Gastrointestinal Side Effects Research Articles

Role of prebiotics and probiotics in the prevention of the gastrointestinal side effects of metformin among the type 2 diabetic patients

Background: Diabetes mellitus (DM) is most common endocrine disorder all over the world. Metformin has been used as a first line drug, however, it has several gastrointestinal side effects. This study aims to determine the frequency of metformin induced gastrointestinal side effects among type 2 diabetic patients and role of prebiotics and probiotics in the prevention of the metformin-induced GI side effects. Methods: This cross-sectional study was performed in a tertiary care hospital, Rawalpindi, among 130 for one year from January 2021 to December 2022. Data was collected by applying a self-structured questionnaire. Descriptive statistics were used for the data analysis. Data analysis was performed via statistical package for the social sciences (SPSS) version 25.0. Results: The means for study variables like age, dose, and duration of therapy were 54.09 years, 1000 mg and 3.6 years respectively. Female patients had more GI side effects than male patients. Similarly, GI side effects frequency was also higher among the patients who were on metformin alone than the patients who were using metformin and combination of prebiotics and probiotics. Patients with higher dose of metformin and shorter duration of metformin therapy had higher frequency of GI symptoms. The most common GI symptom was constipation followed by diarrhea, bloating, abdominal pain, vomiting/nausea, dyspepsia, loss of appetite and flatulence. Conclusions: Metformin induced GI symptoms were common among study population. Use of prebiotics and probiotics combination with metformin, low dose of metformin, and longer duration of metformin use were found protective against the metformin-induced GI side effects.

Implications of Ozempic and Other Semaglutide Medications for Facial Plastic Surgeons.

Obesity is a growing global health concern, leading to various health issues, including diabetes. Semaglutide-based medications, such as Ozempic, Wegovy, and Rybelsus, have emerged as potential treatments. These medications, belonging to the glucagon-like peptide-1 (GLP-1) receptor agonist class, mimic the action of GLP-1, regulating appetite and promoting weight loss. Clinical trials have shown their effectiveness in reducing body weight and improving metabolic parameters. Ozempic, though Food and Drug Administration-approved for diabetes, is also used off-label for weight loss alone. Rapid weight and fat loss with Ozempic can lead to the characteristic "Ozempic face," where facial volume and fat are depleted, resulting in wrinkles and sagging skin. Providers prescribing Ozempic seldom counsel patients about the potential impact on the face. As a result, the plastic surgery community faces a challenge in managing facial changes associated with rapid weight loss. Dermal fillers, skin tightening techniques, and surgical interventions are useful for both restoration of facial volume and to manage excess skin. Discontinuation of Ozempic should be considered prior to general anesthesia due to gastrointestinal side effects including delayed gastric emptying. As the popularity of Ozempic grows, facial plastic surgeons must be aware of both the impact on facial appearance and perioperative considerations.

Adjuvant pharmacological strategies for the musculoskeletal system during long-term space missions.

Despite two hours of daily exercise training, muscle wasting and bone loss are still present after 6-month missions to the international space station. Some crew members lose bone much faster than others. In preparation for Moon and Mars, space agencies are therefore reviewing their countermeasure portfolios. Here, we discuss the potential of current pharmacological strategies. Bone loss in space is fueled by bone resorption. Alendronate, an oral bisphosphonate, reduced bone losses in experimental bed rest and space. However, gastrointestinal side effects precluded its further utilization in space. Zoledronate (a potent bisphosphonate), denosumab (RANKL antagonist) and romosozumab (sclerostin antagonist) are all administered via injection. They effectively suppress bone resorption and are routinely prescribed against osteoporosis. Their serious adverse effects, namely osteonecrosis of the jaw and atypical femur fractures occur very rarely when the usage is limited to one or two years. Hence, utilization of one of these compounds may outweigh the bone risks of space travelling, in particular in those with high bone resorption rates. Muscle wasting in space is likely due to hampered muscle protein synthesis. Even though this might theoretically be countered by the synthesis-boosting effects of anabolic steroids, the practical grounds for such recommendation are currently weak. Moreover, they reveal their full potential only when combined with an anabolic exercise stimulus, e.g. via strength training. It therefore seems that a combination of exercise and pharmacological countermeasures should be considered for musculoskeletal health on the way to Moon and Mars and back.

Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.

Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses. PBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites. Non-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46-7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb. PBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation.

