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Journal of Cellular and Molecular... Mar 2024Cisplatin is an antimitotic drug able to cause acute and chronic gastrointestinal side effects. Acute side effects are attributable to mucositis while chronic ones are...
Cisplatin is an antimitotic drug able to cause acute and chronic gastrointestinal side effects. Acute side effects are attributable to mucositis while chronic ones are due to neuropathy. Cisplatin has also antibiotic properties inducing dysbiosis which enhances the inflammatory response, worsening local damage. Thus, a treatment aimed at protecting the microbiota could prevent or reduce the toxicity of chemotherapy. Furthermore, since a healthy microbiota enhances the effects of some chemotherapeutic drugs, prebiotics could also improve this drug effectiveness. We investigated whether chronic cisplatin administration determined morphological and functional alterations in mouse proximal colon and whether a diet enriched in prebiotics had protective effects. The results showed that cisplatin caused lack of weight gain, increase in kaolin intake, decrease in stool production and mucus secretion. Prebiotics prevented increases in kaolin intake, changes in stool production and mucus secretion, but had no effect on the lack of weight gain. Moreover, cisplatin determined a reduction in amplitude of spontaneous muscular contractions and of Connexin (Cx)43 expression in the interstitial cells of Cajal, changes that were partially prevented by prebiotics. In conclusion, the present study shows that daily administration of prebiotics, likely protecting the microbiota, prevents most of the colonic cisplatin-induced alterations.
Topics: Animals; Mice; Prebiotics; Cisplatin; Kaolin; Weight Gain; Colon
PubMed: 38445787
DOI: 10.1111/jcmm.18161 -
PeerJ 2024Hook F. (MC), belonging to the family Cucurbitaceae, is a plant with several biological activities. This detailed, comprehensive review gathers and presents all the... (Review)
Review
Hook F. (MC), belonging to the family Cucurbitaceae, is a plant with several biological activities. This detailed, comprehensive review gathers and presents all the information related to the geographical distribution, morphology, therapeutic uses, nutritional values, pharmacognostic characters, phytochemicals, and pharmacological activities of MC. The available literature showed that MC fruits are utilized as a stimulant, tonic, laxative, stomachic, and to combat inflammatory disorders. The fruits are used to treat spleen and liver diseases and are applied in folk medicine to induce abortion and treat diabetes mellitus. The phytochemical screening studies report that MC fruits contain tannins, alkaloids, phenols, proteins, amino acids, vitamin C, carbohydrates, -carotenes, palmitic acid, oleic acid, stearic acid, α-eleostearic acid, and γ-linolenic acid. The fruits also contain calcium, sodium, iron, potassium, copper, manganese, zinc, and phosphorus. Notably, momordicosides are cucurbitacin triterpenoids reported in the fruits of MC. Diverse pharmacological activities of MC, such as analgesic, anti-inflammatory, antioxidant, hepatoprotective, nephroprotective, antidiabetic, cardioprotective, antidepressant, anticonvulsant, anticancer, antiangiogenic, antifertility, antiulcer, antimicrobial, antidiarrheal and anthelmintic, have been reported by many investigators. methanolic extract is safe up to 2,000 mg/kg. Furthermore, no symptoms of toxicity were found. These pharmacological activities are mechanistically interpreted and described in this review. Additionally, the microscopic, powder and physiochemical characteristics of MC tubers are also highlighted. In summary, possesses remarkable medicinal values, which warrant further detailed studies to exploit its potential benefits therapeutically.
Topics: Female; Pregnancy; Humans; Momordica; Phytochemicals; Caffeine; Cucurbitaceae; Vitamins
PubMed: 38436002
DOI: 10.7717/peerj.16928 -
Frontiers in Bioscience (Landmark... Feb 2024The leaves of () are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract.
BACKGROUND
The leaves of () are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract.
METHODS
Gas chromatography-mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an antidiarrheal assay. Isolated rat ileum was used as an assay model to study the possible antispasmodic effect and its mechanism(s).
