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Rola systemu endokanabinoidów w patogenezie i terapii otyłości

100%
Pyszniak M., Pogoda K., Mazur A., Tabarkiewicz J.
Endokrynologia Pediatryczna
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2014
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vol. 13
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issue 2 (47)
65-76
EN
Soon after the discovery of the first active component of Cannabis sativa – -∆ 9 -THC, it has been shown that its action is mediated mainly through the activation of specific membrane protein – cannabinoid receptor (CB). So far two types of this protein were isolated: CB1 and CB2. It is already known that they constitute the intracellular signaling system, called Endocannabinoid System (ECS), which also includes their ligands and enzymes involved in the synthesis and degradation of this compounds. ECS is abundant in the brain regions associated with feeding control and also in peripheral organs regulating food intake and glucose and lipids metabolism, suggesting the crucial role of this system in pathogenesis of obesity. Much evidence has proven potent orexigenic action of endocannabinoids induced via the CB1 receptors activation in CNS. They also stimulate lipogenesis, leading to the fat accumulation in such organs like the liver. Moreover, the CB1 receptor agonist-based treatment induced insulin resistance and development of hyperglycaemia - haracteristic metabolic parameters of obesity. These results has led to the development of CB1-blocking drugs with potential efficacy in obesity treatment. Preclinical and clinical studies with the use fantagonist/inverse agonist – rimonabant have shown significant decrease in body weight and improve in cardiometabolic risk factors. However, serious psychiatric effects of this substance contributed to its withdrawal from the market. The main goal is to design a drug which might prevent obesity without these side effects. Therapies based on the CB1 receptor’s neutral antagonists or selective, inverse agonists might be a promising strategy in obesity treatment. Pediatr. Endocrinol.13/2014;2(47):65-76.
PL
Wkrótce po odkryciu pierwszego aktywnego składnika Cannabis sativa -∆ 9 -THC wykazano, iż jego działanie jest zależne od aktywacji specyficznego białka błonowego, tj. receptora kanabinoidowego (CB). Jak dotąd, zidentyfikowano dwa typy tego receptora – CB1 i CB2. Obecnie wiadomo już, że należą one do wewnątrzkomórkowego systemu sygnałowego, nazywanego układem kanabinoidowym (ECS), w którego skład wchodzą także ich ligandy oraz enzymy związane z syntezą i degradacją tych związków. ECS jest obecny w rejonach mózgu związanych z kontrolą odżywiania, a także w tkankach obwodowych odpowiedzialnych za pobór i przetwarzanie energii oraz metabolizm lipidów i glukozy, co wskazuje na udział tego układu w patogenezie otyłości. Liczne badania mówią m.in. o silnym oreksygennym działaniu endokanabinoidów, wywoływanym za pośrednictwem receptorów CB1 w CUN. Co więcej, aktywacja CB1 w tkankach obwodowych nasila lipogenezę, sprzyjając tym samym akumulacji tkanki tłuszczowej w takich narządach, jak wątroba. W trzustce i mięśniach szkieletowych zastosowanie agonistów CB1 indukowało wytworzenie insulinooporności i rozwój hiperglikemii, stanowiących parametry metaboliczne otyłości. Wyniki te dały podstawy do poszukiwania substancji blokujących CB1 o potencjalnej skuteczności w terapii otyłości. Próby przedkliniczne i kliniczne z zastosowaniem rimonabantu – antagonisty/odwrotnego agonisty CB1 – przyniosły korzystne rezultaty w postaci obniżenia masy ciała i zmniejszenia ryzyka powikłań kardiometabolicznych. Jednakże ze względu na poważne psychiatryczne skutki uboczne został on wycofany z obiegu. Celem badań jest przygotowanie leku, który służyłby leczeniu otyłości, jednocześnie nie wywołując powikłań. Ostatnio uwaga naukowców koncentruje się wokół neutralnych antagonistów i selektywnych, odwrotnych agonistów receptorów kanabinoidowych. Endokrynol. Ped. 13/2014;2(47):65-76.
2
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Effects of selected factors on the outcome of rehabilitation of post-stroke patients

