RESUMO
Over 90% of iron deficiency anemia cases are due to iron deficiency associated with depletion of stored iron or inadequate intake. Parenteral iron supplementation is an important part of the management of anemia, and some kinds of intravenous iron are used. However, few studies have evaluated the clinical efficacy of these drugs. The purpose of this study was to compare and assess the clinical efficacy of two types of intravenous iron injection, saccharated ferric oxide (SFO) and cideferron (CF). Medical records were obtained for 91 unrelated Japanese anemia patients treated with SFO (n = 37) or CF (n = 54) from May 2005 to May 2010 at Gunma University Hospital. Patients treated with blood transfusion, erythropoietin or oral iron were excluded. Hemoglobin (Hb) values measured on day 0, 7 and 14 were used to assess the efficacy of intravenous irons. A significant increase was observed in the mean Hb value by day 14 of administration in both the CF group and SFO group, and the mean Hb increase due to administration of CF for 7 days was comparable to that of SFO for 14 days. Age and sex did not affect improvement of Hb value. CF is fast acting and highly effective compared with SFO for the treatment of iron deficiency anemia. The use of CF may shorten a therapeutic period for iron deficiency anemia, and CF may be feasible for reducing the hospitalization period.
Assuntos
Anemia Hipocrômica/tratamento farmacológico , Coloides/uso terapêutico , Meios de Contraste/uso terapêutico , Compostos Férricos/uso terapêutico , Ácido Glucárico/uso terapêutico , Ferro/uso terapêutico , Idoso , Envelhecimento/fisiologia , Povo Asiático , Coloides/administração & dosagem , Meios de Contraste/administração & dosagem , Feminino , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado , Ácido Glucárico/administração & dosagem , Hemoglobinas/análise , Hemoglobinas/metabolismo , Humanos , Injeções Intravenosas , Ferro/administração & dosagem , Masculino , Pessoa de Meia-Idade , Caracteres SexuaisRESUMO
The effects of rosiglitazone or pioglitazone (thiazolidinediones, TZDs) on estrogen production and aromatase activity in human ovarian cells were examined. Human granulosa cells were incubated in the tissue culture medium supplemented with androstenedione or testosterone, with or without insulin, TZDs, or type 1 17ß-hydroxysteroid-dehydrogenase (17ß-HSD) inhibitor. Estrogen concentrations in the conditioned medium, aromatase mRNA and protein expression in the cells and androgen substrate binding to aromatase were measured. With androstenedione as substrate, rosiglitazone or pioglitazone inhibited estrone production by up to 22% (p<0.012) while type 1 17ß-HSD inhibitor enhanced this effect of rosiglitazone or pioglitazone by 37% (p<0.001) and by 67% (p<0.001), respectively. With testosterone as substrate, rosiglitazone or pioglitazone inhibited estradiol production by 32% (p<0.001). With (3)H-testosterone as substrate, rosiglitazone or pioglitazone inhibited the (3)H-tritiated water release by the cultured cells by 45% and 35%, respectively, thus directly demonstrating inhibition of aromatase. Rosiglitazone or pioglitazone, however, had no significant effect on aromatase mRNA or protein expression. Rosiglitazone or pioglitazone inhibited (125)I-androstenedione and (125)I-testosterone binding to aromatase by 38% (p<0.001). It was concluded that rosiglitazone or pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.