RESULTS
The GC-MS analysis of detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency ( < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected.
CONCLUSIONS
Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of and provided a detailed mechanistic basis for the medicinal use of in hyperactive gut motility disorders.
Topics: Rats; Mice; Animals; Antidiarrheals; Origanum; Jejunum; Plant Extracts; Castor Oil; Diarrhea; Verapamil; Calcium Channels; Spasm
PubMed: 38420828
DOI: 10.31083/j.fbl2902047 -
Cancer Control : Journal of the Moffitt... 2024This systematic review and meta-analysis aimed to compare outcomes between stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA with mucosectomy in cases of... (Meta-Analysis)
Meta-Analysis Review
Stapled Anastomosis Versus Hand-Sewn Anastomosis With Mucosectomy for Ileal Pouch-Anal Anastomosis: A Systematic Review and Meta-analysis of Postoperative Outcomes, Functional Outcomes, and Oncological Safety.
PURPOSE
This systematic review and meta-analysis aimed to compare outcomes between stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA with mucosectomy in cases of ulcerative colitis and familial adenomatous polyposis.
METHODS
This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines 2020 and AMSTAR 2 (Assessing the methodological quality of systematic reviews) guidelines. We included randomized clinical trials (RCTs) and controlled clinical trials (CCTs). Subgroup analysis was performed according to the indication for surgery.
RESULTS
The bibliographic research yielded 31 trials: 3 RCTs, 5 prospective clinical trials, and 24 CCTs including 8872 patients: 4871 patients in the stapled group and 4038 in the hand-sewn group. Regarding postoperative outcomes, the stapled group had a lower rate of anastomotic stricture, small bowel obstruction, and ileal pouch failure. There were no differences between the 2 groups in terms of operative time, anastomotic leak, pelvic sepsis, pouchitis, or hospital stay. For functional outcomes, the stapled group was associated with greater outcomes in terms of seepage per day and by night, pad use, night incontinence, resting pressure, and squeeze pressure. There were no differences in stool Frequency per 24h, stool frequency at night, antidiarrheal medication, sexual impotence, or length of the high-pressure zone. There was no difference between the 2 groups in terms of dysplasia and neoplasia.
CONCLUSIONS
Compared to hand-sewn anastomosis, stapled ileoanal anastomosis leads to a large reduction in anastomotic stricture, small bowel obstruction, ileal pouch failure, seepage by day and night, pad use, and night incontinence. This may ensure a higher resting pressure and squeeze pressure in manometry evaluation.
PROTOCOL REGISTRATION
The protocol was registered at PROSPERO under CRD 42022379880.
Topics: Male; Humans; Constriction, Pathologic; Surgical Stapling; Proctocolectomy, Restorative; Anastomosis, Surgical; Colonic Pouches; Postoperative Complications; Treatment Outcome
PubMed: 38410083
DOI: 10.1177/10732748241236338 -
Biomolecules Jan 2024The incidence of human infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with...
The incidence of human infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10 mice starting a week prior to infection. On day 6 post-infection, the gastrointestinal loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced -induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis.
Topics: Animals; Humans; Mice; Campylobacter Infections; Charcoal; Gastrointestinal Microbiome; Interleukin-10; Mice, Inbred C57BL; Administration, Oral; Disease Models, Animal
PubMed: 38397378
DOI: 10.3390/biom14020141 -
International Journal of Molecular... Feb 2024Chronic Obstructive Pulmonary Disease (COPD) exacerbation is known for its substantial impact on morbidity and mortality among affected patients, creating a significant...
Thrombelastography and Conventional Coagulation Markers in Chronic Obstructive Pulmonary Disease: A Prospective Paired-Measurements Study Comparing Exacerbation and Stable Phases.
