Ischemic preconditioning and atenolol on lung injury after intestinal ischemia and reperfusion in rats.

The aim of this study was evaluate the beta blocker atenolol (AT) and ischemic preconditioning (IPC) strategies for tissue protection against systemic effects of intestinal ischemia (I) and reperfusion (R) injury. Forty-two rats were pretreated with AT (1.5 mg · kg(-1)), 0.9% saline solution (SS; 0.1 mL), or IPC and then subjected to prolonged occlusion of the superior mesenteric artery for 60 minutes leading to I followed or not by 120 minutes of R, according to the group. For IPC, 5 minutes of I prior to 10 minutes of R were established. After this process of I or I-R, the right lung of each animal was adequately prepared for staining with hematoxylin and eosin and subsequent histologic analysis for quantification of inflammatory infiltrate was done. The left lung was frozen and prepared for assessment of oxidative stress by the quantification of thiobarbituric acid-reactivity substances (TBARS). Histologic analysis showed an important inflammatory infiltrate in the I-R + SS (I-R + SS = 4.5), which was significantly (P < .05) reduced by IPC (I-R + IPC = 3.0) or AT (I-R + AT = 3.0). Likewise, the TBARS levels were decreased by both strategies (I-R + SS = 0.63; I-R + IPC = 0.23; I-R + AT = 0.38; P < .05). Our results showed that AT and IPC attenuate pulmonary lesions caused by intestinal I and R process.

Cardiac effect of ischemic preconditioning and heparin following intestinal ischemia and reperfusion in rats.

To study the role of heparin and ischemic preconditioning (IPC) in cardiac injury after intestinal ischemia (I) and reperfusion (R), 54 rats underwent 60 minutes of I, which was produced by occlusion of the superior mesenteric artery, and/or 120 minutes of R. The IPC group had the I procedure stimulation for 5 minutes and R for 10 minutes. The control group was subjected to sham surgery only, and the other groups were injected with saline solution (SS; 0.1 mL) or heparin (100 IU/kg) via the inferior cava vein 5 minutes before I and 5 minutes before R and 55 minutes after the R begins in I-R groups. In all animals, cardiac samples were stained with hematoxylin and eosin for optical microscopy analysis, and other sample was processed for lipid peroxidation determination. In I-R groups, both heparin and IPC showed significant protection compared to the SS group; conversely, in animals subjected only to I, no protection was observed. Moreover, when heparin was associated with IPC, I-R protection was compromised and the ischemic injury increased. Data showed that IPC and heparin attenuated cardiac dysfunction caused by intestinal I and I-R, but when used in association did not show beneficial effects.

The long-term outcome of patients with hypertensive cardiomyopathy.

The prognosis of dilated cardiomyopathy due to hypertension (HT-DCM) is surprisingly unknown, particularly in the absence of coronary disease and diabetes. We aimed at investigating the long-term outcome and the predictors of mortality in patients with left ventricular systolic dysfunction exclusively due to hypertension. From October 1995 to May 2001, 90 consecutive patients with echocardiographic fractional shortening (FS) < 30% and 29 control patients with FS > or = 30% were included. Obstructive coronary disease was excluded by dipyridamole myocardial perfusion imaging in all patients and coronary angiography in 60. After a mean follow-up of 4.3+/-1.6 years, the total mortality rate of HT-DCM was twice as much higher than that of patients without left ventricular systolic dysfunction (P = 0.01). In HT-DCM, the 5-year mortality rate was 26%. Univariate analyses selected age and creatinine for being positively related to mortality, and body mass index, FS and blood pressure during follow-up for being negatively related to mortality. Neither the improvement of left ventricular FS nor the decrease in left ventricular mass index was related to survival. Multivariate analysis identified (hazard ratio; 95% confidence interval) age (1.08; 1.02-1.13), body mass index (0.86; 0.75-0.98), and baseline FS (0.88; 0.78-0.98) as independent predictors of mortality. In conclusion, poor survival in HT-DCM can be anticipated by the severity of left ventricular systolic dysfunction and advanced age. Instead of ominous signs, high blood pressure and body mass may predict a more favourable prognosis.

