Suramin inhibits the early effects of PLA(2) neurotoxins at mouse neuromuscular junctions: a twitch tension study

Several phospholipase A(2) (PLA(2)) neurotoxins from snake venoms can affect acetylcholine release at the neuromuscular junction. In isolated nerve-muscle preparations three distinct phases have been described for this phenomenon: An initial transient decrease in twitch tension; a second facilitatory phase during which twitch height is greater than control twitch height; and the last phase which causes a reduction in twitch height that finally results in paralysis. Suramin has been reported to inhibit the toxic effects of β-bungarotoxin and another PLA(2) neurotoxin, crotoxin in vitro and in vivo. We have further examined the effects of suramin on the three phases of the effects of the presynaptic PLA(2) neurotoxins β-bungarotoxin, taipoxin and ammodytoxin on mouse phrenic nerve-hemidiaphragm preparations. When preparations were pre-treated with suramin (0.3mM), the early biphasic effects (depression followed by facilitation) were abolished, and the time taken for final blockade induced by β-bungarotoxin, taipoxin and ammodytoxin A was significantly prolonged. In contrast, suramin did not significantly affect the facilitation induced by the potassium channel blocking toxin dendrotoxin I when applied under the same conditions. In addition, application of 0.3mM suramin did not prevent the facilitatory actions of 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium chloride (TEA). Overall, the mechanism whereby suramin reduces the effects of PLA(2) neurotoxins remains elusive. Since suramin reduces both enzyme-dependent and enzyme-independent effects of the toxins, suramin is not acting as a simple enzyme inhibitor. Furthermore, the observation that suramin does not affect actions of standard K(+) channel blockers suggests that suramin does not stabilise nerve terminals

A report on Platyceps ventromaculatus (Colubridae) from Fereydan County in Isfahan province-Iran

Snakes are among the predatory reptiles in the wild. Due to the importance of knowing the habitats of these reptiles and their distribution, this study has been done. During the study, the specimen snake was found in the garden of a house in the region of Afus, of Fereydan County, in the west of Isfahan province. The city of Afus is 2800 meters above the sea level, on the roof of Iran. Afus is located at 50°5’, 646 East longitude, and at 33°1’, 464 North Latitude. Afus is a mountainous region with a moderate climate, its winters are cold and snowy while its summers are mild and pleasant. The mountainous nature of Afus and the sudden changes in temperature cause seasonal winds to blow. Temperature changes in this city are such that in winter and especially in January reaches minus 30°C and in summer and on the hottest day of the year will be 31°C. This suitable climate and soil type cause the growth of varieties of herbaceous plants and medicinal herbs in this region. The presence of these plants causes Afus land to be green and fertile in the hot season. After initial identification of this species according to the available sources, its photos and videos were presented to a high expert herpetologist who confirmed the identity of the snake. On the basis of morphological characters, the specimen was Platyceps ventromaculatus belong to the Colubridae family and is considered as a non-venomous snake

Cardiac Rehabilitation Using The Family-Centered Empowerment Model Versus Home-Based Cardiac Rehabilitation In Patients With Myocardial Infarction: A Randomised Controlled Trial

Objective To determine if a hybrid cardiac rehabilitation (CR) programme using the Family-Centered Empowerment Model (FCEM) as compared with standard CR will improve patient quality of life, perceived stress and state anxiety of patients with myocardial infarction (MI). Methods We conducted a randomised controlled trial in which patients received either standard home CR or CR using the FCEM strategy. Patient empowerment was measured with FCEM questionnaires preintervention and postintervention for a total of 9 assessments. Quality of life, perceived stress, and state and trait anxiety were assessed using the 36-Item Short Form Health Survey (SF-36), the 14-item Perceived Stress, and the 20-item State and 20-item Trait Anxiety questionnaires, respectively. Results 70 patients were randomised. Baseline characteristics were similar. Ejection fraction was significantly higher in the intervention group at measurements 2 (p=0.01) and 3 (p=0.001). Exercise tolerance measured as walking distance was significantly improved in the intervention group throughout the study. The quality of life results in the FCEM group showed significant improvement both within the group over time (p\u3c0.0001) and when compared with control (p\u3c0.0001). Similarly, the perceived stress and state anxiety results showed significant improvement both within the FCEM group over time (p\u3c0.0001) and when compared with control (p\u3c0.0001). No significant difference was found either within or between groups for trait anxiety. Conclusions The family-centred empowerment model may be an effective hybrid cardiac rehabilitation method for improving the physical and mental health of patients post-MI; however, further study is needed to validate these findings. Clinical Trials.gov identifier NCT02402582. Trial registration number NCT02402582

The effect of Iranian snake, Naja naja oxiana venom on the blood glucose concentration and some biochemical parameters of experimental diabetic rats

