Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

BACKGROUND: Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury. METHODS: Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured. RESULTS: Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group. CONCLUSIONS: Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model.

Carcass characteristics, physicochemical changes and oxidative stress indicators of meat from sheep fed diets with coffee pulp / Características de carcaça, alterações físico-químicas e indicadores de estresse oxidativo de carne de ovinos alimentados com dietas com polpa de café

The purpose of this study was to determine how feeding sheep coffee pulp affects carcass characteristics and what changes occur in physicochemical, antioxidant capacity and oxidation of the meat during refrigerated storage. The experiment was carried out in 15 Blackbelly lambs weighing an average 22.86±0.76kg. The animals were assigned to three treatments: T0=control diet, T1=diet with 8% coffee pulp, and T2=diet with 16% coffee pulp. After fattening for 56 days, the sheep were slaughtered and the carcasses assessed. The inclusion of 16% coffee pulp in the diet increased carcass dressing from 48.19 to 50.83% and decreased the amount of fat in rumen and intestines from 3.43 to 2.53% (P<0.05). The inclusion of coffee pulp in the diet did not alter the amount of crude protein or fat in meat or its oxidation and antioxidant capacity during refrigerated storage. However, the inclusion of coffee pulp in the diet decreased fat in the rumen and intestines, and thus increased the amount of usable meat.

Objetivou-se determinar características de carcaça, alterações físico-químicas, capacidade antioxidante e de oxidação da carne de ovinos alimentados com polpa de café, durante o período de armazenamento refrigerado. O experimento foi realizado com 15 cordeiros Blackbelly com um peso médio de 22,86 ± 0,76kg. Os animais foram distribuídos em três tratamentos: T0=dieta controle, T1=dieta com 8% de polpa de café e T2=dieta com polpa de café de 16%. Depois de 56 dias de engorda, cordeiros foram abatidos, e a carcaça avaliada. Inclusão de polpa de café de 16% na dieta aumentou o rendimento de carcaça de 48.19 para 50.83% e diminuiu a quantidade de gordura no rúmen e nos intestinos de 3.43 para 2.53% (P<0,05). A inclusão de polpa de café na dieta não alterou a proteína ou a gordura na carne nem a oxidação e a capacidade antioxidante durante o armazenamento refrigerado. A inclusão de polpa de café na dieta de cordeiros diminui a gordura no rúmen e nos intestinos e aumenta a quantidade de carne na carcaça.

Carcass characteristics, physicochemical changes and oxidative stress indicators of meat from sheep fed diets with coffee pulp / Características de carcaça, alterações físico-químicas e indicadores de estresse oxidativo de carne de ovinos alimentados com dietas com polpa de café

The purpose of this study was to determine how feeding sheep coffee pulp affects carcass characteristics and what changes occur in physicochemical, antioxidant capacity and oxidation of the meat during refrigerated storage. The experiment was carried out in 15 Blackbelly lambs weighing an average 22.86±0.76kg. The animals were assigned to three treatments: T0=control diet, T1=diet with 8% coffee pulp, and T2=diet with 16% coffee pulp. After fattening for 56 days, the sheep were slaughtered and the carcasses assessed. The inclusion of 16% coffee pulp in the diet increased carcass dressing from 48.19 to 50.83% and decreased the amount of fat in rumen and intestines from 3.43 to 2.53% (P<0.05). The inclusion of coffee pulp in the diet did not alter the amount of crude protein or fat in meat or its oxidation and antioxidant capacity during refrigerated storage. However, the inclusion of coffee pulp in the diet decreased fat in the rumen and intestines, and thus increased the amount of usable meat...

