Felids morphology and ecological role as hypercarnivores are quite constant, despite considerable body size variation among species. Skull morphological and functional features of 34 extant cat species were evaluated under a phylogenetic framework of the Felidae. Twenty skull measurements were analysed through Principal Component Analysis to assess the species morphofunctional spaces. Force indexes were obtained from static equilibrium equations to infer jaw mechanics. Correlations between morphological, functional, and ecological traits were tested by phylogenetically independent contrasts. In spite of the general cat-like pattern, specific features on the skulls allowed differentiation among groups. Acinonyx jubatus, for instance, showed a shorter and shallower temporal fossa than other big cats, and their bite functionality is marked by an increased contribution of the masseteric system. A morphofunctional dichotomy between Neotropical and Eurasian/African small cats was detected, and is associated with the major transversal axes of the skulls. According to the contrast analyses, the skull size is correlated with the bite force and prey size, but it is uncorrelated with the variations on jaw mechanics (from temporalis or masseter muscle optimizations). Also, there was no correlation between functional differences on jaw muscles and the ratio of prey weight to cat weight. The efficiency of the jaw apparatus among cats is quite consistent; therefore, the different evolutionary trends of jaw mechanics seem to be caused by the casuistic fixation of phenotypical variations, rather than by specific adaptative selections.

OBJECTIVE -Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The study included 31 subjects (age 38.3 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n ϭ 15) or metformin (n ϭ 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.RESULTS -The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.CONCLUSIONS -We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

OBJECTIVE -Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The study included 31 subjects (age 38.3 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n ϭ 15) or metformin (n ϭ 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.RESULTS -The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.CONCLUSIONS -We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

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The skulls of 33 extant cat species were characterized through three-dimensional geometric morphometrics using 20 landmarks. A principal component analysis (PCA) was performed with Procrustes fitted coordinates, and the PC-scores were phylogenetically corrected by independent contrasts method. Three PCs allowed for the definition of five cat skull patterns. PC1: 'snouted/massive-headed cats' (genus Panthera) opposing the 'round-headed small cats' (genus Oncifelis, Prionailurus rubiginosus, Prionailurus bengalensis, among other small cats); PC2: 'taperingheaded cats' (Neofelis nebulosa, Herpailurus yagouaroundi, Prionailurus planiceps) opposing the 'stout-headed cats' (Acinonyx jubatus, Uncia uncia, Otocolobus manul, Felis margarita, and Felis nigripes); and PC3: 'low profiledheaded cats' (mostly, Pr. planiceps). A sixth pattern, the 'generalized skull', observed in the Caracal lineage, genus Lynx, Leopardus pardalis, and Catopuma temminckii, indicates a morphological convergence among midsized-cats. The morphological trends 'snouted/massive' and 'round' clearly denote a co-evolution between size and shape. The other skull patterns evolved unrelatedly to the size (i.e. their allometric variations are not a size function). Nevertheless, each species comprises an amalgam of these patterns, so the influence of the size permeates, in some extent, the skull morphology along all cat lineages. The felid ecomorphological fit to hypercarnivory is obvious; however, different skull shapes in same-sized species with similar habits, indicate that the variation in the skull morphology may result from phenotypic fluctuations, whose adaptive value (if indeed there is any) is still obscure.

Objective: Capillary recruitment is impaired in obesity (OB), possibly worsening glucose and insulin availability to target organs. In this study, we investigated whether functional microvascular parameters were correlated with clinical-anthropometrical data and whether these parameters would influence OB-related metabolic disorders, especially glucose homeostasis, in young overweight (OW)/obese women. Design: Cross-sectional clinical study of microvascular reactivity in young OW/obese women. Subjects and methods: A total of 10 lean (23.1 ± 3.2 years, body mass index (BMI) 22.3 ± 1.6 kg m À2 ) and 42 OW/obese (24.9±3.5 years; BMI 34.5±5.7 (25.7-46.5) kg m À2 ) sedentary non-smoking women were evaluated. Lipid profile, fasting plasma glucose (PG), post-load PG (75 g-2 h), insulin, C-reactive protein, HOMA-IR (homeostasis model assessment for insulin resistance) index and anthropometric variables (weight, BMI, waist and hip circumferences, waist-to-hip ratio and blood pressure (BP)) were determined. Functional microvascular parameters (functional capillary density, red blood cell velocity at baseline and peak (RBCV max ), and time taken to reach RBCV max (TRBCV max ) during post-occlusive reactive hyperemia after 1 min arterial occlusion) were evaluated by nailfold videocapillaroscopy. Results: The time taken to reach RBCV max was significantly longer in OW/obese patients compared with control subjects (8.6±2.4 versus 5.7±1.1 s, Po0.001), and its delay was directly associated with adiposity levels, systolic BP and insulin resistance, and inversely related to high-density lipoprotein-cholesterol. Post-load PG could be correlated with TRBCV max (R ¼ 0.48, Po0.05) and RBCV max (R ¼ À0.29, Po0.05), and it was influenced by weight, waist circumference and TRBCV max (adjusted R 2 ¼ 24%) as well. Conclusions: In the investigated group of young OW/obese women, the direct correlation between post-load PG and TRBCV max links microvascular parameters with metabolic variables and suggests a key role for microcirculation in OB-related metabolic disorders.

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During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain) demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cells via toll-like receptor 2 (TLR2). Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responses via cross-talk between bradykinin B2 receptors (B2Rs) and C5aR. Awareness that TCTs invade cardiovascular cells in vitro via interdependent activation of B2R and endothelin receptors [endothelin A receptor (ETAR)/endothelin B receptor (ETBR)] led us to hypothesize that T. cruzi might reciprocally benefit from the formation of infection-associated edema via activation of kallikrein–kinin system (KKS). Using intravital microscopy, here we first examined the functional interplay between mast cells (MCs) and the KKS by topically exposing the hamster cheek pouch (HCP) tissues to dextran sulfate (DXS), a potent “contact” activator of the KKS. Surprisingly, although DXS was inert for at least 30 min, a subtle MC-driven leakage resulted in factor XII (FXII)-dependent activation of the KKS, which then amplified inflammation via generation of bradykinin (BK). Guided by this mechanistic insight, we next exposed TCTs to “leaky” HCP—forged by low dose histamine application—and found that the proinflammatory phenotype of TCTs was boosted by BK generated via the MC/KKS pathway. Measurements of footpad edema in MC-deficient mice linked TCT-evoked inflammation to MC degranulation (upstream) and FXII-mediated generation of BK (downstream). We then inoculated TCTs intracardiacally in mice and found a striking decrease of parasite DNA (quantitative polymerase chain reaction; 3 d.p.i.) in the heart of MC-deficient mutant mice. Moreover, the intracardiac parasite load was significantly reduced in WT mice pretreated with (i) cromoglycate (MC stabilizer) (ii) infestin-4, a specific inhibitor of FXIIa (iii) HOE-140 (specific antagonist of B2R), and (iv) bosentan, a non-selective antagonist of ETAR/ETBR. Notably, histopathology of heart tissues from mice pretreated with these G protein-coupled receptors blockers revealed that myocarditis and heart fibrosis (30 d.p.i.) was markedly and redundantly attenuated. Collectively, our study suggests that inflammatory edema propagated via activation of the MC/KKS pathway fuels intracardiac parasitism by generating infection-stimulatory peptides (BK and endothelins) in the edematous heart tissues.