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1.
Ter Arkh ; 95(6): 511-515, 2023 Aug 17.
Artículo en Ruso | MEDLINE | ID: mdl-38158972

RESUMEN

We report a case of atypical hemolytic uremic syndrome (aHUS) that occurred after childbirth in a patient with a history of numerous recurrent episodes of TMA with nephrotic proteinuria and impaired renal function. At 33 weeks of the first spontaneous pregnancy, proteinuria up to 0.8 g/l was first registered, at 38 weeks she was hospitalized with proteinuria, reaching a maximum of 13 g/l, she was delivered promptly, after which progressive thrombocytopenia was noted over the next few days (up to 44×109/l) and anemia and severe arterial hypertension, which could not be corrected by several groups of antihypertensive drugs. Initiated plasma therapy had no effect. After exclusion of all other causes of TMA, therapy with eculizumab was initiated, which made it possible to quickly and completely stop the phenomena of TMA. The presented observation demonstrates the successful treatment of recurrent course of aHUS with eculizumab with the achievement of complete recovery of kidney function in a patient with a homozygous mutation in the MCP gene. It is worth noting the importance of genetic research even in those situations where clinically aHUS is beyond doubt.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Embarazo , Femenino , Humanos , Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/terapia , Pronóstico , Periodo Posparto , Proteinuria/genética , Pruebas Genéticas , Fenotipo
2.
Dokl Biochem Biophys ; 507(1): 374-379, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36787006

RESUMEN

The effect of temperature on the effectiveness of the incorporation of deuterium into pyrrolylcarnosine (PC) was studied. Deuterium gas and heavy water were used as a source of deuterium. Isotope exchange was carried out using solid-phase and liquid-phase methods. It was found that it is better to use isotope exchange with deuterated water to obtain preparative amounts of labeled pyrrolylcarnosine. When using y solid-phase method, the main label is in pyrrole. The incorporation of deuterium at a higher temperature occurs more evenly. In addition, the use of deuterated water made it possible to reduce the amount of unlabeled isotopomer to almost 0% and to obtain a product with a yield of 70% and a content of more than seven deuterium atoms. It was established that the content of deuterium in the compound can be increased by pretreating the reaction mixture with deuterium gas. This approach opens up additional opportunities for the synthesis of labeled compounds.


Asunto(s)
Agua , Deuterio
3.
Osteoarthritis Cartilage ; 29(5): 667-677, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33617972

RESUMEN

OBJECTIVE: The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). METHOD: This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1,500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0-100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. RESULTS: One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG three and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (-2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE vs four participants (7%) in the placebo group. CONCLUSION: There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).


Asunto(s)
Antiinflamatorios/uso terapéutico , Mano/fisiopatología , Osteoartritis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Anciano , Boswellia , Curcumina/uso terapéutico , Dimetilsulfóxido/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Osteoartritis/fisiopatología , Pinus , Corteza de la Planta , Sulfonas/uso terapéutico , Escala Visual Analógica
4.
Vopr Pitan ; 89(3): 97-105, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-32790262

