RESUMO
BACKGROUND: The most significant problem of intra-arterial chemotherapy for advanced paranasal sinus carcinomas and residual cancers supplied by internal carotid artery (ICA) and involving the skull base is the lack of salvage therapies. OBJECTIVE: The objective of the study was to evaluate the usefulness of intra-arterial chemotherapy including ICA infusion for treating advanced paranasal sinus carcinomas, which have invaded the skull base. METHODS: Forty-six patients with advanced paranasal sinus carcinomas supplied by ICA were treated by intra-arterial chemotherapy using CDDP and sodium thiosulphate (STS) as a neutraliser of CDDP toxicity. After evaluating CT angiography, 150 mg m(-2) of CDDP was superselectively administered weekly to each feeding artery including ICA four times. RESULTS: The 10-year overall survival rate and progression-free survival rate were 70.7 and 60.2%, respectively. Compared with control group without infusing ICA, recurrences at anterior skullbase or anterior ethomoid sinus were significantly diminished. Of 32 patients in which the orbital apex had been invaded, 29 patients were treated with successful preservation of orbital contents. The CT angiography could efficiently determine all feeding arteries supplying the cancers. Consequently, chemotherapy could be administered on schedule, and side effects were minimal and acceptable. CONCLUSIONS: This new method has promising applications in the treatment of advanced paranasal sinus carcinomas involving the skull base.
Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias dos Seios Paranasais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-IdadeRESUMO
Fallow field biotopes that develop from abandoned rice fields are man-made wetlands that provide new habitats for various aquatic animals. Although consideration of such biotopes generally focuses on their positive aspects, this study evaluated the negative aspects of establishing fallow field biotopes with regard to mosquito breeding sites. To determine whether fallow field biotopes become breeding habitats for vector mosquitoes, we evaluated mosquito fauna in fallow field biotopes and adjacent rice fields. We found larvae of Anopheles lesteri, Anopheles sinensis and Culex tritaeniorhynchus (all: Diptera: Culicidae) in the biotopes. Although abundances of mosquito larvae in the biotopes and rice fields were statistically similar, mosquito abundances in rice fields increased dramatically in August when the water level reduced after the rainy season. The abundance and variety of the mosquitoes' natural predators were greater in biotopes than in rice fields because the former are a permanent and stable aquatic environment. A generalized linear mixed model showed a negative effect of predator diversity on mosquito larvae abundance in both habitats. Although fallow field biotopes become breeding habitats for vector mosquitoes, establishing biotopes from fallow fields in order to protect various aquatic animals, including mosquito insect predators, may help to control mosquito breeding.
Assuntos
Culicidae/fisiologia , Cadeia Alimentar , Insetos Vetores/fisiologia , Insetos/fisiologia , Agricultura , Animais , Culicidae/classificação , Culicidae/crescimento & desenvolvimento , Ecossistema , Insetos/classificação , Japão , Larva/classificação , Larva/fisiologia , Controle de Mosquitos , Oryza , Densidade Demográfica , Estações do AnoRESUMO
OBJECTIVE: Differentiated articular chondrocytes express a functional bisoform of the leptin receptor (LRb); however, leptin-LRb signaling in these cells is poorly understood. We hypothesized that leptin-LRb signaling in articular chondrocytes functions to modulate canonical Wnt signaling events by altering the expression of Frizzled (FZD) receptors. METHODS: Human chondrocyte cell lines and primary articular chondrocytes were grown in serum containing growth media for 24h, followed by a media change to Dulbecco's modified Eagle's medium (DMEM) containing 1% Nutridoma-SP to obtain a serum-deficient environment for 24h before treatment. Treatments included recombinant human leptin (10-100nM), recombinant human IL-6 (0.3-3nM), or recombinant human erythropoietin (Epo) (10mU/ml). Cells were harvested 30min-48h after treatment and whole cell lysates were analyzed using immunoblots or luciferase assays. RESULTS: Treatment of cells with leptin resulted in activation of Janus kinase 2 (JAK2) and subsequent phosphorylation of specific tyrosine residues on LRb, followed by dose- and time-dependent increases in the expression of Frizzled-1 (FZD1) and Frizzled-7 (FZD7). Leptin-mediated increases in the expression of FZD1 were blocked by pre-treatment with the protein synthesis inhibitor cycloheximide or the JAK2 inhibitor AG490. Experiments using a series of hybrid Epo extracellular domain-leptin intracellular domain receptors (ELR) harboring mutations of specific tyrosine residues in the cytoplasmic tail showed that increases in the expression of FZD1 were dependent on LRb-mediated phosphorylation of STAT3, but not ERK1/2 or STAT5. Leptin pre-treatment of chondrocytes prior to Wnt3a stimulation resulted in an increased magnitude of canonical Wnt signaling. CONCLUSION: These experiments show that leptin-LRb signaling in articular chondrocytes modulates expression of canonical Wnt signaling receptors and suggests that direct cross-talk between these pathways is important in determining chondrocyte homeostasis.
