Congenital adrenal hyperplasia and Schmid metaphyseal chondrodysplasia in a child

Congenital adrenal hyperplasia [CAH] is a group of hereditary diseases, which are autosomal recessive. CAH occurs due to defect in one of the cortisol coding genes and often clinically presents itself with signs of androgen overproduction. In this article, we report a case of CAH and Schmid metaphyseal dysplasia. Our literature review indicated that this report is the first attempt on CYP11B1 and Schmid dysplasia in a child. The specific diagnosis of 11-beta-hydroxylase deficiency can be determined using high basal levels of deoxycorticosterone and/or 11-deoxycortisol serums

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Effect of inhibiting brain reactive oxygen species on sympathetic nerve activity in DOCA-salt hypertensive rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether brain reactive oxygen species mediate sympathoexcitation and arterial pressure elevation in DOCA-salt hypertensive rats.</p><p><b>METHODS</b>DOCA-salt hypertensive model was established in male SD rats by subcutaneous injection of DOCA after uninephrectomy and drinking 1% NaCl solution for 4 weeks. The baseline mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in the rats under mild anesthesia, and MAP changes following intravenous hexamethonium injection were observed. The responses of MAP, HR and RSNA to intracerebroventricular administration of tempol (20 µmol/L in 10 µl) were evaluated; plasma NE level was measured with ELISA, and ROS level and NAD(P)H oxidase activity in the hypothalamus were detected using chemiluminescence assay.</p><p><b>RESULTS</b>MAP and plasma NE levels were significantly increased in DOCA-salt rats as compared with those in the control group (P<0.01). In DOCA-salt hypertensive rats, intravenous hexamethonium injection induced a blood pressure reduction 240% of that in control rats, and significantly increased the levels of superoxide anion and NAD(P)H oxidase activity in the hypothalamus. Intracerebroventricular microinjection of tempol also resulted in more significant changes of MAP, HR and RSNA in DOCA-salt rats than in the control group (P<0.01).</p><p><b>CONCLUSION</b>Sympathoexcitation due to increased NAD(P)H oxidase-derived ROS levels in the hypothalamus may mediate arterial pressure elevation in DOCA-salt hypertensive rats.</p>

Effects of Tamoxifen in Deoxycorticosterone Acetate-salt Hypertensive Nephropahty

BACKGROUND: The present study was designed to evaluate the possible renoprotective effects of tamoxifen in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats and its role in inflammation and fibrosis in the kidney. METHODS: Male Sprague-Dawley rats, weighing 180 to 200 g, were used. All rats underwent unilateral nephrectomy. One week later, one group of rats (n = 8) was implanted with DOCA strips (200 mg/kg) and another group of rats (n = 8) was implanted with DOCA strips with co-treated with tamoxifen (10 mg/kg) through gavage feeding. Rats that did not implanted DOCA strips served as controls (n = 6). Two weeks later, the systolic blood pressure (SBP) was measured by tail-cuff method. The protein expression of transforming growth factor-beta (TGF-beta), Smad, alpha-smooth muscle actin (alpha-SMA), E-cadherin, ED-1, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) was determined in the kidney by immunoblotting. The mRNA expression of tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1) was determined by real-time polymerase chain reaction. RESULTS: In DSH rats, SBP was increased, which was not affected by tamoxifen treatment. Serum creatinine level was comparable in DSH rats compared with controls, which was not affected by tamoxifen treatment. In DSH rats, the protein expression of TGF-beta, Smad 2/3, Smad 4, alpha-SMA, ED-1, COX-2, iNOS was increased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-beta. The mRNA expression of TNF-alpha, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteracted by tamoxifen treatment. CONCLUSIONS: Tamoxifen is effective in preventing the progression of nephropathy in DSH rats, the mechanism of which is associated with anti-inflammation and anti-fibrotic effects.