RESUMEN

Wilson disease (WD) is a rare hereditary disorder of copper metabolism, based on of the ATP7B gene mutation, resulting in defect of cooper excretion, which leads to accumulation of cooper in tissues and internal organs (especially in the liver and brain). The basic principle of diet therapy for patients with WD is a diet with reduced copper content, adherence to which is accompanied by significant dietary restrictions, so patients with WD, compared to other liver diseases, represent the most difficult contingent for adjustment of diet. The aim: to assess of the effect of diet therapy with modification of the protein component on nutritional status of patients with WD. Material and methods. The study included 33 patients (15 men and 18 women, 31.4±10.2 years old) with WD. All patients had liver damage: non-cirrhotic stages (NCC) - in 12 (36.3%) patients, liver cirrhosis (LC) - in 21 (63.7%) patients. Out of the last, 14 (66.7%) patients had compensated LC, 7 (33.3%) patients had decompensated LC. The average age of the patients. All patients were divided into two groups, comparable by body mass index. For 2 months outpatients of the 1st group (n=17) received a specialized diet with a modification of the protein component, made by incorporating 20 g of dry composite protein mix (containing 50% protein in the form of milk protein concentrate, 4% dietary fiber) into the daily diet. Outpatients of the 2nd group (n=16) received the same diet without modification. All patients were provided anthropometry, including shoulder circumference and triceps skin-fold measurement, and analysis of the body mass composition with bioimpedance analyzer, the index of lean mass was additionally calculated. Clinical and biochemical blood tests were also conducted for all patients. Results and discussion. As a result of the diet therapy, statistically significant (p<0.05) changes were observed in patients of the 1st group who received a diet with a modification of the protein component: an increase in the index of lean mass (by 3.0%) and circumference of the shoulder muscles (by 2.3%), serum total protein and albumin (by 7.9 and 6.1%), an increase in the absolute number of lymphocytes (by 18.8%) and decrease in serum total bilirubin (by 20.2%). A statistically significant decrease in the level of free copper was observed in both groups (by 2.1 and 1.8 fold). Conclusion. The use of a specialized diet with a modification of the protein component, based on the inclusion of a protein composite dry mix in the diet, improves the nutritional status indicators in patients with Wilson disease.


Asunto(s)
Proteínas en la Dieta/administración & dosificación , Alimentos Fortificados , Degeneración Hepatolenticular , Estado Nutricional , Adulto , Femenino , Degeneración Hepatolenticular/dietoterapia , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/patología , Degeneración Hepatolenticular/fisiopatología , Humanos , Hígado/metabolismo , Hígado/patología , Hígado/fisiopatología , Masculino , Persona de Mediana Edad
5.
Bull Exp Biol Med ; 169(2): 242-245, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32651828

RESUMEN

We compared the direct neuroprotective effect of minor food components, antioxidants hesperetin and carnosine, and analyzed their influence on the parameters of the oxidative status of the penumbra zones in the cerebral cortex during focal ischemia (1 h) of with reperfusion in Wistar rats. The animals received hesperetin and carnosine included in the diet in daily doses of 50 and 150 mg/kg, respectively, for 7 days before ischemia induction. The neuroprotective effect of hesperetin manifested in reduction of the ischemic lesion size by 30%, which was comparable with the effect of carnosine. Both hesperetin and carnosine reduced the level of MDA in the penumbra zone of the cerebral cortex and increased the total antioxidant activity of the brain tissue. Hesperetin also increased SOD activity to a level observed in the sham-operated control group.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Carnosina/uso terapéutico , Hesperidina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Isquemia Encefálica/metabolismo , Masculino , Ratas , Ratas Wistar
6.
Biomed Khim ; 66(2): 145-150, 2020 Feb.
Artículo en Ruso | MEDLINE | ID: mdl-32420895

RESUMEN

Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Ubiquinona/análogos & derivados , Animales , Antioxidantes/análisis , Neuronas/citología , Neuronas/efectos de los fármacos , Estrés Oxidativo , Cultivo Primario de Células , Ratas , Ubiquinona/uso terapéutico
7.
Eur J Neurol ; 27(4): 644-652, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31725927

RESUMEN

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.


Asunto(s)
Encéfalo/diagnóstico por imagen , Colinesterasas/metabolismo , Trastorno de la Conducta del Sueño REM/diagnóstico por imagen , Anciano , Encéfalo/metabolismo , Desnervación , Dihidroxifenilalanina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Tomografía de Emisión de Positrones/métodos , Trastorno de la Conducta del Sueño REM/metabolismo
8.
Vopr Pitan ; 88(4): 12-17, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31722136

