Anatomia do sistema reprodutor feminino de Alouatta belzebul (Linnaeus, 1766) / [Anatomy of the female reproductive system of the Alouatta belzebul (Linnaeus, 1766)]

O conhecimento da anatomia de qualquer animal silvestre é de fundamental importância para sua preservação e proteção. Neste contexto, o presente estudo objetivou descrever a morfologia do sistema reprodutor feminino de Alouatta belzebul. Foram utilizados seis espécimes de A. belzebul, fêmeas, adultas, e livres de lesões. Observou-se macroscopicamente que os ovários têm características morfológicas em formato ovoides, com superfície lisa, e, na análise histológica na região de córtex, evidenciou-se folículos ovarianos em diferentes estágios de desenvolvimento. As tubas uterinas anatomicamente são finas e curvilíneas, apresentando uma camada mucosa, uma muscular e outra serosa. O útero possui formato simples, com fundo globoso, com um miométrio altamente vascularizado, sendo organizado em feixes de fibras musculares lisas. A estrutura anatômica da vagina apresentou-se como um tubo muscular longo de paredes finas, onde, na região vestibular, o óstio externo da uretra é marcado por uma papila uretral bilobada e, na região de vulva, em sua porção caudal, contatou-se um clitóris bem desenvolvido. No que concerne à análise histológica da vagina, verificou-se, em região de mucosa vaginal, um extrato basal composto por epitélio estratificado pavimentoso não queratinizado atrófico. As descrições morfológicas fornecem, de forma inédita, informações importantes relativas à anatomia macroscópica e microscópica do sistema reprodutor feminino dessa espécie.(AU)

Knowledge of the anatomy of any wild animal is of fundamental importance for its preservation and protection. In this context the present study aimed to describe the morphology of the female reproductive system of A. belzebul. We used 6 specimens of A. belzebul, female, adult and free of lesions. It was macroscopically observed that the ovaries are ovoid with smooth surface and the histological analysis in cortical region showed ovarian follicles in different stages of development. The fallopian tubes are anatomically thin and curvilinear, with one mucous layer, one muscular and one serous layer. The uterus was presented in a simple format with a globular fundus, with a highly vascularized myometrium, being organized in bundles of smooth muscle fibers. The anatomical structure of the vagina presented itself as a long thin-walled muscular tube where in the vestibular region the external orifice of the urethra is marked by a bilobed urethral papilla and in the caudal portion in its caudal portion a well-developed clitoris. Regarding the histological analysis of the vagina, a basal extract composed of atrophic non-keratinized stratified squamous epithelium was found in the vaginal mucosa region. The morphological descriptions provide important information regarding the macroscopic and microscopic anatomy of the female reproductive system of this species in an unprecedented way.(AU)

CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG.

Myelin oligodendrocyte glycoprotein (MOG), a constituent of central nervous system myelin, is an important autoantigen in the neuroinflammatory disease multiple sclerosis (MS). However, its function remains unknown. Here, we show that, in healthy human myelin, MOG is decorated with fucosylated N-glycans that support recognition by the C-type lectin receptor (CLR) DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) on microglia and DCs. The interaction of MOG with DC-SIGN in the context of simultaneous TLR4 activation resulted in enhanced IL-10 secretion and decreased T cell proliferation in a DC-SIGN-, glycosylation-, and Raf1-dependent manner. Exposure of oligodendrocytes to proinflammatory factors resulted in the down-regulation of fucosyltransferase expression, reflected by altered glycosylation at the MS lesion site. Indeed, removal of fucose on myelin reduced DC-SIGN-dependent homeostatic control, and resulted in inflammasome activation, increased T cell proliferation, and differentiation toward a Th17-prone phenotype. These data demonstrate a new role for myelin glycosylation in the control of immune homeostasis in the healthy human brain through the MOG-DC-SIGN homeostatic regulatory axis, which is comprised by inflammatory insults that affect glycosylation. This phenomenon should be considered as a basis to restore immune tolerance in MS.

Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors.

