RESUMO
The law regulating plant protection products (PPP) in the European Union (EU) was fundamentally revised through the introduction of Regulation (EC) No. 1107/2009 which is due to enter into force on 14 June 2011. EU-wide harmonized maximum residue levels (MRLs) for the active substances of PPP in foods are laid down in Regulation (EC) No. 396/2005 and apply since entry into force of the regulation on 1 September 2008. The goal of both regulations is to strengthen the level of consumer protection. PPP are subject to a strict assessment of active substances, which is regulated at the EU level as well as an authorization procedure in the EU Member States. Prior to application for authorization of a PPP, the active substance(s) it contains must be included in a positive list. Tests regarding the toxicity and residue behavior of PPP must be conducted by the applicant, and the respective documents must be submitted to the authorities for evaluation. Following review of the required data, toxicological threshold values are derived, consumer exposure is assessed, and the risk to health is evaluated. The goal of this evaluation is to ensure that the use of PPP according to good plant protection practice does not have any harmful effects on human health.
Assuntos
Defesa do Consumidor , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Inseticidas/toxicidade , Praguicidas/toxicidade , Plantas/química , Saúde Pública/legislação & jurisprudência , Gestão da Segurança/legislação & jurisprudência , Informação de Saúde ao Consumidor/legislação & jurisprudência , Informação de Saúde ao Consumidor/tendências , União Europeia , Alemanha , Saúde Pública/tendências , Política Pública/tendências , Gestão da Segurança/tendênciasRESUMO
Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor nerve stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal nerve neurotrophic factor expression. We found that transected distal tibial nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neurotrophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal nerve stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory nerve (the cutaneous saphenous nerve) sutured to distal tibial nerve lowered injury-induced BDNF and GDNF mRNA levels in distal stump, but repair with a mixed nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed nerves did not affect nerve growth factor or neurotrophin-3 expression. Thus, distal nerve contributed to a neurotrophic environment for nerve regeneration for at least 6 months, and sensory nerve repair helped normalize distal nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory nerve.
Assuntos
Neurônios Motores/fisiologia , Músculo Esquelético/inervação , Fatores de Crescimento Neural/biossíntese , Regeneração Nervosa/fisiologia , Neurônios Aferentes/fisiologia , Nervo Tibial/lesões , Animais , Regulação da Expressão Gênica/fisiologia , Masculino , Denervação Muscular/métodos , Músculo Esquelético/fisiologia , Fatores de Crescimento Neural/genética , Ratos , Ratos Endogâmicos Lew , Nervo Tibial/fisiologia , TempoRESUMO
Both mature and precursor forms of neurotrophins regulate nerve development, survival and plasticity. Brain-derived neurotrophic factor (BDNF) synthesis and secretion in turn are regulated by neuronal activity, such as epilepsy. Further, neurotrophins themselves are regulated by neurotrophin levels. Neurotrophin-3 (NT-3) and BDNF in particular can be co-expressed and each can regulate the levels of the other. This regulation is thought to be mediated through receptor tyrosine kinase (Trk) activity. It is not known whether this neurotrophin-neurotrophin interaction occurs in hippocampal tissue in vivo, or how it is influenced by neuronal activation. In this study, we explored the reciprocal influences of intraventricular infusions of NT-3 and BDNF in naïve and kindled hippocampi of rats using Western blotting. We confirm that hippocampal kindling resulted in a significant increase in levels of BDNF both in cytochrome C (control) infused and NT-3 infused kindled rats. However, NT-3 infusion significantly reduced BDNF levels in both kindled and non-kindled hippocampi compared to their cytochrome C infused counterparts. These results are consistent with our earlier studies demonstrating lowered levels of TrkA and TrkC (NGF modulates BDNF levels via TrkA) following chronic NT-3 infusion. Although kindling led to an increase in BDNF, this was not accompanied by any detectable change in the levels of proBDNF. However, there was a significant increase in proBDNF following NT-3 infusions, suggesting NT-3 may reduce proBDNF processing. In contrast, neither NT-3 nor proNT-3 levels were affected by kindling or chronic BDNF infusions, consistent with down-regulation of TrkB by chronic BDNF infusion. Thus, modulation of BDNF by NT-3, likely mediated by Trk receptors, occurs in naïve and kindled adult rat hippocampus.