Stem cells-derived exosomes as cardiac regenerative agents.

Heart failure is a root cause of morbidity and mortality worldwide. Due to the limited regenerative capacity of the heart following myocardial injury, stem cell-based therapies have been considered a hopeful approach for improving cardiac regeneration. In recent years, different kinds of cell products have been investigated regarding their potential to treat patients with heart failure. Despite special attention to cell therapy and its products, therapeutic efficacy has been disappointing, and clinical application is not affordable. In the past few years, a subset of small extracellular vehicles (EVs), commonly known as "exosomes," was reported to grant regenerative and cardioprotective signals at a value similar to their donor cells. The conceptual advantage is that they may be ideally used without evoking a relevant recipient immune response or other adverse effects associated with viable cells. The evidence related to their beneficial effects in animal models of heart failure is rapidly growing. However, there is remarkable heterogeneity regarding source cells, isolation process, effective dosage, and delivery mode. This brief review will focus on the latest research and debates on regenerative potential and cardiac repair of exosomes from different sources, such as cardiac/non-cardiac stem, somatic cells, and progenitor cells. Overall, the current state of research on exosomes as an experimental therapy for heart diseases will be discussed.

Comparison of global decolonization efficacy with mupirocin nasal drop and chlorhexidine mouthwash in acute leukemia patients: randomized clinical trial.

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).

Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.

Purpose: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. Conclusion: In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

Delayed presentation of vincristine extravasation.

INTRODUCTION: Vincristine is a vesicant chemotherapeutic agent which may leak from the vessel at the infusion site to the perivascular tissue and cause extravasation. Extravasation, a severe complication of chemotherapeutic drugs, can result in tissue necrosis that is considered an oncological emergency. CASE REPORT: We aimed to report a case of a 29-year-old woman with ALL-B cell (Acute lymphoblastic leukemia) on maintenance chemotherapy regimen including vincristine, methotrexate, prednisolone, and 6-mercaptopurine (POMP). 48 h after administering intravenous vincristine, the patient experienced burning, pain and tenderness at the injection site (left hand - cubital cavity). MANAGEMENT & OUTCOME: 7 days after the onset of symptoms, the patient was hospitalized with a large brown lesion at the site. She was prescribed betamethasone cream, DSMO (Dimethyl sulfoxide) solution, and oral levofloxacin on his second day after admission. The lesion was completely improved 10 days after initiation of therapy and there were no serious problems. DISCUSSION: Due to the ineffectiveness of antidote therapy for the management of delayed extravasation of vincristine and beneficial effect of our clinical approach, it could consider for the management of similar cases with delayed extravasation following vincristine administration.

Management of diabetic neuropathy with memantine: A randomized clinical trial.

BACKGROUND: Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has demonstrated potential benefits for neuropathic pains in preclinical studies. This study aimed to assess the efficacy of memantine in the management of peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM). METHOD: This randomized clinical trial includes 143 diabetic patients (aged between 18 and 75 years) with a confirmed diagnosis of diabetic neuropathy. Patients were randomly assigned to receive memantine 5 mg twice daily for 1 week, followed by 10 mg twice daily plus gabapentin 300 mg daily (n = 72) or just gabapentin 300 mg daily (n = 71) for 8 weeks. The DN4 questionnaire, monofilament, tuning fork, and Tip-therm tests were used to measure neuropathy at baseline and after the 8-week intervention. RESULTS: The mean score of the DN4 questionnaire in the memantine group was significantly lower than the control group (p. value: .001). The number of patients with diabetic neuropathy remarkably decreased in the memantine group at the end of the study based on the performed tests (p. value: .001). CONCLUSION: Memantine functions as a beneficial agent in the management of diabetic neuropathy, which would significantly improve the quality of life in diabetic patients.

Okra ameliorates hyperglycaemia in pre-diabetic and type 2 diabetic patients: A systematic review and meta-analysis of the clinical evidence.

