Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy?

CONTEXTO E OBJETIVO: em crianças, a esteatose hepática pode se relacionar a erros inatos do metabolismo (EIMs) ou à doença hepática gordurosa não-alcoólica (DHGNA). O objetivo deste estudo foi avaliar e caracterizar esteatose de causa indeterminada por meio de análises morfológica e morfométrica em tecido hepático. TIPO DE ESTUDO E LOCAL: Estudo transversal nos Departamentos de Patologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM-Unicamp) e Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (FMB-Unesp). MÉTODOS: Foram utilizadas 18 biópsias hepáticas consecutivas obtidas de 16 pacientes com idade variando de 3 meses a 12 anos e 9 meses, inseridas num banco de dados no período do estudo, que foram analisadas por microscopia óptica e eletrônica. Na microscopia eletrônica, foi realizada determinação da densidade mitocondrial e da área superficial média das mitocôndrias nos hepatócitos. Dez pacientes com idade variando de 1 a 14 anos foram usados como grupo controle. RESULTADOS: Foi detectada esteatose pura, não acompanhada por fibrose ou outra alteração histológica. Foi verificado que, na predominância de esteatose microvesicular, houve aumento significativo da área mitocondrial média. CONCLUSÃO: A esteatose microvesicular pode estar relacionada à hepatopatia mitocondrial primária, principalmente devido à redução na β-oxidação ou parcial estagnação da fosforilação oxidativa. Por essas razões, esta forma de esteatose (que não pode ser chamada de pura) possivelmente represente uma fase inicial no amplo espectro da DHGNA. Chamamos a atenção para casos de esteatose no grupo pediátrico com predomínio da forma microvesicular, uma vez que pode haver associação com desordens mitocondriais.

Avaliação com Doppler colorido e espectral da veia porta de cães

A perfusão total do fígado e suas contribuições relativas, pelo sistema portal e pela artéria hepática, podem estar alteradas por vários processos hepáticos, como doença hepato-celular difusa, neoplasia e shunts intra-hepáticos. O estudo do comportamento do fluxo sangüíneo nos vasos do fígado por meio da ultra-sonografia Doppler tem demonstrado que este é um método viável não-invasivo e de grande auxílio, principalmente na avaliação da hemodinâmica portal. São duas as modalidades de ultra-sonografia Doppler com maior aplicação na rotina para avaliação de fluxo nos vasos abdominais, o Doppler espectral e o Doppler colorido. Na doença hepática crônica, ocorre alteração da complacência hepática devido à fibrose ou à cirrose, as quais acarretam alterações vasculares, levando ao aumento da pressão venosa portal. As principais indicações desse exame são os casos em que há suspeita de hipertensão portal. A hemodinâmica portal é avaliada pela mensuração de sua área, da velocidade média, do volume de fluxo no vaso e do índice de congestão portal. Esta revisão de literatura tem como objetivo descrever os princípios físicos básicos da ultra-sonografia Doppler e sua aplicação na avaliação da hemodinâmica portal nos cães.

Evaluation of renal and hepatic functions in dogs naturally infected by visceral leishmaniasis submitted to treatment with meglumine antimoniate

The present study aimed to evaluate the renal and hepatic responses in eight dogs with visceral leishmaniasis submitted to treatment with meglumine antimoniate and to verify the occurrence of possible side effects. Urinalysis, hepatic and renal function tests were carried out in all animals at up to seven moments. After the end of a six-month observation period, all dogs were euthanized. Before the beginning of the experiment urinary and biochemical alterations were observed in four dogs due to the changes caused by the parasite itself. These alterations included the presence of renal cells, cylindruria, proteinuria, azotemia, hyperproteinemia, and hypoalbuminemia. One dog died on the third day after treatment because an aggravation of the clinical picture, probably due to the medication. During the course of the study, an increase in hepatic enzymes was verified in two animals. Sixty days after the beginning of the treatment four dogs showed remission of clinical signs. The other three were asymptomatic with persistent biochemical alterations. From these, two presented recurrence of clinical signs about 150 days after the beginning of the treatment while in the other, hyperproteinemia persisted. Meglumine antimoniate was not efficient to treat dogs with severe renal dysfunction and the side effects observed were pain at the site of injection and the probable transient hepatotoxicity, evidenced by biochemical examinations, but without the presence of clinical signs. (c) 2006 Elsevier Ltd. All rights reserved.

