RESUMO
In intact tissue studies, intestinal absorptogogues stimulate NaCl absorption that occurs via the dual operation of Na:H and Cl:HCO3 exchanges on the brush border membrane (BBM) of villus cells. To determine the cellular mechanism of action of an intestinal absorptogogue, the effect of clonidine was determined on Na:H and Cl:HCO3 exchange in rabbit ileal villus and crypt cells. Using 2,7-bis(carboxyethyl)-5,6-carboxy-fluorescein we have previously shown that recovery from an acid load occurs via Na:H exchange, whereas recovery from an alkaline load occurs via Cl:HCO3 exchange in both cells. In villus cells, the rate of recovery from a propionate-induced alkaline load was not altered by clonidine. However, clonidine stimulated recovery from an acid load induced by NH4Cl, Na removal, or amiloride. These data suggest that clonidine stimulates Na:H exchange in villus cells. In crypt cells, the rate of recovery from a propionate-induced alkaline load was also not altered by clonidine. However, in crypt cells, unlike the villus cells, clonidine inhibited recovery from an acid load induced by NH4Cl, Na removal, or amiloride. These data suggest that clonidine inhibits Na:H exchange in crypt cells. Stimulation of Na:H exchange on the BBM of villus cells would be expected to stimulate coupled NaCl absorption (which occurs by coupling of Na:H and Cl:HCO3 exchange). Inhibition of Na:H in crypt cells, known to be present only on the basolateral membrane, will acidify the cell and may inhibit Cl:HCO3 exchange on the BBM, resulting in the inhibition of HCO3 secretion.
Assuntos
Clonidina/farmacologia , Íleo/fisiologia , Absorção Intestinal/fisiologia , Animais , Sobrevivência Celular , Células Cultivadas , Concentração de Íons de Hidrogênio , Íleo/citologia , Íleo/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/fisiologia , Cinética , Modelos Biológicos , Coelhos , Sódio/metabolismo , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/metabolismo , Fatores de TempoRESUMO
To determine the mechanism of action of an intestinal secretagogue, serotonin, we have isolated crypt and villus cells and demonstrated Na:H and Cl:HCO3 exchange activity using the intracellular pH-sensitive fluorescent dye, 2,7-bis (carboxy-ethyl)-5,6-carboxy-fluorescein. Serotonin alkalinized both crypt and villus cells. Alkalinization in villus cells was HCO3 dependent and Na independent. In contrast, alkalinization in crypt cells was HCO3 independent and Na dependent. In villus cells, recovery from an alkaline load induced by Cl removal, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid or propionate pulse, known to occur via the Cl:HCO3 exchange, is inhibited by serotonin. In contrast, in crypt cells, recovery from an acid load induced by Na removal, amiloride and NH4Cl pulse, known to occur via Na:H exchange, is stimulated by serotonin. These data suggest that serotonin is inhibiting Cl:HCO3 exchange in villus cells and stimulating Na:H exchange in crypt cells. These effects of serotonin would be expected to inhibit coupled Na and Cl absorption by villus cells and stimulate HCO3 secretion by crypt cells in the intact ileum.
Assuntos
Íleo/metabolismo , Microvilosidades/metabolismo , Serotonina/metabolismo , Animais , Concentração de Íons de Hidrogênio , Íleo/citologia , CoelhosRESUMO
Right brain regions of anesthetized rats were loaded with [3,5,7-3H]methotrexate ([3H]MTX) or with [14C]sucrose by infusing the tracers into the right carotid artery, after the blood-brain barrier had been opened by right carotid infusion of a hypertonic arabinose solution. During the 6 hr following the procedure, the [3H]MTX concentration in 7 right-sided brain regions, when normalized to the plasma concentration integral during tracer infusion, fell, with an average half-time of 4.8 hr as compared to less than 20 min for the initial rate of loss [14C]sucrose. Right-left brain concentration differences 3 hr after treatment were statistically significant (p less than 0.05) for [3H]MTX but not for [14C]sucrose. The results indicate that intracerebral [3H]MTX is lost more slowly than is intracerebral [14C]sucrose, possibly because [3H]MTX enters brain cells, whereas [14C]sucrose remains largely extracellular.