Assuntos
Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Receptores Frizzled/metabolismo , Janus Quinase 2/fisiologia , Fator de Transcrição STAT3/fisiologia , Idoso , Cartilagem Articular/citologia , Cartilagem Articular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Interleucina-6/farmacologia , Leptina/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Wnt/farmacologia , Proteínas Wnt/fisiologia , Proteína Wnt3 , Proteína Wnt3ARESUMO
Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism.
Assuntos
Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Prognatismo , Cefalometria , Seguimentos , Humanos , Má Oclusão Classe III de Angle/cirurgia , MandíbulaRESUMO
We reviewed 36 patients with endodermal cysts occurring at the craniocervical junction. They were aged between 3 and 66 years. Headache, motor weakness, and neck pain were commonly observed symptoms. Radiographically, T1-weighted magnetic resonance imaging of the tumours demonstrated a hypointense, isointense, or hyperintense signal according to the cystic content. In most cases, the cyst walls did not enhance after gadolinium administration. Histologically, the cysts were found to be lined by a single layer of epithelium. Histochemical and immunohistochemical studies showed that almost all were reactive to periodic acid schiff stain, epithelial membrane antigen, and carcino-embryonic antigen, but negative to glial fibrillary acidic protein. Mainly, the suboccipital approach with or without a laminectomy, or the trans-oral approach were selected for surgical excision of these tumours. In 17 of the 36 patients, total or gross total resections were performed, and subtotal resections were achieved in sixteen. Three patients developed recurrences.
Assuntos
Cistos do Sistema Nervoso Central/patologia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/patologia , Neoplasias da Coluna Vertebral/patologia , Adulto , Idoso , Vértebra Cervical Áxis/patologia , Vértebra Cervical Áxis/cirurgia , Cistos do Sistema Nervoso Central/fisiopatologia , Cistos do Sistema Nervoso Central/cirurgia , Atlas Cervical/patologia , Atlas Cervical/cirurgia , Pré-Escolar , Fossa Craniana Posterior/patologia , Fossa Craniana Posterior/cirurgia , Descompressão Cirúrgica/métodos , Endoderma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Procedimentos Neurocirúrgicos/normas , Osso Occipital/patologia , Osso Occipital/cirurgia , Neoplasias da Base do Crânio/fisiopatologia , Neoplasias da Base do Crânio/cirurgia , Canal Medular/patologia , Canal Medular/cirurgia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/fisiopatologia , Neoplasias da Coluna Vertebral/fisiopatologia , Neoplasias da Coluna Vertebral/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: 3D computed tomographic angiography (3DCTA) has been used recently for the evaluation of intracerebral aneurysms, but it is difficult to use this technique to visualize aneurysms near the base of the skull because of the presence of bone. Subtracted 3DCTA could replace digital subtraction angiography (DSA) for evaluation of aneurysms near the base of the skull if the 2 methods were to give similar results. The aim of this study was to compare the evaluation of aneurysms of the internal carotid artery (ICA) near the base of the skull by subtracted 3DCTA and DSA. METHODS: CTA and DSA were obtained in 25 patients with unruptured aneurysms of the ICA. To create subtracted 3DCTA images, we used a volume subtraction (VS) method, wherein nonenhanced volume data are subtracted from enhanced volume data. CTA and DSA were reviewed by 2 neuroradiologists who performed the detection and characterization of aneurysms of the ICA by using 2D multiplanar reformatted (MPR) and VS- and nonsubtracted (NS)-3DCTA images with volume rendering techniques. RESULTS: DSA detected 29 aneurysms in the 25 patients. VS-3DCTA detected all 29 aneurysms in the 25 patients and was equivalent to DSA for evaluating their characteristics (location, size, and direction). NS-3DCTA detected 19 (1 cavernous, 4 ophthalmic, 1 superior hypophyseal, 7 posterior communicating, and 6 anterior choroidal artery) of these 29 aneurysms, but it could not characterize ophthalmic and superior hypophyseal artery aneurysms because they were only partly visible on NS-3DCTA because of bony structures. 2D-MPR images detected all but the small aneurysms (24 of 29 detected). VS-3DCTA and 2D-MPR could visualize all branching arteries (ophthalmic, posterior communicating, and anterior choroidal) detected by DSA, but NS-3DCTA could not visualize ophthalmic arteries because of the presence of bony structures. CONCLUSION: VS-3DCTA can be used as an alternative to DSA for preoperative examination of aneurysms near the skull base, where it provides equivalent identification and characterization.