The effects of mydriatic eye drops on cerebral blood flow and oxygenation in retinopathy of prematurity examinations.

Mydriatic eye drops used during retinopathy examination have been associated with cardiovascular, respiratory, and gastrointestinal side effects. The aim of our study was to investigate the effects of the drops used for pupil dilatation on cerebral blood flow and cerebral oxygenation. The study included 62 infants who underwent retinopathy screening exams. Vital signs, heart rate (HR), arterial oxygen saturation (SpO2), and mean arterial pressure (MAP) were recorded. Cerebral oxygenation and middle cerebral artery blood flow velocity were evaluated using near-infrared spectroscopy (NIRS) and Doppler ultrasonography, respectively, and the cerebral metabolic rate of oxygen (CMRO2) was also calculated. The mean gestational age of the infants included was 31.29 ± 1.42weeks, and the mean birth weight was 1620 ± 265g. Heart rate was found to be significantly decreased after mydriatic eye drop instillation; however, there were no significant differences regarding blood pressure and oxygen saturation levels (HR: p < 0.001; MAP: p = 0.851; SpO2: p = 0.986, respectively). After instillation while cerebral regional oxygen saturation (rScO2) measurements were significantly decreased at the 60th minute (p = 0.01), no significant difference was found in Vmax and Vmean of MCA before and after mydriatic eye drop instillation (p = 0.755, p = 0.515, respectively). Regarding CMRO2 measurements, we also did not find any statistical difference (p = 0.442). Conclusion:Our study has shown that although eye drops may affect heart rate and regional cerebral oxygen saturation, they do not alter cerebral blood flow velocities and metabolic rate of oxygen consumption. Current recommendations for mydriatic eye drop use in retinopathy exam appear to be safe. What is Known: • Mydriatic eye drop installation is recommended for pupil dilatation during ROP screening exams. • It's known that mydriatics used in ROP examination have affects on the vital signs, cerebral oxygenation and blood flow. What is New: • This is the first study evaluating the changes in cerebral oxygenation and blood flow velocity after mydriatic drop instillation using NIRS and Doppler US concomitantly. • While the eye drops may affect heart rate and regional cerebral oxygen saturation, they do not alter cerebral blood flow velocities and metabolic rate of oxygen consumption.

Intramuscularly Administered PLGA Microparticles for Sustained Release of Rivastigmine: In Vitro, In Vivo and Histological Evaluation

Rivastigmine is an acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibitor drug approved by the US Food and Drug Administration (FDA) for the treatment of mild to moderate dementia of Alzheimer's type. However, its first-pass metabolism and gastrointestinal side effects negatively affect the tolerability and efficacy of oral therapy. These adverse effects could be avoided with the use of a sustained -release formulation as an intramuscular (IM) administration system. The objective of this work was to develop polylactic co-glycolic acid (PLGA) microparticles for the sustained release of rivastigmine and to evaluate its stability during storage, tissue tolerance, in vitro release, and in vivo pharmacokinetics after its IM administration. The microparticles were made by the solvent evaporation emulsion method. A series of formulation parameters (the type of polymer used, the amount of polymer used, the initial amount of rivastigmine, and the volume of PVA 0.1% w/v) were studied to achieve an encapsulation efficiency (EE) and a rivastigmine load of 54.8 ± 0.9% and 3.3 ± 0.1%, respectively. The microparticles, whose size was 56.1 ± 2.8 μm, had a spherical shape and a smooth surface. FT-IR analysis showed that there is no chemical interaction between rivastigmine and the polymer. PLGA microparticles maintain rivastigmine retained and stable under normal (5 ± 3 °C) and accelerated storage (25 ± 2 °C and 60 ± 5 % RH) conditions for at least 6 months. The microparticles behaved as a sustained release system both in vitro and in vivo compared to non-encapsulated rivastigmine. The IM administration of the formulation in rats did not produce significant tissue damage. However, it is necessary to reproduce the experiments with multiple doses to rule out a negative effect in terms of tolerability in chronic treatment. To the best of our knowledge, this study is the only one that has obtained the sustained release of rivastigmine from PLGA microparticles after IM administration in an in vivo model.

Selective COX-2 inhibitors do not increase gastrointestinal reactions after colorectal cancer surgery: a systematic review and meta-analysis

BackgroundThe effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward.MethodsIn patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events.ResultsThe study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn’t significantly improved the 1–3 year remission rate (OR, 1.57 [95% CI: 0.95–2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99–1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20–6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66–2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02–1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose.ConclusionsFor patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily.

