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1.
Nutr Metab Cardiovasc Dis ; 24(10): 1112-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24932537

RESUMO

BACKGROUND AND AIMS: Diverse waist circumference thresholds for assessment of metabolic and cardiovascular risk in Caucasians are recommended by different health professional organizations. We aimed to determine optimal sex-specific thresholds for anthropometric measures showing the strongest association with cardiovascular risk factors in a cohort of middle-aged Germans. METHODS AND RESULTS: Statistical analyses are based on data from 426 mothers and 267 fathers of participants of the Ulm Birth Cohort Study undergoing a clinical follow-up examination in 2008 (median age 41 years) using logistic regression analyses. The prevalence of many cardiometabolic risk factors was significantly higher in men than in women; hypertension: 45%/17% (p < 0.0001), apolipoprotein ratio B/A1 > 0.72: 35%/9% (<0.0001), hyperglycemia: 11%/14% (p = 0.3), which is in contrast to the predicted cardiovascular risk of 52%/70% and 24%/36% based on thresholds for waist circumference proposed by International Diabetes Federation and American Heart Association, respectively. We determined optimal thresholds for waist circumference between 90 and 95 cm for men and women. Using a threshold of 92 cm the prevalence of abdominal obesity was 59% in men and 24% in women, which was in agreement with the higher prevalence of overweight and obesity in men than in women (Body Mass Index (BMI) > 25: 64%/35%). The prediction of cardiometabolic risk factors by waist circumference and waist-to-height ratio did not outperform the prediction by BMI. In contrast to BMI, waist circumference was correlated with body height independent of sex. CONCLUSION: Currently proposed thresholds for waist circumference spuriously overestimate the cardiovascular risk in women, but not in men in a German population.


Assuntos
Doenças Cardiovasculares/epidemiologia , Obesidade Abdominal/epidemiologia , Circunferência da Cintura , Adulto , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Glicemia/metabolismo , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Feminino , Seguimentos , Alemanha , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/prevenção & controle , Prevalência , Medição de Risco , Fatores de Risco , Razão Cintura-Estatura
2.
Leukemia ; 21(4): 732-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17301819

RESUMO

Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate with antitumor activity used to treat patients with malignant diseases. ZA treatment induces, as a side effect, inflammatory responses, which are accompanied by expansion of gammadelta T cells. In our study, we analyzed the function and differentiation of monocyte-derived immature and lipopolysaccharide (LPS)-stimulated dendritic cells (moDCs) treated with different ZA concentrations, which are achieved in patients. We found that moDC activation with TLR4 ligand LPS is modulated by ZA. The expression of maturation markers was diminished with increasing ZA levels upon LPS activation. The migratory capacity, interleukin-12 secretion and generation of cytotoxic- T-cell responses were reduced at higher ZA levels. Increasing ZA concentrations downregulated nuclear factor-kappaB family members and interferon-regulatory factor (IRF)-3. Surprisingly, in immature moDCs, low ZA concentrations caused upregulation of RelB, c-Rel, IRF-3 and IRF-8. We conclude that ZA concentrations used to treat patients have inhibitory effects on DC activation. This might lead to immunosuppression or result in infectious complications.


Assuntos
Células Dendríticas/fisiologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Monócitos/citologia , Receptor 4 Toll-Like/fisiologia , Conservadores da Densidade Óssea/farmacologia , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Linfócitos T Citotóxicos/citologia , Receptor 4 Toll-Like/efeitos dos fármacos , Ácido Zoledrônico
3.
Aliment Pharmacol Ther ; 26(6): 879-87, 2007 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-17767472

RESUMO

BACKGROUND: Epidemiological data on chronic atrophic gastritis from general population samples are sparse in Germany. AIM: To assess prevalence of chronic atrophic gastritis according to potential risk factors and clinical outcomes in a large-scale population-based study. METHODS: In the baseline examination of ESTHER, a population-based cohort study conducted in Germany, serological measurements of pepsinogen (PG) I and II and Helicobacter pylori antibodies were taken in 9444 women and men aged 50-74 years. Information on potential risk factors and medical history were obtained by questionnaire. RESULTS: With the definition used in the EUROGAST study (PG I < 25 ng/mL), prevalence of chronic atrophic gastritis increased from 4.8% in age group 50-54 to 8.7% in age group 70-74. An alternative definition of chronic atrophic gastritis (PG I < 70 ng/mL and PG I/PG II < 3), used in multiple studies from Japan, revealed a greater increase with age (from 2.7% to 9.1%) and a strong association with H. pylori infection (adjusted odds ratio: 2.9, 95% confidence interval: 2.4-3.7). With both definitions, a strong inverse association with heartburn was observed. CONCLUSIONS: Overall chronic atrophic gastritis prevalence is low among older adults in Germany, but it strongly increases with age and H. pylori infection.


Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Pepsinogênio C/metabolismo , Distribuição por Idade , Idoso , Feminino , Alemanha/epidemiologia , Infecções por Helicobacter/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/análise , Pepsinogênio A/urina , Prevalência , Inquéritos e Questionários
4.
Hamostaseologie ; 27(2): 98-104, 2007 May.
Artigo em Alemão | MEDLINE | ID: mdl-17479172

RESUMO

OBJECTIVE: Lower-extremity amputation (LEA) is a common complication among patients with diabetes. This study tests the effects of a structured disease management program for the diabetic foot (DF) aiming to reduce the number of LEA. DESIGN, METHODS: In a prospective study design we investigate patients with DF in a system of outpatient treatment, acute in-patient care and rehabilitative treatment. Subjects were recruited since January 1(st), 2000, with the latest admission being December 31, 2004. All study participants undergo a five-year follow-up observation period. The University of Texas Wound Classification System (UT) of foot ulcers serves as basis of the documentation and analysis. We evaluated numbers of LEA, rates of ulcer healing and underlying forms of peripheral vascular disease. RESULTS: We report the results of the first patient group completing the two-year follow-up examination. In 2000, 102 subjects with new foot ulcers were consecutively included into the study. 68.6% were men, the mean age of the study population was 68.1 +/- 11.4 years and the mean diabetes duration was 19.4 +/- 10.3 years. After two years, 68 patients can still be examined. Altogether, 22 patients (21.6%) died, and 12 (11.8%) dropped out for various reasons. At the point of discharge from the clinics 35.3% of the ulcers had healed and another 44.1% were in UT grade 1. After two years, a complete healing could still be determined with 51 patients (50.0% of the cohort of the original 102 patients, or 75.0% of the subjects reaching the two-year follow-up). 10 subjects (9.8% or 14.5%) were in the UT grade 1. Eight diabetics underwent major amputation (MA) during the two-year examination period (amputation rate 7.8%). CONCLUSIONS: The primary objective of the study, a significant reduction of MA with DF patients, has been achieved. The ulcer healing rates are comparable to the reports of leading centers.


Assuntos
Pé Diabético/terapia , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Pé Diabético/mortalidade , Pé Diabético/cirurgia , Humanos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Análise de Sobrevida
5.
Biochim Biophys Acta ; 1224(1): 17-21, 1994 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-7948039

RESUMO

Previous quantification of glucocorticoid receptor (GR) binding in adipose tissue has been performed in cytosol preparations, which did not allow the determination of the total number of GR in the cell. Therefore, GR binding was determined in intact adipocytes. Dexamethasone (dex) was used as a ligand in adipocytes isolated from epididymal (Epi), retroperitoneal (Ret), inguinal (Ing) and mesenteric (Mes) adipose tissue regions in male rats. The binding was saturable and specific with a Kd in the nanomolar range, not different from previously reported affinity of binding in cytosol preparations from adipocytes. Binding capacity rose after removal of endogenous glucocorticoids either by adrenalectomy (ADX) or culture in a glucocorticoid-free medium. Binding capacity of adipocytes was in general higher in Mes adipose cells than in adipocytes from Epi, Ing and Ret tissues from intact and ADX animals when expressed per unit of triglyceride weight of adipose tissues. This seemed to be largely explainable by a higher cellular density in Mes than in other adipose tissues. When comparisons were performed with binding per adipocyte, intraabdominal (Epi, Ret and Mes) cells bound more dex than adipocytes from subcutaneous (Ing) adipose tissue. It is suggested that in comparison with other adipose tissues Mes tissue has a higher density of the GR in situ, due mainly to a higher cellular density. Intraabdominal adipocytes in general seem to have a higher GR density than subcutaneous cells. This might explain the high activity of glucocorticoid-regulated metabolic pathways in intraabdominal particularly Mes adipose tissue.


