Atherosclerosis and Toll-Like Receptor4 (TLR4), Lectin-Like Oxidized Low-Density Lipoprotein-1 (LOX-1), and Proprotein Convertase Subtilisin/Kexin Type9 (PCSK9).

Atherosclerosis is a leading cause of death in the world. A significant body of evidence suggests that inflammation and various players are implicated and have pivotal roles in the formation of atherosclerotic plaques. Toll-like receptor 4 (TLR4) is linked with different stages of atherosclerosis. This receptor is highly expressed in the endothelial cells (ECs) and atherosclerotic plaques. TLR4 activation can lead to the production of inflammatory cytokines and related responses. Lectin-like oxidized low-density lipoprotein-1 (LOX-1), an integral membrane glycoprotein with widespread expression on the ECs, is involved in atherosclerosis and has some common pathways with TLR4 in atherosclerotic lesions. In addition, proprotein convertase subtilisin/kexin type9 (PCSK9), which is a regulatory enzyme with different roles in cholesterol uptake, is implicated in atherosclerosis. At present, TLR4, PCSK9, and LOX-1 are increasingly acknowledged as key players in the pathogenesis of atherosclerotic cardiovascular diseases. Herein, we presented the current evidence on the structure, functions, and roles of TLR4, PCSK9, and LOX-1 in atherosclerosis.

Sodium-glucose cotransporter 2 inhibitors: A comprehensive review from cells to bedside.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) are oral medications approved for type 2 diabetes mellitus. Interestingly, during recent years, they have been promisingly considered as new medications for cardiovascular and kidney diseases. However, the mechanisms underlying these new benefits are not fully understood. Thanks to the discovery of multiple modes of action, the simple picture about mechanisms of action of SGLT2is has become more and more complex. Besides their effects in diabetes, there is increasing evidence for their beneficial effects in heart failure and chronic kidney diseases. In addition, many studies have provided evidence for the fruitful effects of SGLT2is in atherosclerotic cardiovascular disease. In this study, we present mounting evidence for the complex action modes of SGLT2is and their current applications in clinical practice.

Gabapentin as Add-On to Fentanyl and Midazolam in Patients Receiving Mechanical Ventilation: A Randomized, Blinded Study.

OBJECTIVE: Fentanyl and midazolam are popular drugs for sedation and analgesia in intensive care unit. Gabapentin has sedative and analgesic effects, as well. Our purpose was to study gabapentin addition to fentanyl and midazolam to reach the target sedation level in patients requiring mechanical ventilation. METHODS: This was a randomized and double-blinded trial. Fifty patients receiving mechanical ventilation and aged from 18 to 70 years were randomized 1 : 1 to 300 mg gabapentin q8hr or placebo. The initial infusion rates of fentanyl and midazolam were 1-2 µg kg-1 h-1 and 0.06-0.2 mg kg-1 h-1, respectively, in both groups. Treatments continued prior to weaning. Ramsay sedation scale score (2-3) and behavioral pain scale score (≤4) were used for the evaluation of sedation and analgesia levels, respectively. RESULTS: A total of 43 patients were studied. Both treatment modalities reached the target sedation and analgesia levels. In the intervention group, there were significant reductions in daily consumption of fentanyl and midazolam (P < .01). Duration of ventilation was shorter in the intervention group (4.1 ± 1.7 days vs 5.1 ± 1.3 days, P > .05). There was no significant difference in intensive care hospitalization, although it was shorter in the intervention group (201 ± 24 hours vs 224 ± 19 hours, P > .05). CONCLUSIONS: This trail showed that both treatment modalities could reach target sedation and analgesia levels without significant differences. Add-on therapy with gabapentin could reduce the total dose of fentanyl and midazolam.

The efficacy and safety of pimecrolimus 1% cream vs. sertaconazole 2% cream in the treatment of patients with facial seborrhoeic dermatitis: a randomized blinded trial.

