Effects of oral exposure to silver nanoparticles on the sperm of rats.

It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub-chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP-AgNPs induces slight toxicological effects in sperm rat parameters.

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

OBJECTIVES: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. METHODS: Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. RESULTS: HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). CONCLUSIONS: HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.

[Solid-cystic supratentorial hemangioblastoma affecting the falx cerebri. Report of a case]. / Hemangioblastoma sólido-quístico supratentorial afectando la hoz del cerebro. Presentación de un caso.

INTRODUCTION: hemangioblastomas are benign neoplasias that are originated in the central nervous system and constitute between 1.5-2.5% of intracranial tumors. The majority of them are infratentorial, mainly affecting the cerebellum (76%). Supratentorial lessions are rare, being in these cases the frontal, parietal or temporal lobes the most common locations. Meningeal involvement is infrequent. Only eight cases have been reported in the literature. In 30% of the cases, these tumors are associated with von Hippel Lindau syndrome (VHL). CASE REPORT: 67 year old woman without any medical or family history. She presented with 4 month evolution neurological symptoms. The cranial MRI scan showed a solitary solid-cystic lesion on the right paramedian frontal lobe, in contact with the falx cerebri. The pathological analysis showed a cellular proliferation composed of polygonal cells with clear cytoplasm due to the presence of intracytoplasmic vacuoles and round or oval nucleus without cytologic atypia. These cells were accompanied by a rich vascular network of capillary type and blood extravasation. She was diagnosed of supratentorial hemangioblastoma. CONCLUSION: the preoperative diagnosis of these neoplasms is difficult because the clinical suspicion is low in supratentorial location. Imaging techniques are useful but definitive diagnosis is made through pathologic examination. The use of immunohistochemical techniques is helpful for the differential diagnosis with lesions that are more common in this region. The importance of a correct diagnosis of these histologically benign tumors, lies on the possible association with VHL syndrome and its complications.

Hemangioblastoma sólido-quístico supratentorial afectando la hoz del cerebro. Presentación de un caso / Solid-cystic supratentorial hemangioblastoma affecting the falx cerebri. Report of a case

Introducción. Los hemangioblastomas son neoplasias benignas que se originan en el sistema nervioso central y constituyen entre un 1,5-2,5% de los tumores intracraneales. Mayoritariamente son de localización infratentorial, afectando principalmente al cerebelo (76%). Las lesiones supratentoriales son sumamente raras, siendo en estos casos la localización más habitual el lóbulo frontal, parietal o temporal. La afectación meníngea es excepcional, habiéndose descrito sólo ocho casos en la literatura. En un 30% de los casos, estos tumores se asocian al síndrome de von Hippel Lindau (VHL).Caso clínico. Mujer de 67 años sin antecedentes patológicos ni familiares de interés que se presentó conclínica neurológica de 4 meses de evolución. El estudio de resonancia magnética craneal demostró una lesión única sólido-quística frontal paramedial derecha, encontacto con la hoz del cerebro, que se orientó como meningioma. El estudio anatomo-patológico de la pieza quirúrgica objetivó una proliferación celular constituida por células poligonales con citoplasma claro debido a la presencia de vacuolas intracitoplasmáticas y núcleo redondo u oval sin atipia citológica. Estas células estaban acompañadas de una rica red vascular de tipocapilar, con anastomosis y extravasación sanguínea. Se diagnosticó de hemangioblastoma supratentorial. Discusión. El diagnóstico preoperatorio de estas neoplasias es difícil debido a que la sospecha clínica esbaja cuando se halla en localización supratentorial. Las técnicas de imagen son de utilidad, realizándose el diagnóstico definitivo a través del estudio anatomopatológico. El uso de técnicas de inmunohistoquímica es de gran ayuda para el diagnóstico diferencial con lesiones que habitualmente se localizan en esta región. La importancia de un diagnóstico correcto de estos tumores histológicamente benignos, radica, entre otras cosas,en la posible asociación con en síndrome de VHL y suscomplicaciones (AU)