Assuntos
Adipócitos/metabolismo , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/metabolismo , Adrenalectomia , Animais , Sítios de Ligação , Ligação Competitiva , Células Cultivadas , Dexametasona/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
6.
Leukemia ; 18(11): 1839-49, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15457186

RESUMO

The inositol 5-phosphatase SHIP (SHIP-1) is a negative regulator of signal transduction in hematopoietic cells and targeted disruption of SHIP in mice leads to a myeloproliferative disorder. We analyzed the effects of SHIP on the human leukemia cell line Jurkat in which expression of endogenous SHIP protein is not detectable. Restoration of SHIP expression in Jurkat cells with an inducible expression system caused a 69% reduction of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) and a 65% reduction of Akt kinase activity, which was associated with reduced phosphorylation of glycogen synthase kinase 3beta (GSK-3beta) (Ser-9) without changing the phosphorylation of Bad (Ser-136), FKHR (Ser-256) or MAPK (Thr-202/Tyr-204). SHIP-expressing Jurkat cells showed an increased transit time through the G1 phase of the cell cycle, but SHIP did not cause a complete cell cycle arrest or apoptosis. Extension of the G1 phase was associated with an increased stability of the cell cycle inhibitor p27(Kip1) and reduced phosphorylation of the retinoblastoma protein Rb at serine residue 780. Our data indicate that restoration of SHIP activity in a human leukemia cell line, which has lost expression of endogenous SHIP, downregulates constitutively activated phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling and leads to an increased transit time through the G1 phase of the cell cycle.


Assuntos
Fase G1 , Quinase 3 da Glicogênio Sintase/metabolismo , Leucemia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Apoptose , Proteínas de Transporte/metabolismo , Inibidor de Quinase Dependente de Ciclina p27 , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Ativação Enzimática , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead , Glicogênio Sintase Quinase 3 beta , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células Jurkat , Leucemia/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Fosforilação , Proteínas Proto-Oncogênicas c-akt , Proteína do Retinoblastoma , Fatores de Tempo , Fatores de Transcrição/metabolismo , Proteína de Morte Celular Associada a bcl , Domínios de Homologia de src
7.
Am J Hypertens ; 13(3): 268-75, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10777031

RESUMO

Spontaneous baroreceptor reflex sensitivity (BRS) is a well established method for determining baroreflex function, which can be used to assess the potential impact on survival after myocardial infarction, to detect autonomic dysfunction in diabetic patients and in human essential hypertension. The assessment of impaired spontaneous baroreflex function in individual patients contains important clinical information, but age-dependent reference values are still lacking. In the present study we evaluated spontaneous BRS in healthy human controls to determine reference values as a function of age. Two hundred and sixty-two healthy volunteers divided into six age groups (I: <20 years, f = 11, m = 9, II: 20-29 years, f = 42, m = 37, III: 30-39 years, f = 23, m = 37, IV: 40-49 years, f = 27, m = 22, V: 50-59 years, f = 19, m = 17, VI: 60-69 years, f = 5, m = 13). Electrocardiograms (ECG) and finger arterial BP were measured with each subject in the supine position (sup, 7 min) and during deep breathing (dB, 6/min, 15 cycles). BRS was assessed using the sequence technique and the alpha coefficients as obtained from a power spectrum density estimate. Due to the normal logarithmic distribution of the BRS, the limits for impaired baroreflex function at rest were defined from logarithmic data. The limits for the BRS at rest (P = .025) were calculated as (-0.0283 x age) + 2.5198 for the sequence technique. We did not find significant differences in BRS among the female and male healthy volunteers. Our analysis of the six age groups showed the expected significant decrease in BRS, which was most prominent at the transition from group III (<40 years) to group IV (<50 years). BRS at rest and during deep breathing as well as sequential and spectral BRS indices did differ significantly. The results underline the necessity of reference values to evaluate impaired baroreflex function in individual patients.


Assuntos
Pressorreceptores/fisiologia , Reflexo/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Pressão Sanguínea/fisiologia , Criança , Diástole , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Sístole
8.
Am J Med Sci ; 322(1): 24-30, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11465243

RESUMO

BACKGROUND: Early detection of cardiac autonomic neuropathy (CAN) permits individual risk stratification. Spontaneous heart rate variability (HRV) and baroreflex sensitivity (BRS) are suggested to be superior to classic autonomic testing in that they detect CAN earlier, with greater reliability, and do not require the patient's undue attention. METHODS: To test that hypothesis, we studied 53 diabetic patients (mean age, 55 years) and 38 age-matched healthy control subjects (HC). Subjects underwent deep breathing, Valsalva maneuver, and orthostatic testing. Each abnormal test was counted as 1 point. A change in systolic blood pressure during standing of more than 10 mm Hg was graded with a single point; a decrease of more than 20 mm Hg received 2 points. A total score of zero was regarded as no CAN (noCAN), a score > or =4 as severe CAN (sCAN), and scores of 1 to 3 as mild CAN (mCAN). Spontaneous BRS was determined using the sequence technique. HRV was calculated as coefficient of variation (CV), high frequency power (HF) and low frequency power (LF). RESULTS: Mean group values for HRV and BRS were: CV = 3.9+/-1.3; 4.0+/-1.3; 2.4+/-1.1; and 1.2+/-0.4; BRS = 8+/-3; 8+/-5; 5+/-2; and 2+/-2 msec/mm Hg for HC n = 38, noCAN n = 15, mCAN n = 26, and sCAN n = 12, respectively. BRS was similar in HC and patients with noCAN. In sCAN, BRS detected only 10 of 12 patients. HRV and BRS did not improve reclassification based on discriminant analysis. CONCLUSION: BRS and HRV did not detect CAN in older diabetic patients better than classic autonomic testing.


