RESUMO
BACKGROUND AND PURPOSE: Although considerable variability exists as to the overall caliber of radiculomedullary arteries, dominant radiculomedullary arteries such as the artery of Adamkiewicz exist. The existence of a great posterior radiculomedullary artery has attracted little attention and has been a matter of debate. The aim of this anatomic study was to determine the presence or absence of the great posterior radiculomedullary artery. MATERIALS AND METHODS: We performed microsurgical dissection on formaldehyde-fixed cadaveric human spinal cords. The artery of Adamkiewicz in the spinal cord specimens (n = 50) was injected with colored latex until the small-caliber arterial vessels were filled and the great posterior radiculomedullary artery was identified. The course, diameter, and location of great posterior radiculomedullary artery were documented. RESULTS: A great posterior radiculomedullary artery was identified in 36 (72%) spinal cord specimens. In 11 (22%) specimens, bilateral great posterior radiculomedullary arteries were present. In 13 cases (26%), a unilateral left-sided great posterior radiculomedullary artery was identified. In 11 cases (22%), a unilateral right-sided great posterior radiculomedullary artery was identified. In 1 specimen (2%), 3 right-sided great posterior radiculomedullary arteries were noted. The average size of the great posterior radiculomedullary arteries was 0.44 mm (range, 0.120-0.678 mm on the left and 0.260-0.635 mm on the right). CONCLUSIONS: A great posterior radiculomedullary artery is present in most (72%) individuals. The authors describe the microsurgical anatomy of the great posterior radiculomedullary artery with emphasis on its morphometric parameters as well as its implications for spinal cord blood supply. Variations of the arterial supply to the dorsal cord are of great importance due to their implications for ischemic events, endovascular procedures, and surgical approaches.
Assuntos
Artérias/anatomia & histologia , Medula Espinal/anatomia & histologia , Adulto , Idoso , Artérias/anormalidades , Cadáver , Feminino , Humanos , Região Lombossacral/anatomia & histologia , Região Lombossacral/irrigação sanguínea , Masculino , Microdissecção , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Medula Espinal/irrigação sanguínea , Adulto JovemRESUMO
This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ). An in vitro plasma OFZ solubility study provided additional information on plasma saturation. For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n = 6), were treated intravenously, at a dose rate of 5 mg/kg bodyweight, with aqueous formulations containing at 4, 8 or 16% OFZ. Plasma drug concentrations were measured, for up to 72 h post-treatment, by a validated high performance liquid chromatography method with UV detection. OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% formulation, OFZ depleted according to a biexponential concentration vs. time curve. In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident. Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation, and lower AUC's, suggesting that OFZ sulphonation may have been modified. In vitro there was evidence of plasma saturation associated with 8 and 16% OFZ preparations. It is concluded that differences in PK profiles were related to OFZ solubility and/or tissue drug precipitation.
Assuntos
Anti-Helmínticos/farmacocinética , Benzimidazóis/farmacocinética , Ovinos/metabolismo , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/sangue , Anti-Helmínticos/química , Área Sob a Curva , Benzimidazóis/administração & dosagem , Benzimidazóis/sangue , Benzimidazóis/química , Química Farmacêutica , Feminino , Técnicas In Vitro , Injeções Intravenosas , SolubilidadeRESUMO
1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.