Objetivou-se determinar características de carcaça, alterações físico-químicas, capacidade antioxidante e de oxidação da carne de ovinos alimentados com polpa de café, durante o período de armazenamento refrigerado. O experimento foi realizado com 15 cordeiros Blackbelly com um peso médio de 22,86 ± 0,76kg. Os animais foram distribuídos em três tratamentos: T0=dieta controle, T1=dieta com 8% de polpa de café e T2=dieta com polpa de café de 16%. Depois de 56 dias de engorda, cordeiros foram abatidos, e a carcaça avaliada. Inclusão de polpa de café de 16% na dieta aumentou o rendimento de carcaça de 48.19 para 50.83% e diminuiu a quantidade de gordura no rúmen e nos intestinos de 3.43 para 2.53% (P<0,05). A inclusão de polpa de café na dieta não alterou a proteína ou a gordura na carne nem a oxidação e a capacidade antioxidante durante o armazenamento refrigerado. A inclusão de polpa de café na dieta de cordeiros diminui a gordura no rúmen e nos intestinos e aumenta a quantidade de carne na carcaça...

Ca2+ dependence of the response of three adenosine type receptors in rat hepatocytes.

The effect of three different receptor-specific adenosine agonists on the rate of ureagenesis by isolated rat hepatocytes and the dependence on the external free Ca2+ concentration ([Ca2+]e) were investigated. In the presence of high [Ca2+]e all adenosine receptor agonists increased ureagenesis to similar levels. However, with low [Ca2+]e the effects of each agonist varied as follows: (i) the adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine, increased ureagenesis depending partially on [Ca2+]e, (ii) the adenosine receptor A2 agonist, 2-p-(-2-carboxy-ethyl) phenethylamino-5'-N-ethylcarboxyamido adenosine hydrochloride, increased ureagenesis independently of [Ca2+]e and (iii) in contrast, the adenosine receptor A3 agonist N6-2-(-4-aminophenyl) ethyladenosine, increased ureagenesis only in the presence of high [Ca2+]e. The adenosine receptor A1 antagonist, 1-allyl-3,7-dimethyl-8-phenyl xanthine, inhibited the effect of the adenosine receptor A1 agonist on ureagenesis, but not the effect of the adenosine A2 or A3 receptor agonists. The adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine, inhibited only the effect of the adenosine A2 receptor agonist. Thus, in addition to A1 and A2 type adenosine receptors, rat hepatocytes possess an A3-like adenosine receptor which responds to the addition of an adenosine A3 agonist by accelerating ureagenesis a [Ca2+]e dependent manner. Moreover, it was observed that in the presence of extracellular Ca2+ each agonist increased [Ca2+]i and this effect was inhibited by the appropriate specific antagonist.

Hepatic and cardiac oxidative stress and other metabolic changes in broilers with the ascites syndrome.

The objective of this study was to evaluate the gluconeogenic response of in vitro stimulated hepatocytes from control broilers and broilers with clinical manifestations of the ascites syndrome. The basal rate of glucose synthesis from lactate was found to be threefold greater in sick birds than in the control group and stimulation obtained with epinephrine was found to be quantitatively similar in both groups. Under basal conditions, the hepatocytes from the sick broilers exhibited 60% more ammonium than the control birds. In addition, the quantification of thiobarbituric acid reactive substances, as indicators of cellular lipoperoxidation, showed an increase of over 100% in heart and liver of sick broilers fowl. In conclusion, the complex integrated response of gluconeogenesis to epinephrine is maintained in broilers with ascites, although their hepatocytes present changes compatible with those observed in cases of oxidative stress. It is not known whether this stress is a cause or a consequence of the ascites syndrome.

Gonadal steroid modulation of neuroendocrine transduction: a transynaptic view.

