Artemisia campestris leaf extract alleviates early diabetic nephropathy in rats by inhibiting protein oxidation and nitric oxide end products

Chronic hyperglycemia in diabetes leads to free radicals overproduction, which contributes to the development of diabetic nephropathy. The present study investigated the effects of Artemisia campestris (Ac), a plant of the Asteraceae family, on renal impairment and oxidative stress in alloxan-induced diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg kg(-1)) in rats. Ac (200 mg kg(-1)) was administered to diabetic rats for 3 weeks. Diabetic renal injury was associated with hyperglycemia, increased serum creatinine, urea and uric acid levels. This nephropathophysiology was associated with a surproduction of nitric oxide (NO), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels and a decrease in glutathione (GSH) levels. In addition, hyperglycemia increased the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the kidney of diabetic rats. Treatment with Ac effectively ameliorated diabetic renal dysfunction by reducing oxidative and nitrosative stress. Histological studies also supported the experimental findings. The results suggested that Ac might act as a beneficial agent against renal dysfunctions developed in alloxan-induced diabetes.     

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

Background

Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology.

Objective

To verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimer's disease.

Method

This work was conducted as a case–control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls.

Result

Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p = 0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p < 10⁻³). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD.

Conclusion

The MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.     

Acute renal failure in patients over 80 years old: 25-years' experience

Objective: To determine the epidemiological trends, spectrum of etiologies, morbidity and mortality of acute renal failure (ARF) in patients over 80 years old.¶Design: Historical cohort analysis.¶Setting: Intensive care unit (ICU) of nephrology, Tenon Hospital, Paris.¶Patients and participants: The criteria of inclusion was ARF, defined on the basis of a creatinine value over 120 μmol/l, in patients over 80 years of age admitted between October 1971 and September 1996. When moderate chronic nephropathy was pre-existing, ARF was defined by the increase of at least 50 % over the basal creatininemia.¶Measurements and results: Three hundred and eighty-one patients over 80 years of age were included. The etiology and mechanism of ARF are detailed. 29 % of the patients received dialysis. Global mortality at the hospital was 40 %. Factors significantly associated with a poor prognosis are identified. Mean survival after hospitalization was 19 months.¶Conclusion: The frequency of admission to ICUs for ARF in patients older than 80 years seems to be on the increase. Mortality is less severe than expected. These patients could benefit from the renal replacement therapy of modern intensive care medicine.     

Smoking in Casablanca hospitals: knowledge,attitudes and practices

This cross sectional study took place with a self administered questionnaire between June and September 1999 and involved 1,388 subjects of whom 62.4% were men and 37.6% women. The total prevalence of smoking was 14.9%, ranging from 12.5% in paramedical staff to 15.5% in manual workers, 16.2% in doctors, 17.1% in laboratory staff, and 22.2% in administrators. The prevalence was 35.9% among men as against 2.2% among women. The study of smokers showed that 51.5% had started before the age of 21. The most common motive for starting smoking was "pleasure". Among the 45.5% who smoked at the workplace 60.5% felt concerned about it. Evaluation of the degree of nicotine dependence using the Fagerstrom score found high dependence in 21.3% of subjects. Only 24.5% of doctors warned patients against smoking in the absence of smoking related diseases or symptoms. In more than 75% of cases doctors advised against smoking in the workplace and in the home. 66.8% of staff were aware of the anti-smoking law but the legislative measures were poorly understood. Only 9% of those interviewed had taken part in an anti-smoking campaign. In conclusion, the prevalence of smoking in the hospitals of Casablanca has definitely diminished in the past 10 years but it remains relatively high in men. Hospital staff should be more involved in the fight against smoking.     

Postpartum cardiomyopathy revealed by acute lower limb ischemia

Peripartum cardiomyopathy is an uncommon disease defined as a dilated cardiomyopathy during puerperium, with left ventricular dysfunction (ejection fraction < 45%) without any other etiology. The etiology of this disease remains uncertain and it can be revealed in a variety of ways. Thrombo-embolic complications may be, although infrequently, the initial manifestation of peripartum cardiomyopathy, which is usually an intracardiac thrombosis. Lower extremity embolism is uncommon. The case reported is about a 39-year-old woman, multiparous, who presented, 40 days after delivery, a global heart failure with atrial fibrillation, revealed by left lower extremity thromboembolism. After echocardiographic and etiologic examinations, the diagnosis was established as peripartum cardiomyopathy. It evolved favourably after 2 months of medical treatment: the symptoms and cardiomegaly decreased, left ventricular systolic function was improved.     