Assuntos
Androgênios/metabolismo , Aromatase/metabolismo , Regulação para Baixo/efeitos dos fármacos , Estrogênios/biossíntese , Células da Granulosa/metabolismo , Tiazolidinedionas/farmacologia , Aromatase/genética , Células Cultivadas , Estrona/biossíntese , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/enzimologia , Humanos , Pioglitazona , Ligação Proteica/efeitos dos fármacos , RosiglitazonaRESUMO
Vitamin D Receptor (VDR) is expressed in both animal and human ovarian tissue, however, the role of vitamin D in human ovarian steroidogenesis is unknown. Cultured human ovarian cells were incubated in tissue culture medium supplemented with appropriate substrates, with or without 50 pM-150 pM or 50 nM-150 nM of 1,25-(OH)2D3, and in the presence or absence of insulin. Progesterone, testosterone, estrone, estradiol, and IGFBP-1 concentrations in conditioned tissue culture medium were measured. Vitamin D receptor was present in human ovarian cells. 1,25-(OH)2D3 stimulated progesterone production by 13% (p<0.001), estradiol production by 9% (p<0.02), and estrone production by 21% (p<0.002). Insulin and 1,25-(OH)2D3 acted synergistically to increase estradiol production by 60% (p<0.005). 1,25-(OH)2D3 alone stimulated IGFBP-1 production by 24% (p<0.001), however, in the presence of insulin, 1,25-(OH)2D3 enhanced insulin-induced inhibition of IGFBP-1 production by 13% (p<0.009). Vitamin D stimulates ovarian steroidogenesis and IGFBP-1 production in human ovarian cells likely acting via vitamin D receptor. Insulin and vitamin D synergistically stimulate estradiol production. Vitamin D also enhances inhibitory effect of insulin on IGFBP-1 production.
Assuntos
Calcitriol/farmacologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Ovário/citologia , Ovário/metabolismo , Esteroides/biossíntese , Sinergismo Farmacológico , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Humanos , Insulina/farmacologia , Ovário/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismoRESUMO
Peripheral nerve injury results in axonal degeneration and in phenotypic changes of the surrounding Schwann cells, whose presence is critical for nerve regeneration. To identify genes induced after nerve injury in Schwann cells, we developed a strategy that included differential screening of a subtractive library enriched for cDNAs expressed in injured nerve, sequence analysis, and expression profiling. By using real time quantitative reverse transcriptase-polymerase chain reaction, we found that injury-induced genes could be categorized into four temporal expression patterns. Among the clones we identified were a number that were homologous only to expressed sequence tags in the data base. These were stratified based on their expression profile, presence of identifiable sequence motifs, homologies to other proteins, and evolutionary conservation. We chose one representative gene, nin283, to analyze in detail. The nin283 gene encodes a 227-residue protein containing both a zinc finger and a RING finger motif. nin283 is highly expressed in the central nervous system, particularly in the developing cortical plate in embryos. It is also expressed in peripheral ganglia and is induced by nerve growth factor in PC12 cells. Subcellular localization analysis demonstrated that Nin283 is located in the endosome/lysosome compartment, suggesting that it may participate in ubiquitin-mediated protein modification.
Assuntos
Neurônios/metabolismo , Neurônios/fisiologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Células Cultivadas , DNA Complementar/metabolismo , Escherichia coli/metabolismo , Etiquetas de Sequências Expressas , Biblioteca Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Dados de Sequência Molecular , Fator de Crescimento Neural/metabolismo , Hibridização de Ácido Nucleico , Células PC12 , Peptídeos/química , Fenótipo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células de Schwann/metabolismo , Homologia de Sequência de Aminoácidos , Fatores de Tempo , Transfecção , Ubiquitinas/metabolismoRESUMO
We examined the fetal circulatory responses to maternal blood loss in pregnant women during the third trimester. Seven healthy women with placenta previa and singleton pregnancies underwent phlebotomies in an autologous donation program. Four hundred milliliters of blood was collected within 15 min at 34 and 35 weeks of gestation. Continuous electric recordings of fetal heart rate were performed during the first blood collection, and the maternal uterine artery (UtA), umbilical artery (UmA) and fetal middle cerebral artery (MCA) Doppler velocity waveforms were recorded before, immediately after and 24 h after the second collection in each patient. The average fetal heart rate, maternal UtA and UmA pulsatility indices did not change measurably during or after maternal blood collections. However, the average fetal MCA pulsatility index decreased significantly 24 h after maternal blood loss. The observation of a decrease in fetal MCA pulsatility index may indicate delayed fetal asphyxia following mild maternal hemorrhage.