Assuntos
Aneurisma/diagnóstico por imagem , Angiografia Digital , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Angiografia Cerebral , Imageamento Tridimensional , Aneurisma Intracraniano/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnica de SubtraçãoRESUMO
We have studied the effects of dynein binding on the stability of microtubules in vitro, using Tetrahymena ciliary dynein and microtubules (three-cycled purified microtubules: 3 X-Mts and phosphocellulose-column purified microtubules: PC-Mts). To determine the relative stability of the microtubules, we first prepared the microtubules bound with dynein (Mts--dynein complex) and subjected the Mts-dynein complex to treatments that depolymerize the microtubules, such as dilution to below critical concentration of tubulin, calcium ions and lower temperature. Dark-field microscopy revealed that the microtubules in the Mts--dynein complex appeared intact under conditions which otherwise result in microtubule depolymerization. However, when dynein was dissociated from the Mts--dynein complex with addition of ATP, no microtubule was found in the specimens under the same conditions. That is, the microtubules in the Mts--dynein complex did not depolymerize upon dilution with the buffer solution to below critical concentration of tubulin. However, addition of ATP to the diluted specimen caused dynein to become separated from the Mts, resulting in complete depolymerization of the microtubules. Stability of the microtubules was also studied by the turbidity changes and was confirmed by the patterns of stained gel bands in electrophoresis. With the addition of calcium ion, the Mts--dynein complex decomposed into separate molecules dynein and tubulin. At the lower temperature of 0 degrees C, the 3 X-Mts--dynein complex was decomposed into dynein and tubulin, while the microtubules in the PC-Mts--dynein complex did not depolymerize. Although we have not yet studied the effects of cytoplasmic dynein binding on the microtubules, the results suggest that the stabilizing effect of dynein binding to the microtubules is one of the important functions of dynein in vivo.
Assuntos
Dineínas/metabolismo , Microtúbulos/metabolismo , Animais , Cálcio/farmacologia , Dineínas/química , Dineínas/isolamento & purificação , Microtúbulos/química , Microtúbulos/fisiologia , Ligação Proteica , Temperatura , Tetrahymena thermophila/química , Tubulina (Proteína)/isolamento & purificaçãoRESUMO
To characterize oestrus-related factors affecting the induction of and recovery from pyometra in bitches, 60 clinically healthy beagle bitches were used for induction of pyometra by inoculation of Escherichia coli into the uterus during oestrous and metoestrous stages. The animals were classified into the following six groups according to inoculation time: Days 1-10, 11-20, 21-30, 31-40, 41-50 and 51-60 after LH surge. The incidence of pyometra during the periods Days 11-20 and 21-30 after LH surge was 90.9% and 78.9% respectively, while that during Days 1-10 and 51-60 after LH surge was less than 20%, and the patterns of the incidence of pyometra and the serum progesterone levels were similar. There was no difference in the incidence of pyometra induced in bitches less than 5 years old compared to bitches over 6 years old. Oestrus in all of the bitches with pyometra induced by E. coli returned with or without PGF 2alpha treatment, unlike in bitches with spontaneous pyometra. The duration of the oestrous cycle in the non-treated and PGF 2alpha-treated groups was 231.4+/-55.2 days and 162.1+/-40.6 days (P < 0.001), respectively, and there was no difference in the rate of return of oestrus between the two groups. The conception rate in all of the bitches in which oestrus had returned was 81.8%. The above findings indicate that the period during which severe pyometra could be induced was limited to the early stage in metoestrus.
