An investigation on cardioprotective potential of Marrubium vulgare aqueous fraction against ischaemia-reperfusion injury in isolated rat heart.

BACKGROUND: The aim of this study was to evaluate the cardioprotective effects of aqueous fraction of Marrubium vulgare hydroalcoholic extract on cardiac parameters in ischaemic-reperfused isolated rat hearts. MATERIALS AND METHODS: The aerial parts of the plant were extracted with methanol 70% by maceration. The water-soluble portion of the total hydroalcoholic extract was prepared with liquid-liquid extraction (LLE). Afterwards, the antioxidant activity, total phenolic and flavonoids content of the aqueous fraction were determined. In order to evaluate the effects of the aqueous fraction on cardiac parameters and ischaemia-reperfusion (I/R) injury, the Langendroff method was used on male Wistar rats. Harvested hearts were cannulated immediately to the Langendroff apparatus and subjected into 30 min regional ischaemia and 2 h reperfusion, either by a modified Krebs-Henseleit buffer (KHB) solution or enriched KHB solution with plant extract (10, 20, 40 µg/mL). RESULTS: The aqueous fraction was found to be a scavenger of DPPH radical with RC50 value of 47 µg/mL. The total phenolic and flavonoids content of the fraction was 6.05 g gallic acid equivalent and 36.13 mg quercetin equivalent per 100 g of dry plant material. In addition, 40 µg/mL of Marrubium vulgare aqueous fraction significantly decreased infarct size in comparison to control group. All doses considerably reduced the total ventricular ectopic beats during 30 min of ischaemia. The extract at dose of 40 µg/mL noticeably decreased the arrhythmias during the first 30 min of reperfusion. CONCLUSIONS: The results of the study indicated aqueous fraction of Marrubium vulgare possesses a protective effect against I/R injuries in isolated rat hearts.

Dietary cholesterol and oxidised cholesterol: effects on sperm characteristics, antioxidant status and hormonal profile in rats.

Present study was designed to compare the potential effects of high serum levels of LDL and oxidised LDL (OxLDL) on spermatogenesis parameters in male Wistar rats. Animals were allocated into three groups and were fed for 14 weeks with normal, cholesterol-rich and oxidised cholesterol-rich diets. Blood lipid profile, sex hormones level, as well as sex organs weight were evaluated. The sex organs weight in oxidised cholesterol-fed group was significantly reduced (P < 0.05). Spermatozoa count in the group with high serum concentration of OxLDL (64 ± 4.2 × 10(6) ) was markedly lower (P < 0.01) than that of normal rats (87 ± 4.1 × 10(6) ) and rats with high serum level of LDL (90 ± 6.3 × 10(6) ). Similarly, the percentage of viable spermatozoa was significantly (P < 0.001) decreased from 78% to 52% by high level of OxLDL in serum. While, nonoxidised LDL did not have suppressive effects on spermatogenesis and organs weight. Consistent with these effects, the serum concentration of sex hormones including FSH (P < 0.001), LH (P < 0.001) and testosterone (P < 0.01) was significantly decreased only in rats with high level of OxLDL but not in rats with high level of nonoxidised LDL. In conclusion, high OxLDL level showed higher destructive effect on reproductive system compared to the high LDL level.

COVID-19 in Multiple Sclerosis: Clinically reported outcomes from the UK Multiple Sclerosis Register.

BACKGROUND: In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). OBJECTIVES: Examine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. METHODS: Anonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyzes compared the first and second 'waves' of the pandemic. RESULTS: Univariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. CONCLUSIONS: Features associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave.

Relationship of pharmacist interaction with patient knowledge of dispensed drugs and patient satisfaction.

A prospective survey of pharmacists' tasks and patients' knowledge and satisfaction was conducted in 35 randomly selected community pharmacies in Tabriz, Islamic Republic of Iran. The total pharmacist interaction received a mean score of 3.05 out of 5. Providing written directions for use attained the highest score of 0.98 out of 1. Patients scored 3.18 out of 5 for knowledge about their medicines. There was a close correlation between patients' knowledge of dispensed drugs and pharmacist interaction (r = 0.95). Mean total prescription filling time was 7.6 min, but only 1.4 min was spent on pharmacist-patient counselling. The interaction between pharmacist and patient increases patients' knowledge about dispensed medicines and their satisfaction with the pharmacist's activities.