Assuntos
Transfusão de Sangue Autóloga , Feto/irrigação sanguínea , Idade Gestacional , Flebotomia/efeitos adversos , Adulto , Artérias , Feminino , Frequência Cardíaca Fetal , Humanos , Concentração de Íons de Hidrogênio , Fluxometria por Laser-Doppler , Artéria Cerebral Média/embriologia , Artéria Cerebral Média/fisiologia , Placenta Prévia/terapia , Gravidez , Terceiro Trimestre da Gravidez , Fluxo Pulsátil , Artérias Umbilicais/fisiologia , Útero/irrigação sanguíneaRESUMO
Aldosteronism is a rare complication of pregnancy. We report a case of a 26-year-old woman who became pregnant soon after a diagnosis of primary aldosteronism due to left adrenal adenoma was made. Only oral potassium supplementation was required in addition to routine prenatal care until 36 weeks' gestation. Subsequently, antihypertensive medication was needed to control elevated blood pressure. A healthy male infant was delivered by cesarean section because of abruptio placentae. The postoperative course was uneventful. Left adrenalectomy was conducted eight months after delivery under laparoscopic visualization. In this case report, we discuss management of aldosteronism in pregnancy and review the literature.
Assuntos
Hiperaldosteronismo , Complicações na Gravidez , Descolamento Prematuro da Placenta , Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Adrenalectomia , Adulto , Cesárea , Feminino , Humanos , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/terapia , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Recém-Nascido , Laparoscopia , Masculino , Potássio na Dieta/administração & dosagem , Gravidez , Resultado da GravidezAssuntos
Carnitina/uso terapêutico , Mutação , RNA de Transferência de Leucina/genética , Diálise Renal , Adulto , Carnitina/deficiência , DNA Mitocondrial/genética , DNA Ribossômico/genética , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/terapia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologiaRESUMO
We studied the effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal lesions in rats in comparison with those of omeprazole. TU-199 inhibited hog gastric H+, K(+)-ATPase activity and its potency was almost equal to that of omeprazole (IC50 = 6.2 and 4.2 microM, respectively). In vivo, TU-199 inhibited basal gastric acid secretion in pylorus-ligated rats in a dose-dependent manner (ED50 = 4.2 mg/kg p.o.). In gastric fistula rats. TU-199 (2.5 and 5 mg/kg i.d.) also inhibited gastric acid secretion stimulated by histamine, carbachol or tetragastrin. Furthermore, TU-199 prevented the formation of water-immersion restraint stress-, pylorus ligation- and indomethacin-induced gastric lesions, and mepirizole-induced duodenal ulcer in rats. These antisecretory and antiulcer effects of TU-199 were 2-4 times more potent than those of omeprazole. The results demonstrate that TU-199 potently inhibits the acid secretion and formation of ulcers in various experimental rat models via an inhibition of H+, K(+)-ATPase. These findings suggest that TU-199 may have a beneficial effect against peptic ulcer disease in humans.
Assuntos
Antiulcerosos/uso terapêutico , Ácido Gástrico/metabolismo , Imidazóis/farmacologia , Omeprazol/uso terapêutico , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons , Piridinas/farmacologia , 2-Piridinilmetilsulfinilbenzimidazóis , Animais , Avaliação Pré-Clínica de Medicamentos , Imidazóis/uso terapêutico , Masculino , Úlcera Péptica/metabolismo , Piridinas/uso terapêutico , Ratos , Ratos Sprague-DawleyRESUMO
We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium. Although pteleprenine (0.1-1 microM) had no effect on the contraction of the ileum induced by acetylcholine at 10 microM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0.1-10 microM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 microM. From Schild analysis the pA2 of pteleprenine on the guinea-pig ileum was found to be 6.6. The contraction of the ileum induced by 10 microM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine receptors, was concentration-dependently suppressed by 10 nM-10 microM pteleprenine. In contrast, 0.1-10 microM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.