1. Steroid hormones act on neuronal communication through different mechanisms, ranging from transynaptic modulation of neurotransmitter synthesis and release to development and remodeling of synaptic circuitry. Due the wide distribution of putative brain targets for steroid hormones, acute or sustained elevations of their circulating levels may affect, simultaneously, a variety of neuronal elements. In an elementary mode of interaction, steroids are able to modulate both the synthesis and release of a neurotransmitter at a particular synapse, and the response of its target postsynaptic cells. Using two neuroendocrine transducing systems-the rat pineal gland and the GT1-7 cell line-we have examined these interactions and the following findings are discussed in this article. 2. In the rat, pineal melatonin production is partially controlled by gonadal hormones. In females, melatonin synthesis and secretion is reduced during the night of proestrus, apparently as a consequence of elevated estradiol and progesterone levels. In males, circulating testosterone seems to be necessary to maintain the amplitude of the nocturnal melatonin peak. 3. Some gonadal effects on pineal activity are exerted on its noradrenergic input, since changes in circulating steroid hormone levels are able to induce acute modifications of tyrosine hydroxylase activity in pineal sympathetic nerve terminals. 4. Gonadal steroids are also able to regulate the response of pineal cells to adrenergic stimulation, since in vivo treatment of both male and female rats with steroid hormone blockers induces profound modifications in adrenergically-induced accumulation of cyclic AMP (cAMP) in dispersed pinealocytes. 5. Direct exposure of pineal cells from gonadectomized female and male rats to estradiol (E2) or testosterone (T), respectively, potentiates pinealocyte response to adrenergic activation. In addition, short-term (15 min) exposure to either progesterone (Pg) or progesterone coupled to bovine serum albumin (P-3-BSA) suppresses the E2-dependent potentiation of adrenergic response in female rat pinealocytes. 6. Exposure of GT1-7 cells to E2 completely blocked the norepinephrine (NE)-induced elevation of cAMP content. In E2-treated GT1-7 cells, additional exposure (15 min) to either Pg or P-3-BSA abolished E2-dependent inhibition of NE responsiveness. In addition, P-3-BSA alone increased basal cAMP levels in GT1-7 cells, regardless previous exposure to E2. 7. In conclusion, there are evidences, both from the current literature and from the present results, supporting the view that in some neuroendocrine systems gonadal hormones modulate neurotransmission by acting, simultaneously, at pre- and postsynaptic sites. The models presented here constitute appropriate examples of this transynaptic mode of steroid and, therefore, may offer a useful approach to investigate steroid hormone actions on the brain.

Ovarian hormones regulate alpha 1- and beta-adrenoceptor interactions in female rat pinealocytes.

We have examined the effects of alpha 1- and beta-receptor activation on cyclic AMP (cAMP) accumulation in cultured pinealocytes from female ovariectomized rats, and from intact rats at proestrus treated with the antiestrogen Tamoxifen, the antiprogestagen RU486, or with both. Isoproterenol (a beta-agonist) significantly increased cAMP levels in pinealocytes from intact and ovariectomized rats. This response was considerably enhanced in pinealocytes from rats treated with RU486 or Tamoxifen alone, but not with both. Moreover, incubation of pinealocytes with isoproterenol together with phenylephrine (an alpha 1-agonist) produced a synergistic effect in animals that had been ovariectomized, or that had received RU486, either alone or in combination with Tamoxifen. These results suggest that, in female rats, ovarian steroids may regulate the interactions between alpha 1- and beta-adrenergic receptors, and thus modulate pineal melatonin synthesis during the oestrous cycle through these mechanisms.

[Chemical changes in colostrum fermented with sorghum]. / Cambios químicos en el calostro fermentado con sorgo.

Colostrum from Holstein cows was collected during the first three days post partum. Ground sorghum (7.5%) was added to it. Untreated colostrum used as control, and sorghum treated colostrum samples were allowed to ferment for 0, 8 or 21 days at 18-20 degrees C in glass containers; pH, moisture, crude protein, digestible protein, ammonia, lactic acid and total energy were analyzed in untreated and treated samples. Crude protein was not significantly different (P > 0.01) in control colostrum (7.12, 5.76, 5.70%) and treated colostrum (6.66, 5.71, 5.98%) at 0, 8 and 21 days of fermentation respectively. Digestible protein was higher (P < 0.01) in the untreated (90.0, 93.0%) than in the treated colostrum (89.0, 81.0, 86.0%). Ammonia content was also higher (P < 0.01) in the control (0.25, 1.31, 1.37%) than in the treated one (0.23, 0.97, 1.20%). Lactic acid was lower (P < 0.01) in the untreated colostrum (0.82 g/100 ml) than in the treated colostrum (1.24 g/100 ml) after 21 days of fermentation. Total energy values were lower (P < 0.01) at 8 and 21 days of fermentation in the untreated (0.91, 0.84 Kcal/g) than in the treated colostrum (1.16, 0.97 Kcal/g). The addition of sorghum to colostrum reduced the crude, protein degradation and the ammonia content after 8 and 21 days of fermentation, increasing total energy and lactic acid content after 21 days of fermentation.

