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2343. Anthracycline therapy and 24-hour blood-pressure profile in long-term survivors of childhood cancer

Creator:
Zuzana Nováková, Jana Šťastná, Honzíková, K., Hana Hrstková, Nataša Honzíková, Eva Závodná, Bohumil Fišer, and Petr Honzík
Format:
print
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, krevní tlak, chronobiologie, blood pressure, chronobiology, anthracyclines, cardiotoxicity, childhood cancer, 14, and 612
Language:
English
Description:
In our previous studies, a decreased blood pressure was reported in children treated by anthracycline (AC). The aim of this study was to assess the long-term effects of AC anticancer therapy in 45 subjects aged 13-22 years by repeated 24-hour Holter monitoring of blood pressure. Sixty four aged-matched subjects served as controls. The differences between mean values of systolic (SBP) and diastolic blood pressure (DBP) in each hour of both groups were evaluated by Mann-Whitney test. Also the parameters of the least-squares fit of the sinusoidal curve in each subject were estimated (M - mesor, midline-estimating, a mean value of sinusoidal curve corresponds to 24-hours mean pressure; A - amplitude, double amplitude corresponds to nightday difference; Acr - acrophase is a time of maximal value of a sinusoidal curve). SBP and DBP was significantly lower only during night hours in anthracycline patients 19-22 years old. Also M was lower in this age subgroup of patients comparing to age matched controls (SBP: 112±6 mm Hg versus 117±7 mm Hg, p<0.05; DBP: 67±3 mm Hg versus 69±6 mm Hg, p<0.05), A was not different, Acr in patients was shifted one hour earlier (SBP: 2.4 p.m. versus 3.6 p.m., p<0.05; DBP: 2.1 p.m. versus 3.3 p.m., p<0.01). This corresponds to the shift of the morning blood-pressure increase seen on 24-hours blood pressure profiles. M correlated with age in controls (SBP: r=0.374, p<0.01; regression coefficient b=1.34 mm Hg/1 year; DBP: r=0.365, p<0.01; b=0.95 mm Hg/1 year), but not in patients (SBP: r=0.182, DBP: r=0.064). A and Acr were age-independent in all subjects. It is concluded that blood pressure in 19-22 years old AC patients is lower during night hours, the age-dependent increase of blood pressure seen in healthy controls between 13 and 22 years of age does not occur in patients. This finding is consistent with the long-lasting impairment of the sympathetic nervous system caused by anthracyclines., Z. Nováková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

2344. Anthropogenic induced changes in nesting densities of the dune-specialised digger wasp Bembix rostrata (Hymenoptera: Sphecidae)

Creator:
Bonte, Dries
Type:
article, model:article, and TEXT
Subject:
Hymenoptera, Sphecidae, Bembix rostrata, disturbance, population density, recreation, and trampling
Language:
English
Description:
Data on nesting densities of Bembix rostrata, a digger wasp inhabiting dynamic coastal dunes, were used to document the detrimental effects of trampling by cattle and vacationers. Both types of disturbance resulted in similar sand displacement and prey availability. Nesting densities of Europe's largest digger wasp declined dramatically with increasing trampling, probably below the critical population size. Hence, additional human disturbance, although resulting in similar environmental conditions compared to natural disturbance, significantly affected local population sizes. As a result, anthropogenic has to be avoided disturbance in order to restore or conserve natural dynamics and efforts to restore natural dynamics in a more natural way should be promoted. Although this is here only documented for one, large specialised invertebrate, the application of traditional management techniques, such as grazing by large herbivores, within newly evolved landscapes may introduce new pressures that affect pre-adapted species to natural disturbances negatively within short time spans.
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

