RESUMO
BACKGROUND: Brain injury after trauma is an important cause of mortality and morbidity in society. There is evidence in both man and laboratory animals that in addition to necrosis, cell loss may occur as a result of programmed cell death (PCD). The cellular and molecular responses after head injury are partly influenced by genetic polymorphisms of apolipoprotein E and the pro-inflammatory cytokine IL-I. AIM: The principal aim of this study was to determine whether the presence of the ApoE epsilon4, IL- 1 alpha2 or IL- 1beta2 allele types influenced the amounts of PCD after head injury compared with controls. METHODS: Paraffin sections from the hippocampus of 38 patients (32 M : 6 F, aged 15 - 75, mean 38 years, survival 7- 576 hours; mean 36 hours) who died after a head injury were stained by Tunel histochemistry and quantified, and genotyping was undertaken by PCR "blind" to clinical detail. RESULTS: There were more Tunel+ cells (neurons and glia) after head injury than in controls with statistically increased numbers in all sectors of the hippocampus including the dentate fascia. However, there was no correlation between ApoEepsilon4, IL- 1 alpha allele 2 and IL- 1beta allele 2 and the amount of Tunel positivity. CONCLUSION: Given that both the ApoE and IL-1 influence outcome after various forms of acute brain injury, further work will be required to determine the mechanism underlying this relationship.
Assuntos
Apolipoproteína E4/genética , Apoptose/genética , Lesões Encefálicas/genética , Predisposição Genética para Doença/genética , Interleucina-1/genética , Degeneração Neural/genética , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Lesões Encefálicas/imunologia , Lesões Encefálicas/metabolismo , Contagem de Células , Análise Mutacional de DNA , Feminino , Frequência do Gene , Testes Genéticos , Genótipo , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Marcação In Situ das Extremidades Cortadas , Interleucina-1alfa/genética , Interleucina-1beta/genética , Masculino , Pessoa de Meia-Idade , Degeneração Neural/imunologia , Degeneração Neural/metabolismo , Polimorfismo Genético/genéticaRESUMO
Paraffin sections from the hippocampus of 12 head-injured patients (Group A, aged between 4 and 12 years n = 6 and Group B, aged between 64 and 89 years n = 6) and associated age-matched controls were stained by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique for evidence of in-situ DNA fragmentation. TUNEL+ cells were of 2 Types: I (non-apoptotic) and II (apoptotic). In addition sections stained H&E, combined Luxol Fast Blue/Cresyl Violet and by immunohistochemistry for astrocytes (GFAP) and macrophages (CD68) were used to characterize the lesions. Small numbers of Type I TUNEL+ cells were seen in all sectors of the hippocampus except CA2 of both Groups A and B. Type II TUNEL+ cells were mainly found in the white matter. They constituted less than 1% of all TUNEL+ cells. There were similar or fewer TUNEL+ cells in the corresponding areas in the controls compared with the head-injured patients. However, in the dentate fascia and the CA4 sector of the Group B cases, larger numbers of TUNEL+ cells were seen in controls than after trauma. In the grey matter most TUNEL+ cells had the morphology ofnecrosis that corresponded with foci of selective neuronal damage. Only a few TUNEL+ cells were seen in white matter. The occasional Type I TUNEL+ cells were seen in grey matter. It is concluded that the amount and distribution of DNA fragmentation in children and adults is similar and therefore at least in the hippocampus does not provide an explanation for age as an independent variable of outcome after traumatic brain injury in childhood.
