Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes

Background: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. Aim: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. Material and methods: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (Hbak(1c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. Results: Patients were normotensive (systolic arterial pressure: 131.1 +/- 10.6 mmHg) and on good metabolic control (HbA(1c): 6.6 +/- 0.6%). Microalbuminuric patients presented impaired venous (32.9 +/- 17.4 vs 59.3 +/- 26.5%; p=0.004) and arterial vasodilation (1.8 +/- 0.9 vs 5.1 +/- 2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(1c) (r=-0.41; p=0.032). The same was observed between flow-mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(1c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). Conclusions: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis. (J. Endocrinol. Invest. 33: 696-700, 2010) (C) 2010, Editrice Kurtis

Reduced venous endothelial responsiveness after oral lipid overload in healthy volunteers

The aim of this study was to investigate endothelial venous function, mflammatory markers, and systemic oxidative stress after an oral lipid overload (OLO). We studied 18 healthy adults (9 men; age, 29.2 +/- 0.9 years; body mass index, 22.3 +/- 0.4 kg/m(2)). Blood samples were collected in the fasting state and 3, 4, and 5 hour after the OLO (1000 kcal, 58% fat) for metabolic variables, oxidative stress, inflammatory markers, adiponectin, and resistin. Changes in vein diameter to phenylephrine, acetylcholine, and sodium nitroprusside (dorsal hand vein technique) were measured before and after the OLO. Oral lipid overload increased triglycerides (61 +/- 6 vs 134 +/- 17 mg/dL, P <.001), insulin (7.2 +/- 0.8 vs 10.7 +/- 1.3 mu U/mL, P <.05), and resistin (5.38 +/- 0.5 vs 6.81 +/- 0.7 ng/mL, P <.05) and reduced antioxidant capacity (plasma total antioxidant capacity: 186.7 +/- 56 vs 161.8 +/- 50 U Trolox per microliter plasma, P <.01), vascular reactivity (171.3 +/- 85 vs 894.4 +/- 301 ng/mL, P <.001), and maximum acetylcholine venodilation (105.9% +/- 9% vs 61.0% +/- 7%, P <.05). No changes were observed for sodium nitroprusside. Post-OLO triglycerides were positively correlated with phenylephrine dose (rho = 0.38, P <.05) and resistin (rho = 0.43, P <.01) and negatively correlated with the maximum acetylcholine venodilation (rho = -0.36, P <.05). In conclusion, an OLO impaired venoconstriction responsiveness in healthy subjects, probably because of a reduction in the antioxidant capacity. (C) 2008 Elsevier Inc. All rights reserved.

Androgenicity and venous endothelial function in post-menopausal women

Background: Endothelial dysfunction is one of the early signs of cardiovascular damage. High androgen levels have been related to inflammatory endothelial markers in pre- and post-menopausal women. Aim: This cross-sectional study aimed at investigating whether free androgen index (FAI) [estimated by dividing total testosterone (nmol/l) by SHBG (nmol/l) x 100] is related to endothelial function during post-menopause. Subjects and methods: Twenty-six post-menopausal women were assessed with the dorsal hand vein compliance technique. Acetylcholine (Ach) and sodium nitroprusside (SNP) dose-response curves were constructed to test endothelium-dependent and independent relaxation, respectively. Results: Mean age was 54 yr ( 4) and median time since menopause was 6 yr (interquartile range: 3-9). Patients were stratified according to FAI levels into two groups: FAI greater than or less than the group median of 2.5. Waist-to-hip ratio (WHR) was significantly higher in the group with FAI>2.5, as well as median dose of Ach for maximal vasodilation [720 (360-3600) ng/min with FAI>2.5 vs 36 (0.36-360) ng/min with FAI <= 2.5; p=0.005]. Maximal vasodilation with SNP was similar in both groups. Positive correlations were observed between Ach doses and maximal vasodilation and FAI (r=0.473, p=0.015), waist (r=0.510, p= 0.011), and WHR (r=0.479, p=0.021). SHBG was negatively correlated with Ach doses (rs=-0.400, p=0.043). Conclusions: This study suggests that FAI, even within normal limits, is related to early changes in endothelial function in healthy post-menopausal women. Longitudinal studies are required to determine the clinical relevance of these findings. (J. Endocrinol. Invest. 33: 239-243, 2010) (C) 2010, Editrice Kurtis

