Excessive zinc intake elevates systemic blood pressure levels in normotensive rats--potential role of superoxide-induced oxidative stress

OBJECTIVES: The present study was designed to examine whether or not excessive Zn intake affects systemic blood pressure (BP) levels in a normotensive state. METHODS: Systolic BP (SBP) and mean arterial pressure (MAP) before and after administration of the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) or the exogenous superoxide scavenger, tempol and the activity of the endogenous superoxide scavenger, Cu/Zn-superoxide dismutase (SOD) and levels of endothelial type (e)NOS mRNA and protein in the thoracic aorta were analyzed in male Sprague-Dawley rats fed a standard diet containing 0.005% Zn or a high Zn diet containing 0.5% Zn for 8 weeks. RESULTS: SBP and MAP levels observed at the end of dietary conditioning were significantly elevated in rats fed a high Zn diet relative to rats fed a standard diet. Administration of L-NAME caused an increase in MAP levels in rats fed a standard and a high Zn diet, demonstrating the involvement of the vasodilator, nitric oxide (NO) in the regulation of systemic BP in the two groups of rats. However, the expression of eNOS mRNA and protein in the thoracic aorta was not significantly different between rats fed a standard and a high Zn diet. On the other hand, administration of tempol led to a decrease in MAP levels in rats fed a standard and a high Zn diet, indicating the participation of the oxygen free radical, superoxide in the modification of systemic BP in the two groups of rats. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO through the formation of peroxynitrite based on the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment dramatically restored MAP levels in rats fed a high Zn diet to levels comparable with those observed in rats fed a standard diet, indicating that an elevation in systemic BP levels seen in rats fed a high Zn versus a standard diet is presumably brought by a reduction in the action of the vasodilator, NO resulting from an increase in the action of superoxide. The activity of Cu/Zn-SOD in the thoracic aorta was significantly reduced in rats fed a high Zn diet relative to rats fed a standard diet, appearing to at least in part, play a role in an increase in the action of superoxide in the vessel wall of rats fed a high Zn diet. CONCLUSIONS: Excessive Zn intake may be a factor to elevate systemic BP levels in a normotensive state presumably through the oxidative stress caused by superoxide.     

甘露聚糖、壳聚糖、α-酸性糖蛋白和姜黄素对脂蛋白(a)和去唾液酸脂蛋白(a)代谢影响的对比分析

分析多糖和姜黄素对脂蛋白 (a)和去唾液酸脂蛋白 (a)代谢的影响 ,从刺猬腋下静脉注入甘露聚糖、壳聚糖、α -酸性糖蛋白和姜黄素 ,2min后注射12 5I-脂蛋白 (a)或12 5I-去唾液酸脂蛋白 (a) ,1h后处死动物 ,测定血、肝、肾、脾、胆汁和肾上腺的同位素含量。结果发现 ,脂蛋白 (a)去唾液酸后能大量进入肝脏 ,加速在体内的分解代谢 ,使血中浓度迅速降低。α -酸性糖蛋白抑制组织对脂蛋白 (a)和去唾液酸脂蛋白 (a)的摄入 ,使血中脂蛋白 (a)和去唾液酸脂蛋白 (a)含量显著增高。壳聚糖和姜黄素增加肝脏和肾上腺对脂蛋白 (a)的摄取 ,使血中脂蛋白 (a)含量略降低 ,但对去唾液酸脂蛋白 (a)代谢无明显影响。甘露聚糖增加脾脏对脂蛋白 (a)的摄取 ,减少胆囊中脂蛋白 (a)含量 ,但增加肾脏和胆囊对去唾液酸脂蛋白 (a)的摄取 ,降低肾上腺对去唾液酸脂蛋白 (a)的摄取。结果提示 ,脂蛋白 (a)去唾液酸后能使脂蛋白 (a)分解代谢加快 ,脂蛋白 (a)分子中的唾液酸在结构稳定中起重要的作用。α -酸性糖蛋白抑制脂蛋白 (a)和去唾液酸脂蛋白 (a)代谢 ,而壳聚糖和姜黄素则促进脂蛋白 (a)代谢     