Assuntos
Barreira Hematoencefálica , Encéfalo/metabolismo , Metotrexato/metabolismo , Animais , Radioisótopos de Carbono , Masculino , Matemática , Osmose , Ratos , Sacarose/metabolismo , TrítioRESUMO
A series of fungal laccases (Polyporus pinsitus, Rhizoctonia solani, Myceliophthora thermophila, Scytalidium thermophilum) and one bilirubin oxidase (Myrothecium verrucaria) have been studied to determine their redox potential, specificity, and stability. Polyporus and Rhizoctonia laccases possess potentials near 0.7-0.8 V (vs. NHE), while other oxidases have potentials near 0.5 V. It is observed that higher redox potential correlates with higher activity. By EPR, no significant change in the geometry of type 1 copper (II) site is observed over this series. At the optimal pH, the two substrates studied, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) and syringaldazine, show Km values ranging form 10 to 120 and from 1 to 45 microM; and kcat values ranging from 50 to 16 000 and 200 to 3000 per min, respectively. The enzymes are more stable in the neutral-alkaline pH range. The thermal stability is in the order of bilirubin oxidase equivalent to Myceliophthora laccase equivalent to Scytalidium laccase > Polyporus laccase > Rhizoctonia laccase. Based on these results and the sequence alignments made against Zucchini ascorbate oxidase it is speculated that structural differences in the substrate-activation site (a 'blue', type 1 copper center) control the redox potential range as well as substrate specificity, and the cystine content contributes to stability.
Assuntos
Fungos/enzimologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Oxirredutases/química , Oxirredutases/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Estabilidade Enzimática , Temperatura Alta , Concentração de Íons de Hidrogênio , Cinética , Lacase , Oxirredução , Oxirredutases/isolamento & purificação , Potenciometria , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Especificidade da Espécie , Espectrofotometria , Especificidade por Substrato , TermodinâmicaRESUMO
Immobilization stress of conscious, normotensive, freely breathing 10-month-old Wistar-Kyoto rats produced an overall decline in regional cerebral blood flow (rCBF), as measured with [14C]iodoantipyrine, except at the frontal lobe. In 14 brain regions, rCBF fell by an average of 14.3% after 5 min of immobilization and by 11.9% after 15 min. Immobilization stress also stimulated hyperventilation and thereby reduced PaCO2. The slope relating rCBF to PaCO2 averaged 1.5 ml 100 g-1 min-1 mm Hg-1 in 9 significantly affected regions. The findings suggest that rCBF declines during immobilization stress because of cerebrovascular constriction caused by a reduction in PaCO2. Comparison of the average slope with published values in indicates furthermore that were PaCO2 to remain unchanged during immobilization, rCBF would increase by at most 20%.
Assuntos
Circulação Cerebrovascular , Estresse Fisiológico/fisiopatologia , Equilíbrio Ácido-Base , Animais , Artérias , Pressão Sanguínea , Dióxido de Carbono/sangue , Frequência Cardíaca , Concentração de Íons de Hidrogênio , Masculino , Ratos , Ratos Endogâmicos , Restrição FísicaRESUMO
A 33 year old patient with two acute myocardial ischaemic episodes (one, a probable inferior wall infarction and the second, a definitive Q wave anterior wall infarction) within a span of 6 months, with angiographically documented normal coronary arteries, is reported. Coronary artery spasm studies performed using ergonovine during the second coronary angiography, could not provoke spasm. The mechanism of recurrent infarction remains unclear.