Primaquine and chloroquine nano-sized solid dispersion-loaded dissolving microarray patches for the improved treatment of malaria caused by Plasmodium vivax

Malaria is a global parasitic infection that leads to substantial illness and death. The most commonly-used drugs for treatment of malaria vivax are primaquine and chloroquine, but they have limitations, such as poor adherence due to frequent oral administration and gastrointestinal side effects. To overcome these limitations, we have developed nano-sized solid dispersion-based dissolving microarray patches (MAPs) for the intradermal delivery of these drugs. In vitro testing showed that these systems can deliver to skin and receiver compartment up to ≈60% of the payload for CQ-based dissolving MAPs and a total of ≈42% of drug loading for PQ-based dissolving MAPs. MAPs also displayed acceptable biocompatibility in cell tests. Pharmacokinetic studies in rats showed that dissolving MAPs could deliver sustained plasma levels of both PQ and CQ for over 7 days. Efficacy studies in a murine model for malaria showed that mice treated with PQ-MAPs and CQ-MAPs had reduced parasitaemia by up to 99.2%. This pharmaceutical approach may revolutionise malaria vivax treatment, especially in developing countries where the disease is endemic. The development of these dissolving MAPs may overcome issues associated with current pharmacotherapy and improve patient outcomes.

Factors Affecting Patient Adherence to Multivitamin Intake After Bariatric Surgery: Thematic Analysis of Qualitative Data From a Multicenter Study.

Introduction Adherence to daily intake of multivitamin supplementation (MVS) is a major challenge after bariatric surgery (BS). The aim of this study was to identify insights into patients' beliefs and experiences on adherence to MVS intake. Methods A thematic analysis of qualitative data from four high-volume bariatric centers in the Netherlands was conducted. A series of texts from the open-ended question of 1,246 patients were thematically analyzed for common or overarching themes, ideas, and patterns. Results Five key themes emerged regarding participants' suggestions on adherence to daily MVS intake: "gastrointestinal side effects to MVS intake" (n = 850, 68.2%), "negative features of MVS" (n = 296, 23.8%), "satisfaction with advice on MVS" (n = 272, 21.8%), "dissatisfaction with service provision" (n = 160, 12.8%), and "costs" (n = 93, 7.5%). Most problems were experienced when using specialized weight loss surgery (WLS) MVS. These supplements may cause gastrointestinal side effects, and costs are too high. After bariatric surgery, numerous patients strongly felt that information provision was poor in several aspects, and the aftercare pathway process did not provide sufficient support. Conclusion This study found five major themes involved in patient adherence to multivitamin intake after BS: gastrointestinal side effects to MVS intake, negative features of MVS, satisfaction with advice on MVS, dissatisfaction with service provision, and costs of specialized MVS. Challenges lie in stronger education for both patients and healthcare professionals. More personalized care could probably increase patient satisfaction, and MVS companies should look at further optimizing supplements for better tolerability and reducing costs.

Weight loss and side-effects of liraglutide and lixisenatide in obesity and type 2 diabetes mellitus

AimsGlucagon-like peptide-1 receptor agonist (GLP-1 RA) is used to treat obesity or type 2 diabetes mellitus (DM). We compared weight loss and side-effects between patients with and without DM using GLP-1 RA. MethodsThis was a retrospective cohort study based on electronic medical records. Patients were categorized into three groups: liraglutide without DM (LiRa_NL), liraglutide with DM (LiRa_DM), and lixisenatide with DM (LiXi_DM). Six-month outcomes were evaluated for weight loss, side-effect types, and onset discontinuation of GLP-1 RA. ResultsWe enrolled 356 (190 LiRa_NL, 95 LiRa_DM, and 71 LiXi_DM) patients (women, 72.5 %; mean age, 43.7 ± 12.7 years; mean body mass index, 30.7 ± 5.2 kg/m2). The mean glycated hemoglobin (HbA1c) participants were 7.7 ± 2.1 %. Average weight loss was 2.9 ± 0.3 kg. The change in HbA1c was lower in the LiXi_DM group than in the LiRa_DM group (− 1.1 ± 0.2 % vs. − 0.4 ± 0.1 %, P < 0.05). The LiRa_DM group showed a more effective weight loss (− 3.0 ± 0.4 kg) than the LiXi_DM group (− 0.9 ± 0.4 kg) (P < 0.05). Approximately 30 % of the patients reported experiencing side-effects, with gastrointestinal side-effects being the most frequent (20.5 %). The median side-effect onset was 1.9 ± 0.1 months from first treatment. The rate of GLP-1 RA discontinuation was 72.8 %. Discontinuation rates due to side-effects were 75.7 %, 68.9 %, and 64.4 % in the LiRa_NL, LiRa_DM, and LiXi_DM groups, respectively. ConclusionsThe LiRa_NL group showed the most weight loss, although the discontinuation rate was high. Most side-effects occurred at 1–2 months. When prescribing GLP-1 RA, education concerning side-effects and discontinuation is needed to enhance treatment adherence.