Assuntos
Dioxóis/farmacologia , Átrios do Coração/efeitos dos fármacos , Íleo/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Antagonistas Nicotínicos/farmacologia , Plantas Medicinais , Quinolonas/farmacologia , Acetilcolina/farmacologia , Animais , Iodeto de Dimetilfenilpiperazina/farmacologia , Cães , Relação Dose-Resposta a Droga , Feminino , Cobaias , Átrios do Coração/metabolismo , Íleo/metabolismo , Japão , Masculino , Contração Muscular/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologiaRESUMO
The relative contents (RCs) of elements in the femoral arteries as well as the thoracic aorta, coronary, basilar, and radial arteries from 26 subjects within the age range between 55 and 92 yr old, were analyzed by inductively coupled plasma atomic emission spectrometry. The RCs of calcium and phosphorus in the femoral arteries started to increase before the age of 60 yr. The RCs of magnesium increased after the age of 70 yr. However, the RCs of sulfur did not change significantly within the age range between 55 and 92 yr. With regard to localization of the mineral accumulations in the femoral arterial wall, it was found that the accumulations of calcium and phosphorus occurred only in the tunica media, only in the tunica intima, or in both the tunica media and the tunica intima. The manner of accumulation of calcium and phosphorus in the femoral arterial wall was different from that in the aortic wall. The average RCs of calcium in the 26 specimens were the highest in the femoral artery, followed in descending order by the thoracic aorta, coronary, basilar, and radial arteries. The average RCs of phosphorus were highest in the thoracic aorta, followed by the coronary, femoral, basilar, and radial arteries. It is noted that the accumulation of mineral elements never occurred uniformly in all the arteries.
Assuntos
Artéria Femoral/metabolismo , Oligoelementos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Alumínio/análise , Alumínio/metabolismo , Aorta Torácica/química , Aorta Torácica/metabolismo , Artéria Basilar/química , Artéria Basilar/metabolismo , Cálcio/análise , Cálcio/metabolismo , Vasos Coronários/química , Vasos Coronários/metabolismo , Feminino , Artéria Femoral/química , Humanos , Ferro/análise , Ferro/metabolismo , Magnésio/análise , Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Fósforo/análise , Fósforo/metabolismo , Artéria Radial/química , Artéria Radial/metabolismo , Silício/análise , Silício/metabolismo , Sódio/análise , Sódio/metabolismo , Espectrometria por Raios X , Enxofre/análise , Enxofre/metabolismo , Oligoelementos/análise , Zinco/análise , Zinco/metabolismoRESUMO
To elucidate age-related changes of mineral contents in human bones, element contents of human vertebrae and auditory ossicles were determined by inductively coupled plasma atomic-emission spectrometry. The cervical, thoracic, and lumbar vertebrae were removed from 12 vertebral columns. The mallei of auditory ossicle were removed from 27 cadavers. It was found that average relative contents (RCs) of calcium and phosphorus in cervical, thoracic, and lumbar vertebrae remained almost constant within ages ranging from 46 to 99 y. In addition, it was found that the RCs of calcium and phosphorus in men's and women's mallei remained constant within ages ranging from 40 to 98 yr. These results support the view that there is no significant age-dependent change of mineral contents in human bones.
Assuntos
Envelhecimento/metabolismo , Cálcio/metabolismo , Ossículos da Orelha/metabolismo , Fósforo/metabolismo , Coluna Vertebral/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The relative contents (RCs) of mineral elements in aortae and cerebral arteries from 23 subjects, with ages ranging between 45 and 99 yr, were analyzed by inductively coupled plasma atomic emission spectrometry. The RCs of calcium, phosphorus, and magnesium in the aortae increased markedly after the age of 70. While the RC of sulfur in aortae decreased gradually after that age. It was found that accumulation of calcium and phosphorus occurred primarily in the tunica media of aorta, and secondarily in the tunica intima. Furthermore, the RCs of calcium, phosphorus, and magnesium in cerebral arteries increased markedly after the age of 70, whereas the RC of sulfur in cerebral arteries decreased after age 70. It was found that accumulation of calcium and phosphorus in the cerebral arteries were 30 and 60%, respectively, lower than those in the aortae with ages ranging between 45 and 99 yr.