Assuntos
Angiografia Coronária , Infarto do Miocárdio/diagnóstico por imagem , Adulto , Cateterismo Cardíaco , Eletrocardiografia , Hemodinâmica , Humanos , Masculino , Infarto do Miocárdio/terapia , RecidivaRESUMO
Pericardiocentesis was performed in 20 patients using a 7F diagnostic catheter in a cardiac catheterisation laboratory under fluoroscopic control, with haemodynamic and electrocardiographic monitoring. This technique offers several advantages over the bedside technique which utilises a sharp needle. The technique utilised for percutaneous aspiration is safe and simple and allows complete drainage of fluid. The haemodynamic monitoring before and after drainage aids in detecting cases of effusive constriction.
Assuntos
Cateterismo Cardíaco , Hemodinâmica/fisiologia , Monitorização Fisiológica , Derrame Pericárdico/terapia , Técnicas de Janela Pericárdica , Adolescente , Adulto , Função do Átrio Direito/fisiologia , Pressão Sanguínea/fisiologia , Tamponamento Cardíaco/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Punções , Função Ventricular Direita/fisiologiaRESUMO
In the normal ileum, coupled NaCl absorption occurs via the dual operation of Na(+)/H(+) and Cl(-)/HCO(-)(3) exchange on the brush-border membrane (BBM) of villus cells. In a rabbit model of chronic small intestinal inflammation we determined the cellular mechanism of inhibition of NaCl absorption and the effect of steroids on this inhibition. Cl(-)/HCO(-)(3) but not Na(+)/H(+) exchange was reduced in the BBM of villus cells during chronic ileitis. Cl(-)/HCO(-)(3) exchange was inhibited secondary to a decrease in the affinity for Cl(-) rather than an alteration in the maximal rate of uptake of Cl(-) (V(max)). Methylprednisolone (MP) stimulated Cl(-)/HCO(-)(3) exchange in the normal ileum by increasing the V(max) of Cl(-) uptake rather than altering affinity for Cl(-). MP reversed the inhibition of Cl(-)/HCO(-)(3) exchange in rabbits with chronic ileitis. However, MP alleviated the Cl(-)/HCO(-)(3) exchange inhibition by restoring the affinity for Cl(-) rather than altering the V(max) of Cl(-) uptake. These data suggest that glucocorticoids mediate the alleviation of Cl(-)/HCO(-)(3) exchange inhibition in chronically inflamed ileum by reversing the same mechanism that was responsible for inhibition of this transporter rather than exerting a direct effect on the transporter itself, as was the case in normal ileum.
Assuntos
Antiporters/antagonistas & inibidores , Glucocorticoides/farmacologia , Ileíte/metabolismo , Metilprednisolona/farmacologia , Animais , Antiporters/metabolismo , Antiportadores de Cloreto-Bicarbonato , Doença Crônica , Íleo/efeitos dos fármacos , Íleo/metabolismo , Cinética , Masculino , Microvilosidades/efeitos dos fármacos , Microvilosidades/metabolismo , Coelhos , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
This article reports radiologic and manometric findings in dysphagia aortica, with particular attention to the gastroesophageal (GE) junction. Records of three patients, ages 70-78 years, with clinical/radiologic dysphagia aortica were compared to those in control groups. Subsequently, manometric findings of such vascular compression were sought in 10 consecutive patients > or = 65 years old with dysphagia. The three patients with dysphagia aortica had radiologic/endoscopic evidence for compression at the GE junction. Manometric studies, performed in two of them, showed evidence at the GE junction for superimposed rhythmic contractions at 60-72/min (maximum amplitudes, 35 mm Hg), consistent with vascular compression. One patient had marked elevation of "sphincter" pressure to 110 mm Hg and "poor relaxation" of the "sphincter." One of 10 patients with dysphagia had rhythmic contractions of 20 mm Hg; a barium study subsequently showed aortic compression at the GE junction. There are characteristic manometric findings that may help to identify symptomatic vascular compression of the esophagus in the elderly.
