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1.
Ultrasound Obstet Gynecol ; 50(3): 336-341, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28078790

RESUMO

OBJECTIVE: While complete agenesis of the corpus callosum is often suspected on fetal ultrasound due to absence of the cavum septi pellucidi (CSP), suspicion of partial agenesis of the corpus callosum (pACC) is a challenge since the CSP is almost always present. The aim of this study was to measure the length and width of the CSP and calculate the length-to-width ratio (CSP ratio), and compare these between fetuses with pACC and normal fetuses. METHODS: In this retrospective case-control study, the length and width of the CSP were measured in the axial plane of the fetal head, and the CSP length-to-width ratio calculated, in 323 normal fetuses and in 20 fetuses with pACC between 20 and 34 weeks' gestation. From the normal population we constructed reference ranges in relation to biparietal diameter (BPD). For all fetuses we calculated Z-scores for the CSP ratio. RESULTS: In the normal population, the length and width of the CSP increased with increasing BPD, while the CSP ratio decreased. The CSP was short (< 5th centile) in 85% (17/20) of fetuses with pACC and wide (> 95th centile) in 65% (13/20). The CSP ratio was small (< 5th centile) in 95% (19/20) of pACC fetuses, with 16/20 (80%) having a ratio below an empirical cut-off of 1.5. Analysis of Z-scores showed that fetuses with pACC had a significantly smaller CSP ratio (P < 0.0001) compared with the normal population. CONCLUSIONS: Fetuses with a normal-sized corpus callosum have a rectangular-shaped CSP, with a CSP ratio > 1.5 in the second half of gestation. Most fetuses with pACC have an abnormally shaped, wide and short CSP, with a decreased CSP ratio. This simple ratio has the potential to identify fetuses at high risk for pACC. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Agenesia do Corpo Caloso/diagnóstico , Corpo Caloso/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Agenesia do Corpo Caloso/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Valores de Referência , Estudos Retrospectivos
2.
Ultrasound Obstet Gynecol ; 48(2): 171-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26586168

RESUMO

OBJECTIVE: To examine the frontal space (FS) distance in first-trimester fetuses with bilateral, unilateral or median cleft lip and palate and in those with retrognathia. METHODS: This was a retrospective study using stored two-dimensional ultrasound images of fetal profiles that were recorded at the time of the nuchal translucency (NT) scan at three prenatal medical centers. Images of 300 normal fetuses and 53 fetuses with facial defects were obtained. To measure the FS distance, a line was drawn between the anterior edge of the mental protuberance of the mandible and anterior edge of the maxilla (MM line) and extended upwards in front of the forehead. The perpendicular distance (FS distance) between the MM line and the skin at the point of largest excursion of the fetal forehead was measured. In cases in which the MM line was located anteriorly to the forehead, the distance was measured in the same fashion but was multiplied by -1. Two operators measured the FS distance twice, independently of each other. FS distances were transformed into Z-scores based on the linear relationship with crown-rump length (CRL) in normal fetuses. The distribution of FS distances in fetuses with bilateral, unilateral or median cleft lip and palate and those with retrognathia were compared with that in the normal group using Student's t-test. RESULTS: A search of the centers' databases identified 53 abnormal cases including 20, nine and eight with a bilateral, unilateral and median cleft lip and palate, respectively, and 16 cases of retrognathia. In fetuses with bilateral, unilateral and median clefts and those with retrognathia, median delta NT was 1.00 mm, 0.37 mm, 4.00 mm and 0.26 mm, respectively. Among these affected groups, 12 (60.0%), six (66.7%), two (25.0%) and eight (50.0%) fetuses had an abnormal karyotype. In the normal population, FS distance was dependent on CRL measurement (FS = 6.62 - (0.08 × CRL); r = -0.539; P < 0.0001). In fetuses with a bilateral and median cleft and in those with retrognathia, FS distance was significantly different from that in the normal population (all P < 0.0001), however, the difference was not significant in fetuses with unilateral clefts (P = 0.103). The respective Z-scores of FS distance for fetuses with bilateral, unilateral and median clefts and retrognathia were -9.7 ± 2.0, -3.1 ± 5.1, 8.2 ± 3.4 and -7.3 ± 2.3. Measurements were ≥ 99(th) and ≤ 1(st) centiles in all but one (98.1%) case. CONCLUSION: The FS distance appears to be a helpful tool in the detection of facial clefts at 11-13 weeks' gestation. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Testa/embriologia , Medição da Translucência Nucal/métodos , Retrognatismo/diagnóstico por imagem , Adulto , Feminino , Testa/diagnóstico por imagem , Humanos , Interpretação de Imagem Assistida por Computador , Idade Materna , Variações Dependentes do Observador , Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos
3.
Anaesthesist ; 65(6): 430-7, 2016 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-27221390

