RESUMEN
BACKGROUND AND OBJECTIVES: Ocular involvement is common in sarcoidosis. Our study aimed to evaluate the role of screening for uveitis in subjects with sarcoidosis. METHODS: Retrospective case series of 88 subjects with a pre-existing diagnosis of sarcoidosis, with no previous diagnosis of uveitis, reviewed by Ophthalmology at Auckland District Health Board between January 2016 and May 2022. RESULTS: Among those undergoing a screening examination, uveitis was observed in 27.8% (15 out of 54 subjects). In those presenting with acute eye symptoms, uveitis was observed in 94.1% (32 out of 34 subjects). Sarcoid uveitis was diagnosed in a total of 50 out of 88 subjects (56.8%). 45 subjects required ocular treatment. Sarcoid uveitis was observed in 6 out of 27 subjects (22.2%) who were entirely asymptomatic at screening. On multivariate analysis, blurring of vision (OR 26.2 p < 0.001), eye pain (OR 7.3 p = 0.014) and respiratory disease (OR 7.1 p = 0.044) were associated with increased risk of sarcoid uveitis. In the 41 subjects with no uveitis at initial examination, 3 subjects (7.3%) subsequently developed uveitis. CONCLUSION: Our study highlights the importance of ophthalmic screening of all patients with systemic sarcoidosis, even in asymptomatic patients. With a high correlation of ocular symptoms in diagnosis of sarcoid uveitis, ophthalmologists should educate patients to look out for the development of symptoms of ocular inflammation, and clinicians who continue follow up for systemic sarcoidosis should remind patients to watch carefully for these symptoms to facilitate timely diagnosis and intervention.
Asunto(s)
Sarcoidosis , Uveítis , Humanos , Estudios Retrospectivos , Estudios de Seguimiento , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/epidemiología , Trastornos de la VisiónAsunto(s)
Antiinflamatorios/efectos adversos , Edema Corneal/etiología , Infecciones por Citomegalovirus/etiología , Fluocinolona Acetonida/efectos adversos , Adulto , Antiinflamatorios/administración & dosificación , Antivirales/uso terapéutico , Edema Corneal/tratamiento farmacológico , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/tratamiento farmacológico , Implantes de Medicamentos , Femenino , Fluocinolona Acetonida/administración & dosificación , Humanos , Resultado del Tratamiento , Adulto JovenRESUMEN
Creosote-contaminated soil samples from the Libby Ground Water Contamination Superfund Site in Libby, MT, were amended with the potential alternate electron acceptors (AEA) nitrate (KNO3), manganese oxide (MnO2), and amorphous iron oxyhydroxide (FeOOH) and incubated at low oxygen tensions (0-6% O2). The fate of 14C-pyrene was evaluated with respect to the different soil amendments. The fate of 14C from the radiolabeled pyrene with regard to mineralization and bound residue formation within soil humic fractions was not significantly different from controls for the iron and manganese amended soils. Nitrate amendments appeared to stimulate 14C-pyrene mineralization at a level of 170 mg NO3-N kg(-1), and inhibit mineralization at 340 mg NO3-N kg(-1). The stimulatory effect did not appear to be the result of nitrate serving as an electron acceptor. Although AEA amendments did not significantly affect the rate or extent of 14C-pyrene mineralization, results of oxygen-deprived incubations (purged with N2) indicate that AEA may be utilized by the microbial community in the unsaturated contaminated soil system.
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Colorantes Fluorescentes/metabolismo , Pirenos/metabolismo , Contaminantes del Suelo/metabolismo , Biodegradación Ambiental , Disponibilidad Biológica , Electrones , Compuestos de Hierro/química , Cinética , Compuestos de Manganeso/química , Minerales , Nitratos/química , Óxidos/química , Compuestos de Potasio/química , Microbiología del SueloRESUMEN
Contamination of the subsurface environment at the Libby Superfund Site, Montana, includes polycyclic aromatic hydrocarbons and f1p4achlorophenol due to accidental spills and improper disposal of wood preserving wastes. Biodegradation is a treatment technology gaining wide application in the treatment of hazardous waste sites. A microcosm study was conducted to evaluate the effect of temperature, sampling depth, nutrient addition, and oxygen on the biodegradation potential of phenanthrene and pentachlorophenol in aquifer samples using radiolabeled chemicals. Mineralization of phenanthrene reached 14% but was less than 1% for pentachlorophenol over the 56 day incubation period. Phenanthrene mineralization in microcosms at 10 degrees C was not significantly different from those at 20 degrees C. This may have been due to microbial community acclimation to lower temperatures at the site. Average volatilization was less than 2% for both phenanthrene and pentachlorophenol. After 56 days, most of the radiolabeled chemical was either solvent extractable or soil bound.