Chronic Obstructive Pulmonary Disease (COPD) exacerbation is known for its substantial impact on morbidity and mortality among affected patients, creating a significant healthcare burden worldwide. Coagulation abnormalities have emerged as potential contributors to exacerbation pathogenesis, raising concerns about increased thrombotic events during exacerbation. The aim of this study was to explore the differences in thrombelastography (TEG) parameters and coagulation markers in COPD patients during admission with exacerbation and at a follow-up after discharge. This was a multi-center cohort study. COPD patients were enrolled within 72 h of hospitalization. The baseline assessments were Kaolin-TEG and blood samples. Statistical analysis involved using descriptive statistics; the main analysis was a paired -test comparing coagulation parameters between exacerbation and follow-up. One hundred patients participated, 66% of whom were female, with a median age of 78.5 years and comorbidities including atrial fibrillation (18%) and essential arterial hypertension (45%), and sixty-five individuals completed a follow-up after discharge. No significant variations were observed in Kaolin-TEG or conventional coagulation markers between exacerbation and follow-up. The Activated Partial Thromboplastin Clotting Time (APTT) results were near-significant, with = 0.08. In conclusion, TEG parameters displayed no significant alterations between exacerbation and follow-up.
Topics: Humans; Female; Aged; Male; Thrombelastography; Cohort Studies; Prospective Studies; Kaolin; Pulmonary Disease, Chronic Obstructive
PubMed: 38396728
DOI: 10.3390/ijms25042051 -
BMC Psychiatry Feb 2024The prevalence and burden of substance and opium use have increased worldwide over the past decades. In light of rapid population changes in Tehran, we aimed to evaluate...
BACKGROUND
The prevalence and burden of substance and opium use have increased worldwide over the past decades. In light of rapid population changes in Tehran, we aimed to evaluate the prevalence of opium and other substance use among adult residents in Tehran, Iran.
METHOD
From March 2016 to March 2019, we utilized data from 8 296 participants in the Tehran Cohort Study recruitment phase (TeCS). We calculated the age-sex-weighted prevalence of substance use and the geographic distribution of substance use in Tehran. We also used logistic regression analysis to determine possible determinants of opium use.
RESULT
We analyzed data from 8 259 eligible participants with complete substance use data and the average age of participants was 53.7 ± 12.75 years. The prevalence of substance use was 5.6% (95% confidence interval [CI]: 4.6- 7.1%). Substance use was more common in males than females (Prevalence: 10.5% [95% CI: 8.6- 12.6%] vs. 0.5% [95% CI: 0.2- 1.2%], respectively). The age-sex weighted prevalence of substance use was 5.4% (95% CI: 4.6-7.1%). Moreover, opium was the most frequently used substance by 95.8% of substance users. Additionally, we found that male gender (Odds ratio [OR]: 12.1, P < 0.001), alcohol intake (OR: 1.3, P = 0.016), and smoking (OR: 8.5, P < 0.001) were independently associated with opium use.
CONCLUSIONS
We found that the prevalence of substance use in Tehran was 5.6%, and opium was the most frequently used substance. In addition, male gender, lower levels of education, alcohol, and tobacco consumption are the main risk factors for substance use in Tehran. Healthcare providers and policymakers can utilize our results to implement preventive strategies to minimize substance use in Tehran.
Topics: Adult; Female; Humans; Male; Middle Aged; Aged; Opium Dependence; Cohort Studies; Opium; Iran; Risk Factors; Substance-Related Disorders
PubMed: 38365633
DOI: 10.1186/s12888-024-05561-1 -
Crohn's & Colitis 360 Jan 2024Crohn's disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment...
INTRODUCTION
Crohn's disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide.
METHODS
Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output.
RESULTS
We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PN + IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances ( < .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0).
CONCLUSIONS
This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.
PubMed: 38352117
DOI: 10.1093/crocol/otae007 -
PloS One 2024Increasing illicit drug use is one of the main problems in most countries or societies. Monitoring heavy metals and trace elements in this vulnerable group seems to be...
