In vitro investigation on the effect of a plant preparation with antiviral activity on the functions of mice phagocyte cells

A polyphenol extract from the aerial roots of the medicinal plant Geranium sanguineum L. (PC) inhibited the reproduction of influenza viruses type A and B in vitro and in ovo and protected mice from mortality in the experimental influenza infection. The in vivo protective effect was connected with multiple biological activities of the preparation. The present paper focuses on the in vitro effects of the polyphenol extract on the functions of peritoneal and alveolar macrophages and blood polymorphonuclear leucocytes (PMNs), isolated from healthy ICR mice. It was found that PC in doses of 12.5 and 25 microg ml(-1) stimulated the phagocytic activity of peritoneal macrophages and blood PMNs. PC in the same doses did not significantly affect the phagocytic activity of alveolar macrophages, the migration of alveolar and peritoneal macrophages or the adherent activity of PMNs. Used in concentrations of 3.1-25.0 microg ml(-1), PC suppressed spontaneous NO production from peritoneal macrophages, while inducible NO production, provoked by LPS-, Ifn-gamma and LPS + Ifn-gamma inductions was not affected. The cell-toxic concentration of 100 microg ml(-1) increased spontaneous and LPS-inducible NO production. The experimental results demonstrated a stimulating effect of PC on the phagocytic activity of murine PMNs and peritoneal macrophages as well as a beneficial effect of the preparation on spontaneous NO production.     

Health risk for children from lead and cadmium near a non-ferrous smelter in Bulgaria

In an interdisciplinary approach the exposure to lead and cadmium of the population living in the vicinity of a Bulgarian non-ferrous metallurgical plant was studied to determine the routes of exposure. Two exposed villages situated 4 and 6 km SW and W, respectively,--in the plume of the plant's emissions--and a village for comparison situated 14 km SE of the plant were selected for the study. The blood of children aged 3-13 years from the exposed villages (n = 111) and the village for comparison (n = 18) was analyzed for lead (PbB) and cadmium (CdB) as well as for free erythrocyte protoporphyrin (FEP) and haematological parameters. A personal questionnaire concerning nutrition habits and life-style was filled in by interviewers of the children's parents. The cadmium levels in blood were within the variation range stated for Bulgaria. The exposed children had a mean CdB of 0.38 +/- 0.18 microgram/l (range 0.10-0.90 microgram/l) and the comparison group 0.31 +/- 0.35 microgram/l (0.06-1.42 micrograms/l). The mean PbB value measured in the exposed children was 240 +/- 96 micrograms/l (77-631 micrograms/l), while the mean value of PbB for the reference group was 149 +/- 57 micrograms/l (63-285 micrograms/l). Individual PbB levels > 150 and > 200 micrograms/l were found in 85% and 62%, respectively, of the exposed children and FEP > 80 micrograms/dl erythrocytes was detected in 21%. There was a concentration-response and a concentration-effect relationship (r = 0.51, D > 0.001) between PbB and FEP. According to the questionnaire only 10.3% of the interviewed families in the two exposed villages buy all food from the market, the others produce a significant part of their food themselves. The PbB levels of children who consume certain foods of local production (cabbage, cereals, poultry, and beef) were significantly higher compared to the PbB values of children whose families purchase these foods from the market. No significant relationship between lead in children's blood and the use of tin and ceramic utensils, drinking and irrigation water, hygiene habits, family tobacco smoking habits, playgrounds and traffic intensity were revealed. There was a significantly higher incidence of prematurely born babies in the exposed population. The proven relationship between lead intake via the food chain and existing significant health risks is the basis for risk communication. Measures aimed at healthier nutrition and life-style intend to contribute to decreasing the risk of the population living in the smelter region.     

Asymptomatic infections of the genital tract and infertility

Diagnosis of male genital tract inflammations plays a significant role in andrology. Although genital infections are often silent they can severely impair male infertility. In seminal plasma of 100 patients were determined IgG and SigA (radial immunodiffusion) the number of peroxydase-positive cells in addition to conventional semen parameters and microbiological investigations. There was carried out quantitative determination of alpha-amylase in connection with semen liquefaction. The results showed that exact quantitation of above mentioned parameters distinguish inflammatory male adnexal affections, which is appropriate for control of anti-inflammatory treatment and facilitates the diagnosis of inflammatory process in andrology.     

Treatment of adjuvant arthritis in mice with yeast superoxide dismutase

Yeast Cu/Zn superoxide dismutase (SODy) was used for treatment of adjuvant-induced arthritis in mice. SODy was applied intraperitoneally (i.p.) in doses of 10 mg/kg (30,000 U/kg) and 30 mg/kg (90,000 U/kg) one or three times daily on consecutive days. It was very effective in reducing the paw swelling whether administered before or immediately after induction or when the treatment began at the onset of inflammation or at the peak of the arthritic process. The effect of yeast SOD was compared to that of commercial SOD from bovine erythrocytes (SODb), as well as with indomethacin treatment. Histological data confirmed the antiinflammatory effect of yeast SOD. The schedules and doses tested did not elicit anti-SOD antibodies in serum.     

Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice

Laminopathies are a group of disorders caused by mutations in the LMNA gene that encodes the nuclear lamina proteins, lamin A and lamin C; their pathophysiological basis is unknown. We report that lamin A/C-deficient (Lmna(-/-)) mice develop rapidly progressive dilated cardiomyopathy (DCM) characterized by left ventricular (LV) dilation and reduced systolic contraction. Isolated Lmna(-/-) myocytes show reduced shortening with normal baseline and peak amplitude of Ca(2+) transients. Lmna(-/-) LV myocyte nuclei have marked alterations of shape and size with central displacement and fragmentation of heterochromatin; these changes are present but less severe in left atrial nuclei. Electron microscopy of Lmna(-/-) cardiomyocytes shows disorganization and detachment of desmin filaments from the nuclear surface with progressive disruption of the cytoskeletal desmin network. Alterations in nuclear architecture are associated with defective nuclear function evidenced by decreased SREBP1 import, reduced PPARgamma expression, and a lack of hypertrophic gene activation. These findings suggest a model in which the primary pathophysiological mechanism in Lmna(-/-) mice is defective force transmission resulting from disruption of lamin interactions with the muscle-specific desmin network and loss of cytoskeletal tension. Despite severe DCM, defects in nuclear function prevent Lmna(-/-) cardiomyocytes from developing compensatory hypertrophy and accelerate disease progression.     

Mutations in ribosomal proteins and ribosomal RNA confer macrolide resistance in human Ureaplasma spp

Genetic mechanisms of macrolide resistance were investigated in six isolates of Ureaplasma spp. with erythromycin minimum inhibitory concentrations (MICs)≥ 8 μg/mL that were derived from 370 cultures obtained over a several year period. Point mutations in domain V of 23S rRNA and/or mutations in ribosomal protein L4 genes are likely to be responsible for this drug resistance. Overall, macrolide resistance was uncommon, in contrast to tetracycline resistance that was documented in 121 unique isolates (33%).     

Support vector methods for survival analysis: a comparison between ranking and regression approaches

Objective

To compare and evaluate ranking, regression and combined machine learning approaches for the analysis of survival data.

Methods

The literature describes two approaches based on support vector machines to deal with censored observations. In the first approach the key idea is to rephrase the task as a ranking problem via the concordance index, a problem which can be solved efficiently in a context of structural risk minimization and convex optimization techniques. In a second approach, one uses a regression approach, dealing with censoring by means of inequality constraints. The goal of this paper is then twofold: (i) introducing a new model combining the ranking and regression strategy, which retains the link with existing survival models such as the proportional hazards model via transformation models; and (ii) comparison of the three techniques on 6 clinical and 3 high-dimensional datasets and discussing the relevance of these techniques over classical approaches fur survival data.

Results

We compare svm-based survival models based on ranking constraints, based on regression constraints and models based on both ranking and regression constraints. The performance of the models is compared by means of three different measures: (i) the concordance index, measuring the model’s discriminating ability; (ii) the logrank test statistic, indicating whether patients with a prognostic index lower than the median prognostic index have a significant different survival than patients with a prognostic index higher than the median; and (iii) the hazard ratio after normalization to restrict the prognostic index between 0 and 1. Our results indicate a significantly better performance for models including regression constraints above models only based on ranking constraints.

Conclusions

This work gives empirical evidence that svm-based models using regression constraints perform significantly better than svm-based models based on ranking constraints. Our experiments show a comparable performance for methods including only regression or both regression and ranking constraints on clinical data. On high dimensional data, the former model performs better. However, this approach does not have a theoretical link with standard statistical models for survival data. This link can be made by means of transformation models when ranking constraints are included.     

Ginkgo biloba extract EGb 761®, donepezil or both combined in the treatment of Alzheimer's disease with neuropsychiatric features: A randomised,double-blind,exploratory trial

Objective: This randomised, double-blind exploratory trial was undertaken to compare treatment effects and tolerability of EGb 761®, donepezil and combined treatment in patients with AD and neuropsychiatric features.

Method: We enrolled 96 outpatients, aged 50 years or above, who met the NINCDS/ADRDA criteria for probable AD, scored below 36 on the TE4D, a screening test for dementia, below 6 on the Clock-Drawing Test (CDT) and between 9 and 23 on the SKT, a cross-culturally validated cognitive test battery. They scored at least five on the 12-item Neuropsychiatric Inventory (NPI). EGb 761® (240 mg per day), donepezil (initially 5 mg, after 4 weeks 10 mg per day) or EGb 761® and donepezil combined (same doses) were administered for 22 weeks.

Results: Changes from baseline to week 22 and response rates were similar for all three treatment groups with respect to all outcome measures (SKT, NPI, total score and activities-of-daily-living sub-score of the Gottfries–Bråne–Steen Scale, Hamilton Rating Scale for Depression, CDT and Verbal Fluency Test). An apparent tendency in favour of combination treatment warrants further scrutiny. Compared to donepezil mono-therapy, the adverse event rate was lower under EGb 761® treatment and even under the combination treatment.

Conclusion: These exploratory findings helped to develop three hypotheses that will have to be proven in further studies: (1) there is no significant difference in the efficiency between EGb 761® and donepezil, (2) a combination therapy will be superior to a mono-therapy with one of both substances and (3) there will be less side effects under a combination therapy than under mono-therapy with donepezil.     

Psychophysiological assessment of stress and screening of health risk in peacekeeping operations

Medical surveillance for military personnel participating in peacekeeping missions (PKMs) is required to define the effect of stress on health status. The aim of this study was to determine the effect of stress on the autonomic cardiovascular control and health risk of 72 Bulgarian peacekeepers participating in a PKM in Kosovo. The assessment of psychophysiological stress and determination of stress characteristics were implemented with analysis of heart rate variability and personal interviews. As a response to the cumulative exposure to the effect of stress on cognitive function, we observed reductions in parasympathetic function and baroreceptor modulation of heart rhythm. The alteration in cardiovascular control was registered as decreases in short-term variability and spectral powers of cardiointervals in the respiratory sinus arrhythmia and Traube-Hering-Mayer bands. The advantage of psychophysiological stress assessment and screening of health risk in PKMs is that results indicate the mechanisms of the effects of stress on cognitive function and health status.