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1.
J Med Case Rep ; 16(1): 268, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773682

RESUMO

BACKGROUND: Hereditary folate malabsorption-a rare disorder caused by impairment of the folate transporter-can develop into severe folate deficiency manifesting as megaloblastic anemia and occasionally thrombocytopenia. Reportedly, megaloblastic anemia can manifest with hemorrhagic episodes, possibly due to ineffective platelet production and platelet dysfunction. However, life-threatening hemorrhage events in hereditary folate malabsorption have not been well investigated. CASE PRESENTATION: A 3-month-old Japanese boy was transferred to our hospital due to thrombocytopenia and severe megaloblastic anemia. During a thorough examination of hematopoietic abnormalities, the patient suddenly went into cardiac arrest due to pulmonary hemorrhage. Although intravenous folate supplementation was started soon after the identification of folate deficiency, the patient died of circulatory defect and multiple organ failure. The cause of pulmonary hemorrhage, such as respiratory infection, could not be confirmed. Genetic investigation revealed a mutation in the SLC46A1 gene to be the cause of the hereditary folate malabsorption. CONCLUSION: We report an infantile case of hereditary folate malabsorption that progressed to lethal pulmonary hemorrhage before folate deficiency was identified. Clinicians should consider that megaloblastic anemia could lead to severe bleeding without warning, and that nutrient supplementation should be initiated as soon as possible.


Assuntos
Anemia Megaloblástica , Trombocitopenia , Anemia Megaloblástica/etiologia , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico , Hemorragia/etiologia , Humanos , Lactente , Síndromes de Malabsorção , Masculino , Transportador de Folato Acoplado a Próton/genética , Trombocitopenia/complicações
2.
J Epidemiol ; 31(4): 272-279, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32336698

RESUMO

BACKGROUND: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL±P) and cleft palate only (CP) in Japan. METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (<18.5 and ≥25 kg/m2), and non-use of a folic acid supplement during pregnancy for nonsyndromic CL±P and CP in babies. RESULTS: A total of 94,174 pairs of pregnant women and their single babies were included. Among them, there were 146 nonsyndromic CL±P cases and 41 nonsyndromic CP cases. The combined adjusted PAF for CL±P of the modifiable risk factors excluding maternal alcohol consumption was 34.3%. Only maternal alcohol consumption was not associated with CL±P risk. The adjusted PAFs for CL±P of psychological distress, maternal active and passive smoking, abnormal BMI, and non-use of a folic acid supplement were 1.4% (95% confidence interval [CI], -10.7 to 15.1%), 9.9% (95% CI, -7.0 to 26.9%), 10.8% (95% CI, -9.9 to 30.3%), 2.4% (95% CI, -7.5 to 14.0%), and 15.1% (95% CI, -17.8 to 41.0%), respectively. We could not obtain PAFs for CP due to the small sample size. CONCLUSIONS: We reported the population impact of the modifiable risk factors on CL±P, but not CP. This study might be useful in planning the primary prevention of CL±P.


Assuntos
Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Adulto , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Masculino , Gravidez , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
3.
BJU Int ; 99(6): 1495-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17428245

RESUMO

OBJECTIVE: To investigate whether changes in neuronal nitric oxide synthase (nNOS) protein expression and arginase activity are implicated in impairing the neurogenic cavernosal relaxation in aged rabbits, as NO is important in the neurogenic relaxation of corpus cavernosum during the erectile state. MATERIALS AND METHODS: Cavernosal specimens of young adult (3-6 months old) and aged (36-48 months old) rabbits were used for isometric tension experiments, Western blot analysis, cGMP determination and measurements of NOS and arginase activities. RESULTS: The neurogenic relaxation and cGMP production in response to electrical-field stimulation were significantly impaired in aged cavernosal specimens. Western blot analysis showed that nNOS protein was highly expressed in cavernosal specimens from young rabbits, but was undetectable or greatly decreased in old rabbits, with no change in overall NOS activity. Arginase activity in aged cavernosal specimens was significantly higher than in young rabbits. Supplementing with excess l-arginine, or giving S-(2-boronoethyl)-l-cysteine as an arginase inhibitor, significantly increased the neurogenic relaxation at lower frequencies only in the younger rabbits. CONCLUSION: These results suggest that impairment of neurogenic and NO-mediated relaxation in the aged corpus cavernosum possibly results from the down-regulation of nNOS protein. The reduced l-arginine bioavailability to nNOS due to accelerated arginase activity would lead to further impairment of neurogenic NO production, in concert with decreased nNOS protein expression.


