Therapeutic management in paediatric alopecia areata: A systematic review.

Alopecia areata is the third most common cause of dermatology consultations in children but the treatment of paediatric alopecia areata remains challenging. A systematic review of the literature about the treatment of alopecia areata in children (≤18 years old) was performed on 11 May 2020 by searching the PubMed, Scopus and EBSCO databases. The terms used for the search were: 'alopecia areata', 'alopecia totalis' or 'alopecia universalis' combined with 'paediatric', 'children' or 'childhood'. A total of 89 articles were included in final evaluation. The most commonly assessed treatment options in paediatric alopecia areata were topical immunotherapy (response rate in monotherapy: 54%; 187/345) intralesional glucocorticosteroids (75%; 211/280), systemic glucocorticosteroids (73%; 102/140), and anthralin (42%; 31/74). Topical glucocorticosteroids (81%; 35/43), systemic Janus kinase (JAK) inhibitors (90%; 27/30), topical calcineurin inhibitors (42%; 8/19), topical JAK inhibitors (65%; 11/17), PUVA therapy (56%; 9/16) and 308-nm excimer laser (77%; 10/13) were also evaluated. Additionally, evaluation in smaller numbers of paediatric patients included methotrexate (100%; 10/10), topical minoxidil (44%; 4/9) and cyclosporine (83%; 5/6). There were limited data considering children with alopecia areata treated with azathioprine, hydroxychloroquine, topical sildenafil, topical prostaglandin analogues, fractional carbon dioxide laser, leflunomide, mesalazine, apremilast, dupilumab, ustekinumab, efalizumab, botulinum toxin, and compound glycyrrhizin. On the basis of the limited data available glucocorticosteroids (systemic, intralesional or topical) and JAK inhibitors (systemic or topical) may be considered the best documented and most effective treatment options in alopecia areata in children. There are no sufficient paediatric data to compare treatment safety and relapse rates in these therapeutic modalities.

Novel bioactive properties of low-polarity fractions from sea-buckthorn extracts (Elaeagnus rhamnoides (L.) A. Nelson) - (in vitro).

Due to the richness of bioactive substances and easy accessibility, sea-buckthorn can be an ingredient of currently popular functional food supporting anti-cancer therapy. Low-polarity fractions from fruit (OL), twigs (GL) and leaves (LL) were investigated. Compared to the previous scientific reports a more detailed analysis of the chemical composition of individual fractions was performed. Cytotoxicity of low-polarity fractions has been investigated and activity compared in human tumor and normal cells cultured in vitro. The genotoxicity and pro-apoptotic properties of low-polarity fractions were also followed on selected cell lines that had proved to be the most sensitive. In the proposed research model being tested, low-polarity fractions act cytotoxically, even 3 times more strongly in cancer cells than normal ones. Measurement of caspase 3/7 activity indicated that cell death occurs through apoptosis. Furthermore, high concentrations of low-polarity fractions have moderate genotoxic properties. Data obtained on the biological properties of low-polarity fractions from sea-buckthorn show that these fractions can potentially support cancer cells elimination. Phytotochemical analysis indicates the key role of the triterpenoids in this process.

Inhibition of blood platelet adhesion by phenolics' rich fraction of Hippophae rhamnoides L. fruits.

Beneficial influence of fruits on human health may be their ability to prevent the hyperactivation of blood platelets and cardiovascular disorders. Effects of the phenolic fraction from Hippophae rhamnoides fruit on different stages of blood platelet activation (platelet adhesion and aggregation) were studied in vitro. We also examined effects of the H. rhamnoides fraction on metabolism of thiol groups, which plays an important role in platelet functions. The effects of the H. rhamnoides fraction on adhesion of blood platelets to collagen and fibrinogen were determined with Tuszynski's and Murphy's method. The platelet aggregation was determined with turbidimetry. The action of the H. rhamnoides fraction on the level of thiol groups in platelet proteins and a level of glutathione (GSH) in platelets was estimated with 5,5'-dithio-bis(2-nitro-benzoic acid). The tested fraction of H. rhamnoides (0.5 - 50 µg/ml; 30 min of the incubation time 30 min) inhibited blood platelets adhesion to collagen and fibrinogen. The effect of the tested fraction on blood platelet adhesion depended on concentration of fraction. In presence of the highest tested concentration which was 50 µg/ml, inhibition of platelet adhesion for thrombin-activated platelets was about 55%. On the other hand, tested plant fraction had no anti-aggregatory properties. Our results showed anti-adhesive properties of phenolic fraction from H. rhamnoides fruit and we suggest that it may be beneficial for prevention of cardiovascular diseases.

