Gastrointestinal Side Effects Research Articles

Transdermal Microneedles Alleviated Rheumatoid Arthritis by Inducing Immune Tolerance via Skin-Resident Antigen Presenting Cells.

Restoring immune tolerance is the ultimate goal for rheumatoid arthritis (RA) treatment. The most reported oral or intravenous injection routes for the immunization of autoantigens cause gastrointestinal side effects, low patient compliance, and unsatisfied immune tolerance induction. Herein, the use of a transdermal microneedle patch is for the first time investigated to codeliver CII peptide autoantigen and rapamycin for reversing immune disorders of RA. The immunized microneedles efficiently recruit antigen-presenting cells particularly Langerhans cells, and induce tolerogenic dendritic cells at the administration skin site. The tolerogenic dendritic cells further homing to lymph nodes to activate systemic Treg cell differentiation, which upregulates the expression of anti-inflammatory mediators while inhibiting the polarization of Th1/2 and Th17 T cell phenotypes and the expression of inflammatory profiles. As a result, the optimized microneedles nearly completely eliminate RA symptoms and inflammatory infiltrations. Furthermore, it is demonstrated that a low dose of rapamycin is crucial for the successful induction of immune tolerance. The results indicate that a rationally designed microneedle patch is a promising strategy for immune balance restoration with increased immune tolerance induction efficiency and patient compliance.

Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis. We reviewed and examined scientific articles from PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane from the initiation date till June 2023 to identify investigations that examined metformin performance in managing ADPKD. Among the employed search terminology, we searched for terms such as "metformin" and "ADPKD". MA was conducted using the Cochrane Collaboration's RevMan version 5.3.0 (The Cochrane Collaboration, Oxford, UK). We identified 4 investigations, with 164 total subjects who fulfilled our inclusion criteria. The experimental cohort displayed a marked reduction in the decline of estimated glomerular filtration rate (eGFR) relative to controls [mean difference (MD) = 2.31, 95% confidence interval (CI) = 0.82-3.79, p = 0.002]. We observed no obvious difference in the height-adjusted total kidney volume alteration, gastrointestinal side effects, and hypoglycemia between the two cohorts. Metformin was easily tolerable and safe and substantially reduced the eGFR decline among ADPKD patients. Moreover, although metformin-treated patients were more likely to suffer gastrointestinal adverse events, we observed no discernible difference between the two cohorts.

Efficacy of Ferrous Bis-Glycinate versus Ferrous Sulphate in Children with Iron Deficiency Anemia

Iron deficiency anemia is a common pediatric disease and oral iron supplementation is the usual treatment. Newer formulations has been developed to treat iron deficiency anemia in children. Objective: To compare the efficacy of ferrous Bis-Glycinate in children with iron deficiency anemia to the conventional therapy with ferrous sulphate. Methods: In this open labelled prospective clinical trial was performed in children with iron deficiency anemia. Two groups were made, one group was given ferrous sulphate and the other group ferrous bis-glycinate at a dose of 5 mg/kg/day, single daily dose. Patient were followed 04 weekly till 12 weeks and then baselines reviewed. Results: Out of these total 108 children, 64 (59.3%) were male while the remaining 40.7% were female, with mean age was 27.48 in months with SD of 14.1. Iron therapy succefully raised Hb by 3.49 gm/dl as a whole with in Iron Bis –glycinate group as 3.85d/dl while 3.13gm /dl in ferrous sulphate group. The frequency of gastrointestinal adverse symptoms were less in bis-glycinate group. Conclusions: It was concluded that ferrous bis-glyicante has better efficacy to ferrous sulphate in term of Hb rising and has less gastrointestinal side effects.

Metformin-Associated Lactic Acidosis-Is This on Your Radar?