Background: Despite the use of available pharmaceutical drugs, high rates of metabolic diseases and cardiovascular disorders are alarming. This calls for alternative therapies that can attenuate these complications. Therefore, we investigated the beneficial effects of okra on glycaemic control in pre-diabetes and type 2 diabetes mellitus (T2D). Methods: MEDLINE and Scopus were searched for relevant studies. Collected data were analysed using RevMan and reported as mean difference and 95% confidence intervals (CI). Eight studies, including 331 patients with pre-diabetes or T2D, were eligible. Results: Our findings showed that okra treatment reduced the levels of fasting blood glucose: mean difference (MD) = -14.63 mg/dL; 95% CI (-25.25, -4.00, p = 0.007); I 2 = 33%, p = 0.17 compared to placebo. Glycated haemoglobin, however, did not differ significantly between the groups: MD = 0.01%; 95%CI (-0.51, 0.54, p = 0.96); I 2 = 23%, p = 0.28. Conclusion: this systematic review and meta-analysis found that okra treatment improves glycaemic control in patients with pre-diabetes or T2D. The findings suggest that okra may be used as a supplemental dietary nutrient, especially in pre-diabetic and T2D patients due to its potential to regulate hyperglycaemia.

Anti-hyperglycemic effect of Abelmoschus culentesus (Okra) on patients with diabetes type 2: a randomized clinical trial.

Okra (Abelmoschus esculentus) has traditionally been used in diabetes treatment. This study investigated the effect of Okra whole fruit on blood glucose level of patients with diabetes mellitus type 2 with concomitant use of oral hypoglycemic agents. In this double-blind randomized clinical trial, 120 diabetic patients were assigned to okra group (n = 60) and control group (n = 60). The okra group received 1,000 mg of A.esculentus whole fruit capsules orally, every 6 hr for 8 weeks. The control group received placebo capsule in the same manner. The levels of FBS (fasting blood sugar), BS (blood sugar), and Hemoglobin A1C (HgA1c) were measured at baseline and after intervention in both groups. The levels of FBS, BS, and HgA1c were significantly decreased in okra group within the intervention compared to control group (p < .05). Moreover, the numbers to treat (NNT) for FBS, BS, and HgA1C were seven, eight, and seven, respectively. Okra whole fruit supplementation has a promising anti-hyperglycemic effect in patients with diabetes mellitus type 2 who received oral agents. Diabetic patients could benefit from adjuvant therapy of okra with other medication.

Evaluation of Drug Interactions in Hospitalized Patients with Malignancy.

Drug-drug interaction (DDI) occurs when the pharmacological effect of a drug is altered due to concomitant administration with other drugs. DDIs still remain a serious issue; thus, we conducted this retrospective study to evaluate DDIs prevalence in our care center. Methods: All admitted patients with any kind of malignancies that received at least two medications from oncology and non-oncology classifications during six months were enrolled in this study. All relevant data including, patients' demographic information, diagnosis, hospitalization duration, and all administered medication during hospitalization were recorded. The DDI was assessed by using the latest version of Lexi-interact. Results: Each patient received a mean number of 11.6±4.7 medications. The number of non-oncology drugs demonstrated a remarkable correlation with the number of interactions (P<0.001). Whereas, the number of oncology drugs does not have any relation with the number of interactions (P=0.64). Among the 763 detected DDIs during this study, the incidence of major, moderate and minor interactions were 31.2%, 61.4%, and 7.3%, respectively. Conclusion: Our results highlighted the clinical significance of DDIs, considering that 104 (92%) patients had at least one DDI. The main reason that could have potentially contributed to this outcome is the complicated nature of cancer treatment and clinical management. We believe that using computer software to collect all prescribed and OTC collaboration of clinical pharmacists with oncologists can reduce the potential interactions prior to drug administration.

Evaluation of Factors Related to the Survival of Hospitalized Patients With COVID-19: Survival Analysis With Frailty Approach.

