RESUMO
OBJECTIVES: Although the shortened dental arch (SDA) concept is a widely accepted strategy to avoid overtreatment, little is known on its impact on oral health-related quality of life (OHRQoL). This multicenter randomized controlled trial aimed to investigate the OHRQoL for removable partial dental prostheses (RPDP) with molar replacement versus the SDA concept. MATERIAL AND METHODS: In both groups, missing anterior teeth were replaced with fixed dental prosthesis. Two hundred fifteen patients with bilateral molar loss in at least one jaw were included. The Oral Health Impact Profile (OHIP-49) was completed before; 6 weeks (baseline), 6 months, and 12 months after treatment; and thereafter annually until 5 years. RESULTS: Of the initial cohort, 81 patients were assigned to the RPDP group and 71 to the SDA group (age, 34 to 86 years). Before treatment, the median OHIP score was similar in both groups (RPDP, 38.0; SDA, 40.0; n.s.). Results indicate marked improvements in OHRQoL in both groups between pretreatment and baseline (RPDP, 27.0; SDA, 19.0; p ≤ 0.0001) which continued in the RPDP group until the 1-year follow-up (p = 0.0002). These significant reductions in OHIP scores are reflected in its subscales. No further differences were seen within and between groups during the remainder observation period. CONCLUSION: Both treatments show a significant improvement in OHRQoL which continued in the RPDP group until the 1-year follow-up. No significant differences were seen between groups. CLINICAL RELEVANCE: For improving OHRQoL, it is not necessary to replace missing molars with a RPDP.
Assuntos
Arco Dental/anatomia & histologia , Saúde Bucal , Qualidade de Vida , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The study was designed to provide clinical outcome data for two treatments of the shortened dental arch (SDA). MATERIAL AND METHODS: In a multicenter randomized controlled clinical trial, patients with complete molar loss in one jaw were provided with either a partial removable dental prosthesis (PRDP) retained with precision attachments or treated according to the SDA concept preserving or restoring a premolar occlusion. No implants were placed. The primary outcome was tooth loss. RESULTS: Of 152 treated patients, 132 patients reached the 5-year examination. Over 5 years, 38 patients experienced tooth loss. For the primary outcome tooth loss, the Kaplan-Meier survival rates at 5 years were 0.74 (95% CI 0.64, 0.84) in the PRDP group and 0.74 (95% CI 0.63, 0.85) in the SDA group. For tooth loss in the study jaw, the survival rates at 5 years were 0.88 (95% CI 0.80, 0.95) in the PRDP group and 0.84 (95% CI 0.74, 0.93) in the SDA group. The differences were not significant. No Cox regression models of appropriate fit explaining tooth loss on the patient level could be found. CONCLUSIONS: The overall treatment goals of a sustainable oral rehabilitation and the avoidance of further tooth loss over longer periods were not reliably achievable. The influence of the type of prosthetic treatment on tooth loss might have been overestimated. CLINICAL RELEVANCE: Regarding our results, the patient's view will gain even more importance in the clinical decision between removable and fixed restorations in SDAs.
Assuntos
Arco Dental/patologia , Prótese Parcial Removível , Perda de Dente/reabilitação , Idoso , Análise de Variância , Dente Pré-Molar/fisiologia , Índice CPO , Oclusão Dentária , Índice de Placa Dentária , Encaixe de Precisão de Dentadura , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Extração Dentária/estatística & dados numéricos , Perda de Dente/fisiopatologia , Resultado do TratamentoRESUMO
Critical or delayed bone healing in rat osteotomy (OT) models is mostly achieved through large defects or instability. We aimed to design a rat OT model for impaired bone healing based on age, gender and parity. The outcome should be controllable through variations of the haematoma in the OT including a bone morphogenetic protein (BMP) 2 guided positive control. Using external fixation to stabilise femoral a 2 mm double OT in 12 month old, female Sprague Dawley rats after a minimum of 3 litters healing was characterised following in situ haematoma formation (ISH-group)), transplantation of a BMP charged autologous blood clot (BMP-group) and the artificial blood clot only (ABC-group) into the OT-gap. In vivo micro-computer tomography (µCT) scans were performed after 2, 4 and 6 weeks. After 6 weeks specimens underwent histological analyses. In µCT examinations and histological analyses no bony bridging was observed in all but one animal in the ISH-group. In the BMP group complete bridging was achieved in all animals. The ABC-group showed less mineralised tissue formation and smaller bridging scores during the course of healing than the ISH-group. In this pilot study we introduce a model for impaired bone healing taking the major biological risk factors into account. We could show that the in situ fracture haematoma is essential for bone regeneration. Using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.
Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Fêmur/cirurgia , Osteotomia/métodos , Cicatrização/efeitos dos fármacos , Animais , Benchmarking , Coagulação Sanguínea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Feminino , Fêmur/diagnóstico por imagem , Fêmur/fisiologia , Modelos Animais , Projetos Piloto , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Microtomografia por Raio-X/métodosRESUMO
The objective of this investigation was to elucidate the effects of route of exposure and oral dosage regimen on the toxicokinetics (TK) of 1,1-dichloroethylene (DCE). Fasted male Sprague-Dawley rats that inhaled 100 or 300 ppm for 2 h absorbed total systemic doses of (10 or 30 mg/kg DCE, respectively. Other groups of rats received 10 or 30 mg/kg DCE by intravenous injection, bolus gavage (by mouth), or gastric infusion (g.i.) over a 2-h period. Serial microblood samples were taken from the cannulated, unanesthetized animals and analyzed for DCE content by gas chromatography to obtain concentration versus time profiles. Inhalation resulted in substantially higher peak blood concentrations and area under blood-concentration time curves (AUC(0)(2)) than did gastric infusion of the same dose over the same time frame at each dosage level, although inhalation (AUC(0)(infinity)) values were only modestly higher. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltranspeptidase (GGT) activities were monitored as indices of kidney injury in the high-dose groups. NAG and GGT excretion were much more pronounced after inhalation than gastric infusion. Administration of DCE by gavage also produced much higher Cmax and AUC(0)(2) values than did 2-h g.i., although AUC(0)(infinity) values were not very different. The 30 mg/kg bolus dose produced marked elevation in serum sorbitol dehydrogenase, an index of hepatocellular injury. Administration of this dose by inhalation and gastric infusion was only marginally hepatotoxic. These findings demonstrate the TK and target organ toxicity of DCE vary substantially between different exposure routes, as well as dosage regimens, making direct extrapolations untenable in health risk assessments.
Assuntos
Dicloroetilenos/toxicidade , Acetilglucosaminidase/metabolismo , Administração por Inalação , Administração Oral , Animais , Dicloroetilenos/administração & dosagem , Dicloroetilenos/farmacocinética , Dicloroetilenos/farmacologia , Relação Dose-Resposta a Droga , Injeções Intravenosas , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Transglutaminases/metabolismoRESUMO
1,1,2-Trichloroethylene (TCE), a volatile organic contaminant (VOC) of drinking water in the Unites States, is frequently present in trace amounts. TCE is currently classified by the International Agency for Research on Cancer and the U.S. Environmental Protection Agency as a probable human carcinogen, because it produces tumors in some organs of certain strains of mice or rats in chronic, high-dose bioassays. Previous studies (Toxicol Appl Pharmacol 60:509-526, 1981; Regul Toxicol Pharmacol 8:447-466, 1988) used physiological modeling principles to reason that the liver should remove virtually all of a well metabolized VOC, such as TCE, as long as concentrations in the portal blood were not high enough to saturate metabolism. To test this hypothesis, groups of unanesthetized male Sprague-Dawley rats received intravenous injections of 0.1, 1.0, or 2.5 mg TCE/kg as an aqueous emulsion. Other rats were gavaged with 0.0001, 0.001, 0.01, 0.1, 1, 2.5, 5, or 10 mg TCE/kg b.wt. Serial microblood samples were taken via an indwelling carotid artery cannula, to generate blood TCE versus time profiles. Headspace solid-phase microextraction gas chromatography with negative chemical ionization mass spectrometry (limit of quantitation = 25 pg/ml) was used to quantify TCE. TCE was undetectable in rats given 0.0001 mg/kg, but it exhibited linear kinetics from 0.1 to 5.0 mg/kg. Bioavailability was consistent over this dosage range, ranging from 12.5 to 16.4%. The presence of these limited amounts of TCE in the arterial blood disprove the aforementioned hypothesis, yet demonstrate that first-pass hepatic and pulmonary elimination in the rat afford its extrahepatic organs protection from potential adverse effects by the majority of the low levels of TCE absorbed from drinking water.
