A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses.

New strategies are required to identify the most important targets of protective immunity in complex eukaryotic pathogens. Natural selection maintains allelic variation in some antigens of the malaria parasite Plasmodium falciparum. Analysis of allele frequency distributions could identify the loci under most intense selection. The merozoite surface protein 1 (Msp1) is the most-abundant surface component on the erythrocyte-invading stage of P. falciparum. Immunization with whole Msp1 has protected monkeys completely against homologous and partially against non-homologous parasite strains. The single-copy msp1 gene, of about 5 kilobases, has highly divergent alleles with stable frequencies in endemic populations. To identify the region of msp1 under strongest selection to maintain alleles within populations, we studied multiple intragenic sequence loci in populations in different regions of Africa and Southeast Asia. On both continents, the locus with the lowest inter-population variance in allele frequencies was block 2, indicating selection in this part of the gene. To test the hypothesis of immune selection, we undertook a large prospective longitudinal cohort study. This demonstrated that serum IgG antibodies against each of the two most frequent allelic types of block 2 of the protein were strongly associated with protection from P. falciparum malaria.

Long-term (56-week) oral administration of probiotic Enterococcus faecium M-74 decreases the expression of sICAM-1 and monocyte CD54, and increases that of lymphocyte CD49d in humans.

OBJECTIVES: To study the effects of long-term probiotic [Enterococcus faecium (EF) M-74 strain] application in humans with respect to adhesion molecules, both soluble forms (sICAM-1, sPECAM-1) and their expression on leukocytes. METHODS: Double-blinded randomized and placebo controlled study lasting for 60 weeks. A single capsule containing either 2x10(9) of bacteria EF M-74 with 50 microg of organically bound selenium (E-group) or placebo (P-group) was given to volunteers. Peripheral blood was analyzed for the expression of particular adhesive molecules. RESULTS AND CONCLUSIONS: We observed significant changes in CAMs expression in terms of a decrease in sICAM-1, CD54 on monocytes and CD11b on lymphocytes after one-year administration of Enterococcus faecium M-74 in humans. Anti-adhesion-aimed therapeutic modalities may provide the future approach to prevention and treatment of cardiovascular diseases. Application of probiotics may be part of such strategies. (Tab. 2, Fig. 6, Ref. 41.)

One-year application of probiotic strain Enterococcus faecium M-74 decreases serum cholesterol levels.

OBJECTIVES: To investigate the impact of long-term orally administered probiotic strain Enterococcus faecium (EF) M-74 enriched with selenium on lipid profile (total cholesterol, LDH, HDL, and triglycerides) in humans. BACKGROUND: The discovery that hypercholesterolemia plays a major role in the development of atherosclerosis has led to a number of pharmacological and non-pharmacological (including dietary) approaches resulting in its elimination. Up to now, the question of supposed hypocholesterolemic effect of probiotics has not been definitely established. METHODS: 43 volunteers were randomized into two groups. Participants were given single capsule a day containing 2x10(9) of EF M-74 plus 50 microg of organically bound selenium (E-group) or placebo (P-group). The study was double-blind and lasted 60 weeks. Peripheral blood was analyzed for lipid parameters before intervention, after 6, 12, 23, 44, and 56 weeks of capsule administration, and four weeks following interruption of administration. RESULTS: After 56 weeks of application, decrease in total cholesterol in E-group (17/3 women/men, mean age 75.4+/-1.5 year) was observed (5.94+/-0.29 mmol/l at week 0 vs 5.22+/-0.25 mmol/l after 56 weeks, p<0.001). This reduction was achieved mainly due to a fall in LDL cholesterol (3.85+/-0.27 vs 3.09+/-0.21 mmol/l, p<0.001), as no significant alterations in HDL and triglycerides were noted. In placebo group (14/4, 78.1+/-1.7 year), no statistically important changes were observed after one-year capsule administration. CONCLUSIONS: In our study, the administration of E. faecium M-74 probiotic strain was associated with reduction of serum cholesterol concentration by 12% after 56 weeks. The crescent amount of facts on this issue gives a solid reason to assume that probiotics will find their place as a therapeutic alternative in human medicine. (Tab. 4, Fig. 4, Ref: 36.)

Extreme geographical fixation of variation in the Plasmodium falciparum gamete surface protein gene Pfs48/45 compared with microsatellite loci.

Comparing patterns of genetic variation at multiple loci in the genome of a species can potentially identify loci which are under selection. The large number of polymorphic microsatellites in the malaria parasite Plasmodium falciparum are available markers to screen for selectively important loci. The Pfs48/45 gene on Chromosome 13 encodes an antigenic protein located on the surface of parasite gametes, which is a candidate for a transmission blocking vaccine. Here, genotypic data from 255 P. falciparum isolates are presented, which show that alleles and haplotypes of five single nucleotide polymorphisms (SNPs) in the Pfs48/45 gene are exceptionally skewed in frequency among different P. falciparum populations, compared with alleles at 11 microsatellite loci sampled widely from the parasite genome. Fixation indices measuring inter-population variance in allele frequencies (F(ST)) were in the order of four to seven times higher for Pfs48/45 than for the microsatellites, whether considered (i) among populations within Africa, or (ii) among different continents. Differing mutational processes at microsatellite and SNP loci could generally affect the population structure at these different types of loci, to an unknown extent which deserves further investigation. The highly contrasting population structure may also suggest divergent selection on the amino acid sequence of Pfs48/45 in different populations, which plausibly indicates a role for the protein in determining gamete recognition and compatibility.

Physical fitness does not reflect physical activity patterns in middle-aged workers.