Assuntos
Envelhecimento/patologia , Aorta Torácica/metabolismo , Artérias Cerebrais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Aorta Torácica/patologia , Cálcio/metabolismo , Artérias Cerebrais/patologia , Feminino , Humanos , Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Fósforo/metabolismo , Espectrometria por Raios XRESUMO
We investigated the long-term changes in the gerbil brain following three episodes of 2-min forebrain ischemia at 1-h intervals in comparison with a 6-min period of ischemia. The animals were sacrificed after 1 month and 6 months. Following either ischemic insult, the hippocampal CA1 region showed a loss of pyramidal neurons together with a diffuse calcium accumulation as shown by alizarin red S staining. Three 2-min ischemic insults additionally produced neuronal damage in the striatum and thalamus. The thalamic damage was accompanied by an accumulation of small calcium granules after 1 month and large calcium concretions after 6 months. Calcium staining in the striatum was weak. Thus, the thalamic neuronal damage was accompanied by an active process of calcification, which has not been described in experimental cerebral ischemia models. The observations show that repeated ischemic insults produce different long-term effects in different brain regions.
Assuntos
Isquemia Encefálica/metabolismo , Cálcio/metabolismo , Tálamo/metabolismo , Animais , Isquemia Encefálica/patologia , Gerbillinae , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Imuno-Histoquímica , Masculino , Tálamo/patologiaRESUMO
Chronological changes of adenosine A1 receptor binding of the rat brain were determined by in vitro [3H]cyclohexyladenosine (CHA) autoradiography after 90 min of middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. One day after the ischaemia, [3H]CHA binding sites decreased significantly in the cerebral cortex (p < 0.05) and lateral segment of the caudate putamen (p < 0.01), both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischaemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischaemic insult, a significant decrease of [3H]CHA binding sites was first detected in the ipsilateral thalamus and the substantia nigra, both areas which had not been directly affected by the original ischaemic insult. This post-ischaemic delayed phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was studied in our previous study. Based on the present study, alteration of adenosine A1 receptor binding activities is involved not only in the ischaemic foci, but also in the remote areas associated neuroanatomically with the ischaemic foci. We suggest that multi-focal post-ischaemic alterations of adenosine A1 binding activities may exacerbate clinical symptoms of patients at a chronic stage of stroke.
Assuntos
Adenosina/análogos & derivados , Encéfalo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/metabolismo , Animais , Autorradiografia , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/fisiopatologia , Humanos , Masculino , Especificidade de Órgãos , Ratos , Ratos Wistar , Valores de Referência , Substância Negra/metabolismo , Tálamo/metabolismo , Fatores de Tempo , TrítioRESUMO
We studied the chronological changes of protein kinase C (PKC) and muscarinic acetylcholine receptor binding activities of the rat brain which were determined by using [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]quinuclidinyl benzilate (QNB) autoradiographic methods, respectively, after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion, followed by different periods of recirculation. After the ischemic insult followed by 3 h of recirculation, [3H]PDBu binding sites were found to be significantly decreased in the cerebral cortex and lateral segment of the caudate putamen, both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, a significant decrease of [3H]QNB binding sites was first detected in those ischemic foci. Moreover, 3 days after ischemic insult, both [3H]PDBu and [3H]QNB binding sites were concurrently reduced in the ipsilateral thalamus and 1 week after the ischemia, in the substantia nigra, in which both areas had not been directly affected by the original ischemic insult. These alterations of PKC in the postischemic brain areas developed concurrently with 45Ca accumulation, which was detected in our previous study. These results suggest that postischemic alterations of second-messenger (PKC) and neurotransmitter receptor systems were involved not only in the ischemic foci due to ischemia-induced energy failure, but also in the exo-focal remote areas prior to the histologic changes where neuronal damage might be caused by transsynaptic delayed degeneration.