Influence of Tool Geometry and Process Parameters on Torque,Temperature, and Quality of Friction Stir Welds in Dissimilar Al Alloys

In the current investigation, the influence of the tool geometry, the position of the materials in the joint, the welding speed on the temperature and torque developed, and on the quality of the welds in dissimilar and tri-dissimilar T joints were analysed. The aluminium alloys used were AA2017-T4, AA6082-T6, and AA5083-H111 and the friction stir welds were performed with identical shoulder tools, but with either a pin with simple geometry or a pin with progressive geometry. Progressive pin tools proved to be a viable alternative in the production of dissimilar and tri-dissimilar welds, as they provide a larger tool/material friction area and a larger volume of dragged material, which promotes an increase in the heat generated and a good mixing of the materials in the stir zone, although they require a higher torque. Placing a stronger material on the advancing side also results in a higher temperature in the stir zone but requires higher torque too. The combination of these factors showed that tools with a progressive pin provide sound dissimilar and tri-dissimilar welds, unlike single-pin tools. The increase in the welding speed causes the formation of defects in the stir zone, even in tri-dissimilar welds carried out with a tool with a progressive pin, which impairs the fatigue strength of the welds.     

Effect of cardiopulmonary bypass and heparin on plasma levels of Lp(a) and Apo(a) fragments

Fragments of apolipoprotein(a) [apo(a)], the distinctive glycoprotein of lipoprotein(a) [Lp(a)], are present in human plasma and urine and have been implicated in the development of atherosclerosis. The mechanism responsible for the generation of apo(a) fragments in vivo is poorly understood. In this study, we examined the plasma levels of Lp(a) and apo(a) fragments [or free apo(a)] and urinary apo(a) in 15 subjects who underwent cardiac surgery necessitating cardiopulmonary bypass. We also measured the plasma concentration and activity of polymorphonuclear elastase, an Lp(a)-cleaving enzyme in vitro, and plasma levels of C-reactive protein. Despite a marked activation of polymorphonuclear cells and a pronounced inflammatory response, as documented by an 8-fold and a 35-fold increase in plasma levels of polymorphonuclear elastase and C-reactive protein, respectively, the proportion of plasma free apo(a) to Lp(a) and urinary excretion of apo(a) remained unchanged over a 7-day period after surgery, and polymorphonuclear elastase activity remained undetectable in plasma. No fragmentation of apo(a) was observed ex vivo in plasma samples collected before and after surgery. These data indicate that in this model, apo(a) is not fragmented in plasma and are consistent with the hypothesis that apo(a) fragments result from a constitutively active tissue mechanism that is not modified by cardiac surgery with cardiopulmonary bypass.     

Hemodynamic effects of adenosine in conscious hypertensive and normotensive rats

Mean arterial pressure and heart rate were measured during intra-aortic arch (i.a.a.), intravenous, and suprarenal artery (s.r.a.) infusions of adenosine in conscious, unrestrained normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in the absence and presence of ganglionic blockade. In both groups, i.a.a. and i.v. infusions of adenosine induced comparatively larger dose-dependent reductions in mean arterial pressure than did s.r.a. infusions. In WKY, i.a.a. and i.v. infusions of adenosine were equipotent in reducing mean arterial pressure. In contrast, i.a.a. infusion of adenosine was approximately twice as potent as i.v. infusion in SHR. Also, SHR were approximately 6.5 and 2.6 times more sensitive to i.a.a. and i.v. infusions of adenosine, respectively, than were WKY. Further, i.a.a. and s.r.a. infusions of adenosine caused tachycardia in WKY, while i.v. infusions did not alter heart rate. In SHR, neither i.a.a. nor s.r.a. infusion of adenosine altered heart rate, but i.v. infusion induced a profound bradycardia. In ganglionic-blocked WKY that received a norepinephrine infusion to restore blood pressure and heart rate to pre-ganglionic blockade levels, depressor responses to i.a.a. infusion of adenosine were unchanged while the increase in heart rate was abolished. In SHR, ganglionic blockade markedly decreased the depressor response to i.a.a. and i.v. infusions of adenosine and abolished the bradycardic response to i.v. infusion. These results suggest that adenosine is an effective hypotensive agent in both WKY and SHR; however, marked between-strain differences exist in the cardiovascular response to adenosine. These differences most likely are due to changes in adenosine-pulmonary interactions and increases in the importance of adenosine-autonomic interactions in SHR.     