Assuntos
Doenças do Cão/microbiologia , Infecções por Escherichia coli/veterinária , Escherichia coli/crescimento & desenvolvimento , Estro/fisiologia , Doenças Uterinas/veterinária , Animais , Animais Recém-Nascidos , Dinoprosta/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Tamanho da Ninhada de Vivíparos , Hormônio Luteinizante/sangue , Masculino , Parassimpatolíticos/uso terapêutico , Gravidez , Progesterona/sangue , Pirrolidinas/uso terapêutico , Distribuição Aleatória , Doenças Uterinas/tratamento farmacológico , Doenças Uterinas/microbiologiaRESUMO
Probucol is suggested to have antioxidant properties. The direct scavenging action of probucol on hydroxyl radicals, superoxide and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were examined using electron spin resonance (ESR) spectrometry. Probucol scavenged DPPH radicals dose dependently but showed no effect on hydroxyl radicals and superoxide generated by Fenton reaction and by hypoxanthine-xanthine oxidase system, respectively. It inhibited the formation of thiobarbituric acid reactive substances (TBARS) in rat cortex homogenate induced by ascorbic acid and FeCl2 at low dose, but it increased TBARS formation at high doses. Probucol showed no effect on the carbon centered radicals. Iron injection into the rat cortex, which is an experimental model for traumatic epilepsy, increased TBARS level in the cortex, hippocampus, striatum and cerebellum, but pretreatment with probucol inhibited the increase in these brain parts except for the hippocampus. These results suggest that the antioxidant property of probucol is partly due to its free radical scavenging effect.
Assuntos
Bepridil/análogos & derivados , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Compostos Férricos/toxicidade , Sequestradores de Radicais Livres , Picratos , Probucol/farmacologia , Animais , Bepridil/toxicidade , Compostos de Bifenilo , Encéfalo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Cloretos , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/metabolismo , Radicais Livres/farmacologia , Radical Hidroxila/metabolismo , Radical Hidroxila/farmacologia , Masculino , Córtex Motor/efeitos dos fármacos , Córtex Motor/metabolismo , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley , Superóxidos/metabolismo , Superóxidos/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
A novel ammonium ionophore, which exhibits superior NH4+ selectivity compared with that of the natural antibiotic nonactin, was successfully designed and synthesized based on a 19-membered crown compound (TD19C6) having three decalino subunits in the macrocyclic system. This bulky decalino subunit is effective for (1) increasing the structural rigidity of the cyclic compound, (2) introducing the "block-wall effect", which prevents forming a complex with a large ion, and (3) increasing the lipophilicity of the ionophore molecule. In the ammonium ionophore design, the first factor contributes to increasing the NH4+ selectivity relative to smaller ions such as Li+, Na+, or even the closest size, K+, and the second factor increases the NH4+ selectivity over larger ions such as Rb+ and Cs+. The X-ray structural analysis proved that TD19C6 forms a size-fit complexwith NH4+ in its crown ring cavity. As an application of this ionophore, an ion sensor (ion-selective electrode) was prepared, which exhibited NH4+ to K+ and Na+ selectivity of 10 and 3,000 times, respectively. This electrode showed a better performance compared to the electrode based on nonactin, which is the only ammonium ionophore presently used in practical applications.
RESUMO
Mating status markedly affected the lifespan of Drosophila virilis flies but the effects of virginity on lifespan were different between the sexes. In all cases lengthening of female lifespan and shortening of male lifespan were observed as an effect of virginity. Lifespan was also affected either by the population density or by the sex ratio per culture. At a sex ratio (proportion of females) of 0.5, lifespan was constant in both sexes irrespective of the population density and females lived significantly longer than males. At high (0.9) and low (0.1) sex ratios mean lifespan did not differ between sexes, but it was longer at high sex ratios than at low ones. A negative correlation between mean lifespan and the number of males per vial was revealed for both sexes. Effects of mating on egg-laying activity were also analyzed. Although the number of eggs laid during the first 20 days period after eclosion was greater in mated females than in unmated virgin females, lifetime egg production was not always larger in the former than in the latter. No particular relationship between egg-laying activity and female lifespan was proven. The lifespan of D. virillis flies seemed to be determined by complex interactions between both sexes, in which the sexual activity of males may play the most important role.
