsorbents, bismuth and stool texture modifiers are used frequently by the public, but their efficacy is largely unproven. Oral rehydration solutions have had the greatest impact in saving lives and continue to be improved. Many new approaches to the treatment of diarrhoea are yet to be exploited.

Review article: anti‐diarrhoeal pharmacology and therapeutics

https://www.gastrojournal.org/article/0016-5085(82)90066-X/pdf

G.H. Rabbani

Papers

Use of chlorpromazine in the treatment of cholera and other severe acute watery diarrheal diseases