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1.
Eur J Endocrinol ; 182(1): 11-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31652416

RESUMO

Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

2.
Eur J Endocrinol ; 182(1): G1-G32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855556

RESUMO

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.


Assuntos
Índice de Massa Corporal , Hipotireoidismo/diagnóstico , Obesidade/diagnóstico , Comorbidade , Endocrinologia , Humanos , Hipotireoidismo/epidemiologia , Obesidade/epidemiologia , Prevalência , Testes de Função Tireóidea
3.
J Appl Microbiol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782867

RESUMO

AIM: The aim of this study was to test the hypothesis that Manuka honey (MH) chelates iron and promotes an iron-limiting environment, which contributes to its antimicrobial activity. METHODS AND RESULTS: Employing a ferrozine-based assay, we observed that MH is an iron chelator that depletes iron from solution. Siderophores are small molecules that bind ferric iron (III) with high affinity and their levels are upregulated by bacteria under iron-limiting conditions. We demonstrated by quantitating siderophore production that Escherichia coli and Pseudomonas aeruginosa treated with MH sub-minimum inhibitory concentrations (sub-MIC) experience an iron-limiting environment and increase siderophore production. In addition, supplementation with ferrous iron (II) significantly increased growth of E. coli, Staphylococcus aureus and P. aeruginosa cultured at their MH MIC above that observed in nonsupplemented controls. By contrast, supplementation with ferric iron (III) significantly increased growth for only E. coli and P. aeruginosa, above their nonsupplemented controls. CONCLUSIONS: Manuka honey chelates iron, thereby generating an iron-limiting environment for E. coli and P. aeruginosa, and to a lesser extent S. aureus, which contributes to its antimicrobial properties. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work demonstrates that MH-induced iron chelation is an antimicrobial mechanism that differentially impacts the bacterial species tested here. Iron chelation affects multiple diverse physiological processes in bacteria and would contribute to the lack of bacterial resistance to MH. Iron metabolism is tightly regulated; bacteria require this essential nutrient for survival, but in excess it is toxic. Additional exploration of MH's iron chelation mechanism will facilitate its future use in mainstream medicine.

4.
Diabet Med ; 35(3): 360-367, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29055156

RESUMO

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.


Assuntos
Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Perda de Peso/fisiologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Derivação Gástrica/métodos , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Indução de Remissão , Resultado do Tratamento
5.
Sci Rep ; 7: 41903, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28211912

RESUMO

The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8-10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p < 0.05) and a great correlation between both tissues. Therefore, the current study provided new and valuable DNA methylation biomarkers of obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue.


Assuntos
Metilação de DNA , Leucócitos/metabolismo , Obesidade/genética , Gordura Subcutânea/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ilhas de CpG , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética , Serina Endopeptidases/genética , Proteína Smad3/genética
6.
Mol Cell Endocrinol ; 434: 199-209, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27392494

RESUMO

Ghrelin is a growth hormone-releasing peptide that has been suggested to interfere with spermatogenesis, though the underling mechanisms remain unknown. We studied the effect of ghrelin in human Sertoli cells (hSCs) metabolic phenotype. For that, hSCs were exposed to increasing concentrations of ghrelin (20, 100 and 500 pM) mimicking the levels reported in obese, normal weight, and severely undernourished individuals. The metabolite production/consumption was determined. The protein levels of key glycolysis-related transporters and enzymes were assessed. The lactate dehydrogenase (LDH) activity was measured. Mitochondrial complexes protein levels and mitochondria membrane potential were also measured. We showed that hSCs express the growth hormone secretagogue receptor. At the concentration present in the plasma of normal weight men, ghrelin caused a decrease of glucose consumption and mitochondrial membrane potential in hSCs, though LDH activity and lactate production remained unchanged, illustrating an alteration of glycolytic flux efficiency. Exposure of hSCs to levels of ghrelin found in the plasma of severely undernourished individuals decreased pyruvate consumption and mitochondrial complex III protein expression. All concentrations of ghrelin decreased alanine and acetate production by hSCs. Notably, the effects of ghrelin levels found in severely undernourished individuals were more pronounced in hSCs metabolic phenotype highlighting the importance of a proper eating behavior to maintain male reproductive potential. In conclusion, ghrelin acts as an energy status sensor for hSCs in a dose-dependent manner, showing an inverse association with the production of lactate, thus controlling the nutritional support of spermatogenesis.


Assuntos
L-Lactato Desidrogenase/metabolismo , Mitocôndrias/metabolismo , Reprodução , Células de Sertoli/metabolismo , Células Cultivadas , Metabolismo Energético , Grelina , Glicólise , Humanos , Masculino , Potencial da Membrana Mitocondrial , Receptores de Grelina/metabolismo , Espermatogênese
7.
Int J Obes (Lond) ; 40(3): 514-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26443342

RESUMO

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.


