Mass Spectrometry Applications to Study Human Microbiome.

Microbiotas are an adaptable component of ecosystems, including human ecology. Microorganisms influence the chemistry of their specialized niche, such as the human gut, as well as the chemistry of distant surroundings, such as other areas of the body. Metabolomics based on mass spectrometry (MS) is one of the primary methods for detecting and identifying small compounds generated by the human microbiota, as well as understanding the functional significance of these microbial metabolites. This book chapter gives basic knowledge on the kinds of untargeted mass spectrometry as well as the data types that may be generated in the context of microbiome study. While data analysis remains a barrier, the emphasis is on data analysis methodologies and integrative analysis, particularly the integration of microbiome sequencing data. Mass spectrometry (MS)-based techniques have resurrected culture methods for studying the human gut microbiota, filling in the gaps left by high-throughput sequencing methods in terms of culturing minor populations.

Applications of Proteomics in Probiotics Having Anticancer and Chemopreventive Properties.

Proteomics has grown in importance in molecular sciences because it gives vital information on protein identification, expression levels, and alteration. Cancer is one of the world's major causes of death and is the major focus of much research. Cancer risk is determined by hereditary variables as well as the body's immunological condition. Probiotics have increasing medical importance due to their therapeutic influence on the human body in the prevention and treatment of numerous chronic illnesses, including cancer, with no adverse effects. Several anticancer, anti-inflammatory, and chemopreventive probiotics are studied using different proteomic approaches like two-dimensional gel electrophoresis, liquid chromatography-mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. To gain relevant information about probiotic characteristics, data from the proteomic analysis are evaluated and processed using bioinformatics pipelines. Proteomic studies showed the significance of different proteomic approaches in characterization, comparing strains, and determination of oxidative stress of different probiotics. Moreover, proteomic approaches identified different proteins that are involved in glucose metabolism and the formation of cell walls or cell membranes, and the differences in the expression of critical enzymes in the HIF-1 signaling pathway, starch, and sucrose metabolism, and other critical metabolic pathways.

Physicians' adherence to evidence-based guidelines as a major predictor of anticoagulant-related medication error incidence and severity.

AIMS: Anticoagulants represent a main source of medication errors (MEs) and complications that have catastrophic implications, posing an obligation on health care providers to assess anticoagulant-related MEs and factors affecting their occurrence. This study investigates the occurrence and severity of prescribing MEs in patients on anticoagulants and explores their potential predictors. METHODS: This study was a prospective cohort study in a tertiary hospital on 116 patients with a total of 2166 anticoagulant doses. RESULTS: Forty-four percent of prescribed anticoagulant doses resulted in MEs with low molecular weight heparin (LMWH) and unfractionated heparin (UFH) causing 61% and 34%, respectively, of the total MEs. More than 50% of all MEs were incorrect doses (high and low) shared between heparin and tinzaparin. The highest severity of error was Category D followed by Category F and Category C. A Poisson regression analysis model revealed that female (incidence rate ratio [IRR] 1.32, 95% confidence interval [CI] 1.13-1.54, P < .001), bridging (IRR 1.52; 95% CI 1.10-2.09; P = .011), venous thromboembolism (VTE) prophylaxis (IRR 7.65; 95% CI 4.88-12.02; P < .001), physician non-adherence (IRR 2.71; 95% CI 2.22-3.29; P < .001), and polypharmacy (IRR 1.68; 95% CI 1.26-2.23; P = .036) were predictors of the higher incidence of MEs. Ordinal logistic regression analysis demonstrated that physician non-adherence (OR 24.67; 95% CI 5.54-207; P < .001) was the main predictor of increased error severity. CONCLUSION: The major predictor in increasing both the incidence and severity of MEs is physician adherence to evidence-based guidelines (EBG). Strict regulations for anticoagulant prescribing through an anticoagulant stewardship program are a necessity.

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers.