Hemangioblastomas are benign neoplasias that are originated in the central nervous systemand constitute between 1.5-2.5% of intracranial tumors.The majority of them are infratentorial, mainly affectingthe cerebellum (76%). Supratentorial lessions are rare,being in these cases the frontal, parietal or temporallobes the most common locations. Meningeal involvementis in frequent. Only eight cases have been reported in the literature. In 30% of the cases, these tumors areas sociated with von Hippel Lindau syndrome (VHL).Case report. 67 year old woman without any medicalor family history. She presented with 4 month evolution neurological symptoms. The cranial MRI scan showed a solitary solid-cystic lesion on the right paramedianfrontal lobe, in contact with the falx cerebri. The pathological analysis showed a cellular proliferation composed of polygonal cells with clear cytoplasm due to the presence of intracytoplasmic vacuoles and round oroval nucleus without cytologic atypia. These cells wereaccompanied by a rich vascular network of capillarytype and blood extravasation. She was diagnosed ofsupratentorial hemangioblastoma. Conclusion. The preoperative diagnosis of these neoplasmsis difficult because the clinical suspicion is low in supratentorial location. Imaging techniques are useful but definitive diagnosis is made through pathologic examination. The use of immunohistochemical techniquesis helpful for the differential diagnosis with lesions that are more common in this region. The importance of acorrect diagnosis of these histologically benign tumors,lies on the possible association with VHL syndrome and its complications (AU)

Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study.

Caspases are the main point in the apoptotic process. We have collected some information from 210 cases of Ductal breast cancer (pT1 - pT2) such as tumour size, histological differentiation degree, lymph node status and tumor necrosis in the infiltrating component and we have evaluated the number of apoptotic cells or bodies by TUNEL technique as well as immunohistochemical studies to evaluate the expression of caspase 3 and caspase 6, and proliferation index. Our results show that lymph node status and cell atypism are independent prognostic factors for recurrence and mortality and only tumour size is an independent prognostic factor for recurrence. However, the apoptotic index and the immunohistochemical expression of caspases and cell proliferation index have not turned out to be independent prognostic factors neither for recurrence nor mortality. These results show that classic prognostic factors known until now are the most important factors to predict the evolution of the illness.

Tumour necrosis factor alpha in fat redistribution syndromes associated with combination antiretroviral therapy in HIV-1-infected patients: potential role in subcutaneous adipocyte apoptosis.

BACKGROUND: The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infected patients with FRS. MATERIALS AND METHODS: The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infected patients on HAART with FRS, another 60 HIV-1-infected patients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS: HIV-1-infected patients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS: TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy.

Carcinoma adenoescamoso gástrico en un paciente de raza caucásica / Adenosquamous gastric carcinoma in Caucasian patient

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Prognostic value of apoptosis in breast cancer (pT1-pT2). A TUNEL, p53, bcl-2, bag-1 and Bax immunohistochemical study.

Apoptosis or programmed cell death produces cells breaking into several fragments of nuclei, cytoplasm or both nuclei and cytoplasm, known as apoptotic bodies which can be visualized in haematoxylin-eosin staining. Some genes (promoters and suppressors) control this process and certain mutations may induce the expression of abnormal proteins, which can be detected by immunohistochemical staining. Apoptosis can be detected by the TUNEL method either identifying apoptotic bodies or cells at the initial stages of the fragmentation process. We have studied 186 cases of infiltrating ductal breast carcinoma, stages pT1-pT2, and analysed the prognostic significance of tumour recurrence and overall survival of apoptotic index (AI) through univariate and multivariate analysis. We have also studied the immunohistochemical protein expression of apoptosis promoter and suppressors gene (p53, nuclear expression; bcl-2 and Bax, cytoplasm expression; BAG-1, nuclear and cytoplasm expression). The results indicate prognostic significance of p53 and bcl-2 related to patient death and bcl-2 and tumour size to tumour recurrence, bcl-2 acting as a protector factor (apoptotic suppressor) in both situations. On the other hand, we have not found useful prognostic information of AI either to tumour recurrence or overall survival in univariate or multivariate studies. In this study, Bax expression does not provide a new prognostic role in breast carcinoma, although it contrasts to the bcl-2 action and accelerates death.

Carcinoma de cuello uterino. Tipos anatomopatológicos / Uterine cervical cancer. Anatomopathologic types

El carcinoma escamoso de cérvix es el tipo histológico más frecuente en las neoplasias de esta localización. Una variedad en ascenso en su incidencia en los últimos años es el adenocarcinoma. Otras variedades menos frecuentes son los tumores neuroendocrinos, mesenquimales, mixtos y los metastásicos. (AU)

Prognostic value of p53 protein expression and clinicopathological factors in infiltrating ductal carcinoma of the breast. A study of 192 patients.