OBJECTIVE: Considering that coronavirus disease 2019 (COVID-19) is an emerging disease and results in very different outcomes, from complete recovery to death, it is important to determine the factors affecting the survival of patients. Given the lack of knowledge about effective factors and the existence of differences in the outcome of individuals with similar values of the observed covariates, this study aimed to investigate the factors affecting the survival of patients with COVID-19 by the parametric survival model with the frailty approach. METHODS: The data of 139 patients with COVID-19 hospitalized in Imam Reza Hospital in Tabriz were analyzed by the Gompertz survival model with gamma frailty effect. At first, variables with P < 0.1 in univariable analysis were included in the multivariable analysis, and then the stepwise method was used for variable selection. RESULTS: Diabetes mellitus was significantly related to the survival of hospitalized patients (P = 0.021). The rest of the investigated variables were not significant. The frailty effect was significant (P = 0.019). CONCLUSIONS: In the investigated sample of patients with COVID-19, diabetes was an important variable related to patient survival. Also, the significant frailty effect indicates the existence of unobserved heterogeneity that causes individuals with a similar value of the observed covariates to have different survival distributions.

Synthesis and characterization of new surface modified magnetic nanoparticles and application for the extraction of letrozole from human plasma and analysis with HPLC-fluorescence.

Acetic acid-functionalized magnetic nanoparticles modified by (3-amino-propyl)-tri-ethoxy silane was synthesized and used as a new solid-phases adsorbent. Infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), x-ray diffraction (XRD), energy-dispersive x-ray spectroscopy (EDX), vibrating sample magnetometer (VSM) and Electrophoretic Light Scattering (ELS) were used to characterize the modified nanoparticles. The molecular interaction between letrozole and nanoparticles (NPs) was studied using density functional theory (DFT) calculations. The developed nanoparticles were applied for dispersive solid-phase extraction of letrozole (an anticancer drug) from human plasma. Extracted letrozole was quantified using an isocratic HPLC/FL method. The extraction efficiency was optimized using one experiment at a time optimization method based on the adsorbent quantity, sample pH, adsorption time, desorption time, and elution solvent type/volume. The analysis method was fully validated according to the FDA guideline for bioanalytical method validation. The linear quantification range was 0.01-1 µg/mL and the lower limit of quantification (LLOQ) was 0.01 µg/mL. Plasma samples of 6 patients were analyzed and the measured letrozole concentrations range was 0.04-0.31 µg/mL. The newly synthesized magnetic nanoparticles were used successfully for the extraction of letrozole from spiked and clinical plasma samples. The developed method is a precise and simple method that is suitable for pharmacokinetic studies and clinical applications.

Dispersive micro solid phase extraction of busulfan from plasma samples using novel mesoporous sorbent prior to determination by HPLC-MS/MS.

Determination of busulfan concentration in patients undergoing bone marrow transplantation is necessary in order to reduce toxic effects and/or graft rejection due to unadjusted dose exposure. A new extraction method namely dispersive micro solid phase extraction (DMSPE) based on mesoporous sorbent was used for cleaning-up the plasma samples. DMSPE coupling with liquid chromatography with tandem mass spectrometry (LC-MS/MS) was implemented for the determination of busulfan dosage in plasma samples. The linear range was found from 10 to 2000 ng/ml. The precision and accuracy were found better than 15% according to Food and drug Administration (FDA) guideline. This method was successfully used to determine the busulfan in patients administrated busulfan as part of the preparative regimen for bone marrow transplantation.

Developing an Analytical Method Based on Graphene Quantum Dots for Quantification of Deferiprone in Plasma.

In the world of nanotechnology, graphene quantum dots (GQDs) have been considerably employed in numerous optical sensing and bioanalytical applications. Herein, a simple and cost-efficient methodology was developed to the quantification of deferiprone in plasma samples by utilizing the selective interaction of the GQDs and drug in the presence of Fe3+ ions. GQDs were synthesized by a bottom-up technique as an advantageous fluorescent probe. Increasing levels of deferiprone ranging from 5 to 50 mg.L-1, leads to significant fluorescence quenching of GQDs. In addition, the calibration curve was revealed a linear response in this range with a sensitivity of 5 mg.L-1. The method validation was carried out according to the FDA guidelines to confirm the accuracy, precision, stability and selectivity of the developed method. The results show that this green and low-cost fluorescent probe could be used for the analysis of deferiprone.

Effect of vitamin D treatment in children with attention-deficit hyperactivity disorder.