Assuntos
Envelhecimento/fisiologia , Arginase/metabolismo , Disfunção Erétil/etiologia , Relaxamento Muscular/fisiologia , Óxido Nítrico Sintase Tipo I/metabolismo , Ereção Peniana/fisiologia , Animais , Western Blotting , GMP Cíclico/metabolismo , Masculino , Músculo Liso/fisiopatologia , Coelhos
4.
J Cardiovasc Pharmacol ; 48(1): 850-6, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16891914

RESUMO

In a preliminary experiment, we found that lavender essential oil relaxes vascular smooth muscle. Thus, the present experiments were designed to investigate the relaxation mechanism of linalyl acetate as the major ingredient of lavender essential oil in rabbit carotid artery specimens. Linalyl acetate produced sustained and progressive relaxation during the contraction caused by phenylephrine. The relaxation effect of linalyl acetate at a concentration near the EC50 was partially but significantly attenuated by nitroarginine as an inhibitor of nitric oxide synthase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one as an inhibitor of guanylyl cyclase, or by the denudation of endothelial cells. In specimens without endothelium, the phenylephrine-induced contraction and phosphorylation of myosin light chain (MLC) were significantly attenuated after the pretreatment with linalyl acetate. The relaxation caused by linalyl acetate in the endothelium-denuded specimens was clearly inhibited by calyculin A as an inhibitor of MLC phosphatase, although not by ML-9 as an inhibitor of MLC kinase. Furthermore, suppression of the phenylephrine-induced contraction and MLC phosphorylation with linalyl acetate was canceled by the pretreatment with calyculin A. These results suggest that linalyl acetate relaxes the vascular smooth muscle through partially activation of nitric oxide/cyclic guanosine monophosphate pathway, and partially MLC dephosphorylation via activating MLC phosphatase.


Assuntos
Monoterpenos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Cadeias Leves de Miosina/metabolismo , Óleos Voláteis/química , Óleos de Plantas/química , Vasodilatação/efeitos dos fármacos , Animais , Azepinas/farmacologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiologia , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Lavandula , Masculino , Toxinas Marinhas , Modelos Biológicos , Monoterpenos/química , Monoterpenos/isolamento & purificação , Músculo Liso Vascular/fisiologia , Quinase de Cadeia Leve de Miosina/antagonistas & inibidores , Quinase de Cadeia Leve de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve/antagonistas & inibidores , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Oxazóis/farmacologia , Fenilefrina/farmacologia , Fosforilação/efeitos dos fármacos , Coelhos , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia
5.
Vascul Pharmacol ; 44(4): 215-23, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16448858

RESUMO

We analyzed mechanisms decreasing hind-limb perfusion pressure (PP) with blackcurrant concentrate (BC) in the rat. The decrease in PP with BC was abolished by endothelial removal, nitroarginine plus tetraethylammonium, nitroarginine plus catalase or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one as an inhibitor of guanylyl cyclase and potassium channel(s), and accompanied by the increased cyclic GMP level. Partial but significant inhibition caused by KCl was observed during contraction. Authentic H2O2 decreased the PP in a sensitive manner to catalase and tetraethylammonium. The decrease in PP with BC in the presence of nitroarginine was significantly attenuated by diverse potassium channel blockers. Two delphinidins of 4 anthocyanins purified from BC definitely decreased the PP through similar mechanisms to BC. These results suggest that the decreased PP with BC is possibly mediated by endothelial NO and H2O2, and partially through the activation of diverse potassium channels, and that 2 delphinidins play a major role as active components of BC.


Assuntos
Músculo Esquelético/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ribes , Resistência Vascular , 4-Aminopiridina/farmacologia , Animais , Antocianinas/isolamento & purificação , Antocianinas/farmacologia , Catalase/farmacologia , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Frutas , Membro Posterior , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/enzimologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Perfusão , Extratos Vegetais/química , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Ratos , Ratos Sprague-Dawley
6.
J Urol ; 172(1): 360-4, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15201811