Assuntos
Drosophila/fisiologia , Animais , Feminino , Longevidade , Masculino , Oviposição , Densidade Demográfica , Reprodução , Fatores Sexuais , Especificidade da EspécieRESUMO
In the TK strain of Drosophila virilis, age-associated changes in reproductive activities (copulating activity and fertility in males and egg-laying activity in females) and lifespan were examined in individual flies. The mean lifespan of individually aged flies was about 11 weeks for both males and females. Copulating activity was maximum in two-week old males, then decreased gradually and finally ended at the age of 13 weeks at which about half of males were still surviving. Females also had a peak in egg-laying activity at the age of two weeks while no eggs were laid by females older than ten weeks, although more than half of females were alive at the stage. Analyses of the relationship between reproductive activity and lifespan of individual flies revealed that shorter lived males exhibited a higher copulating activity in the early stage of their lives than longer lived males. In males whose lifespan was less than ten weeks the reproductive period increased with the lifespan while the post-reproductive period was almost constant (one to two weeks). In males living longer than ten weeks, the reproductive period remained constant (about eight weeks) while the post-reproductive period increased in parallel with the total lifespan. Similar tendencies were also observed in the egg-laying activity of female flies.
Assuntos
Envelhecimento , Drosophila/fisiologia , Animais , Feminino , Longevidade , Masculino , ReproduçãoRESUMO
We report on a boy with Rieger syndrome, who had an apparently balanced reciprocal translocation between chromosomes 1 and 4. The clinical manifestations of this patient were characterized by irregular shaped pupils with a prominent Schwalbe line and an umbilical hernia. On cytogenetic studies, he was found to have a de novo reciprocal translocation 46,XY,t(1;4) (q23.1;q25), without visible deletion. His parents had normal chromosomes. A review of both cytogenetic and genetic linkage analyses with Rieger syndrome showed that chromosome 4q was involved. This and other previous reports suggested that the gene for Rieger syndrome is mapped to the 4q25-->4q26 segment adjoining the breakpoint.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 4 , Anormalidades do Olho/genética , Translocação Genética , Adulto , Feminino , Genes Dominantes , Hérnia Umbilical/genética , Humanos , Lactente , Cariotipagem , Masculino , SíndromeRESUMO
To evaluate the prevalence of dihydropyrimidinuria (DHPuria), we analyzed urine samples from 21,200 healthy Japanese infants, and found two cases of DHPuria without clinical symptoms. Based on this result, we estimated the prevalence to be approximately 1/10,000 births in Japan. In addition, we analyzed pyrimidine catabolism on a previously reported family with an adult DHPuria case. We newly identified the sister of the propositus as the second case of DHPuria in this family, because she excreted large amounts of dihydrouracil and dihydrothymine. The parents and the child of the propositus showed slight increases of dihydrouracil and dihydrothymine. This is the first family with 2 cases of DHPuria, indicating that DHPuria is an inherited condition. To determine the inheritance of DHPuria in this family and to examine the risk of 5-fluorouracil (5-FU) toxicity, a uracil loading test was performed on the parents. Urinary dihydrouracil concentrations in the parents after the loading were several times higher than those in normal control persons, the finding being consistent with DHPuria heterozygotes. This, along with data on the propositus, his sister, and his child, indicates that DHPuria is an autosomal recessive condition. In addition, DHPuria homozygotes may have a high risk of 5-FU toxicity, while the risk is relatively low in heterozygotes.