RESUMEN

Wilson disease is hereditary disorder of copper metabolism, based on defect of cooper excretion, which leads to accumulation of cooper in the liver and brain. This disease is one of the most difficult to diagnose. Without treatment disease brings to early disability and lethal outcome. In the article, domestic and foreign approaches to dietary management of Wilson disease have been compared. Diet is not recommended as sole therapy. The degree of restriction of the products containing copper now is discussed. According to the Russian clinical guidelines of diagnosis and treatment of Wilson disease exception of products, copper content in which exceeds 0.5 mg/100 g (liver, shellfish, nuts, cocoa products, mushrooms, bean and some grains) is recommended, while in EASL clinical guidelines there are no any information about restriction of the products containing copper. It is necessary to pay attention not only to cooper restriction, but also to qualitative components of diet. Protein is important part of nutrition under liver disease. According to ESPEN guidelines, the recommended protein intake at chronic hepatitis and cirrhosis is 1.2-1.5 g/kg/day. Dairy products and whey protein are good sources of protein, they almost do not contain cooper, therefore they can be used without restrictions at Wilson disease (in case of normal lactose and milk protein tolerance). The reduce of consumption of sugar, refined carbohydrates and trans fats is also recommended. Dietary recommendations must take into consideration the nutrition status of the patient (protein energy malnutrition, normal body weight, obesity) and degree of liver damage (chronic hepatitis, cirrhosis). It is necessary to develop individualization of diet, increasing efficiency of medicinal treatment of Wilson disease.


Asunto(s)
Degeneración Hepatolenticular/dietoterapia , Estado Nutricional , Encéfalo/metabolismo , Encéfalo/patología , Cobre/metabolismo , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/patología , Humanos , Hígado/metabolismo , Hígado/patología , Guías de Práctica Clínica como Asunto
9.
Amino Acids ; 51(1): 139-150, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30353356

RESUMEN

Carnosine (b-alanyl-L-histidine) is an endogenous dipeptide widely distributed in excitable tissues, such as muscle and neural tissues-though in minor concentrations in the latter. Multiple benefits have been attributed to carnosine: direct and indirect antioxidant effect, antiglycating, metal-chelating, chaperone and pH-buffering activity. Thus, carnosine turns out to be a multipotent protector against oxidative damage. However, the role of carnosine in the brain remains unclear. The key aspects concerning carnosine in the brain reviewed are as follows: its concentration and bioavailability, mechanisms of action in neuronal and glial cells, beneficial effects in human studies. Recent literature data and the results of our own research are summarized here. This review covers studies of carnosine effects on both in vitro and in vivo models of cerebral damage, such as neurodegenerative disorders and ischemic injuries and the data on its physiological actions on neuronal signaling and cerebral functions. Besides its antioxidant and homeostatic properties, new potential roles of carnosine in the brain are discussed.


Asunto(s)
Isquemia Encefálica/fisiopatología , Carnosina/farmacología , Enfermedades Neurodegenerativas/fisiopatología , Fármacos Neuroprotectores/farmacología , Neurotransmisores/farmacología , Animales , Homeostasis/efectos de los fármacos , Humanos
10.
Vopr Pitan ; 87(5): 52-62, 2018.
Artículo en Ruso | MEDLINE | ID: mdl-30592890

RESUMEN

In this article the biotechnology of the dairy product based on the probiotic strain of Lactobacillus reuteri LR1 is presented. The following conditions of milk fermentation were screened: fermentation by monoculture of Lactobacillus reuteri LR1, fermentation by monoculture of Lactobacillus reuteri LR1 with addition of yeast extract as growth-promoting factor, and combined fermentation by Lactobacillus reuteri LR1, Lactobacillus helveticus NK1 and Streptococcus thermophilus (HTC). It had been demonstrated that after 8 hours of cultivation the number of Lactobacillus reuteri LR1 cells in the monoculture with introduced yeast extract was up to 5,9×108 CFU/cm3 whereas cell count for the monoculture without yeast extract introduction was 1,6×107 CFU/cm3. The optimized biotechnological parameters of the dairy product fermentation, which provided the required Lactobacillus reuteri LR1 cell count, were as follows: Lactobacillus reuteri LR1 starter dosage of 6%, HTC starter dosage of 3-4%, fermentation temperature of 37±1 °C, and fermentation duration of 6 hours. The developed product possessed an apparent antagonistic activity against test-cultures of such pathogenic and opportunistic microorganisms as E. coli ATCC 25922, Salmonella typhimurium, Staphylococcus aureus ATCC 6538 and Klebsiella pneumoniae. The survival of the test-cultures cultivated with the obtained dairy product on the first cultivation day was from 36 to 46% and on the second - from 8 to 20%, in comparison with the pure test-cultures. The investigation of the functional properties of the obtained dairy product was carried out by the single-factor experiment with the albino Wistar rat-stock (initial body weight 160±10 g, n=10 in each group). Its positive effect on the rats' microbiome composition and lipid exchange indices has been demonstrated. It had been shown that the administration of the obtained dairy product in the rats' diet (5 ml per day per os) during 30 days didn't cause any abnormalities in the health status and behavior of the laboratory animals of spf-category. The number and distribution of leucocytes and lymphocytes, and granulocytes in all rats' populations (intact, control and treatment) were within the normal range. Upon the introduction of the developed dairy product into the rats' diet, the increased levels of bifidobacteria, lactic acid bacteria and typical for normal rats' microflora enterobacteria were observed in the rats' microbiome. As for the biochemical indices that characterize rats' lipid metabolism, the rats consuming fermented dairy products (control and treatment) demonstrated statistically significant reduction of blood serum cholesterol level compared to the intact rat group; additionally the rats consuming the developed in this study dairy product (treatment) demonstrated statistically significant reduction of blood serum triglyceride level compared to the intact rats. Utilized in this study Lactobacillus reuteri LR1 is the first strain that was purified in Russia and characterized as useful for manufacturing of the probiotic food products, since currently only Lactobacillus reuteri strains of foreign origin can be seen on the market.