BACKGROUND: In this research the symptom improvement of attention-deficit hyperactivity disorder (ADHD) of children was assessed by oral vitamin D administration in Tabriz, Iran. METHODS: In this double-blind, randomized clinical trials, 96 children (2-18 years) were enrolled to placebo and vitamin D groups. Children took vitamin D pearl (50,000 IU/week) or placebo for 6 weeks. Children, who had the change in methylphenidate dosage and received any anticonvulsants and corticosteroids were excluded from the research. ADHD symptoms were diagnosed by Conners parent rating scale (CPRS) test at baseline and after intervention. ADHD Conners divided into inattention (IA), hyperactivity/impulsivity (H/I) and combination type (C) subscales. Vitamin D serum level was assessed at baseline and after 8 weeks in both groups. RESULTS: The differences between CPRS and its subscales were not significant at baseline (P > 0.05). The Conners IA score was decreased in vitamin D group (P < 0.05; adjusted with age and baseline values). ADHD Conners and all subscale scores reduced remarkably after intervention in patients with insufficient level of vitamin D compared to placebo (P < 0.05). CONCLUSIONS: Oral vitamin D improved ADHD symptoms with a particular effect on inattention symptoms. In addition, symptoms related to all subscales were improved remarkably in patients with insufficient level of vitamin D. Vitamin D treatment in children with ADHD could be considered due to the expand benefit of vitamin D in body.

Effect of memantine on post-operative cognitive dysfunction after cardiac surgeries: a randomized clinical trial.

BACKGROUND: Post-operative cognitive dysfunction (POCD) is an important complication of cardiac surgeries. Glutamate plays a critical role in physiologic and pathologic conditions in the brain. Due to the role of glutamate in ischemia, this study is designed to identify the effect of memantine in prevention of POCD early and late after cardiac surgeries. METHODS: In this randomized clinical trial, 172 patients with ages 45-75 years old who underwent elective cardiac surgery were enrolled. For patients in memantine group, 5 mg of memantine per day administered at least 48 h before surgery and increased to 10 mg per day during the first 24 h after surgery and continued for 3 months. A brief Wechsler memory test (WMT) was administered before, three to 5 days after, and 3 months after surgery for both groups. RESULTS: Both groups demonstrate standard pattern of cognitive dysfunction after surgery and in follow up. Pre- and post-operative WMT score showed significant improvement in memantine compared to control group (P < 0.001) both in unadjusted and adjusted with confounding factor analysis. Unadjusted pre-, post-operative, and follow up WMT score improved significantly after 3 months in memantine group (P = 0.006). CONCLUSION: Pre-operative administration of memantine protects patients from POCD following cardiac surgeries. In addition, it improves cognitive function 3 months after surgery. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (registration number: IRCT201303168698N12 ). Memantin effect on POCD.

A Novel Practical Equation for Treatment of Emergent Hypernatremia and Dehydration Phase in Infants.

Serum sodium (Na) concentration more than 145 mmol/L is defined as hypernatremia. Hypernatremia carries an acute morbidity and mortality, especially in neonates and infants. Rapid correction of hypernatremia leads to severe cerebral damages, and seizure is the most common neurological complication of hypernatremia. Selection and calculation of an appropriate fluid and its amount is one of the tremendous challenges. It is important to choose the correct amount of suitable fluid and adjust rehydration rate. In this study, we have suggested practical equation to determine the amount of fluid that should be administered to the neonates and infants with hypernatremia. In this equation, the amount of infusate volume will be calculated from changes in serum Na and total body water. However, serum Na and infusate Na will play an important role in equation structure, too. Our suggested equation will help physicians to manage hypernatremic dehydrated patients in a suitable manner with an adjustable rate.

Evaluating the Potential Effect of Melatonin on the post-Cardiac Surgery Sleep Disorder.

