Responses of some matrix metalloproteinases activities to an acute session of endurance exercise and electrical stimulation in induced myocardial infarction in Wistar rats.

OBJECTIVE: Myocardial infarction is the irreversible cell death of cardiac muscle that takes place after the blood flow is cut off to a specific region of the heart muscle. The molecular angiogenesis process that may follow after the incidence, due to any activity or its intensity, is unknown. The purpose of this research was to examine some of the matrix metalloproteinase (MMP) responses to an acute course of endurance exercise and electrical stimulation in induced myocardial infarcted Wistar rats. MATERIALS AND METHODS: In this experimental case-control study, 40 induced myocardial infarcted Wistar rats (8-week-old, mean weight 130±30 g) were randomly assigned into 4 conditions: endurance exercise, exercise + electrical stimulation, only electrical stimulation, and control group. The infarction was induced 24 hours after the subcutaneous injection of 150 mg/kg of Isoproterenol. The exercise and exercise plus electrical stimulation groups performed a session of endurance exercise on an animal treadmill, at 20 m/min for one hour. The electrical stimulation was delivered by foot shock, set with the intensities of 0.5 mA for 20 minutes. Immediately after the cessation of the treatment protocol, MMP1, MMP2, and MMP9 were measured by the ELISA method. Data analysis was performed by using Two-way ANOVA and significance was set at α = 0.05. RESULTS: One session of endurance exercise or electric stimulation, or their combination, had no significant effect on the level of MMPs. CONCLUSIONS: One session of acute endurance exercise, stimulation, or their combination, elicited no significant effect on the level of MMPs of artificially induced myocardial infarcted Wistar rats.

A unified approach for detection of induced epileptic seizures in rats using ECoG signals.

OBJECTIVE: Epileptic seizure detection is a key step for epilepsy assessment. In this work, using the pentylenetetrazole (PTZ) model, seizures were induced in rats, and ECoG signals in interictal, preictal, ictal, and postictal periods were recorded. The recorded ECoG signals were then analyzed to detect epileptic seizures in the epileptic rats. METHODS: Two different approaches were considered in this work: thresholding and classification. In the thresholding approach, a feature is calculated in consecutive windows, and the resulted index is tracked over time and compared with a threshold. The moment the index crosses the threshold is considered as the moment of seizure onset. In the classification approach, features are extracted from before, during, and after ictal periods and statistically analyzed. Statistical characteristics of some features have a significant difference among these periods, thus resulting in epileptic seizure detection. RESULTS: Several features were examined in the thresholding approach. Nonlinear energy and coastline features were successful in epileptic seizure detection. The best result was achieved by the coastline feature, which led to a mean of a 2-second delay in its correct detections. In the classification approach, the best result was achieved using the fuzzy similarity index that led to Pvalue<0.001. CONCLUSION: This study showed that variance-based features were more appropriate for tracking abrupt changes in ECoG signals. Therefore, these features perform better in seizure onset estimation, whereas nonlinear features or indices, which are based on dynamical systems, can better track the transition of neural system to ictal period. SIGNIFICANCE: This paper presents examination of different features and indices for detection of induced epileptic seizures from rat's ECoG signals.

A new framework based on recurrence quantification analysis for epileptic seizure detection.

This study presents applying recurrence quantification analysis (RQA) on EEG recordings and their subbands: delta, theta, alpha, beta, and gamma for epileptic seizure detection. RQA is adopted since it does not require assumptions about stationarity, length of signal, and noise. The decomposition of the original EEG into its five constituent subbands helps better identification of the dynamical system of EEG signal. This leads to better classification of the database into three groups: Healthy subjects, epileptic subjects during a seizure-free interval (Interictal) and epileptic subjects during a seizure course (Ictal). The proposed algorithm is applied to an epileptic EEG dataset provided by Dr. R. Andrzejak of the Epilepsy Center, University of Bonn, Bonn, Germany. Combination of RQA-based measures of the original signal and its subbands results in an overall accuracy of 98.67% that indicates high accuracy of the proposed method.

Inhibition of Murine Systemic Leishmaniasis by Acetyl Salicylic Acid via Nitric Oxide Immunomodulation.

BACKGROUND: The purpose of this study was to evaluate antileishmanial effects of ASA via NO pathway in Leishmania major infected Balb/c mice. Moreover, toxicity and pathological consequences of ASA administration were investigated. METHODS: Balb/c mice were infected with L. major and ASA was inoculated orally after lesion appearance for its ability to modulate NO and to modify Leishmania infection in host, in order to evaluate the effects of NO production on size and lesion macroscopy, delay of lesion formation and proliferation of amastigotes inside macrophages. Liver, spleen, and lymph nodes were also studied as target organs to detect amastigotes. In addition, plasma was investigated for NO induction using Griess microassay. RESULTS: ASA increased NO production in plasma of both naïve and Leishmania test groups at the ultimate of the experimental period. A decline was observed in proliferation of amastigotes inside macrophages of test group when compared with control one. ASA reduced lesion size, inhibited Leishmania visceralisation in spleen, lymph node, and decreased hepato/splenomegaly in ASA treated animals. CONCLUSIONS: Some antileishmanial effects of ASA by NO-modulation were indicated during systemic leishmaniasis in mice. Despite slight effects on lesion size, ASA decreased parasite visceralization in target organs and declined their proliferation inside macrophages. Therefore, ASA may be indicated to inhibit systemic leishmaniasis via NO pathway in mice model.

Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice.

BACKGROUND AND PURPOSE OF THE STUDY: Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests. METHODS: The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p.) and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures induced by MES (50 mA, 50Hz, 1sec) were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. RESULTS: Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. MAJOR CONCLUSION: The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.

Comparison study on the effect of prenatal administration of high dose and low dose folic acid.

OBJECTIVE: To evaluate the effect of high dose and low dose folic acid on the levels of hemocysteine (Hcy) concentration during the first trimester of pregnancy and at delivery, and to examine the association of Hcy serum levels and preeclampsia. METHODS: In a single blinded randomized clinical trial, which was conducted in Tabriz, Iran, from 2005-2008, 246 nulliparous pregnant women in 2 similar groups, received folic acid daily from early pregnancy until delivery (5 mg/day in group one and 0.5 mg/ day in group 2). The incidence of hypertension and laboratory changes in the levels of serum Hcy, lactate dehydrogenase, and uric acid in addition to the levels of urine creatinine and protein were compared between the groups. RESULTS: There was no presence of any type of hypertension in each group. The systolic blood pressures (BP) (mm Hg) at the first trimester were 114.01 +/- 8.78 for group one, 114.16 +/- 9.05 for group 2, and at delivery, 117.24 +/- 6.91 for group one, and 117.23 +/- 11.48 for group 2 (p=0.32). The diastolic BP at the first trimester were 74.90 +/- 7.45 for group one, 73.30 +/- 8.90 for group 2, and at delivery 76.46 +/- 5.58 for group one, and 76.69 +/- 8.62 for group 2 (p=0.42). Although the level of Hcy (micromol/L) decreased significantly at the delivery time in group one (11.81+/- 3.85 decreased to 6.44 +/- 1.88), and 2 (9.08+/- 3.24, decreased to 7.44 +/- 2.99), this decrement was more significant in the first group (p<0.001). CONCLUSION: The results show that folic acid supplement throughout pregnancy, irrespective of the dosage, could eliminate hypertensive disorders, and decreases serum level of Hcy, although it is reduced more significant in the first group.

Pharmacokinetics, efficacy, and safety of Iminoral compared with Neoral in healthy volunteers and renal transplant recipients.

UNLABELLED: This study sought to evaluate the bioequivalence of Iminoral (test) versus Neoral (reference) in healthy volunteers, as well as safety and efficacy of Iminoral treatment in renal transplant recipients following conversion from Neoral. METHODS: After an overnight fast, 18 healthy volunteers received the assigned treatment (test or reference, 200 mg single dose) in a cross-over fashion with a washout period of 14 days. The blood samples were drawn at various times after drug administration. Cyclosporine blood concentration was measured by high-performance liquid chromatography using an ultraviolet detector. In the second phase of study, stable renal transplant patients who were on Neoral were enrolled in the study in an open-label manner. They were converted from Neoral to Iminoral based on a 1:1 dose equivalence. Cyclosporine trough levels and changes in serum creatinine, lipid profile, electrolytes, and uric acid were measured before and periodically after conversion for 6 months. RESULTS: The 90% confidence interval of the test/reference ratio was within the acceptable limits of 0.8 to 1.25. Relative bioavailability of Iminoral in healthy subjects was 99.0%. There was no significant difference in cyclosporine concentrations and serum creatinines following conversion to Iminoral in renal transplant patients (n=41). There were no reports of major toxicity or of graft rejection and no need for dose adjustment related to Iminoral. CONCLUSIONS: Single doses of Neoral and Iminoral are bioequivalent in healthy subjects. Renal transplant recipients maintained on Neoral can be safely and effectively converted to Iminoral on a 1:1 conversion ratio.

Eugenol depresses synaptic transmission but does not prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices.

Using field potential recording in the CA1 region of the rat hippocampal slices, the effects of eugenol on synaptic transmission and long-term potentiation (LTP) were investigated. Population spikes (PS) were recorded in the stratum pyramidal following stimulation of stratum fibers. To induce LTP, eight episodes of theta pattern primed-bursts (PBs) were delivered. Eugenol decreased the amplitude of PS in a concentration-dependent manner. The effect was fast and completely reversible. Eugenol had no effect on PBs-induced LTP of PS. It is concluded that while eugenol depresses synaptic transmission it does not affect the ability of CA1 synapses for tetanus-induced LTP and plasticity.