Reversal of Postprandial Endothelial Dysfunction by Cyclooxygenase Inhibition in Healthy Volunteers

The aim of this study was to evaluate the role of cyclooxygenase (COX) in venous vascular reactivity changes after an oral lipid overload (OLO). Venous endothelial function (dorsal hand vein technique) was evaluated in fasting, 30 minutes after COX inhibition (aspirin-fasting), 2 to 4 hours after an OLO (1000 kcal, 58% fat), and again after COX inhibition (aspirin-OLO, 600 mg/200 mL water) in 10 healthy adults (age, 28.1 +/- 1.3 years; body mass index, 22.3 +/- 0.6 kg/m(2)). Fasting, 2- to 4-hour post-OLO, and 60-minute postaspirin plasma glucose, insulin, and lipids were also evaluated. The OLO increased triglycerides and insulin, reduced low-density lipoprotein and high-density lipoprotein, but glycemia and total cholesterol remained unchanged. There were no metabolic differences between OLO and aspirin-OLO. In fasting, aspirin reduced acetylcholine-induced venodilation (107.0% +/- 14% versus 57.3% +/- 11%; P < 0.001). Vascular reactivity was blunted after the OLO (phenylephrine dose: 0.3 +/- 0.2 fasting versus 1.9 +/- 0.8 nmol/min after OLO; P < 0.001) and was partially corrected by aspirin (0.4 +/- 0.2; P < 0.001). Similar changes were observed in maximum venodilation after acetylcholine (107.0% +/- 14% fasting versus 60.4% +/- 9% after OLO, P < 0.001; aspirin-OLO: 95.9% +/- 6%; P < 0.001). The responses to sodium nitroprusside remained unchanged during the study. We conclude that the OLO reduction in the endothelium-dependent venoconstruction and venodilation is partially the result of the action of COX.

Human Multipotent Mesenchymal Stromal Cells from Distinct Sources Show Different In Vivo Potential to Differentiate into Muscle Cells When Injected in Dystrophic Mice

Limb-girdle muscular dystrophies are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or deficiency of muscle proteins. The murine model of Limb-Girdle Muscular Dystrophy 2B, the SJL mice, carries a deletion in the dysferlin gene. Functionally, this mouse model shows discrete muscle weakness, starting at the age of 4-6 weeks. The possibility to restore the expression of the defective protein and improve muscular performance by cell therapy is a promising approach for the future treatment of progressive muscular dystrophies (PMD). We and others have recently shown that human adipose multipotent mesenchymal stromal cells (hASCs) can differentiate into skeletal muscle when in contact with dystrophic muscle cells in vitro and in vivo. Umbilical cord tissue and adipose tissue are known rich sources of multipotent mesenchymal stromal cells (MSCs), widely used for cell-based therapy studies. The main objective of the present study is to evaluate if MSCs from these two different sources have the same potential to reach and differentiate in muscle cells in vivo or if this capability is influenced by the niche from where they were obtained. In order to address this question we injected human derived umbilical cord tissue MSCs (hUCT MSCs) into the caudal vein of SJL mice with the same protocol previously used for hASCs; we evaluated the ability of these cells to engraft into recipient dystrophic muscle after systemic delivery, to express human muscle proteins in the dystrophic host and their effect in functional performance. These results are of great interest for future therapeutic application.