Background: Metformin is a biguanide hyperglycemic agent used to manage non–insulin-dependent diabetes mellitus. Adverse reactions include mainly mild gastrointestinal adverse effects, but severe complications, such as metformin-associated lactic acidosis (MALA) can occur. Metformin is excreted renally and, therefore, not recommended in patients with renal impairment. The reported incidence of MALA is 3 cases per 100,000 patient-years. Case ReportA 79-year-old woman with a complex medical history, including end-stage renal disease on dialysis and type 2 diabetes, presented to the emergency department (ED) for altered mental status. Prior to arrival, she was found to be hypoglycemic. Her laboratory results were significant for creatinine of 6.56 mg/dL and an anion gap of 52 mmol/L. The venous blood gas revealed a venous pH of 6.857 [reference range (7.32–7.43)], pCO2 of 15.9 mm Hg (40.6–60 mm Hg), HCO3 of 2.7 mmol/L (21–30 mmol/L), lactate of 27 mmol/L (0.5–2 mmol/L), and ammonia of 233 µmol/L. The patient was dialyzed emergently in the ED; repeat laboratory test results showed blood urea nitrogen of 10 mg/dL, creatinine of 1.65 mg/dL, carbon dioxide of 26 mmol/L, and anion gap of 13 mmol/L. The repeat ammonia was 16 µmol/L. The patient's metabolic encephalopathy resolved, and she was discharged home on hospital day 3. Why Should an Emergency Physician Be Aware of This?MALA has a high mortality rate (36%). Laboratory markers have not been found to be a reliable predictor of mortality. Sodium bicarbonate is controversial, but a pH < 7.15 indicates consideration of its use. A pH < 7.1 and a lactate level > 20 mmol/L indicate the need for emergent hemodialysis. Prompt recognition and management in the ED with early hemodialysis can result in good patient outcomes, with a return to their baseline function despite severe laboratory findings.

Causes of Iron Deficiency Anemia in Children Less Than 12 Years Old at Cooper University Hospital and Their Response to Intravenous Iron Replacement

Title of project: Causes of iron deficiency anemia in children less than 12 years old at Cooper University Hospital and their response to intravenous iron Background: Iron deficiency anemia (IDA) is the most common type of anemia in children. Even among industrialized countries like the US, IDA affects many children. Serious adverse outcomes can occur in children with IDA including, cognitive and motor neurodevelopmental delays which may be irreversible. While poor oral intake tends to be the focus of screening and preventative measures, additional causes of IDA include malabsorption from gastrointestinal abnormalities, medications that decrease iron absorption, parasitosis, genitourinary loss, and blood loss. Menorrhagia is a common cause of IDA among adolescents. The average age of menarche for adolescent girls is 12.43 years. Therefore, on data evaluation for the cause of IDA among patients aged 1-21, menstrual bleeding was overrepresented. Objective: This sub-analysis of a single center retrospective chart review analyzed the causes of IDA among children less than 12 years of age at Cooper University Hospital and their response to intravenous iron treatment. Methods: Data on all patients 1-12 years old who received intravenous iron infusions at Cooper University Hospital for IDA between 2016 and 2021 was analyzed. Descriptive statistics on the etiology of IDA and paired t-tests comparing pre-infusion hematologic parameters (hemoglobin, RDW, RBC, MCV, iron, ferritin, TIBC, percent saturation) to post-infusion values were conducted. Results: From the 150 patients included in the original study, 26 patients were 12 years of age or younger. The causes of IDA among these patients included inadequate dietary intake (65.4%), inflammatory bowel disease (15.4%), menorrhagia (15.4%) and one patient with factor II deficiency (3.8%). These patients required between one to eleven infusions to return to normal lab values. When comparing pre-infusion to post-final infusion lab values, there was significant improvement in all values (ferritin, iron, hemoglobin, MCV and RBCs) except total iron binding capacity, RDW and percent saturation. Discussion: Inadequate dietary intake was the most common cause of IDA in children less that 12 years old treated at Cooper University Hospital. Other causes included inflammatory bowel disease, menorrhagia and factor II deficiency. In contrast, the most common cause of IDA in children 12 and older was menorrhagia. Childhood food insecurity has been linked to IDA among low-income patients in the United States. Despite food assistance programs and adequate dietary education, patients continue to remain iron deficient. The current first-line therapy at Cooper University Hospital is oral iron supplementation. However, many patients fail the oral iron trial due to non-adherence, children spitting up or refusing to take the medication, and gastrointestinal side effects. Many pediatric patients in our clinic population are on NJ state insurance which requires a failed oral iron therapy trial prior to qualifying for coverage of intravenous iron. Yet, in a previous retrospective study completed in our clinic, intravenous iron has proven to be effective and safe, with fewer side effects and better adherence. For many patients, especially infants and toddlers, intravenous iron may provide a quicker cure for IDA, preventing irreversible neurodevelopmental delays. We propose that treatment with oral iron and intravenous iron should both be considered for first-line therapies and should be a shared decision between parents and providers.