Influence of experimental inflammatory response on hepatic hepcidin gene expression and plasma iron concentration in sheep

Hepcidin is a highly conserved disulfide-bonded peptide that plays a central role in iron homeostasis. During systemic inflammation, hepcidin up-regulation is responsible for hypoferremia. This study aimed to analyze the influence of the inflammatory process induced by complete Freund's adjuvant (CFA) or lipopolysaccharide (LPS) on the liver expression of hepcidin mRNA transcripts and plasma iron concentration of sheep. The expression levels of hepcidin transcripts were up-regulated after CFA or LPS. Hypoferremic response was observed at 12 h (15.46 +/- 6.05 mu mol/L) or 6 h (14.59 +/- 4.38 mu mol/L) and iron reached its lowest level at 96 h (3.08 +/- 1.18 mu mol/L) or 16 h (4.06 +/- 1.58 mu mol/L) after CFA administration or LPS infusion, respectively. This study demonstrated that the iron regulatory hormone hepcidin was up-regulated in sheep liver in response to systemic inflammation. These findings extend our knowledge on the relationship between the systemic inflammatory response, hepcidin and iron, and provide a starting point for additional studies on iron metabolism and the inflammatory process in sheep. (C) 2011 Elsevier B.V. All rights reserved.

Interaction between supraoptic nucleus and septal area in the control of water, sodium intake and arterial blood pressure induced by injection of angiotensin II

We investigated the effects of injection into the supraoptic nucleus (SON) of losartanand PD 123319 (nonpeptide AT(1) and AT(2)- angiotensin II [ANG II] receptor antagonists, respectively); d(CH2)(5)-Tyr(Me)-AVP (AVPA; an arginine-vasopressin [AVP] V-1 receptor antagonist), FK 409 (a nitric oxide [NO] donor), and N-W-mtro-(L)-arginine methyl ester ((L)-NAME; an NO synthase inhibitor) oil water intake, sodium chloride 3% (NaCl) intake and arterial blood pressure induced by injection of ANG 11 into the lateral septal area (LSA). Mate Holtzman rats (250-300 g) were implanted with cannulae into SON and LSA unilaterally. The drugs were injected in 0.5 mul over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. ANG II was injected at a dose of 10 pmol. ANG II antagonists and AVPA were injected at doses of 80 nmol. FK 409 and (L)-NAME were injected at doses of 20 and 40 mug, respectively. Water and NaCl intake was measured over a 2-h period. Prior administration of losartan into the SON decreased water and NaCl intake induced by injection of ANG II. While there was a decrease in water intake, ANG II-induced NaCl intake was significantly increased following injection of AVPA. FK 409 injection decreased water intake and sodium intake induced by ANG II. L-NAME alone increased water and sodium intake and induced a pressor effect. (L)-NAME-potentiated water and sodium intake induced by ANG II. PD 123319 produced no changes in water or sodium intake induced by ANG II. The prior administration of losartan or AVPA decreased mean arterial pressure (MAP) induced by ANG II. PD 123319 decreased the pressor effect of ANG II to a lesser degree than losartan. FK 409 decreased the pressor effect of ANG II while (L)-NAME potentiated it. These results suggest that both ANG II AT, and AVP V, receptors and NO within the SON may be involved in water intake, NaCl intake and the pressor response were induced by activation of ANG II receptors within the LSA. These results do not support the involvement of LSA AT(2) receptors in the mediation of water and NaCl intake responses induced by ANG II, but influence the pressor response. (C) 2004 Elsevier B.V. All rights reserved.

Vasopressin and angiotensin receptors of the medial septal area of the brain in the control of thirst and salt appetite induced by vasopressin in water-deprived and sodium-depleted rats

In this study we investigated the influence of d(CH2)(5)-Tyr (Me)-AVP (A(1) AVP) and [Adamanteanacatyl(1),D-ET-D-Tyr(2), Va1(4), aminobutyril(6) ,As-8,As-9]-AVP 9 (A(2)AVP), antagonists of V-1 and V-2 arginine(8)-vasopressin (AVP) receptors, respectively, as well as the effects of losartan and CGP42112A, antagonists of angiotensin II (ANGII) AT(1) and AT(2), receptors, respectively, on water and 0.3 M sodium intake induced by water deprivation or sodium depletion (furosemide treatment) and enhanced by AVP injected into the medial septal area (N4SA). A stainless steel carmulawas implanted into the medial septal area (NISA) of male Holtzman rats AVP injection enhanced water and sodium intake in a dose-dependent manner. Pretreatment with V-1 antagonist injected into the MSA produced a dose-dependent reduction, whereas prior injection of V-2 antagonist increased, in a dose-dependent manner, the water and sodium responses elicited by the administration of AVP. Both AT(1) and AT(2) antagonists administered into the MSA elicited a concentration-dependent decrease in water and sodium intake induced by AVP, while simultaneous injection of the two antagonists was more effective in decreasing AVP responses. These results also indicate that the increase in water and sodium intake induced by AvT was mediated primarily by MSA AT(1) receptors. (c) 2007 Published by Elsevier B.V.

