Dietary Patterns and Metabolic Disorders in Polish Adults with Multiple Sclerosis

Diet plays a major role in the aetiopathogenesis of many neurological diseases and may exacerbate their symptoms by inducing the occurrence of metabolic disorders. The results of research on the role of diet in the course of multiple sclerosis (MS) are ambiguous, and there is still no consensus concerning dietary recommendations for patients with MS. The aim of this study was to analyse the dietary patterns (DPs) of patients with MS and to assess the relationships between these DPs and the metabolic disorders. The study participants were comprised of 330 patients aged 41.9 ± 10.8 years. A survey questionnaire was used to collect data related to diet, lifestyle and health. The DPs were identified using a principal component analysis (PCA). Three DPs were identified: Traditional Polish, Prudent and Fast Food & Convenience Food. An analysis of the odds ratios adjusted for age, gender, smoking and education showed that a patient’s adherence to the Traditional Polish and the Fast Food & Convenience Food DPs increased the likelihood of abdominal obesity and low HDL-cholesterol concentration. Conversely, adherence to the Prudent DP was not significantly associated with any metabolic disorder. The results of this study confirmed that an unhealthy diet in patients with MS is connected with the presence of some metabolic risk factors. There is also an urgent need to educate patients with MS on healthy eating, because the appropriate modifications to their diet may improve their metabolic profile and clinical outcomes.     

Low-grade squamous intraepithelial lesions of the cervix with marked cytological atypia-clinical follow-up and human papillomavirus genotyping.

The majority of low-grade squamous intraepithelial lesions (LSILs) of the cervix regress spontaneously; however, a small proportion of LSILs progress to high-grade squamous intraepithelial lesion (HSIL) if the lesion is not excised. The guidelines for which patients with LSIL should be treated and which may be followed safely are not well established. The goal of this study was to identify a subgroup of patients with LSIL who may require surgical treatment. We hypothesized that patients with LSILs with marked cytological atypia (LSIL-MA) may be at higher risk for subsequent HSIL. In addition, we were interested in whether LSIL-MA was associated with specific human papillomavirus genotypes. Consecutive patients with biopsy diagnosis of LSIL (n = 30) and LSIL-MA (n = 30) were identified. Marked atypia was defined as 5 or more cells with nuclear enlargement of at least 5 times the size of an intermediate cell nucleus or multinucleation with 5 or more nuclei. Patient follow-up was recorded for up to 24 months. Human papillomavirus genotyping was performed using SPF10 PCR and line probe assay. High-grade squamous intraepithelial lesion on follow-up was significantly more common in patients with LSIL-MA (36%) than in patients with LSIL (7%), and negative follow-up was significantly more common in patients with LSIL (50%) than LSIL-MA (23%). Cases of LSIL and LSIL-MA showed similar spectrum of human papillomavirus genotypes. Marked cytological atypia in LSILs identifies a subset of patients with a high rate of HSIL on follow-up. In such patients, an excisional cone biopsy should be strongly considered.     

Bioequivalence study of two losartan formulations administered orally in healthy male volunteers

The bioavailability of a new losartan preparation (2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt, CAS 114798-26-4) was compared with the reference preparation of the drug in 24 healthy male volunteers, aged between 19 and 32. The open, randomized, single-blind two-sequence, two-period crossover study design was performed. Under fasting conditions, each subject received a single oral dose of 100 mg losartan as a test or reference formulation. The plasma concentrations of losartan and its active metabolite were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-36h, AUC0-infinity, Cmax, t1/2, and Ke. Values of AUC0-infinity demonstrate nearly identical bioavailability of losartan from the examined formulations. The AUC0-infinity of losartan was 2019.92+/-1002.90 and 2028.58+/-837.45 ng x h/ml for the test and reference formulation, respectively. The AUC0-infinity of the metabolite was 10851.52+/-4438.66 and 11041.18 +/-5015.81 ng x h/ml for test and reference formulation, respectively. The maximum plasma concentration (Cmax) of losartan was 745.94+/-419.75 ng/ml for the test and 745.74+/-329.99 ng/ml for the reference product and the Cmax of the metabolite was 1805.77+/-765.39 and 1606.22 +/-977.22 ng/ml for the test and reference product, respectively. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for both losartan and its active metabolite. 90 % confidence limits calculated for Cmax and AUC from zero to infinity (AUC0-infinity) of losartan and its metabolite were included in the bioequivalence range (0.8-1.25 for AUC). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.     