Antioxidant action of six Trifolium species in blood platelet experimental system in vitro.

This study includes a comparative evaluation of antioxidant effects of plant extracts (1.5-50.0 µg/ml), derived from six clover (Trifolium) species: T. alexandrinum L., T. fragiferum L., T. hybridum L., T. incarnatum L., T. resupinatum var. majus Boiss., and T. resupinatum var. resupinatum L. Chemical profiles of the extracts contained three or four groups of (poly)phenolic compounds such as phenolic acids, clovamides, isoflavones, and other flavonoids. Antioxidant properties of Trifolium extracts were assessed as the efficacy to reduce oxidative and nitrative damage to blood platelets, exposed to 100 µM peroxynitrite-induced oxidative stress in vitro. Antioxidant actions of the examined extracts were determined by the following biomarkers of oxidative stress: thiol groups, 3-nitrotyrosine, lipid hydroperoxides, and thiobarbituric acid-reactive substances (TBARS). Despite the significant differences in the chemical composition (the total phenolic concentrations varied between 11.30 and 52.55 mg/g of dry mass) of Trifolium extracts, we observed noticeable protective effects of almost all tested plant preparations. The T. alexandrinum extract, containing the highest concentration of phenols, was the most effective antioxidant among the tested extracts. On the other hand, the T. incarnatum extract, which contained a comparable total phenolic content (49.77 mg/g), was less efficient in prevention of tyrosine nitration and generation of TBARS. These findings indicate on the important role of individual phenolic components of the examined clover extracts for the final antioxidative effects. Antioxidative properties of the remaining extracts were noticeably weaker.

Plant components with specific activities against rumen methanogens.

A wide range of plant bioactive components (phytochemicals) have been identified as having potential to modulate the processes of fermentation in the rumen. The use of plants or plant extracts as natural feed additives has become a subject of interest not only among nutritionists but also other scientists. Although a large number of phytochemicals (e.g. saponins, tannins and essential oils) have recently been investigated for their methane reduction potential, there have not yet been major breakthroughs that could be applied in practice. A key tenet of this paper is the need for studies on the influence of plant components on methane production to be performed with standardized samples. Where there are consistent effects, the literature suggests that saponins mitigate methanogenesis mainly by reducing the number of protozoa, condensed tannins both by reducing the number of protozoa and by a direct toxic effect on methanogens, whereas essential oils act mostly by a direct toxic effect on methanogens. However, because the rumen is a complex ecosystem, analysis of the influence of plant components on the populations of methanogens should take into account not only the total population of methanogens but also individual orders or species. Although a number of plants and plant extracts have shown potential in studies in vitro, these effects must be confirmed in vivo.

Studies on antioxidant properties of polyphenol-rich extract from berries of Aronia melanocarpa in blood platelets.

The antioxidant properties of extract from berries of Aronia melanocarpa (chokeberry) containing: anthocyanidines, phenolic acids and quercetine glycosides on oxidative/nitrative stress induced by peroxynitrite (ONOO(-), a powerful physiological oxidant, nitrating species and inflammatory mediator) in human blood platelets were studied in vitro. The extract from A. melanocarpa (5 - 50 microg/mL) significantly inhibited platelet protein carbonylation (measured by ELISA method) and thiol oxidation estimated with 5,5'-dithio-bis(2-nitro-benzoic acid) (DTNB) induced by peroxynitrite (0.1 mM) (IC(50)--35 microg/mL for protein carbonylation, and IC(50)--33 microg/mL for protein thiol oxidation). The tested extract only slightly reduced platelet protein nitration (measured by C- ELISA method). The extract also caused a distinct reduction of platelet lipid peroxidation induced by peroxynitrite. Moreover, in our preliminary experiments we observed that the extract (50 microg/mL) reduced oxidative/nitrative stress in blood platelets from patients with breast cancer. The obtained results indicate that in vitro the extract from A. melanocarpa has the protective effects against peroxynitrite-induced oxidative/nitrative damage to the human platelet proteins and lipids. The extract from A. melanocarpa seems to be also useful as an antioxidant in patients with breast cancer.