PURPOSE: The purpose of this study is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of saxagliptin. METHODS: Eighteen healthy volunteers were recruited in sequential; single-center study to determine pharmacokinetic parameters of saxagliptin and sildenafil, and (AUC0-∞), (AUC0-t); Cmax; tmax; t½, ke; ka were measured using validated LC-MS/MS method. Therapeutic doses were given as follows: Sildenafil 50 mg single dose on day one, then washout period from day two till day eight. Saxagliptin 5 mg once/day was given from day 9 till day 12; then on day 13, the two drugs were co-administered. Blood samples for pharmacokinetic analysis were collected on days 1 and 13 for sildenafil and on days 12 and 13 for saxagliptin. RESULTS: Saxagliptin ratios of T/R and 90% CI were 132.1% (122.7-142.3) for AUC0-t, and 167.6% (154.6-181.8) for Cmax. On the other hand, sildenafil pharmacokinetics were not affected. Gmax changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUCg0-t from 512.8 ng.h/ml to 532.75 ng.h/ml (P > 0.001) after co-administration of both drugs. CONCLUSION: Sildenafil significantly affected the pharmacokinetic parameters of saxagliptin when co-administered. REGISTRATION: This trial was registered at clinicaltrials.gov under identifier number: [NCT04170790] in November 2019.

The impact of clinical pharmacist implemented education on the incidence of prescribing errors in COVID-19 patients.

Background: Clinical pharmacists have a vital role during COVID-19 pandemic in mitigating medication errors, particularly prescribing errors in hospitals. That is owing to the fact that prescribing errors during the COVID-19 pandemic has increased. Aim: This study aimed to evaluate the impact of the clinical pharmacist on the rate of prescribing errors on COVID-19 patients in a governmental hospital. Methods: The study was a pre-post study conducted from March 2020 till September 2020. It included the pre-education phase P0; a retrospective phase where all the prescriptions for COVID-19 patients were revised by the clinical pharmacy team and prescription errors were extracted. Followed by a one-month period; the clinical pharmacy team prepared educational materials in the form of posters and flyers covering all prescribing errors detected to be delivered to physicians. Then, the post-education phase P1; all prescriptions were monitored by the clinical pharmacy team to assess the rate and types of prescribing errors and the data extracted was compared to that from pre-education phase. Results: The number of prescribing errors in P0 phase was 1054 while it was only 148 in P1 Phase. The clinical pharmacy team implemented education phase helped to significantly reduce the prescribing errors from 14.7/1000 patient-days in the P0 phase to 2.56/1000 patient-days in the P1 phase (p-value <0.001). Conclusion: The clinical pharmacist significantly reduced the rate of prescribing errors in patients with COVID-19 which emphasizes the great role of clinical pharmacists' interventions in the optimization of prescribing in these stressful conditions.

The efficacy and safety of itopride in feeding intolerance of critically ill patients receiving enteral nutrition: a randomized, double-blind study.

BACKGROUND: Enteral feeding intolerance (EFI) is a frequent problem in the Intensive care unit (ICU) and is associated with poor clinical outcomes leading to worse prognosis in terms of mortality and ICU stay. Nowadays, prokinetic drugs are the mainstay of therapy in EFI. However, available prokinetics have uncertain efficacy and safety profiles. Itopride, is a prokinetic agent which is different and unique from the available prokinetics because of its dual mode of action as well as its tolerability and safety. The current study compared the efficacy and safety of Itopride against metoclopramide for EFI in critically ill patients. Moreover, it tested the utility and applicability of ultrasonography to measure gastric residual volume (GRV) in this population. METHODS: This randomized, double-blind study included 76 EFI patients who were randomly assigned to either Itopride or metoclopramide group. The primary outcome was to measure GRV by ultrasonography. Secondary outcomes included the percentage ratio of enteral feed volume, energy and protein received by patients over 7 days of treatment, ICU length of stay, safety parameters and occurrence of infectious complications or vomiting. RESULTS: Thirty-five patients of each group completed the study. At day 7, itopride significantly decreased GRV compared with metoclopramide group (p = 0.001). Moreover, there was a significant increase in the ratios of received enteral nutrition feed volume, calories, and protein after the one-week therapy in the itopride group more than the metoclopramide group (p = 0.001), (p = 0.002), (p = 0.01), respectively and there were no differences in any secondary outcomes or adverse events between the two groups. CONCLUSION: In critically ill patients with EFI, itopride was well tolerated with superior efficacy to metoclopramide. In addition, we demonstrated that ultrasonography is a simple, non-invasive, inexpensive, and undemanding method for GRV measurements and can offer reliable assessments in the gastric emptying modality. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT03698292). Date: October 5, 2018.

