Improvement of tissue survival of skin flaps by 5α-reductase inhibitors: Possible involvement of nitric oxide and inducible nitric oxide synthase

Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase (iNOS) in graft survival mediated by these agents. Methods: A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1 mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20 mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L-NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Results: Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide (NO) levels in graft tissue (P < 0.05). These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. Conclusion: It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps. © 2015, Pasteur Institute of Iran. All rights reserved

Safety and efficacy of PDpoetin for management of anemia in patients with end stage renal disease on maintenance hemodialysis: Results from a phase IV clinical trial

Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7 of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49 of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis. © A.N. Javidan et al., 2014

Effects of Dexmedetomidine on surgical stress responses at patients under CABG

Cardiopulmonary bypass (CPB) surgery with extracorporeal circulation produce changes in the immune system and plasma levels of inflammatory cytokines. we hypothesize that Dexmedetomidine as an adjuvant , modulates the inflammatory response after CABG. In a prospective, randomized, blind study, 31 patients were assigned to Dexmedetomidine (Dex) group and compared with control group of 30 patients. Dex was administered at a loading dose of 0.5 μg/kg for 10 min , followed by a continuous infusion of 0.5 μg/kg per hour until the completion of CABG with CPB . The endpoints used to assess inflammatory responses to mini - CPB were plasma tumor necrosis factor (TNF) - � , interleukin (IL - 6 ) and interleukin ( IL - 10) levels. The inflammatory markers (IL - 6 , IL - 10 , TNF - � ) were determined after Dex administration , before CPB and 24 hours after admission to ICU. Biochemical factors including glucose , creatinine , lactate , BUN, AST , ALT , LDH were determined before CPB, immediately after entering the ICU , 24 hr , 48 hr and 72 hr post admission to ICU. Hemodynamic variables were also determined. Dex group was associated with a significant reduction in urea and creatinine. There were no significant differences in glucose, lactate, liver enzymes, LDH , IL - 6, IL - 10 and hemodynamic variables. In contrast, the surgery - induced increase in TNF - � levels in the Dex group was significantly higher compared with the control group

Serum level of homocysteine, folate and vitamin-B12 in epileptic patients under carbamazepine and sodium valproate treatment: A systematic review and meta-analysis

Background: Numerous studies have shown that long term treatment with anticonvulsants may be an important risk factor for the onset of atherosclerosis, or worsening of its symptoms. There are many contradictory reports regarding these effects. Objectives: We performed a systematic review and meta-analysis of the published studies in order to see whether the atherogenic outcomes could be related to any serum biochemical abnormalities. Materials and Methods: Published articles indexed in PubMed, ISI web of science, Science Direct and Scopus databases from 1990 to 2011 were retrieved using a comprehensive search strategy. After omitting the unrelated articles and duplicates, articles met the eligibility criteria for critical appraisal were included in the analysis. Data were summarized in standard data abstraction forms and subjected to analysis by STATA software. Results: Finally, ten published studies were included in the meta-analysis. Results showed that carbamazepine and sodium valproate consumption are associated with a significant elevation of the serum homocysteine levels. On the other hand, medication with carbamazepine is associated with a reduction of the level of folate in the serum and that of sodium valproate is associated with a reduction of serum level of vitamin B12. Conclusions: According to the results of this study, as carbamazepine and valproate sodium consumption can result in elevated serum levels of homocysteine and decreased levels of folate and vitamin B12, and the atherogenic effect of increased serum homocysteine level is well established, the patients under these medications should be monitored for possible atherogenic effects. © 2013, Iranian Red Crescent Medical Journal; Published by Kowsar Corp

Clinical outcomes and electrolyte balance factors in complex cardiac operations in adults; del nido versus custodiol cardioplegia solutions: A randomized controlled clinical trial

Background: Cardioplegia is used for protection of myocardium during cardiac operations. Del Nido (DN) and Custodiol cardioplegia solutions are used for prolonged protection of the myocardium during cardiopulmonary bypass (CPB). Custodiol cardioplegia (CC) solution is gaining popularity for myocardial protection during cardiopulmonary bypass. Objectives: This study aimed to compare the effects of Custodiol with another cardioplegia solution, Del Nido, on myocardial protection during cardiopulmonary bypass. Methods: In a randomized controlled clinical trial, forty patients were randomly allocated to DN and Custodiol (CC) groups. Patients in both groups received a normal anesthesia protocol. For cardioplegia, in the DN group, the DN solution was administered every 90 minutes by the antegrade route. In the Custodiol group, the Custodiol solution was administered in the same way at the beginning of the cardioplegia. Demographic information, blood chemistry parameters and other related perioperative and postoperative clinical indices were recorded. Results: Frequency of female patients was 14/21 (66.66) in the DN and 12/19 (63.15) in the CC group (P = 0.816), age was 57.14 ± 12.48 years in the DN and 59.47 ± 11.96 years in the CC group (P = 0.551), weight was 70.95 ± 9.56 kilograms in the DN and 69.63 ± 7.64 kilograms in the CC group (P = 0.635), CPB time was103.19 ± 23.43 minutes in the DN versus 97.36 ± 16.7 minutes in the CC group (P = 0.376), and cross-clamp time was 73.76 ± 19.66 minutes in the DN and 83.95 ± 16.14 minutes in the CC group (P = 0.083). Blood chemistry and blood gas analysis revealed a similar trend between the two groups in these parameters (P > 0.05) except for higher sodium levels after cardioplegia (P = 0.016) and end of CPB (P = 0.002), potassium levels after cardioplegia (P = 0.029), and bicarbonate anions at the end of bypass (P = 0.03) in the custodiol group. Conclusions: In conclusion, CC and DN offer effective myocardial protection during cardiopulmonary bypass. It is recommended to restrict the use of CC in patients susceptible to electrolyte disturbances. © 2018, Author(s)

Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke

Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood�brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 µg/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 µg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 µg/kg improved neurological outcome (P 0.05). Additionally, irisin (7.5 µg/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice. © 2018 Springer Science+Business Media, LLC, part of Springer Natur

Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke

Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood�brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 µg/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 µg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 µg/kg improved neurological outcome (P 0.05). Additionally, irisin (7.5 µg/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

A new design for electrospinner collecting device facilitates the removal of small diameter tubular scaffolds and paves the way for tissue engineering of capillaries

Electrospinning is a technique widely used for tissue engineering. Despite hurdles, electrospun vascular tissue scaffolds has shown great promise in in vitro studies. One problem is the removal of tubular scaffolds from a electrospinning collection device with no unwanted crumpling or tearing, especially for small diameter scaffolds. To tackle this problem we designed a collection device for simple removal of the scaffold from the collector while no chemical pretreatment was required. The scaffolds fabricated on this collecting device maintained their tubular structure and showed favorable surface properties, mechanical strength and biocompatibility. The device offers a new opportunity for tissue engineering researchers to fabricate tubular scaffolds from materials which have not been possible to date and help them improve the quality of synthesized scaffolds. © 2016 Elsevier Inc

Serum levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α, renal function biochemical parameters and clinical outcomes in pediatric cardiopulmonary bypass surgery

Background: Cardiopulmonary bypass causes detrimental effects on remote organs due to inflammatory response. One of these organs is kidney that is frequently affected by cardiac surgery. Acute kidney injury is a post-cardiopulmonary bypass complication, which may result in increased post-operative morbidity and mortality. Post-cardiopulmonary bypass inflammatory response may contribute to remote organ dysfunction. In the present study, we investigated the relation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α, and renal function tests such as creatinine and blood urea nitrogen (BUN). Methods: In total, 91 patients between the ages of 4 and 60 months were enrolled for elective cardiac surgery with cardiopulmonary bypass after informed consent. Data regarding renal function tests and clinical outcomes were carefully recorded until 24 hours after admission to intensive care unit and analyzed. Results: Our findings support that there is a direct correlation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α and cardiopulmonary bypass time, duration of operation, and intensive care unit stay. Longer cardiopulmonary bypass time was associated with higher interleukin-8 at cross-clamp removal and 24 hours post- intensive care unit as well as higher interleukin-10 at declamp time. Higher interleukin-6 at declamp time was directly correlated with higher post-operative BUN. Interleukin-8 level after anesthesia induction was directly correlated with intensive care unit stay duration. Higher blood interleukin-6 and tumor necrosis factor-α levels following 24 hours of admission to intensive care unit were associated with longer mechanical ventilation time. Conclusion: Higher circulatory pro-inflammatory cytokine level is associated with adverse outcomes such as increased intensive care unit stay and longer mechanical ventilation time in pediatric patients. It is also correlated with unfavorable biochemical parameter of renal function, BUN. Findings hint that proper control of the inflammatory response is vital for the control of unfavorable clinical and pathological outcomes. © The Author(s) 2019

Evaluation of the correlations between sodium fluctuations and clinical outcomes in children undergoing cardiopulmonary bypass

Introduction: Sodium abnormalities constitute some of the most common electrolyte disorders during cardiopulmonary bypass (CPB), and they exhibit a rise for various reasons during CPB. The use of CPB for correcting congenital heart diseases in infants has profound physiological effects on most organs. The devastating effects of CPB are often more pronounced in infants. This study aimed to determine the relationship between sodium fluctuations and clinical outcomes in infants undergoing CPB. Methods: This cross-sectional study (correlational) was conducted on 473 children who underwent CPB in 2016 according to our inclusion criteria. The samples were divided into 2 groups according to sodium fluctuations with a cutoff point of 15 mEq/L, and the clinical outcomes were compared between the 2 groups. The data were analyzed by SPSS, version 16, and presented as descriptive and inferential statistics. Results: The incidence of cardiac (P<0.001), pulmonary (P=0.005), renal (P=0.02), neurologic (P=0.001), and hemorrhagic (P=0.02) outcomes were significantly different between the 2 groups. Gastrointestinal outcomes, infection outcomes, intubation time, intensive care unit stay, hospital stay, and mortality were not significantly different between the 2 groups. Conclusions: Sodium fluctuations of 15 mEq/L or higher, as an independent factor, exacerbated cardiac, pulmonary, neurologic, renal, and hemorrhagic outcomes. © 2021, Iranian Heart Association. All rights reserved