Imatinib atenua a fibrose miocárdica em associação com a inibição da atividade do PDGFRα / Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity

FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ). OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA)/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON): grupo deoxicorticosterona (grupo DOCA); grupo deoxicorticosterona e Imatinib (grupo DOCA IMA). A Pressão Arterial Sistólica (PAS) foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.

BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ) activity. OBJECTIVE: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats. METHODS: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed. RESULTS: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were signiflcantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group. CONCLUSION: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.

Antihyperlipidemic effect of Melothria maderaspatana leaf extracts on DOCA-salt induced hypertensive rats

OBJECTIVE@#To investigate the antihyperlipidemic effect of crude ethanolic extract of Melothria maderaspatana (M. maderaspatana) leaf (CEEM) on deoxycorticosterone acetate (DOCA)-salt hypertensive rats.@*METHODS@#A midscapular incision was made on each rat and the left kidney was excised after ligation of the renal artery. The surgical wound was closed using an absorbable suture. After one week recovery period, hypertension was induced by subcutaneous injection of DOCA-salt solution, twice a week, and the rats received a 1% sodium chloride solution as drinking water throughout the experimental period. CEEM or nifedipine was administered orally once a day for 6 weeks.@*RESULTS@#In DOCA-salt hypertensive rats, the level of plasma and tissues of total cholesterol (TC), triglycerides (TG), free fatty acids (FFA) and phospholipids (PL) significantly increased and administration of CEEM significantly reduced these parameters towards normality. Further, the levels of low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) significantly increased while high density lipoprotein-cholesterol (HDL-C) decreased in hypertensive rats and administration of CEEM brought these parameters to normality which proved their antihyperlipidemic action. Histopathology of liver, kidney and heart on DOCA-salt induced rats treated with CEEM showed reduced the damages towards normal histology.@*CONCLUSIONS@#These findings provided evidence that CEEM was found to be protecting the liver, kidney and heart against DOCA-salt administration and the protective effect could attribute to its antihyperlipidemic activities.

Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage.

Activation of the Renal PI3K/Akt/mTOR Signaling Pathway in a DOCA-Salt Model of Hypertension / 전남의대학술지

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-beta1, and alpha-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Activation of the Renal PI3K/Akt/mTOR Signaling Pathway in a DOCA-Salt Model of Hypertension / 전남의대학술지

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-beta1, and alpha-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Reduction of kidney damage by supplementation of vitamins C and E in rats with deoxycorticosterone-salt-induced hypertension

We assessed whether cosupplementation of vitamins C and E has additive beneficial effects on reducing the kidney damage and attenuation of the arterial pressure elevation compared to administration of either vitamin C or vitamin E alone in deoxycorticosterone acetate-salt-induced hypertension. Forty rats were divided into 4 study groups and 1 sham-operated group. Unilateral nephrectomy was carried out in the study groups and hypertension was induced by deoxycorticosterone injection and 1% sodium chloride and 0.2% potassium chloride added to the drinking water. Vitamins C and E [200 mg/kg/day] or combination of them were administered with DOCA-salt for 4 weeks in 3 study groups. The effects of DOCA and salt and treatment with vitamins were compared in terms of blood pressure, urinary protein excretion, antioxidant activity of the kidneys, and renal histological changes. Four weeks of supplementations of vitamins C, vitamin E, and both in the DOCA-salt-treated rats had comparable significant effects in decreasing systolic blood pressure. Urinary protein excretion and histological damage did not significantly change with the combination therapy of vitamins C and E compared to the vitamin C or E alone. The renal levels of glutathione and ferric reducing/antioxidant power in combination therapy group were similar to the two other treatment groups and were significantly higher than non-treated group. Co-administration of vitamin C and E does not have an additive beneficial effect on reducing the kidney damage and hypertension compared to either vitamin C or E alone in DOCA-salt-induced hypertension

Pathophysiological Implications of Sodium Transporters and Water Channels in the Kidney / 대한신장학회지