Assuntos
Encéfalo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Proteína Quinase C/metabolismo , Receptores Muscarínicos/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Animais , Autorradiografia , Sítios de Ligação , Modelos Animais de Doenças , Masculino , Dibutirato de 12,13-Forbol/metabolismo , Quinuclidinil Benzilato/metabolismo , Ratos , Ratos Wistar , Substância Negra/metabolismo , Tálamo/metabolismoRESUMO
We investigated the regional changes in [3H]inositol 1,4,5-triphosphate (IP3) binding in the brain following ischemia using in vitro autoradiography. Three 2-min ischemic insults at 1-hr intervals and a 6-min period of ischemia were induced in gerbils and they were killed after 1, 4, and 28 days. Normal animals had high [3H]IP3 binding in the CA1 subfield of the hippocampus and the striatum. The binding in the CA1 decreased strikingly after both 6-min ischemia and three 2-min ischemic insults. The [3H]IP3 binding also decreased in the lateral striatum after three 2-min ischemic insults but not after 6 min of ischemia. Histological observations confirmed neuronal damage to these areas of reduced binding. By contrast, we found a marked increase in [3H]IP3 binding in the ventral thalamus 28 days after three 2-min ischemic insults. Histological observations with Nissl staining revealed an accumulation of fine granular deposits there. Thus, repeated ischemic insults produced more extensive neuronal damage and changes in [3H]IP3 binding than a single equivalent period of ischemia. The increased [3H]IP3 binding in the thalamus coincidentally with an accumulation of Nissl-positive granules at the chronic stage after repeated ischemia is of considerable interest.
Assuntos
Química Encefálica/fisiologia , Isquemia Encefálica/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Animais , Autorradiografia , Gerbillinae , Hipocampo/metabolismo , Masculino , Neostriado/metabolismo , Tálamo/metabolismoRESUMO
PURPOSE: To determine whether decreased signal intensity of the motor cortex (T2 shortening) at magnetic resonance (MR) imaging is a useful finding for supporting the diagnosis of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: High-field-strength (1.5-T) MR images of 15 patients (seven men and eight women, aged 28-80 years) and 49 neurologically normal age-matched control patients were examined for T2 shortening in the motor cortex. In addition, brains of patients with ALS were examined at autopsy. RESULTS: The MR images of 14 of the 15 patients showed T2 shortening in precentral cortices, while the images of all but one of the control patients showed no such finding. In three of eight brains at autopsy, sections from the precentral cortex showed sparsely distributed, intensely stained astrocytes and macrophages. CONCLUSION: Abnormal iron deposition associated with the degenerative process could be the source of T2 shortening, which is a useful MR imaging finding in the diagnosis of ALS.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Córtex Motor/patologia , Química Encefálica , Feminino , Humanos , Ferro/análise , Masculino , Pessoa de Meia-IdadeRESUMO
The expression of oxytocin receptor (OT-R) mRNA in the rat central nervous system was examined by in situ hybridization histochemistry using cRNA probe. Wide distribution of cells expressing OT-R mRNA was observed not only in the hypothalamus, but also in other regions. There were high levels of OT-R mRNA in the anterior olfactory nuclei, tenia tecta, olfactory tubercle, rostral most region of the frontal cortex, piriform cortex, layers 2 and 3 of the neocortex, bed nucleus of the stria terminalis, anterior medial preoptic nucleus (AV3V region), magnocellular preoptic nucleus, supraoptic nucleus, paraventricular hypothalamic nucleus, retrochiasmatic nucleus, ventromedial hypothalamic nucleus, paraventricular thalamic nucleus, central amygdaloid nucleus, medial amygdaloid nucleus, posterior cortical amygdaloid nucleus, amygdalohippocampal area, subiculum, prepositus hypoglossal nucleus, and dorsal motor nucleus of vagus. In most regions of the brain, our findings concurred with those obtained by receptor binding autoradiography using a ligand specific to OT. However, in the inferior olive nucleus, OT-R mRNA was not detected despite an abundance of binding sites showed by receptor binding autography. Despite this discrepancy OT appears to have central nervous system functions in addition to its hormonal functions.