Co-Occurrence of Familial Mediterranean Fever and Hematologic Malignancies: Case Report Series

Introduction: Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder primarily found among individuals of Mediterranean descent, including Armenians, Italians, Greeks, Arabs, Turks and Jews. In the Armenian population, approximately 90% of FMF cases are associated with three main mutations (M694V, V726A, and M680I) in two alleles of MEFV gene, while more than 300 MEFV variants have been reported worldwide. The homozygous M694V genotype is associated with frequent renal failure due to amyloidosis. Clinical manifestations of FMF include periodic attacks of diffuse serositis with pain and fever that are treated with colchicine or biologic therapy. There is a scarcity of data on patients with FMF and hematologic malignancies. Limited data makes it difficult to generate evidence-based recommendations for the management of these patients, which is mostly based on expert opinions or few case reports. Here we report the case series of patients from Armenia with simultaneous presence of FMF and hematologic malignancies (FMFHM) and evaluate their management challenges. Methods: Data was collected from the Armenian National Registry of Blood Disorders, at the Hematology Center after Prof. R. Yeolyan, and through personal interviews conducted with each patient. Hematology Center is the only institution in Armenia managing hematologic malignancies. We have analyzed 8 patients diagnosed with both FMFHM during 2000-2020, treated in the pediatric (1 patient) and adult (7 patients) hematology departments. Results: 8 patients with FMFHM were identified, from which 4 were diagnosed with myeloproliferative neoplasms (MPN), 2 with acute leukemia (AL), and 2 with non-Hodgkin lymphoma (NHL). The median age of patients was 46, range 20-60 years. Only 5 (62.5%) of patients were regularly taking colchicine for FMF, while the rest refused it. Four MPN patients received treatment only with oral medications (tyrosine kinase inhibitors, hydroxyurea). Autologous hemopoietic stem cell transplantation (auto-HSCT) was performed in 1 NHL patient after indicated 1 st and 2 nd line immuno-chemotherapy. Another 2 AL patients and one NHL patient received protocol-based respective chemotherapy regimens. Moderate gastrointestinal (GI) complications (e.g., epigastric pain, nausea, vomiting, intestinal discomfort) was experienced by 7 (87.5%) patients. Allergic reactions (e.g., moderate skin rash, itching) were seen in 5 patient (62.5%), of which one developed severe anaphylactic shock. A patient with FMF and PMF had ischemic stroke caused by thrombi. Arterial hypertension occurred in 3 (37.5%). Only in one patient reduction of colchicine dosage was performed (1mg/day was reduced to 0.6mg/d), because of interaction with imatinib. The rest of patients received chemotherapy and colchicine treatment as indicated. All 8 patients are alive, 5 of them are in hematologic or molecular remission, two of which received concurrent colchicine treatment. One patient in remission developed renal failure due to FMF (colchicine was refused). Two patients with MPN treated with colchicine experienced disease stabilization. Conclusion: In conclusion, the concurrent appearance of FMFHM may potentially increase the risk of GI side effects, allergic complications, and arterial hypertension, however definitive conclusions require further investigations in larger patient cohorts. While the overall treatment responses were largely positive, the association between MEFV and HM mutations warrants deeper exploration to provide more precise drug administration recommendations for colchicine and cancer medications. Future studies in this area will contribute to a better understanding of the interplay between these conditions and guide optimal treatment strategies.