Assuntos
Tricloroetileno/farmacologia , Animais , Disponibilidade Biológica , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Microextração em Fase Sólida , Distribuição Tecidual , Tricloroetileno/administração & dosagem , Tricloroetileno/sangue , Estados UnidosRESUMO
The alpha proton x-ray spectrometer (APXS) on board the rover of the Mars Pathfinder mission measured the chemical composition of six soils and five rocks at the Ares Vallis landing site. The soil analyses show similarity to those determined by the Viking missions. The analyzed rocks were partially covered by dust but otherwise compositionally similar to each other. They are unexpectedly high in silica and potassium, but low in magnesium compared to martian soils and martian meteorites. The analyzed rocks are similar in composition to terrestrial andesites and close to the mean composition of Earth's crust. Addition of a mafic component and reaction products of volcanic gases to the local rock material is necessary to explain the soil composition.
Assuntos
Meio Ambiente Extraterreno , Marte , Óxidos/análise , Alumínio/análise , Sedimentos Geológicos/química , Ferro/análise , Magnésio/análise , Meteoroides , Potássio/análise , Dióxido de Silício/análiseRESUMO
The purpose of this study was to determine the relationship between sarcoma tumor grade and the quantitative tumor metabolism value for [F-18]fluorodeoxyglucose (FDG) determined by positron emission tomography (PET) imaging. Seventy patients with bone or soft-tissue sarcomas underwent PET scanning with quantitative determination of tumor FDG metabolic rate (MRFDG) before treatment. MRFDG (micromol/g/min) for each tumor was compared with National Cancer Institute tumor grade, S-phase percentage, and percentage of aneuploidy of the tumor population. The pretreatment quantitative determination of tumor MRFDG by PET correlates strongly with tumor grade but not with the other selected histopathological tumor correlates. In addition, overlap of MRFDG PET values with tumor grade suggests that PET, an objective tumor measurement, may provide an alternative means of assessing tumor biological potential or may have the potential to overcome some of the limitations of traditional pathological evaluation. FDG PET can uniquely provide a metabolic profile of a diverse group of sarcomas noninvasively and provide clinically relevant tumor biological information.
Assuntos
Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Sarcoma/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Fluordesoxiglucose F18/farmacocinética , Humanos , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Sarcoma/metabolismo , Sarcoma/patologia , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Tomografia Computadorizada de EmissãoRESUMO
PURPOSE: The purpose of this study was to determine if radiotherapy is a beneficial adjuvant treatment after desmoid tumor resection. METHODS AND MATERIALS: A retrospective analysis was performed on 54 patients who underwent surgery without prior radiation at our institution between 1982 and 1998 to remove a desmoid tumor. Thirty-five patients had adjuvant radiation therapy after surgery, and 19 patients had surgery alone without immediate postoperative radiation. Sixteen of the 35 patients who underwent immediate postoperative radiation treatment had at least one prior resection before reoperation at our institution. Recurrence was defined as radiographic increase in tumor size after treatment. Follow-up interval (mean 39 months) and duration of local control were measured from the date of surgery at our institution. Potential prognostic factors for time to tumor progression were analyzed. RESULTS: Adjuvant treatment with radiation was the only significant prognostic factor for local control. The five-year actuarial local control rate was 81% for the 35 patients who underwent radiation in addition to surgery, compared to 53% for the 19 patients who underwent surgery alone (p = 0.018). For the patients who did not receive adjuvant radiation, only younger age at the time of surgery was associated with increased risk of failure (p = 0.035). Gross or microscopic margin status and number of prior operations were not detected as prognostic for local failure. For patients who did receive postoperative radiation, only abdominal location was associated with increased risk of failure (p = 0.0097). CONCLUSION: Radiation treatment as an adjuvant to surgery improved local control over surgery alone. Multiple operations before adjuvant radiation did not decrease the probability of subsequent tumor control. Radiation should be considered as adjuvant therapy to surgery if repeated surgery for a recurrent tumor would be complicated by a significant risk of morbidity.