Asunto(s)
Creosota/química , Pentaclorofenol/química , Fenantrenos/química , Contaminantes Químicos del Agua/análisis , Biodegradación Ambiental , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Industrias , Temperatura , MaderaRESUMEN
Yang et al. have isolated from bovine brain an octapeptide, FLFQPQRF-NH2 (F-8-F-NH2), with certain antiopiate properties. Malin et al. previously found that ICV injection of this peptide could precipitate an opiate abstinence syndrome in dependent rats. RIA revealed significantly higher levels of F-8-F-NH2 immunoreactivity in CSF withdrawn from the cisterna magna of morphine-dependent rats as opposed to CSF withdrawn from sham-implanted controls. ICV infusion of IgG from antiserum against F-8-F-NH2 significantly reduced the number of abstinence signs subsequently precipitated by naloxone in morphine-dependent rats.
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Dependencia de Morfina/líquido cefalorraquídeo , Oligopéptidos/fisiología , Animales , Inmunoglobulina G/inmunología , Masculino , Morfina/toxicidad , Dependencia de Morfina/fisiopatología , Naloxona/farmacología , Oligopéptidos/inmunología , Ratas , Ratas Endogámicas , Médula Espinal/química , Síndrome de Abstinencia a Sustancias/etiología , Síndrome de Abstinencia a Sustancias/prevención & controlRESUMEN
The effects of adenosine diphosphate (ADP) ribosylation inhibitors on hematopoietic growth factor-induced proliferation were examined. Significant inhibition of interleukin-3 (IL-3), colony-stimulating factor 1, and lung conditioned media-induced clonal agar growth of normal murine hematopoietic cells by 10 mmol/L nicotinamide (NAM), 10 mmol/L 3-aminobenzamide (3AB), and 5 mmol/L N1-methylnicotinamide (1MN) was noted. Nicotinic acid, a related compound that does not inhibit ADP ribosylation, failed to inhibit the growth factor-mediated proliferation. NAM (10 mmol/L), 3AB (10 mmol/L), and 1MN (5 mmol/L) also prevented IL-3 and phorbol ester-stimulated 3H-thymidine incorporation into the IL-3-responsive FDC-P1 cell line. Exposure of FDC-P1 cells to 10 mmol/L NAM led to a significant decrease in nuclear poly-(ADP-ribose) levels. Exposure of FDC-P1 cells to 5 mmol/L 1MN did not affect the interaction of the phorbol ester receptor, protein kinase-C (PK-C), with the cell membrane as determined by assay of phorbol ester binding in cytosol and membrane preparations. Nor did it affect the catalytic activity of PK-C as determined by assaying the in vitro phosphorylation of histone H1 by cytosolic kinase preparations from FDC-P1 as well as EL4 thymoma cells. 1MN markedly enhanced the inhibitory effects of phorbol esters on DNA synthesis of EL4 cells even at concentrations (1.25 mmol/L) that had no effects on DNA synthesis in the absence of phorbol esters. Our findings demonstrate that (a) active ADP ribosylation inhibitors interfere with growth factor-induced proliferation of murine hematopoietic cells and (b) the inhibition occurs at a step that follows the activation and translocation of PK-C and is more closely linked to DNA synthesis.