Renal sodium and water reabsorption occurs through epithelial sodium transporters and aquaporin (AQP) water channels in various segments of tubules. We have demonstrated altered regulation of these transporters and channels in various pathophysiological conditions. In nephrotic syndrome and liver cirrhosis, expression of epithelial sodium channels (ENaC) was increased in the late distal convoluted tubule, connecting tubule, and collecting duct. In spontaneously hypertensive rats, the expression of Na,K-ATPase as well as that of ENaC was increased. In contrast, AQP1-3 and sodium transporters was decreased in the kidney from deoxycorticosterone acetate-salt hypertension. In two-kidney, one clip hypertension, the expression of Na,K-ATPase, NHE3, NKCC2 and ENaC subunits was decreased in the clipped kidney while remained unchanged in the contralateral kidney. We have also shown an increased activity of renal atrial natriuretic peptide system in postobstructive natriuresis/ diuresis. In acute kidney injury (cisplatin-, gentamicin- and ischemia/reperfusion-induced), the expression of Na,K-ATPase, NHE3, NKCC2 and AQP1-3 was decreased. The altered regulation of sodium transporters and AQP may be causally related with various kidney diseases and hypertension.

Pathophysiological Implications of Sodium Transporters and Water Channels in the Kidney / 대한신장학회지

Renal sodium and water reabsorption occurs through epithelial sodium transporters and aquaporin (AQP) water channels in various segments of tubules. We have demonstrated altered regulation of these transporters and channels in various pathophysiological conditions. In nephrotic syndrome and liver cirrhosis, expression of epithelial sodium channels (ENaC) was increased in the late distal convoluted tubule, connecting tubule, and collecting duct. In spontaneously hypertensive rats, the expression of Na,K-ATPase as well as that of ENaC was increased. In contrast, AQP1-3 and sodium transporters was decreased in the kidney from deoxycorticosterone acetate-salt hypertension. In two-kidney, one clip hypertension, the expression of Na,K-ATPase, NHE3, NKCC2 and ENaC subunits was decreased in the clipped kidney while remained unchanged in the contralateral kidney. We have also shown an increased activity of renal atrial natriuretic peptide system in postobstructive natriuresis/ diuresis. In acute kidney injury (cisplatin-, gentamicin- and ischemia/reperfusion-induced), the expression of Na,K-ATPase, NHE3, NKCC2 and AQP1-3 was decreased. The altered regulation of sodium transporters and AQP may be causally related with various kidney diseases and hypertension.

Modulation of Baroreflexes in Hypertensive Rats / 대한신장학회지

PURPOSE: Baroreceptor reflex regulation has been shown to reset towards a higher blood pressure level. This study was designed to assess alterations of chronotropic baroreflexes in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Arterial pressure and heart rate (HR) were monitored continuously during intravenous infusions of phenylephrine or sodium nitroprusside. Ensuing reflex HR responses during each drug infusion were determined in two ways: (a) at 10 s intervals (time analysis), and (b) with every 10 mmHg change in pressure (pressure analysis). RESULTS: Both pressor and depressor responses produced by phenylephrine or sodium nitroprusside were comparable between normotensive and hypertensive rats. Both reflex tachycardia and bradycardia were attenuated in 2K1C hypertensive rats as compared with normotensive rats, whereas no significant differences were shown in DOCA-salt hypertensive rats. CONCLUSION: These results indicate that chronotropic baroreflexes are impaired in 2K1C hypertensive rats, but not in DOCA-salt hypertensive rats.

