Vitamin D deficiency is associated with tuberculosis disease in British children.

BACKGROUND: Basic science, epidemiological and interventional research supports a link between vitamin D and tuberculosis (TB) immunity, infection and disease. We evaluated the association between vitamin D levels and TB infection and disease in UK children recruited to the National Institute for Health Research IGRA Kids Study (NIKS).METHODS: Children presenting between 2011 and 2014 were eligible if they had history of exposure to an adult case with sputum smear/culture-positive TB, or were referred and diagnosed with TB disease. Children were assessed at baseline and at 6-8 weeks for immunological evidence of TB infection (interferon-gamma release assay and/or tuberculin skin test) and evidence of TB disease. Some centres routinely measured total 25-hydroxy vitamin D (25-OHD) levels.RESULTS: A total of 166 children were included. The median 25-OHD levels were higher in non-infected children (45.5 nmol/l) than in those with tuberculous infection (36.2 nmol/l) and TB disease (20.0 nmol/l). The difference between TB infection and disease was statistically significant (P < 0.001). By logistic regression, lower vitamin D levels were associated with TB disease among participants with infection or disease, with no evidence of confounding by age, sex, bacille Calmette-Guérin vaccination status, ethnicity, non-contact referral, season or centre.CONCLUSION: Children with TB disease had lower vitamin D levels than children with infection. Implications for prevention and treatment remain to be established.

Management of paediatric tuberculosis in leading UK centres: unveiling consensus and discrepancies.

SETTING: Large specialist paediatric TB clinics in the UK. OBJECTIVE: To evaluate clinical practice and compare with national and international guidelines. DESIGN: A survey based on an electronic questionnaire on the management of latent tuberculous infection (LTBI) and tuberculosis (TB) disease was conducted in 13 specialist paediatric TB clinics. The consensus and discrepancies were evaluated by descriptive analysis. RESULTS: Practice was reportedly different when choosing age limits for preventive treatment for TB contacts with initially negative tuberculin skin tests (TSTs), interpretation of TST results and use of interferon-gamma release assays (IGRAs) in the context of LTBI. In relation to management of children with TB disease, practices varied for duration of treatment of osteoarticular TB, monitoring for ethambutol ocular toxicity and use of pyridoxine. There was limited experience with multidrug-resistant TB (MDR-TB), and over half of the clinics monitored MDR-TB contacts without giving preventive treatment. CONCLUSIONS: The survey showed heterogeneity in several aspects of clinical care for children with TB. Available paediatric TB guidelines differ substantially, explaining the wide variations in management of childhood TB. Prospective paediatric studies are urgently required to inform and standardise clinical practice, especially in the context of evolving drug resistance.

The effect of crataegus fruit extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.

Crataegus (Hawthorn) fruit extracts (CE) are widely used for the treatment of various cardiovascular diseases (arrhythmias, heart failure, myocardial weakness, etc). Despite the fact that many of these diseases are associated with disturbances of the mitochondria, no data have been found on the effect of CE on their function. The aim of this study was to perform an oxygraphic investigation of the effect of CE (in concentration range from 70 ng/mL to 13.9 microg/mL of Crataegus phenolic compounds (PC)) and its several pure flavonoids on isolated rat heart mitochondria respiring on pyruvate+malate, succinate and palmitoyl-L-carnitine+malate. CE at doses under 278 ng/mL of PC had no effect on mitochondrial functions. At concentrations from 278 ng/mL to 13.9 microg/mL of PC, CE stimulated State 2 respiration by 11%-34% with all used substrates, and decreased the mitochondrial membrane potential by 1.2-4.4 mV measured with a tetraphenylphosphonium-selective electrode and H2O2 production measured fluorimetrically. Similar uncoupling effects on mitochondrial respiration were observed with several pure CE flavonoids. The highest CE concentration also slightly reduced the maximal ADP-stimulated and uncoupled respiration, which might be due to inhibition of the mitochondrial respiratory chain between flavoprotein and cytochrome c. Whether or not the uncoupling and other effects of CE on mitochondria may be realized in vivo remains to be determined.

[Antioxidant activity of tinctures prepared from hawthorn fruits and motherwort herb]. / Antioxidacní aktivita tinktur pripravených z hlohových plodu a nati srdecníku.

The paper aimed to determine and compare the antioxidant activity of two tinctures and selected flavonoids present in the tinctures. The tinctures were prepared from hawthorn fruits and motherwort herb. The group of selected flavonoids included rutin, quercetin, hyperosid, epicatechine, and procyanidin B2. Two methods were employed to determine antioxidant activities: the inhibition of peroxynitrite-induced nitration of tyrosine was measured, and the ability to quench radicals was examined by of the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Both tinctures under study were able to quench radicals and reactive forms of oxygen and nitrogen. The motherwort herb tincture was more effective, but no direct effect of phenolic compounds on the extent of antioxidant activity was demonstrated. The total content of polyphenols in the motherwort herb tincture was higher by 163 %, nevertheless antiperoxynitrite activity was higher just by 19 % (p < 0.05), and the ability to reduce DPPH differed in both tinctures in a minimal manner. Of the individual flavonoids, the substances present in the tinctures in higher concentrations contributed most to antioxidant activity. In the hawthorn fruit tincture it was epicatechine and hyperosid, whereas in the motherwort herb tincture it was rutin.