Comparing therapeutic effects of alternate day versus daily oral iron in women with iron deficiency anemia: A retrospective cohort study.

In order to replenish iron stores and bring hemoglobin (Hb) levels back to normal, oral iron is the primary treatment option for women with iron deficiency anemia (IDA). This study investigated the efficacy and side effects of daily versus alternate-day, given single doses versus double doses oral iron supplementation for treating IDA. A retrospective cohort study was performed between 2021 and 2022, including 120 patients. Study group were divided into 4 age-sex-matched groups; Group I (n = 30) and Group II (n = 30) which were received ferrous sulphate tablets daily in single or double doses, respectively, containing 60 mg of elemental iron each. Groups III (n = 30) and IV (n = 30) were received a single and double dose on alternate days, respectively. The primary outcome was the mean difference in Hb from baseline at week 4. Gastrointestinal (GI) side effects were accepted as a secondary outcome. The daily single dose and alternate day double dose groups had median Hb changes of 2.3 (2.1) and 2.6 (1.8) g/dL. The differences in Hb between Groups I and II, I and III, and Groups IV and II, IV and III were significant (P < .001, P = .001, P < .001, and P < .001, respectively). There is no significant difference between groups regarding improving iron parameters such as serum iron, total iron binding capacity, transferrin saturation, and ferritin. The incidence of GI side effects were greater in double doses than in single doses of daily or alternate-day therapies (43.3% and 30% vs 10% and 3.3%). Daily or alternate-day double dose resulted in more side effects but less therapeutic efficacy in women with IDA. To find the best supplementation method, randomized controlled trials with a larger sample of participants, longer study lengths, and various iron doses may be helpful.

Using a discrete choice experiment to elicit patients’ preferences and willingness-to-pay for knee osteoarthritis treatments in Thailand

Osteoarthritis is the most common type of joint disease among elderly patients around the world. In response to the need for patient-centered care, patients’ and physicians’ preferences for knee osteoarthritis treatments have been studied in multiple countries, but not in Thailand. The objective of this study was to investigate Thai patients’ preferences and their willingness to pay (WTP) for knee osteoarthritis treatments by using a discrete choice experiment (DCE). Six knee osteoarthritis treatment attributes, including pain relief, delayed disease progression, gastrointestinal side effects, kidney side effects, cardiovascular side effects, and cost, were used to develop a paper-based, DCE questionnaire survey. Patients with knee osteoarthritis, who were at least 18 years old and who provided written informed consent, were recruited from the orthopedic department in a tertiary care hospital in Thailand via convenience sampling. The conditional logit model was used to determine patients’ preferences and WTP. The Institutional Review Board at Chulalongkorn University approved this study before it started. A total of 232 patients were collected and analyzed in this study. Patients preferred treatments with a higher efficacy (pain relief and delayed disease progression), a lower probability of side effects (gastrointestinal, kidney, and cardiovascular side effects), and a lower cost. Regarding efficacy and side effects, the patients weighted the importance of a 1% change in cardiovascular side effects (− 0.08) more heavily than 1% changes in kidney (− 0.07) and gastrointestinal (− 0.02) side effects, delayed disease progression (0.02), and pain relief (0.01). Patients were willing to pay 29.56 Thai Baht (THB) and 41.84 THB per month for every 1% increase in pain relief and delayed disease progression, respectively. Conversely, patients were willing to pay 52.04 THB, 145.18 THB and 164.23 THB per month for every 1% decrease in gastrointestinal, kidney, and cardiovascular side effects, respectively. In conclusion, pain relief, delayed disease progression, gastrointestinal side effects, kidney side effects, cardiovascular side effects, and the cost of treatment were significant factors among patients undergoing knee osteoarthritis treatment. Additionally, patients had a higher WTP for delayed disease progression than pain relief and a higher WTP for a reduced probability of cardiovascular side effects than gastrointestinal and kidney side effects. These findings could be used to support treatment decisions for knee osteoarthritis patients in Thailand.