2345. Anthropologia integra: Exaktní, humanitní, celostní (počin jako malina)

Creator:
Filipský, Jan
Format:
111-114, braille, text, and regular print
Type:
model:article, article, Text, historické články, and TEXT
Subject:
antropologie kulturní, antropologie fyzická, and periodika jako téma
Language:
Czech and English
Description:
Příspěvek nabízí stručný přehled odlišných přístupů ke studiu člověka, jež může být pojímáno jako celostní bio-socio-kul- turní disciplina čerpající jak z přírodních / exaktních, tak humanitních věd, či jako dvě odlišné skupiny „vědeckých“ (čti: přírodovědných) a „nevědeckých“ (společenskovědních) výzkumů, jež se vzájemně metodologicky a terminologicky stále vzdalují, ale ze zvyku jsou stále označovány za antropologii, a to na pozadí nedávné kontroverze vyvolané rozhodnutím Americké antropologické asociace vymýtit pojem „věda“ z dlouhodobého programu organizace. Obsaženo je i krátké ohlédnutí za 1. ročníkem našeho časopisu jako otevřené publikační plat- formy integrálně chápané antropologie., The contribution presents a brief overview of different approaches to the study of Man, conceived as a holistic bio-socio-cultural scientific discipline drawing upon natural / exact sciences and humanities, or increasingly diverging “scientific” and “non-scientific” research- es, both from force of habit still termed anthropology, in the background of recent controversy sparkled by the decision of the American Anthropological Association to purge the term “science” from its long-term mission statement. Included is also a short retrospective glance at the first volume of our journal as an open publication platform of integrally conceived anthropology., Jan Filipský, and Literatura
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

2347. Anti-CD38 therapy with daratumumab for relapsed/refractory CD20-negative diffuse large B-Cell lymphoma

Creator:
Vockova, P. , Svaton, M. , Karolova, J. , Pokorna, E., Vokurka, M., and Klener, P.
Format:
bez média and svazek
Type:
model:article and TEXT
Subject:
Non-Hodgkin lymphomas, CD38, daratumumab, and patient-derived xenograft
Language:
English
Description:
Diffuse large B-cell lymphoma (DLBCL) is the most common and one of the most aggressive subtypes of non-Hodgkin’s lymphomas. Front-line therapy consists of chemotherapy in combination with anti-CD20 monoclonal antibody rituximab. Relapses after rituximab-based regimen have poor prognosis and call for new treatment options. Immunohistochemistry analysis of relapsed DLBCL often reveal CD20-negative lymphoma, which limits repeated use of rituximab in combination with salvage chemotherapy. CD38 is a surface antigen that binds to CD38, CD31/PECAM-1 and hyaluronic acid. CD38 is an important mediator of signal transmission from the microenvironment into the cell. Anti-CD38 monoclonal antibody daratumumab has been approved for the treatment of multiple myeloma. Expression of CD38 on the surface of DLBCL is highly variable (compared to strong expression on myeloma cells), but can be easily assessed by flow cytometry or immunohistochemistry. A patient-derived xenograft (PDX) model of CD20-negative, CD38-positive DLBCL derived from a patient with rituximab-refractory DLBCL was used for in vivo experiments. We demonstrated that daratumumab suppressed growth of subcutaneous PDX tumours significantly more effectively than rituximab. Analysis of tumours obtained from mice treated with daratumumab revealed down-regulation of surface CD38, suggesting endocytosis of CD38-daratumumab complexes. The results suggest a potential clinical use of daratumumab in combination with salvage chemotherapy in patients with relapses of CD20-negative DLBCL. In addition, daratumumab might potentially serve as a suitable antibody moiety for derivation of antibodydrug conjugates for the targeted delivery of toxic payloads to the lymphoma cells.
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

2348. Anti-GAD-Positive Patients with Type 1 Diabetes Mellitus Have Higher Prevalence of Autoimmune Thyroiditis than Anti-GAD-Negative Patients with Type 1 and Type 2 Diabetes Mellitus

Creator:
Bárová, H., Perušicová, J., Hill, M., Šterzl, I., Vondra, K., and Mašek, Z.
Type:
article, model:article, and TEXT
Subject:
Diabetes mellitus, Thyroid antibody, Autoimmune thyroiditis, and Glutamic acid decarboxylase antibody
Language:
English
Description:
The aim of our study was to evaluate antibodies against thyroglobulin (anti-TG) and thyroid peroxidase (anti-TPO) – markers of autoimmune thyroiditis – in several groups of adult patients with type 1 and type 2 diabetes mellitus (DM). We were particularly interested whether the presence of thyroid antibodies is related to the positivity of glutamic acid decarboxylase antibodies (anti-GAD). We found elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patients with type 2 diabetes were anti-GAD-negative. At least one thyroid antibody (anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DM and 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM were further grouped according to their anti-GAD status. The anti-GAD-positive patients had a higher prevalence of anti-TG antibodies than the anti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPO antibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody was detected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) of anti-GAD-negative patients with type 1 DM (p=0.006). No significant difference in the frequency of thyroid antibodies was found between anti-GAD-negative patients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with or without thyroid antibodies in both type 1 and type 2 diabetic patients did not differ in actual age, the age at diabetes onset, duration of diabetes, body mass index or HbA1c level. Patients with elevated thyroid antibodies had significantly higher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22 mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). We conclude that there is a higher frequency of thyroid-specific antibodies in anti-GAD-positive adult patients with type 1 DM than in anti-GAD-negative patients or in patients with type 2 DM. Patients with or without thyroid antibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroid antibodies-positive patients have higher levels of thyroid stimulating hormone (TSH).
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

