The impact of probiotics and vitamin C on the prevention of upper respiratory tract symptoms in two preschool children cohorts.

BACKGROUND/OBJECTIVES: The efficacy of Lab4 probiotic and vitamin C combination on the prevention of upper respiratory tract infections (URTIs) was investigated in two studies with children. Our objective was to pool dataset of 57 preschool children from the PROCHILD study (ISRCTN28722693) and the dataset of 50 preschool matched cohort from the PROCHILD-2 study (ISRCTN26587549) to evaluate the impact of probiotic/vitamin C combination on the prevention of upper respiratory tract symptoms and provide a more robust assessment of effect using detailed individual level data. SUBJECTS/METHODS: The children were supplemented daily for 6 months with either the multistrain probiotic (1.25×1010 cfu/tablet consisting of two strains of Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) plus 50 mg vitamin C or a placebo. RESULTS: In the pooled analysis of the individual participant data (per protocol population), significant reductions were observed for the incidence (-25%; 95% confidence interval [CI], 0.66, 0.85; P < 0.0001) and duration (-14.9 days; 95% CI, -24.8, -5.1; P = 0.0030) of typical URTI symptoms in the active group compared with the placebo. The incidence rates of absenteeism from preschool (IR ratio, 0.75; 95% CI, 0.66, 0.86; P < 0.0001), paediatric visits (IR ratio, 0.56; 95% CI, 0.47; 0.68; P < 0.0001) and antibiotic usage (IR ratio, 0.53; 95% CI, 0.39, 0.71; P < 0.0001) were also significantly reduced. CONCLUSION: The pooled analysis findings of comparable preschool cohorts from two studies indicate that the supplementation with probiotic and vitamin C combination is beneficial in the prevention and management of URTI symptoms.

Prevalence of Periodontal Pathogens in Slovak Patients with Periodontitis and Their Possible Aspect of Transmission from Companion Animals to Humans.

Oral health and diseases are greatly influenced by oral bacteria. During dysbiosis, bacterial composition changes, which can lead to periodontitis. Periodontitis in humans is associated with periodontal pathogens such as Treponema denticola, Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans. Animal-to-human transmission of some of these pathogens has also been reported. The aim of this study was to evaluate the prevalence of periodontal pathogens in Slovak patients and to assess the possible risk of transmission of these pathogens from animals to their owners. The presence of periodontal pathogens in dental plaque was monitored by PCR. Amplified products were analysed using Sanger sequencing. T. forsythia isolates were assessed for the susceptibility to different antibiotics using the disk diffusion method. In humans, T. denticola, P. gingivalis, T. forsythia and A. actinomycetemcomitans were present in 69.23%, 69.23%, 100% and 84.62%, respectively. Most isolates of T. forsythia were susceptible to amoxicillin-clavulanic acid, clindamycin and moxifloxacin, but they were resistant to metronidazole. The transmission of T. forsythia from animals to their owners was not proven based on sequence analysing. On the other hand, transmission of Porphyromonas gulae was confirmed, but the risk of its involvement in the pathogenesis of periodontitis in humans must be further investigated.

Oxidative Stress Markers and Antioxidant Enzymes in Children and Adolescents with Depressive Disorder and Impact of Omega-3 Fatty Acids in Randomised Clinical Trial.

Oxidative stress (OS) is thought to play a role in mental disorders. However, it is not clear whether the OS is the cause or consequence of the disorder. We investigated markers of oxidative stress (8-isoprostane (8-IsoP-U), lipoperoxides (LP), advanced oxidation protein products (AOPP) and nitrotyrosine (NT)) and antioxidant protection (Trolox equivalent antioxidant capacity (TEAC), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in 60 paediatric and adolescent patients with depressive disorder (DD) compared to healthy controls. The patients were divided into two groups (1:1). One group received an emulsion of omega-3 fatty acid (FA), and the other group an emulsion of sunflower oil with omega-6 FA for 12 weeks. The levels of 8-IsoP-U, AOPP and NT were increased, and GPx activity was decreased in patients compared to the controls. We found a significant positive correlation of the Children's Depression Inventory score with NT and a negative correlation with TEAC, SOD and GPx. NT correlated positively with the baseline omega-6/omega-3 FA ratio and a negatively with SOD. A supplementation with omega-3 FA, but not with omega-6 FA, decreased 8-IsoP-U, AOPP, NT levels and increased TEAC and SOD activity. Our results suggest that NT may play a role in the pathophysiology of DD, while elevated isoprostane is likely caused by the high omega-6/omega-3 FA ratio. Omega-3 FA supplementation reduces oxidative stress in patients with DD. This study was registered with the ISRCTN registry (ISRCTN81655012).

The Effect of Omega-3 Fatty Acids on Thromboxane, Brain-Derived Neurotrophic Factor, Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial.

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child's Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).