Asunto(s)
Productos Lácteos Cultivados/microbiología , Microbiología de Alimentos , Limosilactobacillus reuteri/crecimiento & desarrollo , Probióticos , Animales , Análisis de los Alimentos , Masculino , Ratas , Ratas Wistar
11.
Bull Exp Biol Med ; 165(6): 746-750, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30353340

RESUMEN

Oxidative status was assessed in different areas of the cerebral cortex of male Wistar rats under normal condition and during permanent 24-h focal ischemia. In intact animals, the level of lipid hydroperoxides in the frontal lobes of both hemispheres was by 36% higher than in other cortical areas, while total antioxidant activity was by 25% higher than in other areas. During ischemia, changes in oxidative status were localized only in the ischemic focus and penumbra zone and did not involve other cortical areas. We demonstrated for the first time a neuroprotective effect of therapeutic administration of carnosine in low doses (50 mg/kg) on parameters of the oxidative status under conditions of focal ischemia comparable to its effect of high doses (500 mg/kg) as well as its local effect in the penumbra zone. A dose-dependent effect of carnosine on antioxidant activity in the penumbra zone during ischemia was also demonstrated. These findings confirm effectiveness of not only preventive carnosine administration, but also its application in the postischemic period of the stroke.


Asunto(s)
Isquemia Encefálica/fisiopatología , Carnosina/farmacología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiología , Estrés Oxidativo , Animales , Antioxidantes/metabolismo , Isquemia Encefálica/metabolismo , Isquemia/tratamiento farmacológico , Masculino , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Wistar , Accidente Cerebrovascular/tratamiento farmacológico
12.
Biomed Khim ; 64(4): 344-348, 2018 Aug.
Artículo en Ruso | MEDLINE | ID: mdl-30135281

RESUMEN

Oxidative stress is one of the key factors in brain tissue damage in ischemia, which indicates the appropriateness of using antioxidants under these conditions. One of the promising antioxidants for the therapy of ischemic stroke is the natural dipeptide carnosine. The neuroprotective effect of dietary carnosine administration was investigated in an experimental model of focal cerebral ischemia/reperfusion in Wistar rats. Animals received carnosine with a diet at a daily dose of 150 mg/kg for 7 days before temporary occlusion of the middle cerebral artery (MCA), performed for 60 min. At 24 h after the onset of ischemia the effect of carnosine on the area of the necrotic core was evaluated in animals. In brain tissue of animals the content of malondialdehyde (MDA), protein carbonyls (PC), total antioxidant capacity (TAC), total activity of superoxide dismutase (SOD), glutathione peroxidase (GP), catalase (CAT) and glutathione transferase (GT), content of isoprostanes and cytokines were measured. Carnosine significantly reduced the infarct size. Carnosine also increased TAC and reduced the level of MDA and isoprostanes in brain tissue. Influence of carnosine on other parameters was not detected. Thus carnosine consumed prophylactically with the diet for 7 days before the induction of ischemia by means of MCA occlusion in rats provides the direct neuroprotective effect, retains high antioxidant activity of brain tissue, reduces the level of oxidative damage markers (MDA and isoprostanes) but does not have any effect on the activity of antioxidant enzyme systems and production of cytokines in brain tissue.


