A study of the role of nitric oxide in the mechanism of action of hydroalcoholic extract of saffron (Crocus sativus) on the electrophysiological properties of the rabbit atrioventricular node

Biologically active substances of plant origin represent an essential branch of modern cardiovascular pharmacotherapy. Furthermore, drugs of plant origin have the advantage of weaker adverse effects and lower prices than synthetic drugs. Pharmacological studies and traditional medical literature point to the anti-ischemic and hypotensive effects of the Crocus sativus L. (Iridacea). The major goals of the present study were: (1) to determine the negative dormotrophic properties of a hydroalcoholic extract of saffron on an isolated AV node and (2) to establish the role of nitric oxide in the mediating effects of saffron on the electrophysiological properties of the AV node. This was an experimental study. Selective stimulation protocols were used to independently quantify AV nodal recovery, facilitation and fatigue. We used isolated perfused rabbit AV node preparation, in three groups (N=32); in each group, we assessed the plant's effect in comparison with the control. In the pilot study, we used different concentrations (A=9 x 10-2 mg/L, B=19 x 10-2 mg/L and C=27 x 10-2 mg/L) to select the optimum concentration (19 x 10-2 mg/L) of the hydroalcoholic extract of saffron. Saffron has a depressant effect on basic and rate-dependent properties of the AV node. We observed an increasing AVCT (38.8 ±4 to 41.7 ±4 msec) and FRP (157.6 ±3 to 163.7 ±4 msec). Also saffron increased the amount of facilitation and the magnitude of fatigue (5.9 ±0.3 to 11.1 ±1 msec). The NOS inhibitor (L-NAME) has a preventative effect on the depressant effect of saffron on AVCT and FRP

Diagnostic value of D-dimer�s serum level in Iranian patients with cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is a longterm debilitating vascular brain disease with high morbidity and mortality. It may be associated with rise in D-dimer level. The aim of this study was to examine this potential association and identify the critical D-dimer cut-off level corresponding to increase the risk of CVT. This case-control study was conducted on two groups of patients with and without CVT attending the Rasool Akram Hospital (Iran) during 2014 and 2015. D-dimer levels were measured by the rapid sensitive D-dimer assay. Data were analyzed by Spearman�s correlation coefficient test, independent-samples t-test, backward-selection multiple linear regression and multiple binary logistic regression analyses. Sensitivity-specificity tests were used to detect D-dimer cut-off for CVT. Differences between the D-dimer levels of the case and control groups were significant (P<0.001). It showed that each level of increase in the number of symptoms could increase the risk of thrombosis occurrence for about 3.5 times. All symptom types except for headache were associated with D-dimer level, while headache has negative association with D-dimer level. D-dimer cut-off point for CVT diagnosis was estimated at 350 ng/mg. We concluded that D-dimer serum level significantly rises in CVT patients. A rounded cut-off point of 350 ng/mg can be used as a diagnostic criterion for CVT prediction. © L. Hashami et al., 2016

Quantitative miRNA Expression Analysis Using Fluidigm Microfluidics Dynamic Arrays

MicroRNA (miRNA) is a small non-coding RNA that can regulate gene expression in both plants and animals. Studies showed that miRNAs play a critical role in human cancer by targeting messenger RNAs that are positive or negative regulators of cell proliferation and apoptosis. Here, we evaluated miRNA expression in formalin fixed, paraffin embedded (FFPE) samples and fresh frozen (FF) samples using a high throughput qPCR-based microfluidic dynamic array technology (Fluidigm). We compared the results to hybridization-based microarray platforms using the same samples. We obtained a highly correlated Ct values between multiplex and single-plex RT reactions using standard qPCR assays for miRNA expression. For the same samples, the microfluidic technology (Fluidigm 48.48 dynamic array systems) resulted in a left shift towards lower Ct values compared to those observed by standard TaqMan (ABI 7900HT, mean difference, 3.79). In addition, as little as 10ng total RNA was sufficient to reproducibly detect up to 96 miRNAs at a wide range of expression values using a single 96-multiplexing RT reaction in either FFPE or FF samples. Comparison of miRNAs expression values measured by microfluidic technology with those obtained by other array and Next Generation sequencing platforms showed positive concordance using the same samples but revealed significant differences for a large fraction of miRNA targets. The qPCRarray based microfluidic technology can be used in conjunction with multiplexed RT reactions for miRNA gene expression profiling. This approach is highly reproducible and the results correlate closely with the existing singleplex qPCR platform while achieving much higher throughput at lower sample input and reagent usage. It is a rapid, cost effective, customizable array platform for miRNA expression profiling and validation. However, comparison of miRNA expression using different platforms requires caution and the use of multiple platforms

Multiple Analytical Approaches Reveal Distinct Gene-Environment Interactions in Smokers and Non Smokers in Lung Cancer