The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study.

BACKGROUND AND AIM: Vascular calcification is an independent risk factor for cardiovascular diseases and all-cause mortality in end stage renal disease, and particularly in hemodialysis patients. Vitamin D deficiency has been shown to be associated with vascular calcification among this category of patients. Cholecalciferol or vitamin D3; the native inactivated 25-hydroxy vitamin D [25(OH)D], has been proposed to have a good impact on vascular calcification and vitamin D deficiency. However, clinical data is still limited. METHODS AND RESULTS: A prospective, randomized, placebo-controlled study was carried out to evaluate the effect of oral cholecalciferol on vascular calcification and 25(OH)D levels in hemodialysis patients. A total of sixty eligible hemodialysis patients were randomly assigned to either a treatment group (Oral 200.000IU Cholecalciferol per month) or a placebo group, for 3 months. Serum 25-hydroxy vitamin D (25(OH)D), fetuin-A, fibroblast growth factor (FGF-23), osteoprotegerin (OPG), calcium, phosphorus, their product (CaXP) and intact parathyroid hormone (iPTH) levels, were all assessed at baseline and at the end of the study. ClinicalTrials.gov registration number: NCT03602430. Cholecalciferol significantly increased serum levels of 25(OH)D and fetuin-A in the treatment group (p-value < 0.001), while no significant difference was observed in the placebo group. Cholecalciferol administration showed no effect on either FGF-23 or OPG. None of the treatment group patients experienced any adverse effects. CONCLUSION: Cholecalciferol was shown to be an effective, tolerable, inexpensive pharmacotherapeutic option to overcome vitamin D deficiency, with a possible modulating effect on fetuin-A, among hemodialysis patients. CLINICALTRIALS. GOV REGISTRATION NUMBER: NCT03602430.

Pharmacovigilance education to healthcare professionals: Will it affect their performance in reporting adverse drug reactions?

AIM: To assess impact of pharmacovigilance (PV) educational program on knowledge, attitude and practice (KAP) of healthcare professionals (HCPs). METHODS: a prospective study was conducted on HCPs at an Egyptian hospital. The study included: pre-education phase; where KAP questionnaire was administered by HCPs to obtain baseline data, intervention phase; where educational sessions were held by clinical pharmacists and Egyptian PV centre, and post-education phase; where the questionnaire was re-administered by participants 9 months post-receiving educational sessions. The questionnaire comprised five sections: participants' demographics, knowledge, attitude and practice sections and two multiple choice questions asking about the importance of establishment of ADRs monitoring centre, and factors hindering ADRs reporting. Pre-education and post-education data were compared. RESULTS: From 221 HCPs invited to participate, only 153 filled the pre-education and post-education questionnaires. At baseline, the median (range) of the total KAP score were 1 (0-7), 1 (0-4) and 4 (0-14) for physicians, nurses and pharmacists, respectively. All KAP scores were low for all HCPs at baseline with the pharmacists having significantly higher knowledge and attitude scores compared with physicians, and nurses (P < .001). After education, all scores significantly increased and 13 ADRs were reported by HCPs compared with only 2 at baseline. CONCLUSION: It was concluded that educational program had a significant impact on enhancing KAP of HCPs towards PV and ADRs reporting.

Impact of Docosahexaenoic acid supplementation on proinflammatory cytokines release and the development of Necrotizing enterocolitis in preterm Neonates: A randomized controlled study.

