Influence of sex and estrus cycle on the sexual dimorphisms of the hypothalamic ventromedial nucleus: stereological evaluation and Golgi study

Neurons in the ventromedial nucleus of the hypothalamus (VMN) display structural and biochemical sex differences in response to estrogen. Despite this fact, reports on sex differences in the morphology of the VMN are restricted to its volume and synaptic patterning. The aim of this study was to characterize the neuroanatomical sexual dimorphisms in the VMN and to investigate whether endogenous changes in ovarian steroid secretion influence such dimorphisms. The VMN of adult male rats and intact, aged-matched female rats killed on proestrus and diestrus day 1 was examined by using stereological methods applied to conventionally stained sections and Golgi-impregnated material. The VMN contained 55,000 neurons in rats of both sexes, but its volume was, on average, 1.25 times larger in males than in females. The volume was greater in proestrus than in diestrus rats due to parallel changes in the neuronal somatic size. Unlike the dorsomedial division, neurons in the ventrolateral division had longer dendritic trees in proestrus than in diestrus females and males. The spine density was consistently higher in females than in males in both VMN divisions. In addition, in the ventrolateral part the magnitude of the sex differences varied across the estrus cycle, and reached the greatest value when females were in proestrus. The volume of the neuropil was significantly larger in males than in females, and was not affected by the estrus phase. Our results reveal that the magnitude of the neuroanatomical sex differences in the VMN vary across the estrus cycle due to the trophic influence of estrogen upon its neurons. They also show that the fundamental sex difference in the structure of the VMN is accounted for by the neuropil components.     

Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology

This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal lymph nodes (PLN) were collected. Peritoneal cell cultures were performed to measure the H₂O₂, O₂^?, NO, IL‐2, IL‐4, IL‐10, IL‐12, IFN‐γ and TNF levels. Serum levels of anti‐PGL‐I antibodies were also quantified. The results showed that the infection was progressive in nude mice with bacterial multiplication, development of macroscopic lesions in the FP and presence of bacilli in the PLN at 8 months. In BALB/c mice, the infection reached a plateau of bacillary multiplication at 5 months and regressed at 8 months. Histopathological analysis of FP revealed a mononuclear inflammatory infiltrate with a large number of neutrophils at 5 months, with a higher number in nude mice. At 8 months, the number of neutrophils decreased and the infiltrate was predominantly mononuclear in both mouse strains. There was no H₂O_2, O₂^?, IL‐2, IL‐4, IL‐10 and IFN‐γ production in the course of infection in nude mice; however, in BALB/c, O₂^? and IL‐12 production was higher at 5 months and NO, IFN‐γ and TNF production was higher at 8 months when there was a decrease in the number of bacilli. The level of anti‐PGL‐I antibodies was higher in BALB/c mice. Thus, nude and BALB/c mice can be used as experimental models for the study of various aspects of leprosy.     

Intralesional Meglumine Antimoniate for Treatment of Cutaneous Leishmaniasis Patients with Contraindication to Systemic Therapy from Rio de Janeiro (2000 to 2006)

Abstract. We evaluated the effectiveness and safety of intralesional meglumine antimoniate (MA) in 24 not submitted to previous treatment patients with cutaneous leishmaniasis (CL) and with contraindication to systemic therapy. Each treatment consisted of one to four intralesional applications of MA at 15-day intervals. Patients' age ranged from 3 to 90 years; fourteen were females. Intralesional treatment in the absence of any relevant toxicity was successful in 20 (83.3%) patients. Three patients required additional treatment with amphotericin B and one required systemic MA. None of the patients developed mucosal lesions when followed up to 60 months. Intralesional MA is an effective and less toxic alternative treatment of patients with CL and contraindication to systemic therapy.     

Immunohistochemical study of hepatic fibropoiesis associated with canine visceral leishmaniasis

