Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings.

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8-10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5-10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.

Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings.

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.

[Surgical treatment options in bulbar urethral stenosis]. / Opciones de tratamiento quirúrgico en la estenosis de uretra bulbar.

OBJECTIVE: To review the outcome of bulbar urethroplasty using two stage surgical techniques. MATERIAL AND METHODS: Twenty-two of the 35 patients studied corresponded to end-to-end urethroplasty (ATT) and 13 to dorsal onlay graft (DOG) in preputial skin or oral mucosa variants. Clinical outcome was considered a failure when postoperative surgery was needed or the uroflowmetry was less than 15ml/s. The following variables were studied: age, previous surgery, number of urethrotomies and stricture length. The curves and log-rank Curves using the log-rank were elaborated for follow-up and comparison, with the Cox regression model for risk factors. RESULTS: Mean follow-up was 40.02 months. Of all the cases. 85.71% were successful. Of these, 86.36% were in the ATT group and 84.61% in the DOG group. There were no significant differences in the comparative LR test based in stricture length, previous surgery between both group and individualized for each management. The Cox regression model showed a risk of failure in the technique for the elderly patients (OR 2.2), it not achieving statistical significance in the remaining variables. CONCLUSIONS: The success rate achieved with the ATT technique is verified a gold standard option in short strictures. The DOG is shown as a valid option in long strictures in bulbar urethral in medium follow-up, using a oral mucosa or preputial onlay graft. More long-term follow-up must be performed with a greater number of patients to better evaluate these results.

[Utility of Tc-99m labeled heat-denatured red blood cell scintigraphy in a case of hepatic splenosis]. / Utilidad de la gammagrafía selectiva con hematíes desnaturalizados Tc-99m en un caso de esplenosis hepática.

The term splenosis, first used in the medical literature in 1939, refers to the autotransplantation of splenic tissue in a heterotopic location. We report the case of a known hepatitis C carrier in whom computed tomography scanning revealed a hepatic lesion suggestive of hepatocarcinoma. Magnetic Resonance imaging was performed for suspected hepatic splenosis, which was confirmed by Tc-99m labeled heat-denatured red blood cell scintigraphy. In addition to confirming the suspected diagnosis, this technique showed several pathological foci in distinct abdominal locations compatible with splenosis that had not previously been identified.

Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1).

OBJECTIVE: To determine the prognostic value of a subset of regulators of the transition from G1-to-S phase of cell cycle in stage T1 grade 3 bladder cancers. METHODS: Fifty-one such cases were investigated to determine the significance on patient's survival of p53, p21Waf1, p27Kip1, Cyclin D1, Cyclin D3, and ki67-MIB1 (proliferation index). The statistical analysis included Kaplan-Meier methodology with Log-rank test and Cox' proportional hazard analysis. RESULTS: Tumor size (p=0.0034), and the labeling index of ki67-MIB1 (p=0.0034), p53 (p=0.0332), p27kip1 (p=0.0059) and Cyclin D1 (p=0.0103) were associated to disease-free survival. Progression-free survival was related to tumor size (p<0.0001), ki67 (p=0.0163), p53 (p=0.0041), p27kip1 (p=0.0161), Cyclin D1 (p<0.0001) and Cyclin D3 (p<0.0001). Patient's overall survival was associated to Cyclin D3 (p<0.0001), p53 (p=0.0017), p21Waf1 (p=0.0142), Cyclin D1 (p<0.0001), ki67-MIB1 (p=0.0450), and tumor size (p=0.0296). Down-regulation of p27kip1 and Cyclin D3 over-expression (disease-free), over-expression of p53, Cyclin D1 and Cyclin D3 (progression-free), and over-expression of Cyclin D3 (overall survival) were independent predictors by Cox's multivariate analysis. Down-regulation of p27kip1 (p<0.001, R.R. 0.997, 95%C.I. 0.995-0.999), and over-expression of Cyclin D1 (p<0.001, R.R. 1.009, 95%C.I. 1.004-1.014) and Cyclin D3 (p=0.005, R.R. 1.013, 95%C.I. 1.004-1.022) were the main independent predictors. CONCLUSION: Down-regulation of p27kip1 and over-expression of Cyclin D1 and Cyclin D3 might be relevant predictors of survival in stage T1 grade 3 bladder cancers, thus selecting a group of patients at higher risk of malignant behavior.

[Localized Castleman's disease: description of a case and review of the literature]. / Enfermedad de Castleman localizada: descripción de un caso y revisión de la literatura.

Castleman's disease is a rare entity which is caracterized by its histological features: hyperplasia of lymph nodes and capillary proliferation. Two histological patterns has been described: hyaline vascular type and plasma cell type. From a clinical viewpoint has been identified two different clinical course: a localized type (ECL) usually of benign clinical course and a multicentric type (ECM) of worst prognosis. We present a case of Castleman"s disease localized in the neck region in which the excision was both diagnostic and therapeutic. The variety histological was hyaline-vascular type.

[Incidence and natural history of hepatocellular carcinoma in patients with chronic hepatitis C virus infection]. / Incidencia e historia natural del carcinoma hepatocelular en los pacientes con infección crónica por el virus de la hepatitis C.