Assuntos
Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Proteínas de Neoplasias/metabolismo , Obesidade/patologia , Gordura Subcutânea/patologia , Animais , Apoptose , Western Blotting , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
8.
Artigo em Inglês | MEDLINE | ID: mdl-24704598

RESUMO

The synthesis and fluorescence characterization of a new pyrrole derivative (PyPDG) containing the electron donor-acceptor dansyl substituent is reported. The effects of temperature and solvent polarity on the steady-state fluorescence of this compound are investigated. Our results show that PyPDG exhibits desirable fluorescent properties which makes it a promising candidate to be used as the photoactive material in optical thermometry and thermography applications. Further, the electrochemical and emission properties of polymeric films obtained from the oxidation polymerization of PyPDG are also analyzed.


Assuntos
Elétrons , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Pirróis/química , Pirróis/síntese química , Estrutura Molecular , Espectrometria de Fluorescência/métodos
9.
Endocr Dev ; 25: 49-58, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23652391

RESUMO

Growth hormone (GH) is secreted by the pituitary gland in a pulsatile manner. It is accepted that this pulsatility is primarily controlled by the hypothalamus, although this secretion can also be modulated by factors from GH-targeted organs, the pituitary and other regions of the central nervous systems, or by factors arriving from peripheral organs. In mammals, hypothalamic control of GH pulsatility is classically regulated by the interplay of two opposing hormones, stimulatory GHRH and inhibitory somatostatin (SS). Recognition of the gastric ghrelin peptide as the natural ligand for GH secretagogue receptor type 1a (GHS-R1a) added a new element to the complex physiological regulation of GH secretion and clarified some of its aspects that were previously not fully understood. In this review, we examine data that suggest that ghrelin may regulate GH secretion, as well as ghrelin's possible use as a therapeutic agent.


Assuntos
Grelina/fisiologia , Hormônio Liberador de Hormônio do Crescimento/fisiologia , Hormônio do Crescimento/metabolismo , Animais , Grelina/genética , Grelina/farmacologia , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Humanos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Via Secretória/efeitos dos fármacos , Via Secretória/genética
10.
Int J Obes (Lond) ; 32(9): 1438-40, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18607381

RESUMO

Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY(3-36) would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY(3-36) or PP+PYY(3-36) (n=7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg(-1) PP and by 6 nmol kg(-1) PYY(3-36) (P<0.05) but not significantly following 3 nmol kg(-1) PP+3 nmol kg(-1) PYY(3-36). In a higher dose study 30 nmol kg(-1) PP, 30 nmol kg(-1) PYY(3-36) and 30 nmol kg(-1) PP+30 nmol kg(-1) PYY(3-36) all inhibited 1 h food intake compared with saline (P<0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg(-1)min(-1) PP, 0.4 pmol kg(-1)min(-1) PYY(3-36) and 4 pmol kg(-1)min(-1) PP+0.4 pmol kg(-1)min(-1) PYY(3-36). A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP+PYY(3-36) treatment (buffet meal energy intake (KJ): saline 2633+/-204, PP+PYY 2693+/-254, PP 2367+/-199, PYY 2511+/-196). These results suggest that PP and PYY(3-36) do not inhibit feeding additively in rodents or humans.


Assuntos
Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Polipeptídeo Pancreático/farmacologia , Peptídeo YY/farmacologia , Adulto , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos/métodos , Sinergismo Farmacológico , Ingestão de Energia/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Fragmentos de Peptídeos
11.
Mamm Genome ; 10(5): 457-62, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10337618

RESUMO

We have previously reported suggestive evidence for a locus on Chromosome (Chr) 7 that affects adiposity in F2 mice from a CAST/Ei x C57BL/6J intercross fed a high-fat diet. Here we characterize the effect of a high-fat (32.6 Kcal% fat) diet on male and female congenic mice with a C57BL/6J background and a CAST/Ei-derived segment on Chr 7. Adiposity index (AI) and weights of certain fat pads were approximately 50% lower in both male and female congenic mice than in control C57BL/6J mice, and carcass fat content was significantly reduced. The reduction of fat depot weights was not seen, however, in congenic animals fed a low-fat chow diet (12 Kcal% fat). The congenic segment is approximately 25 cM in length, extending from D7Mit213 to D7Mit41, and includes the tub, Ucp2 and Ucp3, genes, all of which are candidate genes for this effect. Some polymorphisms have been found on comparing c-DNA sequences of the Ucp2 gene from C57BL/6J and CAST/Ei mice. These results suggest that one or more genes present in the congenic segment modulate the susceptibility to fat deposition on feeding a high-fat diet. We were unable to show any significant difference between the energy intakes of the congenic and the control C57BL/6J mice on the high-fat diet. Also, measurements of energy expenditure in male mice at 6 weeks of age, during the first 2 weeks of exposure to the high-fat diet, failed to show any differences between control and congenic animals.