Assuntos
Fibromatose Abdominal/radioterapia , Fibromatose Abdominal/cirurgia , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Radioterapia/efeitos adversos , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
The influences of glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside intravenously on haemodynamics, coronary circulation and myocardial oxygen consumption were investigated in closed chest dogs (n = 8). In an attempt to simulate heart failure the dogs received blood transfusion (15 ml/kg) in the presence of halothane-induced myocardial depression. All three nitrates reduced the loads for the left ventricle. With isosorbide dinitrate and sodium nitroprusside the preload and pulmonary pressure decreased to a greater extent than with glyceryl trinitrate. The haemodynamic results suggest that sodium nitroprusside is the favourable nitrate in left ventricular failure because it produces a balanced reduction in the ratio of pre- and afterload. Four micrograms/kg X min sodium nitroprusside induced marked coronary dilatation; glyceryl trinitrate had only a slight coronary vasodilating effect. With isosorbide dinitrate the myocardial blood flow remained well adapted to oxygen demand, the coronary vascular resistance did not change. Sodium nitroprusside produced a significant change of the transmural myocardial blood distribution-expressed as the epi/endocardial blood flow ratio. The ratio was increased by sodium nitroprusside, much more than by glyceryl trinitrate or isosorbide dinitrate.
Assuntos
Ferricianetos/farmacologia , Hemodinâmica/efeitos dos fármacos , Dinitrato de Isossorbida/farmacologia , Nitroglicerina/farmacologia , Nitroprussiato/farmacologia , Animais , Circulação Coronária/efeitos dos fármacos , Cães , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacosRESUMO
The functional characteristics of six world-class high-altitude mountaineers were assessed 2-12 mo after the last high-altitude climb. Each climber on one or several occasions had reached altitudes of 8,500 m or above without supplementary O2. Static and dynamic lung volumes and right and left echocardiographic measurements were found to be within normal limits of sedentary controls (SC). Muscle fiber distribution was 70% type I, 22% type IIa, and 7% type IIb. Mean muscle fiber cross-sectional area was significantly smaller than that of SC (-15%) and of long-distance runners (LDR, -51%). The number of capillaries per unit cross-sectional area was significantly greater than that of SC (+ 40%). Total mitochondrial volume was not significantly different from that of SC, but its subsarcolemmal component was equal to that of LDR. Average maximal O2 consumption was 60 +/- 6 ml X kg-1 X min-1, which is between the values of SC and LDR. Average maximal anaerobic power was 28 +/- 2.5 W X kg-1, which is equal to that of SC and 40% lower that that of competitive high jumpers. All subjects were characterized by resting hyperventilation both in normoxia and in moderate (inspired O2 partial pressure = 77 Torr) hypoxia resulting in higher oxyhemoglobin saturation levels in hypoxia. The ventilatory response to four tidal volumes of pure O2 was similar to that of SC. It is concluded that elite high-altitude climbers do not have physiological adaptations to high altitude that justify their unique performance.
Assuntos
Adaptação Fisiológica , Altitude , Montanhismo , Adulto , Coração/anatomia & histologia , Coração/fisiologia , Frequência Cardíaca , Humanos , Locomoção , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/ultraestrutura , Músculos/anatomia & histologia , Músculos/irrigação sanguínea , Músculos/fisiologia , Consumo de Oxigênio , Oxiemoglobinas/metabolismo , Respiração , Fenômenos Fisiológicos RespiratóriosRESUMO
1,1-Dichloroethane (DCE) is a solvent that is often found as a contaminant of drinking water and a pollutant at hazardous waste sites. Information on its short- and long-term toxicity is so limited that the U.S. EPA and ATSDR have not established oral reference doses or minimal risk levels for the volatile organic chemical (VOC). The acute oral LD(50) in male Sprague-Dawley (S-D) rats was estimated in the present study to be 8.2 g/kg of body weight (bw). Deaths appeared to be due to CNS depression and respiratory failure. In an acute/subacute experiment, male S-D rats were given 0, 1, 2, 4, or 8 g DCE/kg in corn oil by gavage for 1, 5, or 10 consecutive days. The animals were housed in metabolism cages for collection of urine and sacrificed for blood and