Assuntos
Química Encefálica , Expressão Gênica , RNA Mensageiro/análise , Receptores de Vasopressinas/genética , Animais , Autorradiografia , Córtex Cerebral/química , Feminino , Hipotálamo/química , Hibridização In Situ , Sondas RNA , Ratos , Ratos Wistar , Receptores de Ocitocina , Telencéfalo/química , Distribuição TecidualRESUMO
We examined the sequential alterations in the binding of selective cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and cAMP-dependent protein kinase (cAMP-DPK) in the gerbil brain following transient cerebral ischemia using in vitro quantitative autoradiography. [3H]Rolipram, a cAMP-PDE inhibitor, and [3H]cAMP were used to label cAMP-PDE and cAMP-DPK, respectively. Gerbils were subjected to 2-min or 6-min ischemia. Two-minute ischemia, which caused no morphological neuronal damage, produced no significant changes in either [3H]rolipram or [3H]cAMP binding throughout the recirculation period. The reduction of [3H]rolipram binding in the CA1 subfield of the hippocampus began 6 h after 6-min ischemia. Seventy percent of [3H]rolipram binding was preserved at 4 days, at which time almost all CA1 pyramidal cells had been destroyed. On the other hand, the reduction of [3H]cAMP-binding sites in the CA1 subfield began 1 day after 6-min ischemia. At 4 days, 47% of [3H]cAMP-binding sites in the CA1 subfield were preserved. Furthermore, we observed a transient reduction of [3H]cAMP binding in the dentate gyrus, which is resistant to ischemia, at 1 day and 4 days. These results indicate that marked alterations of cAMP-PDE and cAMP-DPK precede neuronal death in the hippocampal CA1 subfield, and the dentate gyrus also showed a transient alteration of cAMP-DPK.
Assuntos
Encéfalo/metabolismo , AMP Cíclico/metabolismo , Ataque Isquêmico Transitório/metabolismo , Pirrolidinonas/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Adenilil Ciclases/metabolismo , Animais , Autorradiografia , Encéfalo/enzimologia , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/metabolismo , Gerbillinae , Hipocampo/anatomia & histologia , Hipocampo/metabolismo , Masculino , Proteínas Quinases/metabolismo , Tratos Piramidais/anatomia & histologia , Tratos Piramidais/metabolismo , Rolipram , Tálamo/anatomia & histologia , Tálamo/metabolismoRESUMO
Bipolar depth electrodes were implanted stereotaxically in the thalamus, hippocampus and midbrain reticular formation of cats. Cortical screw electrodes were placed over the bilateral sensorimotor cortex. A guide cannula with an inner injection cannula was inserted unilaterally into the posterolateral ventral nuclei (VPL) of the thalamus. Eight days after the procedures, kainic acid (2.0 micrograms) was injected unilaterally into the VPL via the injection cannula in freely moving animals and electro-clinical observations were made. About 1 h after the kainic acid injection, multiple spikes were observed in the VPL (injection site), which propagated to the subcortical structures. These seizures finally propagated bilaterally to the cortex about 2 h after the injection. About 3-4 h after the injection, small spike and wave complexes repeatedly appeared for a short period of time in cortical leads and cats exhibited behavioral arrest with unresponsiveness during the seizures. About 24 h after the injection, generalized small spike and wave complexes were observed intermittently in cortical and subcortical structures. They persisted for 4-5 s and were associated with behavioral arrest and staring. The results demonstrate that a unilateral microinjection of kainic acid into VPL induced petit mal-like seizure, and suggest that VPL plays an important role in the generation or transfer of spike and wave complexes.