Relevance of the genetic polymorphism of NOD1 in Chlamydia pneumoniae seropositive stroke patients

Background and purpose:  Chronic infections with certain pathogens, such as Chlamydia pneumoniae , and genetic parameters that influence inflammatory reactions have been suggested to contribute to ischaemic stroke. NOD1 is a potent cytosolic receptor for C. pneumoniae. The aim of this study was to investigate the genetic polymorphism of NOD1 from the aspect of the development of stroke.
Materials and methods:  A total of 280 patients with ischaemic stroke were enrolled in the study; 150 healthy blood donors served as controls. The G796A (E266K) NOD1 polymorphism was determined by restriction fragment length polymorphism. Chlamydia pneumoniae seropositivity was tested by ELISA.
Results:  There was a significant difference in NOD1 G796A genotype distribution between the controls and the stroke patients with C. pneumoniae seropositivity. The AA homozygote and GA heterozygote mutant variants were detected in 16% (25 of 152) and in 50% (77 of 152) of the C. pneumoniae- positive stroke patients, as compared with 8% (6 of 84), and 28% (24 of 84), respectively, in the C. pneumoniae- positive healthy controls. (OR = 2.559; 95% CI = 1.105–6.517, P  = 0.04 and OR = 2.567; 95% CI = 1.451–4.540 P  < 0.001, respectively). The stroke patients with the large vessel pathology exhibited the highest frequency of the mutant allele A (51%). In contrast, amongst the C. pneumoniae- negative subjects, no difference in genotype frequency was observed between the stroke patients and the controls.
Conclusion:  Polymorphism in NOD1 G796A alone did not prove to be a risk factor for stroke in general, but in association with C. pneumoniae infection it appeared to be accompanied by an increased risk of the development of stroke.     

Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids

The aim of our study was to investigate the adaptation of the hypothalamic circulation to chronic nitric oxide (NO) deficiency in rats. Hypothalamic blood flow (HBF) remained unaltered during chronic oral administration of the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 1 mg/ml drinking water) although acute NOS blockade by intravenous l-NAME injection (50 mg/kg) induced a dramatic HBF decrease. In chronically NOS blocked animals, however, acute l-NAME administration failed to influence the HBF. Reversal of chronic NOS blockade by intravenous l-arginine infusion evoked significant hypothalamic hyperemia suggesting the appearance of a compensatory vasodilator mechanism in the absence of NO. In order to clarify the potential involvement of vasodilator prostanoids in this adaptation, cyclooxygenase (COX) mRNA and protein levels were determined in the hypothalamus, but none of the known isoenzymes (COX-1, COX-2, COX-3) showed upregulation after chronic NOS blockade. Furthermore, levels of vasodilator prostanoid (PGI(2), PGE(2) and PGD(2)) metabolites were also not elevated. Interestingly, however, hypothalamic levels of vasoconstrictor prostanoids (TXA(2) and PGF(2alpha)) decreased after chronic NOS blockade. COX inhibition by indomethacin but not by diclofenac decreased the HBF in control animals. However, neither indomethacin nor diclofenac induced an altered HBF-response after chronic l-NAME treatment. Although urinary excretion of PGI(2) and PGE(2) metabolites markedly increased during chronic NOS blockade, indicating COX activation in the systemic circulation, we conclude that the adaptation of the hypothalamic circulation to the reduction of NO synthesis is independent of vasodilator prostanoids. Reduced release of vasoconstrictor prostanoids, however, may contribute to the normalization of HBF after chronic loss of NO.     

A new self-expanding nitinol stent (Enterprise) for the treatment of wide-necked intracranial aneurysms: initial clinical and angiographic results in 31 aneurysms

Introduction We report the results of a prospective clinical study using a new self-expanding nitinol stent (Enterprise) designed for the treatment of wide-necked intracranial aneurysms. Methods We treated 31 saccular, wide-necked intracranial aneurysms in 30 patients. Ten aneurysms had recanalized after prior endovascular treatment without a stent, and 21 aneurysms had not been treated before. Results Stent deployment was successful in all procedures. Additional coil embolization was performed in all aneurysms. Initial complete angiographic occlusion was achieved in 6 aneurysms, a neck remnant was left in 18 aneurysms and there were 7 residual aneurysms. Angiographic follow-up examinations of 30 lesions after 6 months demonstrated 15 complete occlusions, 8 neck remnants and 7 residual aneurysms. One patient refused the 6-month angiographic follow-up. Spontaneous occlusion of the aneurysm had occurred in 14 patients, and 6 aneurysms showed recanalization. Four of these residual aneurysms were retreated. At the 6-month follow-up, 29 parent arteries were unaffected, whereas two parent vessels demonstrated minor asymptomatic narrowing at the stent site. Two patients experienced one or more possible or probable device-related serious adverse events during the 6-month follow-up period. There was no procedural morbidity or mortality at 6 months after the procedure. Conclusion The reported results demonstrated the safety and feasibility of the Cordis Neurovascular Enterprise stent in the treatment of wide-necked intracranial aneurysms. Initial clinical and angiographic results are favorable. Werner Weber and Martin Bendszus contributed equally to this work.     