RESUMO

PURPOSE: We investigated the possible role of the endogenous nitric oxide (NO) synthase (NOS) inhibitors N-monomethyl-L-arginine (L-NMMA) and asymmetrical N, N-dimethyl-L-arginine (ADMA) in inhibiting urethral relaxation following estrogen supplementation in ovariectomized rabbits. MATERIALS AND METHODS: A total of 16 mature Japanese White female rabbits were divided into 2 groups. In the control group rabbits were sacrificed 2 weeks after bilateral ovariectomy. In the estrogen group estradiol was administered subcutaneously for 2 weeks with the aid of sustained release pellet from 2 weeks after ovariectomy until sacrifice. Isolated urethra was cut into transverse strips for functional study and processed to determine endogenous NOS inhibitors, NOS activity, dimethylarginine dimethylaminohydrolase (DDAH) activity as a metabolizing enzyme of endogenous NOS inhibitors and cyclic guanosine monophosphate production. RESULTS: Electrical field stimulation produced NO mediated and neurogenic relaxation of the urethral strip in the presence of guanethidine and atropine under contraction with phenylephrine. Relaxation was significantly decreased in the estrogen group and accompanied by decreased cyclic guanosine monophosphate production. Sodium nitroprusside induced relaxation was not different between the 2 groups. The content of L-NMMA plus ADMA in the urethra was significantly increased in the estrogen group. Ca dependent NOS activity in the urethra remained unaffected. DDAH activity was significantly lower in the estrogen group. CONCLUSIONS: Estrogen supplementation leads to decreased NO mediated and neurogenic urethral relaxation through the accumulation of L-NMMA and ADMA in the urethra. The accumulation of NOS inhibitors is possibly brought about by impaired DDAH activity.


Assuntos
Estradiol/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Uretra/efeitos dos fármacos , ômega-N-Metilarginina/fisiologia , Amidoidrolases/metabolismo , Animais , Peso Corporal , GMP Cíclico/análise , Preparações de Ação Retardada , Estimulação Elétrica , Estradiol/administração & dosagem , Feminino , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Tamanho do Órgão , Ovariectomia , Coelhos , Radioimunoensaio , Tela Subcutânea , Uretra/enzimologia
7.
J Urol ; 172(1): 369-73, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15201813

RESUMO

PURPOSE: Arginase shares L-arginine as a common substrate with nitric oxide (NO) synthase (NOS). We examined whether increased arginase activity is involved in impaired cavernous relaxation with aging in the rabbit. MATERIALS AND METHODS: Young adult (3 to 5 months old) and aged (36 to 48 months old) rabbits were used for the current experiments. Cavernous tissues obtained from the 2 groups were processed for isometric tension experiments, cyclic guanosine monophosphate determination, measurements of NOS and arginase activities, endogenous methylarginines and L-arginine. RESULTS: Carbachol (CCh) produced an endothelium dependent and NO mediated relaxation that was significantly impaired in aged cavernous specimens without change in sodium nitroprusside induced relaxation. Stimulated cyclic guanosine monophosphate production with CCh was significantly decreased in aged cavernous specimens. Ca dependent NOS was predominant in rabbit cavernous specimens. Ca dependent and independent NOS activities remained unchanged in the 2 groups. The tissue contents of N-monomethyl-L-arginine and asymmetric N,N-dimethyl-L-arginine as endogenous NOS inhibitors, symmetrical N,N'-dimethyl-L-arginine and L-arginine as a substrate of NOS were decreased in aged cavernous specimens. Arginase activity was significantly higher in aged cavernous specimens. Impaired CCh induced relaxation in aged cavernous specimens was normalized in the presence of N-hydroxy-L-arginine as an arginase inhibitor or by the supplementation of excess L-arginine. CONCLUSIONS: These results strongly suggest that impaired endothelium dependent and NO mediated cavernous relaxation with aging is due to decreased NO production, which would result from increased arginase activity and probably from decreased L-arginine content.


Assuntos
Envelhecimento/fisiologia , Arginase/metabolismo , Arginina/análogos & derivados , Contração Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Pênis/fisiologia , Animais , Arginina/metabolismo , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Endotélio Vascular/fisiologia , Masculino , Óxido Nítrico Sintase/metabolismo , Pênis/enzimologia , Coelhos , ômega-N-Metilarginina/metabolismo
8.
Ann Bot ; 92(3): 445-58, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12930730