Effects of Rosiglitazone on Heat Shock Protein and the Endothelin System in Deoxycorticosterone Acetate-Salt Hypertensive Rats

The deoxycorticosterone acetate (DOCA)-salt rat is known as a model of volume dependent hypertension and characterized by increased cardiac endothelin-1 (ET-1) content. Recently, it has been reported that rosiglitazone (RGT), a peroxisome proliferator-activated subtype gamma receptor agonist, shows blood pressure lowering effect. We investigated whether DOCA-salt hypertension is associated with altered expression of heat shock proteins (HSP) and ET-1 in the heart, aorta, and kidney, and whether RGT changes HSP expression and ET-1 in association with its blood pressure lowering effect. Two weeks after the silastic DOCA (200 mg/kg) strips implantation, DOCA-salt rats were randomly divided to receive control diet with or without RGT (10 mg/kg/day) for another 2 weeks. The mRNA expression of ET-1 was determined by real time polymerase chain reaction. The expression of HSP was determined by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was markedly increased, while creatinine clearance decreased. RGT treatment attenuated high blood pressure and decreased creatinine clearance in DOCA-salt rats. The mRNA expression of ET-1 was increased in DOCA-salt rats compared to controls, which was counteracted by RGT treatment. The protein expression of HSP70, HSP32, and HSP25 was increased in the kidney and heart in DOCA-salt rats, which was attenuated by RGT treatment in the kidney, but not in the heart. In conclusion, increased expression of ET-1 may play a role in the pathogenesis of hypertension in DOCA-salt rats, which was counteracted by the treatment of RGT. Up-regulation of HSP70, HSP32, and HSP25 in the kidney and heart may play a role in organ protection against a variety of stresses.

Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids

OBJECTIVE: The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol. METHOD: Experiment 1: on Day 1 groups of mice were pretreated with saline or with epipregnanolone. After 30 min each group was further divided in subgroups that received ethanol or saline. Thirty, 60 and 90 min after the injections the animals were tested on the rota-rod or the body temperature was measured. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Experiment 2 and 3: On Day 1 groups of mice were treated with epipregnanolone and after 15 min each group was divided into three groups in order to receive pregnenolone sulfate, dehydroepiandrosterone sulfate or saline. Thirty minutes later, each group was further divided into two subgroups in order to receive ethanol or saline, respectively, and 30, 60 and 90 min later the animals were tested as in the experiment 1. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. RESULTS: Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanol-induced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of...

OBJETIVO: O objetivo do presente estudo foi o de investigar o efeito da epipregnanolona sobre a influência de neuroesteróides no desenvolvimento da tolerância rápida aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol. MÉTODO: Experimento 1: no Dia 1, grupos de camundongos foram pré-tratados com salina ou com epipregnanolona. Após 30 min, cada grupo foi subdividido recebendo etanol ou salina. Aos 30, 60 e 90 min após as injeções, os animais foram testados no rota-rod ou a temperatura corporal foi avaliada. No Dia 2, todos os grupos receberam etanol e um procedimento similar foi seguido para avaliar a tolerância rápida. O pré-tratamento com a epipregnanolona (0,10-0,30 mg/kg) bloqueou significantemente o desenvolvimento da tolerância aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol em camundongos. Experimento 2 e 3: no Dia 1, grupos de animais foram tratados com epipregnanolona e, após 15 min, cada grupo foi dividido em três grupos para receber sulfato de pregnanolona, sulfato de dehidroepiandrosterona ou salina. Após 30 min, cada grupo foi dividido em dois subgrupos para receber etanol ou salina, respectivamente, e após 30, 60 e 90 min os animais foram testados como no experimento 1. No Dia 2, todos os grupos receberam etanol e 30 min após foram testados como mencionado no experimento 1. RESULTADOS: Considerando a tolerância ao prejuízo motor induzido pelo etanol, a epipregnanolona (0,15 mg/kg) bloqueou a ação estimulatória do sulfato de dehidroepiandrosterona (0,15 mg/kg), mas não afetou a ação do sulfato de pregnanolona (0,08 mg/kg). Entretanto, a epipregnanolona bloqueou a ação inibitória da alotetrahidrodeoxicorticosterona (0,10 mg/kg). Em relação à hipotermia induzida pelo etanol, os resultados demonstraram que o pré-tratamento com epipregnanolona (0,30 mg/kg) bloqueou significantemente a ação estimulatória do sulfato de dehidroepiandrosterona e do sulfato de pregnanolona, bem como a ação...

