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.

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.

Myxoid leiomyosarcoma of the ovary: analysis of three cases.

The first three cases of myxoid leiomyosarcoma occurring in the ovary are reported. Two cases in stage III were found in postmenopausal patients and a further case was found in stage I in a 32-year-old. All masses were large and gelatinous with cystic change, necrosis, and hemorrhage, but both uteri and ligaments and contralateral adnexa appeared normal. Microscopically, the tumors showed a predominantly reticular meshwork of elongated cells surrounded by abundant basophilic material. While electron microscopy proved inconclusive due to nondifferentiation, the use of monoclonal antibodies against smooth muscle actin demonstrated a smooth muscle type of differentiation. The differential diagnosis of this rare ovarian condition includes other myxoid ovarian lesions, such as ovarian edema, myxoma, endodermal sinus tumors, and the sarcomatous component of malignant mixed müllerian tumor and carcinosarcoma, as well as lymphovascular tumors. Since mitotic count due to decreased cellular density is unusually low in myxoid leiomyosarcoma, capsular rupture and clinical stage seem to be more reliable prognostic markers. The highly aggressive behavior of myxoid leiomyosarcoma parallels that of typical ovarian leiomyosarcoma. Two of the three patients in this series died of tumor at 13 and 24 months after diagnosis; the other patient is free of disease at 3 years after diagnosis.

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.

p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistochemical study of 153 cases.

The mutation of the p53 gene is a common phenomenon in numerous human tumors, leading to the accumulation of nonfunctioning p53 protein in the cell nucleus, which can be detected by immunohistochemistry. In breast cancer, it has been suggested that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, which must be borne in mind in selecting coadjuvant treatment for each patient. This study is an immunohistochemical analysis of p53 expression in 153 cases of mammary carcinoma, correlating it with histological grade, axillary node status, hormone receptors, cell-proliferation fraction and expression of the c-erbB-2 oncoprotein. Of all the breast-cancer tissue analyzed, 43.79% was positive for p53. The overexpression of this protein bears a direct statistically significant relationship to histological grade, cell-proliferation fraction and c-erbB-2, and an inverse relationship to estrogen and progesterone receptors. No statistically significant relationship was found with axillary node status. The expression of p53 in poorly differentiated tumors-commonly receptor negative and with a high proliferation fraction-may indicate greater tumor aggressiveness and a high risk of relapse.

Hormonal receptors, cell proliferation fraction (Ki-67) and c-erbB-2 amplification in breast cancer. Relationship between differentiation degree and axillary lymph node metastases.

In view of the limitations of conventional prognostic factors such as differentiation degree, metastatic lymph nodes, hormonal receptors and others, especially when early lesions are found, additional new markers have been studied, such as gene amplification and cell proliferation index, in order to choose the appropriate treatment. Primary breast carcinoma tumors from 97 patients were examined for differentiation degree, metastatic lymph nodes, hormonal receptors, c-erbB-2 amplification and cell proliferation index (Ki-67). A negative relationship with hormonal receptors and c-erbB-2 amplification, Ki-67 and differentiation degree was found, whereas the relationship between c-erbB-2, Ki-67 and differentiation degree was positive. No relationship was found between these factors and metastatic lymph nodes. The concurrence of high cell proliferation index, c-erbB-2 amplification and negative hormonal receptor presence would indicate a subpopulation with a high risk of recurrence. But a larger survival study is necessary to correlate these factors with clinical outcome.

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.

Reproductive toxicity evaluation of vanadium in male mice.