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Adenosina Difosfato/metabolismo , Inhibidores de Crecimiento , Células Madre Hematopoyéticas/citología , Ribosa/metabolismo , Adenosina Difosfato/antagonistas & inhibidores , Animales , Benzamidas/farmacología , División Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Citosol/metabolismo , Sustancias de Crecimiento/farmacología , Hematopoyesis/efectos de los fármacos , Factores de Crecimiento de Célula Hematopoyética , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Ratones , Ratones Endogámicos CBA , Niacinamida/análogos & derivados , Niacinamida/farmacología , Timidina/metabolismoRESUMEN
We present evidence that ethanol alters intracellular poly(adenosine diphosphoribose) metabolism and we further describe the mechanism by which ethanol exerts its effect on polymer synthesis. One percent ethanol stimulates polymer accumulation as much as 2.5-fold but does not alter polymer degradation in intact cells following DNA damage. Ethanol directly stimulates polymer synthesis following low doses of DNA damage induce by deoxyribonuclease I in a nucleotide-permeable cell system that does not possess a functional polymer turnover system. Ethanol has no measurable effect on polymer synthesis in undamaged nucleotide-permeable cells or in permeable cells treated with high doses of deoxyribonuclease I. Ethanol concentrations that stimulate poly(adenosine diphosphoribose) polymerase activity in vitro specifically lower KDNA without affecting KNAD or Vmax. The results clearly show that ethanol alters the binding of this enzyme to the DNA component of chromatin and that this altered binding is responsible for the activation of the enzyme. Altered affinity of poly(adenosine diphosphoribose) polymerase and perhaps other regulatory proteins for chromatin may play an important role in the pathology of alcohol.
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Etanol/farmacología , Azúcares de Nucleósido Difosfato/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Animales , Bovinos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Células Cultivadas , Cinética , Metilnitronitrosoguanidina/farmacología , NAD/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Timo/enzimologíaRESUMEN
The effects of nicotinamide analogues on cellular recovery following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment have been characterized in the transformable cell line, C3H10T1/2. The recovery of cell division potential was measured under conditions which allow simultaneous quantification of intracellular levels of poly(adenosine diphosphate ribose), nicotinamide adenine dinucleotide, and rates of RNA, DNA, and protein synthesis. 3- Methoxybenzamide (MBA), 3-aminobenzamide, and benzamide, which are effective inhibitors of adenosine diphosphate ribosyltransferases , blocked recovery of cell division following treatment with 34 microM MNNG, while the noninhibitors , 3- methoxybenzoate and benzoate, had no effect. In the presence of MBA, cells progressively lost the ability to resume cell division during the first 24 to 36 hr following DNA damage. The intracellular levels of poly(adenosine diphosphate ribose) increased approximately 7-fold within 20 min following MNNG treatment, and 1 mM MBA inhibited this increase by approximately 82%. In the presence of MBA, a dramatic decrease in the rate of DNA synthesis occurred approximately 16 hr after MNNG treatment, while RNA and protein synthesis continued at rates similar to those in cells treated with MNNG alone.
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Reparación del ADN , Replicación del ADN/efectos de los fármacos , Niacinamida/análogos & derivados , Animales , Línea Celular , Células Cultivadas , Humanos , Cinética , Metilnitronitrosoguanidina/toxicidad , Ratones , Ratones Endogámicos C3H , Niacinamida/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Transcripción Genética/efectos de los fármacosAsunto(s)
Adenosina Difosfato Ribosa/análisis , Azúcares de Nucleósido Difosfato/análisis , Poli Adenosina Difosfato Ribosa/análisis , Animales , Radioisótopos de Carbono , Células Cultivadas , Cromatografía Líquida de Alta Presión/métodos , Cromatografía por Intercambio Iónico/métodos , Indicadores y Reactivos , Técnica de Dilución de Radioisótopos , Espectrometría de Fluorescencia/métodos , TritioRESUMEN
Inhibitors of poly(ADP-ribose) polymerase stimulated the level of DNA, RNA, and protein synthesis in DNA-damaged L1210 cells but had negligible effects in undamaged L1210 cells. The poly(ADP-ribose) polymerase inhibitors stimulated DNA repair synthesis after cells were exposed to high concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (68 and 136 microM) but not after exposure to low concentrations (13.6 and 34 microM). When the L1210 cells were exposed to 136 microM N-methyl-N'-nitro-N-nitrosoguanidine, the activation of poly(ADP-ribose) polymerase resulted in the rapid depletion of oxidized nicotinamide adenine dinucleotide (NAD+) levels and subsequent depletion of adenosine 5'-triphosphate (ATP) pools. After low doses of N-methyl-N'-nitro-N-nitrosoguanidine (13.6 microM), there were only small decreases in NAD+ and ATP. Poly(ADP-ribose) polymerase inhibitors prevented the rapid fall in NAD+ and ATP pools. This preservation of the ATP pool has a permissive effect on energy-dependent functions and accounts for the apparent stimulation of DNA, RNA, and protein synthesis. Thus, the mechanism by which poly(ADP-ribose) polymerase inhibitors stimulate DNA, RNA, and protein synthesis in DNA-damaged cells appears to be mediated by their ability to prevent the drastic depletion of NAD+ pools that occurs in heavily damaged cells, thereby preserving the cells' ability to generate ATP and maintain energy-dependent processes.