[An orientational examination of the effects of extracts from mixtures of herbal drugs on selected renal functions]. / Orientacní sledování vlivu výluhu ze smesí rostlinných drog na vybrané funkce ledvin.

The paper aimed to determine the effects of mixtures of selected medicinal plants on some physiological renal functions, i.e. excretion of urine and electrolytes and changes in the quantity of prostaglandins E2 (PGE2) and kallikrein-kinins in rat blood plasma after water and salt load. The following medicinal plants were selected for the examination: downy birch (Betula pubescens EHRH.), everlasting flower (Helichrysum arenarium L. MOENCH.), hawthorn (Crataegus oxyacantha L.), woodland strawberry (Fragaria vesca L.), sweet corn (Zea mays L.), German chamomile (Matricaria recutita L.), and field horsetail (Equisetum arvense L.). Herbal drugs were used to compose 6 mixtures. Extracts from these mixtures were administered to Wistar strain males and their effects were compared with the effects of an administered suspension of hydrochlorothiazide, an extract from field horsetail herb alone, and a control group of animals which was not administered any preparation. The greatest diuretic effect was found in a mixture composed of birch leaves (Betulae folium), hawthorn berries (Crataegi fructus), strawberry leaves (Fragariae folium), corn silk (Maydis stigmata), chamomile flowers (Matricariae flos), and horsetail herb (Equiseti herba). Its effect was greater by 47% and 34% than the effect of a horsetail herb extract and a hydrochlorothiazide suspension (p < 0.05), respectively. The extract from this mixture also increased the quantity of prostaglandins E2 and kallikrein-kinins in rat blood plasma in water and salt load.

The effect of flavonoids on rat heart mitochondrial function.

In this study the effects of flavonoids (quercetin and its derivatives as rutin, hyperoside, quercitrin) on the oxidative phosphorylation in rat heart mitochondria were investigated. We found that all investigated flavonoids possessed uncoupling activity. Thus, quercetin, rutin, and quercitrin in dose-dependent manner induced a stimulation of the State 2 respiration rate by 10-110% with pyruvate + malate as substrate. The maximal stimulation of the State 2 respiration rate was obtained at 1.08 ng/ml of quercetin, 15.2 ng/ml of hyperoside and 44.4 ng/ml of rutin. Quercitrin had clearly lower effects. The State 3 respiration rate was also affected by flavonoids. Quercetin (from 1.08 ng/ml), hyperoside (from 10 ng/ml) and rutin (from 60 ng/ml) caused the decrease in State 3 respiration rate by 16-51%. We assume, that partial mitochondrial uncoupling (without affecting the State 3 respiration rate) induced by flavonoids could have a cardioprotective effect, and that mitochondria could be involved in the mechanism of this process.

[Liquid ginger extract: technology of production and quality evaluation]. / Tekutý zázvorový extrakt: technologie výroby a hodnocení jakosti.

The paper aimed to elaborate the technology of the production of a liquid ginger extract and to select and verify the methods of quality evaluation of the final preparation. The experiment revealed 70% ethanol as a suitable extraction agent. The optimal conditions for the development of an extract of good quality are established when the herbal drug is crushed to form particles passing through a sieve with a mesh size of 4000 microm, the extraction method is repercolation with the division of the charge of the drug in the relation 5:3:2, and the liquid flows from the percolator at a rate of 0.2ml/min/100 g of the drug. The presence of amino acids, saccharides, glycosides, reducing agents, phenolic substances, and alkaloids in the finished extract was demonstrated by means of colour or precipitation reactions. Thin-layer chromatography was employed to demonstrate gingerols and shogaols. Evaporation residue, ethanol concentration, and the amount of essential oils were determined quantitatively.

[Composite tincture from the tops of the purple coneflower (Echinacea purpurea) and the fruits of the dog rose (Rosa canina): technology of production and evaluation of quality]. / Slozená tinktura z nati trapatky nachové (Echinacea purpurea) a plodu ruze sípkove (Rosa canina): technologie výroby a hodnocení jakosti.

This paper aimed to elaborate the technology of the production of a composite tincture with an immunostimulatory and adaptogenic effect, to select suitable methods of quality evaluation, and perform stability tests. The tops of the purple coneflower (Echinaceae herba) and fruits of the dog rose (Cynosbati fructus) in a ratio of 1:1 were employed to prepare the tincture. The tincture itself was prepared in a ratio of 1:5. The experiment revealed that ethanol 50% was the most suitable extracting agent. The optimal conditions for the obtaining of a quality tincture are formed when the drug is disintegrated into the required degree by grinding, percolation is used for extraction, and the rate of flowing of the extract from the percolator is 0.2 ml/min/100g of the drug. The determination of the dry residue, relative density, ethanol concentration and content of cichoric acid (spectrophotometrically), ascorbic acid (oxidimetrically), and tannins (manganometrically) served to evaluate the quality of prepared extracts. Stability tests (temperature 25+/-2 degrees C, relative humidity 60+/-5%, period of 2 years) have shown that the prepared tincture maintains its quality parameters for the given period.