Effect of interactive group discussion among physicians to promote rational prescribing.

This study assessed the effect of an educational intervention (interactive group discussion) on the prescribing behaviour of 51 general physicians from the north-west of Tabriz. Prescriptions were analysed pre-intervention and post-intervention (control and intervention groups) using a proforma with 8 indicators of correct prescribing. The mean number of drugs per prescription pre-intervention was 3.82. The percentage of prescriptions with antibiotics, corticosteroids and injections were 40.8%, 25.9% and 58.0%, respectively. Following the intervention there were slight but not significant changes in the indicators in both intervention and control groups compared with pre-intervention results.

Evidence that iron overload plus croton oil induce skin tumours in mice.

Iron overload is known to occur due to different factors including genetic disorders. It has been shown that iron overload predisposes humans to an increased risk of cancer. However, the mechanism by which iron overload enhances chemically induced carcinogenesis is not known. In this report, for the first time it is shown that iron overload acts as a tumour initiator. Female albino Swiss mice were given iron dextran 1 mg/mouse per day intramuscularly for 15 days and croton oil 0.5 mg in 200 microL acetone/mouse topically twice a week for 30 weeks. During this period, the animals were observed for tumour incidence. There were significantly higher yields of tumours in those animals receiving both iron and croton oil. However, the group of animals treated only with acetone, iron, croton oil and 7,12-dimethylbenz(a)anthracene (DMBA) alone did not develop any tumours during 30 weeks of observation. Further, croton oil-mediated induction in cutaneous lipid peroxidation (LPO) level was higher in the iron-overload group. The results of this study suggest that oxidative stress generated by iron overload is responsible for croton oil-mediated skin carcinogenesis.

Investigation of the memory impairment in rats fed with oxidized-cholesterol-rich diet employing passive avoidance test.

BACKGROUND: Recent studies have shown that hypercholesterolemia, besides being a risk factor for cardiovascular diseases, has also toxic effects on central nervous system. The design of the present study was to investigate the effects of dietary cholesterol and oxidized cholesterol on cognitive function. METHODS: Male Wistar rats were randomly divided into 3 groups. The animals were fed with three normal, 2% cholesterol-rich, and 2% oxidized cholesterol-rich diets for 14 weeks. Memory impairment was analyzed by passive avoidance test. Coenzyme Q10 content was also measured by a validate RP-HPLC method. Besides, lipid peroxidation in serum and brain tissue was determined by malondialdehyde concentration measurement. RESULTS: The results showed that feeding rats with high oxidized cholesterol diet for 14 weeks significantly impaired the cognitive function compared to the normal (P<0.001) and high cholesterol-fed groups (P<0.01). The memory impairment was positively correlated to the serum level of the oxidized LDL; it was significantly associated with the increased malondialdehyde concentration on the brain tissue of both groups (P<0.05 and P<0.001, respectively). The total antioxidant level in the serum was also decreased in rats fed with the oxidized cholesterol (P<0.05). Moreover, the brain coenzyme Q10 content was significantly declined in the animals fed with the oxidized cholesterol-rich diet compared to the animals fed with the normal (P<0.01) and cholesterol-rich diets (P<0.05). CONCLUSION: The results suggested that the high dietary intake of the oxidized-cholesterol might impair the memory that could be correlated to the oxidative stress and declined the coenzyme Q10 content of the brain tissue.

Potent anti-inflammatory activities of hydroalcoholic extract from aerial parts of Stachys inflata on rats.

Extracts obtained from aerial parts of Stachys inflata have been used in Iranian folk medicine in infective, rheumatic and other inflammatory disorders. In the present study, the anti-inflammatory properties of total methanol extract isolated from aerial parts of Stachys inflata were investigated in two well-characterised inflammatory models in rats, carrageenan-induced paw oedema and formalin-induced paw licking. Intraperitoneal injection of the extract, 60 min before induction of inflammation, revealed a dose-related inhibition of carrageenan-induced rat paw oedema over the dose range 50-200 mg/kg. In the formalin test, the extract (50, 100 and 200 mg/kg) had no effect against the first phase (0-5 min) of the formalin-induced pain, but all three doses produced a significant blockade of the second phase (P < 0.001). Myeloperoxidase (MPO) activity was determined, and a histopathological study was carried out in paw tissue 4 h after induction of inflammation. The hydroalcoholic extract (200 mg/kg) substantially reduced MPO activity (P < 0.05), which was increased in the control group. Histological examination showed a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with the extract (200 mg/kg).

