RESUMO
Parkinson's disease, a major neurodegenerative disorder in humans whose etiology is unknown, may be associated with some environmental factors. Nocardia otitidiscaviarum (GAM-5) isolated from a patient with an actinomycetoma produced signs similar to Parkinson's disease following iv injection into NMRI mice. NMRI mice were infected intravenously with a non-lethal dose of 5 x 10(6) colony forming units of N. otitidiscaviarum (GAM-5). Fourteen days after bacterial infection, most of the 60 mice injected exhibited parkinsonian features characterized by vertical head tremor, akinesia/bradykinesia, flexed posture and postural instability. There was a peak of nocardial growth in the brain during the first 24 h followed by a decrease, so that by 14 days nocardiae could no longer be cultured. At 24 h after infection, Gram staining showed nocardiae in neurons in the substantia nigra and occasionally in the brain parenchyma in the frontal and parietal cortex. At 21 days post-infection, tyrosine hydroxylase immunolabeling showed a 58% reduction of tyrosine hydroxylase in the substantia nigra, and a 35% reduction of tyrosine hydroxylase in the ventral tegmental region. Dopamine levels were reduced from 110 +/- 32.5 to 58 +/- 16.5 ng/mg protein (47.2% reduction) in brain from infected mice exhibiting impaired movements, whereas serotonin levels were unchanged (191 +/- 44 protein in control and 175 +/- 39 ng/mg protein in injected mice). At later times, intraneuronal inclusion bodies were observed in the substantia nigra. Our observations emphasize the need for further studies of the potential association between Parkinson's disease or parkinsonism-like disease and exposure to various nocardial species.
Assuntos
Encéfalo/microbiologia , Nocardiose/microbiologia , Nocardia , Transtornos Parkinsonianos/microbiologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Nocardiose/metabolismo , Nocardiose/patologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Organismos Livres de Patógenos Específicos , Substância Negra/microbiologia , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Parkinson's disease, a major neurodegenerative disorder in humans whose etiology is unknown, may be associated with some environmental factors. Nocardia otitidiscaviarum (GAM-5) isolated from a patient with an actinomycetoma produced signs similar to Parkinson's disease following iv injection into NMRI mice. NMRI mice were infected intravenously with a non-lethal dose of 5 x 10(6) colony forming units of N. otitidiscaviarum (GAM-5). Fourteen days after bacterial infection, most of the 60 mice injected exhibited parkinsonian features characterized by vertical head tremor, akinesia/bradykinesia, flexed posture and postural instability. There was a peak of nocardial growth in the brain during the first 24 h followed by a decrease, so that by 14 days nocardiae could no longer be cultured. At 24 h after infection, Gram staining showed nocardiae in neurons in the substantia nigra and occasionally in the brain parenchyma in the frontal and parietal cortex. At 21 days post-infection, tyrosine hydroxylase immunolabeling showed a 58 percent reduction of tyrosine hydroxylase in the substantia nigra, and a 35 percent reduction of tyrosine hydroxylase in the ventral tegmental region. Dopamine levels were reduced from 110 ± 32.5 to 58 ± 16.5 ng/mg protein (47.2 percent reduction) in brain from infected mice exhibiting impaired movements, whereas serotonin levels were unchanged (191 ± 44 protein in control and 175 ± 39 ng/mg protein in injected mice). At later times, intraneuronal inclusion bodies were observed in the substantia nigra. Our observations emphasize the need for further studies of the potential association between Parkinson's disease or parkinsonism-like disease and exposure to various nocardial species.
