Onset Of Diarrhea Research Articles

Food protein-induced enterocolitis syndrome to peanuts: A case series

Food protein-induced enterocolitis (FPIES) is a non–IgE-mediated food allergy that manifests as repetitive emesis, pallor, lethargy, and diarrhea onset 1 to 4 hours after the ingestion of a food.1 Since the implementation of guidelines advocating the early introduction of peanut, there has been an increase in publications about peanut FPIES (p-FPIES).2-4 Many have hypothesized that the early introduction may be the reason for FPIES to peanut in susceptible individuals. Although clinicians often see this in the clinic, there is much uncertainty regarding the characteristics and prognosis of p-FPIES.

Anti-Diarrheal Activities of Hydromethanolic Crude Extract and Solvent Fractions of Acacia seyal (Fabaceae) Roots in Mice.

Traditionally, the root of Acacia seyal is used for the treatment of diarrhea. However, its efficacy has not been scientifically evaluated. Thus, this study aimed to validate the antidiarrheal activities using hydromethanolic crude extract and solvent fractions of Acacia seyal roots in mice. In each model, mice were divided into five groups of six mice at random. Group I mice (negative controls) were given 1mL/100 g distilled water for hydromethanolic crude extract tests as well as n-hexane, ethyl acetate and aqueous fractions, while groups II, III, and IV were given 100 mg/kg, 200 mg/kg, and 400 mg/kg of hydromethanolic crude extract or solvent fractions. Group V mice (positive control) were given 3 mg/kg Loperamide for the castor oil-induced diarrhea and enteropooling test. All of the doses were taken orally. However, Atropine sulfate, 5 mg/kg, was given intraperitoneally for the gastrointestinal motility test. Statistical Package for the Social Sciences (SPSS) version 26 was used to examine the statistical significance of differences in the number and weight of wet and total feces, distance traveled by a charcoal meal, and intestinal fluid accumulation across groups. When compared to the vehicle-treated group, the crude extract and n-hexane fraction notably delayed the onset of diarrhea, reduced the weight and volume of intestinal contents, and hindered the intestinal transit at all tested doses (P < 0.001). The ethyl acetate fraction also significantly (P < 0.001) decreased the weight of intestinal content at all doses examined. Only at 400 mg/kg did the aqueous fraction statistically (P < 0.01) prolonged the onset of diarrhea and impeded gastrointestinal motility. According to this study, the hydromethanolic crude extract and solvent fractions of Acacia seyal roots have promising antidiarrheal effects.

DESENSITIZATION TO EXTENSIVELY HYDROLYZED FORMULA IN INFANT WITH COW'S MILK PROTEIN ALLERGY

<h3>Introduction</h3> Cow's Milk Protein Allergy (CMPA) is typically managed by avoidance. Limited evidence of oral desensitization for delayed-type hypersensitivity (DTH) reactions exist in the drug literature. We present a case of desensitization with hydrolyzed formula in an infant with CMPA. <h3>Case Description</h3> Allergy was consulted by NICU for a 5-month-old male infant with formula intolerance. Infant was born at term with gastroschisis and short bowel syndrome, with need for small bowel resection and gastrostomy tube placement. Maternal breast milk was insufficient to meet the infant's needs. Transition to formula was complicated by the development of bloody stools with cow's milk and hydrolyzed cow's milk formula consistent with CMPA. Introduction of elemental formulas was limited by the development of delayed onset vomiting and diarrhea felt to be consistent with Food Protein Induced Enterocolitis Syndrome (FPIES) to cornstarch. Donor breast milk was not available for outpatient use. Oral desensitization to Alimentum RTF, a cornstarch free hydrolyzed formula was successful, and the patient was discharged on this formula. <h3>Discussion</h3> Both FPIES and CMPA are predominantly delayed type hypersensitivity reactions. While desensitization approaches initially developed for management of IgE mediated drug allergy, similar approaches have been successful in management of both IgE mediated food allergy and delayed type hypersensitivity reactions to drugs. We report a potential option for oral desensitization in a patient with CMPA for whom typical therapy was contraindicated.

Abundance of selected bacterial groups in healthy calves and calves developing diarrhea during the first week of life: Are there differences before the manifestation of clinical symptoms?