Asunto(s)
Antioxidantes/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Carnosina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/prevención & control , Animales , Antioxidantes/administración & dosificación , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Carnosina/administración & dosificación , Modelos Animales de Enfermedad , Masculino , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología
13.
Biomed Khim ; 64(3): 268-275, 2018 Jun.
Artículo en Ruso | MEDLINE | ID: mdl-29964264

RESUMEN

Synthesis of lipoilcarnosine (LipC) - a conjugated molecule based on two natural antioxidants, carnosine and a-lipoic acid, is described. Its physico-chemical, antioxidant properties and biological activity are characterized. According to reversed-phase HPLC with a UV detector, purity of the final product was 89.3%. The individuality of the obtained sodium salt of LipC was confirmed by tandem HPLC-mass spectrometry. High resistance of LipC to hydrolysis with serum carnosinase was demonstrated. The antioxidant activity of LipC measured by reaction with the formation of thiobarbituric acid reacting substances and kinetic parameters of iron-induced chemiluminescence was higher than that of carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human neuroblastoma culture cells, differentiated towards the dopaminergic type, at concentrations not exceeding 5 mM. At the concentration range of 0.1-0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP + )-induced toxicity.


Asunto(s)
Antioxidantes , Carnosina , Intoxicación por MPTP/tratamiento farmacológico , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Carnosina/análogos & derivados , Carnosina/síntesis química , Carnosina/química , Carnosina/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Intoxicación por MPTP/metabolismo , Intoxicación por MPTP/patología
14.
Biochemistry (Mosc) ; 83(2): 140-151, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29618300

RESUMEN

Binding to Na+,K+-ATPase, cardiotonic steroids (CTS) activate intracellular signaling cascades that affect gene expression and regulation of proliferation and apoptosis in cells. Ouabain is the main CTS used for studying these processes. The effects of other CTS on nervous tissue are practically uncharacterized. Previously, we have shown that ouabain affects the activation of mitogen-activated protein kinases (MAP kinases) ERK1/2, p38, and JNK. In this study, we compared the effects of digoxin and bufalin, which belong to different subclasses of CTS, on primary culture of rat cortical cells. We found that CTS toxicity is not directly related to the degree of Na+,K+-ATPase inhibition, and that bufalin and digoxin, like ouabain, are capable of activating ERK1/2 and p38, but with different concentration and time profiles. Unlike bufalin and ouabain, digoxin did not decrease JNK activation after long-term incubation. We concluded that the toxic effect of CTS in concentrations that inhibit less than 80% of Na+,K+-ATPase activity is related to ERK1/2 activation as well as the complex profile of MAP kinase activation. A direct correlation between Na+,K+-ATPase inhibition and the degree of MAP kinase activation is only observed for ERK1/2. The different action of the three CTS on JNK and p38 activation may indicate that it is associated with intracellular signaling cascades triggered by protein-protein interactions between Na+,K+-ATPase and various partner proteins. Activation of MAP kinase pathways by these CTS occurs at concentrations that inhibit Na+,K+-ATPase containing the α1 subunit, suggesting that these signaling cascades are realized via α1. The results show that the signaling processes in neurons caused by CTS can differ not only because of different inhibitory constants for Na+,K+-ATPase.