Assuntos
Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Dano ao DNA/genética , Fragmentação do DNA/genética , Hipocampo/lesões , Hipocampo/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Índices de Gravidade do TraumaRESUMO
Paraffin sections from the hippocampus, the cingulate gyrus and the insula of 18 head-injured patients who survived between 5 hours and 10 days, and 18 age-matched controls, were stained by the terminal deoxynucleotidyl transferase mediated biotinylated deoxyuridine triphosphate nick end labelling (TUNEL) technique for evidence of in situ DNA fragmentation. Additional staining techniques (HE, combined LFB/CV and immunohistochemistry for GFAP and CD68) were used to characterize any lesions and their time course. Only the occasional TUNEL+ cell per area was seen in the control brains. TUNEL+ cells were identified in both grey and white matter of the head-injured material and their numbers peaked between 24 and 48 hours and were still present at 10 days. Within the hippocampus, fewer TUNEL+ cells were seen in grey (between 3-5 per area) than in the white matter, (up to 51+ per area) whereas in the cingulate gyrus and in the insula, the number of TUNEL+ cells was always greater in the cortex (between 11-20 per area) than in white matter (6-10 per area). In the grey matter, most TUNEL+ cells had the morphology of necrosis. However, the histological appearances of some of the neurons (2-3%), and of oligodendroglia and macrophages in white matter (about 5%) were those of apoptosis.
Assuntos
Encéfalo/patologia , Traumatismos Craniocerebrais/patologia , Marcação In Situ das Extremidades Cortadas , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Feminino , Hipocampo/patologia , Histocitoquímica , Humanos , Imunoquímica , Masculino , Pessoa de Meia-Idade , Necrose , Substância Cinzenta Periaquedutal/patologia , Coloração e Rotulagem , Fatores de TempoRESUMO
Using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick-end labelling (TUNEL) histochemical technique, evidence for DNA fragmentation was sought in the hippocampus, cingulate gyrus and insula from 18 patients who survived for up to 12 months after head injury, and 15 matched controls. Both conventional (haematoxylin and eosin and Luxol-fast blue/cresyl violet) and immunohistochemical (glial fibrillary acidic protein, CD68) staining techniques were used to identify the cellular response and its time course in the regions of interest. Only the occasional TUNEL-positive (+) cell/unit area was seen in any area of the control brains. In contrast there were more TUNEL+ cells/unit area in the injured brains. TUNEL+ cells were present in white matter and their average numbers ranged from three to five per unit area for up to 3 months survival in the extreme capsule and the parasagittal white matter, with similar numbers in the hippocampus, and between two and three per unit area in the parasagittal white matter and hippocampus of the cases surviving up to 12 months post injury. Between one and two TUNEL+ cells/unit area were also seen in grey matter, of which most appeared as neurones. About 5% of the TUNEL+ cells in white matter had the morphological features of apoptosis: the corresponding figure in grey matter was less than 1%. In many instances the TUNEL+ cells were also CD68+ and appeared by light microscopy to be macrophages. It was concluded that, as reflected by TUNEL histochemistry, long-term DNA fragmentation is present in white matter after traumatic brain injury in man.
Assuntos
Lesões Encefálicas/patologia , Encéfalo/patologia , Fragmentação do DNA/fisiologia , Degeneração Neural/patologia , Fibras Nervosas Mielinizadas/patologia , Neurônios/patologia , Adolescente , Adulto , Idoso , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Corpo Caloso/patologia , Corpo Caloso/fisiopatologia , Feminino , Giro do Cíngulo/patologia , Giro do Cíngulo/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Degeneração Neural/etiologia , Degeneração Neural/fisiopatologia , Neuroglia/patologia , Fatores de TempoRESUMO
In frontal lobe contusions obtained post mortem from 18 patients who survived between 6 h and 10 days after head injury, DNA fragmentation associated with either apoptotic and/or necrotic cell death was identified by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labelling (TUNEL) histochemical technique. Additional histological techniques were also used to identify regional and temporal patterns of tissue damage. TUNEL-positive cells were present in both the grey and white matter of the contusion, where they peaked in number between 25 and 48 h, and were still identifiable at 10 days post injury. Fewer TUNEL-positive cells were observed in grey than in white matter; and most TUNEL-positive neurons in the grey matter demonstrated the morphological features of necrosis. However, the morphology of some TUNEL-stained neurons, and of TUNEL-stained oligodendroglia and macrophages in white matter was suggestive of apoptosis. Apoptosis was not seen in age- and sex-matched controls, none of whom had died from intracranial pathology or had pre-existing neurological disease. These findings suggest that multiple cell types in frontal lobe contusions exhibit DNA fragmentation and that both necrosis and apoptosis are likely to contribute to post-traumatic pathology. These findings provide further evidence that the observations made in animal models of traumatic brain injury have fidelity with clinical head injury.