BACKGROUND: Facial seborrhoeic dermatitis (FSD) is a chronic inflammatory skin disorder characterized by remission and exacerbation episodes. In most cases, FSD requires long-term treatment. AIM: To compare the efficacy and safety of pimecrolimus and sertaconazole in patients with FSD. METHODS: In total, 60 patients with FSD were enrolled in this double-blind, active-controlled, randomized trial, and instructed to topically apply either pimecrolimus 1% cream (30 patients) or sertaconazole 2% cream (30 patients) twice daily for 4 weeks. Assessment of disease severity was performed using the Scoring Index (SI) at baseline, on Days 14 and 28, and at 4 weeks after treatment cessation. The levels of satisfaction from treatment and any adverse effects (AEs) were also assessed in both groups. RESULTS: Although the severity of disease reduced upon treatment in both groups, application of pimecrolimus caused a significantly better improvement than sertaconazole on Days 14 and 28 (P < 0.01 and P < 0.001, respectively). The rate of relapse was significantly lower in the pimecrolimus compared with the sertaconazole group at 4 weeks after treatment cessation (P = 0.01). The highest level of satisfaction (46.7%) was observed on Day 28 in the pimecrolimus group. Both topical treatments had acceptable safety profiles; however, pimecrolimus 1% cream was significantly (P < 0.01) less irritating than sertaconazole 2% cream. CONCLUSION: Pimecrolimus is associated with faster response and fewer AEs than sertaconazole in patients with FSD.

Effect of atorvastatin on testosterone levels.

BACKGROUND: Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial. OBJECTIVES: Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work. SELECTION CRITERIA: RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 µmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels. AUTHORS' CONCLUSIONS: We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.

Sirolimus versus cyclosporine for the treatment of pediatric chronic immune thrombocytopenia: A randomized blinded trial.

INTRODUCTION: Chronic immune thrombocytopenia (ITP) of childhood is still a problem. For treating ITP, several immunosuppressive medications can be considered with various response rates. Our goal was to compare effects of sirolimus and cyclosporine on children with chronic ITP. METHODS: This randomized and blinded trial was carried out on 67 children over 5 years old with chronic ITP. Patients were assigned 1:1 to cyclosporine and sirolimus for 6 months. Platelet count was assessed and compared between 2 study groups at different intervals. The clinical trial registry number was IRCT20180501039499N1. RESULTS: Sixty-one children completed the 6-month treatment. Mean age was 9.3 years with an excess of females. Compared to baseline values, both drugs caused a significant increase in number of platelets over the course of treatment; sirolimus group: 15,800/mcL vs 96,566/mcL, (P < 0.001), cyclosporine group: 14,400/mcL vs 111,266/mcL, P < 0.001,). In addition, differences of platelet number were statistically significant at some treatment intervals (3rd and 6th month, P < 0.05). A quicker response was observed in children receiving cyclosporine. Both drugs had similar rate of response which occurred in 50% of included patients. Finally, sirolimus had a better safety profile. CONCLUSIONS: Our study showed that cyclosporine and sirolimus had an equal rate of response in treating chronic ITP of children. At the same time, the two medications showed significant differences in their side effects.

A 1-year randomized trial of deferasirox alone versus deferasirox and deferoxamine combination for the treatment of iron overload in thalassemia major.

AIM: Iron chelators are extensively used to reduce iron overload. Our purpose was to compare effects of deferasirox versus deferasirox and deferoxamine in patients with thalassemia major. METHODS: This randomized and double blind trial was performed on 62 patients. Patients were assigned 1:1 to oral 30 mg/kg deferasirox daily or oral 30 mg/kg deferasirox daily plus SC 50 mg/kg deferoxamine for 5 days a week. Treatment continued for 12 months in both groups. RESULTS: Fifty-five patients completed the 1 year of treatment. Mean age was 24.5 years with an excess of females. Combined therapy caused a significant increase in myocardial T2* from 23.1 ± 7.5 ms at baseline to 27.1 ± 7.0 ms at 12 months (P < 0.05). This difference was statistically significant between 2 groups at 12 months (P = 0.01). Combined therapy and monotherapy had no significant effect on liver T2*. At 12 months, serum ferritin levels were reduced in two groups; however, the difference was significant (737 ± 459 µg/ml vs 1085 ± 919 µg/ml, P < 0.01). CONCLUSION: Our study indicates that combined treatment with deferasirox and deferoxmaine is more effective than deferasirox for reduction of iron over load in patients with thalassemia major.

Pantoprazole reduces serum ferritin in patients with thalassemia major and intermedia: A randomized, controlled study.