Oxidatvive Stress in Rat Model of Preeclampsia and Clinical Correlates

There are growing evidences suggesting a pivotal role of oxidative stress in the pathophysiology of preeclampsia. We investigated oxidative stress in the rat model of preeclampsia, and in clinical cases. Pregnant female rats were injected intraperitoneally with deoxycorticosterone acetate (DOCA) and given 0.9% saline as drinking water during their pregnancy. We assessed plasma F2-isoprostane (8-iso-PGF2alpha) and malondialdehyde (MDA) in a rat model, and the same markers in the plasma of maternal blood and fetal cord blood in pregnant women with preclampsia. Blood samples from the umbilical arteries and veins were collected separately. The concentrations of MDA were increased in the preeclampsia groups of animal and humans, compared with the control group; it was significantly increased in the umbilical artery and vein of the preeclampsia group. The concentrations of F2-isoprostane were elevated in the preeclampsia groups of animal and humans, compared with the control group, and the increase in F2-isoprostane concentration was prominent in the umbilical vein than umbilical artery of the preeclampsia group. Therefore, it appears that the placenta has an important role in the pathophysiology of preeclampsia, and the F2-isoprostanes of the umbilical vein may serve as a relatively reliable marker for ischemic/hypoxic injury to the fetus during the perinatal period.

Altered Regulation of 11beta-hydroxysteroid Dehydrogenase II in the Kidney of Rats with Experimental Hypertension

The present study was aimed at investigating the role of type II 11beta-hydroxysteroid dehydrogenase (IIbeta- HSD II) in the development of hypertension. Two-kidney, one-clip (2K1C), deoxycorticosterone acetate (DOCA)/salt, or NG-nitro-L-arginine methyl ester (L-NAME) hypertension was induced in male Sprague- Dawley rats. Four weeks later, the expression of 11beta-HSD II mRNA was determined in the kidney by Northern blot analysis. The plasma level of aldosterone was measured by radioimmunoassay. In 2K1C hypertension, the expression of 11beta-HSD II was decreased in the clipped kidney and increased in the non-clipped kidney. The expression was increased in the remnant kidney of DOCA/salt hypertension, while decreased in the kidneys of L-NAME hypertension. The plasma level of aldosterone was increased, decreased, and remained unchanged in 2K1C, DOCA/salt, and L-NAME hypertension, respectively. The down-regulation of 11beta-HSD II may contribute to the sodium retention, thereby increasing the blood pressure in 2K1C and L-NAME hypertension. On the contrary, the up-regulation in DOCA/salt hypertension may play a compensatory role to dissipate the sodium retention.

study of anticonvulsant effect of some steroids on induced seizures in adult male mice

