Differential macrophage expression of IL-12 and IL-23 upon innate immune activation defines rat autoimmune susceptibility

Rodents typically demonstrate strain-specific susceptibilities to induced autoimmune models such as experimental arthritis and encephalomyelitis. A common feature of the local pathology of these diseases is an extensive infiltration of activated macrophages (MPhi). Different functional activation states can be induced in MPhi during innate immune activation, and it is this differential activation that might be important in susceptibility/resistance to induction or perpetuation of autoimmunity. In this study, we present an extensive, comparative analysis of the activation phenotypes of MPhi derived from autoimmune-susceptible and autoimmune-resistant rat strains to describe a cellular phenotype that defines the disease phenotype. We included investigation of receptor function, intracellular signaling pathways, cytokines, and other soluble mediators released after activation of cells using a panel of stimuli embracing many activation routes. We report that activation of MPhi from the autoimmune-susceptible strain was associated with alternative activation indicated by induction of arginase activity, a lower production of classical proinflammatory mediators, and a high production of interleukin (IL)-23, and MPhi from the autoimmune-resistant strains were associated with a higher production of proinflammatory mediators, a classical activation phenotype, and preferential induction of IL-12. These MPhi phenotypes thus reflect disparate, genetic cellular programs that define autoimmune susceptibility.     

Microcirculatory changes in patients with chronic venous and lymphatic insufficiency and heavy leg symptoms before and after therapy with procyanidol oligomers (laser-Doppler study)

INTRODUCTION: To study the efficacy of venotonica and medicaments having anti-edema effect is very actual. AIMS: Patients suffering from venous-lymphatic insufficiency were treated with procyanidol oligomers in an open, prospective study. The effective substance of this medication protects the fibrous connective tissue protein, thus improving the function of the venous and lymphatic capillaries. METHODS: For three months, the daily dose was 2 x 150 mg 30 patients were included into the study. The efficacy of the treatment was evaluated by statistical methods analysing the changes of the clinical symptoms and the satisfaction of the patients. For the first time, laser-Doppler method was used to determine the pathological condition of the dermal microcirculation before and after 3 months of treatment. The laser-Doppler tests used as indicators of the functional changing of the microcirculations were as follows: venoarterial response, reactive hyperemic response, and thermal stimulation response. The authors established the standard values and compared the measurement scores to those. According to the resulting scores, the status before and after the treatment can be compared by statistic analysis. Subjective complaints of the patients such as pain, heaviness of the leg, nightly muscle cramps were estimated by a visual analog scale. RESULTS: The treatment (procyanidol oligomers) significantly reduced lymphedema (p < 0.001) in the "heavy leg" syndrome. Symptoms as pain, heaviness of the leg, muscle cramps, improved significantly (p < 0.001) after treatment. The microcirculatory status was pathologic before treatment. After treatment, there was no significant improvement in the laser-Doppler results. CONCLUSIONS: The study revealed that in venous-lymphatic insufficiency, the arterial-capillary system is also damaged. The authors bring to attention that the disorder of the dermal arteries playing a role in the pathogenesis of venous-lymphatic insufficiency first detected in this study needs to be further investigated.     

Incidence of risk factors in parents with acute myocardial infarction at young age and in their children

INTRODUCTION: The preliminaries of the cardiovascular diseases can be traced back to the childhood. The authors tried to find relationship between parents with early onset myocardial infarction (AMI) and incidence of risk factors for ischemic heart disease in their children as compared to respective data for families with no incidence of myocardial infarction. METHODS: The study population consisted of 38 persons with early onset AMI myocardial infarction (age < 55 y) and their 66 children, and 38 adult control subjects and their 33 children. In each person arterial blood pressure, body weight, body height, waist circumference were recorded and body mass index (BMI: kg/m2) was calculated. Eating habits and life style practices were recorded in a questionnaire in the case of each participant. Laboratory variables were determined in the blood sera as follows, glucose, triglycerides (Tg), total cholesterol (T-C), HDL-cholesterol, LDL-cholesterol, apolipoprotein-A, apolipoprotein-B, and lipoprotein (a). The atherogenic index (LDL-C/HDL-C) (LDL-cholesterol/HDL-cholesterol) was also calculated. STATISTICAL EVALUATION: Data were evaluated statistically using the SPSS for Windows 9. RESULTS: According to the mean BMI values all groups of parents belonged to the overweight category. The mean cholesterol levels of all adults were in the borderline high category. In males with early onset myocardial infarction sera concentrations of HDL-cholesterol and apolipoprotein-A were significantly lower, whereas triglyceride and atherogenic index were significantly higher than respective data for control parents. In all groups of parents, fasting mean serum glucose concentrations were higher than the reference value, serum total-cholesterol concentrations were in the borderline high category. In the daughter of the parents with early onset myocardial infarction had a higher atherogenic index than that of controls. Eating habits did not essentially differ between case vs. control families. Consumption of milk, dairy products, fruit and vegetables was insufficient in each group. Incidences of smoking for parents and children were 55% and 35% in the myocardial infarction group and 44% and 37% in the control group, respectively. Physical activity was completely insufficient in each group studied. CONCLUSION: Since no considerable differences were seen between the case vs control families in the parameters tested, therefore it is presumed that the offspring born to parents with or without early onset myocardial infarction are at equal risk to develop cardiovascular diseases unless lifestyle practices are profoundly changed.     