Quality of life in seizure-free patients with epilepsy on monotherapy

Epilepsy is a multifaceted chronic disorder which has diverse and complex effects on the well-being of the patient. Although it is evident that seizure type and frequency play a critical role in the quality of life (QOL) of patients with epilepsy, it is less clear what the major determinants are that influence QOL in seizure-free patients receiving monotherapy. The aim of this study was to evaluate demographic, clinical, and socioeconomic factors influencing the QOL of seizure-free patients receiving monotherapy. All participants were patients from four medical centers who had epilepsy, were on monotherapy, and had been seizure-free for at least 1 year. Responders completed three questionnaires on demographic and clinical information, QOL, and antiepileptic drug (AED) side effects during routine follow-up visits in the epilepsy clinics. We present the data of 103 patients: 59 females (57.3%), mean age 37.75+/-13.66 years. Treatment side effects and unemployment (p<0.0001, p=0.037, respectively) were significant predictors for poor overall QOL, whereas age, gender, education, family status, comorbidity, seizure type, age of seizure onset, and epilepsy duration did not significantly affect overall QOL. There was no significant difference in side effects and QOL between patients receiving older versus newer AEDs. Ninety-four (92.2%) patients reported experiencing at least one side effect of AEDs when queried about specific symptoms, while only 11 (10.7%) patients replied affirmatively when asked whether they experienced "any" side effects. The most common side effects involved the central nervous system. In conclusion, this study reveals that the most significant factor influencing the QOL in seizure-free patients on monotherapy is AED side effects. QOL is a crucial component in the clinical care of patients with epilepsy, and physicians should take the time to ask specific questions on side effects of AEDs.     

Protective effect of Cassia fistula fruit extract against bromobenzene-induced liver injury in mice

In the present study, hepatoprotective effect of Cassia fistula fruit extract was investigated in mice. Animals were divided into six groups receiving normal saline (1), bromobenzene (460 mg/kg) alone (2) and together with increasing doses (200, 400, 600, 800 mg/kg) of a crude hydro-alcoholic extract of Cassia fistula fruit (3-6, respectively). All administrations were carried out orally, daily, for 10 days. On the 11th day, animals were sacrificed. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT) were determined; serum levels of direct and total bilirubin were measured; furthermore, livers were prepared for histological examination. Our results showed that bromobenzene treatment alone elicited a significant increase in activities of AST, ALT, ALP (but not γGT), and it significantly elevated the levels of direct and total bilirubin. Co-treatment with Cassia fistula fruit extract, however, significantly and dose-dependently decreased the above-mentioned enzyme activities (with exception of γGT) and bilirubin levels, producing a recovery to the naive state. The protective effect of Cassia fistula fruit extract against liver injury evoked by bromobenzene was confirmed by histological examination as well. In conclusion, the Cassia fistula fruit extract has significant hepatoprotective effect in our murine model.     

Effect of hormone replacement therapy on plasma lipoprotein levels and coronary atherosclerosis progression in postmenopausal women according to type 2 diabetes mellitus status

Type 2 diabetes mellitus is associated with dyslipidemia and with an increased risk of coronary heart disease (CHD). Our objective was to compare the effects of hormone replacement therapy (HRT) on plasma lipoproteins and coronary disease progression in postmenopausal women with and without diabetes. Study subjects were participants in the Estrogen Replacement and Atherosclerosis trial, a placebo-controlled, randomized trial of HRT (conjugated equine estrogen 0.625 mg/d with or without medroxyprogesterone acetate 2.5 mg/d) in postmenopausal women with established CHD (mean age, 65 ± 7 years). Plasma remnant lipoprotein levels and high-density lipoprotein (HDL) subpopulation levels were measured at baseline and year 1. Quantitative coronary angiography was assessed at baseline and at follow-up. At baseline, remnant lipoprotein levels were significantly higher and HDL cholesterol (HDL-C) levels were significantly lower in diabetic women than in women without diabetes. Hormone replacement therapy lowered remnant lipoproteins and increased HDL-C and large HDL particle levels in both groups. However, during HRT, levels of these parameters were still significantly worse in diabetic women than in nondiabetic women. A significant interaction between HRT and diabetes status, with greater increases in plasma atheroprotective HDL α1 particles in nondiabetic women than in diabetic women during HRT, was observed. Coronary heart disease progressed significantly more in women with diabetes than in women without diabetes. Our findings indicate that diabetes attenuates the HRT-related increase in atheroprotective HDL α1 particles. Faster progression of coronary atherosclerosis in women with diabetes could be mediated in part by a worse lipoprotein profile in these women than in women without diabetes, both before and during HRT.     

Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel

Depending on stage and risk factors, up to 30% of patients with advanced Hodgkin lymphoma (HL) progress or relapse. Patients with pleural effusions have a particularly poor prognosis and this stage of HL is regularly resistant to chemotherapy. All currently available HL cell lines are derived from late stage HL patients. In the present study we measured the sensitivity of these HL lines against the 26 most frequently used cytostatic drugs. We used a novel fluorescent short-term survival assay where the cell was incubated with the drugs for 4 days. The precise number of differentially stained live and dead cells was determined using a custom-built automated laser confocal fluorescent microscope. We found that HL cells, independently of their origin, showed very similar sensitivity patterns for several of the drugs. All HL cell lines were highly sensitive to dactinomycin, paclitaxel and etoposide. Our data suggest that the inclusion of dactinomycin and paclitaxel into chemotherapy protocols against late stage Hodgkin lymphoma with pleural effusion may be justified.