Assuntos
Amidoidrolases/deficiência , Fluoruracila/efeitos adversos , Genes Recessivos , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Pirimidinas/urina , Adulto , Criança , Pré-Escolar , Feminino , Homozigoto , Humanos , Lactente , Japão/epidemiologia , Masculino , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/urina , Núcleo Familiar , Prevalência , Pirimidinas/metabolismo , Risco , Timina/análogos & derivados , Timina/urina , Uracila/análogos & derivados , Uracila/sangue , Uracila/urinaRESUMO
To clarify the metabolic pathway of guanidinosuccinic acid (GSA), we investigated the relationship between GSA synthesis and the urea cycle. In isolated rat hepatocytes, GSA formation increased as urea concentration was raised; the effect of urea was not modified by the addition of ammonium chloride. Other urea cycle intermediates, including arginine and cyanate, a degradation product of urea, failed to stimulate GSA synthesis. Ornithine and arginine, which stimulate urea synthesis, strongly inhibited urea-stimulated GSA synthesis in the presence of 10 mM ammonium chloride, but the inhibitory effect of ornithine was not observed when ammonium chloride was not present. Citrulline (5 mM) strongly inhibited urea-stimulated GSA synthesis with or without ammonium chloride. D,L-norvaline, which inhibits urea cycle enzymes, strongly inhibited GSA synthesis. Following urea injection, hepatic GSA levels also increased in vivo, but there was little change in hepatic arginine. However, the addition of ornithine or D,L-norvaline inhibited the production of hepatic GSA, although arginine was increased substantially. These results indicate that GSA synthesis occurs in rat hepatocytes and is stimulated by urea. The data also suggest that the urea cycle enzymes catalyze some of the biochemical reactions in the GSA synthetic pathway.
Assuntos
Guanidinas/biossíntese , Fígado/metabolismo , Succinatos/biossíntese , Aminoácidos/metabolismo , Cloreto de Amônio/farmacologia , Animais , Arginina/farmacologia , Citrulina/farmacologia , Guanidinas/antagonistas & inibidores , Técnicas In Vitro , Fígado/citologia , Masculino , Ornitina/farmacologia , Ratos , Ratos Endogâmicos , Succinatos/antagonistas & inibidores , Ureia/biossíntese , Ureia/farmacologia , Valina/farmacologiaRESUMO
BACKGROUND: We propose that reactive oxygen and argininosuccinic acid (ASA) form guanidinosuccinic acid (GSA). An alternative to this hypothesis is the so-called guanidine cycle, which consists of a series of hydroxyurea derivatives that serve as intermediates in a pathway leading from urea to GSA. We compare the role of the guanidine cycle to that of nitric oxide (NO) in the synthesis of GSA. METHODS: The members of the guanidine cycle (hydroxyurea, hydroxylamine plus homoserine, L-canaline, and L-canavanine) were incubated with isolated rat hepatocytes. The known NO donors, NOR-2, NOC-7, and SIN-1, were incubated with ASA in vitro. Ornithine, arginine, or citrulline, which increase arginine, a precursor of NO, were incubated with isolated rat hepatocytes. GSA was determined by high-performance liquid chromatography. RESULTS: None of guanidine cycle members except for urea formed GSA. SIN-1, which generates superoxide and NO formed GSA, but other simple NO donors, did not. Both carboxy-PTIO, a scavenger of NO, and dimethyl sulfoxide, a hydroxyl radical scavenger, completely inhibited GSA synthesis by SIN-1. GSA formation by SIN-1 reached a maximum at 0.5 mmol/L and decreased at higher concentrations. GSA synthesis, stimulated by urea in isolated hepatocytes, was inhibited by ornithine, arginine, or citrulline with ammonia, but not by ornithine without ammonia, where arginine production is limited. CONCLUSION: GSA is formed from ASA and the hydroxyl radical. When arginine increased in hepatocytes, GSA synthesis decreased. These data suggest that increased NO, which results from high concentrations of arginine, or SIN-1 scavenges the hydroxyl radical. This may explain the decreased GSA synthesis in inborn errors of the urea cycle where ASA is decreased, and also the diminished GSA excretion in arginemia.