RESUMO

BACKGROUND: Complications and comorbidities are encodable in the German diagnosis related groups (G-DRG) system and can improve revenues. In this study, secondary diagnoses were identified through drug administrations during anaesthesia and were economically evaluated by regrouping these cases. METHODS: All intraoperative drug administrations from 2008 were extracted from a database. After exclusion of synonyms and procedure-specific drug administrations, all remaining drugs were matched to explicit secondary diagnoses. All cases were regrouped with their newly defined secondary diagnoses by G­DRG grouper software, and changes in cost weight were evaluated. RESULTS: A total of 29 drugs could be assigned to 18 secondary diagnoses. From 22,440 anaesthesia the § 21 data record could be extracted in 1,929 cases and was regrouped with 2,976 secondary diagnoses, according to additional proceeds of 125,330.25 € in 2008 and 103,542.35 € in 2014. Intraoperative secondary diagnoses influence cost weight only in small parts. The average increase in revenue in this study could have been about 50 € per case. From 2008 to 2014 secondary diagnoses were continuously devaluated, although some of them, e. g. afibrinogenemia, have were revaluated. DISCUSSION: Our retrospective method of making a diagnosis and assuming a correct indication of drug administration is inapplicable to daily routine. The anaesthesiologic documentation has to make drug administration and thereby the secondary diagnosis plausible.


Assuntos
Grupos Diagnósticos Relacionados/economia , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/economia , Período Intraoperatório , Anestésicos/efeitos adversos , Análise Custo-Benefício , Bases de Dados Factuais , Documentação , Combinação de Medicamentos , Custos de Medicamentos , Toxidermias/diagnóstico , Toxidermias/economia , Interações Medicamentosas , Alemanha , Humanos , Estudos Retrospectivos
4.
J Hosp Infect ; 146: 37-43, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38224856

RESUMO

INTRODUCTION: Immunocompromised patients are at an increased risk of severe legionella infections. We present the results of an outbreak investigation initiated following a fatal case of hospital-acquired legionellosis linked to contaminated water from a toilet-flushing cistern. Additionally, we provide experimental data on the growth of Legionella spp. in flushing cisterns and propose a straightforward protocol for prevention. METHODS: We monitored the growth of Legionella spp. in the building's hot- and cold-water systems using quantitative bacterial culture on selective agar. Molecular typing of Legionella pneumophila isolates from the infected patient and the water system was conducted through core-genome multi-locus sequence typing (cgMLST). RESULTS: Legionella contamination in the hospital building's cold-water system was significantly higher than in the hot-water system and significantly higher in toilet flushing cistern's water compared with cold water from bathroom sinks and showers. Isolates from the patient and from the flushing cistern of the patient's bathroom were identical by cgMLST. In an experimental setting, daily toilet flushing for a period of 21 days resulted in a 67% reduction in the growth of Legionella spp. in the water of toilet flushing cisterns. Moreover, a one-time disinfection of cisterns with peracetic acid, followed by daily flushing, decreased legionella growth to less than 1% over a period of at least seven weeks in these setting. CONCLUSIONS: One-time disinfection of highly contaminated cisterns with peracetic acid and daily toilet flushing as short-term measure can significantly reduce legionella contamination in flushing cisterns. These measures may aid in preventing legionella infection among immunocompromised patients.


