Calcium antagonists and renal protection: emerging perspectives

During the past two decades, major investigative interest has focused on the determinants of chronic renal disease and interventions that retard the inexorable progression to end-stage renal disease. Recent studies have provided a theoretic framework for anticipating that angiotensin-converting enzyme (ACE) inhibitors, and possibly calcium antagonists, may preferentially retard the progression of renal disease. Whereas the majority of available clinical trials have assessed the effects of ACE inhibitors in patients with insulin-dependent diabetes mellitus, relatively few long-term studies have evaluated the renoprotective effects of ACE inhibitors and calcium antagonists in patients with nondiabetic renal disease. Recent observations suggest that the two classes of drugs act in a complementary manner to countervail pathogenetic mechanisms at the level of the mesangium. Such observations recently prompted randomized prospective studies that compare the renoprotective effects of calcium antagonist versus ACE inhibitor monotherapy in both diabetic patients and patients with nondiabetic renal disease.     

Assessing stress-buffering effects: a cautionary note

Research on the stress-buffering functions of social support is equivocal. The purpose of this study was to suggest that part of the reason for these contradictory findings may be due to the fact that researchers have misspecified the relationship between stress and support. Instead of always being an effective coping resource, this study tested the view that there are limits to the beneficial effects of assistance provided by others and that beyond a certain level support may actually exacerbate the noxious impact of stress. Data from a recent nationwide survey of older adults support this more complex perspective. More specifically, the data suggest that although emotional support initially reduces the effects of chronic financial strain on depressive symptoms, further increments in emotional assistance are associated with increased psychological distress.     

Assessing the effects of clinic-based psychotherapy with children and adolescents.

Recent meta-analyses suggest that psychotherapy is quite effective with children and adolescents. However, most research in those analyses involved controlled laboratory interventions that may not represent typical therapy in clinics. We studied more representative treatment as it routinely occurs, in 9 clinics. We compared 93 youngsters who completed a course of therapy with 60 who dropped out after intake. At intake, the groups did not differ on demographic, family, or clinical measures, including Child Behavior Checklist (CBCL) scores. Six months later (when therapy had ended for 98% of the treated children) and again 1 year later, the 2 groups were compared on CBCL scores, parent ratings of each child's major referral problem, and (for a subsample) teacher reports. No comparison showed significant main effects of therapy. The findings (a) raise questions about the generalizability of findings from research-oriented therapy and (b) suggest that the control and precision of research therapy may be needed in clinical practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessing the effects of stress on physical symptoms.

Stress researchers, in attempting to circumvent methodological problems in correlation studies, have resorted to analytical techniques that increase the likelihood of a Type II error. For instance, studies suggesting that stress plays no role in irritable bowel syndrome are at variance with a large body of clinical experience and may be in error. Several measurement issues are discussed, but the most significant concerns the way investigators deal with individual differences in chronic levels of stress and symptoms. J. Suls et al (see record 1994-34099-001) recommend correcting for these individual differences before estimating the relationship between stress and symptoms, but this is illogical because most stressors are chronic (i.e., they are related to the social and economic circumstances in which people live). A more important confound, not considered by most investigators, is the contribution of somatization to stress assessment and symptom reports. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Verapamil protection against mercuric chloride-induced renal glomerular injury in rats

We have examined the effects of the calcium channel blocker verapamil on the renal glomerular structural damage produced by mercuric chloride in rats. Verapamil (75 micrograms/kg body wt iv) was administered 30 min prior to mercuric chloride injection (HgCl2, 5 mg/kg body wt sc). Verapamil prevented the glomerular proteinuria observed in HgCl2-treated rats. Isolated glomeruli from mercury-treated rats 1 h after injection presented a diminished cross-sectional area as compared with control glomeruli (control [micron2], 26,310 +/- 2545; HgCl2 [micron2], 18,474 +/- 1828) and increased glomerular calcium content (control, 23 +/- 6 nmol/mg protein; HgCl2, 43 +/- 7 nmol/mg protein). Verapamil pretreatment prevented glomerular cross-sectional area (GCSA) diminution and glomerular calcium content rise (GCSA [micron2] Vp + Hg, 28,281 +/- 4654, Ca2+ [nmol/mg protein] Vp + Hg, 18 +/- 5). Renal sections prepared for immunohistochemical detection and histochemical analysis showed increased deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl2-treated rats. Renal sections from animals pretreated with verapamil showed fibronectin and lipid contents not different from control sections and their histological studies did not show any changes when compared with control. Verapamil pretreatment also protected glomeruli from enhanced leukocyte content (myeloperoxidase activity/mg protein): control, 59 +/- 7; HgCl2, 134 +/- 10; Vp + Hg, 79 +/- 11). HgCl2 also contracts GCSA in vitro; Vp prevented this GCSA diminution. The results described in this study indicate that mercuric chloride nephrotoxicity may be associated not only with changes in renal glomerular haemodynamics, but also with a direct effect on glomerular cells.     