Assuntos
Barorreflexo , Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Cardiopatias/diagnóstico , Frequência Cardíaca , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Análise Discriminante , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Cardiopatias/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Decúbito Dorsal
9.
Angew Chem Int Ed Engl ; 38(18): 2741-2745, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10508367

RESUMO

A stabilization of the liquid-crystalline mesophase and thus an enlarged temperature range of the mesogenic phase is achieved by adding perfluorotriphenylene to a chiral liquid-crystalline triphenylene. This mesophase is based on 1:1 perfluoroarene-arene interactions (see picture). In a polymer with triphenylenes as mesogens in the side chains, the addition of perfluorotriphenylene led to crystallization.

10.
Pediatr Obes ; 9(2): 121-34, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23420701

RESUMO

BACKGROUND: Although many epidemiological studies have shown an association between maternal smoking during pregnancy and offspring overweight, it is still under debate whether intrauterine tobacco smoke exposure directly affects offspring obesity or if the association is rather due to confounding by lifestyle factors. OBJECTIVES: The association of parental smoking habits at pre- and post-natal periods with offspring body mass index (BMI) was investigated, whereas maternal smoking during pregnancy was validated by cord serum cotinine measurements. METHODS: Multivariable linear regression analysis, based on the German Ulm Birth Cohort Study of 1045 children born in 2000 with annual/biennial follow-up until the age of 8 years (n = 609), was conducted. RESULTS: BMI of offspring from mothers who smoked during pregnancy and non-smoking mothers differed significantly at 8 years. Maternal smoking during pregnancy was associated with an increase in BMI of 0.73 kg m(-2) [95% confidence interval: 0.21-1.25] in 8-year-old children after adjustment for multiple potential confounding variables. Both pre- and post-natal smoking of fathers (0.34 [0.01-0.66]/0.45 [0.08-0.81]) and of both parents (1.03 [0.43-1.63]/0.56 [0.14-0.98]) were likewise significantly associated with offspring BMI. CONCLUSIONS: The observed patterns suggest that residual confounding by living conditions in smoking families rather than specific intrauterine exposure to tobacco smoke may account for the increased risk of offspring overweight.


Assuntos
Pai , Estilo de Vida , Mães , Obesidade Infantil/etiologia , Efeitos Tardios da Exposição Pré-Natal , Fumar , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Composição Corporal , Índice de Massa Corporal , Criança , Pré-Escolar , Comportamento Alimentar , Feminino , Seguimentos , Alemanha/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Obesidade Infantil/epidemiologia , Obesidade Infantil/prevenção & controle , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores Socioeconômicos , Inquéritos e Questionários
11.
Dtsch Med Wochenschr ; 137(43): 2223-8, 2012 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-23076670

RESUMO

The prevalence of obesity and related health problems is increasing worldwide and also in Germany. It is well known that substantial and sustained weight loss is difficult to accomplish. Therefore, a variety of studies has been performed in order to specify causes for weight gain and create hypotheses for better treatment options. Key factors of this problem are an adaptation of energy metabolism, especially resting metabolic rate (RMR), non-exercise thermogenesis and diet induced thermogenesis. The extremely high failure rate (> 80%) to keep the reduced weight after successful weight loss is due to adaptation processes of the body to maintain body energy stores. This so called "adaptive thermogenesis" is defined as a smaller than predicted change of energy expenditure in response to changes in energy balance. Adaptive thermogenesis appears to be a major reason for weight regain. The foremost objective of weight-loss programs is the reduction in body fat. However, a concomitant decline in lean tissue can frequently be observed. Since lean body mass (LBM) represents a key determinant of RMR it follows that a decrease in lean tissue could counteract the progress of weight loss. Therefore, with respect to long-term effectiveness of weight reduction programs, the loss of fat mass while maintaining LBM and RMR seems desirable. In this paper we will discuss the mechanisms of adaptive thermogenesis and develop therapeutic strategies with respect to avoiding weight regain successful weight reduction.