CoQ10 and L-carnitine attenuate the effect of high LDL and oxidized LDL on spermatogenesis in male rats.

BACKGROUND: It is estimated that one-third of infertility cases are due to male factors. Hyper-cholesterolemia is a social problem in many developed countries and contributed with a heterogeneous group of disorders characterized by an excess of cholesterol and its derivatives in the blood stream. PURPOSE: The objective of the present study was to investigate the protective effects of coenzyme Q10 and L-Carnitine supplementation on semen parameters, sperm function and reproductive hormone profiles in male Wistar rats with high LDL and Oxidized LDL (OxLDL) blood levels. METHODS: Animals were fed with cholesterol and oxidized cholesterol-rich diets for 14 weeks to elevate the LDL and OxLDL blood level, respectively. Pretreatment with coenzyme Q10 (10 mg/kg/day, oral) and L-Carnitine (350 mg/kg/day, oral) were conducted for 5 consecutive weeks. Sex hormones levels, malondialdehyde and total antioxidant concentrations, as well as testis, epididymis and seminal vesicle weight were also analyzed. RESULTS: Following high LDL and OxLDL blood levels, decrease in the sperms count and viability, weights of testis, epididymis and seminal vesicle as well as concentration of testosterone and LH hormone were observed. On the other hand, in contrast to reduction of total antioxidant level, malondialdehyde concentration, both in serum and testis, was increased. However, pretreatment with L-carnitine and coenzyme Q10 increased serum sex hormones level and improved semen parameters significantly. CONCLUSION: Overall, pretreatment with coenzyme Q10 and L-Carnitine attenuated the destructive effects of high LDL and oxidized LDL levels on spermatogenesis parameters in male rats.

Reduction of coenzyme q10 content: a possible effect of isoproterenol on heart failure and myocardial infarction in rat.

Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of myocardium and subsequent effects on lipid peroxidation, electrocardiogram pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100 mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days, respectively. The effects of ISO on myocardium CoQ10 content, concentration of malondialdehyde, ECG pattern and hemodynamic parameters of heart were analyzed.ISO-treated rats showed significant alteration in heart hemodynamic parameters such as reduction of left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, besides increase of left ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content (from 4.57 and 4.55 µg/100 mg tissue in control groups to 2.85 and 2.89 µg/100 mg tissue in ISO-induced HF and MI groups respectively) and increase in tissue levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and MI groups, respectively) were also observed in ISO-treated animals compared with the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups, respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters and ECG pattern in ISO-induced HF and myocardial injury.The present findings have demonstrated that the cardiotoxic effects of ISO such as oxidative damage and hemodynamic declination might be related to depletion of CoQ10 concentration.

Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by isoproterenol in male rats.

Nowadays, cardiovascular diseases and male infertility are two big health problems in industrial countries.The aim of the present study was to investigate the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100 mg/kg) in ISO treated groups. Before ISO administration, pretreatment with Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20 consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant concentration as well as testis, epididymis and seminal vesicle weight were investigated.Increase in the concentration of MDA and decrease in total antioxidant level was observed following ISO administration. Accordingly, the sperm viability as well as testis, epididymis and seminal vesicle weights were decreased. In the case of sex hormones, the testosterone and LH levels were decreased and the concentration of FSH was increased. Pretreatment with L-carnitine and Coenzyme Q10 significantly decreased the MDA level and increased total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and Coenzyme Q10 also improved semen parameters and organs weight which were impaired by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect spermatogenesis in male rats with ISO administration.

Atorvastatin reduces the myocardial content of coenzyme Q10 in isoproterenol-induced heart failure in rats.