Assuntos
Aparelho Sanitário , Legionella pneumophila , Legionella , Legionelose , Humanos , Legionelose/prevenção & controle , Tipagem de Sequências Multilocus , Ácido Peracético , Água , Microbiologia da Água , Abastecimento de Água , Alemanha
5.
J Hosp Infect ; 138: 1-7, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37127148

RESUMO

BACKGROUND: The virulence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) changed during the pandemic. In order to provide a rationale for treatment priorities of respiratory infections and the adaption of in-house infection control strategies, this study evaluated treatment on an intensive care unit (ICU), requirement for mechanical ventilation (MV), requirement for extracorporeal membrane oxygenation (ECMO) and death for inpatients infected with the influenza virus or SARS-CoV-2 during the wild-type, Alpha, Delta, Omicron BA.1/2 and Omicron BA.5 waves of the pandemic. DESIGN: Single-centre retrospective case-control study. SETTING: Tertiary hospital in Germany. PARTICIPANTS: One thousand three hundred and sixteen adult inpatients infected with SARS-CoV-2 and 218 adult inpatients infected with influenza virus. METHODS: Demographic data, outcome parameters and underlying comorbidities of patients were obtained from the hospital information system. Multi-variate regression analysis was performed for the assessment of significant associations between risk factors and outcome variables. RESULTS: Compared with inpatients infected with influenza virus, patients infected with SARS-CoV-2 showed significantly higher rates for in-hospital mortality, admission to ICU and requirement for MV in the wild-type, Alpha and Delta waves, and a significantly higher rate for requirement for ECMO in the wild-type wave. In the Omicron BA.1/BA.2 and Omicron BA.5 waves, patients infected with SARS-CoV-2 did not show significantly higher risk of in-hospital mortality, admission to ICU, or requirement for MV or ECMO compared with patients infected with influenza virus. The length of hospital stay of patients infected with SARS-CoV-2 decreased from 10.8 to 6.2 days, which was less than that of patients infected with influenza virus (8.3 days). CONCLUSIONS: Treatment capacities should be shared equally between SARS-CoV-2 and influenza virus infections. Similar levels of infection control could be applied, at least regarding the severity of infection.


Assuntos
COVID-19 , Influenza Humana , Adulto , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , SARS-CoV-2 , Pacientes Internados , Pandemias
6.
Orthopadie (Heidelb) ; 51(11): 920-928, 2022 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-36227361

RESUMO

In winter sports, skiers, snowboarders and ice hockey players have the highest risk of traumatic brain injuries (TBI). In skiing/snowboarding severe TBIs are of concern; in ice hockey, repetitive minor TBIs are frequent. The main causes of TBI in recreational skiing are collisions with trees; in professionals falls due to technical or tactical mistakes are the main causes. In ice hockey 10-15% of all injuries are due to a sports-related concussion (SRC), mostly caused by player-opponent contact. The pathomechanism in TBI is a combination of rotational and linear acceleration during head impact, which causes a diffuse axonal injury. Long-term complications such as neurodegenerative diseases and functional deficits are of relevance. Prevention by wearing helmets is effective, but less effective in TBI/SRC than in focal injuries.


Assuntos
Concussão Encefálica , Hóquei , Esqui , Humanos , Esqui/lesões , Dispositivos de Proteção da Cabeça , Concussão Encefálica/epidemiologia , Aceleração
7.
Vaccine X ; 11: 100194, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35855061

RESUMO

The vaccination coverage in Flanders is high, but some regions show lower vaccination willingness as compared to the overall vaccination coverage. Beginning November of 2021, the vaccination rate in Flanders was above 93% in age groups above 45 years, and around 85% in the age groups 12 to 44 years. Apart from Flanders as a whole, focus here is on the health sector Maasland, which has a slightly lower vaccination rate, especially in the age groups 12 to 44 years. In the Maasland region, located on the eastern border of Flanders, there are between 1% and 10% less vaccinated individuals than expected according to the vaccination rate in the whole of Flanders, with lowest vaccination rates in the south of the Maasland region. We study the impact of ethnic diversity in the population, population composition with respect to the ethnicity of individuals (in the sense of how the local population composition differs from the Flemish average), and socio-economic status on the vaccination rate at the level of the statistical sector, apart from the effect of age. We explain the statistical methods to investigate geographical differences and illustrate how one can deal with incomplete information in vaccination registries. Ethnic diversity in a region is associated with lower vaccination rates, as is a lower regional socio-economic status. The composition of the population in Maasland is associated with a 35% reduction in the odds to get vaccinated as compared to the overall Flemish population.