OBJECTIVE: The aim of this study was to examine the effects of recombinant human Fgf18 on chondrocyte proliferation and matrix production in vivo and in vitro. In addition, the expressions of Fgf18 and Fgf receptors (Fgfr) in adult human articular cartilage were examined. METHODS: Adenovirus-mediated transfer of Fgf18 into murine pinnae and addition of FGF18 to primary cultures of adult articular chondrocytes were used to assess the effects of FGF18 on chondrocytes. In situ hybridization was used to examine the expression of Fgf18 and Fgfr s in adult human articular cartilage. RESULTS: Expression of Fgf18 by adenovirus-mediated gene transfer in murine pinnae resulted in a significant increase in chondrocyte number. Chondrocytes were identified by staining with toluidine blue and a monoclonal antibody directed against type II collagen. Fgf18, Fgfr 2-(IIIc), Fgfr 3-(IIIc), and Fgfr 4 mRNAs were detected within these cells by in situ hybridization. The nuclei of the chondrocytes stained with antibodies to PCNA and FGF receptor (FGFR) 2. Addition of FGF18 to the culture media of primary articular chondrocytes increased the proliferation of these cells and increased their production of extracellular matrix. To assess the receptor selectivity of FGF18, BaF3 cells stably expressing the genes for the major splice variants of Fgfr1-3 were used. Proliferation of cells expressing Fgfr 3-(IIIc) or Fgfr 2-(IIIc) was increased by incubation with FGF18. Using FGFR-Fc fusion proteins and BaF3 cells expressing Fgfr 3-(IIIc), only FGFR 3-(IIIc)-Fc, FGFR 2-(IIIc)-Fc or FGFR 4-Fc reduced FGF18-mediated cell proliferation. Expression of Fgf18, Fgfr 3-(IIIc) and Fgfr 2-(IIIc) mRNAs was localized to chondrocytes of human articular cartilage by in situ hybridization. CONCLUSION: These data demonstrate that Fgf18 can act as a trophic factor for elastic chondrocytes and their progenitors in vivo and articular chondrocytes cultured in vitro. Expression of Fgf18 and the genes for two of its receptors in chondrocytes suggests that Fgf18 may play an autocrine role in the biology of normal articular cartilage.

Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis.

The amino and carboxyl propeptides of procollagens I and II are removed by specific enzymes as a prerequisite for fibril assembly. Null mutations in procollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I. We have found that procollagen II is processed normally in dermatosparactic nasal cartilage, suggesting the existence of another N-propeptidase(s). We investigated such a role for ADAMTS-3 in Swarm rat chondrosarcoma RCS-LTC cells, which fail to process the procollagen II N-propeptide. Stable transfection of RCS-LTC cells with bovine ADAMTS-2 or human ADAMTS-3 partially rescued the processing defect, suggesting that ADAMTS-3 has procollagen II N-propeptidase activity. Human skin and skin fibroblasts showed 30-fold higher mRNA levels of ADAMTS-2 than ADAMTS-3, whereas ADAMTS-3 mRNA was 5-fold higher than ADAMTS-2 mRNA in human cartilage. We propose that both ADAMTS-2 and ADAMTS-3 process procollagen II, but ADAMTS-3 is physiologically more relevant, given its preferred expression in cartilage. The findings provide an explanation for the sparing of cartilage in dermatosparaxis and, perhaps, for the relative sparing of some procollagen I-containing tissues.

Incorporation of structurally defective type II collagen into cartilage matrix in kniest chondrodysplasia.

Kniest dysplasia, a human chondrodysplasia that severely affects skeletal growth, is caused by mutations in the type II collagen gene, COL2A1. We report here on abnormal type II collagen in the cartilage from a lethal Kniest dysplasia case and identify a novel exon-skipping mutation. Screening of cyanogen bromide (CB) peptides from the cartilage samples by SDS-PAGE indicated an abnormality in peptide alpha1(II)CB11. Further peptide mapping and N-terminal sequence analysis showed a 15-amino-acid deletion encoded by exon 15 in about 25% of the alpha1(II) chains in the cartilage. The mutation responsible for exon skipping was found by sequencing amplified genomic DNA. The baby was heterozygous for a G to A transition at the first position of the splice donor of intron 15. Pepsin-solubilized type II collagen from the cartilage matrix contained both normal alpha1(II) and shortened chains expressed from the mutant allele. Trypsin cleaved the native molecules below 37 degrees C selectively at a site within the exon 15-encoded domain of the normal alpha1(II) chains. This is best explained by the coassembly of normal and truncated alpha1(II) chains into heterotrimers in which the triple helix is normally folded in both directions from the deletion site but the latter presents a region of local disruption. The findings support an emerging pattern of COL2A1 mutations that can cause Kniest dysplasia. Short deletions (single or partial exon) clustered in one region of the alpha1(II) chain are favored, resulting in abnormal heterotrimeric molecules that become a significant component of the cartilage extracellular matrix.