Immobilized Kidney 28-kDa Endostatin- Related (KES28kDa) Fragment Promotes Endothelial Cell Survival

Background/Objective: Renal ischemia-hypoxia is a leading cause of acute kidney injury (AKI). Ischemia causes extracellular matrix breakdown of the tubular basement membrane. Endostatin (ES) is the C-terminal fragment of collagen XVIII generated by proteolytic cleavage. Recent studies have demonstrated that ES expression is upregulated in ischemic kidneys. The present study aimed to characterize ES from ischemic kidneys. Methods: Ischemic renal failure was induced via 45 min of occlusion of the left renal artery and vein. After the ischemic period, blood was collected. Kidneys were harvested and used for immunohistochemical testing and protein extraction. Three-step purification was used. Soluble and immobilized purified ES were tested in cell viability and adhesion assays. Results: The soluble KES28kDa inhibited endothelial cell proliferation: 25 versus 12.5 mu g (p < 0.05); 12.5 versus 3.15 mu g (p < 0.05). Immobilization of KES28kDa supports endothelial cell survival over the control p = 0.021). Human umbilical vein endothelial cells plated on immobilized KES28kDa showed an increase in membrane ruffles and stress fibers. Conclusion: These data demonstrate the local synthesis of a 28-kDa ES-related fragment following AKI and suggest its role in endothelium survival. Copyright (C) 2010 S. Karger AG, Basel

NITRIC OXIDE MEDIATES LUNG VASCULAR PERMEABILITY AND LYMPH-BORNE IL-6 AFTER AN INTESTINAL ISCHEMIC INSULT

Acute lung injury following intestinal I/R depends on neutrophil-endothelial cell interactions and on cytokines drained from the gut through the lymph. Among the mediators generated during I/R, increased serum levels of IL-6 and NO are also found and might be involved in acute lung injury. Once intestinal ischemia itself may be a factor of tissue injury, in this study, we investigated the presence of IL-6 in lymph after intestinal ischemia and its effects on human umbilical vein endothelial cells (HUVECs) detachment. The involvement of NO on the increase of lung and intestinal microvascular permeability and the lymph effects on HUVEC detachment were also studied. Upon anesthesia, male Wistar rats were subjected to occlusion of the superior mesenteric artery during 45 min, followed by 2-h intestinal reperfusion. Rats were treated with the nonselective NO synthase (NOS) inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) or with the selective inhibitor of iNOS aminoguanidine 1 h before superior mesenteric artery occlusion. Whereas treatment with L-NAME during ischemia increased both IL-6 levels in lymph and lung microvascular permeability, aminoguanidine restored the augmented intestinal plasma extravasation due to ischemia and did not induce IL-6 in lymph. On the other hand, IL-6 and lymph of intestinal I/R detached the HUVECs, whereas lymph of ischemic rats upon L-NAME treatment when incubated with anti-IL-6 prevented HUVEC detachment. It is shown that the intestinal ischemia itself is sufficient to increase intestinal microvascular permeability with involvement of iNOS activation. Intestinal ischemia and absence of constitutive NOS activity leading to additional intestinal stress both cause release of IL-6 and increase of lung microvascular permeability. Because anti-IL-6 prevented the endothelial cell injury caused by lymph at the ischemia period, the lymph-borne IL-6 might be involved with endothelial cell activation. At the reperfusion period, this cytokine does not seem to be modulated by NO.

Differential Antitumor Effects of IgG and IgM Monoclonal Antibodies and Their Synthetic Complementarity-Determining Regions Directed to New Targets of B16F10-Nex2 Melanoma Cells