100%
Przysada G., Kwolek A., Mazur A.
Medical Rehabilitation
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2007
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vol. 11(3)
29-37
EN
The aim of the study was to evaluate the impact of selected factors, such as: gender, age, stroke type, side of paresis, time to initiation of rehabilitation, first or successive in-patient rehabilitation and severity of paresis at admission on the final clinical status of patients and on the outcome of treatment at the department of rehabilitation, district hospital.Material and methods: All 431 post-stroke patients qualified for the treatment at the department of rehabilitation between January 2002 and December 2003 were included in the study. Patients were divided into four age groups. Results of rehabilitation were analyzed in male and female groups separately. Patients were divided according to the stroke type into four groups either suffering from an ischaemic or a hemorrhagic stroke; another selection cirterion was left-sided vs. right-sided paresis. The so-called general fitness, Barthel Index and Brunnström test were used to evaluate clinical status of the patients and the progress of rehabilitation. Statistical analysis was carried out using the t-test or – alternatively – the non-parametric Wilcoxon signed rank test, analysis of variance (ANOVA) or the nonparametric Kruskal-Wallis test, and the chi-square test.Results: Based on the obtained results, it was proven that multidimensional, complex rehabilitation in a specialist centre, carried out by rehabilitation team resulted in significant improvement of post-stroke patients’ clinical status. The improvement was observed for all measurements of fitness used in the study. Analysis of the effects of rehabilitation with regard to patients’ age indicated that an improvement in general fitness, motor activity (reduction of paresis) and independency in activities of daily living was obtained in each age group. Based on the analysis conducted in groups of patients with different stroke aetiologies, it was found that effects of the treatment in patients with haemorrhagic stroke were better than in patients with ischaemic stroke, which was observed in each of the applied measures used for the evaluation of patients’ clinical status. Mean improvement observed after the treatment was greater in patients with right-sided paresis than in patients with left-sided paresis. Gender had no significant effect on the extent of rehabilitation results.Conclusions: Results of the study indicate that in post-stroke patients, gender, advanced age, stroke location, stroke type or motor skills at admission do not constitute a criterion determining the possibility of conducting rehabilitation procedures.
3
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Congenital adrenal hyperplasia: clinical symptoms and diagnostic methods

88%
Podgórski R., Aebisher D., Stompor M., Podgórska D., Mazur A.
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2018
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vol. 65
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issue 1
25-33
EN
The aim of this paper is a straightforward presentation of the steroidogenesis process and the most common type of congenital adrenal hyperplasia (CAH) - 21-hydroxylase deficiency - as well as the analytical diagnostic methods that are used to recognize this disease. CAH is a family of common autosomal recessive disorders characterized by impaired adrenal cortisol biosynthesis with associated androgen excess due to a deficiency of one or more enzymes in the steroidogenesis process within the adrenal cortex. The most common and prototypical example of the CAH disorders group (90-95%) is caused by 21-hydroxylase deficiency. Less frequent types of CAH are 11β-hydroxylase deficiency (up to 8% of cases), 17α-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, P450 oxidoreductase deficiency and StAR deficiencies. In the 21-hydroxylase and 11β-hydroxylase deficiency, only adrenal steroidogenesis is affected, whereas a defect in 3β-hydroxysteroid dehydrogenase or 17α-hydroxylase also involves gonadal steroid biosynthesis. Many countries have introduced newborn screening programs based on immunoassays measuring 17-hydroxyprogesterone from blood spots used for other neonatal screening tests which enable faster diagnosis and treatment of CAH. Currently, chromatographic techniques coupled with mass spectrometry are gaining popularity due to an increase in the reliability of the test results.
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Measurement of functional independence level and falls-risk in individuals with undiagnosed phenylketonuria

76%
Mazur A., Jarochowicz S., Ołtarzewski M., Sykut-Cegielska J., Kwolek A., O'Malley G.
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issue 4
613-618
EN
The aim of the study was to determine the level of functional independence in adult patients with previously undiagnosed or untreated phenylketonuria (PKU). The study was conducted among 400 intellectually impaired adult residents of Social Welfare Homes in South-Eastern Poland born prior to the introduction of neonatal PKU screening programs. PKU was screened by filter paper test using tandem mass spectrometry methods, and confirmed by gas chromatography-mass spectrometric analysis of PKU organic acids in urine. Degree of functional independence included the assessment of activities of daily living (Barthel Index) and measures of balance and gait (Tinetti scale). Eleven individuals with previously untreated PKU were identified whereby eight presented with moderate disability and three with mild disability. Six had a high risk of falls and five had a moderate risk of falls. This study indicates that there is considerable number of undiagnosed PKU patients within the Polish population who require assessment and management in order to reduce the impact of the neurological and neuropsychiatric problems associated with the condition. Appropriate therapy for those with undiagnosed PKU should, in particular, address the risk of falls.
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Dihydropyrimidine dehydrogenase deficiency presenting with psychomotor retardation in the first Polish patient

64%
Mazur A., Figurski S., Płoskoń A., Meijer J., Zoetekouw L., Wątróbska S., Sykut-Cegielska J., Gradowska W., Kuilenburg A. B. P. v.
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2008
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vol. 55
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issue 4
787-790
EN
Dihydropyrimidine dehydrogenase (DPD) deficiency is a rare defect of the first step of the pyrimidine catabolic pathway. Patients with a complete enzyme deficiency may be clinically asymptomatic or suffer from neurological abnormalities of various severity. We report a case of an 8-year-old girl with psychomotor retardation and mild course of the disease. Analysis of urine showed strongly elevated levels of uracil and thymine, and no DPD activity could be detected in peripheral blood mononuclear cells. Sequence analysis of the DPD gene (DPYD) revealed that our patient was homozygous for the common splice-site mutation IVS14+1G > A, which suggest that the carrier status for this mutation may be not rare in the Polish population.
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