2349. Anti-Helicobacter pylori, anti-thyroid peroxidase, anti-thyroglobulin and anti-gastric parietal cells antibodies in Czech population

Creator:
Ivan Šterzl, Pavlína Hrdá, Petr Matucha, Jarmila Čeřovská, and Václav Zamrazil
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, endokrinologie, Helicobacter pylori, protilátky, endocrinology, antibodies, thyroid peroxidase, thyroglobulin, gastric parietal cells, 14, and 612
Language:
English
Description:
Autoimmune thyropathies are frequently linked to many infections, such as Helicobacter pylori, which are also supposed to play a role in their pathogenesis. The aim of this study was to evaluate the relationships between thyroid and gastric autoimmunity and H. pylori infection on a large sample of Czech population (n=1621) by monitoring the autoantibodies against thyroglobulin (anti-Tg) and thyroid peroxidase (anti-TPO) and gastric parietal cell (anti-GPC, representing thyrogastric syndrome) in correlation with antibodies against Helicobacter pylori (anti-H. pylori) of classes IgG and IgA. The interrelation between autoantibodies and H. pylori antibodies was assessed by H. pylori seropositivity. In H. pylori seropositive persons as compared to seronegative irrespective of age and sex, a higher occurrence of anti-TPO (10.4 % vs. 5.8 %, p=0.001) and anti-GPC (6.1 % vs. 1.7 %, p<0.001) was found. Differences in anti-TPO occurrence were significant in both men (7.0 % vs. 3.3 %, p=0.03) and women (12.7 % vs. 8.0 %, p=0.02), differences in anti-GPC occurrence were significant only in women (7.2 % vs. 1.7 %, p<0.001). Results of this study support the idea of a connection between infection of H. pylori and the occurrence of anti-TPO autoantibodies representing thyroid autoimmunity and gastric parietal cells autoantibodies representing the thyrogastric syndrome., I. Šterzl, P. Hrdá, P. Matucha, J. Čeřovská, V. Zamrazil., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