Assuntos
Humanos , Animais , Feminino , Camundongos , Encéfalo , Nocardia , Nocardiose , Doença de Parkinson , Encéfalo , Imuno-Histoquímica , Nocardiose , Doença de Parkinson , Organismos Livres de Patógenos Específicos , Substância Negra , Tirosina 3-Mono-OxigenaseRESUMO
Thermospray mass spectral (TSP-MS) analyses were carried out on methyl corynomycolates, their 3-O-acetyl and 3-O-benzoyl derivatives, and on corynomycolic acids and their 3-O-acetyl derivatives, using an ion generating solvent system consisting of water/isopropanol (99:1, v/v) containing 0.1 M ammonium acetate. Methyl corynomycolates generated three groups of peaks corresponding to adducts M-18 + H, M + H and M + NH4, while two groups of peaks representing adducts M-60 + H and M + H + NH4 were seen in the spectra of 3-O-acetyl methyl corynomycolates. The 3-O-benzoyl methyl corynomycolates gave a series of peaks representing the adducts M-122 + H, M + 2H and M + H + NH4. In the spectra of 3-O-acetyl corynomycolic acids, a series of peaks which represented M-60 + H and M + NH4 was observed, and in turn, mass spectra of corynomycolic acids revealed peaks that represented the adducts M-18 + H and M + NH4. Therefore, methyl corynomycolates, 3-O-acyl derivatives of methyl corynomycolates,. 3-O-acetylated derivatives of corynomycolic acids and the underivatized corynomycolic acids all exhibited the formation of an adduct of the anhydro compounds. These anhydro forms were generated by a generalized process.
Assuntos
Ácidos Micólicos/química , Espectrometria de Massas , Estrutura Molecular , Ácidos Micólicos/isolamento & purificaçãoRESUMO
Virulent Nocardia asteroides GUH-2 and avirulent N. asteroides 10905 contained 8.2% and 10.6% of diethyl ether soluble lipids (DESL) per dry cell mass, respectively. Intraperitoneal (i.p.) inoculation of 250 micrograms of DESL from GUH-2 dissolved in mineral oil was toxic to mice, resulting in weight loss and death of 100% of the animals (20/20) within 20 days. In contrast, DESL from 10905 had very little toxicity, and only one mouse (1/10) died within 30 days. Three fractions resulted from DESL by silicic acid column chromatography: (1) neutral lipids and fatty acids (NFA); (2) glycolipids (GL); and (3) phospholipids (PL). Each fraction dissolved in mineral oil was inoculated into mice as described above. The NFA and PL were not toxic. GL from 10905 had low toxicity (30% of the animals died, 3/10) whereas GL from GUH-2 expressed high toxicity (100% of the animals became cachetic and died, 10/10). GL from 10905 represented a minor component (0.6% of dry cell weight) whereas GL from GUH-2 was more prominent (1.5% of dry cell wt.). Approximately 95% of GL from GUH-2 had properties of an authentic trehalose-6,6'-dimycolate standard. Infrared spectrum of the major glycolipid (GUH-2 GL) had characteristic absorptions in the fingerprint region between 800 cm-1 and 1500 cm-1. Upon alkaline hydrolysis GUH-2 GL released 76% mycolic acids in the C50 size range plus 24% trehalose.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Éter/química , Glicolipídeos/análise , Glicolipídeos/toxicidade , Nocardia asteroides/química , Animais , Técnicas de Química Analítica , Cromatografia em Camada Fina , Glicolipídeos/química , Concentração de Íons de Hidrogênio , Hidrólise , Espectrometria de Massas , Camundongos , SolubilidadeRESUMO
Methyl esters of normal fatty acids, corynomycolate and corynomycolenate were used as model compounds for thermospray mass spectrometric procedures for molecular weight determination of the related nocardial mycolic acids. By using ammonium acetate at the positive ion generator, in both cases, a family of ions was produced. The following members were found and corresponded to the adducts: (1) M + H; M + NH4 and M + H + NH4 for methyl esters of normal fatty acids, whereas M + H, M + 2H and M + H + NH4 were the adducts most frequently observed with methyl corynomycolates. The methyl esters of C40-C48 mycolic acids from Rhodococcus rhodochrous exhibited prominent peaks corresponding to adducts M + H + NH4 whereas those corresponding to M + 2H showed slightly lower intensities. The structure M + H had no significant representatives with this subclass of mycolic acids. A similar pattern was observed with methyl esters of C50-C54 mycolic acids from Nocardia asteroides GUH-2. Ion peaks C50-C54 representing adducts M + 2H and M + H + NH4 prevailed in the mass spectrum. In this case, the intensities of peaks corresponding to M + 2H were slightly higher than those of the M + H + NH4. Essentially three main species of nocardomycolic acids were detected: (1) monounsaturated C50:1, C52:1 and C54:1; (2) diunsaturated C50:2, C52:2 and C54:2 and (3) triunsaturated C52:3 and C54:3 mycolic acids. The most abundant mycolic acid was C52:2 followed in decreasing abundance by C52:1, C54:2, C50:2, C52:3 and C54:3 mycolic acids.