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1.
Br J Haematol ; 202(6): 1137-1150, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37460273

RESUMO

Adaptor chimeric antigen receptor (CAR) T-cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T-cell therapy in myeloid malignancies. The adaptor CAR T-cell platform 'UniCAR' is currently under early clinical investigation. Recently, the first proof of concept of a well-tolerated, rapidly switchable, CD123-directed UniCAR T-cell product treating patients with acute myeloid leukaemia (AML) was reported. Relapsed and refractory AML is prone to high plasticity under therapy pressure targeting one single tumour antigen. Thus, targeting of multiple tumour antigens seems to be required to achieve durable anti-tumour responses, underlining the need to further design alternative AML-specific target modules (TM) for the UniCAR platform. We here present the preclinical development of a novel FMS-like tyrosine kinase 3 (FLT3)-directed UniCAR T-cell therapy, which is highly effective for in vitro killing of both AML cell lines and primary AML samples. Furthermore, we show in vivo functionality in a murine xenograft model. PET analyses further demonstrate a short serum half-life of FLT3 TMs, which will enable a rapid on/off switch of UniCAR T cells. Overall, the presented preclinical data encourage the further development and clinical translation of FLT3-specific UniCAR T cells for the therapy of AML.


Assuntos
Leucemia Mieloide Aguda , Tirosina Quinase 3 Semelhante a fms , Humanos , Animais , Camundongos , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Imunoterapia Adotiva , Linfócitos T , Antígenos de Neoplasias , Leucemia Mieloide Aguda/tratamento farmacológico
3.
EJNMMI Radiopharm Chem ; 1(1): 14, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29564390

RESUMO

BACKGROUND: Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68Ga-labelled analogues, endoradiotheraphy with 177Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. METHODS: Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTAPAM and DOTAZOL(MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68Ga and the ß- emitting nuclide 177Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [18F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. RESULTS: The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68Ga and >98 % with 177Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [68Ga]DOTAZOL (SUV Femur = 5.4 ± 0.6) followed by [18F]NaF (SUV Femur = 4.8 ± 0.2), [68Ga]DOTAPAM (SUV Femur = 4.5 ± 0.2) and [68Ga]BPAPD (SUV Femur = 3.2 ± 0.3). [177Lu]DOTAZOL showed a similar distribution as the diagnostic 68Ga complex. CONCLUSION: The 68Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [68Ga]DOTAZOL, which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177Lu. The therapeutic compound [177Lu]DOTAZOL showed a high target-to-background ratio. SPECT experiments showed concordance to the PET scans in healthy rats. [68Ga/177Lu]DOTAZOL appears to be a potential theranostic combination in the management of disseminated bone metastases.

4.
Gesundheitswesen ; 78(11): 695-707, 2016 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-26335658

RESUMO

Aim: 20 years after establishment of the National Breastfeeding Committee, the present work, based on published data on breastfeeding, is aimed at providing insight into the development of breastfeeding behaviour in Germany. Methods: To identify relevant publications, a comprehensive literature search was conducted in PubMed and Web of Science using the search terms "breast feeding" or "breastfeeding" in combination with "Germany". The publication period was limited to the period 1995-2014. Results: A total of 35 studies with data on breastfeeding for the birth cohorts of 1990-2012 were identified. Most of the data had been collected in regional or local surveys, often retrospectively. About 60% of the studies had been conducted with the primary aim of collecting data on breastfeeding or infant nutrition. Over the past 2 decades, breastfeeding rates were always relatively high at the beginning (72-97%). However, they declined significantly within the first 2 months, and by the age of 6 months, only about 50% of infants were still breastfed. Conclusion: Breastfeeding support and early assistance should be offered to a greater extent in order to achieve sustainable improvement of breastfeeding frequency and duration in Germany. Regarding the quality of data collected on breastfeeding, it seems crucial to implement standardised approaches to monitor breastfeeding in Germany.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Aleitamento Materno/tendências , Comportamento Materno , Adolescente , Adulto , Distribuição por Idade , Feminino , Alemanha/epidemiologia , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Adulto Jovem
5.
Geburtshilfe Frauenheilkd ; 75(8): 819-826, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26366001