Electrovectorcardiographic manifestations of supraventricular ectopic rhythms (an interpretive hypothesis)

When a low right atrial rhythm is present, P waves are negative in the low leads, they are variable in a VR and positive in a VL and LI. The figure eighth PF loop is located in the first quadrant, the PH loop has a counterclockwise rotation, and the PS can rotate in either direction. In the presence of upper left atrial rhythms, P waves are positive in the low leads and negative in a VL and a VR. The PF and PH loops can be found in the third quadrant of both planes with a clockwise rotation. If the rhythm originates in low left atrial regions, negative P waves are recorded in left precordial leads and positive ones in a VR and a VL. The PF loop has counterclockwise rotation or its branches superimposed and is situated in the second quadrant; PH with clockwise rotation is registered in the third quadrant; PS with either counterclockwise or clockwise rotation develops above and slightly ahead of the E point. When a nodal rhythm exists, P waves are negative in the low leads. The P loops show a counterclockwise rotation or a figure eight morphology. In the absence of atrial enlargements, the PF loop can be recorded in the first quadrant and the PH in the first or the fourth quadrant.     

外周血miR-10a和miR-29a水平对早期脓毒症急诊患者预后有预测作用

目的：探讨外周血miR-10a、miR-29a水平对早期脓毒症急诊患者预后的预测作用。方法：收集早期脓毒症急诊患者94例为观察组，选取同期82例健康体检者为对照组。其中观察组根据病情严重程度分为轻、中、重度3组。比较2组外周血miR-10a和miR-29a的表达水平，以及观察组不同预后患者治疗前miR-10a和miR-29a的表达水平。分析外周血miR-10a、miR-29a表达水平及miR-10a联合miR-29a检测对早期脓毒症急诊患者预后的预测价值。结果：观察组外周血miR-10a和miR-29a表达水平高于对照组（P均<0.05）；观察组病情严重程度不同患者外周血miR-10a和miR-29a表达水平中，与轻度组比较，中度组和重度组患者表达水平升高，而重度组患者又显著高于中度组（P均<0.05）；治疗1个月后，预后不良者18例，预后良好者治疗前外周血miR-10a和miR-29a的表达水平低于预后不良者（P均<0.05）；miR-10a、miR-29a表达水平的最佳截断点分别为2.74和1.39，miR-10a、miR-29a两者联合检测的灵敏度、特异度和曲线下面积（AUC）均高于单独检测，分别为83.33%、85.53%和0.895。结论：早期脓毒症急诊患者外周血miR-10a、miR-29a表达水平均升高，可反应患者病情严重程度，两者联合检测预测早期脓毒症急诊患者的预后效能较高。     

Meaning in life as an important component of functioning in old age

The purpose was to locate different measures of meaning in life in a multidimensional space of functioning in old age. Fifty-five persons born in 1910 and 1914 participated in laboratory tests, a medical examination, and interviews over a three-year period from 1994 to 1997. Measures of meaning in life included a sense of meaning in life, a sense of coherence, and four indices derived from a life-line drawing (linearity, trend, mean level in the past, and mean level in the future). The other measures of functioning were the number of chronic diseases, functional disability, walking speed, self-rated health, cognitive capacity, provision of social relationships, loneliness, depressive mood, number of activities, life satisfaction, and wisdom. Using a multidimensional scaling method, a two-dimensional model of functioning was arrived at. In the first dimension, "subjective vs. objective," all the measures of meaning in life were located in the subjective half. The location of the measures along the second dimension, "psychosocial vs. physical," varied considerably. Some of the measures of meaning in life (a sense of coherence, life-line trend, and linearity) were located in the physical half, while others (sense of meaning in life, life-line mean level in the past) were in the psychosocial half The life-line mean level in the future was located in the center of the dimension. The space of functioning provided a novel and illustrative approach to functioning as a multifaceted behavioral competence with meaning in life as an integral part of it.     