Asunto(s)
Bufanólidos/metabolismo , Digoxina/metabolismo , Neuronas/metabolismo , Ouabaína/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Bufanólidos/química , Bufanólidos/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cerebro/citología , Digoxina/química , Digoxina/toxicidad , Activación Enzimática/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Microsomas/enzimología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neuronas/citología , Neuronas/efectos de los fármacos , Ouabaína/química , Ouabaína/toxicidad , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
Biochemistry (Mosc) ; 83(1): 26-31, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29534665

RESUMEN

The ability of the ascomycete Aspergillus niger N402 to transform exogenous progesterone was investigated. We found that this strain has steroid-hydroxylating activity and can introduce a hydroxyl group into the progesterone molecule mainly at positions C11(α) and C21 with predominant formation of 21-hydroxyprogesterone (deoxycortone). In addition, formation of 6ß,11α-dihydroxyprogesterone was also observed. Studying the effects of the growth medium composition and temperature on progesterone conversion by A. niger N402 showed that the most intense accumulation of 21-hydroxyprogesterone occurred in minimal synthetic medium at 28°C. Increasing the cultivation temperature to 37°C resulted in almost complete inhibition of the hydroxylase activity in the minimal medium. In the complete medium, a similar increase in temperature inhibited 11α-hydroxylase activity and completely suppressed 6ß-hydroxylase activity, but it produced no effect on 21-hydroxylating activity.


Asunto(s)
Aspergillus niger/metabolismo , Biotransformación , Progesterona/metabolismo , Conformación Molecular , Progesterona/química , Progesterona/aislamiento & purificación
16.
Bull Exp Biol Med ; 163(2): 195-198, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28730388

RESUMEN

Parameters of the oxidative status of the brain and blood plasma were measured in rats 24 h after 1-h focal cerebral ischemia. In the brain of rats exposed to cerebral ischemia, activities of superoxide dismutase and catalase were elevated. Ischemia reduced the total antioxidant activity of the brain and the levels of malonic dialdehyde and protein carbonyl derivatives. In the blood plasma of experimental rats, superoxide dismutase activity and malonic dialdehyde level increased and total antioxidant activity decreased, i.e. the shifts were similar to those in the brain. The ischemia-induced changes in the brain and blood were not always co-directed.


Asunto(s)
Isquemia Encefálica/sangre , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Daño por Reperfusión/sangre , Daño por Reperfusión/metabolismo , Animales , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
17.
Acta Crystallogr D Struct Biol ; 73(Pt 5): 388-401, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28471364

RESUMEN

The laccase from Steccherinum murashkinskyi is a member of the large family of multicopper oxidases that catalyze the oxidation of a wide range of organic and inorganic substrates, accompanied by the reduction of dioxygen to water. The reducing properties of X-ray radiation and the high quality of the laccase crystals allow the study of the catalytic reduction of dioxygen to water directly in a crystal. A series of diffraction data sets with increasing absorbed radiation dose were collected from a single crystal of Steccherinum murashkinskyi laccase at 1.35 Šresolution. Changes in the active-site structure associated with the reduction of molecular oxygen to water on increasing the absorbed dose of ionizing radiation were detected. The structures in the series are mixtures of different states of the enzyme-substrate complex. Nevertheless, it was possible to interpret these structures as complexes of various oxygen ligands with copper ions in different oxidation states. The results allowed the mechanism of oxygen reduction catalyzed by laccases to be refined.


Asunto(s)
Lacasa/metabolismo , Oxígeno/metabolismo , Polyporales/enzimología , Agua/metabolismo , Biocatálisis/efectos de la radiación , Dominio Catalítico/efectos de la radiación , Cristalografía por Rayos X , Lacasa/química , Modelos Moleculares , Oxidación-Reducción/efectos de la radiación , Polyporales/química , Polyporales/efectos de la radiación , Conformación Proteica/efectos de la radiación , Rayos X
18.
Zh Nevrol Psikhiatr Im S S Korsakova ; 117(12. Vyp. 2): 60-64, 2017.
Artículo en Ruso | MEDLINE | ID: mdl-29411747

RESUMEN

AIM: To assess neuroprotective properties of preventive injections of carnosine in experimental focal cerebral ischemia in rats. MATERIAL AND METHODS: A focal ischemia in Wistar rats induced by the 60 min-occlusion of the middle cerebral artery with the following 24h-reperfusion was used. Animals received carnosine mixed with ration in daily dose of 150 mg/kg of body mass during 7 days before surgery. RESULTS AND CONCLUSION: Carnosine decreased the size of the lesion by 20%, neurological deficit by 43% with a simultaneous increase in the antioxidant status of blood plasma and brain tissue compared to the animals of the control group. The authors showed for the first time the neuroprotective effect of low dose of carnosine (150 mg/kg of body mass) mixed with ration used in preventive treatment courses in the experimental focal cerebral ischemia-reperfusion model.