Malignant melanoma has increased incidence worldwide and causes most skin cancer-related deaths. A few cell surface antigens that can be targets of antitumor immunotherapy have been characterized in melanoma. This is an expanding field because of the ineffectiveness of conventional cancer therapy for the metastatic form of melanoma. In the present work, antimelanoma monoclonal antibodies (mAbs) were raised against B16F10 cells (subclone Nex4, grown in murine serum), with novel specificities and antitumor effects in vitro and in vivo. MAb A4 (IgG2ak) recognizes a surface antigen on B16F10-Nex2 cells identified as protocadherin beta(13). It is cytotoxic in vitro and in vivo to B16F10-Nex2 cells as well as in vitro to human melanoma cell lines. MAb A4M (IgM) strongly reacted with nuclei of permeabilized murine tumor cells, recognizing histone 1. Although it is not cytotoxic in vitro, similarly with mAb A4, mAb A4M significantly reduced the number of lung nodules in mice challenged intravenously with B16F10-Nex2 cells. The V(H) CDR3 peptide from mAb A4 and V(L) CDR1 and CDR2 from mAb A4M showed significant cytotoxic activities in vitro, leading tumor cells to apoptosis. A cyclic peptide representing A4 CDR H3 competed with mAb A4 for binding to melanoma cells. MAb A4M CDRs L1 and L2 in addition to the antitumor effect also inhibited angiogenesis of human umbilical vein endothelial cells in vitro. As shown in the present work, mAbs A4 and A4M and selected CDR peptides are strong candidates to be developed as drugs for antitumor therapy for invasive melanoma.

Bendadaite, a new iron arsenate mineral of the arthurite group

Bendadaite, ideally Fe(2+)Fe(2)(3+)(AsO(4))(2)(OH)(2 center dot).4H(2)O, is a new member of the arthurite group It was found as a weathering product of arsenopyrite on a single hand specimen from the phosphate pegmatite Bendada. central Portugal (type locality) Co-type locality is the granite pegmatite of La via do Almerindo (Almerindo mine), Linopolis, Divmo das Laranjeiras county, Minas Gerais, Brazil Further localities are the Vein Negra mine, Copiapo province, Chile, mid-East, Bou Azzer district, Morocco, and Para Inferida yard, Fenugu Sibirt mine, Gonnosfanadiga, Medio Campidano Province, Sardinia. Italy Type bendadaite occurs as blackish green to dark brownish tufts (<0 1 mm long) and flattened radiating aggregates. in intimate association with an intermediate member of the scorodite-mansfieldite series It is monoclinic. space group P2(l/c). with a = 10 239(3) angstrom. b = 9 713(2) angstrom, c = 5 552(2) angstrom. beta = 94 11(2)degrees. = 550 7(2) angstrom(3). Z = 2 Electron-microprobe analysis yielded (wt %). CaO 0 04, MnO 0 03. CuO 006, ZnO 004. Fe(2)O(3) (total) 43 92, Al(2)O(3) 115. SnO(2) 0 10, As(2)O(5) 43 27. P(2)O(5) 1 86, SO(3) 0.03 The empirical formula is (Fe(0 52)(2+)Fe(0 32)(3+)rectangle(0 16))(Sigma 1 00)(Fe(1 89)(3+)Al(0 11))(Sigma 2 00)(As(1 87)P(0 13))(Sigma 2 00)O(8)(OH)(2 00) 4H(2)O based. CM 2(As,P) and assuming ideal 80, 2(OH), 4H2O and complete occupancy of the ferric on site by Fe(3+) and Al Optically, bendadaite is biaxial, positive, 2V(est) = 85+/-4 degrees, 2V(eale) = 88 degrees, with alpha 1 734(3). 13 1 759(3), 7 1 787(4) Pleochrosim is medium strong X pale reddish brown. Y yellowish brown, Z dark yellowish brown. absorption Z > V > X, optical dispersion weak, r > v. Optical axis plane Is parallel to (010), with X approximately parallel to a and Z nearly parallel to c Bendadaite has vitreous to sub-adamantine luster, is translucent and non-fluorescent It is brittle, shows irregular fracture and a good cleavage parallel to 1010} 3 15 0 10 g/cm(3), 3 193 g/cm3 (for the empirical formula) The five strongest powder diffraction lines [d in angstrom (I)(hkl] are 10 22 (10)(100), 7 036 (8)(110), 4 250 (5)(11 I), 2 865 (4)(311), 4 833 (3)(020,011) The d spacings are very similar to those of its Zn analogue, ojelaite The crystal structure of bendadaite was solved and refined using a crystal from the co-type locality with the composition (Fe(0 95)(2+)rectangle(0 05))(Sigma 1 00)(Fe(1 80)(3+)Al(0 20))Sigma(2 00)(As(1 48)P(0 52))(Sigma 2 00)O(8)) (OH)(2) 4H(2)O (R = 16%) and confirms an arthurite-type atomic arrangement

