Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)‐β1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF‐β1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01–p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001–p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO‐induced kidney fibrosis and dysfunction.     

The Effect of Altitude on Breaking Seed Dormancy and Stimulation of Seed Germination of Persian Hogweed (Heracleum Persicum)

Persian hogweed is a perennial herb and aromatic plant which has pharmaceutical and fodder values, and the main propagation method of this species is seed. The goal of this study was to investigate the effect of altitude on breaking dormancy and stimulate seed germination of this species. The study was designed and carried out using the test of seed analysis. For our purpose, seeds were collected from three different altitudes (1700, 2200, 2700 masl) in Kojoor area. After initial purification, germination percent (GP) and speed (GS) of each elevation were determined by cold stratification compared to control. According to results, control seeds did not germinate, showing that the seeds of this species need to be treated. Statistical analysis of results showed that there are significant differences between GP and GS of each elevation, as seeds of higher elevation had slower and less germination in longer periods. So, changes in elevation are an effective factor on seed germination characteristics of this species and this factor has to be considered in seed preparation and restoration with this species.     

How does blood glucose control with metformin influence intensive insulin protocols? Evidence for involvement of oxidative stress and inflammatory cytokines

INTRODUCTION: Recent investigations have revealed that control of hyperglycaemia with insulin improves outcomes. The cornerstone of hyperglycaemia in critically ill patients is insulin resistance and it remains refractory to intensive insulin protocols. We designed this study to evaluate the efficacy and safety of a new intensive insulin therapy (IIT) protocol combined with metformin. METHODS: Twenty-one patients with systemic inflammatory response syndrome and a blood glucose level of >120 mg/dl admitted to an intensive care unit (ICU) were randomised to receive either intravenous infusion of IIT alone (n=11) or combined with metformin (IIT+MET; n=10) to maintain a blood glucose level (BGL) of 80-120 mg/dl. Blood samples were obtained at baseline and at 48 hours, 96 hours and 7 days after initiation of the study. Samples were analysed for interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO) as inflammatory mediators; plasminogen activation inhibitor-1 (PAI-1) as a coagulation mediator; and thiobarbituric reactive substances (TBARS), total antioxidant power (TAP) and total thiol molecules (TTM) as oxidative stress parameters. RESULTS: The addition of metformin to the IIT protocol decreased insulin requirement and concentration of insulin and C-peptide. With both treatments at most time points, the mean plasma levels of IL-6, TNF-alpha, NO, PAI-1 and TBARS were found to be significantly lower compared with baseline. Antioxidant activity was increased in both arms with increasing TAP and TTM (P<0.05). There was no significant difference between the two groups regarding reported beneficial effects on these parameters. Therapeutic Intervention Scoring System-28 (TISS-28) score, an index of nursing workload and number of therapeutic interventions, decreased in the IIT+MET group (P<0.01). We did not observe any occurrence of hyperlactataemia or acidosis in the IIT+MET group. CONCLUSION: Metformin plus insulin appears to lower the incidence of insulin resistance, lower insulin requirement while maintaining blood glucose level control, and consequently lower the incidence of adverse effects related to high-dose insulin therapy, particularly hypoglycaemia, and also declined nursing workload. Both treatment protocols showed improvements in inflammatory cytokine levels. Further studies with larger sample sizes are warranted to determine the undiscovered facts of insulin-sensitising agents in critically ill patients.     

The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine

Oxidative stress has a proven role in pathophysiology of acute respiratory distress syndrome. The antioxidant drugs, especially N-acetylcysteine (NAC) have been used for years to overcome oxidative stress effects in patients. In the present study we have investigated the effects of NAC treatment (IV NAC in 150mg/kg at the first day followed by 50mg/kg/day for three days) on 27 ICU patients with ALI/ARDS considering the glutathione-S-transferase genetic variations, as an important enzyme contributing in oxidative stress pathways. The results indicated that NAC improved oxygenation (increase in PaO(2)/FiO(2)) and decreased mortality rate in treated patients compared to control group (p<0.05). Evaluation of three isoforms of glutathione-S-transferase (GST M1, P1 and T1), in these patients have showed an association between GST M1 null, and GST M1 and T1 double null polymorphisms with increased mortality in control group, suggesting antioxidant therapy critical for this group of patients.     

Hemorrhage detected using MR imaging in the setting of acute stroke: an in vivo model

BACKGROUND AND PURPOSE: The treatment algorithm for acute cerebrovascular accidents has traditionally sorted these accidents as either hemorrhagic or nonhemorrhagic, and MR imaging, with its ability to allow expeditious assessment of vascular substrates and regional blood volume, is well suited for this purpose. Our purpose was to delineate the accuracy of MR imaging in acute, hemorrhagic forms of stroke during the time frame considered beneficial for intervention in an animal model. METHODS: Eighteen dogs with small, iatrogenic parenchymal, subarachnoid hemorrhage (SAH), or both were serially scanned over the initial 6-hour postictal period. Confirmatory pathologic specimens and 3-hour postictal CT scans were obtained in all animals. The MR and CT studies were then interpreted in a blinded fashion by two neuroradiologists for the presence of hemorrhage. The results were subjected to receiver operating characteristic analysis. RESULTS: MR imaging depicted acute parenchymal hemorrhage and SAH with a high degree of accuracy at 1.5 T. This finding was independent of each of the time points studied during the 6-hour window. For SAH, the MR accuracy for reader 1 was 0.86 (95% CI, 0.76-0.97); for reader 2, accuracy was 0.85 (95% CI, 0.71-0.99). The CT accuracy for the two readers was 0.42 (95% CI, 0.26-0.58) and 0.66 95% CI, 0.43-0.89), respectively. Fluid-attenuated inversion-recovery images improved the conspicuity of SAH on MR images and, along with spin-density-weighted spin-echo sequences, helped to establish the hemorrhagic nature. For parenchymal hemorrhage, the MR accuracy for reader 1 was 0.90 (95% CI, 0.81-0.99); for reader 2, accuracy was 0.93 (95% CI, 0.84-1.00). With CT, the accuracy of reader 1 was 0.91 (95% CI, 0.85-0.97) whereas for reader 2 accuracy was 0.76 (95% CI, 0.69-.83). Parenchymal hemorrhage detection and diagnosis was best with T2*-weighted gradient-echo images. CONCLUSION: MR imaging with appropriately selected sequences appears able to provide information regarding the presence (or absence) of hemorrhage in an acute stroke model requisite to the initiation of treatment.