RESUMO

Introduction: Preterm birth is a global scourge, the leading cause of perinatal mortality and morbidity. This study set out to identify the principal risk factors for preterm birth, based on the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). A range of possible factors influencing preterm birth were selected for inclusion in the questionnaire, covering factors such as gender, national origin, immigrant background, demography, living standard, family structure, parental education and vocational training. Methods: All data were taken from the aforementioned KiGGS survey conducted between 2003 and 2006. A total of 17 641 children and adolescents (8656 girls and 8985 boys) drawn from 167 German towns and municipalities deemed to be representative of the Federal Republic of Germany were included in the study. Gestational age at birth was available for 14 234 datasets. The questionnaire included questions from the following areas as possible factors influencing preterm birth: gender, national origins, immigrant background, demography, living standard, family structure, parental education and vocational training. Results: The preterm birth rate was 11.6 %, higher than that of other national statistical evaluations. Around 57.4 % of multiple pregnancies and 10 % of singleton pregnancies resulted in preterm delivery. Multiple pregnancy was found to be the most important risk factor (OR 13.116). With regard to national origins and immigration background, mothers from Turkey, the Middle East, and North Africa had a higher incidence of preterm birth. Preterm birth was more prevalent in cities and large towns than in small towns and villages. Conclusion: Risk factors associated with preterm birth were identified. These should help with the early identification of pregnant women at risk. The preterm birth rate in our survey was higher than that found in other national statistical evaluations based on process data. More than half of all multiple pregnancies ended in preterm birth.

6.
Forensic Sci Int ; 241: 190-4, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24967869

RESUMO

Despite emergent research initiatives, significant knowledge gaps remain of soil microbiology-associated cadaver decomposition. Nevertheless, preliminary studies have shown that the vast diversity and complex interactions of soil microbial communities have great potential for forensic applications such as clandestine grave location and postmortem interval estimation. This study investigated changes in soil bacterial communities during pig (Sus scrofa domesticus) leg decomposition. 16S rRNA, instead of the usually applied 16S rDNA marker, was used to compare the metabolically active bacteria. Total bacterial RNA was extracted from soil samples of three different layers on day 3, 28 and 77 after the shallow burial of a pig leg. The V3 region of the 16S rRNA was amplified, analysed by RT-PCR DGGE, and compared with control soil bacterial community profiles. Statistically significant differences in soil bacterial biodiversity were observed. For the control, bacterial diversity (H') and species richness (S) of the three layers averaged 2.48±0.14 (H') and 18.8±2.5 (S), respectively, while for the test soil increases (p=0.027) were recorded between day 3 (H'=2.71±0.02; S=21.3±2.0) and 28 (H'=3.46±0.32; S=60.3±16.9), particularly in the middle (10-20 cm) and bottom (20-30 cm) soil layers. Between day 28 and 77 the diversity and richness then decreased on average for all three layers (H'=3.43±0.20; S=60.0±17.3) but remained higher than on day 3. Thus, responses in soil bacterial profiles and activity to carcass decomposition, detected and characterised by RNA-based DGGE, could be used together with RNA sequencing data, changes in physico-chemical variables (carbon, nitrogen, phosphorus, temperature, redox potential, water activity and pH) and conventional macroecology markers (e.g. insects and vegetation), to develop a suite of analytical protocols for different forensic scenarios.


Assuntos
Microbiota , Mudanças Depois da Morte , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Microbiologia do Solo , Animais , Eletroforese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sus scrofa
7.
Z Rheumatol ; 73(4): 323-8, 2014 May.
Artigo em Alemão | MEDLINE | ID: mdl-24728601

RESUMO

BACKGROUND: [corrected] There are many drugs which can cause osteoporosis or at least favor its initiation. The effect of hormones and drugs with antihormonal activity, such as glucocorticoids and aromatase inhibitors, on initiation of osteoporosis is well known. In addition, proton pump inhibitors, glitazones and diuretics also influence the formation of osteoporosis. MATERIAL AND METHODS: The results of currently available studies on the correlation between proton pump inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated and summarized. RESULTS: Proton pump inhibitors and glitazones increase the risk for osteoporotic fractures. Loop diuretics may slightly increase fracture risk, whereas thiazides were shown to be osteoprotective by reducing fracture probability on a relevant scale. CONCLUSION: Proton pump inhibitors should not be prescribed without serious consideration and then only as long as necessary. Alternatively, the administration of the less effective H2 antagonists should be considered when possible due to the reduction of acid secretion. Because the long-term intake of thiazides is associated with a clinically relevant reduction in the risk of fractures and they are economic and well-tolerated, prescription can be thoroughly recommended within the framework of differential diagnostic considerations in an appropriate clinical context. The briefly increased risk of falling immediately after starting diuretic therapy is the only point which needs to be considered.