HYDROTHERMAL REE FLUOROCARBONATE MINERALIZATION AT BARRA DO ITAPIRAPUA, A MULTIPLE STOCKWORK CARBONATITE, SOUTHERN BRAZIL

The Barra do Itapirapua ( BIT) carbonatites in southern Brazil belong to the final stages of the Early Cretaceous alkaline rock - carbonatite magmatism of the Ponta Grossa Arch Province. The BIT complex is a dyke and vein stockwork in which four main carbonatitic phases are recognized, mainly magnesiocarbonatites and ferrocarbonatites. These carbonatites are generally overprinted by pervasive hydrothermal events. The C-O stable isotopic data indicate re-equilibration under hydrothermal conditions at temperatures between 375 and 80 degrees C. Significant amounts of REE fluorocarbonate minerals, relatively Sr- and Th-rich, were deposited. Syntaxy between synchysite-(Ce) and parisite-(Ce) is very common owing to the similarity in structures, with alternating (001) layers of (CeF), (CO3) and (Ca). However, bastnasite-(Ce) occurs as individual crystals, overgrown by the synchysite and parisite polycrystals. Textural and chemical reactions between the REE fluorocarbonates provide insights into the mobility of rare-earth elements during fluid-rock interaction. The BIT complex is considered to be of potential economic interest for production of the rare-earth concentrates.

Mafic dykes at the southwestern margin of Eastern Ghats belt: Evidence of rifting and collision

The southwestern margin of the Eastern Ghats Belt characteristically exposes mafic dykes intruding massif-type charnockites. Dykes of olivine basalt of alkaline composition have characteristic trace element signatures comparable with Ocean Island Basalt (OIB). Most importantly strong positive Nb anomaly and low values of Zr/Nb ratio are consistent with OIB source of the mafic dykes. K-Ar isotopic data indicate two cooling ages at 740 and 530 Ma. The Pan-African thermal event could be related to reactivation of major shear zones and represented by leuco-granite vein along minor shear bands. And 740 Ma cooling age may indicate the low grade metamorphic imprints, noted in some of the dykes. Although no intrusion age could be determined from the present dataset, it could be constrained by some age data of the host charnockite gneiss and Alkaline rocks of the adjacent Prakasam Province. Assuming an intrusion age of similar to 1.3 Ga, Sr-Nd isotopic composition of the dykes indicate that they preserved time-integrated LREE enrichment. In view of the chemical signatures of OIB source, the mafic dykes could as well be related to continental rifting, around 1.3 Ga, which may have been initiated by intra-plate volcanism.

Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide ROLE IN ARGININE AND NITRIC OXIDE PRODUCTION

Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-dependent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, alpha-methyl-DL-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases.

Trombose da veia porta em crianças e adolescentes : deficiência das proteínas C, S e Antitrombina e pesquisa das mutações fator V Leiden, G20210A da Protrombina e C677T da Metileno-tetraidrofolato redutase