Hepatic fibropoiesis has been confirmed in canine visceral leishmaniasis. In fibrotic disease, hepatic stellate cells (HSC) play an important role in fibropoiesis, undergoing activation by TGF‐β to acquire characteristics of myofibroblasts. These cells show extensive capacity for proliferation, motility, contractility, collagen synthesis and extracellular matrix component synthesis. The aim of this work was to identify markers of HSC activation in 10 symptomatic and 10 asymptomatic dogs naturally infected with Leishmania (Leishmania) infantum. Eight uninfected dogs were used as controls. Alpha‐actin (α‐SMA), vimentin and cytokeratin were investigated by immunohistochemistry as HSC markers. The cytokine TGF‐β in tissue was also evaluated by immunohistochemistry. All infected dogs showed higher numbers of reticular fibres than controls. Fibropoiesis found in infected dogs was always associated with the presence of parasites and chronic granulomatous hepatitis. Positive correlation was found among fibropoiesis, parasite tissue load and expression of α‐SMA. There was no correlation between fibropoiesis, vimentin and cytokeratin markers. The expression of cytokine TGF‐β was higher in infected dogs than in controls, but not significantly different between symptomatic and asymptomatic dogs. These results confirm previous work describing the intense hepatic fibropoiesis in dogs naturally infected with Leishmania infantum, but now associated them with overexpression of TGF‐β, where α‐SMA may be a superior marker for activated HSC cells in CVL.     

Evaluation of the progesterone receptor status in breast cancer using three different antibodies: a comparison by Allred score system

Breast cancer (BC) hormonal receptors status is assessed by immunohistochemistry (IHC), a specific, sensitive, and accessible method that guide breast cancer treatment. In this study, we evaluated progesterone receptor (PR) expression in 53 BC cases using 3 anti-PgR antibodies (AB): monoclonal (SP42 and PgR636) and polyclonal ab62621. Primary BC cases (with signed informed consent) were used to generate tissue microarray platforms, where PR expression was accessed by IHC and evaluated by the Allred score. Categorical and quantitative data are shown in percentage and mean, respectively. Concordance (CON) and correlation among ABs were analyzed by Kappa factor (Κ), Spearman’s correlation coefficient (ρ) or intraclass correlation coefficient. Staining patterns of each AB were compared by paired T-Test. We noted poor CON and Κ between ab62621 vs SP42 (CON=64.1%; Κ=0.247), and ab62621 vs PgR636 (CON=62.3%; Κ=0.204), but higher CON between SP42 vs PgR636 (CON 90.6%; Κ=0.738). Data were corroborated by Mc Nemar statistical test (p=0.019, p=0.014 and p>0.05, respectively). Regarding staining intensity (SI) among PgR+ samples, we found higher proportion of weak staining and lower SI for ab62621 (48.3%; mean IS=1.6), when compared to SP42 (20.0%, mean IS=2.1, T-test p<0.01) and PgR636 (2.3, 21.9%, T-test p<0.01). Within the entire sample, similar results were observed following ρ: SP42 vs PgR636 (ρ=0.8103); ab62621 vs SP42 (ρ=0.3524); ab62621 vs PgR636 (ρ=0.4075). As for proportion of stained cells and proportion score (PS), among PgR+ samples, the mean values for ab62621 (75.4%; 4.8) were significantly higher than those of SP42 (56.3%, 4.3; T-test p<0.01) and RPG636 (60.1%; 4.2; T-test p<0.01). Similar data were found after analyzing PS for the entire sample: SP42 vs PgR636 (ρ=0.8588); SP42 vs ab62621 (ρ=0.4832); RPG636 vs ab62621 (ρ=0.4050). Our data indicate that anti-PgR monoclonal ABs, PgR636 and SP42, are, unlike ab62621, equally suitable to test BC PgR status by IHC due to their higher accuracy. Therefore, we suggest their clinical use during BC diagnosis; thus, enabling more precise therapeutic decisions to treat BC.     

Cementoblastoma: A case report in deciduous tooth

Background

The benign cementoblastoma is an odontogenic tumor originated from neoplastic cementoblasts, a rare lesion mainly associated to impacted and deciduous teeth. It affects mostly young people with an average age of 20 years old, and its preferred location is in the posterior region of the mandible; the lesion will present itself fused both radiologically and microscopically to a root of an erupted permanent tooth, and the anatomopathological diagnosis is obtained through the analysis of the piece sent together with the involved dental element.

Case report

The present study presents a case of cementoblastoma in the mandible involving the second deciduous molar tooth and preventing the eruption of the premolar tooth in a girl aged 11 years old.

Discussion

This report discusses relevant aspects concerning clinical, radiographic, and histopathological characteristics and treatments.     

Executive testing predicts functional loss in subjects with white matter lesions

In order to assess ecological validity of executive function (EF) tests and the impact of EF dysfunction on functional status in elderly subjects with moderate and severe subcortical white matter hyperintensities (WMHs), we made a correlation analysis between EF scores and two measures of Instrumental Activities of Daily Living (IADL). Trail-making test and CLOX correlated with the ability to perform IADL in subjects with severe WMH. EF tests might present low ecological validity for those with WMH below severe stage.