Increasing illicit drug use is one of the main problems in most countries or societies. Monitoring heavy metals and trace elements in this vulnerable group seems to be necessary. Therefore, we assessed the urinary trace element and toxic metals/metalloids concentrations (Zinc (Zn), Iron (Fe), Copper (Cu), Chromium (Cr), Lead (Pb), Cadmium (Cd), Arsenic (As), Nickel (Ni), and Mercury (Hg)) in opium, tramadol, and cannabis users compared to healthy subjects. In this cross-sectional study, patients with substance use disorder (SUD) (n = 74) were divided into four groups: cannabis, tramadol, opium, and mixed (simultaneous use of more than one of the three studied substances), along with a healthy group (n = 60). Urine samples were prepared by dispersive liquid-liquid microextraction method so that heavy metals/metalloids could be measured by ICP-MS. The mean urinary concentration of Cu (48.15 vs. 25.45; 89.2%, p<0.001), Hg (1.3 vs. 0.10; 1200%, p < 0.001), and Zn (301.95 vs. 210; 43.8%, p < 0.001) was markedly lower among patients with SUD. The mean urinary concentration of other elements including As (1.9 vs. 4.1; 115.8%), Cd (0.1 vs. 1.10; 1000%), Cr (6.80 vs. 11.65; 71.3%), Ni (2.95 vs. 4.95; 67.8%), and Pb (1.5 vs. 7.9; 426.6%) were significantly higher among patients with SUD compared to healthy subjects. When sub-groups were compared, no significant differences were observed between their trace element levels (Kruskal-Wallis test, p > 0.05). This can be an indication that regardless of the type of drug, the levels of trace elements are changed with respect to healthy individuals. Our results showed that illicit drug use causes changes in urinary trace element/heavy metal/metalloid levels and highlights the need for monitoring heavy metals and trace elements in individuals with substance use disorder. Assessment of different elements in biological samples of drug dependents may be useful for implementing new prevention and treatment protocols. In case of changes in their levels, complementary recommendations, attention to diet, and periodic assessment of toxic metal levels within treatment programs will be needed.
Topics: Humans; Trace Elements; Cadmium; Cross-Sectional Studies; Lead; Opium; Tramadol; Metals, Heavy; Chromium; Nickel; Arsenic; Mercury; Metalloids; Substance-Related Disorders; Illicit Drugs
PubMed: 38315674
DOI: 10.1371/journal.pone.0294740 -
World Journal of Gastroenterology Jan 2024Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Calcium-sensing receptor (CaSR) inhibits both...
BACKGROUND
Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Calcium-sensing receptor (CaSR) inhibits both actions. The latter has been well documented but not . The hypothesis to be tested was that activating CaSR inhibits diarrhea .
AIM
To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin (CTX) in mice.
METHODS
CTX was given orally to C57BL/6 mice to induce diarrhea. Calcium and calcimimetic R568 were used to activate CaSR. To maximize their local intestinal actions, calcium was administered luminally oral rehydration solution (ORS), whereas R568 was applied serosally using an intraperitoneal route. To verify that their actions resulted from the intestine, effects were also examined on intestine-specific CaSR knockouts. Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl or clinically by assessing stool consistency and weight loss.
RESULTS
CTX induced secretory diarrhea, as evidenced by increases in fecal Cl, stool consistency, and weight loss following CTX exposure, but did not alter CaSR, neither in content nor in function. Accordingly, calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines. Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts () and neuronal CaSR knockouts ().
CONCLUSION
Treatment of acute secretory diarrheas remains a global challenge. Despite advances in diarrhea research, few have been made in the realm of diarrhea therapeutics. ORS therapy has remained the standard of care, although it does not halt the losses of intestinal fluid and ions caused by pathogens. There is no cost-effective therapeutic for diarrhea. This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
Topics: Animals; Mice; Calcium; Cholera Toxin; Diarrhea; Mice, Inbred C57BL; Receptors, Calcium-Sensing; Weight Loss
PubMed: 38314127
DOI: 10.3748/wjg.v30.i3.268