INTRODUCTION: Preterm neonates have under-developed immune-regulatory system; consequently, there is a risk for developing chronic inflammation. Necrotizing enterocolitis (NEC) is an acute devastating neonatal intestinal inflammatory disorder. Due to the obscure multifactorial etiology, early diagnosis and effective treatment of NEC are limited. Consequently, effective strategies in the prevention of NEC, including nutritional approaches, are critically needed. The current study was conducted to assess the potential immunomodulatory effect of Docosahexaenoic Acid (DHA) supplementation in preterm neonates at neonatal intensive care unit (NICU) and subsequently its effect on preventing or reducing NEC incidence. METHODS: This was a prospective randomized controlled study. A total of 67 neonates, with gestational age equal or less than 32 weeks at birth and weight less than or equal 1500 g, were randomly assigned to either DHA group or the control group. Modified Bell's staging criteria for NEC was used as an objective tool for diagnosis and staging of NEC. Levels of Interleukin 1 beta (IL-1ß) were measured at baseline and after 10 days. Mortality and NICU length of stay (LOS) were also monitored. RESULTS: Thirty neonates of each group completed the study. A statistically significant difference was observed between the two groups regarding diagnosis and staging of NEC (p = 0.0001). There was also a statistically significant difference between DHA group 22(73.3), 95% CI [55.9, 86.5] and the control group 8 (26.7), 95% CI [13.5, 44.1] in the percentage change in IL-1ß levels (p = 0.0001).A statistically significant association was found between IL and 1 ß change and NEC diagnosis (p = 0.001). NICU LOS was significantly lower among DHA group 21.63 ± 6.67 compared to the control group 25.07 ± 4.67 (p = 0.025). Mortality n (%) among the control group 4 (11.8) was higher than DHA group 3 (9.1), however, no significant difference was detected (p = 1.0). CONCLUSION: Findings of this study suggest that enteral DHA supplementation can reduce NEC incidence in preterm neonates through its immunoregulatory effect that modulates production of regulatory cytokines.Trial registration: Registered at clinical trials.gov (NCT03700957), 6 October 2018.

Evaluation of pharmacist-led educational interventions to reduce medication errors in emergency hospitals: a new insight into patient care.

BACKGROUND: Medication errors made by nurses are common in general practice and can lead to harm in patients. The aim of this study was to evaluate the impact of pharmacist-led educational implementations in reducing medication errors made by nurses in an emergency hospital in Cairo, Egypt. METHODS: A prospective pre-post-interventional study was conducted in an emergency hospital using direct observation for the detection of errors. The rate and severity of medication errors were determined before and after the implementation of educational tools. RESULTS: In total, 1025 and 1024 patients were examined pre- and post-intervention, respectively. Pharmacist interventions resulted in a significant reduction in the medication error rate from 351 (34.2%) in the pre-intervention phase to 157 (15.3%) in the post-intervention phase (P < 0.001). In both the pre- and post-intervention phases, none of the medication errors were associated with harm/death. Furthermore, all types of medication errors declined as a result of the interventions. CONCLUSION: Clinical pharmacists' interventions focusing on improving nurses' drug knowledge and awareness of errors were shown to be effective in reducing the rate and severity of medication administration errors among nurses in an emergency hospital environment.

Randomized controlled open-label study of the effect of vitamin E supplementation on fertility in clomiphene citrate-resistant polycystic ovary syndrome.

AIM: To evaluate the effect of vitamin E on ovulation and pregnancy in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: A prospective, randomized, controlled, open label study was conducted on women with CC-resistant PCOS. Patients were randomized, to either control group (n = 30), who received metformin 500 mg thrice daily, in addition to 150 mg/day CC for 5 days starting from day 3 of menstruation for three menstruation cycles, or vitamin E group (n = 30) who received vitamin E 1500 IU/day for the whole study period in addition to metformin and CC with the same previous regimen. The primary outcome was cumulative ovulation rate, while secondary outcomes were pregnancy rate, serum midluteal progesterone, mean follicular diameter, number of dominant follicles and endometrial thickness. RESULTS: Ovulation was reported in 57 (64.8%) of 88 cycles in the control group and 63 (73.3%) of 86 cycles in the vitamin E group (P = 0.227), while pregnancy was reported in 4 (4.5%) of 88 cycles in the control group and 6 (7%) of 86 cycles in the vitamin E group (P = 0.491).There were nonsignificant differences between groups regarding serum midluteal progesterone, number of dominant follicles and mean follicular diameter. Endometrial thickness was significantly higher in the vitamin E group compared to the control group. CONCLUSION: The findings of this trial do not support the hypothesis that vitamin E may increase the ovulation and pregnancy rates in women with clomiphene citrate-resistant PCOS.

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment.