RESUMO

Trimenia moorei (Oliv.) Philipson is an andromonoecious liane with >0.40 of the total flower buds maturing as bisexual flowers. Male and bisexual flowers are strongly scented with pollen, anther sacs and receptacle scars testing positively for volatile emissions. Scent analyses detect over 20 components. The major fatty acid derivative is 8-heptadecene, and 2-phenylethanol dominates the benzenoids. While hover-flies in the genera Melangyna and Triglyphus contact the stigma with their probosces, the stigma secretes no free-flowing, edible fluids. Copious pollen is the only edible reward consumed by hover-flies (Syprhidae), sawflies (Pergidae) and bees in the families Apidae, Colletidae and Halictidae. All these insects carried pollen of T. moorei on their heads, legs and thoraces and female bees in the genera Apis, Exoneura, Leioproctus and Lasioglossum stored pollen on their hind legs. Pollen traps also indicate that pollen is shed directly into the air, permitting wind pollination. When bisexual flower buds are bagged (isolated from insect foragers) on the liane then subjected to a series of hand-pollination experiments after perianth segments open, the structural analyses of pollen-carpel interactions indicate that T. moorei has a trichome-rich dry-type stigma with an early-acting self-incompatibility (SI) system. Bicellular pollen grains deposited on stigmas belonging to the same plant germinate but fail to penetrate intercellular spaces, while grains deposited following cross-pollination reach the ovule within 24 h. Fluorescence analyses of 76 carpels collected at random from unbagged (open-pollinated) flowers on five plants indicates that at least 64% of carpels are cross-pollinated in situ. Trimenia moorei is the first species within the ANITA group, and second within reilictual-basal angiosperm lineages, to exhibit stigmatic SI in combination with dry-type stigma and bicellular pollen, a condition once considered to be atypical for angiosperms as a whole but now known to be present in numerous taxa.


Assuntos
Flores/fisiologia , Magnoliopsida/fisiologia , Animais , Austrália , Fertilização/fisiologia , Frutas/crescimento & desenvolvimento , Insetos , Odorantes , Pólen/fisiologia , Volatilização , Vento
9.
Am J Physiol Regul Integr Comp Physiol ; 282(6): R1730-8, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12010755

RESUMO

We examined whether endogenous inhibitors of nitric oxide (NO) synthesis are involved in the impaired cavernosal relaxation with ischemia in rabbits. Two weeks after cavernosal ischemia caused by partial vessel occlusion, endothelium-dependent and electrical field stimulation (EFS)-induced neurogenic NO-mediated relaxations, but not sodium nitroprusside (SNP)-induced relaxation, were significantly impaired in the isolated corpus cavernosum. The Ca(2+)-dependent NO synthase (NOS) activity and the basal and stimulated cGMP productions with carbachol or EFS were significantly decreased after ischemia. Supplementation of excess L-arginine partially recovered both of the impaired relaxations. The contents of N(G)-monomethyl-L-arginine (L-NMMA) and asymmetric N(G), N(G)-dimethyl-L-arginine (ADMA) but not L-arginine and symmetric N(G),N'(G)-dimethyl-L-arginine (SDMA) were increased in the cavernosal tissues after ischemia. Authentic L-NMMA and ADMA but not SDMA concentration dependently inhibited both relaxations without affecting the relaxation produced by SNP in the control. Excess L-arginine abolished the inhibition with L-NMMA and ADMA. These results suggest that the impaired NO-mediated cavernosal relaxations after ischemia are closely related to the decreased NOS activity and the increased accumulation of L-NMMA and ADMA.


Assuntos
Arginina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Impotência Vasculogênica/tratamento farmacológico , Impotência Vasculogênica/fisiopatologia , Isquemia/fisiopatologia , Óxido Nítrico Sintase/antagonistas & inibidores , Pênis/fisiopatologia , Animais , Arginina/metabolismo , Arginina/farmacologia , Cálcio/metabolismo , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , GMP Cíclico/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estimulação Elétrica , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Artéria Ilíaca/fisiopatologia , Impotência Vasculogênica/etiologia , Técnicas In Vitro , Isquemia/complicações , Masculino , Óxido Nítrico Sintase/metabolismo , Pênis/irrigação sanguínea , Pênis/efeitos dos fármacos , Coelhos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , ômega-N-Metilarginina/metabolismo , ômega-N-Metilarginina/farmacologia
10.
Chem Pharm Bull (Tokyo) ; 50(4): 541-3, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11964006

RESUMO

A new lignan 1 was isolated together with the five known lignans 2-6 and four sesquiterpenes 7-10 from the seeds of Magnolia praecocissima. The structure of 1 was elucidated by analysis of spectroscopic data and chemical reaction. Furthermore, the absolute configurations of 1, 2, and 3 were determined by the modified Mosher's method.


Assuntos
Lignanas/isolamento & purificação , Magnoliaceae/química , Sesquiterpenos/isolamento & purificação , Acetilação , Cromatografia em Gel , Lignanas/química , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Sementes/química , Sesquiterpenos/química
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