AIM: Complications due to iron overload exert a problematic situation in patients with thalassemia. Proton pump inhibitors (PPIs) like pantoprazole are effective agents to reduce acid gastric acid secretion and perhaps to interrupt iron absorption in conditions with increased iron absorption. Our purpose was to study effects of pantoprazole addition to chelators on iron levels in patients with thalassemia major and intermedia. METHODS: This randomized, controlled, and single center trial was performed on 60 patients with thalassemia major and intermedia in Amir Kabir hospital, Iran. Patients were randomized 1:1 to pantoprazole group (iron chelator plus pantoprazole) or control group (iron chelator) for 6 months. Serum ferritin was measured by ELISA. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*. RESULTS: After 6 months of treatment, a significant reduction was seen in serum ferritin levels in the pantoprazole group (1444±613µg/mL to 1197±956µg/mL; P<0.001). A further reduction was seen in patients with thalassmeia intermedia. There were no significant changes in myocardial T2* values in pantoprazole group compared to control group (23.6±7.3ms to 24.1±6.4ms). Compared to the control group, pantoprazole therapy had no effect on hepatic T2* value (9.7±2.3ms to 9.8±2.6ms). However, between-group difference was significant (P<0.05). CONCLUSION: Pantoprazole therapy for 6 months has benefits for reducing serum ferritin in patients with thalassemia major and intermedia. Pantoprazole addition to iron chelators seems safe.

Impact of Oral Clonidine on Duration of Opioid and Benzodiazepine Use in Mechanically Ventilated Children: A Randomized, Double-Blind, Placebo-Controlled Study.

Long term use of opioids and benzodiazepines are associated with important untoward effects. The α2 adrenergic agonist clonidine has sedative effects. Our goal was to study clonidine addition to total doses of fentanyl and midazolam and duration of ventilation in pediatric ICU (PICU). This randomized, double-blind, and placebo-controlled trial was conducted in PICU of Mofid Children Hospital. Hundred children aged from 2 to 15 years were randomized in 1:1 ratio to receive 5 µg/kg oral clonidine every 6 h or placebo plus 1-5 µg/kg/hr IV fentanyl and 0.05- 0.1 mg/kg/hr IV midazolam. Daily use of fentanyl and midazolam were measured. Ramsay sedation score was used for evaluation of sedation. A total of 96 patients were studied. The patients in placebo group received more midazolam and fentanyl compared with the patients in intervention group. Mean total dose of midazolam was 4.3 ± 2.2 mg in the placebo group and 2.7 ± 2.9 mg in the intervention group (P<0.05). Mean total dose of fentanyl was 34.4 ± 23.1 µg in the placebo group and 18.9 ± 10 µg in the intervention group (P<0.01). No significant differences were observed in duration of ventilation and length of PICU stay. No case of severe adverse effects was seen. This trial showed a reduction in total doses of midazolam and fentanyl given in ventilated children who were administered clonidine as add-on therapy. Clonidine addition had no effect on duration of mechanical ventilation.

Effect of red sugar on functional constipation in children compared to figs syrup; a randomized controlled trial study.

AIM: The present study is aimed to investigate the effect of red sugar on functional constipation in children compared to figs syrup. BACKGROUND: Treatment of constipation in childhood improves gastrointestinal function in the future and regular bowel habit. Red sugar is an effective ingredient in the treatment of constipation. Figs syrup is the other common natural substance used to treat constipation in children. Conducted studies on these two substances and similar herbal substances have shown their beneficial effects, but in a conducted study, it is reported that the effect of fig syrup is less than the chemical material. METHODS: This Randomized Controlled Trial (RCT) Study was done in 2016. First, by performing an examination and filling out the identifying form of the patient's health status, mothers respond to the designed questionnaire. 30 children with constipation were treated with the usual drug, fig syrup, and 30 other children received red sugar. After a 4-week treatment period, the examination was conducted again and the questionnaire was filled out again. The changes following the intervention were measured and the status before and after treatment were compared as well. The analyses were performed using SPSS 20 (SPSS for Windows, SPSS Inc., Chicago, IL, USA). RESULTS: In this study, there was no significant difference between effects of red sugar and fig syrup in terms of the frequency of fecal excretion, and pain at the time of excretion (p = 0.264). However, the fig syrup was more effective in reducing the anorexia (p < 0.001) and abdominal pain compared with fig syrup (p < 0.001). Also fig syrup was more effective in inducing diarrhea (p = 0.019). CONCLUSION: In general, treatment by red sugar has been effective in improving the functional characteristics of constipation in children; and did not show any complication and toxic effects. It is easily accessible at affordable prices to resolve childhood constipation.