Complete transposition of the great vessels: Clinical and pathologic features

We have had the opportunity to study four cases of complete transposition of the great vessels clinically and post mortem. In one case there was, in addition, a patent foramen ovale, a patent interventricular septum, and a patent ductus arteriosus; in the second, a patent interventricular septum; in the third, a patent foramen ovale and a patent ductus arteriosus; and in the fourth, a patent foramen ovale, a patent ductus arteriosus, and complete interruption of the isthmus of the aorta. Each had its own individual variations, but all showed the characteristic features of complete transposition of the great vessels, namely, (1) persistent cyanosis; (2) cardiac enlargement, especially of the right ventricle; (3) a narrow aortic shadow in the anteroposterior roentgenogram; and (4) an increase in the width of the roentgenographic shadow cast by the great vessels when the patient is placed in the left anterior oblique position.     

ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet

Intercellular adhesion molecule (ICAM)-1, a major adhesion molecule, plays a critical role in the homing of leukocytes to sites of atherosclerotic lesions. However, very little is known on the role of ICAM-1 in initiating and perpetuating vascular lesions in ApoE(-/-) mice fed a chow or a fat diet. This study has investigated the mean aortic lesions in mice (C57BL6 background) with a single-knockout (ApoE(-/-)) or double-knockout (DKO; ApoE(-/-), ICAM-1(-/-)) fed a chow or a fat diet over a period of 3, 6, 15, and 20 weeks. A 3-fold reduction in lesion size was observed at all time points in DKO mice fed a chow diet. However, in DKO mice fed a fat diet, a marked reduction in the aortic lesion was observed at 3 and 15 weeks, which did not reach a significant level at 6 and 20 weeks. This study shows in essence that DKO mice are protected from developing significant lesions for up to 6 weeks when fed a chow diet and from 3 to 6 weeks when fed a fat diet. After 6 weeks, the lesion size of the DKO mice follows that of the single-knockout mice when fed a chow diet and gets to the same level in mice fed a fat diet. Plasma cholesterol levels were not altered as a result of ICAM-1 deficiency. These studies show that ICAM-1 is implicated in the formation and progression of atherosclerotic lesions.     

Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase

Using spontaneously hypertensive rats (SHR) fed a standard or a Zn-deficient diet for 4 weeks, we examined whether Zn deficiency affects systemic blood pressure (BP) levels in a genetically hypertensive state through a fall in the activity of Cu/Zn-superoxide dismutase (SOD). SHR fed a Zn-deficient diet had a progressive increase in systolic BP during the dietary conditioning. Consequently, SHR fed a Zn-deficient diet exhibited significantly increased levels of systolic BP by 2 weeks after the start of dietary treatment when compared with SHR fed a standard diet. Similarly, levels of basal mean arterial pressure (MAP) observed at the end of dietary treatment were SHR fed a Zn-deficient diet > SHR fed a standard diet. Administration of the nitric oxide synthase (NOS) inhibitor, L-NAME, caused an increase in MAP levels in the two groups of rats, demonstrating the involvement of the vasodilator, nitric oxide (NO), in the regulation of systemic BP in a genetically hypertensive state. The expression of endothelial (e) NOS mRNA and protein in the thoracic aorta paralleled basal MAP levels in the two groups of rats, suggesting the counter-regulation of eNOS against the developed hypertensive state in SHR fed a Zn-deficient diet. On the other hand, administration of the superoxide scavenger, tempol (a SOD mimetic compound), led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in an increase in systemic BP in a genetically hypertensive state. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO, based on the formation of peroxynitrite coming from the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment completely restored MAP levels in SHR fed a Zn-deficient diet to levels comparable to those observed in SHR fed a standard diet, indicating that a further increase in systemic BP levels seen in SHR fed a Zn-deficient vs. a standard diet is presumably brought by a reduction in the action of the vasodilator, NO, resulting from an increase in the action of superoxide. The activity of the superoxide scavenger, Cu/Zn-SOD, in the thoracic aorta was significantly decreased in SHR fed a Zn-deficient diet relative to SHR fed a standard diet. It appears that a decrease in the activity of Cu/Zn-SOD observed in the thoracic aorta of SHR fed a Zn-deficient diet at least in part plays a role in an increase in the action of superoxide in this model. Thus, Zn deficiency may be a factor to develop genetic hypertension presumably through the oxidative stress caused by superoxide.     