The present study was aimed to study the effects of different doses of atorvastatin on Co Q10 content in the myocardium tissue in rats. A subcutaneous injection of isoproterenol (5 mg/kg/day) for 10 days was used for the induction of heart failure. Rats were randomly assigned to control, treatment with atorvastatin (5, 10, 20 mg/kg/day) and treatment with atorvastatin plus coenzyme Q10 (10 mg/kg/day). Coenzyme Q10 content of myocardium was measured using HPLC method with UV detector after hemodynamic parameters measurements. The malondialdehyde (MDA) content of the myocardium was evaluated in order to determine coenzyme Q10 antioxidative effect. A high dose of atorvastatin (20 mg/kg/day) was significantly reduced the myocardium content of coenzyme Q10 as compared with isoproterenol treated group (p<0.001). Compared with atorvastatin alone treated animals, co-administration of coenzyme Q10 with atorvastatin was improved the level of coenzyme Q10 in the myocardium (p<0.05, p<0.001). Increasing the dose of atorvastatin also led to increase in MDA content of the myocardium (p<0.01). Serum lipid profile showed no changes in atorvastatin treated groups. The results of this study demonstrate that high doses of atorvastatin reduce coenzyme Q10 content of the myocardium and increase lipid peroxidation in myocardium which is reversed by coenzyme Q10 co-administration.

Effects of LDL and oxidized LDL on cardiac function in isoproterenol-induced myocardial infarction in rat.

Notable discussions have been developed over the distinctive effects of LDL and oxidized LDL (OxLDL) on myocardial functions. The aim of the present study was to investigate the effects of OxLDL on electrocardiogram and hemodynamic parameters of rat's heart in isoproterenol (ISO)-induced myocardial infarction (MI) model.Male Wistar rats were allocated in to 6 groups and receive one of the 3 formulated diets (standard, cholesterol-rich and oxidized cholesterol-rich diets). After 14 weeks to induce MI, rats in 3 groups were received ISO (100 mg/kg) for 2 consecutive days subcutaneously. Lipid profiles, electrocardiogram patterns and hemodynamic parameters of all groups were investigated.Serum levels of LDL, cholesterol and triglycerides were significantly higher in the fat-rich diet fed groups compared to control group (P<0.001). The ISO-treated rats showed a marked reduction in the R-amplitude, R-R interval, LVSP, left ventricular contractility (LVdP/dtmax) and relaxation (LVdP/dtmin) as well as severe elevation in ST-segment and LVEDP value compared to the respective normal rats. High serum level of OxLDL resulted in significant exacerbation in the destructive effects of ISO on R-amplitude, R-R interval, LVSP, left ventricular contractility (LVdP/dtmax), relaxation (LVdP/dtmin), ST-segment and LVEDP values. Additionally, heart to body weight ratio as an index of myocardial edematous was also increased significantly. However, changes in these parameters in rats fed with cholesterol-rich diet were not significant.Generally, results indicated that the effects of high OxLDL level on electrocardiogram and hemodynamic parameter after MI was more reliable than effects of high LDL level.

Antiarrhythmic and arrhythmogenic effects of L-carnitine in ischemia and reperfusion.

Isolated rat hearts were subjected to 30-min coronary artery occlusion followed by 120-min reperfusion. The hearts (n=8-12) were perfused with Krebs-Henseleit solution enriched with L-carnitine (0.5, 2.5 and 5 mM) for 10 min before and after ischemia or reperfusion and for the whole period of ischemia and reperfusion. Two-hour perfusion with L-carnitine during ischemia/reperfusion markedly (p<0.05) and dose-dependently decreased the incidence of ventricular tachycardia (VT, maximum 65%). The incidence of reperfusion ventricular fibrillation (VF) also decreased from 63% (control) to 17% in hearts perfused with 5 mM L-carnitine, as reflected by a significant (p<0.05) decline in VF duration from 218+/-99 sec in control to 19+/-19 sec. Perfusion of etomoxir (palmitoylcarnitinetransferase-1 inhibitor) along with L-carnitine reversed the antiarrhythmogenic action of L-carnitine. Interestingly, short time preischemic administration of L-carnitine produced a concentration-dependent arrhythmogenic effects on both ischemia and reperfusion-induced arrhythmias. These results show that L-carnitine produced a protective effect against reperfusion arrhythmias only when it was perfused for the whole period of the experiment. This protective action was reversed by concomitant use of etomoxir, suggesting that the efficacy of L-carnitine is due to its mitochondrial action but cannot be solely attributed to increased fatty acid oxidation.

Effects of extracts from flowering tops of Crataegus meyeri A. Pojark. on ischaemic arrhythmias in anaesthetized rats.