The p53 gene is located on the short arm of chromosome 17. It encodes a 53-kd nuclear protein (p53) found in scant amounts in normal tissue. Mutations of the p53 gene have been reported in different human tumours. In breast cancer, it has been noted that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, although there is a high degree of variability, which may be due to different immunohistochemical techniques, varying assessment of results and the type of monoclonal antibody used. This study is an immunohistochemical analysis of p53 expression in 192 cases of infiltrating ductal carcinoma of the breast, correlating it with clinicopathological factors and the clinical course of the disease. Of all the breast-cancer tissue analysed, stains for p53 antibody were found in 87 tumours (45.3%). The results of multivariate analysis show that the independent predictors related to recurrence are tumour size, lymph-node metastasis and p53, while those related to death are necrosis, lymph-node metastasis and p53. In summary, our series showed prognostic significance between the expression of p53 and shorter survival time and disease-free interval for all patients in general as well as those who presented lymph-node metastases at the time of diagnosis.

Nephrotoxicity of simultaneous exposure to mercury and uranium in comparison to individual effects of these metals in rats.

Both inorganic mercury and uranium are known nephrotoxicants in mammals. In this study, the renal toxicity of a concurrent exposure to inorganic mercury and uranium was compared with the nephrotoxic effects of the individual metals in a rat model. Eight groups of rats, 10 animals per group, were subcutaneously given a single administration of mercuric chloride (HgCl2, 0.34 mg/kg and 0.68 mg/kg), uranyl acetate dihydrate (UAD, 2.5 mg/kg and 5 mg/kg), or combinations of both compounds at the same doses. A ninth group of rats received sc injections of 0.9% saline and was designated as the control group. Necrosis of proximal tubules, which was observed in all experimental groups, was the most relevant morphologic abnormality. Marked changes, which were remarkably greater than those induced by the individual elements, were noted in some urinary parameters in the groups concurrently exposed to HgCl2 and UAD. It could be an indicator of a synergistic interaction between mercury and uranium. In contrast, compared with the urinary levels found after individual administration of the highest doses of mercury and uranium, significant reductions in the urinary concentrations of these elements were noted following simultaneous exposure to both metals. At these doses, the reduction in the urinary metal excretion was also accompanied by significant decreases in the renal content of mercury and uranium. Whereas the results of some parameters pointed out a possible synergistic interaction between mercury and uranium, other measures hinted that an antagonistic interaction between these elements is also present.

Efectos sistémicos del implante de partículas de desgaste del polietileno en el hueso. Estudio experimental / Systemic effects of implantation of polyethylene wear particles on bone. Experimental study

Objetivo: Se ha estudiado el efecto que provoca el implante de partículas de desgaste de polietileno de alta densidad sobre los ganglios linfáticos, el hígado y el pulmón de la rata.Diseño experimental: Se ha implantado 1 mg de polvo de polietileno, constituido por una mezcla hetereogénea de partículas de un tamaño entre 1 y 100 micras, en un orificio practicado en la tibia de 16 ratas de la cepa Sprague-Dawley y se han examinado las muestras de los ganglios de la cadena ilíaca y cervical, tejido hepático y pulmonar a los 15 y 60 días de la intervención. El grupo control ha quedado constituido por 16 ratas a las que se ha realizado la misma intervención pero a las que no se han implantado partículas.Resultados: Un gran número de ganglios presentan hiperplasia difusa con un gran infiltrado macrofágico.Estos cambios no se observan en el grupo control. No se han observado partículas de polietileno en el interior de los ganglios linfáticos. No se han detectado cambios patológicos en las muestras de tejido hepático. En la mitad de las ratas que recibieron partículas se han detectado infiltrados inflamatorios peribronquiales y perivasculares en el pulmón, que no se han observado en el grupo control.Conclusiones: Las partículas de desgaste del polietileno provocan cambios patológicos en órganos a distancia de su lugar de implante. El mecanismo fisiopatológico y las consecuencias de estas alteraciones no son aun bien conocidos (AU)