tissue sampling 24 h after their last dose. There were decreases in body weight gain and relative liver weight at all dosage levels, as well as increased renal nonprotein sulfhydryl levels at 2 and 4 g/kg after 5 and 10 days. Elevated serum enzyme levels, histopathological changes, and abnormal urinalyses were not manifest. For the subchronic study, adult male S-D rats were gavaged with 0.5, 1, 2, or 4 g DCE/kg 5 times weekly for up to 13 weeks. Animals receiving 4 g/kg exhibited pronounced CNS depression, with more than one-half dying by week 11. The 2-g/kg rats exhibited moderate CNS depression. One 2-g/kg rat died during week 6. There were very few manifestations of organ damage in animals that succumbed or in survivors at any dosage level. Decreases in bw gain and transient increases in enzymuria were noted at 2 and 4 g/kg. Serum enzyme levels and blood urea nitrogen were not elevated, nor were glycosuria or proteinuria present. Chemically induced histological changes were not seen in the liver, kidney, lung, brain, adrenal, spleen, stomach, epididymis, or testis. Hepatic microsomal cytochrome P450 experiments revealed that single, high oral doses of DCE did not alter total P450 levels, but did induce CYP2E1 levels and activity and inhibit CYP1A1 activity. These effects were reversible and regressed with repeated DCE exposure. There was no apparent progression of organ damage during the 13-week subchronic study, nor appearance of adverse effects not seen in the short-term exposures. One g/kg orally (po) was found to be the acute, subacute, and subchronic LOAEL for DCE, under the conditions of this investigation. In each instance, 0.5 g/kg was the NOAEL.
Assuntos
Cloreto de Etil/análogos & derivados , Cloreto de Etil/toxicidade , Acetilglucosamina/urina , Fosfatase Ácida/urina , Animais , Peso Corporal , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Dicloroetilenos , Poluentes Ambientais/toxicidade , Feminino , Isoenzimas , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Nível de Efeito Adverso não Observado , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Testes de Toxicidade , Testes de Toxicidade AgudaRESUMO
1,1,1-Trichloroethane (TRI) is a widely used solvent that has become a frequent contaminant of drinking water supplies in the U.S. There is very little information available on the potential for oral TRI to damage the liver or to alter its P450 metabolic capacity. Thus, a major objective of this investigation was to assess the acute, short-term, and subchronic hepatotoxicity of oral TRI. In the acute study, male Sprague-Dawley (S-D) rats were gavaged with 0, 0.5, 1, 2, or 4 g TRI/kg bw and killed 24 h later. No acute effects were apparent other than CNS depression. Other male S-D rats received 0, 0.5, 5, or 10 g TRI/kg po once daily for 5 consecutive days, rested for 2 days, and were dosed for 4 additional days. Groups of the animals were sacrificed for evaluation of hepatotoxicity 1, 5, and 12 days after initiation of the short-term experiment. This dosage regimen caused numerous fatalities at 5 and 10 g/kg, but no increases in serum enzymes or histopathological changes in the liver. For the subchronic study, male S-D rats were gavaged 5 times weekly with 0, 0.5, 2.5, or 5.0 g TRI/kg for 50 days. The 0 and 0.5 g/kg groups were dosed for 13 weeks. A substantial number of rats receiving 2.5 and 5.0 g/kg died, apparently due to effects of repeated, protracted CNS depression. There was evidence of slight hepatocytotoxicity at 10 g/kg, but no progression of injury nor appearance of adverse effects were seen during acute or short-term exposure. Ingestion of 0.5 g/kg over 13 weeks did not cause apparent CNS depression, body or organ weight changes, clinical chemistry abnormalities, histopathological changes in the liver, or fatalities. Additional experiments did reveal that 0.5 g/kg and higher doses induced hepatic microsomal cytochrome P450IIE1 (CYP2E1) in a dose- and time-dependent manner. Induction of CYP2E1 activity occurred sooner, but was of shorter duration than CYP2B1/2 induction. CYP1A1 activity was not enhanced. In summary, 0.5 g/kg po was the acute, short-term, and subchronic NOAEL for TRI, for effects other than transient CYP2E1 induction, under the conditions of this investigation. Oral TRI appears to have very limited capacity to induce P450s or to cause liver injury in male S-D rats, even when administered repeatedly by gavage in near-lethal or lethal dosages under conditions intended to maximize hepatic effects.