Effect of electrolytic and chemical lesion by ibotenic acid of the septal area on water and salt intake

Water and sodium chloride intake was studied in male Holtzman rats weighing 250-300 g that had been subjected to electrolytic and chemical lesions of the septal area (SA). Water intake increased in animals with electrolytic lesion of the SA bilaterally from 169.37 +/- 8.55 (sham) to 214.87 +/- 23.10 ml/5 days (lesioned). Water intake decreased after ibotenic acid lesion of the SA from 229.33 +/- 27.60 to 127.33 +/- 22.84 ml/5 days. Sodium chloride intake (1.5%) increased in animals with electrolytic lesion of the SA from 10.0 +/- 1.73 to 15.5 +/- 1.95 ml/5 days after lesion. Also sodium chloride (1.5%) intake increased after ibotenic acid injection into the SA to a greater extent (from 7.83 +/- 1.25 to 14.33 +/- 1.87 ml/5 days). The results indicate that the water intake response may be due to lesions that involve cell bodies and fibers of passage and that the sodium intake response can also be induced by lesions which involve only cell bodies. Finally, these results led us to conclude that the SA uses its cell bodies and afferent bodies and fibers for processing inputs mediating water intake and salt appetite and that the cells bodies of the SA are implicated in increased water intake. (C) 1998 Elsevier B.V.

Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine

We determined the effects of moxonidine and rilmenidine 20 mol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12 +/- 3 mg min(-1)) vs. control (99 +/- 9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20 +/- 5 mg min(-1)) vs. control (94 +/- 7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60 +/- 8 and 95 +/- 10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70 +/- 6 and 24 +/- 6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially These receptors of the medial septal area have an inhibitory mechanism on salivary secretion. (C) 2004 Elsevier B.V. All rights reserved.

Novel evidence that nitric oxide of the medial septal area influences the salivary secretion induced by pilocarpine

Our studies have focused on the effect of injection of L-NAME and sodium nitroprussiate (SNP) on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine which was injected into the medial septal area (MSA). Rats were anesthetized with urethane (1.25 g/kg b. wt.) and a stainless steel cannula was implanted into their MSA. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into MSA. Injection of pilocarpine (10, 20, 40, 80, 160 mug/mul) into MSA produced a dose-dependent increase in salivary secretion. L-NG-nitro arginine methyl-esther (L-NAME) (40 mug/mul), a nitric oxide (NO) synthase inhibitor, was injected into MSA prior to the injection of pilocarpine into MSA, producing an increase in salivary secretion due to the effect of pilocarpine. Sodium nitroprussiate (SNP) (30 mug/mul) was injected into MSA prior to the injection of pilocarpine into MSA attenuating the increase in salivary secretion induced by pilocarpine. Medial arterial pressure (MAP) increase after injections of pilocarpine into the MSA. L-NAME injected into the MSA prior to injection of pilocarpine into MSA increased the MAP. SNP injected into the MSA prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (40 mug/mul) injected into the MAS induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the MSA increased the urinary sodium excretion and urinary volume induced by pilocarpine. SNP injected prior to pilocarpine into the MSA decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the MSA. We may also conclude that the MSA is involved with the cholinergic excitatory mechanism that induce salivary secretion, increase in MAP and increase in sodium excretion and urinary volume. (C) 2002 Elsevier B.V. All rights reserved.

Effects of V-1 and angiotensin receptor subtypes of the paraventricular nucleus on the water intake induced by vasopressin injected into the lateral septal area

In this study, we investigated the influence of d(CH2)(5)-Tyr (Me)-AVP (AAVP) an antagonist of V-1 receptors of arginine(8)-vasopressin (AVP) and the effects of losartan and CGP42112A (selective ligands of the AT, and AT, angiotensin receptors, respectively) injections into the paraventricular nucleus (PVN) on the thirst effects of AVP stimulation of the lateral septal area (LSA). AVP injection into the LSA increased the water intake in a dose-dependent manner. AAVP injected into the PVN produced a dose-dependent reduction of the drinking responses elicited by LSA administration of AVP. Both the AT(1) and AT(2) ligands administered into the PVN elicited a concentration-dependent inhibition in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A the increase in the AVP response. These results indicate that LSA dipsogenic effects induced by AVP are mediated primarily by PVN AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple angiotensin II (ANG II) receptor subtypes. These results also suggests that facilitatory effects of AVP on water intake into the LSA are mediated through the activation of V-receptors and that the inhibitory effect requires V-receptors. Based on the present findings, we suggest that the administration of AVP into the LSA may play a role in the PVN control of water control. (C) 2003 Elsevier B.V. All rights reserved.