Gangliosideos e a resposta de hipersensibilidade retardada em camundongos / Gangliosides and the delayed hypersensitivity response in mice

Em trabalhos anteriores mostrou-se que os gangliosídeos (GSLs) têm um efeito inibitório sobre a proliferação linfocitária e a síntese de IL-2, assim como sobre a reação mista de linfócitos. Neste estudo objetivou-se avaliar o efeito dos GSLs sobre a resposta de hipersensibilidade retardada. Foram utilizados 12 camundongos BALB/c, machos, pesando em média 30 gramas, provenientes do biotério setorial da Disciplina de Parasitologia e mantidos por 5 dias para adaptação no biotério setorial da Disciplina de Técnica Operatória e Cirurgia Experimental da UNIFESP-EPM, recebendo água e ração própria para a espécie. Os animais foram distribuídos em três grupos, de acordo com as doses de GSLs, da seguinte forma: grupo 3mg. kg-1, grupo 9mg. kg-1 e grupo simulado (veículo). Os animais foram tratados, por via intramuscular, nos dias 0 e 4. O parâmetro avaliado foi o edema da pata traseira esquerda no local da inoculação do antígeno. Os animais foram anestesiados com Cetamina (60mg.kg-1) e Xilazina (10mg.kg-1), por via intramuscular, sendo em seguida submetidos à dissecção da veia jugular direita, por onde foram inoculadas 10(6) hemácias de Carneiro no dia 0, para sensibilização. No dia 4 subsequente, os animais foram novamente anestesiados e receberam, por via subcutânea, 10(8) hemácias de Carneiro, num volume de 0,02ml. Foram realizadas medidas do edema da pata traseira com paquímetro 24, 48, 72 e 96 horas após o desafio. Os dados mostraram que após 48h houve um aumento do edema em animais dos grupos simulado e 3mg (médias=2,3 and 2,1mm, respectivamente), e os camundongos do grupo 9mg não apresentaram aumento importante (média=0,1mm). Entretanto, após 72h, o grupo 9mg apresentou aumento de 1,7mm enquanto, os outros grupos não apresentaram mudança significativa no edema da pata (médias=0,2 e 0,8mm), grupos simulado e 3mg, respectivamente) comparados aos dados do dia antecedente. Após 96h, todos os grupos apresentaram desaparecimento do edema. Com base nos dados obtidos pode-se concluir que a resposta de hipersensibilidade retardada alterou-se na vigência de alta dose de GSLs.

Aortic valve assessment. Anatomical study of 100 healthy human hearts.

PURPOSE: To assess anatomical characteristics of the aortic valve, so that they may be useful in diagnostic situations and surgical treatment. METHODS: The study analyzed 100 healthy fixed human hearts; 84% of them obtained from males, 61% of them from Caucasian individuals. The ages of the individuals ranged from 9 to 86 years (mean 30 +/- 15.5 years). The characteristics assessed related to age, sex, and race were the following: number and height of the cusps, size of the lunulae, internal and external intercommissural distance, position of the coronary ostium in relation to the aortic valve, position of the ventricular septum in relation to the aortic valve, thickness of the cusps. RESULTS: All hearts assessed had a tricuspidal aortic valve. In regard to the height of the cusps and size of the lunula, the left coronary cusp was larger, followed by the right coronary cusp and the noncoronary cusp. The internal and external intercommissural distances had mean values of 24.6 +/- 5.7 mm and 19.7 +/- 7 mm, respectively. In regard to the position of the coronary ostia, in one heart two ostia emerged from the left coronary sinus, and in another, the ostium was supracommissural. The mean diameter of the aorta was 21.8 +/- 3.6 mm, and there were no significant sexual or racial differences, but the diameter increased progressively with the increase in age. The thickness of the cusps did not show any significant difference in the 3 points assessed. CONCLUSION: The aortic valve annulus did not show a perfect circumference, with some variations in the measurements of the annulus, in the cusps and in the relation with the ventricular septum.

Nitric oxide may trigger lactation in humans.