Assuntos
Fígado/efeitos dos fármacos , Solventes/toxicidade , Tricloroetanos/toxicidade , Administração Oral , Alanina Transaminase/sangue , Animais , Sistema Enzimático do Citocromo P-450/biossíntese , Relação Dose-Resposta a Droga , Indução Enzimática , L-Iditol 2-Desidrogenase/sangue , Fígado/patologia , Longevidade/efeitos dos fármacos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Tamanho do Órgão/efeitos dos fármacos , Ornitina Carbamoiltransferase/sangue , Ratos , Ratos Sprague-Dawley , Solventes/administração & dosagem , Testes de Toxicidade , Tricloroetanos/administração & dosagem , Aumento de Peso/efeitos dos fármacosRESUMO
We tested the hypothesis of whether high dietary protein intake is linked to oxidative stress as measured by the concentration of reactive carbonyl residues in plasma proteins. Three groups of male Wistar rats ( approximately 230 g, n = 10) were fed either 15% (15C), 30% (30C), or 60% (60C) casein diets over a period of 18 weeks. For comparison, a vitamin E deficient diet (60C-E) based on diet 60C was given to an additional group to provoke oxidative stress. Concentrations of alpha-tocopherol in plasma and of reactive carbonyl residues in total plasma proteins were measured by high performance liquid chromatography using fluorescence and by diode array detection after 2,4-dinitrophenylhydrazine reaction, respectively. After 1 week the concentration of reactive carbonyl residues in plasma proteins was found to be significantly (P < 0.05) higher in the 60C and 60C-E groups ( approximately 2.7 nmol/mg protein) compared with the 15C and 30C groups ( approximately 1.7 nmol/mg protein). After 14 weeks the 15C (3.4 +/- 1.2 nmol/mg protein) and 60C-E groups (3.9 +/- 1.7 nmol/mg protein) showed a significantly increased concentration of reactive carbonyl residues in plasma protein compared with the 30C and 60C groups (2.5 +/- 1.0 nmol/mg protein; 2.6 +/- 0.8 nmol/mg protein). As expected, chronic vitamin E deficiency (60C-E) resulted in significantly decreased alpha-tocopherol concentrations (3.91 +/- 2.42 micromol/mL vs. 31.3 +/- 4.8 micromol/mL) and a higher concentration of reactive carbonyl residues in plasma proteins. These results do not support the hypothesis that a chronic intake of high-protein diets leads to oxidative stress in adult rats. However, in the non-adapted state (1 week) a high protein intake contributes to oxidative modifications of protein-bound amino acid residues.
RESUMO
A primary culture system of postnatal rat hepatocytes was utilized to study the cytotoxicity of acetaminophen and the toxicological significance of glutathione (GSH) depletion. The relative time of onset and magnitude of GSH depletion, lipid peroxidation and cytotoxicity were contrasted in order to gain insight into their interrelationships. Exposure of the hepatocytes to acetaminophen resulted in time- and dose-dependent depletion of cellular GSH. The acetaminophen-induced GSH depletion and ensuing lactate dehydrogenase (LDH) leakage were quite modest and delayed in onset, in contrast to that caused by iodoacetamide (IAA) and by diethylmaleate (DEM), 2 well-known depletors of GSH. There was comparable LDH leakage, irrespective of drug treatment, when GSH levels decreased to about 20% of normal. Reduction of GSH levels below the 20% threshold by IAA treatment resulted in marked LDH leakage and loss of viability. Maximal LDH leakage in response to IAA and acetaminophen preceded maximal malondialdehyde (MDA) formation, suggesting that lipid peroxidation may be a consequence of cell damage as well as GSH depletion. IAA and DEM produced a comparable, modest accumulation of MDA, yet IAA was much more cytotoxic. These findings indicate that lipid peroxidation does not play a central role in hepatocellular injury by compounds which deplete GSH, although it may contribute to degeneration of the cell. As events in the cultured postnatal hepatocytes paralleled those reported in vivo, the system can be a useful and valid model with which to study mechanisms of chemical toxicity.