Cranberries for preventing urinary tract infections.

Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012. To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included. At least two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. For this update, 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo, water or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%; moderate certainty evidence), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%; moderate certainty evidence), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%; low certainty evidence). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs, as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving a placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs. This update adds a further 26 studies, taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.

OAGB Bowel Function in Patients With up to 5 Years Follow-Up: Updated Outcomes.

One-anastomosis gastric bypass (OAGB) is considered an effective technique in weight reduction and remission of comorbidities. However, in common with many bariatric and metabolic/bariatric procedures, gastrointestinal side effects are frequently reported, but clinical experience varies.The objective of this study was to analyze the bowel function of patients who undergo OAGB looking at 5-yearpostoperative outcomes. This study is cross-sectional, descriptive and analytical, developed with individuals undergoing OAGB (n = 208)in yhe period between 2015 and 2020. The time periods evaluated were 1 to 6 months (T1), 6 to 12 months (T2),and 1 to 5 years (T3). Data analysis was performed using SPSS v.28.0, considering a significance level p ≤ 0.05. 114 participants (54.8%), 79.8% women, mean age 47.0 ± 12.6 years, and BMI 40.1 ± 5.6 kg/m2, 51.9%dyslipidemia, 43.6% arterial hypertension, and 19.1% diabetes mellitus. The T1 group had more severesymptoms/nausea than the T2 group. The T2 group had a significantly lower defecation frequency than the T1 andT3 groups. As for the occurrence of diarrhea, associations were not found in the considered groups. The T3 grouphad a greater severity of constipation associated with greater difficulty in consuming red meat, white meat, rice,vegetables, and salads. Gastrointestinal symptoms are prevalent in the first postoperative months. However, diarrhea was not common. The patient selection policy and surgical technique were decisive in this result. Constipation was prevalent in patients between 1 and 5 postoperative years. It was also prevalent in those who had food intolerance, which from a nutritional point of view is an adverse factor for optimal bowel function.

Endomorphin-2 analogs with C-terminal esterification display potent antinociceptive effects in the formalin pain test in mice

Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test. Our results demonstrated that intracerebroventricular (i.c.v.) administration of 0.67–20 nmol EM-2 analogs EM-2-Me, EM-2-Et and EM-2-Bu produced dose-dependent antinociceptive effects in both phase Ⅰ and phase Ⅱ of formalin pain. EM-2-Me and EM-2-Bu displayed more potent antinociception than morphine. Especially, EM-2-Bu exhibited the highest antinociception in phase Ⅱ of formalin pain, with the ED50 value being 2.1 nmol. Naloxone (80 nmol, i.c.v.) completely antagonized the antinociceptive effects of EM-2-Me, EM-2-Et and EM-2-Bu (20 nmol, i.c.v.) in both phase I and phase Ⅱ of formalin pain, suggesting a central opioid mechanism. Nevertheless, the antinociception induced by EM-2-Me might be involved in the release of dynorphin A, which subsequently acted on κ- opioid receptor. EM-2-Bu produced the antinociception probably by the direct activation of both μ- and δ-opioid receptors. EM-2-Me, EM-2-Et and EM-2-Bu also produced significant analgesic effects after peripheral administration, and the central opioid receptors were involved. Furthermore, EM-2-Bu had no influence on the locomotor activity after i.c.v. injection. The present investigation demonstrated that C-terminal esterified modifications of EM-2 will be beneficial for developing novel therapeutics in formalin pain.