Diarrhea is still the most common and economically most significant disease of newborn calves. Analysis of the development of selected bacterial groups in the feces of neonatal calves and its significance regarding diarrhea. A total of 150 newborn Simmental calves reared in 13 Bavarian farms were included in the study. Fecal samples of calves taken at 0/6/12/24/48/72/168 hours (h) since birth were analyzed qualitatively and quantitatively for aerobic and anaerobic bacteria, such as Enterobacteriaceae, E. coli, enterococci, and lactobacilli, using cultural, biochemical, and molecular-biological methods. Concurrently, the health status of the animals was recorded. The bacterial levels of healthy and diarrheic animals were compared using statistical methods. In addition, feces samples from calves that developed diarrhea were examined by ELISA for the presence of rotaviruses, coronaviruses, E. coli F5, and Cryptosporidium (Cr.) parvum. Fifty-seven out of 150 calves (37.3 %) that were examined developed diarrhea within the first week of life. In the feces of calves with diarrhea on day 1 of life, the levels of aerobes, Enterobacteriaceae, and E. coli were significantly increased (p < 0.05), while no significant differences in enterococci and lactobacilli were found. In animals with the onset of diarrhea on day 2 after birth, the load of lactobacilli was significantly reduced up to 24 h before the manifestation of clinical symptoms compared to healthy calves. For enterococci, this was only the case on the day of the onset of diarrhea. In addition, the ratios of aerobic and anaerobic bacteria, Enterobacteriaceae or E. coli to lactobacilli, of calves with diarrhea starting on day 2 after birth are significantly higher than those of healthy calves. The detection frequency of specific pathogens in diarrheic calves increased over the first week of life. The results suggest that the incidence of neonatal diarrhea in calves is favored by low levels of lactobacilli in the feces. From this, the hypothesis can be derived that, in addition to an optimal supply of colostrum, the earliest possible administration of lactobacilli might reduce neonatal diarrhea in calves. However, this must be verified in a subsequent feeding experiment.

Antidiarrheal Activity of Dialium guineense Willd Fruit Pulp in Wistar Rats.

Objective This study is aimed at evaluating the effects of Dialium guineense Willd fruit pulp powder on diarrhea induced by castor oil in Wistar rats. Materials and Methods Three different tests were carried out. A preventive test by administration of a single dose of 250, 500, 1000, 2000, and 4000 mg/kg before the induction of diarrhea by castor oil. Another preventive test after repeated administration of Dialium guineense at 250, 500, and 1000 mg/kg/day for 8 days, before the induction of diarrhea, was done. The third test was a curative test with a single dose of 250, 500, 1000, and 2000 mg/kg after the induction of diarrhea by castor oil. Results D. guineense fruit pulp at 1000, 2000, and 4000 mg/kg administered before the induction of diarrhea, has significantly delayed diarrhea; reduced the frequency of defecation, reduced the amount of diarrheal stools, and also reduced the purging index, with a degree of inhibition comparable to that of loperamide. But the water content of the stools of the group treated with D. guineense does not change significantly compared to the controls. D. guineense has reduced significantly from 500 mg/kg the diarrhea induced by castor oil after 8 days of treatment. It appears that the doses of 250 and 500 mg/kg, which were not effective with the single-dose preventive test, significantly delayed diarrhea; reduces the frequency of diarrheal stools and also reduces the purging index. D. guineense administered, after the induction of diarrhea, by castor oil has significantly reduced the diarrhea from 250 mg/kg. Conclusion The fruit pulp of D. guineense has showed antidiarrheal activities in Wistar rats by reducing the frequency of defecation, the amount of diarrheal fecal matter emitted as well as the water content. It also delayed the onset of diarrhea and significantly reduced the purging index like loperamide.

PO115 / #286 A COMBINED BENEFIT OF REGULATED GASTROINTESTINAL FUNCTION AND IMPROVED BACK AND LOWER EXTREMITY PAIN FOLLOWING THORACIC SCS: A CASE REPORT: E-POSTER VIEWING

The therapeutic targets of SCS have broadly expanded, yet its influence on central and peripheral neuronal pathways, as well as the autonomic nervous system remains poorly understood. Few case reports have demonstrated significant changes in gastrointestinal function and symptomatology with neurostimulation targeted to the thoracic dorsal column. In reports by La Grua and Thakkar, et al, patients developed either new onset diarrhea or abdominal distension and constipation following SCS activation.