First European interlaboratory study of the analysis of benzoxazinone derivatives in plants by liquid chromatography.

Six laboratories from four different countries participated in the first European interlaboratory comparison exercise within the framework of the "Fate and toxicity of allelochemicals (natural plant toxins) in relation to environment and consumer" (FATEALLCHEM) European Union Project. The study, organized between November 2002 and March 2003, involved the analyses of seven benzoxazinone derivatives in two standard solutions and one purified extract of root material. Results are reported from the first phase of the study that examined the variability associated with different detection methods and different laboratories. The analytical strategies were based on liquid chromatography (LC) with diode array detection, LC coupled to mass spectrometry (MS) and LC coupled to tandem MS. When data from all laboratories were pooled, the relative standard deviation values ranged from 2 to 14% for the determination of target compounds in standard solutions, and between 19 and 47% for the analysis in root material. Comparison of the three detection techniques leads to the conclusion that MS approaches are the most accurate and precise techniques for the determination of benzoxazinone derivatives at ng/microL level in plant material.

Alfalfa (Medicago sativa L.) flavonoids. 2. Tricin and chrysoeriol glycosides from aerial parts.

Ten flavone glycosides have been isolated and identified in aerial parts of alfalfa. These included six tricin, one 3'-O-methyltricetin, and three chrysoeriol glycosides. Most of these compounds were acylated with ferulic, coumaric, or sinapic acids, and acylation occurred on the terminal glucuronic acid. Eight of these compounds, including 7-O-beta-D-glucuronopyranosyl-3'-O-methyltricetin, 7-O-beta-D-glucuronopyranosyl-4'-O-beta-D-glucuronopyranosidechrysoeriol, 7-O-[2'-O-feruloyl-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]chrysoeriol, 7-O-[2'-O-feruloyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]chrysoeriol, 7-O-[2'-O-sinapoyl-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]tricin, 7-O-[2'-O- feruloyl-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]tricin, 7-O-[2'-O-p-coumaroyl-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]tricin, and 7-O-[2'-O-feruloyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]tricin, have not been reported previously in the plant kingdom. Two previously identified alfalfa flavones, 7-O-beta-D-glucuronopyranosidetricin and 7-O-[beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]tricin, were also isolated.

Steroidal saponins of Yucca schidigera Roezl.

Eight steroidal saponins have been isolated from Yucca schidigera Roezl. trunk, and their structures were established by spectral (MS and NMR) techniques. These included three novel furostanol glycosides including 3-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranosyl-5 beta(25R)-furostan-3 beta,22 alpha,26-triol 26-O-beta-D-glucopyranoside, 3-O-beta-D-glcopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranosyl-5 beta(25R)-furost-20(22)-en-3 beta,26-diol-12-one 26-O-beta-D-glucopyranoside, 3-O-beta-D-glcopyranosyl-(1-->2)-beta-D-glucopyranosyl-5 beta(25R)-furostan-3 beta,22 alpha,26-triol 26-O-beta-D-glucopyranoside, and five known spirostanol glycosides. On the basis of the extraction efficiency, furostanol glycosides made up only 6.8% of total saponins isolated.

Acylated apigenin glycosides from alfalfa (Medicago sativa L.) var. Artal.

Three flavones, including 4'-O-[2'-O-E-feruloyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]apigenin, 7-O-beta-D-glucuronopyranosyl-4'-O-[2'-O-E-feruloyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]apigenin and 7-O-beta-D-glucuronopyranosyl-4'-O-[2'-O-p-E-coumaroyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]apigenin have been identified in alfalfa var. Artal. The known flavone 7-O-[2-O-E-feruloyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucurono-pyranoside] apigenin was also isolated. The structures of these compounds were deduced on the basis of their spectral data.

Resveratrol and other phenolics from the bark of Yucca schidigera roezl.