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Excitação Neurológica/fisiologia , Neurotrofina 3/fisiologia , Precursores de Proteínas/metabolismo , Actinas/metabolismo , Animais , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Citocromos c/metabolismo , Densitometria , Regulação para Baixo/efeitos dos fármacos , Masculino , Ratos , Ratos Long-Evans , Receptor trkA/metabolismo , Receptor trkC/metabolismoRESUMO
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that mediates synaptic plasticity and excitability in the CNS. Recent evidence has shown that increased BDNF levels can lead to hyperexcitability and epileptiform activities, while suppression of BDNF function in transgenic mice or by antagonist administration retards the development of seizures. However, several groups, including our own, have reported that increasing BDNF levels by continuous intrahippocampal infusion inhibits epileptogenesis. It is possible that the continuous administration of BDNF produces a down-regulation of its high-affinity TrkB receptor, leading to a decrease of neuronal responsiveness to BDNF. If so, then animals should respond differently to bolus injections of BDNF, which presumably do not alter Trk expression, compared with continuous infusion. To test this hypothesis, we compared the effects of intrahippocampal BDNF continuous infusion and bolus injections on kindling induction. We showed that continuous infusion of BDNF inhibited the development of behavioral seizures and decreased the level of phosphorylated Trks or TrkB receptors. In contrast, multiple bolus microinjections of BDNF accelerated kindling development and did not affect the level of phosphorylated Trks or TrkB receptors. Our results indicate that different administration protocols yield opposite effects of BDNF on neuronal excitability, epileptogenesis and Trk expression. Unlike nerve growth factor and neurotrophin-3, which affect mossy fiber sprouting, we found that BDNF administration had no effect on the mossy fiber system in naive or kindled rats. Such results suggest that the effects of BDNF on epileptogenesis are not modulated by its effect on sprouting, but rather by its effects on excitability.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Excitação Neurológica/efeitos dos fármacos , Fibras Musgosas Hipocampais/efeitos dos fármacos , Receptor trkA/efeitos dos fármacos , Convulsões/fisiopatologia , Animais , Western Blotting , Injeções Intraventriculares , Masculino , Microinjeções , Fibras Musgosas Hipocampais/fisiologia , Fosforilação , Ratos , Ratos Long-Evans , Receptor trkA/biossínteseRESUMO
Neurotrophin-3 (NT-3), a member of the neurotrophin family of neurotrophic factors, is important for cell survival, axonal growth and neuronal plasticity. Epileptiform activation can regulate the expression of neurotrophins, and increases or decreases in neurotrophins can affect both epileptogenesis and seizure-related axonal growth. Interestingly, the expression of nerve growth factor and brain-derived neurotrophic factor is rapidly up-regulated following seizures, while NT-3 mRNA remains unchanged or undergoes a delayed down-regulation, suggesting that NT-3 might have a different function in epileptogenesis. In the present study, we demonstrate that continuous intraventricular infusion of NT-3 in the absence of kindling triggers mossy fiber sprouting in the inner molecular layer of the dentate gyrus and the stratum oriens of the CA3 region. Furthermore, despite this NT-3-related sprouting effect, continuous infusion of NT-3 retards the development of behavioral seizures and inhibits kindling-induced mossy fiber sprouting in the inner molecular layer of the dentate gyrus. We also show that prolonged infusion of NT-3 leads to a decrease in kindling-induced Trk phosphorylation and a down-regulation of the high-affinity Trk receptors, TrkA and TrkC, suggesting an involvement of both cholinergic nerve growth factor receptors and hippocampal NT-3 receptors in these effects. Our results demonstrate an important inhibitory role for NT-3 in seizure development and seizure-related synaptic reorganization.