Hormones influence brain functions throughout life and might alter seizures susceptibility by affecting neuronal excitability. Alterations in gamma amino butyric acid [GABA,] ergic neurotransmission are associated with seizures disorders and consequently much of antiepileptic therapy is directed towards the GABA A receptor complex. In humans, seizures patterns are affected by some factors such as the onset of puberty, pregnancy and stress suggesting that there is an underlying hormonal component. the present study was conducted to evaluate the anticonvulsant effect and the possible mechanism of action of some steroid hormones. Progesterone, deoxycorticosterone [DOC] and dehydroepiandrosterone [DHEA] in experimentally induced seizures in male mice. This study was carried out on adult albino male mice weighing 24-26gm and included two experiments: experiment I, in which two models of seizures were used; pentylenetetrazol [PTZ] model and maximal electro-convulsive shock seizures [MES] model. In each model, the animals were divided into 5 groups. The first group was kept as a control group and each of the other 4 groups was subdivided into 3 subgroups, 20 animal each. The treated groups included: diazepam, progesterone, DOC and DHEA treated groups at different doses. In PTZ model, PTZ was given in a dose of 70 mg/kg by intraperifoneal [i.p.] injection to induce chemoconvulsant seizures while in MES model, the animal received a stimulus train of electric current 25 mA, 50 Hz through the brain via ear electric clip. Diazepam and hormones were given 30 mm prior to PTZ injection or MES induced seizures. Experiment II in which bicuculline, a GABA A receptor antagonist was used in a dose of 1 mg/kg subcutaneously [s.c] 15 mm prior to administration of hormones. The ictal activity [latency, duration of myoclonic seizures and percent of protection against seizures and mortality] was recorded in either experiment. It was observed that progesterone suppressed PTZ induced seizures where it significantly [P<0. 001] prolonged the latency and shortened the duration of myoclonic seizures as compared to control with median effective dose [ED 50] of about 20 mg/kg s.c. The protection against seizures was 60, 70 and 75% and against mortality was 100%. Also, DOC administration exhibited a potent significant anticonvulsant activity in PTZ model in comparison to control and nearly equal to diazepam treatment. The ED 50 of DOC was 5 mg/kg and complete protection against seizures and mortality was observed at 20 and 80 mg/kg. In MES model, administration of progesterone at.20 and 80 mg/kg induced no significant anticonvulsant effect and ED 50 war observed at a higher dose [160 mg/kg]. Treatment with DOC 5 mg/kg produced no anticonvulsant activity, ED 50 was 20 mg/kg and complete protection against seizures was reached at 80 mg/kg. Both in PTZ and MES model, diazepam at the all tested doses induced a significant anhiconvulsant effect, while DHEA lacked any anticonvulsant activity, even it has a convulsant effect. Pretreatment with. bicuculline prior to progesterone and DOC administration caused a significant reversal of the anticonvulsant activity of these hormones. These findings indicate that the steroid hormones; progesterone and DOC have a broad spectrum anticonvulsant activity in animal seizures models [especially PTZ model] mediated by GABA A receptor modulation. Therefore, they might be involved in the modification of seizures frequency and epilepsy and might have a clinical importance in the future treatment of seizures disorders in conjunction with the usual antiepileptic drugs. On the other hand, DHEA has no anti convulsant effect

A Case of Male Pseudohermaphroditism due to 17alpha-Hydroxylase Deficiency / 대한불임학회지

Female phenotype of a 46,XY male may originates from male pseudohermaphroditism due to 17alpha-hydroxylase deficiency. Lack of cortisol increases adrenocorticotropic hormone (ACTH) and mineralocorticoid production, leading to low renin hypertention and hypokalemia. A 41-year-old phenotypic female presented primary amenorrhea and hypertension. In the hormonal profile, the levels of serum estradiol, testosterone, rennin, and cortisol were decreased and ACTH and deoxycorticosterone were increased. Laparoscopic bilateral gonadectomy was performed, and corticosteroid, antihypertensive drugs, and estrogen were administered. We report this case with a brief review of the literatures.

Detection of serum autoantibodies against AT₁A-receptor during the development of the four types of hypertensive rat models / 生理学报

Using two-kidney one-clip renal hypertensive (2K1C group), stress-induced hypertensive (neural group), DOCA-salt treated hypertensive (DOCA group) and spontaneously hypertensive rats (SHR group), to investigate the change in AT(1A)-receptor autoantibodies (AT(1A)-AAs) during the development of the four types of hypertension. The biological activities of AT(1A)-AAs were examined. It was shown that the frequency of occurrence and titres of AT(1A)-AAs increased significantly during the development of hypertension. In the four hypertensive groups studied, the occurrence of AT(1A)-AAs was most prominent in SHR, 2K1C and neural groups. The biological effects of AT(1A)-AAs were shown to increase the beating frequency of cultured neonatal myocardial and vascular contractile tension. It is suggested that autoimmune mechanisms are involved the pathogenesis of different types of hypertension and the AT(1A)-AAs may be one of the mechanisms leading to cardiac hypertrophy.