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Adenosina Trifosfato/metabolismo , ADN/biosíntesis , NAD+ Nucleosidasa/antagonistas & inhibidores , NAD/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Animales , Benzamidas/farmacología , Células Cultivadas , Reparación del ADN , ADN de Neoplasias/biosíntesis , Leucemia L1210/enzimología , Metilnitronitrosoguanidina , Ratones , Proteínas de Neoplasias/biosíntesis , Niacinamida/farmacología , ARN Neoplásico/biosíntesisRESUMEN
Treatment of cells with DNA damaging agents results in a dose dependent decrease in NAD+ and ATP pool sizes. The decrease in NAD+ is associated with the activation of poly(ADP-ribose) polymerase and the decrease in ATP is consequent to the fall in NAD+. Depletion of both NAD+ and ATP can be blocked or retarded by inhibitors of poly(ADP-ribose) polymerase. Both the stimulation of poly(ADP-ribose) synthesis and the effect of enzyme inhibitors have been confirmed in intact cells by using enzymatic cycling techniques to measure the disappearance of NAD+ and high pressure liquid chromatography (HPLC) to measure fluctuations in polymer levels. As a consequence of the depletion of NAD+ and ATP pools, cells exhibit a marked impairment in their ability to conduct all energy dependent functions. Thus cells treated with high levels of DNA damaging agents exhibit severe suppression of DNA replication and repair, RNA synthesis and protein synthesis. The use of inhibitors of poly(ADP-ribose) polymerase to prevent the depletion of NAD+ and ATP partially restores the cells' ability to conduct DNA, RNA, and protein synthesis. This preservation of the NAD+ and ATP pools accounts for the recent observations that inhibitors of poly(ADP-ribose) stimulate the level of DNA repair synthesis in cells treated with high levels of DNA damaging agents. We have also examined cells from patients with several of the disorders of DNA repair and have found that cells from patients with Fanconi's anemia have lower than normal NAD+ levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Reparación del ADN , NAD+ Nucleosidasa/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Humanos , Técnicas In Vitro , Leucemia L1210/metabolismo , Metilnitronitrosoguanidina/farmacología , NAD/metabolismo , Niacinamida/farmacología , Inhibidores de Poli(ADP-Ribosa) PolimerasasAsunto(s)
ADN/biosíntesis , Linfocitos/metabolismo , NAD+ Nucleosidasa/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Benzamidas/farmacología , Reparación del ADN/efectos de los fármacos , Humanos , Metilnitronitrosoguanidina/farmacología , NAD/metabolismo , Niacinamida/análogos & derivados , Niacinamida/farmacología , Purinas/farmacología , Pirazinamida/análogos & derivadosRESUMEN
The effect of nicotinamide on unscheduled DNA synthesis was studied in resting human lymphocytes. In cells treated with UV irradiation or with MNNG, nicotinamide caused a two-fold stimulation of unscheduled DNA synthesis and retarded the rate of NAD+ lowering caused by these treatments. Nicotinamide also reduced the burst of poly(ADP-ribose) synthesis caused by MNNG treatment. Thus under conditions that it enhances unscheduled DNA synthesis, nicotinamide causes marked effects on the metabolism of NAD+ and poly(ADP-ribose). The effect of nicotinamide on unscheduled DNA synthesis was shown to be independent of protein or polyamine synthesis.
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Reparación del ADN , Replicación del ADN/efectos de los fármacos , Linfocitos/metabolismo , NAD/metabolismo , Niacinamida/farmacología , Azúcares de Nucleósido Difosfato/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Humanos , Cinética , Metilnitronitrosoguanidina/farmacologíaRESUMEN
We encountered a case of systemic mast cell disease associated with rheumatoid factor; to our knowledge, this has not been reported in the literature. Rheumatoid arthritis as an unrelated second disease cannot be excluded, but there is support for a relation between joint symptoms, rheumatoid factor, and the mast cell disease.