Questionnaires and a sub-maximal exercise test were used to assess occupational and leisure time physical activity as well as physical fitness in a standardized prospective study in 2,565 Belgian and Slovakian middle-aged healthy workers. Less than 5% of the subjects engaged in strenuous work requiring an energy expenditure above 31.5 kJ.min-1. One-third of the Belgians and 50% of the Slovakians reported no heavy leisure time activity during the preceding 12 months. Physical fitness, defined as the workload at heart rate 150 beats.min-1 (standardized for body weight), was significantly higher in Slovakians as compared to Belgians (1.52 +/- 0.28 W.kg-1 and 1.48 +/- 0.28 W.kg-1; P less than 0.001). Occupational physical activity in Belgians and heavy leisure time activity in Slovakians were independently related to fitness levels. However, each activity score explained less than 1% of the variance of physical fitness. We conclude that in these mainly sedentary, middle-aged subjects, fitness levels are independent from the usual physical activity patterns.

The effect of cardiovascular autonomic neuropathy on resting ECG in type 1 diabetic patients.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. AIM: To assess the manifestations of CAN on ECG at rest. SUBJECTS AND METHODS: 100 type I diabetic patients, mean age 36.5 (range 17-62) years, mean duration of diabetes 14.6 (range 0-49) years were examined. The control group consisted of 88 healthy subjects, mean age 37 (range 15-65) years. Cardiovascular reflexes (respiration sinus arrhythmia, orthostatic test and Valsalva's maneuvre) were examined, and ECG at rest was analysed. RESULTS: In 35 (35%) diabetics CAN was established. In comparison to diabetic patients without neuropathy, patients with CAN had a higher heart rate (94, 89-99 vs. 79, 75-82 heart beats.min-1, p < 0.001), higher P wave voltage (0.13, 0.12-0.15 vs 0.11, 0.09-0.12 mV, p < 0.001), as well as QTc interval length (422, 410-433 vs 396, 388-404 ms, p < 0.001), but they had a lower voltage of R wave (0.83, 0.72-0.94 vs. 1.0, 0.91-1.09 mV, p < 0.05) and lower T wave voltage (0.18, 0.15-0.21 vs 0.23, 0.19-0.27 mV, p < 0.05). CONCLUSIONS: The higher voltage of P wave, lower voltage of T wave, shorter PQ interval and prolonged QTc interval with tachycardia may be the manifestation of relative sympatheticotonia. Lower R wave voltage and the prolonged QRS complex are the possible signs of cardiomyopathy. (Tab. 4, Ref. 31.)

[Immunostimulatory and other beneficial health effects of lactic acid bacteria]. / Imunostimulacné a iné zdravotne prospesné úcinky baktérií mliecneho kysnutia.

Lactic acid bacteria in functional foods can transiently colonize the intestine of man and exert beneficial probiotic effects. These were observed in a group of adult subjects administered daily by a lyophilized Enterococcus faecium M-74 in the form of waffles (Dr. Ebi) during nine weeks of a double blind placebo controlled clinical trial. The results showed significant immunostimulatory effect on both phagocytosis by neutrophils and antibody production.

[Successful modification of human intestinal microflora with oral administration of lactic acid bacteria]. / Prospesná modifikácia crevnej mikroflóry cloveka perorálne podávanými baktériami mliecneho kysnutia.

Lactic acid bacteria in food can transiently colonize the intestine and exert health beneficial (probiotic) effects. These include: 1. Lactose digestion, improvement of diarrheal disorders (including traveller's diarrhea), prophylaxis of intestinal and urogenital infections--as a result of formation or reconstruction of a balanced indigenous microflora. 2. Inhibition of the mutagenicity of the intestinal contents and reduction of the incidence of intestinal tumours. 3. Immunomodulatory effects resulting in the improved host resistance. 4. Depression of the serum cholesterol level. The most of these effects were observed in a group of adult subjects administered daily by a lyophilized Enterococcus faecium M-74 in the form of waffles (Dr. Ebi) during nine weeks of a double blind placebo controlled clinical trial. The bacterium temporarily colonized the host intestine and its secretion in stool persisted for six weeks after the last dose. The mean activities of beta-D-glucuronidase in stools of subjects given waffles containing enterococci were reduced comparing to stools of placebo subjects. After six weeks of daily eating the waffles with enterococci, an increased production of superoxide and other reactive oxygen intermediates by peripheral neutrophils was observed. The increase corresponded in time with an elevated formation of IgG by peripheral blood mononuclear cells after polyclonal activation with mitogenes. Higher activities of myeloperoxidase and elastase in peripheral neutrophils were also ascertained during eating of waffles containing of E. faecium M-74. Hence, intake of E. faecium M-74 in the form of waffles may have an significant immunostimulatory effect on both phagocytosis performed by neutrophils and antibody production. (Tab. 6, Ref. 29.)

[Methods in stress ECG]. / Zát'azové EKG metódy.

In spite of the continuous development of methods of examination, the exercise ECG still retains its position in the palette of examination methods for ischaemic heart disease. The examination mostly employs a mechanical load on bicycle ergometer or a treadmill. In the changes in the ST segment (horizontal or descending regression of ST surpassing 1 mm, i.e. 0.1 mV, measured 60-80 ms from junction) is still considered as the most indicative ECG index. The detection rate of ischaemic changes is proportional to the number of used leads. Sensitivity of visually evaluated exercise ECG is in the rang of 54 to 66%, specificity is around 82%. The elevation of ST-segment in aVR and V1 leads during exercise is considered as a manifestation of ischaemia. The regions affected by myocardial infarction it may indicate an aneurysm or dyskinesis and is considered as a manifestation myocardial ischaemia and a marker of poor prognosis. An adequate heart rate is presently considered significant. Sensitivity of the test is increased by ECG registration up to 8 to 10 minutes of the recovery phase.