Assuntos
Epilepsia/metabolismo , Cones de Crescimento/metabolismo , Excitação Neurológica/metabolismo , Fibras Musgosas Hipocampais/metabolismo , Plasticidade Neuronal/fisiologia , Neurotrofina 3/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Contagem de Células , Grupo dos Citocromos c/farmacologia , Esquema de Medicação , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Cones de Crescimento/efeitos dos fármacos , Excitação Neurológica/efeitos dos fármacos , Masculino , Peso Molecular , Fibras Musgosas Hipocampais/efeitos dos fármacos , Fibras Musgosas Hipocampais/crescimento & desenvolvimento , Plasticidade Neuronal/efeitos dos fármacos , Neurópilo/citologia , Neurópilo/efeitos dos fármacos , Neurotrofina 3/farmacologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Long-Evans , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptor trkA/efeitos dos fármacos , Receptor trkA/metabolismo , Receptor trkB/efeitos dos fármacos , Receptor trkB/metabolismo , Receptor trkC/efeitos dos fármacos , Receptor trkC/metabolismo , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Convulsões/fisiopatologiaRESUMO
Brain derived neurotrophic factor (BDNF) promotes cholinergic neuron function and survival. In Alzheimer's disease, BDNF mRNA and protein are decreased in basal forebrain cholinergic neuron target tissues such as cortex and hippocampus. Using RT-PCR, we demonstrate that BDNF is synthesized in basal forebrain, supplying cholinergic neurons with a local as well as a target-derived source of this factor. BDNF mRNA levels are decreased 50% in nucleus basalis of Alzheimer disease patients compared to controls. Thus, not only do the basal forebrain cholinergic neurons have a reduced supply of target-derived BDNF, but also of local BDNF. We also show by Western blotting that human CNS tissue contains both proBDNF and mature BDNF protein. Moreover, we demonstrate a significant (2.25-fold) deficit in proBDNF protein in Alzheimer's disease parietal cortex compared to controls. Thus, reduced BDNF mRNA and protein levels in Alzheimer's disease suggests that BDNF administration may be an effective therapeutic strategy for this disorder.
Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/genética , Idoso , Idoso de 80 Anos ou mais , Núcleo Basal de Meynert/fisiologia , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/análise , Humanos , Pessoa de Meia-Idade , Lobo Parietal/química , Lobo Parietal/patologia , Precursores de Proteínas/análise , Precursores de Proteínas/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Proliferative and angiogenic activity of tissue specimens taken from women with various vulvar pathologies were evaluated by determining the number of mRNA VEGF molecules and H4 histone mRNA molecules, by means of the QRT-PCR (TaqMan) technique. Following a cluster analysis the results, where normalised. Euclidean distances were used, all the cases were classified into three groups of pathologies. Group I included low degree vulvar pathologies, group II included high degree vulvar pathologies and group III included vulvar pathologies with high proliferative and angiogenic activity. Significant differences were found in the proliferative and angiogenic activity between groups I and III, and between groups II and III, while no statistically significant differences were found between groups I and II.
Assuntos
Carcinoma in Situ/patologia , Fatores de Crescimento Endotelial/genética , Histonas/genética , Linfocinas/genética , Neovascularização Patológica/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Vulvares/patologia , Carcinoma in Situ/fisiopatologia , Divisão Celular , DNA de Neoplasias/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neovascularização Patológica/fisiopatologia , RNA Mensageiro/análise , Taq Polimerase , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Neoplasias Vulvares/fisiopatologiaRESUMO
Using own diagnostic and prognostic model, 1157 pregnant women with breech presentation in term were analysed. In 1008 cases (87.1%) they delivered according to prognosis established formerly. Manual support in delivery was required in 748 cases (64.6%). Elective caesarean section was performed in 260 women (22.5%). In 149 cases (12.9%) immediate caesarean section appeared, because of additional reasons, despite normal delivery prognosis.
Assuntos
Apresentação Pélvica , Complicações na Gravidez/diagnóstico , Feminino , Humanos , Gravidez , PrognósticoRESUMO
The aim of the study was a comparison of expression of angiogenesis genes: vascular endothelial growth factor (VEGF), KDR, suppressor gene p53, E6-HPV16 and HPV18, in tissue samples of normal, dystrophic, lymph nodes and malignant cancers of vulva and uterine cervix. The results demonstrate that molecular diagnostics of cancers using gene expression profiling indicates the definitive difference in expression profiles of aforementioned genes in tissues of the same malignancy.