Five phenolic constituents have been identified in Yucca schidigera bark, and their structures were established by spectral (FABMS and NMR) experiments. These included two known stilbenes, trans-3,4',5-trihydroxystilbene (resveratrol) and trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, as well as three novel compounds, yuccaols A, B, and C, with spiro-structures rarely occurring in the plant kingdom. It is suggested that yuccaols A-C are biosynthethized via attachment of a stilbenic derivative to the carbocationic intermediate of the oxidative flavanone-flavonol conversion.

Alfalfa (Medicago sativa L.) flavonoids. 1. Apigenin and luteolin glycosides from aerial parts.

Nine flavones and adenosine have been identified in aerial parts of alfalfa, and their structures were established by spectral (FABMS and NMR) techniques. Five of the identified compounds, including apigenin 7-O-[beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranosyl]-4'-O-beta-D-glucuronopyranoside, apigenin 7-O-[2-O-feruloyl-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranosyl]-4'-O-beta-D-glucuronopyranoside, apigenin 7-O-[2-O-feruloyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside], apigenin 7-O-[2-O-p-coumaroyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside], and luteolin 7-O-[2-O-feruloyl-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranosyl]-4'-O-beta-D-glucuronopyranoside, have not been reported before in the plant kingdom. Additionally, five known compounds, including apigenin 7-O-beta-D-glucuronopyranoside, apigenin 4'-O-beta-D-glucuronopyranoside, apigenin 7-O-[beta-D- glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside], luteolin 7-O-beta-D-glucuronopyranoside, and adenosine, were identified.

Determination and toxicity of saponins from Amaranthus cruentus seeds.

The concentrations of four triterpene saponins present in amaranth seeds were determined with high-performance liquid chromatography. It was shown that the total concentration of saponins in seeds was 0. 09-0.1% of dry matter. In germinating seeds an increase in concentration to 0.18% was observed after 4 days of germination, which remained stable for the next 3 days and later dropped to 0.09%. Highly purified extracts from the seeds were tested for their toxicity against hamsters. The hydrophobic fraction obtained by the extraction of seeds with methylene chloride showed no toxicity; the behavior of tested animals was similar to that of the group given an equivalent dose of rapeseed oil. A crude saponin fraction, containing approximately 70% of pure saponins in the matrix, showed some toxicity; the approximate lethal dose was calculated as 1100 mg/kg of body weight. It is concluded that low contents of saponins in amaranth seeds and their relatively low toxicity guarantee that amaranth-derived products create no significant hazard for the consumer.

Silent myocardial ischaemia in patients with essential arterial hypertension and non-insulin dependent diabetes mellitus.

The concomitant presence of diabetes mellitus and arterial hypertension significantly impairs myocardial function through a direct negative effect on cardiac myocytes, coronary microvessels and precipitation of atherosclerosis in major coronary arteries. The purpose of the present study was to establish to what extent non-insulin dependent diabetes mellitus (NIDDM) modified silent myocardial ischaemia (SMI) in patients with essential hypertension and without documented coronary artery disease (CAD). The study population consisted of 41 patients with essential arterial hypertension associated with NIDDM, treated with diet and oral hypoglycaemic agents (group I) and 40 patients with essential arterial hypertension without diabetes mellitus (group II). Both groups were comparable with respect to age, gender, duration, severity and complications of hypertension. A mean duration of diabetes mellitus in group I was 6.8 years. Conventional and automatic blood pressure and heart rate measurements, continuous ECG recordings, echocardiograms and laboratory tests were obtained in all patients. SMI was more frequent in group I than in group II (29.3% vs 12.5%, P < 0.05). In group I the total duration of SMI was longer (37.3 vs 2.8 min, P < 0.001) and the total number of silent episodes was larger (15.5 vs 2.6, P < 0.001). No inter-group differences were seen in conventional and automatic blood pressure and heart rate measurements. Both groups did not differ significantly in left ventricular mass index (LVMI) or the proportion of patients with left ventricular hypertrophy (LVH) (75.6% vs 60%). Lipid profile in both groups indicated an increased risk of CAD, but without significant differences. In conclusion, in patients with essential arterial hypertension and diabetes mellitus, the incidence and severity of SMI were clearly higher than in hypertensives with normal carbohydrate metabolism. Employment of modern diagnostic techniques in hypertensives permits identification of those at greater risk, which may have further clinical implications.