OBJECTIVE: To determine whether nitric oxide is synthesized in the breast and plays a role in lactation. DESIGN: Concentrations of biopterin, neopterin, and the total concentration of nitrite plus nitrate, a marker for nitric oxide generation were measured in 242 samples of breast milk obtained from 39 women during postpartum days 1 to 30. The total concentration of nitrite plus nitrate was measured in 17 sets of breast milk and serum obtained from 17 women on postpartum day 4 or 5. RESULTS: (1) The total concentration of nitrite plus nitrate rose and peaked just before an increase in the volume of milk secreted was observed. (2) The total concentration of nitrite plus nitrate in breast milk was not correlated with that in the serum. (3) High levels of neopterin and biopterin were found in breast milk. (4) The volume of breast milk on day 5 was correlated with the total concentration of nitrite plus nitrate observed in breast milk on days 1 to 3. (5) The total concentration of nitrite plus nitrate in the breast milk of the high secretors significantly exceeded that seen in the low secretors. CONCLUSIONS: We suggest that nitric oxide is synthesized in the breast and may trigger lactation in humans.

Differential expression of fibronectin receptors during myeloid differentiation and in marrow- and peripheral blood-derived leukemic cells.

A 125I-labeled 120-kDa fibronectin fragment (FN120) containing the RGD binding site was employed to assess FN120 receptor levels in control and dimethylsulfoxide (DMSO)-differentiated HL60 cells, as well as in leukemic peripheral and bone marrow blast cells from acute lymphoid (ALL) and myeloid (AML) patients. Fibronectin CS1 fragment receptor alpha 4 (VLA4-alpha) and RGD-dependent alpha 5 integrin subunits (VLA5-alpha) were characterized by specific monoclonal antibodies (MoAb). HL60 cells, induced along the granulocytic pathway with DMSO, displayed low FN120 binding level densities (36,070 +/- 5142 sites/cell (s/c) vs. 19,780 +/- 4564 s/c, P < 0.005), respectively, for untreated and treated cells) together with decreased VLA5-alpha expression. Granulocytes displayed low levels of FN120 receptors (3167 +/- 1165 s/c) with weak VLA5-alpha expression and absence of VLA4-alpha. Normal lymphocytes displayed 17,670 +/- 8,705 s/c FN120 receptors and VLA4-alpha and VLA5-alpha. The mean FN120 binding levels and mean VLA5-alpha expression were lower in peripheral blast cells, both in ALL and AML, than in the bone marrow leukemic cells. VLA4-alpha remained the same irrespective of cell localization. FN120 binding sites and differential expression of VLA4-alpha and VLA5-alpha integrin molecules on hemopoietic cells could be related to lineage characteristics or cell type distribution within hemopoietic tissue.

Vitamin D3 binding activity during leukemic cell differentiation.

In this paper we report that differentiation of the human promyelocytic leukemia cell line, HL60, along the myelocytic pathway, induced by retinoic acid (RA), or monocytic pathway, induced by phorbol-myristate acetate (PMA) and gamma interferon (IFN), was accompanied by a significant decline in 1,25-dihydroxycholecalciferol (1,25(OH)2D3) binding (control: 30.3 +/- 3.0 fM/10(6) cells; RA treated: 6.8 + 2.5 fM/10(6) cells; PMA treated: 12.3 +/- 6.7 fM/10(6) cells and IFN treated: 16.0 +/- 5.0 fM/10(6) cells). When differentiation and proliferation were uncoupled, by incubation with IFN or by inhibition of proliferation by cell density saturation, 1,25(OH)2D3 binding was better related to differentiation than to proliferation. Additionally we have compared 1,25(OH)2D3 binding levels in blasts from acute lymphocytic leukemia (ALL) patients (25.4 +/- 18.1 fM/10(6) cells) and normal, mature lymphocytes (10.6 +/- 2.1 fM/10(6) cells). Receptor binding was significantly higher (p < 0.05) in the immature blasts. Our data suggest that 1,25(OH)2D3 receptor levels could be considered a marker of functional immaturity, in these cells.