Interaction between paraventricular nucleus and medial septal area on the renal effects induced by adrenaline

The aim of the present study was to analyze the role of alpha(1),alpha(2)-adrenoceptors, and the effects of losartan and PD123319 (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) injected into the paraventricular nucleus (PVN) on the diuresis, natriuresis, and kaliuresis induced by administration of adrenaline into the medial septal area (MSA). Male Holtzman rats with a stainless steel cannula implanted into the MSA and bilaterally into the PVN were used. The administration of adrenaline into the MSA increased in a dose-dependent manner the urine, sodium, and potassium excretions. The previous administration of prazosin (an alpha(1)-adrenoceptor antagonist) injected into the PVN abolished the above effects of adrenaline, whereas yohimbine (an a-adrenoceptor antagonist) doesn't affect the diuresis, natriuresis, and kaliuresis induced by adrenaline. Pretreatment with losartan into the PVN decreased in a dose-dependent manner the urine, sodium, and potassium excretions induced by MSA administration of adrenaline (50 ng), while PVN PD123319 was without effect. These results indicate that urinary and electrolyte excretion effects induced by adrenaline into the MSA are mediated primarily by PVN AT, receptors. However, the doses of losartan were more effective when combined with the doses of PD123319 than given alone, suggesting that the urinary, natriuretic, and kaliuretic effects of MSA adrenaline may involve activation of multiple angiotensin II receptors subtypes into the PVN. (C) 2004 Elsevier B.V All rights reserved.

Role of the alpha(1)- and alpha(2)-adrenoceptors of the paraventricular nucleus on the water and salt intake, renal excretion, and arterial pressure induced by angiotensin II injection into the medial septal area

In this study we investigated the influence of cu-adrenergic antagonists injections into the paraventricular nucleus (PVN) of the hypothalamus on the thirst and salt appetite, diuresis, natriuresis, and presser effects of angiotensin II (ANG II) stimulation of medial septal area (MSA). ANG II injection into the MSA induced water and sodium intake, diuresis, natriuresis, and presser responses. The previous injection of prazosin (an alpha (1)-adrenergic antagonist) into the PVN abolished, whereas previous administration of yohimbine (an alpha (2)-adrenergic antagonist) into the PVN increased the water and sodium intake, urinary, natriuretic, and presser responses induced by ANG ii injected into the MSA. Previous injection of a nonselective alpha -adrenergic antagonist, regitin, into the PVN blocked the urinary excretion, and reduced the water and sodium intake, sodium intake, and presser responses induced by ANG II injected into the MSA. The present results suggest that alpha -adrenergic pathways involving the PVN are important for the water and sodium excretion, urine and sodium excretion, and presser responses, induced by angiotensinergic activation of the MSA. (C) 2001 Elsevier B.V.

Effects of angiotensin and vasopressin V-1 receptors on water and sodium intake induced by injection of vasopressin into lateral septal area

The specific arginine(8)-vasopressin (AVP) V, receptors antagonist (AAVP) was injected (20, 40 and 80 nmol) into the lateral septal area (LSA) to determine the effects of selective septal V, receptor on water and 3% sodium intake in rats. Was also observed the effects of losartan and CGP42112A (select ligands of the AT(1) and AT(2) ANG II receptors, respectively) injected into LSA prior AVP on the same appetites. Twenty-four hours before the experiments, the rats were deprived of water. The volume of drug solution injected was 0.5 mul. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2,0 h. Injection of AVP reduced the water and sodium ingestion vs. control (0.15 M saline). Pre-treatment with AAVP (40, 80 and 160 nmol) did not alter the decrease in the water ingestion induced by AVP, whereas AAVP abolished the action of AVP-induced sodium intake. Losartan (40, 80 and 160 nmol) did not alter the effect of AVP on water and sodium intake, whereas CGP42112A (20, 40 and 60 nmol) at the first 30 min increased water ingestion. Losartan and CGP42112A together increased the actions of AVP, showing more pronounced effects than when the two antagonists were injected alone. The results showed that AVP inhibited the appetites and these effects were increased by the AAVP. The involvement of angiotensinergic receptors in the effects of AVP is also suggested. (C) 2004 Elsevier B.V. All rights reserved.