[Antihypertensive drug therapy in relation to lipid disorders]. / Leczenie nadcisnienia tetniczego w aspekcie wplywu na zaburzenia lipidowe.

Essential arterial hypertension is frequently accompanied by metabolic disorders, including hyperlipidemia. In Polish epidemiological studies hyperlipidemia has been detected in 70% of men and 67% of women. Metabolic disorders associated with arterial hypertension increase with the increasing severity of the disease and affect its course. However, hypotensive therapy may modify the metabolic parameters. Therefore, the appropriate antihypertensive therapy should be selected individually taking into account actual metabolic abnormalities. At present it is recommended to use ACE inhibitors, calcium antagonists and alpha-receptor blockers as the first line therapy in patients with arterial hypertension combined with hyperlipidemia.

Apo E isoforms, insulin output and plasma lipid levels in essential hypertension.

BACKGROUND: The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential hypertension and in control subjects (non-obese, non-diabetic normotensive subjects) was estimated. METHODS: According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output. RESULTS: The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups. CONCLUSION: The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.

[Syncope as a cardiologic problem]. / Omdlenia jako problem kardiologiczny.

Syncope is a frequent clinical event. It is mainly caused by a suddenly reduced cerebral blood flow. There are two reasons for sudden cerebral underperfusion: cardiogenic - associated with cardiac disorders and neurocardiogenic - resulting from a sudden fall of arterial blood pressure due to impaired autoregulation of the circulation. Cardiogenic syncopes prevail in cardiac diseases associated with impaired blood flow and cardiac arrhythmias. They develop in aortic stenosis, hypertrophic cardiomyopathy, atrial myxoma, myocardial infarction, pulmonary embolism, cardiac tamponade. Cardiac arrhythmias associated with syncope include ventricular tachycardia, supraventricular tachycardia in the preexcitation syndrome, sinus bradycardia, II degrees and III degrees atrioventricular block, atrial fibrillation with rapid ventricular response. The prognostic value and pathomechanisms loss of consciousness in these disease states have been discussed. Neurocardiogenic syncopes include vasovagal syncope, carotid sinus syndrome, orthostatic hypotension, event-induced syncope. It is frequently difficult to establish the reason for syncope. Physical examination and a history should be taken first followed by noninvasive studies such as standard ECG, exercise testing, carotid sinus compression, Holter monitoring, tilt testing, signal-averaged ECG. Noninvasive diagnosis helps establish the cause of syncope in 53-62% of cases and is indispensable before proceeding to electrophysiological testing. Such testing should be limited to patients with organic heart disease, in whom previous examinations did not reveal the etiology of loss of consciousness.

Relation between insulinaemia and lipoprotein composition in men with primary arterial hypertension with and without hypertriglyceridaemia.

The purpose of the study was to evaluate a relationship between HDL, triglyceride levels and insulinaemia in primary arterial hypertension. The study population consisted of 60 men aged 32-68 years (mean age 50.87 years, s.d. 8.4) with hypertension duration of 11.1 years (s.d. 6.4 years) who were compared with 60 normotensives matched for sex, age and BMI. We examined blood pressure, plasma lipoprotein content, sum of glucose and sum of insulinaemia (sum ins) during OGTT (oral glucose tolerance test). OGTT revealed insulin secretion almost twice as high in hypertensives (P < 0.001 sum ins 11002 microU min/ml, s.d. 4846) than in normotensives (sum ins 6662 microU min/ml, s.d. 3099). Comparison of concentration of selected VLDL components shows that hypertensives were characterised by markedly higher concentration of triglycerides (1.46 mmol/L, s.d. 0.87 in hypertensives and 1.04 mmol/L, s.d. 0.54 in normotensives), free and esterified cholesterol and protein, including apolipoprotein B than normotensives. It was also found that hypertensives had higher levels of apo CIII0 and lower levels of CIII1 VLDL than normotensives. Hypertensive patients showed also a higher frequency of apo E2 isoforms (three-fold) and apo E4 isoforms (two-fold) than healthy subjects. No changes were detected in the composition of LDL and HDL between the groups. Analysing the discriminating ability of biochemical parameters chosen in a step-wise manner it was found that sum ins and HDL, protein and cholesterol concentrations were the factors most powerfully differentiating men with hypertension from healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)