S3419 Ileocolitis Associated With the Checkpoint Inhibitor Palbociclib (PAL)

Introduction: Cancer treatments are continuously being updated to optimize survival. Newer checkpoint inhibitors (CDK4/6 inhibitors) have demonstrated promising responses in ER-positive breast cancers. We report a rare side effect of ileocolitis with Palbociclib (PAL) treatment. Case Description/Methods: A 30-year-old female with biopsy confirmed stage IV ER+, PR+, HER2− ductal breast carcinoma with metastasis to liver and bone presented with abdominal pain, diarrhea, and hematochezia 2 months into therapy with letrozole and PAL. Subsequent colonoscopy 4 months after onset of symptoms showed diffuse colitis with congestion, erythema, and shallow ulceration scattered through the whole colon, and several superficial aphthous ulcerations in the ileum. Stool for C. difficile by PCR was negative and biopsies revealed nonspecific ileitis and colitis. There was concern for IBD vs drug induced enteritis/colitis. PAL was held and the patient was started on prednisone taper with resolution of symptoms after 1 month. Given concern for disease progression, PAL was restarted 1 month later with return of symptoms and hospital admission. Laboratory studies showed WBC 1.84 TH/uL, Hgb 7.6 g/dL, plt 24 TH/uL, LDH 4211 U/L, ALT 450 U/L, AST 221 U/L, alk phos 223 U/L, total bilirubin 1.3 mg/dL, ESR 49 mm/hr and CRP 45 mg/L. Infection was excluded via stool studies including C. difficile PCR and blood culture. Colonoscopy was performed and showed erythema, friability, congestion, erosions, and ulceration in the TI compatible with ileitis (Figure) as well as patchy erythema, edema, erosions, and ulcers throughout the colon with skip lesions and sparing of the rectum. Biopsies were reported as normal TI and colon. PAL was discontinued indefinitely and the patient had complete resolution of symptoms within weeks. Discussion: CDK4/6 inhibitors are new first-line treatment for metastatic HR-positive breast cancer. There are no prior reports of PAL induced enterocolitis without concomitant radiation. In our patient, symptoms could not be easily distinguished from infectious colitis or IBD clinically. Ileal and colonic biopsies showed nonspecific ileitis and colitis or were reported as normal. As CDK4/6 inhibitors become used more as the first-line treatment of metastatic HR-positive breast cancer, additional evidence of GI related toxicities may emerge. Checkpoint inhibitor induced ileitis/colitis should be considered in a patient with new onset hematochezia and diarrhea after initiation of these agents.Figure 1.: Erythema, friability, congestion, erosions, and ulceration in the terminal ileum.

Mucin O-glycan-microbiota axis orchestrates gut homeostasis in a diarrheal pig model

BackgroundPost-weaning diarrhea in piglets reduces growth performance and increases mortality, thereby causing serious economic losses. The intestinal epithelial cells and microbiota reciprocally regulate each other in order to maintain intestinal homeostasis and control inflammation. However, a relative paucity of research has been focused on the host-derived regulatory network that controls mucin O-glycans and thereby changes gut microbiota during diarrhea in infancy. At the development stage just after birth, the ontogeny of intestinal epithelium, immune system, and gut microbiota appear similar in piglets and human infants. Here, we investigated the changes of mucin O-glycans associated with gut microbiota using a diarrheal post-weaned piglet model.ResultsWe found that diarrhea disrupted the colonic mucus layer and caused aberrant mucin O-glycans, including reduced acidic glycans and truncated glycans, leading to an impaired gut microenvironment. Subsequently, the onset of diarrhea, changes in microbiota and bacterial translocation, resulting in compromised epithelial barrier integrity, enhanced susceptibility to inflammation, and mild growth faltering. Furthermore, we found the activation of NLRP3 inflammasome complexes in the diarrheal piglets when compared to the healthy counterparts, triggered the release of proinflammatory cytokines IL-1β and IL-18, and diminished autophagosome formation, specifically the defective conversion of LC3A/B I into LC3A/B II and the accumulation of p62. Additionally, selective blocking of the autophagy pathway by 3-MA led to the reduction in goblet cell-specific gene transcript levels in vitro.ConclusionsWe observed that diarrheal piglets exhibited colonic microbiota dysbiosis and mucosal barrier dysfunction. Our data demonstrated that diarrhea resulted in the activation of inflammasomes and autophagy restriction along with aberrant mucin O-glycans including reduced acidic glycans and truncated glycans. The results suggested the mucin O-glycans-microbiota axis is likely associated with diarrheal pathogenesis. Our study provides novel insights into the pathophysiology of early-weaning-induced diarrheal disease in piglets and potentially understanding of disease mechanisms of diarrhea for human infants. Understanding the molecular pathology and pathogenesis of diarrhea is a prerequisite for the development of novel and effective therapies. Our data suggest that facilitating O-glycan elongation, modifying the microbiota, and developing specific inhibitors to some key inflammasomes could be the options for therapy of diarrhea including human infants.Graphical abstract79ZKnZ6nbqMhwNgSiMAsGZVideo abstract

Antidiarrheal and Antibacterial Activities of Calpurnia aurea: Benth Seed Different Extracts.