Our experience using autofluorescence bronchoscopy

INTRODUCTION: Lung cancer is responsible for most cancer deaths in the world. The main reason for the poor prognosis is late diagnosis. Many patients could be successfully treated in early stage. AIMS: The authors performed 369 bronchological examination on 336 patients using autofluorescence bronchoscopy between 1998 and 2003 to detect preinvasive lesions and early forms of lung cancer. METHODS: Storz D-Light autofluorescence system has been used to perform the examinations. RESULTS: In one third of these patients invasive lung cancer developed during follow-up. Combining traditional white light and autofluorescence technique 50% more intraepithelial lesions have been observed and sensitivity has been increased by 69% compared to the lone use of white light bronchoscopy. CONCLUSIONS: Supported by most international studies these results emphasise that autofluorescence bronchoscopy has a major role in the early diagnosis of preinvasive bronchial lesions and may help in the prevention and early therapy of lung cancer.     

Phenotypic variants of A3243G mitochondrial DNA mutation in a Hungarian family

The first Hungarian case with typical features of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) in a young girl is presented. MELAS is a multisystem disorder inherited by the mitochondrial DNA with onset typically in childhood. Our patient presented the first symptoms at the age of 6 years with recurrent vomiting, nausea and transient visual loss. Several stroke-like episodes followed gradually impairing motor abilities and mental development. Molecular analysis of the mitochondrial DNA confirmed a heteroplasmic A3243G transition. The maternal family members were also tested for the mutation in peripheral blood DNA. In the mother of the proband, who suffers from bilateral hypacusis the mutation was detected in 20% of heteroplasmy, while in one of her asymptomatic sisters the mutation was present in 10% only. The bilateral hypacusis of the mother may be associated with this mutation and seems to differentiate the pedigree reported here from others published in the literature.     

In vitro and in vivo antitumor effect of 2-methoxyestradiol on human melanoma

2-methoxyestradiol (2ME(2)) is an endogenous metabolite of estradiol with estrogen-receptor-independent antitumor and antiangiogenic activity. We examined the effects of 2ME(2) on the cellular proliferation of 8 human melanoma cell lines. We show that 2ME(2) inhibited cell proliferation by inducing apoptosis and an arrest in the G(2)/M phase, and the mechanism of action involved microtubules, mitochondrial damage and caspase activation. In male SCID mice, 2ME(2) was effective in reducing primary tumor weight and the number of liver metastases after intrasplenic injection of human melanoma cells. In the metastases, we found a significantly higher rate of apoptotic cells after 2ME(2) treatment. These findings on the antitumor effect of 2ME(2) in cell culture as well as in an animal model may have implications for designing alternative treatment options for patients with advanced malignant melanoma.     

Image quality of the temporal bone window examined by transcranial Doppler sonography and correlation with postmortem computed tomography measurements

BACKGROUND AND PURPOSE: The major limitation of native transcranial colour-coded duplex sonography (TCCS) in older stroke patients is the relatively frequent occurrence of an insufficient temporal window. Our goal was to investigate the relationship between the in vivo Doppler ultrasound image quality of the temporal bone, and computed tomography (CT)-determined thickness, density, and homogeneity of cadaver temporal bone. METHODS: Thirty-three moribund neurological patients who eventually died were examined by TCCS using the transtemporal approach. The sonographer categorized the quality of the TCCS image (excellent, intermediate, and poor). During autopsy, a rectangular sample of the temporal squama was removed, which corresponded to the area of the in vivo acoustic window. The thickness of the whole temporal bone, cortical, and cancellous (= diploe) bone as well as the density and homogeneity were determined by high-resolution CT. RESULTS: Thirty-seven temporal bones were obtained. The quality of the acoustic window was classified as excellent in 13, intermediate in 6 and poor in 18 cases. A significant correlation between the complete bone thickness, as well as between the absolute thickness of the diploe and the quality of the acoustic window was found: the thinner the bone/diploe, the better the colour Doppler signal. The thickness of the cortical plates and the homogeneity of the bones were identical in the three image quality categories. CONCLUSION: The transtemporal TCCS image quality depends mainly on the thickness of the cancellous component of the temporal bone.