Assuntos
Cortisona/efeitos adversos , Diuréticos/efeitos adversos , Osteoporose/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Cortisona/uso terapêutico , Diuréticos/uso terapêutico , Substituição de Medicamentos , Humanos , Assistência de Longa Duração , Osteoporose/diagnóstico , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco , Estatística como Assunto , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico
8.
Eur J Med Chem ; 70: 434-46, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24184988

RESUMO

The bifunctional chelating agent 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid, DMPTACN-COOH, has been found to bind strongly to copper(II), resulting in a radiocopper(II)-ligand complex that exhibits high in vivo stability. The pendant carboxylic acid group enables this derivative to be conjugated to the N-terminal amino acid residues of peptides. Exploiting this, two stabilized bombesin (BBN) derivatives, ßAla-ßAla-[Cha(13),Nle(14)]BBN(7-14) and ßhomo-Glu-ßAla-ßAla-[Cha(13),Nle(14)]BBN(7-14) have been coupled to DMPTACN-COOH and radiolabeled with the positron emitter copper-64 ((64)Cu-1 and (64)Cu-3). The in vitro binding characteristics of the [(64)Cu]Cu-labeled bombesin conjugates in gastrin-releasing peptide receptor (GRPR) over-expressing prostate cancer (PC-3) cells have been evaluated. Biodistribution studies performed in Wistar rats indicate a specific uptake in the GRPR-rich pancreas and rapid renal elimination for both (64)Cu-1 and (64)Cu-3. Small animal PET imaging studies performed in NMRI nu/nu mice bearing the human prostate tumor PC-3 demonstrated a very high degree of tumor accumulation for (64)Cu-1 and (64)Cu-3. Incorporation of a single additional glutamic acid residue within the spacer between bombesin and the radiolabeled complex ((64)Cu-3) leads to a higher tumor-to-muscle uptake ratio (amounting to >30 at 100 min post injection) compared to (64)Cu-1.


Assuntos
Bombesina , Quelantes , Radioisótopos de Cobre , Neoplasias da Próstata/química , Compostos Radiofarmacêuticos , Animais , Bombesina/química , Bombesina/farmacocinética , Linhagem Celular Tumoral , Quelantes/química , Quelantes/farmacocinética , Radioisótopos de Cobre/química , Radioisótopos de Cobre/farmacocinética , Humanos , Masculino , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Receptores da Bombesina/biossíntese , Distribuição Tecidual
9.
Appl Radiat Isot ; 82: 100-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23974304

RESUMO

The formation of ß-amyloid deposits is considered a histopathological feature of Alzheimer's disease (AD). In vivo molecular imaging by means of amyloid-avid radiotracers will allow for an early and conclusive diagnostic of AD. Herein, we describe the radiosynthesis of the radiofluorinated styryl benzoxazole derivative [¹8F]-[2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole] ([¹8F]-1) and its pre-clinical evaluation, including metabolic and biodistribution studies in male Wistar rats. The in vivo biological evaluation of [¹8F]-1 showed that this new radiotracer has a moderate brain uptake with a slow brain washout and a poor in vivo stability.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Benzoxazóis/síntese química , Radioisótopos de Flúor , Compostos Radiofarmacêuticos/síntese química , Doença de Alzheimer/diagnóstico por imagem , Animais , Benzoxazóis/farmacocinética , Barreira Hematoencefálica , Radioisótopos de Flúor/farmacocinética , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Distribuição Tecidual
10.
Mol Cell Endocrinol ; 371(1-2): 189-94, 2013 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-23267837