Assuntos
Metabolismo Energético/fisiologia , Obesidade/fisiopatologia , Obesidade/terapia , Redução de Peso/fisiologia , Tecido Adiposo/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Metabolismo Basal/fisiologia , Índice de Massa Corporal , Dieta Redutora , Ingestão de Energia/fisiologia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Termogênese/fisiologia , Testes de Função Tireóidea
12.
Aliment Pharmacol Ther ; 32(2): 296-302, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20456301

RESUMO

BACKGROUND: Obesity and overweight have been positively related to gastro-oesophageal reflux disease (GERD). It has been suggested that this relationship is as a consequence of an increased gastric acid reflux, which is caused by an enhanced intra-abdominal pressure. AIM: To assess potential interaction of the association between body mass index (BMI) and GERD by chronic atrophic gastritis, which goes along with decreased acid production. METHODS: In the baseline examination of ESTHER, a study conducted in 9953 older adults in Saarland, information on frequency of heartburn, potential risk factors and medical history was obtained by self-administered standardized questionnaire. Serological measurements of pepsinogen I and II were taken for definition of chronic atrophic gastritis. RESULTS: In total, 2565 (28.7%) of the included subjects experienced heartburn within the previous 4 weeks. A pronounced dose-response relationship was observed between BMI and heartburn occurrence (P < 0.001) among people without chronic atrophic gastritis, but not among people with chronic atrophic gastritis (P-value for interaction = 0.018). Obese/overweight people with chronic atrophic gastritis had a much lower risk of heartburn compared with obese/overweight people without chronic atrophic gastritis (OR = 0.31, 95% CI = 0.24-0.40). CONCLUSION: Our results are consistent with the hypothesis that BMI is related positively to GERD symptoms by its impact on acid reflux.


Assuntos
Índice de Massa Corporal , Gastrite Atrófica/etiologia , Azia/etiologia , Obesidade/complicações , Idoso , Doença Crônica , Estudos de Coortes , Feminino , Ácido Gástrico , Refluxo Gastroesofágico/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/metabolismo , Pepsinogênio C/metabolismo , Prevalência , Testes Sorológicos , Inquéritos e Questionários
13.
Leukemia ; 23(3): 535-44, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19005481

RESUMO

Toll-like receptors (TLRs) act to sense the environment for microbial products and submit danger signals to antigen-presenting cells (APCs) resulting in activation of complex immune responses. In this study, we analyzed the function of human monocyte-derived APCs generated in vitro in the presence of interleukin (IL)-10 upon activation by TLR ligands. Exposure of these APCs to IL-10 resulted in a skewed phenotypic maturation in response to stimuli provided by the TLR ligands, a reduced cytokine production, such as IL-12, IL-6 or tumor necrosis factor-alpha, and impaired capacity to stimulate T-cell activation. Furthermore, CCR7 upregulation in APCs exposed to TLR stimulation as well as migration towards CCL19/MIP-3beta were strongly reduced. IL-10 was found to downregulate MyD88, IRAK1 (IL-1 receptor-associated kinase) and tumor necrosis factor receptor-associated factor 6, essential adaptor molecules for TLR signaling, and to decrease TLR-induced nuclear expression of the nuclear factor-kappaB transcription factors c-Rel and Rel-B as well as interferon regulatory factor (IRF)-3 and IRF-8. This was not due to the inhibition of the mitogen-activated protein kinase pathway, but was rather mediated by the blockage of the PI3K signaling cascade. Interestingly, the inhibition of proteins involved in TLR signaling, such as MyD88, IRAK1 and mammalian target of rapamycin, was due to a selective post-transcriptional regulation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Apresentação de Antígeno/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-10/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/imunologia , Quimiocina CCL19/fisiologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/metabolismo , Células Dendríticas/imunologia , Humanos , Quinases Associadas a Receptores de Interleucina-1/biossíntese , Quinases Associadas a Receptores de Interleucina-1/genética , Interleucina-10/fisiologia , Ligantes , Ativação Linfocitária , NF-kappa B/biossíntese , NF-kappa B/genética , Fagocitose/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Receptores CCR7/biossíntese , Receptores CCR7/genética , Linfócitos T/imunologia
14.
Z Gesamte Inn Med ; 37(3): 73-83, 1982 Feb 01.
Artigo em Alemão | MEDLINE | ID: mdl-7043921