Assuntos
Dexametasona/administração & dosagem , Fenbendazol/administração & dosagem , Fenbendazol/sangue , Ovinos/metabolismo , Administração Oral , Animais , Dexametasona/análogos & derivados , Dexametasona/química , Interações Medicamentosas , Feminino , Fenbendazol/análogos & derivados , Fenbendazol/química , Injeções Intramusculares , Isomerismo , Taxa de Depuração MetabólicaRESUMO
Co-administration of piperonyl butoxide (PB) potentiates fenbendazole (FBZ) in small ruminants. The resultant increase in bioavailability of FBZ and its metabolite oxfendazole (OFZ) has important implications for the efficacy of these drugs against benzimidazole (BZD)-resistant strains of Teladorsagia circumcincta. This study evaluated the racemic (achiral) and enantiomeric (chiral) plasma disposition kinetics of OFZ and its metabolites after the co-administration of PB and OFZ in sheep. Six 6-8-month-old, parasite-free, female Dorset sheep (30-40 kg) were used in a two-phase crossover experiment. In phase I, three sheep received 30 mg/kg PB orally, followed by a single intravenous (i.v.) injection of OFZ at 5 mg/kg. The other three animals were treated similarly except that 5 mL of water replaced PB. In phase 2, treatments for the two groups were reversed and were given 14 days after the initiation of phase I. Three analytes OFZ, FBZ and fenbendazole sulphone (FBZSO(2)) were recovered in plasma up to 48 h post-treatment in both experimental groups. Achiral and chiral pharmacokinetic (PK) profiles for OFZ, after the co-administration of PB, were characterized by a significantly greater area under the concentration--time curve (AUC) and a longer mean residence time (MRT). Chiral OFZ distribution ratios were comparable in both treatment groups. Piperonyl butoxide treatment markedly influenced the plasma PK profiles for FBZ and FBZSO(2) following OFZ administration. Production of FBZ was enhanced as reflected by increased (> 60%) AUC, delayed T(max) and a significantly delayed (> 45%) elimination (t(1/2)(el)). Although AUC values for FBZSO(2) were not significantly different between groups, this metabolite was depleted more slowly from plasma (t(1/2)(el) > 60% and MRT > 42%) following PB treatment. This study demonstrated that PB co-administration is associated with an inhibition of OFZ biotransformation, as evidenced by the significantly higher plasma concentrations of OFZ and FBZ, and this could have important implications in terms of anti-parasite therapy against BZD-resistant parasite strains.
Assuntos
Anti-Helmínticos/farmacocinética , Benzimidazóis/farmacocinética , Sinergistas de Praguicidas/farmacocinética , Butóxido de Piperonila/farmacocinética , Ovinos/metabolismo , Administração Oral , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/sangue , Anti-Helmínticos/química , Área Sob a Curva , Benzimidazóis/administração & dosagem , Benzimidazóis/sangue , Benzimidazóis/química , Disponibilidade Biológica , Estudos Cross-Over , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Infusões Intravenosas/veterinária , Isomerismo , Sinergistas de Praguicidas/administração & dosagem , Sinergistas de Praguicidas/sangue , Butóxido de Piperonila/administração & dosagem , Butóxido de Piperonila/sangueAssuntos
Doença da Altitude/prevenção & controle , Cocaína/administração & dosagem , Chá , Doença da Altitude/urina , Bolívia , Cocaína/farmacocinética , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Humanos , Detecção do Abuso de Substâncias/legislação & jurisprudência , Chá/químicaRESUMO
An outbreak of cutaneous leishmaniasis occurred in a unit of 608 Puerto Rican national guardsmen conducting jungle warfare training in the Panama Canal Area in July 1984. An epidemiologic investigation of reported nonhealing, ulcerating skin lesions was conducted among 540 (89%) unit members in November and December 1984. Fifteen (88%) of 17 individuals with chronic, ulcerating skin lesions were confirmed as cases of cutaneous leishmaniasis by culture or histopathology. Twelve cases yielded positive Leishmania cultures, identified as L. braziliensis panamensis by cellulose acetate electrophoresis. Evaluation of different diagnostic techniques revealed that direct examination of tissues by Giemsa-stained histological examination was the most sensitive test (87% sensitivity), with an indirect immunofluorescent antibody test being rather insensitive (67%). All but one of the confirmed cases operated in small units that trained and slept overnight at a mortar firing site for a period of three days, yielding a site-specific attack rate of 22% (14 of 64). This contrasted with a much lower attack rate of 0.2% (1 of 476), experienced by unit members who trained at other locations during the same time frame (P less than 0.001). The median incubation period calculated from day of arrival at the mortar firing site was 17 days (range 2-78) for the 15 confirmed cases. Available personal protection methods, such as the use of insect repellents, were not appropriately implemented by unit personnel and thus, were not found to effectively protect against Leishmania infection. This is the largest reported outbreak of cutaneous leishmaniasis in military personnel associated with a single geographic focus of infection and contrasts with the usual sporadic disease experience in Panama.