The relationship between fibrosis and lactate dehydrogenase isoenzymes in the experimental hypertrophic heart of rabbits.

Cardiac hypertrophy was induced in rabbits by injecting either thyroxine or isoprenaline or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the lactate dehydrogenase isoenzyme pattern and an increase in fibrosis (as measured by hydroxyproline concentrations). Isoprenaline treatment led to a moderate increase in heart weight, a marked decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase, and a marked increase in hydroxyproline. Thyroxine treatment led to a small increase in both heart weight and hydroxyproline and a small decrease in the heart/skeletal muscle subunit ration. Coarctation of the aorta, in contrast, caused a marked increase in heart weight, a moderate decrease in heart/skeletal muscle subunit ratio, and a moderate increase in hydroxyproline. These results suggest that the decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase in the experimental hypertrophic heart reflects the extent of myocardial fibrosis, rather than changes within the hypertrophied myocardial cells.     

Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban

Phospholamban (PLN), a regulator of sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs), interacts with both the cytosolic N domain and transmembrane helices M2, M4, M6, and M9 of SERCA. Amino acids in the transmembrane domain of PLN that are predicted to interact with SERCA1a are conserved in sarcolipin (SLN), a functional PLN homologue. Accordingly, the effects of critical mutations in SERCA1a, PLN, and NF-SLN (SLN tagged N-terminally with a FLAG epitope) on NF-SLN/SERCA1a and PLN/NF-SLN/SERCA1a interactions were compared. Critical mutations in SERCA1a and NF-SLN diminished functional interactions between SERCA1a and NF-SLN, indicating that NF-SLN and PLN interact with some of the same amino acids in SERCA1a. Mutations in PLN or NF-SLN affected the amount of SERCA1a that was coimmunoprecipitated in each complex with antibodies against either PLN or SLN, but not the pattern of coimmunoprecipitation. PLN mutations had more dramatic effects on SERCA1a coimmunoprecipitation than SLN mutations, suggesting that PLN dominates in the primary interaction with SERCA1a. Coimmunoprecipitation also confirmed that PLN and NF-SLN form a heterodimer that interacts with SERCA1a in a regulatory fashion to form a very stable PLN/NF-SLN/SERCA1a complex. Modeling showed that the SLN/SERCA1a complex closely resembles the PLN/SERCA1a complex, but with the luminal end of SLN extending to the loop connecting M1 and M2, where Tyr-29 and Tyr-31 interact with aromatic residues in SERCA1a. Modeling of the PLN/SLN/SERCA1a complex predicts that the regulator binding cavity in the E(2) conformation of SERCA1a can accommodate both SLN and PLN helices, but not two PLN helices.     

A study of lymphocyte subsets in the peripheral blood, liver and spleen of patients with idiopathic portal hypertension (IPH)

Lymphocyte subsets in the peripheral blood, liver and spleen of patients with idiopathic portal hypertension (IPH) were examined by means of flow cytometry and immunohistochemical analysis using monoclonal antibodies. The patients with IPH showed a slight decrease in the percentage of Leu2a+ cells and a slight increase of the ratio of Leu3a+ to Leu2a+ cells in the peripheral blood compared with the normal subjects. Flow cytometry analysis of the intrasplenic lymphocyte subsets in the patients with IPH revealed a significant elevation in the percentage of Leu2a+ cells (p less than 0.01) and a reduction of the Leu3a+ to Leu2a+ ratio (p less than 0.05) compared with the normal subjects, and also showed an increase in the percentage of Leu2a+ cells (p less than 0.05) in comparison to the patients with cirrhosis of the liver. An immunohistochemical and histometrical study of the spleen in the patients with IPH revealed an elevation of the amount of red pulp area compared to the normal subjects, and also a significantly increased number of Leu2a+ cells in the red pulp (p less than 0.02) in comparison to the patients with cirrhosis of the liver. Most of the Leu2a+ cells in the spleen were considered to be Leu2a+.15- cells by double immunostaining method. In lymphoid follicles, the IPH cases showed an increase in the size of follicle and germinal center, and an increased number of Leu3a+ cells in the germinal center and the marginal zone compared with the normal subjects. In the liver, the IPH cases showed a similar distribution but fewer lymphocyte subsets in comparison to the patients with cirrhosis of the liver. These results suggested that some immunological disorder is present in patients with IPH.     