RESUMO

The estimation of apoprotein profiles makes an essential contribution to the study of the lipid metabolism, particularly of the normal and deranged lipid transport. For the clinician patterns of apoproteins might open new possibilities of the differential diagnosis of dyslipoproteinaemias. Four fundamental apoprotein profiles are presented by Alaupovic et al. (2): 1. Significantly reduced serum levels of the apolipoproteins AI, AII and B (essentially corresponding to HLP type I) 2. Increased values of apo-B (types IIa, IIb) 3. Increased concentration of apo-C-III reduction of the CI/CII-quotient (types IIb, IV) 4. Increased levels of the apolipoproteins C and E (types III, V). The authors suppose that these four basic patterns of apolipoproteins reflect the fundamental biochemical defects of the lipoprotein transport. The biochemical characterization of certain, genetically determined disturbances of the lipid transport with the help of apoprotein profiles is the best example for the essential role of these proteins in the lipid metabolism with regard to the clinical diagnostics it is at present not yet possible to get additional informations with the help of the estimation of apoproteins as they would not be got by far simpler methods. As was already mentioned, in these cases the rare genetically determined disturbances of the lipid metabolism and the diagnostics of the HLP type III form an exception. Only few authors try to prove that the proportion of proteins in lipoproteins seems to be somewhat better suited for the differentiation of persons endangered by arteriosclerosis than the proportion of lipids. Especially the increase of concentration of the apo-B is to be regarded as significant factor of risk of a chronic ischaemic heart disease. This is unequivocally confirmed, but the essentially simpler estimation of the LDL-cholesterol yields well comparable results with regard to the characterization of persons, endangered by chronic ischaemic heart disease.


Assuntos
Apolipoproteínas , Reações Antígeno-Anticorpo , Apolipoproteínas/análise , Apolipoproteínas/classificação , Apolipoproteínas/metabolismo , Arteriosclerose/metabolismo , Transporte Biológico , Fenômenos Químicos , Química , Colesterol/sangue , LDL-Colesterol , Diabetes Mellitus/metabolismo , Humanos , Técnicas Imunológicas , Erros Inatos do Metabolismo Lipídico , Lipoproteínas LDL/sangue , Nefelometria e Turbidimetria , Risco
15.
Int J Obes ; 13 Suppl 2: 33-7, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2693383

RESUMO

VLCD is an effective and safe measure to reduce overweight in NIDDM. It substantially improves glucose control and corrects associated coronary risk factors, in particular dyslipoproteinaemia and hypertension. Both insulin secretion and insulin resistance were ameliorated by perfect glucose control with VLCD. Reliable data on long term efficacy and factors determining weight loss and success in permanent glucose control are urgently needed.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus/dietoterapia , Dieta Redutora , Ingestão de Energia , Obesidade , Glicemia/metabolismo , Pressão Sanguínea , Colesterol/sangue , Feminino , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue , Redução de Peso
16.
Acta Med Austriaca ; 24(5): 180-4, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9428944

RESUMO

Our objective was to investigate the relationship between gastric emptying and mesenteric blood flow in type 1 diabetic patients with (CAN+) and without (CAN-) cardiac autonomic neuropathy. CAN was determined by a series of cardiovascular reflex tests and power spectral analysis of heart rate variations (HRV) using a computerized system. We calculated from these data a score for cardiac autonomic neuropathy with a maximum of 7 points (1 point for abnormal value of: CV of HRV at supine rest, CV of HRV during deep breathing, Valsalva ratio, lying-to-standing ratio, PSA of HRV in the low frequency band, PSA of HRV in the mid frequency band, blood pressure response to standing). Patients were considered to have CAN if at least 3 of the 7 parameters were found to be abnormal (CAN score > or = 3). The resulting groups (CAN-, n = 14 vs. CAN+, n = 16) were well matched with respect to age (53 +/- 11 vs. 51 +/- 12 years), BMI (27.2 +/- 3.3 vs. 25.9 +/- 3.6 kg/m2), duration of diabetes (162 +/- 157 vs. 158 +/- 100 months), fasting blood glucose (6.9 +/- 2.6 vs. 6.8 +/- 2.4 mmol/l) and HbA1c (7.2 +/- 1.5 vs. 7.3 +/- 2.0%). Gastric emptying was determined by real-time ultrasonography (antral planimetry) during 60 min after a semiliquid test meal (Fresubin diabetes 300 ml, 53% carbohydrate, 32% lipid, 15% protein) and the blood flow of the superior mesenteric artery was measured by Doppler ultrasound technique. Type I diabetic patients with CAN had a significantly higher CAN score than those without CAN (6.1 +/- 0.4 vs. 1.3 +/- 0.7). Mean preprandial (before ingestion of the test meal) as well as postprandial (immediately after ingestion of test meal) antral areas of CAN+ (5.2 +/- 2.0v/10.9 +/- 2.8 cm2) and CAN- (5.1 +/- 1.5/10.8 +/- 2.2 cm2) were comparable. CAN+ had significantly slower decrease of postprandial antral areas at 15, 30, 45 and 60 min after ingestion of test meal (-1.7 +/- 0.4/-8.3 +/- 1.2/-9.5 +/- 0.9/-19.5 +/- 2.0 delta % compared to postprandial value) compared to CAN- (-8.9 +/- 1.8/-22.5 +/- 2.6/-29.1 +/- 2.9/-35.5 +/- 2.9 delta %). The increase in mesenteric blood flow at 15, 30 and 45 min after the meal was significantly reduced in CAN+ compared to CAN- patients. Significantly negative correlations were found between the CAN score and the decrease of antral area as well as between CAN score and the increase of diastolic mesenteric blood flow and significantly positive correlations between the decrease of antral area and the increase of diastolic mesenteric blood flow. In conclusion, type 1 diabetic patients with cardiac autonomic neuropathy showed delayed gastric emptying and diminished mesenteric blood flow during 60 min after ingestion of a semiliquid test meal.