Drug-induced bone loss: a major safety concern in Europe.

INTRODUCTION: Drug-induced bone loss remains the major cause of vertebral and hip fractures and significantly associated to morbidity and mortality. This article will review the common drugs identified as the causes of bone loss and the risk factors and management in European countries. AREAS COVERED: Beyond glucorticoid - the most cause of osteoporosis, many different drugs could cause harmful skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists, aromatase inhibitors are well-known cause of bone loss. Osteoporosis and fractures risk also increased with calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral anticoagulants, high doses of thyroxine and proton pump inhibitors. EXPERT OPINION: Drugs are an important secondary cause of osteoporosis. Healthcare professionals should reassess the requirement for drugs and use the lowest dosage and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement, appropriate monitoring of bone status and initiating osteoporosis treatment if indicated are recommended when drugs having potential deleterious effects on bone are used, particularly in high risk patients. The update and further studies would provide concluded evidences of controversial drugs induced bone loss and determine the best prevention and treatment strategies.

A 24-Week Treatment of Pediatric Hemangioma with Oral Propranolol.

Hemangioma is a benign vascular tumor that shouldbe treated in problematic situations.Propranolol efficacy, target dose, range of age, duration of treatment and complications arenot conclusive for treatment of pediatric hemangioma. Our goal was to study efficacy and safety of propranolol for hemangioma treating in children. A randomized, open label crossover trial with two twenty four-week treatment phases separated by a one-week washout period, was conducted in Amir-Kabir Hospital, Arak, Iran. Thirty two patients with age of 1 month to 15 years were randomized to receive either oral propranolol 2 mg/Kg/day or receivedno treatment. The primary outcome measure changed in hemangioma size assessed at baseline, day 3, day 7, and every month. At baseline, the mean surface area was 36.9 ± 36.3 cm2. After 1 week of treatment, a decrease was seen in size of hemangiomas. After one month, a significant reduction was seen in size of lesionsin treatment group compared to observation group (30 cm2vs 16 cm2, P < 0.01). Significant reductions were present at other intervals (P < 0.05). In the second phase of the study, a significant reduction was observed only after one month of treatment (P < 0.05). The trial suggested that 24 week treatment with oral propranolol was effective for treatment of pediatric hemangiomas with acceptable safety profile.

A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major.

AIM: Cardiomyopathy due to iron overload can be fatal in patients with thalassemia major. Calcium channel blockers seem to be effective to reduce iron loading. Our goal was to study effects of amlodipine addition to chelators on iron loading in patients with thalassemia major. METHODS: This randomized, controlled, and single-center trial was performed on 56 patients with thalassemia major. Patients were randomized 1:1 to combined group (iron chelator plus amlodipine) or control group (iron chelator) for 1 year. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*. Serum ferritin was also measured. RESULTS: After 12 months of treatment, myocardial T2* values had significant improvement in combined group (21.9 ± 8.0 ms to 24.5 ± 7.6 ms; P < .05); Difference between two groups was significant (P = .02). Combined treatment had no effect on hepatic T2* value (9.6 ± 2.8 ms to 9.5 ± 3.6 ms); difference between two groups was not significant (P = .2). In addition, a significant reduction was seen in serum ferritin levels in two groups. Mild gastrointestinal upset was the most common untoward effect. CONCLUSION: Addition of amlodipine to iron chelators has beneficial effects for reduction of iron loading in patients with thalassemia major. This combination therapy seems safe.

Thrombolytic Therapy Up-regulates Inflammatory Mediators Compared to Percutaneous Coronary Intervention (PCI).