Acute Colonic Pseudo-Obstruction: A Comprehensive Review

Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie's syndrome, is a rare but potentially life-threatening condition characterized by a large dilation of the colon without any physical blockage. It predominantly affects elderly individuals with multiple underlying health conditions, postoperative patients, and those receiving medications that impact gastrointestinal motility. The exact underlying mechanisms leading to ACPO remain unclear, but it is believed to result from dysfunction in the autonomic neural system, causing impaired colonic motility. Patients with ACPO typically present with symptoms such as abdominal distension, pain, and constipation. The diagnosis of ACPO is established based on clinical assessment, X-ray imaging, and the exclusion of mechanical obstruction. Treatment for ACPO involves promptly identifying and addressing any underlying medical conditions that may contribute to its development, such as correcting electrolyte imbalances or discontinuing medications with gastrointestinal side effects. Non-invasive measures, such as decompressing the colon using a rectal tube or administering a medication called neostigmine, are often effective in relieving symptoms. In refractory cases where conservative measures fail, surgical intervention may be necessary. Despite the rarity of ACPO, its potential for significant morbidity and mortality emphasizes the importance of promptly recognizing and managing the condition. Healthcare providers should exercise caution in patients with risk factors and clinical features suggestive of ACPO. By understanding the pathophysiology and promptly initiating appropriate interventions, healthcare professionals can optimize outcomes and minimize the potential complications associated with ACPO.

Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study

Guidelines to treat iron deficiency recommend daily provision of oral iron, but this may decrease fractional iron absorption and increase side effects. Our objective was to compare consecutive-day versus alternate-day iron supplementation. In a double-masked, randomized, placebo-controlled trial, young Swiss women (n=150; serum ferritin ≤30μg/L) were assigned to: daily 100mg iron for 90d, followed by daily placebo for another 90d (consecutive-day group) or the same daily dose of iron and placebo on alternate days for 180d (alternate-day group). The study period was 24/11/2021-10/8/2022. Co-primary outcomes, at equal total iron doses, were serum ferritin and gastrointestinal side effects; secondary outcomes were iron deficiency and serum hepcidin. Compliance and side effects were recorded daily using a mobile application. Data were analysed using mixed models and longitudinal prevalence ratios (LPR). The trial was registered at ClinicalTrials.gov (NCT05105438). 75 women were assigned to each group and included in the intention-to-treat analysis. Capsule adherence and side effect reporting was >97% in both groups. At equal total iron doses, comparing consecutive-day and alternate-day groups, median serum ferritin was 43.8μg/L (31.7-58.2) versus 44.8μg/L (33.8-53.6) (P=0.98), the LPR for gastrointestinal side effects on days of iron intake was 1.56 (95% CI: 1.38, 1.77; P<0.0001), and median serum hepcidin was 3.0nM (IQR 2.0-5.0) versus 1.9nM (1.4-2.9) (P<0.0001). Iron deficiency prevalence after 3 months was 5.5% versus 4.3% (P=0.74) and after 6 months was 11.4% and 3.0% (P=0.049). At equal total iron doses, compared to consecutive day dosing of iron, alternate day dosing did not result in higher serum ferritin but reduced iron deficiency at 6 months and triggered fewer gastrointestinal side effects. Swiss National Science Foundation, Bern, Switzerland.

Ferric derisomaltose and Outcomes in the Recovery of Gynecologic oncology: ERAS (Enhanced Recovery After Surgery) (FORGE) – a protocol for a pilot randomised double-blinded parallel-group placebo-controlled study of the feasibility and efficacy of intravenous ferric derisomaltose to correct preoperative iron-deficiency anaemia in patients undergoing gynaecological oncology surgery

IntroductionIron-deficiency anaemia is common in gynaecological oncology patients. Blood transfusions are immunosuppressive and carry immediate and long-term risks. Oral iron replacement remains the standard of care but requires prolonged treatment...

Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes.