Inhibition of adenosine mediated responses in isolated hepatocytes by depolarizing concentrations of K+.

Isolated rat hepatocytes, incubated in a high K+ medium which depolarizes their plasma membrane, were used to investigate the response to adenosine. High K+ concentration blocked both the adenosine mediated increase of calcium influx and the increase in the rate of urea synthesis. It is concluded that a) adenosine stimulates calcium influx in hepatocytes probably through receptor-operated Ca2+ channels which are closed by depolarization of the plasma membrane, b) the higher cytosolic calcium concentration triggers a regulatory step that fully stimulates the rate in urea synthesis.

"Hormone-like" effect of adenosine and inosine on gluconeogenesis from lactate in isolated hepatocytes.

In isolated rat hepatocytes adenosine and inosine showed a dose-dependent increase in the rate of glucose synthesis from lactate with a Ka of 7.5 x 10(-8) and 9 x 10(-8) M, respectively. Absence of this action was recorded with: IMP, xanthosine, adenine, hypoxanthine, and uric acid. A reciprocal inhibition of individual gluconeogenic stimulation was found in cells incubated with glucagon or epinephrine and adenosine, but not with inosine. 5'-(N-ethyl) carboxamido adenosine was more potent than adenosine, whereas N6-(L-2-phenylisopropyl)-adenosine antagonized the stimulation of gluconeogenesis by adenosine. Neither of the analogs used modified the stimulatory role of inosine on the studied pathway. Adenosine and inosine may be involved in the short term regulation of gluconeogenesis.

[Idiopathic pulmonary hemosiderosis; long-term follow-up in 10 patients treated with corticoids and immunosuppressive agents]. / Hemosiderosis pulmonar idiopática; seguimiento a largo plazo de 10 pacientes tratados con corticoides e inmunosupresores.

A long-term follow-up of idiopathic pulmonary hemosiderosis in 10 patients treated with corticoids and immunosuppressors. Ten patients with I.P.H. are studied from the clinical, radiological, hematologic and respiratory functional viewpoints. The long-term evaluation (mean 7.4 years) is described together with the response to steroidal treatment (prednisone) associated with an immunosuppressor (6 +/- mercaptopurine). Only one out of the 9 patients did not return to control following 1 year of treatment. A relationship between the decrease or suppression of one or both drugs and the appearance of relapses is observed in all patients. Comments are made on the usefulness of the associated treatment and its administration is suggested for long periods giving prednisone every 48 hours. The possibility to discontinue both drugs is discussed, but not before the patient has remained asymptomatic for at least one year. Recent studies with ultramicroscopy tending out the pathogenesis of the disease are stressed.

Severe right ventricular outflow tract obstruction caused by an intracavitary cardiac neurilemoma: succesful surgical removal and postoperative diagnosis.

A 32-year-old woman with a one-year history of progressive shortness of breath and chest pain was found to have a grade 4/6 systolic murmur at the base of the heart and left sternal border. Right ventricular enlargement was found by physical examination, ECG, and chest roentgenogram. Cardiac catheterization showed elevated right ventricular pressure, an intracavitary pressure gradient, and inability to enter the pulmonary artery. Angiography revealed a mass in the right ventricular outflow tract. Successful surgical removal of a large, well-encapsulated tumor mass was accomplished, and the tumor was interpreted as a benign neurilemoma. Postoperatively, the patient improved remarkably.