Assuntos
Arritmias Cardíacas/diagnóstico , Doenças do Sistema Nervoso Autônomo/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Angiopatias Diabéticas/diagnóstico , Neuropatias Diabéticas/diagnóstico , Esvaziamento Gástrico/fisiologia , Circulação Esplâncnica/fisiologia , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Eletrocardiografia , Feminino , Gastroparesia/diagnóstico , Gastroparesia/fisiopatologia , Coração/inervação , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Processamento de Sinais Assistido por Computador
17.
Dtsch Med Wochenschr ; 126(20): 590-2, 2001 May 18.
Artigo em Alemão | MEDLINE | ID: mdl-11402925

RESUMO

HISTORY AND ADMISSION FINDINGS: A 70 year old woman had suffered from diabetes mellitus type 2 since she was 52. Three years before the surgery she had begun to experience weakness together with altered sensitivity in the right leg, which was regarded as having been caused by diabetic polyneuropathy. During the admission examination the level for algesia on the right-hand side was at about D 11, a distal paraparesis of the leg (3-4 degrees, Janda's classification), more intense on the right, hyperactive deep tendon reflexes, Babinski's reflex on both sides, and depressed abdominal cutaneous reflexes. The sensitivity to vibrations on the Malleolus medialis on both sides was 0/8. The patient could walk only with the help of a Rollator. INVESTIGATIONS: Over the three-year period following onset of symptoms the following tests were carried out: motor nerve conduction speeds of the N. tibialis and N. peronaeus, electromyogram of the N. tibialis anterior and the M. gastrocnemius, somatosensory evoked potentials (SSEP) of the N. tibialis, which indicated a lesion in the peripheral nerves or nerve roots. Cranial computed tomography (CCT), CT scan of the lumbar spine (L3-S1) and angiological investigation elicited no significant pathological findings. An MRI of the thoracal spine showed a vertebra-sized dorsal tumor pressing on the spinal cord from left to right. TREATMENT AND COURSE: By means of microsurgery the spinal tumor was completely removed. Suspected meningeoma was confirmed by histological analysis. During the post-surgical period, the incomplete paraplegia quickly regressed, and 7 weeks after the removal of the spinal meningeoma the patient was able to climb stairs. CONCLUSION: In case of slowly-developing paresis of the legs in diabetic patients, diabetic polyneuropathy should not be diagnosed without careful consideration, and rare spinal tumors should be considered as part of the differential diagnosis, especially if the blood glucose level is normal, and intensive physiotherapy brings no improvement in the patient's condition.


Assuntos
Neuropatias Diabéticas/diagnóstico , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Compressão da Medula Espinal/diagnóstico , Neoplasias da Coluna Vertebral/diagnóstico , Vértebras Torácicas , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Exame Neurológico , Tomografia Computadorizada por Raios X
18.
Hum Genet ; 64(2): 186-8, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6885058

RESUMO

Using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) five different beta-chain patterns of denaturated human C4 were observed: C4 beta H, beta H greater than L, beta H = L, beta H less than L, and beta L. In 32 families with 174 offspring the segregation of C4 beta-chain types followed that of the other major histocompatibility complex (MHC) markers. It is concluded that the C4 beta-chain patterns represent a genetically determined polymorphism, coded within the known C4A and B gene region.