Assuntos
Aorta Torácica , Aneurisma da Aorta Torácica/complicações , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Junção Esofagogástrica/diagnóstico por imagem , Idoso , Estudos de Casos e Controles , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Constrição Patológica/fisiopatologia , Transtornos de Deglutição/fisiopatologia , Junção Esofagogástrica/fisiopatologia , Feminino , Humanos , Masculino , Manometria , Peristaltismo , RadiografiaRESUMO
The effect of chronic inflammation on electrolyte transport in rabbit ileal villus and crypt cells was determined with the use of a rabbit model of chronic ileitis. In both cells, Na+/H+ exchange was monitored by following recovery from an acid load, and Cl-/HCO3- exchange was monitored by following recovery from an alkaline load. In villus cells, recovery from an acid load was not affected; however, recovery from an alkaline load was slowed. These data suggest that chronic inflammation inhibits Cl-/HCO3- exchange in villus cells. In contrast, in crypt cells, recovery from an alkaline load was unaffected, whereas recovery from an acid load was accelerated. These data suggest that chronic inflammation stimulates Na+/H+ exchange in crypt cells. Inhibition of Cl-/HCO3- exchange in villus cells would be expected to inhibit coupled NaCl absorption, which occurs by the coupling of brush-border membrane (BBM) Na+/H+ and Cl-/HCO3- exchange. Stimulation of Na+/H+ exchange in crypt cells, known to be present only on the basolateral membrane, alkalinizes the cell. This alkalinization may stimulate BBM Cl-/HCO3- exchange, resulting in HCO3- secretion. Thus these unique alterations in transporter activity suggest that different endogenous immune-inflammatory mediators may have differing effects on specific transporters in villus and crypt cells in the chronically inflamed ileum.
Assuntos
Eletrólitos/metabolismo , Ileíte/metabolismo , Ileíte/patologia , Íleo/metabolismo , Íleo/patologia , Animais , Antiporters/metabolismo , Transporte Biológico , Separação Celular , Sobrevivência Celular , Antiportadores de Cloreto-Bicarbonato , Doença Crônica , Íleo/fisiopatologia , Masculino , Microvilosidades/metabolismo , Microvilosidades/patologia , Microvilosidades/fisiologia , Coelhos , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
Cardiac catheterization and selective coronary angiography were performed in ten patients with intra-cardiac tumors [left atrial myxoma (7), right atrial myxoma (1), angiosarcoma of right heart (1), and right ventricular tumor (1)]. The patient with angiosarcoma had characteristic hemodynamics suggesting cardiac compression. The coronary arteriographic finding included: neovascularization (8); filling defect due to emboli (1); and displacement of coronary artery (1). Tumor neovascularization from branches of the left circumflex or right coronary artery was invariably observed in patients with myxoma. We conclude that invasive studies are safe, provide additional information of academic interest, and occasionally aid in the diagnosis.
Assuntos
Angiografia Coronária/métodos , Doença das Coronárias/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Adulto , Cateterismo Cardíaco , Ecocardiografia , Estudos de Avaliação como Assunto , Feminino , Hemangiossarcoma/diagnóstico por imagem , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagemRESUMO
Cyclic AMP-dependent secretagogues such as cholera toxin inhibit the coupled absorption of Na+ and Cl- and stimulate the secretion of HCO3- and Cl- in the ileum. Aside from Cl- secretion, little is known about the mechanism of these cyclic AMP-mediated effects. We therefore determined the effect of forskolin, an agent known to increase intracellular cyclic AMP by stimulation of adenylyl cyclase, on Na+/H+ and Cl-/HCO3- exchange in isolated crypt and villus cells from rabbit ileum. Forskolin increased cyclic AMP in the villus cells and decreased intracellular pH. The effect of forskolin on pH in villus cells was HCO3- independent, Na+ dependent, and amiloride sensitive. Further, the rate of recovery from an acid load was decreased by forskolin. These data suggest that increasing cyclic AMP inhibits Na+/H+ exchange in villus cells. In crypt cells also, forskolin increased cyclic AMP; however, forskolin increased intracellular pH in these cells. The effect of forskolin in crypt cells was also HCO3- independent, Na+ dependent, and amiloride sensitive. However, the rate of recovery from an acid load was increased by forskolin, the opposite effect of that seen in villus cells. These data suggest that increasing cyclic AMP in crypt cells stimulates Na+/H+ exchange. Inhibition of Na+/H+ exchange on the brush border membrane in villus cells would be expected to inhibit coupled NaCl absorption (which occurs by coupling of Na+/H+ and Cl-/HCO3- exchange). Stimulation of Na+/H+ exchange in crypt cells, present only on the basolateral membrane, alkalinizes the cell, which would be expected to stimulate HCO3- secretion by stimulating the Cl-/HCO3- exchanger on the brush border membrane. Thus, these results provide a mechanism for some of the previously unexplained in vivo and in vitro effects of cyclic AMP on ileal electrolyte transport.