Incomplete processing of type II procollagen by a rat chondrosarcoma cell line.

The Swarm rat chondrosarcoma cell line, RCS-LTC, deposits an extracellular matrix that contains the typical type II, IX, and XI collagen phenotype of hyaline cartilage, but the fibrils appear abnormally thin. By N-terminal sequence analysis, the type II collagen from the matrix was shown to have retained its N-propeptides with no evidence of normal processing to type II collagen. Amplification and sequencing of cDNA prepared from the pro alpha1(II) mRNA of these cells showed a normal N-propeptide cleavage site. Furthermore, the type II N-procollagen could be processed to type II collagen by incubation with culture medium from normal chondrocytes. The findings indicate that the RCS-LTC cell line fails to express an active type II procollagen N-proteinase and, therefore, offers a useful culture system in which to study the role of N-propeptide removal in fibrillogenesis.

Familial aggregation of medial arterial calcification in Pima Indians with and without diabetes.

OBJECTIVE: Little is known about medial arterial calcification (MAC) other than its association with age, sex, diabetes, and diabetes complications. Familial aggregation of this disorder was studied to determine the importance of potential genetic factors and to assess whether such familial aggregation was independent of that of diabetes. RESEARCH DESIGN AND METHODS: Members of 1,256 Pima Indian nuclear families with 3,339 offspring were examined radiologically for MAC of the feet. Multiple logistic regression analyses were used to compare the presence of the disorder in a parent with the presence of MAC in an offspring and to determine whether familial aggregation of MAC was independent of parental diabetes. RESULTS: Controlled for age, sex, diabetes, serum cholesterol, and blood pressure, offspring of one parent with MAC had 3.3 (95% CI 1.5-7.6) times the odds of MAC as did offspring of parents without MAC, and offspring with both parents affected had an even higher risk (odds ratio, 8.1; 95% CI 3.4-18.8). Controlled for offspring age and sex and for parental age and diabetes, parental MAC was associated with the disorder in offspring (P < 0.001), but the effect of parental diabetes on MAC in the offspring was not significant when controlled for parental MAC (P = 0.36). Furthermore, offspring of nondiabetic parents with MAC, controlled for age, sex, diabetes, and diabetes duration, had 1.7 (95% CI 0.9-3.1) times the odds of MAC than did offspring of diabetic parents with MAC. CONCLUSIONS: Independent of parental age and diabetes and offspring age, sex, diabetes, and diabetes complications, parental MAC confers an increased risk of MAC in offspring. These findings suggest that the factors responsible for the familial clustering of MAC may be different from those for diabetes.

Prevalence and patterns of smoking in Delhi: cross sectional study.

OBJECTIVE: To determine the prevalence and predictors of smoking in urban India. DESIGN: Cross sectional. SETTING: Delhi, urban India, 1985-6. SUBJECTS: Random sample of 13,558 men and women aged 25-64 years. MAIN OUTCOME MEASURES: Smoking prevalence; subjects who were currently smoking and who had smoked > or = 100 cigarettes or beedis or chuttas in their lifetime were defined as smokers. RESULTS: 45% (95% confidence interval 43.8 to 46.2) of men and 7% (6.4 to 7.6) of women were smokers. Education was the strongest predictor of smoking, and men with no education were 1.8 (1.5 to 2.0) times more likely to be smokers than those with college education, and women with no education were 3.7 (2.9 to 4.8) times more likely. Among smokers, 52.6% of men and 4.9% of women smoked only cigarettes while the others also smoked beedi or chutta. Compared with cigarette smokers, people smoking beedi or chutta were more likely to be older and married; have lower education, manual occupations, incomes, and body mass index; and not drink alcohol or take part in leisure exercise. CONCLUSION: There are two subpopulations of smokers in urban India, and the prevention strategy required for each may be different. The educated, white collar cigarette smoker in India might respond to measures that make non-smoking fashionable, while the less educated, low income people who smoke beedi or chutta may need strategies aimed at socioeconomic improvement.