Asunto(s)
Isquemia Encefálica , Carnosina , Infarto Cerebral , Infarto de la Arteria Cerebral Media , Fármacos Neuroprotectores , Animales , Isquemia Encefálica/tratamiento farmacológico , Carnosina/farmacología , Infarto Cerebral/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Wistar
19.
Ter Arkh ; 89(12): 28-33, 2017.
Artículo en Ruso | MEDLINE | ID: mdl-29411757

RESUMEN

AIM: By using mathematical modeling, to evaluate the impact of upper respiratory tract diseases, retro- and micrognathia, and body mass index (BMI) on nocturnal pulse oximetry indicators (oxygen saturation level and oxygen desaturation index) in outpatients examined for suspected obstructive sleep apnea syndrome (OSAS). SUBJECTS AND METHODS: The study enrolled 260 subjects with a mean age of 47.8±12.0 years. All the examinees underwent outpatient pulse oximetry screening during nocturnal sleep because of suspected OSAS. Multislice spiral computed tomography was carried out to assess the paranasal sinuses and nasal septum. BMI was calculated. Variance factor analysis using an original programming application intended to create binary and ternary dispersion complexes was employed as a main mathematical tool. RESULTS: There were statistically significantly sets of risk factors for OSAS: nasal septum deviation + increased BMI + male gender = 68.66%; chronic allergic rhinitis + increased BMI + male gender = 63.09%; retromicrognathia + increased BMI + male ganger = 59.48%; and chronic tonsillitis + increased BMI + male gander = 60.88%. Higher BMI and male gender are a most statistically significant set of risk factors. CONCLUSION: Pulse oximetry screening during nocturnal sleep in snoring patients with suspected OSAS in combination with an assessment of age, sex, BMI, ENT comorbidity, retro- and micrognathia can predict the severity of the disease and serve as a basis for elaborating an OSAS screening program.


Asunto(s)
Micrognatismo/epidemiología , Sobrepeso/epidemiología , Oximetría/métodos , Enfermedades Respiratorias/epidemiología , Apnea Obstructiva del Sueño , Adulto , Análisis de Varianza , Índice de Masa Corporal , Comorbilidad , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Pacientes Ambulatorios/psicología , Polisomnografía/métodos , Factores de Riesgo , Federación de Rusia/epidemiología , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Ronquido/diagnóstico , Ronquido/etiología
20.
Pol J Vet Sci ; 19(3): 477-484, 2016 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-27760031

RESUMEN

The aim of the research was to evaluate two chemical tests for non-invasive pregnancy diagnosis from urine, the Cuboni reaction and the barium chloride test, in donkeys (Equus asinus) and alpacas (Vicugna pacos). The research was carried out from April 2013 to September 2014. Urine samples were collected on five private Czech farms from 18 jennies and 12 alpaca females. Urine was collected non-invasively into plastic cups fastened on a telescopic rod, at 6-9 week intervals. In total, 60 and 54 urine samples from alpacas and jennies, respectively, were collected. The Cuboni reaction was performed by the State Veterinary Institute Prague. The barium chloride test was done with 5 ml of urine mixed together with 5 ml of 1% barium chloride solution. Results of the Cuboni reaction were strongly influenced by the reproductive status of jennies; the test was 100% successful throughout the second half of pregnancy. However, no relationship was found between the real reproductive status of alpaca females and results of the Cuboni reaction. It was concluded that the barium chloride test is not suitable for pregnancy diagnosis either in donkeys, due to significant influence of season on the results, or in alpacas, because no relationship between results of the test and the reproductive status of alpaca females was found. In conclusion, the Cuboni reaction has potential to become a standard pregnancy diagnostic method in donkeys.


Asunto(s)
Compuestos de Bario , Camélidos del Nuevo Mundo , Cloruros , Equidae , Pruebas de Embarazo/veterinaria , Preñez , Animales , Femenino , Embarazo , Pruebas de Embarazo/métodos , Preñez/orina
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