Background Calpurnia aurea is believed to have antidiarrheal potential but with limited scientific evidence. This study aimed investigating antidiarrheal and antibacterial activity of aqueous and 80% methanol seed extracts of the plant in mice and selected diarrhea-causing bacterial strains, respectively. Methods Castor oil-induced diarrhea, prostaglandin-induced enteropooling, and castor oil-induced charcoal meal test models in mice of either sex using three dose levels (60, 120, and 240 mg/kg) were applied to evaluate antidiarrheal activity. Parameters, including onset, number, wet stool weight, weight and volume of secretion, and intestinal motility, were taken into consideration. The antibacterial activity was assessed on Shigella soni, Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa using disk diffusion and microdilution techniques. Results Compared to controls, pretreatment of mice at the graded dose (60, 120, and 240 mg/kg) resulted in a significant (p < 0.05) drop in frequency of wet stools and watery content of diarrhea as well as in delaying onset of diarrhea. Both extracts exhibited inhibition of diarrhea in a dose-dependent manner in all models used. The extracts also showed significant (p < 0.05) reduction in intestinal motility in castor oil-induced models. Both extracts showed a marginal activity against the selected bacterial strains; a better effect was seen with 80% methanol seed extract. Conclusion Both extracts of the plant have beneficial effect in controlling diarrhea. This finding supports the use of the plant as a traditional antidiarrheal remedy.

Acute abdomen due to anaphylactic intestinal edema associated with systematic mastocytosis: a case report

BackgroundAmong various anaphylactic conditions resulting in acute abdomen, mast cell activation disorders, although rare, are included in the differential diagnosis.Case presentationThis report describes a 63-year-old Caucasian man who was brought to the emergency room with sudden onset abdominal pain, vomiting, and diarrhea, with breathing difficulty, and with facial swelling after quarrelling with an acquaintance. Computed tomography showed edematous and swollen intestines, consistent with splenomegaly. Physical findings included maculopapular cutaneous mastocytosis. He also had a long history of repeated episodes of anaphylaxis requiring occasional epinephrine auto-injector administration; however, the precise cause of anaphylaxis was previously undetermined. Blood tests showed high serum concentrations of soluble IL-2R and tryptase, suggesting mast cell-related disease. Subsequent biopsies of his bone marrow and cutaneous rash confirmed the diagnosis of systemic mastocytosis (SM).ConclusionSM was diagnosed in a patient with acute abdomen who visited the emergency room.

In Vivo Efficacy, Toxicity Assessment, and Elemental Analysis of Traditionally Used Polyherbal Recipe for Diarrhea.

A polyherbal formulation consisting of Mentha piperita L., Camellia sinensis L. Kuntze, and Elettaria cardamomum (L.) Maton with a ratio of 10 : 5 : 2, respectively, was recommended for curing nausea, vomiting, and diarrhea. Experimental validation is crucial to affirm its therapeutic property leads toward the development of modified antidiarrheal agents. This research aimed to investigate the in vivo antidiarrheal efficacy of traditionally used polyherbal recipe in a castor oil-induced animal model. Moreover, the study also presents the elemental screening and in vivo toxicity of tested polyherbal recipe. Individual plant parts of the polyherbal recipe were mixed according to the traditional prescription ratio, and hydromethanolic extract was prepared by the cold maceration process. The antidiarrheal activity was assessed by castor oil induction method, charcoal meal test, and enteropooling procedure in Sprague-Dawley rats. Elemental analysis and in vivo subacute toxicity were carried out, followed by biochemical, hematological, and histopathological analyses. Polyherbal extract significantly delayed the diarrhea onset in a dose-dependent manner and showed marked inhibition at 200 and 400 mg/kg. Fecal weight was reduced significantly (p < 0.05) at 200 mg/kg (0.26 ± 0.25) in comparison with the control (1.63 ± 0.15). The diarrhea score was zero at a concentration of 200 and 400 mg/kg. Antienteropooling effect of the extract was greater than that of loperamide. Following subacute toxicity, all the treated rats were normal, survived, and showed no changes in behavior. There were no significant differences between values of blood parameters in both the control and extract-treated groups except a significant decrease in monocytes (control 8.4; polyherbal 2.2). Elemental analysis showed a slight increase in the amount of manganese (Mn, 8.076 ppm) as compared to the WHO recommended level (2 ppm). Traditionally used polyherbal recipe is effective and safe for combating diarrheal diseases. In vivo evidence supported the use, safety, and efficacy of the polyherbal recipe that has been used as an alternative medicine for diarrhea in the study area. Inhibition of castor oil-induced diarrhea and antisecretory effect of the studied polyherbal recipe makes it a potent antidiarrheal drug without no or limited toxic effects at the tested dose after further analysis.