Relationship between serum lipoprotein(a) level and thrombin generation to the circadian variation in onset of acute myocardial infarction

A high incidence of acute myocardial infarction (AMI) has been reported between 06:00 and 12:00 h. This may be related to an abnormality in hemostasis. An association has been founded between the serum lipid level and coronary atherosclerosis, as well as the serum lipid level and a hemostatic abnormality. We investigated the association between the time of AMI, the level of serum lipid, and of hemostatic factor. Of the 42 subjects evaluated retrospectively, 20 had experienced an AMI between 06:00 and 12:00 h (group A), while 22 had developed an AMI during some other period (group B). All patients received emergency coronary angiography, which identified a total occlusion of coronary artery in the proximal portion of the left antecedent branch. The serum level of several lipid factors and of hemostatic factors were compared between the two groups. Characteristics of patients were similar in both groups. The serum levels of lipoprotein(a) (Lp(a)) and of thrombin-antithrombin III complex (TAT) were higher in group A than in group B, respectively. The level of other factors were similar in both groups. Group A showed a significant correlation between the level of Lp(a) and TAT, with a tendency (not statistically significant), toward a positive correlation between Lp(a) and PAI-1, and a negative correlation between Lp(a) and t-PA. In a subgroup that experienced AMI in the early morning, a higher level of Lp(a) was associated with an elevation of TAT, a marker for thrombin generation, and with the level of fibrinolytic factor. This suggests that Lp(a) is closely related to the increase in the early morning incidence of AMI via a change in the prothrombotic state.     

Up-regulation of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide by aspirin but not indomethacin

Infection with Helicobacter pylori and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are recognized as the two primary factors in the etiology of gastric disease. In this study, we applied the animal model of H. pylori-induced gastritis to assess the influence of NSAIDs on the course of mucosal inflammatory responses to H. pylori. Two days following intragastric application of H. pylori lipopolysaccharide, rats were divided into groups and administered daily for up to 8 days either indomethacin, aspirin or the vehicle, and their gastric mucosal tissue subjected to histological and biochemical assessment. H. pylori lipopolysaccharide elicited within 2 days a pattern of acute mucosal inflammatory responses accompanied by a massive epithelial cell apoptosis, and a marked increase in the expression of membrane-bound and soluble forms of TNF-alpha. The extent of mucosal inflammatory involvement reached a maximum by the 4th day and showed a decline by the 10th day; this was reflected in a 38.1% reduction in apoptosis, a 53.2% decline in membrane-bound TNF-alpha and a 63.8% decrease in soluble TNF-alpha. Compared to the vehicle controls, aspirin caused a 36.2% increase in the severity of the mucosal inflammatory involvement by the second day of administration and a 25.9% increase in the inflammatory involvement occurred by the 8th day; this effect of aspirin was accompanied by a significant (54.5%) induction in apoptosis, a 58.2% decline in membrane-bound TNF-alpha and a 61% increase in soluble TNF-alpha. In contrast, administration of indomethacin evoked only a marginal increase (5-7%) in apoptosis, and caused no discernible changes in the severity of gastric mucosal involvement and the expression of TNF-alpha forms elicited by H. pylori lipopolysaccharide. The findings indicate that aspirin, but not indomethacin, increases the severity of gastric mucosal inflammatory responses to H. pylori. This detrimental influence of aspirin appears to result from up-regulation in the mucosal expression of soluble form of TNF-alpha, which leads to the amplification of apoptotic events that potentiate gastric mucosal inflammatory reaction to H. pylori.     