Assuntos
Lesões Encefálicas/etiologia , Lesões Encefálicas/genética , Traumatismos Craniocerebrais/complicações , Fragmentação do DNA , Adulto , Idoso , Apoptose , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Traumatismos Craniocerebrais/mortalidade , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Necrose , Coloração e Rotulagem , Análise de SobrevidaRESUMO
Several topical treatments for hydrofluoric acid dermal burns (Zephiran, calcium acetate and magnesium hydroxide antacid soaks, and calcium gluconate gel) were assessed for efficacy in a pig model. Gross appearance and histopathology of treated and untreated burn sites were evaluated. For superficial burns, Zephiran was most effective; calcium acetate, magnesium hydroxide antacid, and calcium gluconate gel were less effective. For deep burns, gross observations showed that calcium acetate and Zephiran were most efficacious, whereas histopathology indicated comparable efficacy of Zephiran, calcium acetate, and calcium gluconate gel for all skin layers. Magnesium hydroxide antacid demonstrated efficacy only for the subdermis. The clinically beneficial effects of both Zephiran and calcium gluconate gel were affirmed. Although results suggest that calcium acetate and magnesium-containing antacids may be beneficial for human hydrofluoric acid dermal burns, these are not established clinical treatments.
Assuntos
Acetatos/administração & dosagem , Antiácidos/administração & dosagem , Compostos de Benzalcônio/administração & dosagem , Queimaduras Químicas/tratamento farmacológico , Gluconato de Cálcio/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Ácido Fluorídrico , Hidróxido de Magnésio/administração & dosagem , Ácido Acético , Administração Tópica , Animais , Queimaduras Químicas/patologia , Modelos Animais de Doenças , Masculino , Suínos , Fatores de Tempo , Resultado do TratamentoRESUMO
There currently exist various opinions concerning the best therapy for managing hydrogen fluoride (HF) dermal burns. Previously reported animal studies designed to evaluate the efficacy of certain therapies are not completely convincing. Studies initially were conducted to develop a reliable animal model for assessing efficacy of treatment. Evaluation of several animal species, dosing regimens (HF concentrations, exposure periods), and application techniques showed that the most consistent and reproducible dermal lesions were produced with 38% HF applied to the skin of anesthetized pigs for exposures of 9, 12, or 15 minutes using Hill Top Chamber patches. Using this model, the efficacy of six clinically applicable treatments was assessed by subjectively scoring and statistically analyzing photographic and histopathological data obtained from treated and untreated control lesions. Photographic data analysis ranked treatments with respect to effectiveness as follows: iced Zephiran and 10% calcium acetate soaks--highly effective; 2.5% calcium gluconate gel, 5.0% calcium gluconate injection and iced Hyamine soaks--effective; 10% calcium gluconate injection--ineffective. Histopathological data analysis showed the topical treatments (2.5% calcium gluconate gel, iced Hyamine, or iced Zephiran soaks) to be most effective in reducing superficial epidermal damage, and the 5% calcium gluconate injection or 10% calcium acetate soaks to be beneficial to deeper tissues of the dermis and subdermis. Injection of 10% calcium gluconate was ineffective. This study suggests that the anesthetized pig model has good applicability for assessing efficacy of HF dermal burn therapies. In addition, it indicates that further experimentation with 10% calcium acetate soaks is warranted.