Assuntos
Mapeamento Cromossômico , Gorduras na Dieta/administração & dosagem , Proteínas de Membrana Transportadoras , Proteínas Mitocondriais , Obesidade/genética , Animais , Sequência de Bases , Primers do DNA , Feminino , Canais Iônicos , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas/genética , Proteína Desacopladora 2
12.
Obes Res ; 7(1): 68-75, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10023732

RESUMO

OBJECTIVE: This study was designed to characterize changes in peripheral vascular resistance with weight gain, and whether these changes are correlated with insulin and/or sympathetic activity. RESEARCH METHODS AND PROCEDURES: Femoral vascular resistance (FVR), mean arterial pressure, heart rate, and plasma insulin were measured before and during overfeeding in seven dogs with unilateral lumbar ganglionectomy (L3 to L6). Measurements were taken standing and while walking on a treadmill. RESULTS: There was a significant main effect of weight gain to increase mean arterial pressure (16.5+/-8.4 mmHg and 12.5+/-6.8 mmHg increase for standing and walking baseline, respectively) and heart rate (increase from week 1 of 31.6+/-10.6 beats/minute standing and 38.3+/-9.1 walking beat/minute). FVR increased immediately with overfeeding/ weight gain [standing: denervated (DNX):1.32+/-0.3 to 2.34+/-0.5; intact: 0.88+/-0.17 to 1.9+/-0.33 mmHg/mL.min(-1)], but returned to baseline with continued weight gain. Return of FVR to baseline occurred between weeks 2 and 3 of overfeeding in the DNX limb, but did not return to baseline until week 6 in the innervated limb. These changes were not correlated with plasma insulin levels. DISCUSSION: These data suggest that vascular resistance may be normal in the obese, but increases in vascular resistance occur early with weight gain (before changes in arterial pressure). This initial increase in vascular resistance could initiate the series of events leading to obesity-associated hypertension. Additionally, changing vascular resistance during weight gain may be influenced by sympathetic activity, because DNX limb FVR returned to baseline approximately 3 weeks earlier than the innervated limb.


Assuntos
Insulina/fisiologia , Músculo Esquelético/irrigação sanguínea , Sistema Nervoso Simpático/fisiopatologia , Resistência Vascular , Ganho de Peso/fisiologia , Ração Animal , Animais , Pressão Sanguínea , Composição Corporal , Catecolaminas/sangue , Cromatografia Líquida de Alta Pressão , Cães , Feminino , Artéria Femoral/fisiopatologia , Ganglionectomia , Frequência Cardíaca , Membro Posterior , Insulina/sangue , Condicionamento Físico Animal , Radioimunoensaio
13.
Obes Res ; 6(2): 137-46, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9545021

RESUMO

Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs before and after they became obese on either a saturated fat (LD, lard, n=8) or unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased significantly in both groups, although no differences occurred between diet groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial pressure than those receiving the CO diet (p<0.01; 15.9 +/- 2.1 vs. 9.8 +/- 3.3 mm Hg increase). The CO diet stimulated a greater increase in heart rate than the LD diet (p<0.05; 32.8 +/- 7.8 vs. 14.1 +/- 5.8 bpm increase). Ganglionic blockade with chlorisondamine caused an increase in HR in both lean groups and in the obese CO group, but not the obese LD group, consistent with a decrease in parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity enhanced the heart rate response to beta-adrenergic stimulation by isoproterenol in the LD, but not CO group. The LD diet increased circulating insulin and decreased insulin sensitivity, whereas the CO diet had no effect on either parameter. These findings suggest that the composition of dietary fat can modulate the autonomic and metabolic adaptations induced by dietary obesity.


Assuntos
Pressão Sanguínea , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/análise , Insulina/sangue , Obesidade/etiologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Glicemia/metabolismo , Composição Corporal , Clorisondamina/farmacologia , Óleo de Milho/administração & dosagem , Cães , Feminino , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca , Isoproterenol/farmacologia , Ganho de Peso
15.
J Biol Buccale ; 4(4): 279-94, 1976 Dec.
Artigo em Francês | MEDLINE | ID: mdl-1069727

RESUMO

The author made a morphological study of Selachii (Suborder Galeoidae) of the Brazil coast using ground sections. Dental structures undergo modifications as one studies species of different evolutionary stages. The lower Selachii have an osteodentine nucleus which suffer alterations until it disappears leaving a pulp chamber in its place. The layer of pseudodentine shows modification too. It consists of pseudodentine in lower Selachii but its modifications are such that in higher Selachii (Sphyrnidae, for instance) one may suppose it is made of orthodentine. Based on these and other published data the author concludes that the degree of evolution of the pulp chamber and pseudodentine allows the establishment, with great probability, of the phylogenitic position of the Selachii within the Galeoidea Suborder.


Assuntos
Cavidade Pulpar/anatomia & histologia , Dentina/anatomia & histologia , Tubarões/anatomia & histologia , Animais , Evolução Biológica , Brasil , Filogenia
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