8.
Mater Today Bio ; 11: 100114, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34169268

RESUMO

Materials made of recombinant spider silk proteins are promising candidates for cardiac tissue engineering, and their suitability has so far been investigated utilizing primary rat cardiomyocytes. Herein, we expanded the tool box of available spider silk variants and demonstrated for the first time that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes attach, contract, and respond to pharmacological treatment using phenylephrine and verapamil on explicit spider silk films. The hiPSC-cardiomyocytes contracted for at least 14 days on films made of positively charged engineered Araneus diadematus fibroin 4 (eADF4(κ16)) and three different arginyl-glycyl-aspartic acid (RGD)-tagged spider silk variants (positively or negatively charged and uncharged). Notably, hiPSC-cardiomyocytes exhibited different morphologies depending on the spider silk variant used, with less spreading and being smaller on films made of eADF4(κ16) than on RGD-tagged spider silk films. These results indicate that spider silk engineering is a powerful tool to provide new materials suitable for hiPSC-based cardiac tissue engineering.

9.
Case Rep Cardiol ; 2018: 2509502, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780642

RESUMO

Prenatal diagnosis of a huge coronary artery fistula between the left coronary artery and the right ventricle was made by Doppler echocardiography at 22 weeks of gestation. Progression of the dilated fistula was monitored throughout pregnancy. The size of the fistula increased enormously up to 11 mm. Death occurred at birth. Monitoring of these fetuses is essential as severe complications can occur during pregnancy or at birth.

10.
Neuroscience ; 301: 439-53, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-26102006

RESUMO

Y-box-binding protein (YB-1) is a member of the cold-shock protein family and participates in a wide variety of DNA/RNA-dependent cellular processes including DNA repair, transcription, mRNA splicing, packaging, and translation. At the cellular level, YB-1 is involved in cell proliferation and differentiation, stress responses, and malignant cell transformation. A general role for YB-1 during inflammation has also been well described; however, there are minimal data concerning YB-1 expression in microglia, which are the immune cells of the brain. Therefore, we studied the expression of YB-1 in a clinically relevant global ischemia model for neurological injury following cardiac arrest. This model is characterized by massive neurodegeneration of the hippocampal CA1 region and the subsequent long-lasting activation of microglia. In addition, we studied YB-1 expression in BV-2 cells, which are an accepted microglia culture model. BV-2 cells were stressed by oxygen/glucose deprivation (OGD), OGD-relevant mediators, lipopolysaccharide (LPS), and phagocytosis-inducing cell debris and nanoparticles. Using quantitative polymerase chain reaction (PCR), we show constitutive expression of YB-1 transcripts in unstressed BV-2 cells. The functional upregulation of the YB-1 protein was demonstrated in microglia in vivo and in BV-2 cells in vitro. All stressors except for LPS were potent enhancers of the level of YB-1 protein, which appears to be regulated primarily by proteasomal degradation and, to a lesser extent, by the activation (phosphorylation) of the translation initiation factor eIF4E. The proteasome of BV-2 cells is impaired by OGD, which results in decreased protein degradation and therefore increased levels of YB-1 protein. LPS induces proteasome activity, which enables the level of YB-1 protein to remain at control levels despite enhanced protein ubiquitination. The proteasome inhibitor MG-132 was able to increase YB-1 protein levels in control and LPS-treated cultures. YB-1 upregulation was not accompanied by its translocation from the cytoplasm to the nucleus. YB-1 induction appeared to be related to microglial proliferation because it was partially co-regulated with Ki67. In addition, YB-1 protein levels correlated with microglia phagocytic activity because its upregulation could also be induced by inert NPs.