Assuntos
Guanidinas/metabolismo , Óxido Nítrico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Succinatos/metabolismo , Animais , Ácido Argininossuccínico/metabolismo , Guanidina/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Técnicas In Vitro , Masculino , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Doadores de Óxido Nítrico/farmacologia , Ratos , Ratos Wistar , Ureia/metabolismoRESUMO
The aim of this study was to determine the phenotypic modulation in mesangial cells of glomeruli damaged by hypertension. Salt-loaded stroke-prone spontaneously hypertensive rats were untreated or treated with a calcium antagonist, manidipine (2 mg/kg/day) for eight weeks. In normotensive Wistar-Kyoto rats, alpha-smooth muscle actin was not expressed in any glomerular cells and a non-muscle myosin heavy chain isoform, SMemb, was slightly expressed in glomerular visceral epithelial cells. In the untreated hypertensive rats, the glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared. Notably, alpha-smooth muscle actin-positive fibroblast-like cells appeared in the interstitium, especially around the Bowman's capsules. Manidipine ameliorated the glomerulosclerosis and reduced the expression of alpha-smooth muscle actin in mesangial cells. In conclusion, the mesangial cells changed their phenotypes and expressed alpha-smooth muscle actin and SMemb in the glomeruli during the development of hypertensive renal damage. These phenotypically changed mesangial cells are considered to be activated and to produce various kinds of cytokines and extracellular matrix, which leads to glomerulosclerosis. Manidipine attenuated the glomerular damage and the phenotypic changes. The functional relevance of phenotypic changes in these cells should be elucidated in future studies.
Assuntos
Actinas/biossíntese , Hipertensão/patologia , Glomérulos Renais/patologia , Músculo Liso/metabolismo , Miosinas/biossíntese , Animais , Pressão Sanguínea/fisiologia , Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/metabolismo , Matriz Extracelular/metabolismo , Mesângio Glomerular/metabolismo , Hipertensão/genética , Hipertensão/metabolismo , Imuno-Histoquímica , Glomérulos Renais/metabolismo , Masculino , Fenótipo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
The pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment were compared with those in healthy volunteers, and the factors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plasma concentration of tamsulosin was measured by a combination of equilibrium dialysis and liquid chromatography tandem mass spectrometry methods to examine the effect of protein binding on the pharmacokinetics of tamsulosin. Mean values for maximum concentration (Cmax) and area under the concentration-time curve (AUC) of total drug (Cmax,t and AUC1) in patients with renal impairment were 73% and 211% greater, respectively, than those in healthy volunteers. Mean Cmax and AUC of unbound drug (Cmax,u and AUCu), however, were almost the same in the two groups. A high correlation was found between alpha 1-acid glycoprotein (alpha 1-AGP) concentration and AUCt, but no correlation was found between alpha 1-AGP concentration and AUCu,0-36) or between creatinine clearance (ClCR) and AUCu,0-36). These results show that in patients with renal impairment, the pharmacokinetics of tamsulosin are affected by the change in protein binding that is associated with alteration of plasma alpha 1-AGP concentration, but are not largely affected by the decrease in the renal excretion. Although total tamsulosin levels increased as plasma protein binding increased, unbound tamsulosin levels (which are directly associated with the pharmacologic effects) remained unchanged in these patients.
Assuntos
Antagonistas Adrenérgicos alfa/farmacocinética , Nefropatias/metabolismo , Orosomucoide/metabolismo , Sulfonamidas/farmacocinética , Antagonistas Adrenérgicos alfa/sangue , Idoso , Proteínas Sanguíneas/metabolismo , Interações Medicamentosas , Humanos , Nefropatias/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Valores de Referência , Sulfonamidas/sangue , TansulosinaRESUMO
A papilloma in the renal pelvis of a five-year-old girl is reported. The transitional cell tumors of the renal pelvis in the pediatric age group are reviewed, and this is found to be the first case of a benign papilloma in childhood. We believe this pathologic entity should be included in the differential diagnosis of hematuria in a child.
Assuntos
Neoplasias Renais/diagnóstico , Papiloma/diagnóstico , Pré-Escolar , Feminino , Hematúria/etiologia , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Pelve Renal/cirurgia , Papiloma/complicações , Papiloma/cirurgiaRESUMO
The antithrombotic effect of a synthetic symmetrical triglyceride having eicosapentaenoic acid (EPA) at positions 1 and 3, and gamma-linolenic acid (GLA) at position 2 was investigated. Administration of the triglyceride significantly increased thrombus formation time and thrombotic occlusion time induced by light irradiation and a fluorescent dye in guinea pigs after 14 days administration compared to that of soybean oil. The antithrombotic effect of the triglyceride was similar to that of EPA ethyl ester. Administration of the triglyceride increased GLA, dihomo-gamma-linolenic acid (DGLA) and EPA contents in plasma and the liver, and the ratio of DGLA to arachidonic acid. These results might be responsible for this antithrombotic effect.