An observational study of childhood iron deficiency anaemia and the factors affecting the outcome of oral iron therapy

Background: Iron deficiency is the most common cause of anaemia worldwide. In-depth studies examining facilitators and barriers to oral iron therapy are lacking. The aim of our study is to determine the factors affecting the outcome of oral iron therapy in iron deficiency anaemia. Methods: This is an observational study conducted in a tertiary hospital in Mumbai in children in the age group of 12 to 60 months. Out of a total of 416 children screened, 208 were eligible for oral iron therapy and were given oral iron in the dose of 3 milligrams per kilogram per day and reviewed after two months. A comprehensive questionnaire was given to parents after the completion of therapy to study the factors affecting iron therapy. The details were then analysed using Excel sheets, and correlation was calculated using SPSS program version 20.0. Results: After 2 months of oral iron therapy, IDA was corrected in 68.98%. Factors that led to an unsatisfactory outcome with iron therapy were, history of low birth weight, past hospital admissions, gastrointestinal side effects, malnutrition, and children who had tea, milk, or food with iron therapy. In contrast, children who took iron on an empty stomach and along with vitamin C-rich foods had a significant increase in haemoglobin levels. Conclusions: Various modifiable factors affect adherence and outcome of oral iron therapy. Tea and Coffee are to be avoided when the child is on iron therapy. Meticulous counselling of parents and children is pivotal for the successful management of IDA with oral iron therapy.

Inhibitory potential of Phaseolus lunatus L. Seeds to Digestive Enzymes

Introduction: Study was taken with an objective to investigate the inhibitory effect of Phaseolus lunatus seeds extract on three enzymes (α-amylase, maltase and glucoamylase) which are involved in diabetes. The disadvantages related with the use of synthetic drugs make it necessary to search for alternative drugs from medicinal plants. One therapeutic approach for the treatment of postprandial hyperglycaemia is to decrease the plasma glucose level which can be attained by lowering the starch hydrolysis by digestive enzymes such as α-amylase, maltase and glucoamylase. The use of synthetic antidiabetic agents caused gastrointestinal side effects. Methods: Hence, the research was aimed to evaluate the potential of Phaseolus lunatus seeds extract to inhibit α-amylase, maltase and glucoamylase as a possible mechanism of hypoglycemia caused by this plant with less side effects. Phaseolus lunatus, also known as Lima bean, is native to Tropical America and are grown throughout the world. Lima bean has been prescribed traditionally to treat different diseases including diabetes. Result: The results of the present study showed that Phaseolus lunatus seeds extract have exerted both time and concentration dependent significant inhibitory effect on these digestive enzymes which might be due to cumulative effect of phytoconstituents present in the plant extract. Conclusion: Therefore, it can be said that the part of mechanisms by which Phaseolus lunatus exhibited its antidiabetic activity might be through the inhibition of these digestive enzyme.

Inhibitory potential of Phaseolus lunatus L. Seeds to Digestive Enzymes

Introduction: Study was taken with an objective to investigate the inhibitory effect of Phaseolus lunatus seeds extract on three enzymes (α-amylase, maltase and glucoamylase) which are involved in diabetes. The disadvantages related with the use of synthetic drugs make it necessary to search for alternative drugs from medicinal plants. One therapeutic approach for the treatment of postprandial hyperglycaemia is to decrease the plasma glucose level which can be attained by lowering the starch hydrolysis by digestive enzymes such as α-amylase, maltase and glucoamylase. The use of synthetic antidiabetic agents caused gastrointestinal side effects. Methods: Hence, the research was aimed to evaluate the potential of Phaseolus lunatus seeds extract to inhibit α-amylase, maltase and glucoamylase as a possible mechanism of hypoglycemia caused by this plant with less side effects. Phaseolus lunatus, also known as Lima bean, is native to Tropical America and are grown throughout the world. Lima bean has been prescribed traditionally to treat different diseases including diabetes. Result: The results of the present study showed that Phaseolus lunatus seeds extract have exerted both time and concentration dependent significant inhibitory effect on these digestive enzymes which might be due to cumulative effect of phytoconstituents present in the plant extract. Conclusion: Therefore, it can be said that the part of mechanisms by which Phaseolus lunatus exhibited its antidiabetic activity might be through the inhibition of these digestive enzyme.