Lipid Profile, Lipoprotein Subfractions, and Fluidity of Membranes in Children and Adolescents with Depressive Disorder: Effect of Omega-3 Fatty Acids in a Double-Blind Randomized Controlled Study.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids such as total cholesterol (TCH), LDL-, and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. The primary endpoint of the study was the effect of omega-3 FA on the severity of depression in children and adolescents. This study aimed to investigate the secondary endpoint, relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities, and erythrocyte membrane fluidity in 58 depressed children and adolescents (calculated by the statistical program on the effect size), as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, and LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. Improvement of symptoms in the group supplemented with a fish oil emulsion rich in omega-3 FA in contrast to omega-6 FA (emulsion of sunflower oil) has been observed. We are the first to report that omega-3 FAs, but not omega-6 FA, increase large HDL subfractions (anti-atherogenic) after 12 weeks of supplementation and decrease small HDL subfractions (proatherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and the large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder. The study was registered under ISRCTN81655012.

High density lipoprotein subfractions and paraoxonase 1 in children.

The Lipoprint system (Quantimetrix Corp., CA, USA), enables the determination of 10 high density lipoprotein (HDL) subfractions in contrast to the 5 HDL subfractions that can be determined by ultracentrifuge analysis. HDL subfractions, and their relationships to the arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1), together with total-, very low density lipoprotein- and low density lipoprotein (LDL)-cholesterol and LDL subfractions were investigated in the serum of 27 mildly hypercholesterolemic children and 21 healthy controls. Our results suggest the antiatherogenity of large HDL (L-HDL) subfractions and the atherogenity of small HDL (S-HDL) subfractions in the study groups. However, the relationship between the intermediate HDL (I-HDL) subfractions with the LDL subfractions and other lipoproteins did not suggest that I-HDL subfractions are antiatherogenic. No significant association between PON1-A and the HDL subfractions was found. In contrast, PON1-L activity positively correlated with the antiatherogenic large HDL1 subfraction and negatively with intermediate HDL subfractions 4, 5 and 6. Our results contribute to the knowledge of the roles of total HDL and ten individual HDL subfractions in children and adolescents.

Paraoxonase 1 and HDL subfractions in hypercholesterolemic children and adolescents.

BACKGROUND: Assessment of the cardiovascular disease (CVD) risk factors in children can predict clinical manifestations of atherosclerosis in adulthood. The arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and lipid parameters (Total cholesterol (TCH), VLDL-cholesterol (VLDL), triacylglycerols (TAG), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and LDL- and HDL-subfractions and their mutual associations in 27 hypercholesterolemic children and adolescents were investigated. METHODS: Serum levels of TCH and TAG were determined using a Hitachi 911 analyser (Roche Diagnostics, Switzerland). LDL- and HDL-subfractions were determined by Lipoprint® system (Quantimetrix, Corp., USA). PON1-A and PON1-L activities were determined according to Gan et al. (1991) and Aviram and Rosenblat (2008). RESULTS: PON1-A activity was higher compared to healthy children (134.1±26.2 vs. 118.16±7.05 U/ml) and PON1-L was not different from healthy controls. Increased levels of atherogenic risk factors TCH, VLDL, IDL1 subfraction and decreased levels of the antiatherogenic IDL3 and LDL1 subfractions were observed in the hypercholesterolemic children compared to reference values. Increased levels of large HDL subfractions, comparable levels of intermediate HDL and lower levels of small HDL subfractions were observed in hypercholesterolemic children compared to healthy adults (in absence of data available for healthy children). No significant correlation between PON1-A and HDL subfractions was found. PON1-L activity positively correlated with antiatherogenic large HDL1 subfraction and negatively correlated with intermediate HDL4, 5 and 6 subfractions. CONCLUSIONS: The findings suggest that the PON1-L activity rather than PON1-A activity play a protective role in atherosclerosis. We confirmed atheroprotective effect of large and atherogenic properties of small HDL subfractions. The intermediate HDL subfractions probably play no atheroprotective role.

Fungal neuroinfections and fungaemia: unexpected increase of mortality from invasive fungal infections in 2005-2011 in comparison to 1989-1998: analysis of 210 cases.

OBJECTIVE: In this short communication we compared the data of fungaemia cases in Slovak hospitals from 1989-1998 published in 1999-2000 with data from 2005-2011. METHODS: Risk factors, etiology and outcome of fungaemia between two periods (1989-1998 vs. 2005-2011) were compared and risk factors for death assessed by univariate analysis (CDC 2006 Statistical Package). RESULTS: In comparison to 1989-1998 when only amphotericin B and fluconazole has been used (55%), in 2005-2011 only 35.2% patients received FLU, but 26.4% received voriconazole, 22% caspofungin and anidulafungin and about 6.6% lipid formulations of Amphotericin B. In etiology, while in 1989-1998 only 37.1% (115/310) represented non-albicans Candida (NAC) and non-Candida yeasts in 2005-2011 already reached 63.7%. The significant increase of breakthrough fungaemia may be a sign of inappropriate empiric therapy.

Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study.

BACKGROUND: Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine. METHODS: Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 µg), B6 (2.5 mg), folic acid (800 µg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16. RESULTS: The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, ß-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05). CONCLUSIONS: Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents. TRIAL REGISTRATION: Current Controlled Trials ISRCTN89549017.