Multidrug and toxin extrusion transporter 1 (MATE1), encoded by the SLC47A1 gene and single nucleotide polymorphisms of organic cation transport 1, may impact metformin's responsiveness and side effects. Inward-rectifier potassium channel 6.2 (Kir 6.2) subunits encoded by KCNJ11 may affect the response to sulfonylurea. This study aimed to evaluate the association between SLC22A1 rs72552763 and rs628031, SLC47A1 rs2289669 and KCNJ11 rs5219 genetic variations with sulfonylurea and metformin combination therapy efficacy and safety in Egyptian type 2 diabetes mellitus patients. This study was conducted on 100 cases taking at least one year of sulfonylurea and metformin combination therapy. Patients were genotyped via the polymerase chain reaction-restriction fragment length polymorphism technique. Then, according to their glycated hemoglobin level, cases were subdivided into non-responders or responders. Depending on metformin-induced gastrointestinal tract side effects incidence, patients are classified as tolerant or intolerant. KCNJ11 rs5219 heterozygous and homozygous mutant genotypes, SLC47A1 rs2289669 heterozygous and homozygous mutant genotypes (AA and AG), and mutant alleles of both polymorphisms were significantly related with increased response to combined therapy. Individuals with the SLC22A1 (rs72552763) GAT/del genotype and the SLC22A1 (rs628031) AG and AA genotypes were at a higher risk for metformin-induced gastrointestinal tract adverse effects. The results implied a role for SLC47A1 rs2289669 and KCNJ11 rs5219 in the responsiveness to combined therapy. SLC22A1 (rs628031) and (rs72552763) polymorphisms may be associated with increased metformin adverse effects in type 2 diabetes mellitus patients.

Lactulose in cirrhosis: Current understanding of efficacy, mechanism, and practical considerations.

HE is a complication of cirrhosis characterized by neuropsychiatric and motor dysfunction, and results in decreased quality of life and increased mortality. Lactulose is a synthetic disaccharide used to treat HE since 1966, though many questions about its use remain unanswered. Lactulose reverses minimal HE, prevents overt HE, improves quality of life, increases the rate of recovery from overt HE, and improves survival rates. Lactulose's clinical effect appears to be derived from its impact on intestinal microbes, likely a result of its enteric acidifying effect, positive pressure on beneficial taxa, and improvement of gut barrier function. There are several practical considerations with lactulose including (1) a need to avoid excessive bowel movements and subsequent dehydration, (2) treatment titration protocols need further investigation, (3) baseline or treatment-induced gastrointestinal side effects limit adherence in some cases, and (4) the utility of monitoring stool consistency or pH remains unknown. Further research is needed to optimize our use of this effective treatment for HE.

Curcumin supplementation prevents cisplatin-induced nephrotoxicity: a randomized, double-blinded, and placebo-controlled trial.

Cisplatin-induced nephrotoxicity (CIN) remains the most prevailing unfavorable influence and may affect its clinical usage. This study sought to explore the possible impacts of curcumin on preventing CIN in human subjects. The investigation was a placebo-controlled, double-blinded, randomized clinical trial conducted on 82 patients receiving nano-curcumin (80 mg twice daily for five days) or an identical placebo with standard nephroprotective modalities against CIN. Data was gathered on patients' demographics, blood, urinary nitrogen, creatinine (Cr) levels, urinary electrolytes, and urine neutrophil gelatinase-associated lipocalin (NGAL) levels in treatment and placebo groups, 24 h and five days after initiating the administration of cisplatin. Both investigation groups were alike considering the demographic characteristics and clinical baseline data. Curcumin administration led to a significant improvement in blood-urine nitrogen (BUN). BUN, Cr, glomerular filtration rate (GFR), and the ratio of NGAL-to-Cr considerably altered during the follow-up periods. However, the further alterations in other indices, including urinary sodium, potassium, magnesium, NGAL values, and potassium-to-Cr ratio were not statistically noteworthy. The significant differences in the NGAL-to-Cr ratio between the two groups may indicate the potential protective impact of curcumin supplementation against tubular toxicity. Curcumin management was safe and well-accepted; only insignificant gastrointestinal side effects were reported. Curcumin supplementation may have the potential to alleviate CIN and urinary electrolyte wasting in cancer patients. Future research investigating the effects of a longer duration of follow-up, a larger participant pool, and a higher dosage of curcumin are recommended.