RESUMO

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Feocromocitoma/tratamento farmacológico , Receptores de Neuropeptídeos/efeitos dos fármacos , 2-Hidroxifenetilamina/análogos & derivados , 2-Hidroxifenetilamina/farmacologia , Compostos de Anilina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacologia , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Camundongos , Pirróis/farmacologia , Receptores LHRH/biossíntese , Receptores LHRH/efeitos dos fármacos , Receptores LHRH/metabolismo , Receptores de Neuropeptídeos/biossíntese , Receptores de Neuropeptídeos/metabolismo , Receptores de Hormônios Reguladores de Hormônio Hipofisário/biossíntese , Receptores de Hormônios Reguladores de Hormônio Hipofisário/efeitos dos fármacos , Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo , Receptores de Somatostatina/biossíntese , Receptores de Somatostatina/efeitos dos fármacos , Receptores de Somatostatina/metabolismo , Sermorelina/análogos & derivados , Sermorelina/farmacologia , Somatostatina/análogos & derivados
11.
Nuklearmedizin ; 51(6): 239-43, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22684530

RESUMO

Diagnosis of Alzheimer's disease (AD) with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) relies on typical alterations of brain glucose metabolism which are, however, not disease specific. Amyloid-ß imaging has not entered clinical routine yet. Post mortem histological specimen of brain tissue from AD patients revealed enhanced expression of the chemotactic cytocine receptor 1 (CCR1). PARTICIPANTS, METHODS: CCR1-antagonist ZK811460 was labeled with fluorine-18 to explore its possible use as specific diagnostic tool in AD. Tracer characterization comprising PET imaging of brain and metabolite analysis was performed in AD patients and controls. RESULTS: Neither qualitative evaluation nor quantitative compartment analysis of PET data did show any enhanced binding of the 18F-labeled CCR1-antagonist in the brain of AD patients or controls. CONCLUSION: 18F-ZK811460 did not fulfill the expectation as diagnostic tracer in PET imaging of AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Radioisótopos de Flúor , Compostos de Fenilureia , Piperazinas , Receptores CCR1/antagonistas & inibidores , Idoso , Doença de Alzheimer/metabolismo , Feminino , Radioisótopos de Flúor/química , Humanos , Marcação por Isótopo , Masculino , Compostos de Fenilureia/síntese química , Piperazinas/síntese química , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Poult Sci ; 90(10): 2169-73, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21933997

RESUMO

The breeding of male layer chickens is currently considered to be highly uneconomical. In Germany alone, 40 to 50 million newly hatched male chickens were killed annually immediately after hatching. Therefore, it is necessary to find a method for sexing chickens early in the embryonic development, preferably before incubation. The genotypic sex of an egg can be determined using information found in the germinal disc, so knowledge of the exact position of the germinal disc is essential for further sexing, or for other actions such as the in ovo injection of agents. Previous studies have shown that the germinal disc is located somewhere on top of the yolk. However, no studies have yet been performed that investigate the influence of time spent in horizontal storage on the position of the germinal disc. Magnetic resonance imaging was chosen to determine this influence on the position of the germinal disc. It was found that eggs placed horizontally for long periods of time before scanning had significant changes in the positions of their germinal discs compared with those of eggs scanned minutes after positioning. The position of the germinal disc in eggs, minutes after horizontal positioning, deviated 14.7 ± 0.6 mm from the maximum vertical plane of the egg (zero position) in the z-direction; eggs scanned after 96 h of horizontal positioning showed a deviation of only 4.9 ± 1.6 mm. The x-axis also exhibited changes in the position of the germinal disc over time. Immediately after horizontal positioning, the eggs showed a deviation of 0.4 ± 0.4 mm in the x-direction, whereas the deviation after 96 h was 2.9 ± 0.5 mm. These results show that horizontal positioning of the egg hours before the measurement is necessary.


Assuntos
Blastodisco/anatomia & histologia , Embrião de Galinha/anatomia & histologia , Animais , Blastodisco/química , Cruzamento , Feminino , Imageamento por Ressonância Magnética , Masculino , Análise para Determinação do Sexo/métodos , Análise para Determinação do Sexo/veterinária , Fatores de Tempo
13.
Gesundheitswesen ; 71(11): 709-21, 2009 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-19750459