Methods to study the phytochemistry and bioactivity of essential oils

Many essential oils are extracted, analysed and their main components are identified, characterised and then published without any biological testing whatsoever. Their useful biological activities can remain unknown for years. Yet, the search for these activities often increases our knowledge of the potential use of oils in therapeutics. Therefore, there is a real need for a simple, reliable and reproducible methods to study the bioactivity of essential oils and their constituents which can detect a broad spectrum of action or specific pharmacological activities in aromatic plants. These methods can then be employed by natural product chemists, pharmacologists and biologists to conduct their scientific research and to valorize natural products. Standardisation of some of these methods is therefore desirable to permit more comprehensive evaluation of plant oils, and greater comparability of the results obtained by different investigators.     

Pressor responsiveness to intravenous quinpirole is blunted in malnourished, conscious rats: central vs. peripheral and spinal mechanisms

In conscious rats, intravenous treatment with the dopamine D2-like receptor agonist quinpirole, elicited a pressor effect, which is attributed to central dopamine D2 receptor-mediated activation of sympathetic outflow associated with arginine vasopressin release. This prominent central effect is opposed to peripheral sympathoinhibitory and spinal depressor effects. The present study investigated the effects of pre- and postnatal undernutrition on the central pressor responsiveness to quinpirole. Malnourished (MalN) rats were obtained by feeding dams a multideficient diet (providing 8% protein) during pregnancy and nursing. At 90 days of age, MalN rats weighed significantly less than control (CNT) rats born to dams fed standard commercially diet (23% protein) during pregnancy and nursing. Baseline mean arterial pressure and heart rate in MalN rats were comparable to those of CNT. Intravenous treatment with quinpirole (0.3 mg/kg) in MalN conscious rats induced a pressor effect, which was significantly reduced in both magnitude and duration, when compared with CNT rats. In both groups studied, pressor response to quinpirole was fully abolished by the peripheral and central dopamine D2 receptor antagonist, metoclopramide (5 mg/kg, i.v.) whereas was significantly enhanced after pretreatment with either intravenous (0.5 mg/kg) or intrathecal (40 microg per rat at T9-T10 level) domperidone, a dopamine D2 receptor antagonist that does not cross the blood-brain barrier. However, even under peripheral and spinal dopamine D2 receptor blockade, maximum pressor effect of quinpirole remained significantly reduced in MalN when compared with CNT rats. Neither the maximum pressor nor the bradycardiac responses to intravenous phenylephrine or arginine vasopressin differed between CNT and MalN rats. This study shows that undernutrition imposed during fetal life and suckling blunted the pressor response to quinpirole in conscious rats. This blunted response appears mainly related to desensitization of brain dopamine D2 receptors rather than enhanced peripheral and/or spinal dopamine D2 receptor-mediated depressor effect or vascular hyporesponsiveness to alpha1-adrenoceptor and vasopressin receptor stimulation.     

Cardiovascular effects of the essential oil of Aniba canelilla bark in normotensive rats

Cardiovascular effects of intravenous (i.v.) treatment with the essential oil of the bark of Aniba canelilla (EOAC) were investigated in normotensive rats. In both pentobarbital-anesthetized and conscious rats, i.v. bolus injections of EOAC (1 to 20 mg/kg) elicited similar and dose-dependent hypotension and bradycardia. Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardia without affecting the hypotension. In conscious rats, pretreatment with hexamethonium (30 mg/kg, i.v.) significantly reduced the EOAC-induced bradycardia without affecting the hypotension. The opposite effect was observed after i.v. pretreatment with the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl esther (L-NAME, 20 mg/kg). However, both EOAC-induced hypotension and bradycardia were significantly reduced by pretreatment with methylatropine (1 mg/kg, i.v.). In rat endothelium-containing aorta preparations, EOAC (1-600 microg/mL) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction [IC50 (geometric mean+/-95% confidence interval)=64.5 (45.6-91.2) microg/mL)], an effect that was significantly reduced by the addition of atropine (10 microM) in the perfusion medium [IC50=109.5 (72.5-165.4) microg/mL)]. Furthermore, the vasorelaxant effects of the EOAC were also but significantly reduced [IC50=139.1 (105.2-183.9) microg/mL)] by removal of the vascular endothelium. Furthermore, the CaCl2-induced contractions in calcium-free medium were reduced and even fully abolished by EOAC (100 and 600 microg/mL), respectively. However, EOAC (600 microg/mL) was without significant effect on caffeine-induced contractions in calcium-free medium. These data show that i.v. treatment of rats with EOAC induces dose-dependent hypotension and bradycardia, which occurred independently. The bradycardia appears mainly dependent upon the presence of an operational and functional parasympathetic drive to the heart. However, the hypotension is due to an active vascular relaxation rather than withdrawal of sympathetic tone. This relaxation seems partly mediated by an endothelial L-arginine/nitric oxide pathway through peripheral muscarinic receptor activation (endothelium-dependent relaxation) and predominantly through an inhibition of calcium inward current (endothelium-independent relaxation).     