Assuntos
Acetaminofen/toxicidade , Glutationa/análise , Fígado/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Técnicas In Vitro , Iodoacetatos/toxicidade , Ácido Iodoacético , L-Lactato Desidrogenase/análise , Peróxidos Lipídicos/análise , Fígado/metabolismo , Maleatos/toxicidade , Ratos , Ratos EndogâmicosRESUMO
Self-intoxication by inhalation of vapors of trichloroethylene (TCE) and other solvents is widespread. In order to develop exposure protocols which typify episodes of TCE "sniffing", male Wistar-Munich rats were exposed to TCE vapor levels ranging from 9000 to 16 000 ppm. TCE in concentrations of 14 000 ppm and greater quickly produced loss of righting reflex. Recovery from the narcosis was very rapid. Central nervous system (CNS) depression was found to be cumulative in rats subjected for 5 h to alternating periods of 5 min of 15 000 ppm TCE and 15 min of fresh air. Ethanol markedly potentiated depression in these subjects. No evidence of liver or kidney damage was seen in rats subjected to the repetitive 5-h TCE inhalation regimen, nor in rats fasted for 16 h before the TCE-exposure session. Oral administration of 5 ml/kg body wt of ethanol 1 h, 16 h, or once daily for 3 days before the TCE-exposure regimen had little if any potentiating effect on hepatorenal toxicity potential. Animals that received ethanol and were fasted before TCE exposure exhibited slight elevations in SGOT and SGPT levels.
Assuntos
Modelos Animais de Doenças , Transtornos Relacionados ao Uso de Substâncias , Tricloroetileno/toxicidade , Animais , Depressores do Sistema Nervoso Central/toxicidade , Indução Enzimática , Etanol/toxicidade , Jejum , Humanos , Fígado/efeitos dos fármacos , Masculino , Oxigenases de Função Mista/biossíntese , Ratos , Reflexo/efeitos dos fármacosRESUMO
The pharmacokinetics of pentobarbital, 30mg/kg iv, were studied in untreated rats and rats pretreated with 1,5, and 25 ppm of polychlorinated biphenyls in food for up to 140 days. Environmental contaminants may contribute to variations in metabolic rates of drugs by causing enzyme induction. The objective of this work was to quantitate the effects of environmental levels of the contaminant and enzyme inducer, a polychlorinated biphenyl, on the pharmacokinetics of pentobarbital, a drug whose primary elimination route is liver metabolism. The pharmacokinetics of pentobarbital in rats could be fit to a biexponential equation of the type Cp = Ae-alpha t+ Be-beta t. After 35 days of pretreatment, only the 25-ppm-treated rats showed any significant acceleration of pentobarbital elimination. At the 70- and 140-day samplings, both the 5- and 25-ppm pretreatments showed significant acceleration of pentobarbital elimination. There were no significant effects on A, alpha, B, and Vd for any pretreatment. The beta-values for the 25-ppm-pretreated rats reached a constant value from the 35-day pretreatment period onward. A calculation of total body clearance suggested that pentobarbital elimination in those rats had approached portal blood flow rate-limited metabolism.
Assuntos
Pentobarbital/metabolismo , Bifenilos Policlorados/farmacologia , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Exposição Ambiental , Cinética , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Pentobarbital/sangue , Ratos , Fatores de TempoRESUMO
Primary cultures of rat renal cortical epithelial cells were used to assess the in vitro nephrotoxicity of cephaloridine (Cph). Several different indices were used to follow the course of Cph-induced nephrotoxicity in the cultures. Plasma membrane integrity was determined by the effect of Cph on lactate dehydrogenase (LDH) leakage, cellular K(+) content and plasma membrane Na(+)/K(+) ATPase activity. Significant LDH leakage and decreased cellular K(+) content occurred after 8 hr of exposure to Cph. Na(+)/K(+) ATPase activity was depressed as early as 4 hr after Cph treatment. Brush border integrity was assessed by the effect of Cph on the activity of the brush border enzyme alkaline phosphatase, which was significantly decreased following 12 hr of exposure to Cph. Treatment with Cph resulted in an initial elevation of cellular glutathione (GSH)-as indicated by cellular non-protein sulphydryl content-followed by a decrease in GSH content 16 hr later. The mitochondrial response to Cph was assessed by determining mitochondrial succinate dehydrogenase (SDH) activity and cellular ATP content. SDH activity was significantly depressed after 4 hr of Cph exposure; ATP content was not significantly depressed until 12 hr after treatment. The time course of Cph-induced injury in our culture system suggests that early injury involves alterations at the level of the mitochondrial membrane and the plasma membrane. The most sensitive indicators of Cph-induced toxicity in this system were mitochondrial SDH activity and plasma membrane Na(+)/K(+) ATPase activity.