Antiepileptogenic and anticonvulsant activity of interleukin-1 beta in amygdala-kindled rats.

Ischaemic, excitotoxic and traumatic brain injuries have been associated with the occurrence of epileptic seizures. Microglia, the principal immune cells in the brain, produce a variety of proinflammatory and cytotoxic factors especially interleukin-1 (IL-1) early after an acute insult. We studied the effect of intracerebroventricularly administered IL-1beta on seizure acquisition and on fully kindled seizures in amygdala kindling model of epilepsy. IL-1beta (0.01 ng/rat) retarded acquisition of kindled behavioral seizures and growth of afterdischarges (AD). IL-1beta (0.01-10 ng/rat) also exhibited significant anticonvulsant effect on established kindled seizures and AD duration. This effect began 0.5 h after administration and was continued up to 72 h. Pretreatment of the kindled animals with nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, or cyclooxygenase inhibitor, piroxicam, reversed the anticonvulsant effect of IL-1beta at early time points. Although most of the previous studies indicate a proconvulsant or convulsant property of IL-1, our results support a protective and antiepileptogenic role of IL-1beta.

The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice: involvement of proinflammatory factors: nitric oxide and prostaglandins.

Central nervous system (CNS) inflammation in cases such as head trauma, infection and stroke has been associated with the occurrence of epileptic seizures. Microglia, the principal immune cells in the brain, readily become activated in response to injury, infection or inflammation. The bacterial endotoxin lipopolysaccharide (LPS) induces the activation of microglia and the production of proinflammatory factors including nitric oxide (NO) and prostaglandins (PGs). We examined the effect of LPS on seizure susceptibility of mice, by using the sensitive test, threshold of clonic seizures induced by i.v. infusion of pentylenetetrazole. LPS decreased the seizure threshold in a dose- and time-dependent manner. Pretreatment of mice with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester or cyclooxygenase inhibitor, piroxicam or the opioid receptor antagonist, (-)-naloxone completely reversed the proconvulsant effect of LPS. These results indicate that NO, PGs and endogenous opioid peptides seem to be involved in LPS-induced decrease in seizure threshold.

Analgesic and anti-inflammatory activity of the leaf essential oil of Laurus nobilis Linn.

The leaf essential oil of Laurus nobilis Linn. (Lauraceae) has been evaluated for antinociceptive and anti-inflammatory activities in mice and rats. The essential oil exhibited: (1) a significant analgesic effect in tail-flick and formalin tests; (2) a dose-dependent anti-inflammatory effect in the formalin-induced edema and (3) a moderate sedative effect at the anti-inflammatory doses. The analgesic and anti-inflammatory effect of the essential oil was comparable to reference analgesics and non-steroid anti-inflammatory drugs: morphine and piroxicam. Present results make the essential oil worthy of further investigations.

Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole- and maximal electroshock-induced seizures.

The leaf essential oil of Laurus nobilis Linn., Lauraceae, which has been used as an antiepileptic remedy in Iranian traditional medicine, was evaluated for anticonvulsant activity against experimental seizures. The essential oil protected mice against tonic convulsions induced by maximal electroshock and especially by pentylenetetrazole. Components responsible for this effect may be methyleugenol, eugenol and pinene present in the essential oil. At anticonvulsant doses, the essential oil produced sedation and motor impairment. This effect seems to be related in part to cineol, eugenol and methyleugenol. Although the essential oil had an acceptable acute toxicity, further studies are required before any absolute conclusions can be drawn.

The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice.

This study investigates anticonvulsant effects of an essential oil of the fruits of Pimpinella anisum (Umbelliferae), a folkloric remedy in the Iranian traditional medicine, against seizures induced by pentylenetetrazole (PTZ) or maximal electroshock (MES) in male mice. The essential oil suppressed tonic convulsions induced by PTZ or MES. It also elevated the threshold of PTZ-induced clonic convulsions in mice. The essential oil produced motor impairment. However, this effect was not observed at the doses and time courses needed for anticonvulsant activity.

Evaluation of the anticonvulsant activity of the essential oil of Eugenia caryophyllata in male mice.

In this study, the effect of an essential oil of Eugenia caryophyllata (Myrtaceae), an antiepileptic remedy in Iranian folk medicine, against seizures induced by maximal electroshock (MES) or pentylenetetrazole (PTZ) in male mice was studied. The essential oil exhibited anticonvulsant activity against tonic seizures induced by MES. Although it was not effective against clonic convulsions induced by intraperitoneal administration of PTZ, the seizure threshold which was determined by an increase in the dose of intravenously infused PTZ required to induce clonus, was elevated by the essential oil. In addition, at some anticonvulsant doses, the essential oil produced motor impairment on the rotarod.