Uterine fibroids (UFs) are the most common benign neoplastic threat to women's health and associated with DNA damage and genomic instability. Hypovitaminosis D is a known risk factor for UFs, especially among African Americans. Vitamin D3 has been shown to effectively inhibit UF phenotype, but its mechanisms remain unclear. We hypothesize that Vitamin D3 ameliorates UFs by recovering the damaged DNA repair system, thus inhibits tumor progression. We compared the DNA damage status and Vitamin D receptor (VDR) expression between normal myometrial and UF primary cells. Unrepaired DNA double-strand breaks (DSBs) accumulated but VDR expression decreased in UFs. The RNA and protein levels of key DNA repair members belonging to DNA DSB sensors (MRE11, NBS1, RAD50), mediators and effectors (CHECK2, BRCA1, RAD51) were downregulated in UFs compared with myometrial cells. VDR KD induced DSB accumulation and DNA damage response (DDR) defects in myometrial cells. Using the DNA damage PCR array, the expression of many additional DNA repair genes was downregulated in VDR KD cells. Treatment of UF cells with Vitamin D3 (100 nM) significantly decreased DNA damage and restored DDR concomitant with VDR induction. Notably, the PCR array demonstrated that among 75 downregulated genes after VDR KD, 67 (89.3%) were upregulated after vitamin D3 treatment. These studies demonstrate a novel link between DNA damage and the vitamin D3/VDR axis in UFs. Vitamin D3 suppresses the UF phenotype through orchestrated targeting at multiple molecules in DNA repair pathways, thus offering novel mechanistic insights into the clinical effectiveness of vitamin D3 on UFs.

Effect of Febuxostat on the Endothelial Dysfunction in Hemodialysis Patients: A Randomized, Placebo-Controlled, Double-Blinded Study.

BACKGROUND: Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. METHODS: A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study. RESULTS: Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups. CONCLUSION: Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns.

Effect of Omega-3 Fatty Acids on Serum Lipid Profile and Oxidative Stress in Pediatric Patients on Regular Hemodialysis: A Randomized Placebo-Controlled Study.

OBJECTIVE: We sought to evaluate the effects of omega-3 fatty acids supplementation on serum lipid profile and oxidative stress markers in pediatric patients with end-stage renal disease on regular hemodialysis (HD). DESIGN: This study was a double-blinded, randomized, placebo-controlled trial conducted on 49 pediatric patients on regular HD for at least 6 months. INTERVENTION: Patients were randomly divided into either omega-3 group (n = 25) who received 1-g oral omega-3 capsule once daily for 16 weeks or placebo group (n = 24) who received 1-g matching oral placebo capsule once daily for 16 weeks. MAIN OUTCOME MEASURE: Lipid profile markers including: total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and oxidative stress markers including the following: malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured at baseline and after 16 weeks of supplementation. RESULTS: By the end of the study, children in omega-3 group showed a highly significant reduction in total cholesterol and a highly significant increase in glutathione peroxidase and superoxide dismutase levels. CONCLUSION: The administration of omega-3 has a beneficial effect on serum lipid profile and oxidative stress in children undergoing HD.

Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis.

BACKGROUND: Hyperphosphatemia is a common problem in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (HD) and contributes to the development of secondary hyperparathyroidism and cardiovascular complications. Nicotinamide (NAM) has been shown in some studies to inhibit intestinal and renal sodium/phosphorus co-transporters and reduce serum phosphorus levels. We have therefore evaluated the efficacy and safety of NAM as adjunctive therapy to calcium-based phosphate binders to control hyperphosphatemia in hemodialysis patients. METHODS: Sixty pediatric HD outpatients were randomly divided into two equally sized groups (30 children each). One group received calcium-based phosphate binder (control group), and the other received both the calcium-based phosphate binder + NAM at a dose of 100 mg twice or three times daily (nicotinamide group). Both groups were followed for a 6-month period. RESULTS: Over the 6-month treatment period, children in the NAM group showed a significant decline in the levels of serum phosphorus (p = 0.0001), serum calcium-phosphorus (Ca × P; p = 0.0001) product and parathyroid hormone (p = 0.02) versus baseline values and those of the control group. After 6 months of NAM treatment, the mean serum high-density lipoprotein cholesterol levels had increased significantly (p = 0.01), and the median serum triglyceride levels had decreased (p = 0.009). There was no significant change in any of these parameters among the children of the control group. The major adverse events associated with the NAM therapy were diarrhea, flushing and nausea. CONCLUSION: The addition of NAM to therapy with phosphate binders is effective in lowering phosphorus levels and has a beneficial effect on the lipid profile with only mild side effects.