Assuntos
Colforsina/farmacologia , AMP Cíclico/fisiologia , Íleo/fisiologia , Amilorida/farmacologia , Animais , Sobrevivência Celular , Concentração de Íons de Hidrogênio , Íleo/citologia , Íleo/efeitos dos fármacos , Íleo/metabolismo , Técnicas In Vitro , Cinética , Microvilosidades/efeitos dos fármacos , Microvilosidades/fisiologia , Coelhos , Sódio/farmacologiaRESUMO
Current evidence suggests that intestinal crypt and villus cells have different functions in electrolyte transport. To study the regulation of transporters, we isolated and separated these two cell types. This was accomplished by sequential collection of enterocytes from rabbit ileal loops incubated with buffered solutions of calcium chelators. Alkaline phosphatase and thymidine kinase activity, sodium-glucose cotransport, and morphological criteria were used to determine cell separation. Cell viability was evaluated with trypan blue exclusion, leucine incorporation into protein, and morphological features. The role of Na(+)-H+ and Cl(-)-HCO3- exchange in the regulation of intracellular pH was analyzed using an intracellular pH sensitive dye, BCECF. Removal of external Na+ or the addition of amiloride resulted in acidification of both crypt and villus cells. Removal of Cl- or the addition of DIDS resulted in alkalinization of both cell types. The cells could be acidified with NH4Cl, and recovery from this acid load was dependent on Na+ and inhibited by amiloride. Similarly, the cells could be alkalinized with propionate and recovery was Cl- dependent and DIDS sensitive. These data are consistent with the presence of Na(+)-H+ and Cl(-)-HCO3- exchange in both crypt and villus cells. Both exchanges appear to be involved in the regulation of basal pH as well as in recovery from alterations in intracellular pH. Having demonstrated the presence of Na(+)-H+ and Cl(-)-HCO3- exchange activity in both crypt and villus cells, we can now use these cells to determine the regulation of these exchangers by intracellular second messengers.