Valor pronóstico de los receptores hormonales, índice de proliferación celular (Ki-67) y factores clinicopatológicos en el carcinoma ductal infiltrante de mama. estudio inmunohistoquímico de 192 pacientes / Prognostic value of hormonal receptors, cell proliferation index (Ki-67) and clinicopathologic factors of invasive ductal carcinoma of the breast. An immunohistochemical study of 192 patients

Objetivo. Valorar la relación entre los factores pronósticos clínicos, histológicos e inmunohistoquímicos en el carcinoma ductal infiltrante de mama. Material y métodos. Se estudiaron variables clínicas e histológicas, receptores hormonales e índice de proliferación celular (Ki-67) en 192 pacientes con carcinoma ductal infiltrante. Los receptores de estrógenos y progesterona fueron medidos de acuerdo con la intensidad de la tinción (I), con valores comprendidos entre 0 y 3, y el porcentaje de células positivas (P). Se calculó un histoscore para la fórmula (I + 1) × P (rango: 0-400). Los casos con un valor de histoscore por encima de 100 fueron considerados positivos. El índice de proliferación celular (Ki-67) fue medido contando 500 células, expresando el número de células positivas en porcentaje. Resultados.En 64,24 por ciento de los tumores se encontró tinción positiva para los receptores de estrógenos, mientras que el 49,12 por ciento fueron receptores de progesterona positivos. En 21,87 por ciento de los pacientes se encontró un índice de proliferación celular alto (> 25 por ciento). El tamaño tumoral, el número de mitosis, la presencia de necrosis y el estado ganglionar fueron factores pronósticos independientes en nuestro estudio estadístico. Conclusiones. Los receptores hormonales y el Ki-67 no son factores pronósticos independientes para la recidiva y la supervivencia global en nuestro estudio. Sólo los factores histológicos clásicos se han mostrado como factores pronósticos independientes. (AU)

[Death caused by designer drugs]. / Muerte por drogas de diseño.

OBJECTIVE: To draw pediatrician's attention to the risks of the use of designer drugs among adolescents and to review the problem. MATERIAL AND METHODS: We report the case of a 15-year-old girl admitted for seizures, who rapidly developed acute liver failure and died. Clinical and pathological details are reviewed. COMMENT: The use of designer drugs has increased considerably amongst Spanish adolescents and has been related to deaths in young adults with a variety of symptoms. Differential diagnosis should be made with the adverse effects of recreational drugs when clinical symptoms are confusing and in any unexplained deaths. Information on the effects of designer drugs should be disseminated among the population.

Muerte por drogas de diseño / Death due to designer drugs

Llamar la atención de los pediatras sobre los riesgos del consumo de drogas de diseño entre los adolescentes y revisar el problema. Se presenta el caso clínico de una adolescente de 15 años que ingresa con un cuadro convulsivo y desarrolla una insuficiencia hepática aguda con evolución fatal. Se revisan los detalles clínicos y anatomopatológicos. El consumo de drogas de diseño se ha extendido considerablemente entre la población joven en nuestro país. El consumo de drogas de diseño se ha relacionado con casos de muerte entre jóvenes adultos con manifestaciones diversas. Se debe establecer el diagnóstico diferencial con los efectos secundarios de las drogas recreativas en las situaciones en que la clínica no sea clara y ante cualquier muerte inexplicada. Se debe extender la información sobre las drogas de diseño y sus efectos (AU)

Intraosseous neurilemmoma of the radius: a case report.

Neurilemmomas are benign tumors that arise from Schwann cells. They are rarely found on bone. We describe a neurilemmoma in a 45-year-old patient that affected the distal metaphysis of the radius. Only 1 previous case has been described in the literature. We discuss the clinical presentation, the radiographic aspect, particularly the magnetic resonance imaging characteristics, and the microscopic findings.

Synchronus renal cell carcinoma and Bellini duct carcinoma: a case report on a rare coincidence.

Bellini duct carcinoma or collecting duct carcinoma (CDC) is a rare but aggressive primary renal neoplasm. The coexistence of two synchronous neoplasms in the same kidney is highly infrequent. As a result, it is hardly surprising that there are no references to renal cell carcinoma (RCC) combined with CDC of the same kidney in the literature. Histology and immunohistochemistry are important tools for differentiating between the two types of tumors involved. We present the first case of a synchronous occurrence of RCC and CDC of the same kidney.