Different species of Crataegus, commonly called Hawthorn, were reported to possess wide pharmacological effects on the cardiovascular system. In the present study, chloroform, ethylacetate and methanol (70%) extracts of the flowering tops of Crataegus meyeri A. Pojark. were studied. The extracts were tested on the incidence and severity of arrhythmias induced by a period of myocardial ischaemia in open-chest anaesthetized male Wistar rats. Infusion of a hydroalcohol extract (1 mg/kg/min) resulted in a significant decrease in the total number of ventricular ectopic beats (from 1494 +/- 362 in the control to 634 +/- 102), mainly by reduction of beats occurring as ventricular tachycardia. A chloroform extract (1 mg/kg/min) also reduced the total number of ventricular ectopic beats but this reduction was due to the decrease of single extrasystoles. A significant reduction in the time spent for ventricular fibrillation was seen by the hydroalcohol and ethylacetate extracts. There were no significant changes in the heart rate and blood pressure during the extract infusion. However, bolus injection of all the extracts caused a significant reduction in the blood pressure. Thus, the extracts of Crataegus meyeri have a hypotensive and a potential antiarrhythmic action on ischaemic myocardium and may possess active principles.

Effects of endothelin-1 and the ETA-receptor antagonist, BQ123, on ischemic arrhythmias in anesthetized rats.

The effects of intravenous (i.v.) infusions of exogenous endothelin-1 (ET-1, 0.05 and 0.1 nmol/kg/min) on incidence and severity of ventricular arrhythmias during 30-min period of acute myocardial ischemia were assessed in anesthetized rats. We examined the role of ETA-receptors in the proarrhythmic effects of both exogenous and endogenous ET using the ETA-receptor antagonist, BQ123. Exogenous ET-1 increased the severity and incidence of ischemic arrhythmias dose dependently. Both doses increased the total incidence of ventricular fibrillation (VF: from 30% in controls to 100 and 88% in rats given 0.05 and 0.1 nmol/kg/min ET-1, respectively); the higher dose also increased total arrhythmia count and duration of ventricular tachycardia (VT). BQ123 (10 micrograms/kg/min) completely abolished this proarrhythmic effect of exogenous ET-1. To assess the role of endogenous ET-1 in the genesis of ischemic arrhythmias, we studied the effects of a range of doses of BQ123 (5-100 micrograms/kg/min) on ischemic arrhythmias. Only one dose of BQ123 (10 micrograms/kg/min) attenuated arrhythmias by reducing total ventricular ectopic count (from 1,423 +/- 112 in controls to 677 +/- 159). The highest dose of BQ123 tested (100 micrograms/kg/min) increased arrhythmias by significantly increasing the incidence of irreversible VF (from 25 to 75%). These results suggest that exogenous ET-1 can aggravate ischemia-induced arrhythmias, an effect that is sensitive to ETA-receptor blockade. However, although endogenous ET-1 may make some contribution to the genesis of arrhythmias resulting from coronary occlusion through an action at ETA receptors, the observed proarrhythmic effect of BQ123 at high doses suggests that this may unmask an effect of ET-1 at other receptors.

Modulation of kinin outflow from isolated perfused rat hearts by endothelin-1.

Bradykinin has previously been shown to suppress ET-1 secretion by endothelial cells. In the present study, rat isolated hearts have been perfused with Krebs solution using the Langendorff method. Immunoreactive bradykinin (IRBK) was measured in the perfusate and the basal level was found to be constant for up to 3 h. Ten min perfusions of the hearts with ET-1 at concentrations of 0.2-20 pM produced a dose-related suppression of kinin outflow by over 90% (P < 0.05). At these concentrations ET-1 had no detectable effect on the coronary vasculature or ECG. At 200 pM ET-1 and above, the hearts showed arrhythmias of increasing severity, accompanied at the highest doses by marked coronary constriction and an increase in IRBK outflow.

Enhancement of dissolution rate and anti-inflammatory effects of piroxicam using solvent deposition technique.

Piroxicam solid depositions were prepared by means of the solvent deposition technique using different concentrations of microcrystalline cellulose as carrier material. The solvent deposition system (SDS) with drug to carrier ratio of 1:9 had a rapid dissolution rate in vitro. When this SDS was administered perorally to rats with a previous experimentally induced inflammation in their paws, it exhibited a pronounced anti-inflammatory action. X-ray diffraction and infrared (IR) spectroscopy showed no differences in the crystal state of piroxicam in SDS formulation and physical mixture of piroxicam and carrier. The increase in the dissolution rate and consequent enhancement of anti-inflammatory effect of piroxicam in SDS were attributed to the reduced particle size of drug deposited on the carrier and enhanced wettability of the particles brought about by the carrier.