Thymol as an Adjuvant to Restore Antibiotic Efficacy and Reduce Antimicrobial Resistance and Virulence Gene Expression in Enterotoxigenic Escherichia coli Strains.

The continuous spread of antimicrobial resistance is endangering the efficient control of enterotoxigenic Escherichia coli (ETEC), which is mainly responsible for post-weaning diarrhea onset in piglets. Thymol, the key constituent of thyme essential oil, is already used in animal nutrition for its antimicrobial action. The aim of this study was to investigate the potential adjuvant effect of thymol to re-establish antibiotic efficacy against highly resistant ETEC field strains. Secondly, we evaluated the modulation of virulence and antibiotic resistance genes. Thymol showed the capacity to control ETEC growth and, when combined with ineffective antibiotics, it increased their antimicrobial power. In particular, it showed significant effects when blended with colistin and tetracycline, suggesting that the adjuvant effects rely on the presence of complementary mechanisms of action between molecules, or the absence of resistance mechanisms that inactivate antibiotics and target sites. Furthermore, our findings demonstrate that, when added to antibiotics, thymol can help to further downregulate several virulence and antibiotic resistance genes, offering new insights on the potential mechanisms of action. Therefore, in a one-health approach, our study supports the beneficial effects of combining thymol with antibiotics to restore their efficacy, together with the possibility of targeting gene expression as a pioneering approach to manage ETEC pathogenicity.

Irinotecan decreases intestinal UDP-glucuronosyltransferase (UGT) 1A1 via TLR4/MyD88 pathway prior to the onset of diarrhea.

Irinotecan is a first-line treatment for colorectal cancer and the prodrug of 7-ethyl-10-hydroxy-camptothecin (SN-38). However, its fatal gastrointestinal (GI) toxicity raises serious concern. In liver, irinotecan generates its inactive metabolite, SN-38G via UDP-glucuronosyltransferase (UGT)1A1. Subsequently, SN-38G is excreted into GI tract where it is reactivated by microbiome to yield the toxic metabolite, SN-38. Activation of toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) by bacterial endotoxin decreases drug-metabolizing enzymes. In this study, we treated C57BL6/J mice with 50 mg/kg irinotecan once daily until observing grade 4 diarrhea. Mice were sacrificed on day0, day2 and day8. Based on the finding in C57BL6/J mice, we repeated the treatment in Tlr2-/-, Tlr4-/- and Myd88-/- mice to determine the impact of inflammation on UGT metabolism. Our toxicity study in C57BL6/J mice showed that mice started bloody diarrhea after 6 days' injection of irinotecan. Ugt1a1 expression in GI tract started decreasing after 24h since first dose, before the onset of diarrhea. In Tlr4-/- and Myd88-/- mice, no Ugt1a1 reduction was observed in distal GI tract after irinotecan injection. In Tlr2-/- mice, intestinal Ugt1a1 expression was down-regulated. Our results indicate that after two doses of irinotecan, mice started losing capability of detoxifying SN-38. TLR4 plays more important role in Ugt1a1 reduction than TLR2, despite that TLR2 and TLR4 share MyD88 as common adaptor protein. We concluded that irinotecan reduced intestinal Ugt1a1 via TLR4/MyD88 pathway, which eventually triggers the onset of diarrhea. Our finding unveils a novel mechanism underlying irinotecan-induced diarrhea and provides a new direction to prevent chemotherapy side effect.

The Epidemiology of Invasive, Multipleantibiotic-resistant Klebsiella pneumoniae Infection in a Breeding Colony of Immunocompromised NSG Mice.