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p<0.001 and OR = 0.51;95%CI = 0.33–0.78,p = 0.002 respectively). In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His), SULT1A1 213GG (Arg/Arg) or AA (His/His) and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33–10.55,p = 0.006), whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg) and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15–7.51,p = 0.01). MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His) and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His) with testing balance accuracy (TBA) of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with SULT1A1 Arg213His and EPHX1 Tyr113His in smokers and SULT1A1 Arg213His with GSTP1 Ile105Val and CYP1A1*2C in nonsmokers. These results identified distinct gene-gene and gene environment interactions in smokers and non-smokers, which confirms the importance of multifactorial interaction in risk assessment of lung cancer

The effect of aqueous extract of Croucus sativus on the basic and functional electrophysiological properties of isolated perfused rabbit AV-Nodal preparation

Background&Objective: Herbal remedies are suitable alternatives for synthetic drugs due to their availability, minimal side effects and lower price. Biologically active substances of plant origin represent an essential branch of modern cardiovascular pharmacotherapy. The aim of the present study was to determine concentration-dependent effects of aqueous extract of Croucus sativus on the nodal basic and functional properties. Materials&Methods: This was an experimental study. Male Newsland rabbits (1-1.3 kg) were used in all of experiments various experimental stimulating protocols (WBCL, Recovery, Facilitation, Fatigue) were applied to assessing electrophysiological properties of Node in two groups (first group n=10 and second group n=7). We used isolated preparation including some post up AV-nodal tissue preparation. All protocols were repeated in the presence and absence (control) of different concentration (A=9×10-2, B=19×10-2, C=28×10-2 mg/l) of Croucus sativus and verapamil (0.1μM). Results were shown as Mean±SE and a probability of 5% was taken to indicate statistical significance. Results: Our results showed concentratration dependent depressant effects of extract of Croucus.s on Wenchebach Cycle Length (WBCL), AV Conduction Time (AVCT), Functional Refractory Periods (FRP).Rate-dependent properties such as Facilitation and fatigue significantly increased by 19×10-2 mg/l of Croucus.s. The effect of extract was prominent on fast pathway. Conclusion: The above results indicated potential antiarrhythmic effect of Croucus.s in treating supraventricular tachyarrhythmia

Distribution and amount of stresses caused by insertion or removal of orthodontic miniscrews into the maxillary bone: A finite element analysis

Objective > Initial stability of miniscrews is an important factor in their success as orthodontic anchorages. One of the factors affecting this stability is the stresses exerted to the bone by the screw. Since the distribution and extent of stresses and strains produced during insertion or removal of miniscrews had not been measured before, this study used finite element analysis (FEA) to measure these parameters in tapered versus cylindrical screws with or without pilot sockets. Materials and methods > An FEA model of maxilla, pilot hole, and tapered/cylindrical miniscrews were created from 875 CT scan data. The bone cortex was considered 2 mm thick. The cancellous bone was reconstructed below the cortical bone. Miniscrews were modelled on the basis of commercial titanium tapered and cylindrical miniscrews (1.6 mm wide, 8 mm long). The diameter and length of the guiding hole were considered to be 1.1 and 1.5 mm, respectively. The miniscrews were inserted (and removed) between the maxillary second premolar and first molar. Stress/strain produced in the bones or screws were measured. Results > During screw insertion, in all setups, the highest stress existed within both the bone and screw, when the screw was in the cortical bone; after insertion into the cancellous bone, the stress suddenly dropped. In cylindrical screws, the highest amount of stress was distributed around the neck which was used for screw driving. In tapered screws, the stress was mostly distributed around the front one-third of the screw. During screw removal, the results of four setups were rather similar with stresses concentrated around screw necks, in the depth of the screw hole, and around the bone surface. The greatest bone stress during insertion was caused by the pilot-less tapered screw (10.18 MPa) and the lowest stress was exerted by a pilot-less cylindrical screw (0.74 MPa). Conclusion > Most of the stress and strain is tolerated by the cortical bone and not the cancellous one. Using cylindrical miniscrews might be more bone-friendly. However, all cases had stresses below tolerable thresholds, and hence are safe

Role of anterior compact node extension (fast pathway) ablation on the basic and rate-dependent properties of the atrioventricular node

Objectives: The aim of this study was to obtain new insight into possible relation between functional properties of slow concealed pathway and rate-dependent properties of atrioventricular (AV) node. Material and methods: Rate-dependent nodal properties of recovery, facilitation, and fatigue were characterized by stimulation protocols in one group of (n=7) isolated superfused AV-nodal rabbits. Small miniature lesions were made by delivering constant voltage (110 V, 30 s) with unipolar silver electrode. Results: Fast pathway ablation decreased facilitation and had no significant effect on fatigue and nodal refractoriness. The most important effect of fast pathway ablation was prolongation of minimum conduction time. Conclusion: The FP-ablation revealed the presence of the concealed SP. Rate-dependent properties of node dependent to dynamic interaction between concealed slow with slow pathway. Fast pathway involved in the mechanism of facilitation