Vasorelaxation induced by methyl cinnamate,the major constituent of the essential oil of Ocimum micranthum,in rat isolated aorta

The aim of the present study was to investigate the vascular effects of the E‐isomer of methyl cinnamate (E‐MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1–3000 μmol/L, E‐MC concentration‐dependently relaxed endothelium‐intact aortic preparations that had been precontracted with phenylephrine (PHE; 1 μmol/L), with an IC₅₀ value (geometric mean) of 877.6 μmol/L (95% confidence interval (CI) 784.1–982.2 μmol/L). These vasorelaxant effects of E‐MC remained unchanged after removal of the vascular endothelium (IC₅₀ 725.5 μmol/L; 95% CI 546.4–963.6 μmol/L) and pretreatment with 100 μmol/L N^G‐nitro‐l ‐arginine methyl ester (IC₅₀ 749.0 μmol/L; 95% CI 557.8–1005.7 μmol/L) or 10 μmol/L 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (IC₅₀ 837.2 μmol/L; 95% CI 511.4–1370.5 μmol/L). Over the concentration range 1–3000 μmol/L, E‐MC relaxed K⁺‐induced contractions in mesenteric artery preparations (IC₅₀ 314.5 μmol/L; 95% CI 141.9–697.0 μmol/L) with greater potency than in aortic preparations (IC₅₀ 1144.7 μmol/L; 95% CI 823.2–1591.9 μmol/L). In the presence of a saturating contractile concentration of K⁺ (150 mmol/L) in Ca²⁺‐containing medium combined with 3 μmol/L PHE, 1000 μmol/L E‐MC only partially reversed the contractile response. In contrast, under similar conditions, E‐MC nearly fully relaxed PHE‐induced contractions in aortic rings in a Ba²⁺‐containing medium. In preparations that were maintained under Ca²⁺‐free conditions, 600 and 1000 μmol/L E‐MC significantly reduced the contractions induced by exogenous Ca²⁺ or Ba²⁺ in KCl‐precontracted preparations, but not in PHE‐precontracted preparations (in the presence of 1 μmol/L verapamil). In addition, E‐MC (1–3000 μmol/L) concentration‐dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E‐MC‐induced endothelium‐independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca²⁺ influx through voltage‐dependent Ca²⁺ channels. However, the involvement of a myogenic mechanism in the effects of E‐MC is also possible.     

Antioxidant effect of vitamin E and selenium on hepatotoxicity induced by dimethoate in female adult rats

Acute exposure to pesticides can cause hepatotoxicity. Our study pertains to the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate oxidative stress induced by dimethoate. Female Wistar rats were randomly divided into seven groups of six each: group I served as controls; group II received in their drinking water dimethoate (2 g L⁻¹); group III received both dimethoate and selenium (0.5 mg/kg of diet); group IV was treated with dimethoate and vitamin E (100 mg/kg of diet); group V received dimethoate+selenium+vitamin E and groups VI and VII received either selenium or vitamin E. The exposure of rats to dimethoate for 30 days promoted oxidative stress with an increase in malondialdehyde and a decrease in glutathione and non-protein thiol levels. A decrease in glutathione peroxidase, superoxide dismutase and catalase activities was also observed. While, plasma transaminases, lactate dehydrogenase activities and bilirubin levels increased. Co-administration of selenium and/or vitamin E through diet improved the biochemical parameters cited above. Liver histological studies confirmed biochemical parameters and the beneficial roles of selenium and vitamin E.