Klebsiella pneumoniae (Kp) is a gram-negative opportunistic pathogen that causes severe pneumonia, pyelonephritis, and sepsis in immunocompromised hosts. During a 4-mo interval, several NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) breeders and pups in our facilities were diagnosed with Kp infections. An initial 6 adult and 1 juvenile NSG mice were submitted for necropsy and histologic examination because of acute onset of diarrhea and death. The evaluation revealed typhlocolitis in 2 of the mice and tritrichomoniasis in all 7. Escherichia coli positive for polyketide synthase (pks+) and Kp were isolated from the intestines. Given a history of sepsis due to pks+ E. coli in NSG mice in our facilities and determination of its antimicrobial susceptibility, trimethoprim-sulfamethoxazole (TMP-SMX) was administered to the colony in the drinking water for 4 wk. After this intervention, an additional 21 mice became ill or died; 11 of these mice had suppurative pneumonia, meningoencephalitis, hepatitis, metritis, pyelonephritis, or sepsis. Kp was cultured from pulmonary abscesses or blood of 10 of the mice. Whole-genome sequencing (WGS) indicated that the Kp isolates contained genes associated with phenotypes found in pore-forming Kp isolates cultured from humans with ulcerative colitis and primary sclerosing cholangitis. None of the Kp isolates exhibited a hyperviscous phenotype, but 13 of 14 were resistant to TMP-SMX. Antimicrobial susceptibility testing indicated sensitivity of the Kp to enrofloxacin, which was administered in the drinking water. Antibiotic sensitivity profiles were confirmed by WGS of the Kp strains; key virulence and resistance genes to quaternary ammonia compounds were also identified. Enrofloxacin treatment resulted in a marked reduction in mortality, and the study using the NSG mice was completed successfully. Our findings implicate intestinal translocation of Kp as the cause of pneumonia and systemic infections in NSG mice and highlight the importance of identification of enteric microbial pathogens and targeted antibiotic selection when treating bacterial infections in immunocompromised mice.

Evaluation of Antidiarrheal Activity of Leea aequata L. (Family: Vitaceae) in Mice Models

Diarrhea is one of the most common reasons for why thousands of people die every year particularly in the underdeveloped and developing country. Furthermore, the identification of new antidiarrheal medication sources has become one of the most prominent areas of contemporary study. In addition, the plants of the Leea species are used traditionally for the treatment of diarrhea in different cultures. Considering this background, present study was to look into the antidiarrheal effects of an ethanolic extract of Leea aequata L. leaves in mice. The castor oil induced diarrhea and the small intestinal transit models were utilized in this study to examine the extract's potential antidiarrheal efficacy. The extract was given to the test groups in various quantities (100, 200 mg/kg), whereas positive controls got loperamide (3 mg/kg) and negative controls received distilled water (10 ml/kg). In a model of diarrhea caused by castor oil, 200 mg/kg of the extract significantly (p&lt;0.01) decreased the total number of bowel movements. The extracts also demonstrate a substantial (p&lt;0.05) reduction in the frequency of wet defecation at all doses. The onset of diarrhea was extended with dose of the extracts which is statistically significant (p&lt;0.001). At higher doses, the extract caused a significant (p&lt;0.05) reduction in the weight and volume of wet feces. Furthermore, in the charcoal meal test, increasing doses of the extract caused a substantial (p&lt;0.01) reduction in gastrointestinal motility. Phytochemical screening of the extract revealed the presence of flavonoids, alkaloids, tannins, and phytosterols that may play a key role in its antidiarrheal activity. The results of our study indicate that bioactive compounds are present in ethanolic leaf extract of our plant including significant antidiarrheal activity and thus provide the scientific basis for the traditional uses of this plant as a treatment for diarrhea. Bangladesh Pharmaceutical Journal 25(2): 180-187, 2022 (July)

Antidiarrheal activity of the extracts of Valeriana jatamansi Jones on castor oil-induced diarrhea mouse by regulating multiple signal pathways