Capecitabine-induced Gastrointestinal Injury Shows a Graft-Versus-Host Disease (GVHD)-like Pattern.

Capecitabine is a commonly used oral chemotherapeutic agent. Gastrointestinal (GI) side effects are clinically well-known, however, the histopathologic changes have not been comprehensively studied. This study describes the largest case series (8 patients) characterizing the histopathology of capecitabine-induced GI injury. All patients were adults (median age: 64.5y, range: 61 to 76y) and there was gender parity. Patients were receiving treatment for malignancies of the colorectum (n=5), breast (n=1), pancreas (n=1), and appendix (n=1). All had GI symptoms, including 7 with diarrhea and abdominal pain and 1 with melena. Five of 8 (63%) showed graft-versus-host disease (GVHD)-like histologic changes in small intestinal and/or colonic biopsies characterized by crypt disarray and dropout, crypt atrophy, dilated crypts lined by attenuated epithelium, and increased crypt apoptosis. Neuroendocrine cell aggregates were present in 4 of 5 cases. Four of 5 showed patchy prominence in lamina propria eosinophils. One patient receiving concomitant radiation therapy had a small intestinal biopsy showing regenerative changes. Two patients had histologically unremarkable biopsies. On follow-up, capecitabine was discontinued or dose-reduced in all patients. Three of 5 patients with a GVHD-like pattern had clinical improvement, whereas 2 died shortly after biopsy. One with regenerative changes also had radiation dose reduction and improved clinically. Two with unremarkable biopsies improved symptomatically. In summary, capecitabine-related GI injury shows a GVHD-like pattern. Knowledge of this is important to confirm the diagnosis as patients typically improve with dose reduction or discontinuation of the drug.

Prevalence and Risk Factors of Anemia in Inflammatory Bowel Diseases: A Case-Control Study.

Introduction Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis may induce anemia, ranging from 25% to 75% depending on the study population and diagnostic criteria. It might negatively impact their health and quality of life. Objectives The aim of this work is to study the effectiveness and safety of treatments for anemia in patients with IBD. Methodology This case-control study compared patients with IBD who have anemia (cases; n=60) with patients who have IBD but do not have anemia (controls; n=60) from June 2019 to August 2021 in Hayatabad Medical Complex, Peshawar, Pakistan. Data were collected through interviews, from patients` medical records, and from lab test reports. Statistical analysis was performed using SPSS, Version 23.0 (IBM Corp., Armonk, NY). Results Cases had a greater mean age (45.2 years) than controls (42.8 years). Cases included 60% females and controls 45%. Also, cases earned less (p = 0.019). Anemic patients (group 1) had lower mean hemoglobin (10.2 g/dL) and iron than non-anemic controls (group 2) (p = 0.042 and 0.009, respectively). Anemia increased Crohn's Disease Activity Index and Mayo Score. Group 1 has iron deficiency anemia, whereas group 2 has chronic disease. Group 1 reacts rapidly, but gastrointestinal side effects, allergies, and iron overload are more prevalent. Conclusion IBD patients exhibited low hemoglobin and iron, suggesting anemia. Anemia increased disease activity, but not statistically. IBD patients need iron and anemia treatment. Comparing groups demonstrates differences in anemia types, iron replacement history, treatment response, and bad effects, proposing targeted iron supplementation for deficiency anemia and managing chronic illness factors for chronic disease anemia. IBD anemia treatment involves individualization.

Shouldn’t Stage 4 And 5 Chronic Kidney Disease Patients Use Metformin?