Assuntos
Carcinoma de Células Escamosas/genética , Fatores de Crescimento Endotelial/genética , Expressão Gênica/genética , Genes p53/genética , Proteínas Oncogênicas/genética , Papillomaviridae/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Neoplasias Vulvares/virologia , Sondas de DNA de HPV/genética , Feminino , Humanos , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , RNA Viral/genética , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologia , Neoplasias Vulvares/genéticaRESUMO
Kinins are peptides involved in inflammatory processes, vascular permeability, proliferation and mitogenesis of tumor cells. The majority of kinins actions are mediated through an interaction with cell surface bradykinin receptors BR1 and BR2. Kinins precursor is kininogen (kng). The changes in proteins are initiated by changes in the expression of genes coding these proteins, thus can be a valuable diagnostic markers of malignant processes including cervical carcinoma. The paper presents an analysis of kininogen-kinins receptor genes expression in women treated surgically because of a carcinoma of uterine cervix. Among the studied women in 5 cases previously brachyHDR therapy was applied. In all studied cases HPV 18 infection and in 2 cases a co-infection HPV 16/18 by use of Consensus Primers MY09, MY 11 and type specific primers for HPV 16, 18 was ascertained. In RNA extracts the number of the mRNA copies for kiningen, BR1 and BR2 was assessed using QRT-PCR Taq Man. The higher expression of BR1 than BR2 was marked in the tissue with cancer cells. In the patients after brachytherapy higher expression of BR2 than BR1 mRNA was found. The higher BR1 expression was also shown in iliac lymph nodes in patients with active neoplastic process, opposite to the patients after brachytherapy in whom higher BR2 expression was ascertained. The lack of expression of kng mRNA was found only in 3 specimens. The high expression of kinin receptors especially BR1 in infiltrating carcinoma margin can be a marker of pathology intensity: proliferative potential of neoplasms cells or chronic inflammatory state in the presence of invasive carcinoma.
Assuntos
Cininogênios/genética , Cininas/genética , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Receptores da Bradicinina/genética , Infecções Tumorais por Vírus/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto , Biomarcadores Tumorais/genética , Braquiterapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias do Colo do Útero/terapiaRESUMO
PURPOSE: The diagnostic value of examinations performed with the use of pocket-size echocardiograph by medical professionals with different levels of experience remains to be determined. The aim of this study was to assess the diagnostic value of bedside echocardiographic examinations performed with the use of pocket-size echocardiograph by experienced cardiologist and medical students. MATERIAL/METHODS: The study group comprised 90 patients (63 men, 27 women; mean age 64±14 years) admitted to the cardiac intensive care unit and 30 patients from an out-patient clinic (21 men, 9 women; mean age 62±17 years). All patients underwent bedside echocardiographic examination performed with pocket-size echocardiograph by two briefly trained medical students (n=90 patients) or cardiologist (n=30 patients). Major findings were recorded using a simplified questionnaire. Within 24 hours standard echocardiographic examination was performed in all patients by another cardiologist using a full sized echocardiograph. The study group was divided into 4 subgroups: A / B - first / second half of in-patients examined by students, group C - inpatients examined by cardiologist, group D- out-patients examined by students. RESULTS: The agreement between standard transthoracic echocardiography (sTTE) and major findings on bedside transthoracic echocardiography (bTTE) was fair to moderate (kappa 0.293-0.57) in group A, moderate to very good (kappa 0.535-1.00) in group B, good to very good (kappa 0.734-1.00) in group C and moderate to very good (kappa 0.590-1.00) in group D. CONCLUSIONS: Pocket-size echocardiograph enables an expert echocardiographer to perform reliable bedside examinations. When used by briefly trained medical students it provides an acceptable diagnostic value with notable learning curve effect.