Assuntos
Bicarbonatos/metabolismo , Proteínas de Transporte/metabolismo , Íleo/metabolismo , 3-O-Metilglucose , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/farmacologia , Fosfatase Alcalina/metabolismo , Amilorida/farmacologia , Cloreto de Amônio/farmacologia , Animais , Antiportadores de Cloreto-Bicarbonato , Cloretos/farmacologia , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/ultraestrutura , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Cinética , Leucina/metabolismo , Metilglucosídeos/metabolismo , Microscopia Eletrônica , Músculo Liso/metabolismo , Biossíntese de Proteínas , Coelhos , Sódio/farmacologia , Trocadores de Sódio-HidrogênioRESUMO
Short-chain fatty acids (SCFA) have been demonstrated to at least partially ameliorate chronic intestinal inflammation. However, whether and how intestinal SCFA absorption may be altered during chronic intestinal inflammation is unknown. A rabbit model of chronic ileitis produced by coccidia was used to determine the effect of chronic inflammation on ileal SCFA/HCO(-)(3) exchange. SCFA/HCO(-)(3) exchange was present in the brush-border membrane (BBM) of villus but not crypt cells from normal rabbit ileum. An anion-exchange inhibitor, DIDS, significantly inhibited SCFA/HCO(-)(3) exchange. Extravesicular Cl(-) did not alter the uptake of SCFA, suggesting that SCFA/HCO(-)(3) exchange is a transport process distinct from Cl(-)/HCO(-)(3) exchange. In chronically inflamed ileum, SCFA/HCO(-)(3) exchange was also present only in BBM of villus cells. The exchanger was sensitive to DIDS and was unaffected by extravesicular Cl(-). However, SCFA/HCO(-)(3) exchange was significantly reduced in villus cell BBM vesicles (BBMV) from chronically inflamed ileum. Kinetic studies demonstrated that the maximal rate of uptake of SCFA, but not the affinity for SCFA, was reduced in chronically inflamed rabbit ileum. These data demonstrate that a distinct SCFA/HCO(-)(3) exchange is present on BBMV of villus but not crypt cells in normal rabbit ileum. SCFA/HCO(-)(3) exchange is inhibited in chronically inflamed rabbit ileum. The mechanism of inhibition is most likely secondary to a reduction in transporter numbers rather than altered affinity for SCFA.
Assuntos
Bicarbonatos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Ileíte/metabolismo , Íleo/metabolismo , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Animais , Bicarbonatos/antagonistas & inibidores , Doença Crônica , Coccidiose , Ácidos Graxos Voláteis/antagonistas & inibidores , Ileíte/parasitologia , Ileíte/patologia , Íleo/patologia , Absorção Intestinal , Cinética , Microvilosidades/metabolismo , Coelhos , Distribuição TecidualRESUMO
In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immune-inflammatory mediator pathways. We previously demonstrated that Na+-glucose cotransport in the chronically inflamed ileum was inhibited by a decrease in cotransporter number without a change in glucose affinity. The aim of this study was to determine the alterations in Na+-amino acid cotransport in chronically inflamed ileum produced by coccidial infection in rabbits. [3H]alanine uptake was performed in cells and vesicles by rapid filtration. In villus cells from chronically inflamed ileum, Na+-K+-ATPase was reduced 50% and Na+-alanine cotransport was also reduced (5.8 +/- 1.2 in normal and 1.4 +/- 0.5 nmol/mg protein in inflamed; n = 6, P < 0.05). [3H]alanine uptake in brush-border membrane vesicles was reduced in chronically inflamed ileum (73.2 +/- 1.2 in normal and 21.5 +/- 3.2 pmol/mg protein in inflamed; n = 3, P < 0.05), suggesting a direct effect on the cotransporter itself. Na+-amino acid cotransport in chronically inflamed ileum was inhibited by a decrease in affinity without a change in the maximal rate of uptake, and unaltered steady-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na+-amino acid cotransport and Na+-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammatory mediators may regulate different transport pathways during chronic ileitis.
Assuntos
Alanina/metabolismo , Sistemas de Transporte de Aminoácidos , Proteínas de Transporte/metabolismo , Coccidiose/metabolismo , Eimeria , Doenças do Íleo/metabolismo , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Microvilosidades/metabolismo , Sódio/metabolismo , Simportadores , Sistemas de Transporte de Aminoácidos Neutros , Animais , Transporte Biológico , Proteínas de Transporte/genética , Doença Crônica , Doenças do Íleo/parasitologia , Íleo , Mucosa Intestinal/parasitologia , Cinética , Reação em Cadeia da Polimerase , RNA Mensageiro/biossíntese , Coelhos , Transcrição GênicaRESUMO
In a rabbit model of chronic ileal inflammation, we previously demonstrated inhibition of Na-glucose cotransport (SGLT-1). The mechanism of inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na-K-ATPase or altered affinity for glucose. In this study, we determined the effect of methylprednisolone (MP) on SGLT-1 inhibition during chronic ileitis. Treatment with MP almost completely reversed the reduction in SGLT-1 in villus cells from the chronically inflamed ileum. MP also reversed the decrease in Na-K-ATPase activity in villus cells during chronic ileitis. However, MP treatment reversed the SGLT-1 inhibition in villus cell brush-border membrane vesicles from the inflamed ileum, which suggested an effect of MP at the level of the cotransporter itself. Kinetic studies demonstrated that the reversal of SGLT-1 inhibition by MP was secondary to an increase in the maximal velocity for glucose without a change in the affinity. Analysis of immunoreactive protein levels of the cotransporter demonstrated a restoration of the cotransporter numbers after MP treatment in the chronically inflamed ileum. Thus MP treatment alleviates SGLT-1 inhibition in the chronically inflamed ileum by increasing the number of cotransporters and not solely secondary to enhancing the activity of Na-K-ATPase or by altering the affinity for glucose.