The reproductive toxicity of vanadium was studied in mice. Male Swiss mice were exposed to sodium metavanadate at doses of 0, 20, 40, 60, and 80 mg/kg per day given in the drinking water for 64 days. To evaluate the fertility of the vanadium-treated animals, males were mated with untreated females for 4 days. A significant decrease in the pregnancy rate was observed at 60 and 80 mg/kg per day of sodium. metavanadate. However, metavanadate did not reduce fertility in male mice at 20 and 40 mg/kg per day. Reproductive toxicity was measured by sperm count, sperm motility, organ weights, and histologic evaluation of the testes. Decreased body and epididymis weight was only observed in the 80 mg/kg per day group, while testicular weights were not altered by the treatment with all doses used. Sperm count was significantly decreased at 40, 60, and 80 mg/kg per day, but the sperm motility was unaffected. Histopathological examination revealed that the testes were normal and that the epididymis of treated male mice contained normal appearing sperm. The no observed adverse effect level (NOAEL) was 40 mg/kg per day. Consequently, vanadium would not cause any adverse effect on fertility or testicular function in male mice at the concentrations usually ingested by humans through the diet and drinking water.

Evaluation of the reproductive toxicity of gallium nitrate in mice.

Reproduction studies were performed with gallium nitrate, an antihypercalcaemic drug that is also used as a chemotherapeutic agent for the treatment of certain malignancies. Male mice were injected subcutaneously with gallium nitrate at doses of 0 (controls), 24, 48 and 96 mg/kg/day every other day for 14 days before mating with untreated females. Fertility and reproductive performance in the gallium nitrate-treated groups did not differ significantly from controls. No significant changes were observed in the relative testes and epididymis weights. Sperm counts in the gallium nitrate-dosed groups were comparable with those in the control group, whereas the percentage of motile cells was similar between treated and untreated animals. Histopathological examination of the testes and epididymis did not reveal any changes at any dose of gallium nitrate. The no-observed-adverse effect level was 96 mg/kg body weight. This dose is about 30 times higher than the current doses of gallium nitrate administered to humans.

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.

[Clinical and methodological considerations in the quantification of estrogen and progesterone receptors using monoclonal antibodies in breast cancer]. / Consideraciones clínicas y metodológicas en la cuantificación de receptores de estrógenos y progesterona con anticuerpos monoclonales en el cáncer de mama.

BACKGROUND: The aim of the present study was to provide information on several clinical and methodological aspects of the measurement of the contents of estrogen (ER) and progesterone (PgR) receptors in breast tumoral tissue using monoclonal antibodies. METHODS: The contents of ER and PgR were measured in 94 tumor specimens of breast carcinoma from pre- and postmenopausal women by the classical method of dextran-charcoal (DC) and an enzyme immunoassay (EIA) with monoclonal antibodies against receptors. RESULTS: The most remarkable results were: a significant difference for ER depending on the menopausal status, an increasing concentration of ER and PgR with age, a greater frequency of the phenotypes ER positive (+)-PgR (+) and ER negative (-) -PgR (-), a lower frequency of positive than negative receptors in the tumors measuring more than 10 cm, a greater presence of tumors with negative than with positive receptors in those located in the lower half of the breast, and the high diagnostic sensitivity of ER and PgR measurement with this method. CONCLUSIONS: There was a remarkable difference in contents of total ER in breast tumors from pre- and post menopausal women. This finding confirms that these tumors may have a different hormone modulation and a different capacity for protein induction depending on the menopausal status.

[Biphasic viral hepatitis "A" associated with autoimmune phenomena]. / Hepatitis vírica "A" bifásica asociada a fenómenos autoinmunes.

Acute hepatitis A virus infection (HAV) is a benign, self limited disease with infrequent extrahepatic features unlike the hepatitis B or the nonA-nonB virus infection. We describe the case of a 37 year old white woman with HAV who had a relapse with a second elevation of the alanine aminotransferase level together with joint pain, skin lesions, angioneurotic edema, and autoantibodies (ANA, anti smooth muscle, antiparietal gastric cells). The liver biopsy showed piecemeal and early bridging necrosis. She had a rapid reversal of her clinical, biochemical and histological abnormalities. As far as we known, this is the first reported case of autoantibodies or angioneurotic edema associated with HAV. We comment on the pathogenesis of this rare association.

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.