Assuntos
Queimaduras Químicas/terapia , Ácido Fluorídrico/efeitos adversos , Pele/patologia , Acetatos/uso terapêutico , Ácido Acético , Animais , Compostos de Benzalcônio/uso terapêutico , Benzetônio/uso terapêutico , Queimaduras Químicas/etiologia , Queimaduras Químicas/patologia , Gluconato de Cálcio/administração & dosagem , Gluconato de Cálcio/uso terapêutico , Géis , Injeções , Masculino , Suínos , Resultado do Tratamento , Água/uso terapêuticoRESUMO
In patients with reflux disease, pH monitoring has shown that omeprazole virtually eliminates oesophageal exposure to a pH of less than 4. Motility studies concurrent with pH monitoring have indicated that reflux continues on omeprazole, its effect on acid exposure being entirely dependent on elevation of gastric pH. Omeprazole and placebo have been compared in 64 patients with erosive or ulcerative oesophagitis; the 4-week healing rates were 81% with omeprazole, 20 mg or 40 mg daily, and 6% with placebo. The efficacies of omeprazole at doses of 20 mg and 40 mg daily, were then compared in 164 patients. At 4 weeks, oesophagitis was healed in 70% and 82% of patients for the 20 mg and 40 mg doses respectively (p = 0.05). Eight-week healing rates (79% for 20 mg and 85% for 40 mg) did not differ significantly. Symptom response was excellent for both doses. Relapse of oesophagitis was determined over 6 months for patients healed with omeprazole. Relapse was shown to occur in 88 of 107 patients by 6 months. Omeprazole is a highly effective treatment for erosive/ulcerative peptic oesophagitis, 40 mg daily being marginally superior to 20 mg. Relapse is almost inevitable within 6 months of cessation of therapy.
Assuntos
Esofagite Péptica/tratamento farmacológico , Omeprazol/uso terapêutico , Relação Dose-Resposta a Droga , Esofagoscopia , Seguimentos , Determinação da Acidez Gástrica , Humanos , Estudos Multicêntricos como AssuntoRESUMO
Hydrofluoric acid burns create unique problems that require specialized treatment to prevent serious sequelae. The most important factors to remember are the delay in the onset of signs and symptoms related to concentration of acid and the penetration and destruction of tissues by fluoride ions, which bind calcium and magnesium cations with subsequent serious systemic effects. In this article, an attempt has been made to describe these factors and to offer recommended treatment protocols which, if appropriately applied, can offset the destructive nature of HF burns. Several methods of treatment have been offered, and it is recommended that one or more be used according to circumstances. The most important initial point in treatment is the recognition that an HF burn has occurred. Then, with a clear understanding of the mechanisms of injury, one can properly manage such a burn. It is hoped that this report will assist the practitioner in dealing with this potential serious and complex problem.
Assuntos
Queimaduras Químicas/etiologia , Ácido Fluorídrico/efeitos adversos , Doenças Profissionais/induzido quimicamente , Administração Tópica , Adulto , Compostos de Benzalcônio/administração & dosagem , Benzetônio/administração & dosagem , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/fisiopatologia , Cálcio/administração & dosagem , Gluconato de Cálcio/administração & dosagem , Humanos , Infusões Intra-Arteriais , Injeções Subcutâneas , Masculino , Doenças Profissionais/tratamento farmacológico , Doenças Profissionais/fisiopatologiaRESUMO
The possibility that smoking induces duodenogastric reflux was examined in 13 healthy male volunteers. Gastric juice was aspirated for four consecutive 20-minute periods, and reflux quantitated by measuring total bile acids (TBA), chenodeoxycholic acid (CDCA) and glycocholic acid (GCA) in the juice. One cigarette was smoked during either period 2 or period 3. Amounts of bile acids (mumoles: means +/- SEM) refluxing into stomach during the pre-smoking, smoking, and post-smoking periods respectively were: TBA-4.5 +/- 1.1, 5.4 +/- 3.0 and 3.9 +/- 1.6, CDCA-1.7 +/- 0.6, 1.5 +/- 0.9 and 2.0 +/- 1.1; GCA-1.8 +/- 1.1, 1.1 +/- 0.6 and 1.0 +/- 0.6. Paired analysis revealed no significant effect of smoking on any of these parameters. These findings, based on quantitative methods, do not confirm those of previous unblinded and semiquantitative studies. We conclude that smoking one cigarette does not provoke duodenogastric reflux.