Objetivo: A trombose da veia porta é uma causa importante de hiper-tensão porta em crianças e adolescentes, porém, em uma proporção importante dos casos, não apresenta fator etiológico definido. O objetivo desse estudo é determinar a freqüência de deficiência das proteínas inibidoras da coagulação – proteínas C, S e antitrombina − e das mutações fator V Leiden, G20210A no gene da protrombina e C677T da metileno-tetraidrofolato redutase em crianças e adolescentes com trom-bose da veia porta, definir o padrão hereditário de uma eventual deficiência das pro-teínas inibidoras da coagulação nesses pacientes e avaliar a freqüência da deficiên-cia dessas proteínas em crianças e adolescentes com cirrose. Casuística e Métodos: Foi realizado um estudo prospectivo com 14 crianças e adolescentes com trombose da veia porta, seus pais (n = 25) e dois gru-pos controles pareados por idade, constituídos por um grupo controle sem hepato-patia (n = 28) e um com cirrose (n = 24). A trombose da veia porta foi diagnosticada por ultra-sonografia abdominal com Doppler e/ou fase venosa do angiograma celíaco seletivo. A dosagem da atividade das proteínas C, S e antitrombina foi determinada em todos os indivíduos e a pesquisa das mutações fator V Leiden, G20210A da pro-trombina e C677T da metileno-tetraidrofolato redutase, nas crianças e adolescentes com trombose da veia porta, nos pais, quando identificada a mutação na criança, e nos controles sem hepatopatia. Resultados: Foram avaliados 14 pacientes caucasóides, com uma média e desvio padrão de idade de 8 anos e 8 meses ± 4 anos e 5 meses e do diagnóstico de 3 anos e 8 meses ± 3 anos e seis meses. Metade dos pacientes pertenciam ao gênero masculino. O motivo da investigação da trombose da veia porta foi hemorra-gia digestiva alta em 9/14 (64,3%) e achado de esplenomegalia ao exame físico em 5/14 (35,7%). Anomalias congênitas extra-hepáticas foram identificadas em 3/14 (21,4%) e fatores de risco adquiridos em 5/14 (35,7%) dos pacientes. Nenhum pa-ciente tinha história familiar de consangüinidade ou trombose venosa. A deficiência das proteínas C, S e antitrombina foi constatada em 6/14 (42,9%) (p < 0,05 vs con-troles sem hepatopatia), 3/14 (21,4%) (p > 0,05) e 1/14 (7,1%) (p > 0,05) pacientes com trombose da veia porta, respectivamente. A deficiência dessas proteínas não foi identificada em nenhum dos pais ou controles sem hepatopatia. A mutação G20210A no gene da protrombina foi identificada em um paciente com trombose da veia porta e em um controle sem hepatopatia (p = 0,999), mas em nenhum desses foi identificado a mutação fator V Leiden. A mutação C677T da metileno-tetraidrofo-lato redutase foi observada na forma homozigota, em 3/14 (21,4%) dos pacientes com trombose da veia porta e em 5/28 (17,9%) controles sem hepatopatia (p = 0,356). A freqüência da deficiência das proteínas C, S e antitrombina nos pacientes com cir-rose foi de 14/24 (58,3%), 7/24 (29,2%) e 11/24 (45,8%), respectivamente (p < 0,05 vs controles sem hepatopatia), sendo mais freqüente nos pacientes do subgrupo Child-Pugh B ou C, que foi de 11/12 (91,7%), 5/12 (41,7%) e 9/12 (75%), respectivamente (p < 0,05 vs controles sem hepatopatia). Conclusões: A deficiência de proteína C foi freqüente nas crianças e adolescentes com trombose da veia porta e não parece ser de origem genética. A deficiência de proteína S, antitrombina e as presenças das mutações G20210A da protrombina e C677T da metileno-tetraidrofolato redutase foram observadas mas não apresentaram diferença estatística significativa em relação ao grupo controle sem hepatopatia. O fator V Leiden não foi identificado. Os resultados deste estudo sugerem que a deficiência da proteína C pode ocorre como conseqüência da hiper-tensão porta. Os distúrbios pró-trombóticos hereditários não parecem apresentar um papel importante em relação à trombose nas crianças e adolescentes estudadas.