RESUMO
The Bankart repair for chronic anterior shoulder instability effectively addresses the pathologic components responsible for repeated dislocation or subluxation. However, contrary to popular belief, the Bankart repair does not precisely restore the premorbid anatomy. The capsule is reattached to the boney rim of the anterioinferior glenoid deep to and lateral to the torn cartilagenous labrum, thus excluding the labrum from the joint anteriorly. This was demonstrated by cross-sectional cadaver dissections performed to illustrate this complex surgical anatomy to orthopaedic residents in training. In addition, when correlated with double-contrast computerized axial tomography, we noted five predominant patterns of anatomical lesions which by common use have been collectively termed the "Bankart lesion." These are: 1) the rare "classic" Bankart lesion in which the cartilagenous labrum and capsular origin are torn from the glenoid rim; 2) the capsule stripped from the scapular neck and the labrum detached from the glenoid rim remaining fixed to the overlying capsule; 3) the capsule stripped from the scapular neck and the labrum separated from the glenoid rim, but separately; 4) the labrum abraded away and no longer radiographically detectable; and 5) glenoid rim fracture.
Assuntos
Instabilidade Articular/cirurgia , Lesões do Ombro , Humanos , Instabilidade Articular/complicações , Instabilidade Articular/patologia , Métodos , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/etiologia , Luxação do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Articulação do Ombro/cirurgia , Tomografia Computadorizada por Raios XRESUMO
To correlate clinical results after anterior cruciate ligament reconstruction with tunnel placement measured radiographically, we prospectively studied 128 patients who had arthroscopically assisted bone-patellar tendon-bone reconstructions. Patients with bilateral anterior cruciate ligament reconstructions, other significant knee ligament injuries, or those undergoing chondroplasty or meniscal repairs were excluded, leaving 42 patients. The relationship between radiographic tunnel position and clinical results was determined using the Lysholm score, KT-1000 arthrometer testing, the Tegner activity level, and the pivot shift and Lachman tests. Clinical results correlated positively with posterior femoral tunnel placement on lateral radiographs and negatively with excessive anterior tibial tunnel placement. Specifically, when femoral tunnels were placed at least 60% posterior along Blumensaat's line and tibial tunnels were at least 20% posterior along the tibial plateau, 69% of patients had good or excellent Lysholm scores and 79% had KT-1000 arthrometer maximum manual side-to-side differences of 3 mm or less. When the above criteria were not met, 50% of patients had good or excellent Lysholm scores and 22% had KT-1000 arthrometer maximum manual side-to-side differences of 3 mm or less. This close correlation indicates that satisfactory radiographic tunnel position influences outcome after anterior cruciate ligament reconstruction.
Assuntos
Ligamento Cruzado Anterior/cirurgia , Fêmur/cirurgia , Tíbia/cirurgia , Adolescente , Adulto , Ligamento Cruzado Anterior/fisiopatologia , Lesões do Ligamento Cruzado Anterior , Artroscopia , Endoscopia , Feminino , Fêmur/diagnóstico por imagem , Humanos , Instabilidade Articular/fisiopatologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Masculino , Ligamento Patelar/transplante , Estudos Prospectivos , Radiografia , Amplitude de Movimento Articular , Tíbia/diagnóstico por imagem , Resultado do TratamentoRESUMO
A method has been developed for preparing primary monolayer cultures of postnatal rat kidney cortical epithelial cells. These cultures maintained differentiated cell functions and epithelial-like morphology for several days in culture. The presence of alkaline phosphatase and maltase was used to confirm the presence of cells from the renal cortex. The concentrations of these enzymes were maintained in culture until day 3, but had declined significantly by day 5. Similar patterns were observed with cytochrome P-450 and glutathione content, although their concentrations remained stable from day 3 to day 5. Mercuric chloride, cadmium chloride and acetaminophen were evaluated for nephrotoxicity in this culture system. Treatment with these compounds resulted in dose-dependent changes in cell morphology and in biochemical parameters such as lactate dehydrogenase leakage, alkaline phosphatase activity and cellular glutathione content. With this culture system, it was possible to detect the acute toxicities of compounds that produce varying degrees of renal injury. Further development of this kidney culture system may have value in detecting potential nephrotoxins and in studying their mechanisms of toxicity.