RESUMO

In June 1909, The Empress Auguste Victoria House in Berlin was opened. This first institute for preventive paediatrics had the objective to overcome infant mortality in Germany. This objective was attained. Since then, an unprecedented decrease of mortality in all age groups occurred as well as a doubling of life expectancy. With this "retreat of death", our concepts of health changed fundamentally, and a new spectrum of diseases emerged. This article discusses some mile stones of this change, and explains why we find more illness despite the great improvement in the field of health. The "new diseases" amenable to early prevention are presented in a table. To make disease prevention successful requires the participation of the individual. Therefore, it is important to know the demand to make a good programme effective in the population. Empirical results of a nationwide representative study on the demand by expecting and young parents for preventive consultation are presented. Anticipatory guidance of young parents is a modern approach to health promotion and disease prevention. A controlled trial shows that this approach improved knowledge, behaviour, health risk indicators, health, and development during the first two years after delivery. Future studies should focus on long term effects of early health promotion.


Assuntos
Promoção da Saúde/história , Serviços Preventivos de Saúde/história , Medicina Preventiva/história , Alemanha , História do Século XX , História do Século XXI
14.
Gesundheitswesen ; 71(6): 332-8, 2009 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-19530058

RESUMO

AIMS: The aim of this study was to collect information on and to evaluate the impact of the timing of first suckling and breast-feeding initiation in Berlin and to assess the practicability and acceptance of using a short questionnaire to collect breast-feeding data in hospitals and birth centres. METHODS: A three-month observational study was conducted in 19 maternity units and 4 birth centres, using a short questionnaire to collect quantitative data on the timing of first suckling and breast-feeding from mother-child pairs on the day of discharge. RESULTS: The data indicate a breast-feeding rate of 96.1% at discharge. Infants born in birth centres were more frequently put to their mother's breast within the first hour after birth (p<0.05), and were more frequently mainly (p<0.05) or exclusively (p<0.01) breast-fed at discharge than infants born in hospitals. Hospitals' breast-feeding policies (i.e., following the 'ten steps to successful breast-feeding') were not associated with a higher prevalence of early first suckling and any breast-feeding at discharge, but rather with exclusivity of breastfeeding (p<0.001). CONCLUSIONS: Breast-feeding initiation rates are satisfactorily high in Berlin. Rates of early first suckling and (exclusive) initial breast-feeding are highest in birth centres. No consistent association was found between hospitals' breast-feeding policy and initial breast-feeding variables. The questionnaire was well accepted and is deemed suitable for monitoring purposes.


Assuntos
Centros de Assistência à Gravidez e ao Parto/estatística & dados numéricos , Aleitamento Materno/epidemiologia , Aleitamento Materno/estatística & dados numéricos , Inquéritos Epidemiológicos , Maternidades/estatística & dados numéricos , Adulto , Feminino , Alemanha/epidemiologia , Humanos , Prevalência , Adulto Jovem
15.
Z Geburtshilfe Neonatol ; 212(3): 80-6, 2008 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-18709626

RESUMO

UNLABELLED: Knowledge of the risks of smoking during pregnancy induces only part of the pregnant women to give up smoking. How many pregnant women in Germany smoke from the beginning to delivery, and what characterises these smokers, is the topic of this article. METHODS: Results from the German Mikrozensus, several national surveys, perinatal statistics and Euro-scip III are presented, compared, and assessed. Findings of our own studies conducted between 1999 and 2002 at the obstetric department and gynacological practices in Berlin allow an insight into the magnitude of "underreporting". RESULTS: In the ages 15-45 years 36-45 % of German women smoke, prevalence rates that probably are valid even for the beginning of pregnancy. While smoking prevalence in men has decreased during the last 20 years, there is an increasing trend in women. The prevalence is higher in pregnant women of low social status, living with smoking partners and those of German nationality. At most, half of the women give up smoking during pregnancy. Assuming an "underreporting" in pregnant women of at least one third, the prevalence of smoking up to delivery is 24 %. Although 76 % of the practicing gynacologists in Berlin feel responsible for smoking counselling, only 12 % are convinced that it is successful. CONCLUSIONS: A quarter of the pregnant women in Germany smoke through to delivery, which means that 150 000 newborns per year have been exposed to passive smoking in utero, and its long-term health effects, which is a national disaster.