Assuntos
Complemento C4/genética , Polimorfismo Genético , Complemento C4/análise , Feminino , Genótipo , Humanos , Alótipos de Imunoglobulina/genética , Masculino , Linhagem , Peptídeos/análise , Peptídeos/genética , Fenótipo
19.
Wien Med Wochenschr ; 145(22): 616-25, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8585217

RESUMO

Assessment of heart rate and heart rate variability (HRV) are used in sports medicine and space medicine to give conclusions about the functional state of the autonomic nervous system. Furthermore, reduced HRV and changed blood pressure variability (BPV) are accepted as risk factors in patients with cardiovascular diseases, metabolic syndrome and neurologic disorders. The aim of the first studies was to combine the evaluation of central hemodynamic (impedance cardiography) with HRV and BPV evaluation in the time and frequency domain (fft tracking) based on a standardized clinical test with automated protocol output. Data acquisition and -analysis was realized beat to beat (Kohto Ltd., Moscow) during forced breathing (150 s, 6 breath/min) and postural tilt (7 min, supine, transition to 55 degrees in 4 s, 7 min upright) allowing one to evaluate: orthostatic response type including impedance cardiography; activation of vagal afferences and efferences by forced breathing; vagal and sympathetic components during initial heart rate and blood pressure responses; characteristic changes of spectral balance of HRV and BPV (measured at the finger) during early regulation. First investigations on 34 normal volunteers subdivided into two age groups and on 13 patients with different diseases indicate that besides the age dependent changes (reduced HRV, reduced cardiac performance, reduced regulatory amplitudes and baroreflex sensitivity) individual response types can be described and dysfunction of different reflex loops can be detected. Consequently, the assessment of specific influences onto circulatory control by therapy, sport and rehabilitative training is possible and further studies are necessary.


Assuntos
Pressão Sanguínea/fisiologia , Cardiografia de Impedância , Frequência Cardíaca/fisiologia , Postura/fisiologia , Adulto , Idoso , Sistema Nervoso Autônomo/fisiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Hemodinâmica/fisiologia , Humanos , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/fisiopatologia , Pressorreceptores/fisiologia , Valores de Referência , Respiração/fisiologia , Processamento de Sinais Assistido por Computador , Decúbito Dorsal/fisiologia , Teste da Mesa Inclinada , Nervo Vago/fisiopatologia
20.
Acta Med Austriaca ; 24(5): 175-9, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9428943

RESUMO

The objective of the study was to define the impairment of sympathovagal balance in patients with diabetes mellitus (DM) and coronary heart disease (CHD) compared to healthy controls (HC) showing similar heart rate variability (HRV) at supine rest. 88 DM (41 m, 47 f; age 62 +/- 1 years; BMI 27.1 +/- 1.5 kg/m2; HbA1c 7.9 +/- 0.4%), 49 CHD (27 m, 22 f; age 62 +/- 1 years; BMI 27.1 +/- 1.6 kg/m2; HbA1c 5.2 +/- 0.1%) and 16 HC (8 m, 8 f; age 59 +/- 1 years; BMI 26.4 +/- 0.5 kg/m2; HbA1c 5.0 +/- 0.1%) were investigated. Time series of heart period duration (HPD) were obtained during 2 min deep breathing (6/min), 5 min of supine rest and for 5 min at upright position using a RR memory device (BHL 6000, Baumann-Haldi Switzerland, modified ECG lead, 1 kHz). Mean HPD, coefficient of variation (CV), total power (TP) and integral power in the HF (0.15 to 0.5 Hz), MF (0.05 to 0.15 Hz) and LF (0.015 to 0.05 Hz) frequency bands as well as (MF-HF)/(MF + HF) as spectral index were calculated. As to be expected we found significantly lower values of CV, TP and HPD in DM compared to HC. The CV of HRV did not differ significantly between DM and CHD but TP and HPD of CHD patients were significantly higher in comparison to DM. Therefore, the deterioration of HRV was most pronounced in the DM group. For further analysis we calculated data of subjects with CV's in the upper quartile (> or = 3.52) of the CV at supine rest. The aim of this procedure was to compare subjects with similar high HRV at supine rest. With this method we obtained from all subjects 12 HC, 11 DM and 12 CHD. These DM had a significant decrease of CV, TP and the integral power at the HF frequency band during active orthostasis compared to HC and CHD. The spectral index increased significantly during standing in HC and CHD but was unchanged in DM. These changes were accompanied by a nearly similar increase of HRV during deep breathing. In conclusion, DM with normal reaction to deep breathing did not activate the sympathetic baroreflex loop during active orthostasis. This could be an early sign of sympathetic dysfunction in DM with normal HRV at supine rest.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Barorreflexo/fisiologia , Neuropatias Diabéticas/diagnóstico , Frequência Cardíaca/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Doença das Coronárias/diagnóstico , Doença das Coronárias/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Eletrocardiografia , Feminino , Coração/inervação , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Descanso , Processamento de Sinais Assistido por Computador , Decúbito Dorsal/fisiologia , Nervo Vago/fisiopatologia
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