The important role of reperfusion therapies in the treatment of acute myocardial infarction is well documented. However, reperfusion therapies can initiate inflammatory response and may damage the myocardium. The purpose of current study was to compare the effects of percutaneous coronary intervention and thrombolytic therapy on inflammatory markers in the setting of ST elevation myocardial infarction (STEMI). Eighty three patients with STEMI were enrolled in this study. 40 patients underwent percutaneous coronary intervention (PCI), and 43 patients received streptokinase (1.5 million IU) as a main medical reperfusion therapy. Monocyte expression of Toll-like receptor 4 (TLR4),  serum levels of TNF-α and IL-1ß, red cell distribution width (RDW) and C- reactive protein (CRP) were compared between groups at admission time, two hours and four hours after termination of treatment. p<0.05 was considered as statistically significant for all tests. Compared to baseline, both treatments increased monocyte expression of TLR4, serum levels of cytokines and CRP. Compared to PCI, medical reperfusion therapy significantly raised both monocyte expression of TLR4 (39.8±4.7 % vs 49.1±3.6 %, p<0.01), and serum levels of TNF-α (13.2±3.7 pg/ml vs 25.1±2.6pg/mlp<0.05). No effect was seen on RDW levels. Moreover, medical reperfusion therapy caused significant rise in CRP levels (p<0.01). The present study demonstrates that thrombolytic therapy is associated with higher inflammatory responses compared to PCI. Our findings suggest that thrombolytic therapy may increase the likelihood of detrimental effects of reperfusion therapy on the myocardium.

Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 µg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P < 0.001). Both drugs caused a significant rise in number of platelets on the 7th and the 14th day of treatment. Compared to IVIG, except a significant drop in hemoglobin concentration (P < 0.001), anti-D had lower rate of side effects including fever (P < 0.05), allergy (P < 0.01), and headache (P < 0.001). Our results showed that anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile.

Drug Reaction With Eosinophilia and Systemic Symptoms Induced by Valproic Acid: A Case Report.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but life-threatening reaction to drugs such as carbamazepine and allopurinol. The condition is characterized by skin rashes, fever, hematological disturbances, lymphadenopathy, and organ failure, most probably hepatic dysfunction. To date, only a few cases of valproate-induced DRESS syndrome have been reported. CASE PRESENTATION: We report on the case of a 60-year-old man who had been treated with valproic acid some time before being referred to Kowsar Hospital, Semnan, Iran in December 2015. He was given valproic acid 1000 mg PO, and after 20 days, he had developed widespread rashes, fever, esophagitis, cervical lymphadenopathy, and tender hepatomegaly. Laboratory results at Kowsar showed a drop in hemoglobin, in addition to lymphocytosis, thrombocytopenia, and elevated serum transaminases. DRESS was diagnosed, and corticosteroid therapy was initiated. Administration of the culprit drug to the patient was also stopped. Intravenous immunoglobulin (IVIG) improved the general condition of the patient. CONCLUSIONS: Only a small number of case reports have described valproic acid-induced DRESS syndrome; therefore, the condition is difficult to prevent. Rechallenge with valproic acid should be avoided in patients with a history of reaction to the drug.

Efficacy of nebulized L-epinephrine for treatment of croup: a randomized, double-blind study.

The objective of this study was to compare the effect of L-epinephrine plus dexamethasone vs. dexamethasone for treatment of croup in children. A randomized, double-blind clinical trial was implemented on 174 patients with croup, aged from 6 months to 6 years, and admitted to the Amir Kabir Pediatric Hospital (Arak, Iran). After randomized allocation, patients were administered dexamethasone, and then, they received either saline or L-epinephrine. Westley croup scores, heart rate, respiratory rate, and blood pressure were recorded every half an hour for a total of 120 min. There was a significant difference in mean of croup scores between two groups (P < 0.009). In addition, a significant difference was seen on mean of heart rate between two groups (P < 0.026). Our results showed a considerable difference in reduction of velocity of croup scores in patients who received nebulized L-epinephrine compared to patients who received placebo.

Everolimus-Eluting Stents Reduce Monocyte Expression of Toll-Like Receptor 4.