BACKGROUND: Postoperative neurological injuries, including cognitive dysfunction, sleep disorder, delirium, and anxiety, are the important consequences of coronary artery bypass graft surgery (CABG). Evidence has shown that postoperative sleep disturbance is partly due to disturbed melatonin secretion in the perioperative period. The aim of this study was to evaluate the effect of melatonin on postoperative sleep disorder in patients undergoing CABG. METHOD: One hundred forty-five elective CABG patients participated in a randomized double-blind study during the preoperative period. The patients were randomized to receive either 3 mg of melatonin or 10 mg of Oxazepam one hour before sleep time. Each group received the medication from 3 days before surgery until the time of discharge. Sleep quality was evaluated using the Groningen Sleep Quality Score (GSQS), and the incidence of delirium was evaluated by nursing records. Sleep quality and anxiety scores were compared before and after surgery through the Wilcoxon signed-rank test. The analysis of covariance (ANCOVA) and independent t-test were used to compare the sleep and anxiety scores between the groups. P values ≤ 0.05 were considered statistically significant. RESULTS: Totally, 137 patients at a mean age of 60 years completed the study (76% male). The analysis of the data showed that sleep was significantly disturbed after surgery in both groups. The patients in the Oxazepam group demonstrated significantly higher disturbance in their mean postoperative GSQS score than did their counterparts in the melatonin group (p value < 0.001). A smaller proportion of the participants experienced delirium in the melatonin group (0.06%) than in the Oxazepam group (0.12%); however, this difference was not statistically significant. CONCLUSION: The result of the present study revealed that melatonin improved sleep in post-cardiac surgery patients more than what was observed with Oxazepam. Therefore, melatonin may be considered an effective alternative for Benzodiazepines in the management of postoperative sleep disorder.

Association between Perioperative Parameters and Cognitive Impairment in Post-Cardiac Surgery Patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been an important complication of cardiac surgery over the years. Neurocognitive dysfunction can affect quality of life and lead to social, functional, emotional, and financial problems in the patient's life. To reduce POCD, we sought to identify the association between cognitive dysfunction and perioperative factors in patients undergoing cardiac surgery. METHODS: One hundred one patients aged between 45 and 75 years undergoing elective cardiac surgery were enrolled in this study. All the surgeries were performed on-pump by the same medical team. A brief Wechsler Memory Test (WMT) was administered before surgery, 3 to 5 days after the surgery, and 3 months after discharge. All related perioperative parameters were collected in order to study the effect of these parameters on the postoperative WMT scores and WMT score change. RESULTS: The study population consisted of 101 patients, comprising 14 (13.8%) females and 87 (86.2%) males aged between 45 and 75 years. In univariate analysis, the baseline WMT score, serum levels of lactate dehydrogenase and T3, cross-clamp time, and preexistence of chronic obstructive pulmonary disease showed significant effects on the postoperative WMT score (p value < 0.05), whereas only the baseline WMT score and chronic obstructive pulmonary disease showed strong effects on the postoperative WMT score in the multiple regression model. In addition, the multiple regression model demonstrated a significant association between the baseline WMT score, serum creatinine level, and nitrate administration and the WMT score change. CONCLUSION: Our study showed that preexisting chronic obstructive pulmonary disease and preoperative high serum creatinine levels negatively affected cognitive function after surgery. In addition, there was a strong relationship between the patients' basic cognition and POCD. Preoperative nitrate administration led to a significant improvement in POCD. It is also concluded that the preoperative administration of specific medicines like nitrates can reduce neurological complications after cardiac surgery.

Prolonged preconditioning with natural honey against myocardial infarction injuries.

Potential protective effects of prolonged preconditioning with natural honey against myocardial infarction were investigated. Male Wistar rats were pre-treated with honey (1%, 2% and 4%) for 45 days then their hearts were isolated and mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during 30 min regional ischemia fallowed by 120 min reperfusion. Two important indexes of ischemia-induced damage (infarction size and arrhythmias) were determined by computerized planimetry and ECG analysis, respectively. Honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (P<0.001). At the ischemia, honey (1%) significantly reduced (P<0.05) the number and duration of ventricular tachycardia (VT). Honey (1% and 2%) also significantly decreased number of ventricular ectopic beats (VEBs). In addition, incidence and duration of reversible ventricular fibrillation (Rev VF) were lowered by honey 2% (P<0.05). During reperfusion, honey produced significant reduction in the incidences of VT, total and Rev VF, duration and number of VT. The results showed cardioprotective effects of prolonged pre-treatment of rats with honey following myocardial infarction. Maybe, the existence of antioxidants and energy sources (glucose and fructose) in honey composition and improvement of hemodynamic functions may involve in those protective effects.