OBJECTIVE: To report the natural history of patients with hepatitis C virus (HCV) infection and hepatocarcinoma (HCC) and to define clinico-biological variables with prognostic and predictive value of this complication. MATERIALS AND METHODS: A total of 543 patients consecutively diagnosed of chronic infection with HCV were included and followed prospectively and observationally regarding the development of HCC by means of semestral abdominal ultrasonography and measurement of serum alpha-fetoprotein (AFP). To determine variables with predictive value of HCC, the parameters determined at the start were compared, and all subjects diagnosed of hepatoma during the first twelve months after admission were excluded from the analysis. The Kaplan-Meier method was used to evaluate both survival and accumulated probability of HCC. RESULTS: During a mean follow-up period of 28.9 months, an incidence density of HCC of 2.6 per 100 inhabitants-year was obtained (n = 35). 52.6% of those with HCC in the first year were asymptomatic. The only initial variables associated with further development of HCC were age (64.6 vs 58.4 years; p = 0.0039) and alkaline phosphatase (373.5 vs 259 U/l; p = 0.001). Patients with cirrhosis at the start of the study had a higher risk of developing hepatoma than non-cirrhotic patients (RR: 11.5; 95% CI: 4.25-29.9; p < 0.0001). The presence of HCC decreased the survival of patients with cirrhosis (median 20 vs 75 months; log rank < 0.0001), with the exception of patients in stage C of the Child-Pugh classification. CONCLUSIONS: a) In the chronic infection with HCV, HCC showed to be an oligosymptomatic complication affecting almost exclusively patients with long-lasting cirrhosis. b) Survival in patients in the stage C of the Child-Pugh classification is independently associated with the coexistence of hepatoma; therefore, the early diagnosis of this complication should be restricted to those with a better liver functional reserve.

Absence of the inferior vena cava causing repeated deep venous thrombosis in an adult--a case report.

Agenesis of the inferior vena cava is an uncommon congenital vascular malformation. Although theoretically it may favor venous stasis, it is not normally associated with venous thrombosis. The authors found only three reports of the coexistence of both entities, and only one of these rules out the existence of associated hypercoagulability. They report the case of a patient with a history of repeated venous thrombosis. Magnetic resonance angiography and venography demonstrated complete agenesis of the inferior vena cava and persistence of a cardinal venous system with azygos and hemiazygos continuation, associated with right renal hypoplasia. Studies ruled out hypercoagulability syndrome, either primary or secondary to an occult neoplasm. The authors conclude that venous malformations, although rare, may cause thromboembolic disease, especially in young patients, and that magnetic resonance angiography is a useful diagnostic alternative to conventional phlebography.

[A 73 year-old patient with thrombocytopenia and a giant cerebral vascular malformation]. / Paciente de 73 años con trombopenia y malformación vascular cerebral gigante.

We report the case of a patient who was seen by purpura and thrombocytopenia. The differential diagnosis in this patient included the presence of cerebral giant vascular malformation, the intake antiepileptic drugs and the presence of a chronic liver disease caused by viral hepatitis C infection. However the final diagnoses of Idiopathic Thrombocytopenia Purpura was made because of the presence of antiplatelets antibodies, the fluctuate evolution, and the increase of platelet count after costicosteroid therapy.

[The prevalence of hepatitis C antibodies among volunteer blood donors with elevated blood transaminase and antibodies to the B virus core antigen]. / Prevalencia de anticuerpos frente al virus de la hepatitis C entre donantes voluntarios de sangre con hipertransaminasemia y anticuerpos frente al core del virus B.

The use of non-specific markers before 1989 (increased serum transaminase values and antibodies to hepatitis B core antigen) as a screening method for blood donors in an attempt to decrease the incidence of post-transfusional non-A non-B hepatitis (currently hepatitis C virus) was a matter of controversy. To determine the impact of the use of these markers on the detection of blood donors infected with hepatitis C virus, a prospective study was undertaken in Málaga (1988-1989) with 5,003 volunteer donors with two objectives: a) to know the prevalence of these non-specific markers (anti-HBc and increased serum transaminase) and antibodies to HCV (anti-C100) in our blood donor population; b) to determine whether the presence of some of these non specific markers in blood donors was associated with a higher rate of virus C infection. The prevalence of antibodies to HCV in blood donors with increased serum transaminase and/or anti-HBc was significantly higher than the prevalence found among the general blood donor population.

Human papillomavirus DNA as a factor determining the survival of bladder cancer patients.

The natural history of transitional cell carcinoma (TCC) of the urinary bladder is somewhat variable, with a significant number of tumour recurrences that occasionally evolve towards an infiltrating disease. The aim of this study was to investigate the presence of human papillomavirus (HPV) DNA in 76 TCC specimens, and then correlate such findings with the overall patient survival. However, other classical prognostic clinical and pathological variables such as pathological grade and stage, koilocytosis, age and sex were also tested. HPV DNA was investigated by means of the highly sensitive polymerase chain reaction (PCR). DNA primers specific for HPV types 6, 11, 16 and 18 were used. Our results showed that 7 (9.21%) out of 76 such cases were reactive for HPV 16 DNA; one of them also reacted with HPV 6 DNA. The statistical analysis was done by the Kaplan-Meier method, Wilcoxon's generalised test for studying the differences in survival curves and Cox's regression analysis for independent prognostic factors. A significant P-value was found for pathological grade (P < 0.0001) and stage (P < 0.0001), HPV 16 DNA (P = 0.0418) and koliocytosis (P = 0.0140). Thus, pathological grade was the only independent factor in the bladder cancer survival. These observations may prove useful in prognostic stratification of patients with TCC of the bladder.