Assuntos
Anti-Inflamatórios/farmacologia , Ileíte/metabolismo , Íleo/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Metilprednisolona/farmacologia , Proteínas de Transporte de Monossacarídeos/antagonistas & inibidores , Animais , Western Blotting , Doença Crônica , Ileíte/patologia , Íleo/efeitos dos fármacos , Íleo/patologia , Glicoproteínas de Membrana/metabolismo , Microvilosidades/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Coelhos , Transportador 1 de Glucose-Sódio , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
We expanded the application of percutaneous balloon valvotomy (PBV) to 4 adults (age 14 to 30 years, average 22.2 years) with combined rheumatic mitral and tricuspid stenosis. Double balloon dilatation reduced the transmitral gradient from 17.36 +/- 3.54 to 5.52 +/- 0.89 (P less than 0.025) and transtricuspid gradient from 12.65 +/- 2.67 to 3.67 +/- 0.95 (P less than 0.025). Mitral and tricuspid valve area increased from 0.73 +/- 0.20 to 2.57 +/- 0.67 (P less than 0.005) and from 0.77 +/- 0.24 to 2.67 +/- 0.24 cm2 (P less than 0.005), respectively. The procedures were well tolerated, with no significant increase in valvular regurgitation or left to right shunt across the atrial septum. The excellent symptomatic and haemodynamic benefits are sustained at 3-24 months follow-up. It is concluded that combined dilatation of stenotic valves by double balloon technique can emerge as an alternative to surgery in selected patients with polyvalvar rheumatic heart disease.
Assuntos
Cateterismo/métodos , Estenose da Valva Mitral/terapia , Cardiopatia Reumática/terapia , Estenose da Valva Tricúspide/terapia , Adolescente , Adulto , Cateterismo/instrumentação , Feminino , Humanos , MasculinoRESUMO
In a rabbit model of chronic ileal inflammation, we previously demonstrated that coupled NaCl absorption was reduced because of an inhibition of Cl-/HCO3- but not Na+/H+ exchange on the brush-border membrane (BBM) of villus cells. In this study we determined the alterations in Na+-stimulated glucose [Na+-O-methyl-D-glucose (Na+-OMG)] absorption during chronic ileitis. Na+-OMG uptake was reduced in villus cells from the chronically inflamed ileum. Na+-K+-adenosinetriphosphatase (ATPase), which provides the favorable Na+ gradient for this cotransporter in intact cells, was found to be reduced also. However, in villus cell BBM vesicles from the inflamed ileum Na+-OMG uptake was reduced as well, suggesting an effect at the level of the cotransporter itself. Kinetic studies demonstrated that Na+-OMG uptake in the inflamed ileum was inhibited by a decrease in the maximal rate of uptake for OMG without a change in the affinity. Analysis of steady-state mRNA and immunoreactive protein levels of this cotransporter demonstrates reduced expression. Thus Na+-glucose cotransport was inhibited in the chronically inflamed ileum, and the inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na+-K--ATPase or altered affinity for glucose.