Assuntos
Ecocardiografia/instrumentação , Desenho de Equipamento/métodos , Miniaturização/instrumentação , Idoso , Cuidados Críticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos Testes , Estudantes de MedicinaRESUMO
PURPOSE: Helicobacter pylori (H. pylori) infection and smoking of cigarettes increase individual risk to gastric carcinoma. In stomach tumors, an expression of somatostatin receptor 3 (SSTR3) is diminished or completely lost. The purpose of these studies was to determine the influence of smoking cigarettes and H. pylori infection on the expression of SSTR3 in patients with functional dyspepsia. MATERIALS AND METHODS: The study comprised 109 patients with functional dyspepsia in the age range 28-61 years. The total 218 biopsies used for analysis were divided into two groups: group I - 176 biopsies from non-smokers (72 from H. pylori positive ones), and group II - 42 biopsies from cigarette smokers (28 from H. pylori positive patients). The SSTR3 mRNA amount in the gastric mucosa (1 biopsy from the antrum and 1 biopsy from the corpus) was determined by real time RT-PCR. The presence of H. pylori colonization in the stomach tissue was evaluated by multiplex PCR. RESULTS: In the H. pylori negative samples the amount of the SSTR3 mRNA was significantly lower for smokers than for non-smokers (by 40%, p < 0.010). Infection with H. pylori caused reduction of the level of SSTR3 mRNA in non-smoking patients by ca. 30% (p < 0.01), while in samples from smokers the SSTR3 mRNA level was similar regardless of H. pylori infection. CONCLUSIONS: The cigarettes smoking and H. pylori infection are independent factors leading to decreasing of the SSTR3 mRNA level in gastric mucosa of patients with functional dyspepsia.
Assuntos
Dispepsia/etiologia , Mucosa Gástrica/metabolismo , RNA Mensageiro/genética , Receptores de Somatostatina/genética , Fumar/efeitos adversos , Dispepsia/metabolismo , Dispepsia/microbiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/fisiologia , Humanos , Reação em Cadeia da Polimerase , Fatores de RiscoAssuntos
Idoso , Habitação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saskatchewan , Inquéritos e QuestionáriosRESUMO
This review concerns structural and functional properties of human vascular endothelial growth factor as well as the process of alternative splicing of its transcript. Regulation of VEGF gene transcription and participation of the protein in the angiogenesis of tumours are also broadly discussed.
Assuntos
Fatores de Crescimento Endotelial/genética , Linfocinas/genética , Neoplasias/fisiopatologia , Neovascularização Patológica/genética , Animais , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Transcrição Gênica , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Nerve growth factor (NGF) is important for regulation, differentiation, and survival of peripheral and central nervous system neurons, including basal forebrain cholinergic neurons (BFCN) which degenerate in Alzheimer's disease (AD). Mature NGF protein is processed from a larger precursor, proNGF. We demonstrate that proNGF is the predominant form of NGF in mouse, rat, and human brain tissue, whereas little or no mature NGF is detected. Previous reports showed NGF protein, measured by ELISA, is increased in AD BFCN target regions such as hippocampus and cortex. Using Western blotting, we demonstrate a twofold increase in proNGF in AD parietal cortex compared to controls, indicating that it is this precursor form, proNGF, that accumulates in AD. This increase may reflect either a role for biologically active proNGF or posttranslational disturbances in NGF biosynthesis that decrease the processing of proNGF to mature NGF in AD.
Assuntos
Doença de Alzheimer/metabolismo , Sobrevivência Celular/fisiologia , Fator de Crescimento Neural/metabolismo , Lobo Parietal/metabolismo , Precursores de Proteínas/metabolismo , Regulação para Cima/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Ratos , Ratos Long-Evans , Ratos Sprague-DawleyRESUMO
Nineteen New Zealand white rabbits received one (n = 5), two (n = 5), or three (n = 9) injections of 60 mg methylprednisolone and were sacrificed 10, 20, 30, and 60 days following the last treatment. They were compared to 15 controls for histological examination of femoral and humeral epiphyses and femoral condyles. Treated animals had a significant rise in serum triglycerides (p less than 0.01) 10 days following treatment. 15 treated animals and 6 controls had grade I lesions of bone marrow (p less than 0.05). Lesions of grades II and III were only observed in 5 treated animals. The severity of histological lesions were not correlated with steroid doses. Tetracycline fixation was suppressed in treated rabbits.