Synthesis and pharmacological characterization of new curcumin ester pro-drugs with enhanced anti-inflammatory, anti-ulcerogenic and improved tissue distribution

In this work, curcumin- Non steroidal anti-inflammatory drugs (NSAIDs) conjugates were synthesized by esterification of the phenolic group of curcumin with the acid group of NSAIDs using the Steglich esterification method to enhance the anti-inflammatory activity of curcumin and to reduce the gastrointestinal side effects of NSAIDs. A set of bis C-NSAIDs conjugates was prepared by direct coupling of curcumin with Aceclofenac and Diflunisal respectively in good yield and characterized by Fourier-transform infrared spectra (FTIR) and Proton Nuclear Magnetic Resonance Spectra (1HNMR). In vivo, studies were performed to evaluate the toxicity, anti-inflammatory activity, bio-distribution, and anti-ulcerogenic studies of selected conjugates using different animal models. In Vivo, studies reveal enhanced biological activity with better tissue distribution of conjugates than that of parent curcumin and it could be a curcumin-based therapeutic molecule that might be explored further for its efficacy in managing inflammatory diseases.

Detailed review on Bevacizumab and its target therapies

The review in this article focuses on bevacizumab, an agent widely used in a variety of treatment strategies. It provides an overview of the pharmacokinetics and pharmacodynamics of bevacizumab, with a focus on intravenous administration and available specific dose strengths. This article discusses treatment strategies with bevacizumab and emphasizes the importance of understanding its pharmacokinetic properties to optimize its efficacy. In addition, this review covers a wide range of side effects associated with bevacizumab, including cardiovascular, gastrointestinal, hematological, immune, musculoskeletal, nervous, renal, respiratory, and other side effects. The importance of close monitoring and prompt management of adverse events is emphasized to ensure patient safety and optimize patient outcomes. Overall, this literature review provides valuable insight into the use of bevacizumab and helps health professionals make informed decisions regarding dosing, monitoring, and management of side effects.

The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.

Oxidative stress is increasingly recognized as a central player in a range of gastrointestinal (GI) disorders, as well as complications stemming from therapeutic interventions. This article presents an overview of the mechanisms of oxidative stress in GI conditions and highlights a link between oxidative insult and disruption to the enteric nervous system (ENS), which controls GI functions. The dysfunction of the ENS is characteristic of a spectrum of disorders, including neurointestinal diseases and conditions such as inflammatory bowel disease (IBD), diabetic gastroparesis, and chemotherapy-induced GI side effects. Neurons in the ENS, while essential for normal gut function, appear particularly vulnerable to oxidative damage. Mechanistically, oxidative stress in enteric neurons can result from intrinsic nitrosative injury, mitochondrial dysfunction, or inflammation-related pathways. Although antioxidant-based therapies have shown limited efficacy, recognizing the multifaceted role of oxidative stress in GI diseases offers a promising avenue for future interventions. This comprehensive review summarizes the literature to date implicating oxidative stress as a critical player in the pathophysiology of GI disorders, with a focus on its role in ENS injury and dysfunction, and highlights opportunities for the development of targeted therapeutics for these diseases.

Possibilities for reducing toxicity in colon cancer patients receiving adjuvant polychemotherapy