Valor percebido e a nova lógica dominante de serviço : estudo da indústria brasileira de equipamentos de refrigeração para transporte de cargas

Levitt (1960) apresentou o termo Miopia em Marketing e discutiu sobre o perigo de as organizações centralizarem seu foco no produto e descuidarem da real necessidade dos clientes, já que o produto é apenas um meio para atender à necessidade do cliente e não o fim em si. Na mesma linha, Shostack (1977), quase duas décadas mais tarde, enfatizou a urgência de se entender a posição do Marketing na economia pós-industrial de serviços, em que a lógica tradicional focada em produtos não mais atendia adequadamente o mercado. Portanto, não é recente a visão de que a posse do bem físico é secundária para o atendimento das necessidades do consumidor, sendo fundamental pensar no benefício que o bem proporciona ao cliente quando do seu uso. Mais recentemente, Vargo e Lusch (2004a) retomaram a discussão sobre a importância de as organizações atentarem para as necessidades dos clientes em vez de apenas focarem na transação, ou seja, na ideia de troca de um produto por um valor monetário. Estes autores emergiram novamente com a ideia de que as empresas precisam entregar benefícios aos seus clientes e a que apropriação do serviço gerado pela oferta da empresa é mais importante do que a transferência de posse do bem físico. Eles retomam, desta forma, as ideias de Levitt e Shostack e as modificam para criar a Service-Dominant Logic ou S-D Logic, como eles denominam. A ênfase desta proposta é que o Marketing deixe de considerar a transação de produtos ou serviços como central para a criação de valor, para uma lógica centrada no serviço produzido pelo bem – produto ou serviço. Assim, passa ser fundamental entender como o valor é percebido pelo cliente na fase de uso e focar os esforços na geração desse valor, possibilitando, assim, que empresas que entendam as reais necessidades do mercado, criem vantagem competitiva sustentável. Considerando a proposta destes autores, este trabalho testou a aplicação deste conceito na indústria de equipamentos de refrigeração para transporte de cargas com temperatura controlada no Brasil. Foram entrevistados seis importantes transportadores de carga frigorificada do país, os quais foram questionados sobre o valor do serviço usufruído pela posse do bem em contraposição ao valor percebido de usufruir o serviço sem ter que comprar o bem para tal. Os entrevistados associam muito valor à posse do bem, pois, para eles, isso garante que o serviço não sofrerá interrupções, algo muito valioso para eles. Isso evidencia uma falta de confiança nas alternativas possíveis à compra do ativo pela empresa. A confiança no prestador do serviço é, portanto, elemento chave na avaliação dos benefícios, reforçando achados de estudos anteriores. Foram identificadas diferenças de atribuição de valor para as propostas alternativas de fornecimento em razão da relevância do serviço de transporte refrigerado para a empresa – negócio central ou função de apoio para o negócio central da empresa.

The ileum as a determinant organ of the functional liver cell mass in rats

PURPOSE: To evaluate if the ileum resection changes the functioning liver cell mass, the hepatic metabolism and the biodistribution of radiopharmaceutical in rats. METHODS: Twelve Wistar rats weighing 285g±34g were randomly divided into the ileum resection group (n = 6) and sham group rats (n = 6). After 30 days, they were anesthetized and 0.1mL of 99m-Tc-phytate(0.66MBq) was injected via femoral vein. After 30 minutes, blood samples were collected for red blood cells radioactive labeling and serum ALT, AST and gammaGT. Liver samples were used for 99m-Tc-phytatepercentage of radioactivity/gram of tissue and histopathology. Student’s t test was used with significance 0.05. RESULTS: There was a higher uptake of 99m-Tc-phytate in the liver of sham rats, compared to the ileum resection group (p<0.05). GammaGT, ALT and AST were increased in ileum resection rats compared to sham (p<0.05). The he patocytes count was significantly lower in ileum resection group than in sham (p<0.05). Liver: body mass ratio was lower in experimental animals than in sham group (p<0.05). CONCLUSION: These data support that the ileum has important role in liver function and liver mass regulation, and they have potential clinical implications regarding the pathogenesis of liver injury following lower bowel resection.