Assuntos
Regulação da Expressão Gênica/fisiologia , Parada Cardíaca/patologia , Microglia/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Animais , Asfixia/complicações , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Transformada , Modelos Animais de Doenças , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Glucose/deficiência , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Parada Cardíaca/etiologia , Antígeno Ki-67/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Oxigênio/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteína 1 de Ligação a Y-Box/genética
11.
Gastroenterol Hepatol ; 19(10): 497-502, 1996 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-9044747

RESUMO

The effects of chronic anemia on gastric damage induced by ethanol or aspirin have been investigated in rats. The role of free radicals and lipid peroxidation in that circumstance was also assessed. Chronic anemia was induced by replacement of 1.5 ml of blood by a plasma expander during 5 days. Under anesthesia, the stomach was perfused with 100% ethanol or acidified aspirin during 30 minutes. Thereafter, the rats were sacrificed, the stomachs removed and analyzed planimetrically for macroscopic damage. In addition, gastric tissue was collected and homogenized for assessment of toxic free radicals generation by chemoluminicense and lipid peroxidation by measuring reactive species of thiobarbituric acid (TBA-RS). Chronic anemia significantly protected against damage induced by ethanol or aspirin. The rate of toxic free radicals and the TBA-RS in the gastric mucosa was significantly reduced by anemia, either under ethanol or aspirin injury. It is concluded that anemia offers a general protection against gastric mucosal damage and that this protection is in part mediated by limitations on lipid peroxidation and toxic free radicals generation.


Assuntos
Anemia/fisiopatologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Peroxidação de Lipídeos , Anemia/metabolismo , Animais , Doença Crônica , Radicais Livres , Mucosa Gástrica/irrigação sanguínea , Ratos , Ratos Wistar
12.
Ultrasound Obstet Gynecol ; 23(3): 293-7, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15027021

RESUMO

We report the prenatal findings of congenital adrenal hyperplasia (CAH) in two consecutive fetuses of one family. The first pregnancy was terminated at 23 weeks' gestation due to the presence of a complex heart anomaly. The adrenal glands appeared enlarged on prenatal ultrasound examination and autopsy confirmed CAH. The parents were subsequently examined and were found to be heterozygous for nucleotide 656 of the CYP21B gene. In a subsequent pregnancy, chorionic villus sampling at 11 weeks confirmed CAH in the male fetus. At this gestational age, mild body edema was present and the nuchal translucency measured 2.1 mm. From 14 weeks onwards, enlargement of the adrenal glands was the only sign of CAH. These findings suggest that enlarged adrenal glands may be a prenatal sign for CAH. In fetal medicine, when a pregnancy is terminated due to fetal malformations, autopsy should be performed because it can provide additional information that is helpful in counseling women with regard to subsequent pregnancies.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Hiperplasia Suprarrenal Congênita/patologia , Adulto , Feminino , Doenças Fetais/patologia , Humanos , Masculino , Gravidez , Ultrassonografia Doppler em Cores
13.
J Occup Med ; 31(4): 331-4, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2715839

RESUMO

California experiences episodes of suspected agricultural field worker poisonings annually. These episodes are not only disruptive to ongoing agricultural operations, but the prospect of such poisoning is a source of great concern to workers, employers, and government agencies alike. Three episodes of group illness are examined in which actual poisoning does not seem to be involved. Factors contributing to the generation of these episodes include fear, uncertainty, incomplete understanding of hazards, and social pressures. Physicians can minimize extended disability for workers by reassuring victims and waiting until circumstances are verified before issuing statements which may further alarm or add to already existing fears.