Assuntos
Gravidez/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Previsões , Alemanha , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Abandono do Hábito de Fumar , Fatores Socioeconômicos , Poluição por Fumaça de Tabaco/prevenção & controle , Poluição por Fumaça de Tabaco/estatística & dados numéricos
16.
Bioconjug Chem ; 19(8): 1596-603, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18651757

RESUMO

The interest in using small peptides for therapeutic and diagnostic in vivo applications is based on several advantageous features such as good penetration into tissues and rapid clearance from the body. Because of their size, they can easily be synthesized chemically. The recently discovered cell-penetrating peptides (CPP) and among them CPP derived from the native peptide hormone human calcitonin (hCT) could meet these requirements. Therefore, they are nowadays widely used as delivery vectors for a variety of bioactive molecules. However, the knowledge about the distribution and metabolism of CPP in vivo is very limited. Hence, evaluation of the pharmacological features of any promising peptide is a crucial challenge in its development process. Herein, we studied the in vivo radiopharmacology of (68)Ga radiolabeled DOTA-modified, hCT-derived CPP in rats using small animal PET. Furthermore, the arterial blood at different time points and urine were analyzed for radio-metabolites. It was shown that d-amino acid modifications of the sequence hCT(9-32) resulted in an increased in vivo stability and lower retention in the kidney cortex of this peptide.


Assuntos
Calcitonina/metabolismo , Calcitonina/farmacocinética , Peptídeos/metabolismo , Peptídeos/farmacocinética , Sequência de Aminoácidos , Animais , Calcitonina/química , Permeabilidade da Membrana Celular , Quelantes/metabolismo , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel/metabolismo , Humanos , Masculino , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/química , Fenilalanina , Tomografia por Emissão de Pósitrons , Ratos , Ratos Wistar , Distribuição Tecidual
17.
Gesundheitswesen ; 69(8-9): 448-56, 2007.
Artigo em Alemão | MEDLINE | ID: mdl-17926261

RESUMO

TOPIC: We studied those characteristics of mothers that are related to occupational activity two years after the birth of the first child. Differences in the health-related quality of life between working mothers and mothers who are not working were also analysed, taking other parameters into account, in particular household income. METHODOLOGY: 311 mothers with a first child were given a questionnaire on the quality of life based on WHOQOL-BREF, on depression (also surveyed one year before for 139 mothers), on their work situation, socio-demography and other possible confounders. The probability of vocational activity was analysed using logistic regression and the influence of multiple roles on the quality of life was analysed using multiple linear regression. RESULTS: About 60% of mothers were not working two years after the birth of their first child, 25% were working part-time and 11% full time, with 4% in training or education. Working mothers were more likely to have a higher level of education (60% vs. 31%) and less likely to have a household income below the poverty line (13% vs. 47%). The results of the logistic regression showed that the odds ratio for being employed was six times higher for mothers with higher education than mothers with a lower level of education [OR 5.99; 95% confidence interval (CI) 2.58-13.91], whereas the odds ratio for mothers with additional children against those with only one child was 0.14; (95% CI 0.05-0.40), and for mothers with German nationality against those of other ethnicities the odds ratio was 2.37 (95% CI 1.12-5.04). Working mothers give more positive ratings than non-working mothers for their physical and mental quality of life (both p<0.01), their social relationships (p<0.05), as well as their global quality of life and their depression score (p<0.10). Even after adjusting for the depression score one year before working mothers reported less depression (p<0.05). The influence of income on the quality of life was low, except for the assessment of the quality of the environment, and this explains only a small part of the positive effect of the vocational activity. CONCLUSIONS: Vocational activity of mothers of two-year old children reduces the risk of poverty and additionally contributes to an improved physical and mental quality of life of the mother and also to improved social relationships.


Assuntos
Emprego/estatística & dados numéricos , Relações Mãe-Filho , Mães/estatística & dados numéricos , Qualidade de Vida , Papel (figurativo) , Adolescente , Adulto , Escolaridade , Feminino , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Pobreza/estatística & dados numéricos , Classe Social
18.
Nuklearmedizin ; 46(5): 181-4, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17938751