A comet assay study reveals that aluminium induces DNA damage and inhibits the repair of radiation-induced lesions in human peripheral blood lymphocytes

Although it is known that many metals induce DNA damage and inhibit DNA repair, information regarding aluminium (Al) is scarce. The aim of this study was to analyze the level of DNA damage in human peripheral blood lymphocytes treated with Al and the impact of Al on the repair of DNA damage induced by ionizing radiation. Cells were treated with different doses of aluminium chloride (1, 2, 5, 10 and 25 microg/ml AlCl(3)) for 72 h. The level of DNA damage and of apoptosis was determined by the comet assay. The level of oxidative damage was determined by the application of endonuclease III and formamidopyrimidine DNA glycosylase. The results on apoptosis were confirmed by flow cytometry. Based on the fluorescence intensity, cells were divided into cohorts of different relative DNA content that corresponds to G(1), S and G(2) phases of the cell cycle. Our results revealed that Al induces DNA damage in a dose-dependent manner, however, at the dose of 25 microg/ml the level of damage declined. This decline was accompanied by a high level of apoptosis indicating selective elimination of damaged cells. Cells pre-treated with Al showed a decreased repair capacity indicating that Al inhibits DNA repair. The possible mechanisms by which Al induces DNA damage and inhibits the repair are discussed.     

Brain tumor oncolysis with replication-conditional herpes simplex virus type 1 expressing the prodrug-activating genes, CYP2B1 and secreted human intestinal carboxylesterase, in combination with cyclophosphamide and irinotecan

The treatment of malignant glioma is currently ineffective. Oncolytic viruses are being explored as a means to selectively lyse tumor cells in the brain. We have engineered a mutant herpes simplex virus type 1 with deletions in the viral UL39 and gamma(1)34.5 genes and an insertion of the two prodrug activating genes, CYP2B1 and secreted human intestinal carboxylesterase. Each of these can convert the inactive prodrugs, cyclophosphamide and irinotecan (CPT-11), into their active metabolites, respectively. This new oncolytic virus (MGH2) displays increased antitumor efficacy against human glioma cells both in vitro and in vivo when combined with cyclophosphamide and CPT-11. Importantly, cyclophosphamide, CPT-11, or the combination of cyclophosphamide and CPT-11 does not significantly affect oncolytic virus replication. Therefore, MGH2 provides effective multimodal therapy for gliomas in preclinical models when combined with these chemotherapy agents.     

Cardiac rupture in acute myocardial infarction with ST segment elevation. Clinical course and prognosis

INTRODUCTION: Cardiac rupture (CR), involving left ventricular free wall, interventricular septum or papillary muscles, accounts for 15% of all deaths in the acute phase of myocardial infarction (MI). After cardiac arrhythmias and cardiogenic shock, CR is the third most common cause of death in acute MI. In spite of progress in the treatment of MI, mortality due to CR did not change in recent years.Aim. To assess the incidence, clinical course and outcome in patients with acute MI complicated by CR who were treated in our centre. METHODS: The study group consisted of 697 consecutive patients who were hospitalised due to acute MI with ST segment elevation (STEMI). The in-hospital and three-month follow-up data were analysed in 27 (3.9%) patients who developed CR. In 20 patients CR occurred in the left ventricular free wall, in 5 interventricular septum, in one both of these structures, and in one papillary muscle. The diagnosis of CR was based on clinical presentation and echocardiography. RESULTS: The overall mortality in 697 patients with STEMI was 10.5%. Mortality rate in patients with CR was 55.6% (15 patients) which accounted for 20.5% of all deaths. Nine patients with CR underwent cardiac surgery whereas 18 were treated conservatively. Two (22.2%) patients from the former group and 13 (72.2%) patients from the latter group died. CONCLUSIONS: 1. Mortality due to CR was increased in patients who were treated conservatively, who received thrombolysis and those who were females. 2. Rapid and accurate diagnosis, proper correction of hemodynamical disturbances and timely introduction of cardiac surgery improve prognosis in patients with CR complicating STEMI.     

No donor age effect of human serum on collagen synthesis signaling and cell proliferation of human tendon fibroblasts

The aging process of tendon tissue is associated with decreased collagen content and increased risk for injuries. An essential factor in tendon physiology is transforming growth factor-β1 (TGF-β1), which is presumed to be reduced systemically with advanced age. The aim of this study was to investigate whether human serum from elderly donors would have an inhibiting effect on the expression of collagen and collagen-related genes as well as on cell proliferative capacity in tendon cells from young individuals. There was no difference in systemic TGF-β1 levels in serum obtained from young and elderly donors, and we found no difference in collagen expression when cells were subjected to human serum from elderly versus young donors. In addition, tendon cell proliferation was similar when culture medium was supplemented with serum of different donor age. These findings suggest that factors such as the cell intrinsic capacity or the tissue-specific environment rather than systemic circulating factors are important for functional capacity throughout life in human tendon cells.     

Flat-detector computed tomography in the assessment of intracranial stents: comparison with multi detector CT and conventional angiography in a new animal model

Objective  

Careful follow up is necessary after intracranial stenting because in-stent restenosis (ISR) or residual stenosis (RS) is not rare. A minimally invasive follow-up imaging technique is desirable. The objective was to compare the visualisation of stents in Flat Detector-CT Angiography (FD-CTA) after intravenous contrast medium injection (i.v.) with Multi Detector Computed Tomography Angiography (MD-CTA) and Digital Subtracted Angiography (DSA) in an animal model.