Ethnopharmacological relevanceValeriana jatamansi Jones, a traditional medicine, is used for various medicinal purposes worldwide. This species is popular for its gastro-protective properties and has been verified to exert antidiarrheal effects. Qiuxieling mixture, an oral liquid preparation used to treat diarrhea in children in clinical practice, was extracted from V. jatamansi Jones.Aim of the study: Although Qiuxieling mixture has a good preventive effect on diarrhea children, the disgusting smell makes it intolerable. Therefore, we extracted odorless products from V. jatamansi Jones and Qiuxieling mixture. The present study is aimed to investigate the protective effects of two ethanolic extracts of V. jatamansi Jones and Qiuxieling mixture against castor oil-induced diarrhea and their possible mechanisms in mice. Materials and methodsThe two extracts of V. jatamansi Jones and Qiuxieling mixture were detected by HPLC. A castor oil-induced diarrheal model was used to evaluate the antidiarrheal effects. The expression of Occludin in the small intestine was measured by IHC. Western blotting and immunofluorescence were used to detect the expression of proteins related to the oxidative stress and GSDMD-mediated pyroptosis signaling pathways. ELISA was used to detect the expression of IL-6 and IL-1β in the small intestine of mice with diarrhea. ResultsThe two extracts of V. jatamansi Jones and Qiuxieling mixture dose-dependently reduced the diarrhea index and the diarrhea rate, delayed the onset of diarrhea, and decreased the weight of the intestinal content. Meanwhile, they reversed the decreased expression of Occludin and restored the activity of Na+-K+-ATPase in the intestines of diarrheal mice. In addition, they reversed the depletion of GSH, attenuated the activation of the ERK/JNK pathway, promoted the Nrf2/SOD1 signaling pathways, and decreased the release of ROS in the intestines of diarrheal mice. Moreover, they suppressed GSDMD-mediated pyroptosis by downregulating the NLRP3/caspase-1/GSDMD signaling pathway. ConclusionsThe two extracts of V. jatamansi Jones and Qiuxieling mixture exerted protective effects on castor oil-induced diarrhea in mice through a variety of mechanisms, including antioxidant stress, restoration of tight junctions between intestinal mucosal cells and regulation of the GSDMD-mediated pyroptosis pathway.

Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study

BackgroundUp to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial. MethodsIn this single centre interventional pre post study, the safety of Low Dose Naltrexone (LDN) was explored in patients with Post COVID-19 Syndrome (PCS), defined by NICE as patients with ongoing symptoms 12 or more weeks after initial infections with SARS-CoV-2 where alternative explanation for symptoms cannot be found. Patients were recruited through a Post COVID clinic, had a baseline quality of life questionnaire in symmetrical Likert format, were prescribed 2 months (1 mg month one, 2 mg month two) of LDN and repeated the same questionnaire at the end of the second month. Patients were monitored to adverse events. FindingsIn total 52 patients participated of whom 40(76.9%) were female. The median age was 43.5 years(IQR 33.2–49). Healthcare workers represented the largest occupational cohort n = 16(34.8%). The median time from diagnosis of COVID-19 until enrolment was 333 days (IQR 171–396.5). Thirty-eight participants (73.1%) were known to commence LDN, two of whom (5.3%) stopped taking LDN post commencement due to new onset diarrhoea and also described fatigue. In total 36(69.2%) participants completed the questionnaire at the end of the two-month period. Improvement was seen in 6 of 7 parameters measured; recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤ 0.001), improvement in mood approached but was not significant (p = 0.054). ConclusionsLDN is safe in patients with PCS and may improve well-being and reduce symptomatology in this cohort. Randomised control trials are needed to further explore this.

Experimental Study of the Efficacy and Safety of a New PEG-Based Laxative

Bowel-cleansing PEG-based agents, including Moviprep®, are commonly used to prepare the large intestine for diagnostic examinations. PLNV-next is a newly developed fixed combination medicinal product with a composition similar to that of Moviprep®.The aim of the study was to estimate the pharmacological efficacy and toxicity of PLNV-next.Materials and methods: The study evaluated pharmacological efficacy of four formulations of PLNV-next in comparison with Moviprep® after a single administration in a therapeutic dose to outbred rats. The evaluation was carried out based on the laxative effect of the medicinal products. The authors recorded diarrhoea onset latency and the number of defecation boluses and diarrhoea spots produced during the 6-hour observation period. Toxicity of PLNV-next was studied in the formulation containing maximum amounts of the ingredients according to the patent. In the single-dose toxicity study, PLNV-next was administered intragastrically to rats at doses of 4.2 g/kg (maximum human therapeutic dose, MHTD), 21 g/kg (5 MHTD), and 42 g/kg (10 MHTD) and to ferrets at doses of 4.2 g/kg (MHTD) and 21 g/kg (5 MHTD). In the repeated-dose toxicity study, PLNV-next was administered for 14 days at 4.2 g/kg (rats and ferrets), 21 g/kg (5 MHTD, rats), and 12.6 g/kg (3 MHTD, ferrets). Additionally, the repeated-dose toxicity study evaluated safety pharmacology parameters for the cardio-vascular, respiratory and central nervous systems.Results: All PLNV-next formulations tested exerted a laxative effect equivalent to that of Moviprep®. No clinical signs of toxicity were observed in rats, with the exception of the laxative effect. Ferrets demonstrated decreased behavioral activity and diarrhoea. Nausea or emesis were noted in 75–90% of the ferrets receiving the doses exceeding the MHTD. A single administration of PLNV-next affected blood sodium concentrations: a slight increase was noted in the 5 MHTD and 10 MHTD groups of rats and in the 5 MHTD group of ferrets. The repeated-dose toxicity study in rats revealed a slight increase in sodium levels with both test doses. After a single administration of 5 MHTD to ferrets, the authors observed a decrease in potassium levels. All the changes were mild and within physiological ranges. PLNV-next toxic effects observed in the rat and ferret studies were similar to those reported in rat and dog toxicity studies of Moviprep®. Conclusion: PLNV-next exerts a marked laxative effect and has a favourable safety profile.