Assuntos
Doenças dos Trabalhadores Agrícolas/psicologia , Surtos de Doenças , Praguicidas/efeitos adversos , Transtornos Psicofisiológicos/epidemiologia , Doenças dos Trabalhadores Agrícolas/epidemiologia , California , Carbamatos , Feminino , Fungicidas Industriais/efeitos adversos , Herbicidas/efeitos adversos , Humanos , Inseticidas/efeitos adversos , Masculino
14.
Vet Hum Toxicol ; 31(3): 231-6, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2741311

RESUMO

In order to evaluate consumer uses of first-aid recommendations on pesticide labels and the appropriateness of current label first-aid statements, callers to the University of California, Davis Regional Poison Control Center (RPCC) reporting pesticide exposures were questioned during the period from August 27 to September 30, 1987. Of 2,650 calls received by the RPCC during the study period, 160 (6.0%) of the calls related to pesticides. Eighty-nine (55.6%) of the callers in these cases participated in our label evaluation survey. Only 47 (53%) of the survey participants reported having a product container or label available at the time they called the RPCC. Of 15 participants identifying themselves as physicians or nurses inquiring about exposures to patients, only 1 (7%) reported having access to a product label, compared to 46 (63%) of 74 other callers, a difference in proportion which was highly significant (p less than 0.001). All calls received relating to pesticides were reviewed in order to identify product labels from the registration file at the California Department of Food and Agriculture (CDFA). Of the 160 calls received, 133 contained information sufficient to allow for identification of the product involved and an understanding of the exposure event. Label first-aid information in these cases was appropriate to the circumstances of exposure in 63 (47%) of these cases, completely or partially incorrect in 20 (12%), and missing from the label in the remaining 50 (37%) of the cases. Inappropriate first-aid advice was limited to cases involving ingestion while missing first-aid advice was common for all routes of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Primeiros Socorros , Praguicidas/intoxicação , Rotulagem de Produtos , Humanos , Centros de Controle de Intoxicações
15.
Chem Res Toxicol ; 4(2): 162-7, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1664255

RESUMO

Aldrin and many other cyclodiene and polychlorocycloalkane insecticides interact with both the [35S]-tert-butylbicyclophosphorothionate ([35S]TBPS) binding site of the mammalian brain gamma-aminobutyric acid (GABA) gated chloride channel and several cyclodiene monoclonal antibodies (MAbs) at concentrations ranging from 0.06 to 8.7 microM. A survey of other classes of GABAA receptor antagonists (including picrotoxinin and several trioxabicyclooctanes) for possible interactions with the cyclodiene MAbs revealed only one potent inhibitor, the heteroadamantane tetramethylenedisulfotetramine (TETS) [mouse intraperitoneal LD50 0.24 mg/kg; TBPS binding site IC50 0.5 microM as a competitive inhibitor (Scatchard analysis); cyclodiene MAb IC50 3 microM]. These findings prompted comparative studies on the structure-activity relationships of other sulfamides as they apply to both the ligand-nerve and ligand-MAb interactions. TETS is active on only one (MAb 8H11) of four cyclodiene MAbs. Several hetero(homo)adamantanes were synthesized and compared with TETS for neurotoxicity and recognition by the TETS-sensitive cyclodiene MAb. The toxicity to mice and/or houseflies decreases in the following order: TETS much greater than the heterotetracyclic compound hexamethylenetrisulfohexamine (HEXS) and two TETS analogues in which one sulfamide group is replaced with o-phenylenediamine or 1,1-dimethyl-1,2-diaminoethane much greater than seven other hetero(homo)adamantanes. The TETS-sensitive cyclodiene MAb recognizes HEXS (IC50 0.4 microM) and, to a lesser extent, two related sulfamides. However, the cross-reactivity noted for the cyclodiene insecticides and TETS relative to the GABA-gated chloride channel (inhibition of TBPS binding) and the cyclodiene MAb does not extend to several TETS analogues including HEXS.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Amidas/metabolismo , Anticorpos Monoclonais/metabolismo , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Cicloparafinas/imunologia , Antagonistas GABAérgicos , Ativação do Canal Iônico/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Amidas/farmacologia , Animais , Ligação Competitiva , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Canais de Cloreto , Cicloparafinas/farmacologia , Moscas Domésticas , Técnicas Imunoenzimáticas , Inseticidas/farmacologia , Cinética , Masculino , Proteínas de Membrana/efeitos dos fármacos , Camundongos , Tecido Nervoso/efeitos dos fármacos , Tecido Nervoso/fisiologia , Relação Estrutura-Atividade , Ácido gama-Aminobutírico/fisiologia
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