Distribution and rearrangements of alleles of c-Ha-ras-1 protooncogene and their correlation with the development of lung, ovarian and thyroid cancers

The protooncogene c-Ha-ras-1 locus in 84 cancer patients was examined for allelic restriction fragment length polymorphism. The distribution of four common c-Ha-ras-1 alleles (a1, a2, a3 and a4) in lung, ovarian and thyroid cancer patients was analyzed. In approximately half (8 out of 15) of lung and ovarian carcinomas possessing the a4 allele, alterations of the c-Ha-ras-1 locus (deletion of allele with the shorter fragment length, amplification of a4 allele, change of allele fragment length) were detected as compared to 2 cases of rearrangement out of 40 tumors lacking the a4 allele. An increased a4 allele frequency was found in individuals with lung and ovarian tumors as compared to controls presented in literary data and thyroid cancer patients. On the other hand, homozygosity for the a2 locus resulting from the deletion of another allele, and increased a2 allele frequency in thyroid cancer patients were observed. Thus the a4 and a2 alleles of c-Ha-ras-1 may perhaps be viewed as genetic markers of predisposition to lung, ovarian and thyroid cancer, respectively, in combination with other clinical parameters.     

How Long Shall the Patient Rest Before Clinic Blood Pressure Measurement?

BACKGROUND: The optimal time at rest before clinic blood pressure (BP) measurement is still undefined. In this study in patients with essential hypertension, the time course of the hemodynamic changes during a 16-min rest in the chair-seated position was evaluated and compared with that observed in a stabilized postural condition, such as after a prolonged supine rest. METHODS: In 55 untreated essential hypertensive patients, BP, heart rate, stroke volume (impedance cardiography), and systemic vascular resistances were measured every other minute during a 16-min rest in the chair-seated position and, in random sequence, in the last 16 min of a 60-min supine rest. RESULTS: Overall, systolic BP (SBP) and diastolic BP (DBP) decreased by 11.6 and 4.3 mm Hg, respectively, during the chair-seated rest; only a 1.8-mm Hg decrease in SBP was observed in the control supine study. The chair-seated fall in BP was associated with a decrease in systemic vascular resistances, in the absence of significant changes in cardiac index. From the logarithmic curve of SBP and DBP decrements, a half-time of 5.8 and 5.5 min respectively, was calculated. Decrements in SBP, but not DBP, were inversely related to the corresponding baseline values. CONCLUSIONS: In untreated essential hypertensive patients a significant decrease in SBP and DBP associated with a systemic vasodilation was observed during a 16-min rest in the chair-seated position. Because approximately 75% of the spontaneous fall in BP occurred within 10 min, it appears that this time at rest before clinic BP evaluation could improve the precision and accuracy of the measurement.     

Monotherapy versus Combination Therapy in Patients Hospitalized with Community-Acquired Pneumonia

Current international guidelines for the management of community acquired pneumonia (CAP) recommend therapy with a beta-lactam plus a macrolide or a 'respiratory' fluoroquinolone alone in patients hospitalized in a medical ward, and combination therapy with a beta-lactam plus a macrolide or a fluoroquinolone in patients hospitalized in the intensive care unit. However, which of the available options should be preferred remains a matter of debate, and there are surprisingly few prospective randomized trials strictly comparing mono- versus dual therapy strategies in CAP patients. Thus, the recommendation of combining a macrolide with a beta-lactam rather than using a beta-lactam alone in hospitalized patients is derived mainly from observational data, and the suggested combination of a beta-lactam with a fluoroquinolone in severe CAP has been rarely examined in a clinical trial.As there have been sound theoretical arguments for and against combination therapy regimens, the rationale for the different options is discussed and available clinical trial data are reviewed in this article. A final conclusion about the superiority of one antibacterial regimen over another in hospitalized patients with CAP cannot be drawn on the basis of the limited data available. So far, combination therapy probably should be preferred in all patients presenting with severe pneumonia, whereas in general, combination therapy is not necessary in patients in a medical ward, and combination therapy with a beta-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone should be considered equivalent in this latter patient group. On the other hand, the available data demonstrate that empirical coverage of atypical bacteria in all patients with mild-to-moderate CAP seems unnecessary, and beta-lactam monotherapy might perform equally well when compared with respiratory fluoroquinolones in patients with non-severe CAP. Thus, the alternative use of a beta-lactam alone at adequate dosage in clinically stable patients seems justified, if CAP due to Legionella pneumophila is unlikely.