Introduction. According to the World Health Organization, colorectal cancer is the third most common type of cancer in the world. The surgical method of treatment is the main one in locally advanced stages; however, a large proportion of patients require complex treatment, including adjuvant chemotherapy. When conducting adjuvant chemotherapy, it is extremely important to maintain the rhythm of cycles and minimize adverse events that may lead to dose reduction. Prevention of dose-limiting toxicity allows us to achieve the following goals – improving the quality of life of the patient and adherence to treatment, as well as performing a full-fledged stage of the planned complex treatment.Aim. Evaluation of the effectiveness of Polisorb MP in the occurrence of gastrointestinal side effects of adjuvant polychemotherapy in patients with colorectal cancer.Materials and methods. The prospective study included 40 patients with a verified diagnosis of CCR, received treatment and observation at the St. Petersburg City Clinical Oncology Centre from April 2022 to October 2022. All patients received radical surgery and subsequent adjuvant chemotherapy in the XELOX regimen were divided into two groups. The first group of patients (n = 20) received only ACT, patients of group 2 from 16 to 20 days after the completion of each session of ACT received Polysorb MP. Both groups were comparable in terms of gender and age. In the studied cohort of patients there were 20 (50.0 %) men and 20 (50.0 %) women. The age of patients ranged from 31 to 75 years; the median age was 62 years [54.00–68.50]. The quality of life of patients receiving adjuvant polychemotherapy was assessed using the QLQ-C30 questionnaires with the QLQ-CR29, EQ-5D module.Results. The use of Polysorb MP made it possible to significantly reduce the level of creatinine in the blood of patients, which can increase after one cycle of ACT, especially with the use of platinum preparations. In addition, our results indicate that the use of Polysorb MP after ACT in patients with colorectal cancer can significantly improve the quality of life of patients, both by minimizing the symptoms associated with previous treatment and the adverse effects of the drug treatment itself, as well as by improving the general condition of the patient. In patients who received Polysorb MP as an accompanying therapy against the background of AHT, significant deterioration in general and functional health (according to the results of the analysis of the QLQ-C30 questionnaires), increased severity of disease symptoms and treatment complications (according to the results of the analysis of the QLQ-C29 and QLQ-C30 questionnaires), as well as a significant decrease in the general state of health according to the results of the analysis of the dynamics on the EQ-5D scale, was not detected.Conclusions. In patients receiving adjuvant polychemotherapy for locally advanced colon cancer, it can be concluded that it is advisable to use Polysorb MP in order to reduce the manifestation of gastrointestinal toxicity and improve the quality of life of patients, which, in turn, allows a full course of treatment, avoiding dose-limiting adverse events.

Effect of partially hydrolyzed synbiotic formula milk on weight gain of late preterm and term infants-a multicenter study.

Data on the effectiveness of hydrolyzed infant formula containing both pre- and probiotics (synbiotic formula) on the growth of infants is still scarce. This retrospective study was designed to evaluate the effect of a partially hydrolyzed synbiotic formula on growth parameters and the possible occurrence of major gastrointestinal adverse events or morbidities in infants born via cesarean section (C-section) delivery. C-section-delivered term and late preterm infants who received either partially hydrolyzed synbiotic formula, standard formula, or maternal milk and followed at seven different hospitals from five different regions of Turkey, during a 1-year period with a minimum follow-up duration of 3 months were evaluated retrospectively. All the included infants were evaluated for their growth patterns and any kind of morbidity such as diarrhea, constipation, vomiting, infection, or history of hospitalization. A total of 198 infants (73 in the human milk group, 61 in the standard formula group, and 64 in the partially hydrolyzed synbiotic formula group) reached the final analysis. The groups were similar regarding their demographic and perinatal characteristics. No difference was observed between the three groups regarding gastrointestinal major side effects. Growth velocities of the infants in the human milk and partially hydrolyzed synbiotic formula groups during the first month of life were similar whereas the weight gain of infants in the standard formula group was significantly less than these two groups (p < 0.001). Growth velocities were similar among the three groups between 1st and 3rd months of age. A partially hydrolyzed synbiotic formula provided better weight gain in late-preterm and term infants who were delivered via C-section delivery compared to the standard formula during the first month of life. This weight gain was similar to the infants receiving exclusively human milk. This difference was not observed in length and head circumference gain. No difference was observed in any of the parameters during the 1st-3rd months of age. Specially formulated partially hydrolyzed synbiotic formulas may reverse at least some of the negative impacts of C-section delivery on the infant and help to provide better growth, especially during the early periods of life.