Evaluation of In vivo antidiarrheal activity of hydro-methanolic extract of the root of Rumex nepalensis in Swiss Albino mice

BackgroundNatural products have been utilized by human beings for thousands of years to relieve a variety of ailments, including diarrhea. Conventional antidiarrheal drugs are associated with multiple adverse effects and contraindications. Traditionally, Rumex nepalensis by crushing the root, mix with water and then drunk the juice is extensively used for treating diarrhea. However, no scientific research has been done yet to support its antidiarrheal efficacy and safety. Hence, the aim of the study was to evaluate the antidiarrheal activity and safety profile of the plant in mice. MethodsThe hydro-methanolic extract was extracted through a cold maceration technique using 80% methanol. Castor oil-induced diarrheal, gastro-intestinal transit, and enteropooling models have been employed to assess the antidiarrheal activity of the test extract at doses of 100, 200, and 400 mg/kg. ResultsThe crude root extract caused no mortality at a single limit test dose of 2 g/kg throughout the first 24 h and for the rest of the 14 days. In a castor oil-induced diarrheal model, the hydro-methanolic extract markedly delayed the onset of diarrhea, reduced the weight of wet and total feces at 100 (P<.05), 200 (P<.01), and 400 mg/kg (P<.001) test doses. Meanwhile, at 200 (P<.01) and 400 mg/kg (P<.001) doses, the plant extract considerably lowered the weight and volume of intestinal contents. In the gastro-intestinal transit model, however, a dramatic inhibition in the charcoal meal travel was noticed at 100 (P<.05), 200 (P<.01), and 400 mg/kg (P<.001) test doses. The peak antidiarrheal index was exhibited at the highest dose of the test extract. ConclusionThe study speculated that Rumex nepalensis root extract possesses antidiarrheal activity, which could be owing to its inhibitory effect on both gastro-intestinal motility and fluid secretion.

Hyaline fibromatosis syndrome with a novel 4.41‐kb deletion in ANTXR2 gene: A case report and literature review

BackgroundHyaline fibromatosis syndrome is a rare autosomal recessive disorder with ANTXR2 mutations characterised by the accumulation of hyaline substances in tissues. We present a case with the severe form—infantile systemic hyalinosis (ISH)—with long survival and review the literature.Methods and resultsTrio‐exome sequencing revealed compound heterozygous mutations, including a novel 4.41 kb deletion on 4q21.21 and the previously reported c.1294C > T mutation, in the ANTXR2 gene. He was diagnosed with ISH and treated symptomatically. After follow‐ups until 4 years of age, his recurrent respiratory infections and diarrhoea improved after one severe diarrhoea attack treated with intravenous gamma globulin. He is now awaiting surgical excision of gingival hypertrophy and joint contractures.ConclusionThe novel gross deletion in ANTXR2 enriches the genetic mutation spectrum of hyaline fibromatosis syndrome. The manifestation of decreased foetal movement, acute‐infection attack or intravenous gamma globulin treatment may be associated with hyaline fibromatosis syndrome. A review of 116 reported cases reveals that missense mutations in the vWA domain are associated with joint symptoms, respiratory tract infection and diarrhoea, while frameshift mutations are associated with facial deformities and speech delays.We have enriched the current knowledge of the clinical manifestations and genetic mutation spectrum of HFS.