Melatonin: A potential protective multifaceted force for sepsis-induced cardiomyopathy.

Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are among the affected organs. Sepsis-induced cardiomyopathy is a common cause of death among septic patients. Sepsis-induced cardiomyopathy is characterized by an acute and reversible significant decline in biventricular both systolic and diastolic function. This is accompanied by left ventricular dilatation. The pathogenesis underlying sepsis-induced cardiomyopathy is multifactorial. Hence, targeting an individual pathway may not be effective in halting the extensive dysregulated immune response. Despite major advances in sepsis management strategies, no effective pharmacological strategies have been shown to treat or even reverse sepsis-induced cardiomyopathy. Melatonin, namely, N-acetyl-5-methoxytryptamine, is synthesized in the pineal gland of mammals and can also be produced in many cells and tissues. Melatonin has cardioprotective, neuroprotective, and anti-tumor activity. Several literature reviews have explored the role of melatonin in preventing sepsis-induced organ failure. Melatonin was found to act on different pathways that are involved in the pathogenesis of sepsis-induced cardiomyopathy. Through its antimicrobial, anti-inflammatory, and antioxidant activity, it offers a potential role in sepsis-induced cardiomyopathy. Its antioxidant activity is through free radical scavenging against reactive oxygen and nitrogen species and modulating the expression and activity of antioxidant enzymes. Melatonin anti-inflammatory activities control the overactive immune system and mitigate cytokine storm. Also, it mitigates mitochondrial dysfunction, a major mechanism involved in sepsis-induced cardiomyopathy, and thus controls apoptosis. Therefore, this review discusses melatonin as a promising drug for the management of sepsis-induced cardiomyopathy.

Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients.

Aim: ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). Methods: 43 patients were randomized to pentoxifylline (PTX) 400 mg thrice daily (n = 22) or placebo (n = 21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) were assessed at baseline and 2 months. Results: After 2 months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p = 0.032. Conclusion: PTX for 2 months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. Clinical Trial Registration: NCT04367935 (ClinicalTrials.gov).

This study examined the effect and the safety of a drug called pentoxifylline in patients who have recently had a heart attack. Pentoxifylline can possibly reduce inflammation and is used for patients with blood flow issues. The study involved 43 participants, 22 receiving pentoxifylline and 21 receiving a placebo for 2 months. We measured different markers related to inflammation and heart health before and after. Overall, there was no significant difference between the groups, but patients who received pentoxifylline experienced less inflammation according to only one of the markers measured. This study concluded that the prescription of pentoxifylline after a heart attack is safe, well-tolerated and without notable side effects. Still, we recommend larger and longer studies to be sure of its effect.

Different modalities to manage rheumatoid arthritis: an A to Z story.

Aim: To investigate different approaches to RA treatment that might lead to greater efficacy and better safety profiles. Methods: The Search strategy was based on medical subject headings, and screening and selection were based on inclusion/exclusion criteria. Results & discussion: Early therapy is critical for disease control and loss of bodily function. The most promising outcomes came from the development of disease-modifying anti-rheumatic drugs. Different foods have anti-inflammatory and antioxidant qualities that protect against the development of rheumatoid arthritis (RA). Some dietary patterns and supplements have been shown to have potential protective benefits against RA. Conclusion: Improvement in the quality of life of RA patients requires a tailored management approach based on the current patient medical data.

Rheumatoid arthritis is a complex disease with an unclear origin that affects the joints. In this systematic review, we aimed to investigate different effective ways of treating rheumatoid arthritis. Study results indicate that rheumatoid arthritis treatment requires coordination between different healthcare teams. As much as we can, when we start disease treatment early, this will lead to a better disease cure. Different drugs showed promising results in the treatment of rheumatoid arthritis, but the most promising treatment results came from a group of medicinal agents called 'disease-modifying anti-rheumatic drugs'. Different foods have anti-inflammatory and antioxidant effect and help in protection against rheumatoid arthritis, but others, such as red meat and salt, have the opposite effect. Some dietary patterns and supplements, such as the Mediterranean Diet, vitamin D and probiotics, have been shown to have potential protective benefits against rheumatoid arthritis. Improvement in the quality of patient life requires an individualized management roadmap based on current patient medical data.