PURPOSE: Toll-like receptors (TLR) are well known components of the innate immune system. Among them, TLR4 is related to the inflammatory processes involved in atherosclerotic plaque formation. Our purpose was to compare the monocytic expression of TLR4 following implantation of drug-eluting (DES) and bare stents (BMS). METHODS: In this study, patients with chronic stable angina undergoing elective percutaneous coronary intervention (PCI) in ShahidMadani Heart Hospital, Tabriz, Iran were included. Ninety-five patients receiving DES and 95 patients receiving BMS were selected between 2012 and 2014.Everolimus eluting stents were implanted for DES group. Both groups received similar medications and procedure. Blood samples were taken before PCI, 2 hours and 4 hours after termination of PCI. Expression of TLR4 on monocytes was measured using flowcytometry. Patients were matched for age, sex and coronary artery disease risk factors, but not for TLR4 expression rate before PCI. RESULTS: A significant difference was seen between DES and BMS in TLR4 expression before (21.3±2.8% vs. 15.5±2.7%; P< 0.05) and four hours after PCI (30.1 ± 3.3% vs 39.2 ± 3.2%, P< 0.05). Due to the unmatched rate of TLR4+ expression before PCI, we measured the percentage of increase in TLR4 expression between groups. DES compared to BMS significantlycaused less increase in the TLR4 expression (50.23%±10.03% vs. 446.35%±70.58%, p<0.001). CONCLUSION: Our findings suggest thateverolimuseluted from the stents can decrease PCI induced increase in the TLR4 expression on the surface of monocytes.

Hydrocortisone reduces Toll-like receptor 4 expression on peripheral CD14+ monocytes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Evidence from several lines of investigations suggests that Toll-like receptor 4 (TLR4) is involved in atherosclerosis as a bridge between innate and acquired immunity. Percutaneous coronary intervention (PCI) can trigger inflammation through activation of human TLR4 (hTLR4) on monocytes. Hydrocortisone as an anti-inflammatory and immuno-suppressant agent has multiple mechanisms of action. In this study, we aimed at assessing the effects of hydrocortisone on monocyte expression and activity of hTLR4 in patients underwent PCI. METHODS: Blood samples were taken from a total of 71 patients with chronic stable angina who were scheduled for a PCI, before the intervention. Thirty patients received 100 mg hydrocortisone prior to the procedure. Control group was composed of 41 patients underwent PCI without receiving hydrocortisone. Blood collection was repeated 2 and 4 h after PCI. The expression of hTLR4 on the surface of CD14+ monocytes and the serum levels of TNF-α and IL-1ß were measured using flowcytometry and Sandwich ELISA. RESULTS: Compared with controls, hydrocortisone significantly reduced monocyte expression of hTLR4 in test group (P<0.01). In addition, it had a significant effect on reduction of serum concentrations of TNF-α and IL-1ß in test group in a time-dependent manner (P<0.01). CONCLUSION: In this study, hydrocortisone was able to reduce the hTLR4/CD14 positive monocytes and its related pro-inflammatory cytokines, thus it can decrease inflammatory responses following PCI.

Prevalence of pulmonary hypertension in patients undergoing hemodialysis.

INTRODUCTION: Pulmonary hypertension (PH) is one of the most important accompanying comorbidities with hemodialysis in patients with end-stage renal disease. The prevalence of hemodialysis-induced PH is still a subject of debate. The goal of the present work was to determine the prevalence of PH in patients undergoing hemodialysis. MATERIALS AND METHODS: This study was carried out on patients undergoing hemodialysis for at least 6 months. Pulmonary artery pressure (PAP) was measured by a cardiologist using echocardiography, and a value equal to or higher than 35 mm Hg was considered PH. The relationship of a high PAP with demographic and clinical characteristics of the patients was assessed. RESULTS: A total of 102 patients were included in the study. The mean of age was 59 +/- 18 years. The most common cause of end-stage renal disease was diabetes mellitus (35%). The mean duration of hemodialysis was 24 +/- 17 months. The mean ejection fraction and PAP were 57 +/- 5% (range, 44% to 73%) and 39 +/- 9 mm Hg (range, 25 mm Hg to 70 mm Hg), respectively. Overall, 66% of the patients had PH. These patients were more likely to be on dialysis for a longer duration and to have low ejection fractions. They were also older than other patients. CONCLUSION: Our findings show that PH is associated with duration of dialysis, age, and ejection fraction. Due to the high prevalence of PH among hemodialysis patients, it is necessary to screen this disorder and minimize its effects.