RESUMO

AIM: The preparation and stability of a new (188)Re-S(4)-complex [S(4) = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH(2))(3)-NH-(CH(2))(3)-NHC(O)-C(SH)-C(SH)-C(O)(1-aza-18-crown-6] was studied at therapeutic relevant radioactive concentrations. The results were compared with (188)Re-MAG(3) (MAG(3): mercaptoacetyltriglycine) and (188)Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [(188)Re]perrhenate solution (12-15 GBq/ml). METHODS: The (188)Re complexes were prepared by direct reduction of perrhenate ((188)Re-S(4)-complex) as well as via the (188)Re-EDTA precursor complex ((188)Re-MAG(3), (188)Re-DMSA). The preparations were stabilised with 15 mg of ascorbic acid and analysed after 1, 2, and 24 hours by TLC and HPLC. Additionally, in vitro and in vivo stability studies were performed with the purified complexes. RESULTS: After stabilisation with 15 mg of ascorbic acid, all of the complexes were nearly stable under nitrogen for hours, and only 2-8% of perrhenate was observed after 24 h. In contrast, only the (188)Re-S(4) complex was completely stable in vitro and in all investigated in vivo samples after separation of ligand excess and reducing agent by HPLC. CONCLUSION: The bridging amine group or free carboxylic groups of the S(4)-ligand framework make available reactive positions for coupling biomolecules to the chelate. Thus it appears that the new (188)Re-S(4) complexes offer the possibility of stable and high specific activity labelling of biomolecules for therapeutic application.


Assuntos
Marcação por Isótopo/métodos , Radioisótopos , Rênio , Estabilidade de Medicamentos , Ligantes , Modelos Moleculares , Rênio/análise
19.
Artigo em Alemão | MEDLINE | ID: mdl-17514446

RESUMO

Breast milk is the most natural and best type of nutrition for almost all infants. Moreover, breastfeeding is associated with health benefits for mother and child: breast milk supports the development of the infant and protects it against diseases; the health benefits for the mothers also extend beyond the period after birth. Therefore, the WHO recommends exclusive breastfeeding for at least six months. Until now, no representative data on the breastfeeding rate have been available in Germany. The KiGGS results show an increase in the breastfeeding rate from 1986 to 2005. Across all age groups studied, 76.7 % (95 % CI: 75.2 %-78.1 %) of the children were ever breastfed. The rate of ever-breastfed children was significantly lower in mothers from socially disadvantaged population groups, children of mothers who had smoked during pregnancy or in situations with problems after birth. Children with migration background were more frequently ever-breastfed than children without migration background. The average duration of breastfeeding was - across all age-groups - 6.9 months (95 % CI: 6.8-7.0); the duration of full breastfeeding was 4.6 months (95 % CI: 4.5-4.7) on average. 22.4 % (95 % CI: 21.4 %-23.5 %) of all children from the KiGGS study population were exclusively breastfed for a period of six months. The results emphasises the necessity to further promote breastfeeding, especially to support the socially disadvantaged, and most of all to encourage a positive attitude towards breastfeeding in the society.


Assuntos
Aleitamento Materno/epidemiologia , Adulto , Emigração e Imigração/estatística & dados numéricos , Feminino , Alemanha , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Meio Social , Fatores Socioeconômicos
20.
Artigo em Alemão | MEDLINE | ID: mdl-17514451

RESUMO

KIGGS is a health survey on 17,641 children and adolescents in 167 communities representative for Germany, conducted between May 2003 and May 2006. Of the perinatal indicators, only a small proportion of data important for long-term outcomes was available for statistical analysis, and is presented here. In the past 20 years the mean weight gain during pregnancy has increased significantly by 2 kg, the mean birth weight has increased significantly by an average of 50 g, there has been no significant time trend for smoking and alcohol consumption in pregnancy. Birth weight and pregnancy weight gain of the mother correlate significantly. Pregnancy weight gain explains 5% of the birth weight in first-born infants. 17-18% of the mothers smoked during pregnancy, 4 times as many in the lower than the upper social class. 14% of the mothers consumed alcohol in pregnancy, but only 1% regularly. Only 5% of the migrants, but 3 times as many of the non-migrants consumed alcohol in pregnancy, and 2 1/2 times as many of the upper class compared to the lower class. With respect to smoking and alcohol consumption during pregnancy there seems to be an urgent need for political action.


Assuntos
Doenças do Prematuro/epidemiologia , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Peso ao Nascer , Criança , Pré-Escolar , Emigração e Imigração , Feminino , Alemanha , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Estatística como Assunto , Aumento de Peso
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