Diabetes is a chronic disease resulting from impaired insulin production and function; leading to hyperglycaemia and long-term complications. The treatment for Type I diabetes treatment involves insulin injections while Type II diabetes treatments include drugs such as metformin and sulfonylureas, along with lifestyle changes. These medicines can be expensive and may have adverse effects. Therefore, the search for new therapeutic agents continues. Venoms from various animals yield numerous pharmacologically active compounds. In this study, we investigated the effects of the venom from an Iranian snake, Naja naja oxiana, on blood glucose concentration and certain serum biochemical parameters in male rats with induced diabetes.Diabetes was induced in male rats using either a single injection of streptozotocin (STZ) alone (55 mg/kg i. p.) or STZ (65 mg/kg i. p.) preceded by nicotinamide (230/kg i. p.) administered 15 min earlier. The diabetic rats produced by either method received a single injection of either vehicle or venom (0.2 or 0.4 mg/kg i. p.). In the STZ rats, this was done 13 days after diabetes induction, while in the STZ-nicotinamide rats, venom was injected 3 days after diabetes induction.The venom from Naja naja oxiana significantly reduced blood glucose levels in male rats with diabetes induced by either method. Additionally, the venom decreased serum cholesterol and triglycerides concentrations. However, the venom had no effect on the blood glucose levels of healthy male rats. Pretreatment with the venom did not prevent the induction of diabetes by STZ. These findings suggest that Naja naja oxiana venom exhibits an anti-diabetic effect and could be a potential candidate for effectively controlling diabetes

Antagonistic Effects of Suramin Against the Venom of Snake, Echis Carinatus, on the Circulatory System of Developing Chicken Embryos

Background: The snake, Echis carinatus, one of the most venomous snakes in Asia, possesses a deadly hemotoxic venom. It has been reported that suramin, an anti-trypansomiasis drug, can inhibit the toxic effects of some snake venoms. This study was conducted to evaluate the possible antagonistic effects of suramin against the hemorrhagic activity of the venom from an Iranian snake, Echis carinatus, in developing chicken embryos. Methods: One day old fertile eggs (n=250) were incubated for six days at 37ºC and 60% humidity. Paper discs (5 mm diameter) containing different concentrations of E. carinatus venom (5, 10, 20 & 30 μg) were placed on the chorioallantoic membrane over the major bilateral vein and were left in place until hemorrage occurred and the embryos died. Results: We found the standard hemorrhagic dose (SHD) of E. carinatus venom to be (5 μg/disc). Various concentrations (5, 10 & 20 μg) of suramin were tested against SHD of E. carinatus venom in different protocols. Control experiments were performed with the buffered saline solution, venom and suramin individually. The results demonstrated that suramin at 5, 10 and 20 μg significantly (P<0.05) delayed time to death (717, 521 & 208 min) of embryos poisoned with E. carinatus venom in a dose-dependent manner. Conclusion: Suramin exerted protective and inhibitory effects against the deadly E. carinatus venom, and therefore, may potentially offer future therapeutic applications against poisoning with E. carinatus venom

The effect of temperature on the effects of the phospholipase A₂ neurotoxins β-bungarotoxin and taipoxin at the neuromuscular junction

Snake venom neurotoxins with phospholipase A₂ affect the neuromuscular junction with three distinct phases. There is a transient decrease in twitch height, followed by a facilitatory phase and finally a progressive blockade. It has been suggested that the initial phase is a direct consequence of the binding of the toxins to nerve terminals. This study was designed to determine whether the initial phase is present under conditions that would reduce the enzyme activity of the toxins. At 27 °C, β-bungarotoxin and taipoxin exhibited all three phases, i.e. 5-6 min after exposure to the preparation, twitch height was significantly reduced (P <0.5) to 50 ± 4% and 64 ± 9% of control respectively. This was followed by facilitation and subsequent blockade. However, at 20 °C, neither toxin exhibited the first phase while the second phase, although reduced, clearly occurred and the blocking activity of these toxins always appeared. The data clearly demonstrate that the initial fall is temperature dependent as reducing the temperature from 27 °C to 20 °C blocks the first phase. As the second phase still occurs the toxins must have bound to their target. Therefore, the first phase cannot simply be a toxin binding step

The New Scramble for Faure Sequence Based on Irrational Numbers

This article intends to review quasirandom sequences, especially the Faure sequence to introduce a new version of scrambled of this sequence based on irrational numbers, as follows to prove the success of this version of the random number sequence generator and use it in future calculations. We introduce this scramble of the Faure sequence and show the performance of this sequence in employed numerical codes to obtain successful test integrals. Here, we define a scrambling matrix so that its elements are irrational numbers. In addition, a new form of radical inverse function has been defined, which by combining it with our new matrix, we will have a sequence that not only has a better close uniform distribution than the previous sequences but also is a more accurate and efficient tool in estimating test integrals

The Pro12Ala polymorphism in the PPAR­γ2 gene is not associated with an increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus

Abstract Background The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Several studies have demonstrated a significant association between Pro12Ala polymorphism of the PPAR­γ2 gene and metabolic disorders. Therefore, this study aimed to evaluate the association of Pro12Ala polymorphism with increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus. Methods This cross-sectional study was performed on 145 healthy control subjects and 145 NAFLD patients with a history of type 2 diabetes. Pro12Ala polymorphism genotyping was performed using PCR–restriction fragment length polymorphism (RFLP) technique with the Bs1I restriction enzyme. Results Our results demonstrated that CC and GG genotypes of Pro12Ala were found in the participants, but there was no statistically significant difference between NAFLD patients and healthy controls (P = 0.64 and χ2 = 0.21). Conclusion This study suggests that Pro12Ala polymorphism of the PPAR­γ2 gene cannot be considered as a risk factor for NAFLD in the Iranian population