2350. Anti-inflammatory effect of flavonoids from Comfort-G and the changes in arachidonic acid metabolism

Creator:
Vecka, Marek, Prokeš, Libor, Tvrzická, Eva, Karpaš, Karel, Pernický, Aleš, Pfleger, R., and Votruba, Miloš
Type:
model:article, article, Text, and TEXT
Subject:
antiflogistika, zánět--farmakoterapie--prevence a kontrola, flavonoidy--farmakologie--metabolismus, kyselina arachidonová--sekrece, inhibitory cyklooxygenázy, and Comfort-G
Language:
Czech and English
Description:
Cíl práce: Flavonoidy, obsažené v preparátu Comfort-G, působí nejen jako antioxidanty, ale mají také protizánětlivý účinek. Comfort-G inhibuje nejen cyklooxygenázu-2 (COX-2), ale také 5-lipoxygenázu (5-LO), a to tím, že snižuje tvorbu prostaglandinů, tromboxanů a leukotrienů, pocházejících z metabolismu kyseliny arachidonové (AA). Naším úkolem bylo potvrdit toto tvrzení analýzou molárního zastoupení AA v synoviální tekutině a v séru pacientů, léčených pro synovialitidu kolenního kloubu. Typ studie: Intervenční studie. Název a sídlo pracoviště: IV. interní klinika, Univerzita Karlova v Praze, 1. lékařská fakulta a Všeobecná fakultní nemocnice v Praze Materiál a metody: Comfort-G byl podáván skupině deseti pacientů (4 muži/6 žen) ve věku 27–79 let v předepsané dávce (odpovídající 250 mg extraktu flavonoidů užívaných dvakrát denně) po dobu jednoho měsíce. Odběr synoviální tekutiny a séra se uskutečnil jednak v den 0, tj. před podáním první dávky preparátu a v den 31., jeden den po poslední dávce. Volné radikály byly stanoveny přímou spektrofotometrickou metodou založenou na chlorofylinové reakci. Molární poměr mastných kyselin včetně arachidonové kyseliny byl stanoven plynovou chromatografií. Účastníci studie podstoupili klinické vyšetření a poskytli subjektivní hodnocení pomocí dotazníku, které se týkalo stavu kolenního kloubu. Statistická analýza byla uskutečněna softwarem STATISTICA pro Windows, verze 4.0. Výsledky: Výsledky, ukazující statisticky významný pokles koncentrace volných radikálů, a to jak v synoviální tekutině, tak v séru, jsme prezentovali a diskutovali v předchozí studii, stejně jako zlepšení stavu pacientů. V této práci přinášíme výsledky měření obsahu kyseliny arachidonové v synoviální tekutině a séru ve stejné skupině pacientů. Po ukončení studie jsme zjistili zvýšené zastoupení AA jak v synoviální tekutině (4,54 ± 0,39 vs 6,73 ± 0,83 mol%, p = 0,005), tak v séru (4,78 ± 0,90 vs 6,57 ± 0,98 mol%, p = 0,01) ve sledované skupině pacientů. Závěr: Naše výsledky potvrdily, že flavonoidy, obsažené v přípravku Comfort-G, jsou schopny snižovat množství volných radikálů a zvyšovat zastoupení kyseliny arachidonové, a to zejména v synoviální tekutině, ale i v séru pacientů. Toto zjištění souhlasí s tvrzením, že následující enzymatické reakce AA, které produkují prozánětlivé sloučeniny, jsou zřejmě zablokovány. Další souvislosti, týkající se jiných částí organismu, a význam našich výsledků pro jiná další onemocnění jsou předmětem diskuse, Objective: Flavonoids from preparation Comfort-G have, beside of antioxidant effects, the anti-inflammatory effect, too. Comfort-G inhibits both COX-1 (cyclooxygenase-1)/COX-2 (cyclooxygenase-2) and 5-LO (5-lipoxygenase) enzymatic activity thereby decreasing the transformation of arachidonic acid (AA) to prostaglandins, thromboxanes, and leukotrienes. Our goal was to confirm this finding by the analysis of the content of AA in synovial fluid and serum of patients suffering by synovialitis of knee joint. Design: Interventional study. Settings: IV Department of Internal Medicine, Charles University in Prague, First Faculty of Medicine and General Teaching Hospital in Prague. Material and Methods: Comfort-G was given to the group of ten patients (4M/6F) aged 27–79 years in prescribed dose (equal to 250 mg of flavonoid extract twice a day) for one month. Synovial fluid and serum were drawn before first application of the preparation (day 0) and one day after the last application (day 31). Free radicals (FR) were determined by direct spectrophotometric method based on chlorophyllin reaction with FR; composition of fatty acids, including arachidonic acid, was measured by gas chromatography. The probands were also asked to respond to a questionnaire (subjective evaluation) and they were also examined by the physician. Following changes of knee joint were evaluated: swelling and degree of motion-angle. Statistical analysis was performed with the help of software STATISTICA for Windows, version 4.0. Results: The results showing the statistically significant decrease of free radical concentration in both synovial fluid and serum were presented and discussed in previously presented paper as well as the observed amelioration of patient stage. After the trial period, we found increased content of AA in both synovial fluid (4.54 ± 0.39 vs. 6.73 ± 0.82 mol%, p = 0.005) and serum (4.78 ± 0.90 vs. 6.57 ± 0.98 mol%, p = 0.01) in the same group of patients. Conclusion: Our results confirm that flavonoids from Comfort-G are able to decrease the amount of FR and increase the concentration of AA especially in synovial fluid, but also in serum of patients. This finding corresponds with the suggestion that the enzymatic transformations of AA resulting in production of pro-inflammatory compounds are blocked. The next consequences concerning other parts of organism and impact of our results in case of other diseases are discussed., Marek Vecka, Libor Prokeš, Eva Tvrzická, Karel Karpaš, A. Pernický, R. Pfleger, Miloš Votruba, and Lit.: 18
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

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