Metformin tip 2 diyabetes mellitus (DM) tanılı hastaların tedavisi için birçok kılavuzda yaşam tarzı değişikliği ile birlikte ilk sırada önerilen anti diyabetik ajandır. İlacın etki mekanizması periferik dokuda insülin duyarlılığını arttırması ve karaciğerden glukoz salınımını azaltmasıdır. Metformin düşük maliyetli, etkin ve güvenilir bir ilaçtır. Sık yan etkisi gastrointestinal yan etkiler olması yanında en korkulan yan etkisi laktik asidozdur. Bu yan etkisi nedeniyle kronik böbrek hastalığı (KBH) tanılı hastalarda birçok klavuzda kullanımı sınırlandırılmıştır. Biz bu yazıda KBH’nin her evresinde metformin kullanımını inceledik. Metfomin ilişkili laktik asidoz (MALA) gelişim sıklığını araştırdık. Evre 4 ve evre 5 KBH hastaları metformin kullanmamalı mı? Sorusuna cevap aradık. Sonuç olarak MALA gibi yan etkilerin son derece nadir olduğuna karar verdik. Bu yan etkilerin daha çok enfeksiyon, ciddi kardiyovasküler olay, hipotansiyon gibi doku perfüzyonunun bozulduğu hastalıklar varlığında ortaya çıktığını gözlemledik. Dolayısıyla metformin kullanımının MALA gibi yan etkilerden ziyade hastanın klinik durumunun stabil olmadığı durumlarda ve ilacın artmış birikim riski nedeniyle özellikle evre 5 hastalarda kontrendike olabileceği kanaatine vardık.vre 4 ve evre 5 KBY’li hastalarda çok da korkmadan kar zarar ilişkisi göz önünde bulundurularak kullanılması gerekliliği kanaatine vardık.

Development of chitosan-hyaluronic acid based hydrogel for local delivery of doxycycline hyclate in an ex vivo skin infection model

Doxycycline hyclate (DOXY) is a tetracycline derivative known as the broad-spectrum bacteriostatic drug. DOXY has been suggested as the first-line antibiotic for diabetic foot ulcers (DFU). Unfortunately, the long-term availability of DOXY in both oral and conventional topical dosage forms reduces its therapeutic effectiveness, which is closely linked to gastrointestinal side effects and acute pain during therapy, as well as uncontrolled DOXY release at the wound site. To address these shortcomings, we present for the first time a DOXY hydrogel system (DHs) built on crosslinks between carboxymethyl chitosan (CMC) and aldehyde hyaluronic acid (AHA). Three formulations of DHs were developed with different ratios of CMC and AHA, consisting of F1 (3:7, w/w), F2 (5:5, w/w), and F3 (7:3, w/w). Viscosity, rheology, gel strength, pH, swelling, gel fraction, wettability, stability, in vitro drug release, ex vivo antibacterial, and dermatokinetic studies were used to evaluate the DHs. According to the in vitro release study, up to 85% of DOXY was released from DHs via the Fickian diffusion mechanism in the Korsmeyer–Peppas model (n < 0.45), which provides controlled drug delivery. Because of its excellent physicochemical characteristics, F2 was chosen as the best DHs formulation in this study. Essentially, the optimum DHs formulation could greatly improve DOXY’s ex vivo dermatokinetic profile while also providing excellent antibacterial activity. As a consequence, this study had promising outcome as a proof of concept for increasing the efficacy of DOXY in clinical therapy. Further extensive in vivo studies are required to evaluate the efficacy of this approach.

The frequency and duration of side-effects associated with the use of oral metronidazole; A prospective study of VITA trial participants.

The tolerability of metronidazole is often perceived as being poor and in particular as being a cause of gastrointestinal side effects, but the frequency, severity and duration of adverse effects (AE) is not well characterised. This study assessed the frequency and type of metronidazole associated AEs in women treated for bacterial vaginosis. An exploratory study of participants from the lactic acid gel versus metronidazole for treating bacterial vaginosis (VITA) randomised controlled trial. In this sub-study, women aged ≥16years, diagnosed with bacterial vaginosis and who received oral MTZ (400mg twice daily, for 7days) were followed up prospectively over 2weeks. Baseline demographic and clinical data, and self-reported data on the incidence, time to onset, and duration of AEs were analysed. 155 women were included, of whom 64% (99/155) reported at least one metronidazole AE, including 47% (72/155) who reported gastrointestinal symptoms (nausea and/or vomiting [52/155], abdominal pain [31/154] or diarrhoea [31/154]) mostly within 3days of starting treatment and resolving within 5days of onset. Treatment discontinuation occurred in 8% (12/148) overall and AEs were given as the reason for discontinuing in only 3% (4/148). Overall, metronidazole side effects occurred commonly, but resolved within a few days and had a limited impact on treatment completion.