Baroreceptor effects on renal and adrenal nerve activity

Spontaneous efferent discharges were recorded from nerve filaments dissected from adrenal and renal nerve bundles in the rabbit. Raising of the systemic blood pressure or stimulation of the depressor nerve caused a decrease in discharge rate in these nerve filaments. Portal vein occlusion or elevation of mesenteric venous pressure caused a depression of activity in these nerves. It is suggested that adrenal and renal sympathetic nerve cells receive inputs from baroreceptors in the systemic arterial system and from mechanoreceptors in the portal and mesenteric veins that cause reflex inhibition of activity in these nerve cells.     

Assessing the statistical and social importance of the effects of psychotherapy.

Provides a general framework for putting into perspective a variety of meta-analytic procedures (MAPs); illustrates the MAPs within this framework so that they can be applied directly to one's own research or to reanalyses of others' research, or so that they can be understood in clearer perspective when employed by others; and describes a procedure for aiding in the evaluation of the social importance of the effects of psychotherapy or of other interventions. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contrasting renal effects of nicotine in smokers and non-smokers

BACKGROUND: Cigarette smoking is associated with acute increase in arterial pressure due to systemic vasoconstriction and decreased skin and coronary blood flow. Virtually all cardiovascular effects of cigarette smoking are due to nicotine. However, whether nicotine also affects the renal circulation and function in humans is at present unknown. METHODS: In the current study the acute effects of a 4-mg nicotine gum on arterial pressure, heart rate as well as renal haemodynamics and function were assessed in non-smokers and chronic smokers. RESULTS: In non-smokers, mean arterial pressure (+8 +/- 1 mmHg, P<0.001) and heart rate (+13 +/- 3 beats/min, P<0.001) increased whereas effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) decreased by 15 +/- 4% and 14 +/- 4% respectively; in addition, urinary cyclic GMP decreased by 51 +/- 12% in response to nicotine administration. In smokers, mean arterial pressure and heart rate increased similarly; however, in contrast with non-smokers, ERPF and GFR remained unchanged whereas urinary cyclic GMP rose by 87 +/- 43%. Changes in ERPF induced by nicotine were positively correlated with changes in urinary cyclic GMP. CONCLUSIONS: These findings indicate that nicotine administration is associated with renal vasoconstriction in healthy non-smokers, possibly through alteration of a cyclic-GMP-dependent vasoactive mechanism. Tolerance to the renal effect of nicotine was observed in chronic smokers, despite the maintenance of the systemic response to nicotine.     

Saphenous vein graft protection: effects of c-myc antisense

The nu1 and nu3 bands of D11BO and the nu1 band of D10BO were observed by using an infrared diode laser spectrometer. The DBO molecule was generated by an ac discharge in a mixture of BCl3, D2, O2, and He. As inferred previously, a strong Coriolis interaction was in fact found to take place between the nu1 and nu2 + nu3 states, and an analysis of the observed nu1 spectra, which explicitly took into account this Coriolis interaction, predicted the pure rotational transition frequencies of DBO in the nu1 state. Pure rotational lines were then detected by microwave spectroscopy, confirming the validity of the infrared assignment. In the microwave experiment DBO molecules were generated by a discharge in a mixture of B2D6 and O2. The three fundamental bands and a hot band of D11BO, as well as the nu1 and nu3 bands of D10BO, were subsequently recorded in emission with a Fourier transform infrared spectrometer. DBO molecules were generated by the reaction of D2 with HBO at temperatures above 800 degreesC in a ceramic tube furnace. All of the observed spectra were simultaneously subjected to a least-squares analysis to obtain molecular parameters in the ground, nu1, nu2, nu3, and nu2 + nu3 states. The results thus obtained improved the force field and molecular structure of the HBO/DBO molecules reported in a previous study (Y. Kawashima, Y. Endo, and E. Hirota, 1989, J. Mol. Spectrosc. 133, 116-127). Copyright 1998 Academic Press.     

模铸注流氩气保护技术的工艺研究

随着产品质量与性能的不断提升,模铸钢材质量控制也更为苛刻,其中浇铸环节是模铸工艺中的关键,而氩气保护是确保浇铸质量的前提。只有合格的氩气保护浇铸才能保证浇铸质量,进而才能不断地提升产品质量。主要介绍氩气保护浇铸用保护罩的发展情况以及40 t产线模铸浇铸过程中采用全封闭式氩气保护浇铸的生产工艺,研究影响保护罩内氧含量的相关因素,并通过在线测氧装置的氧含量监测结果,确定模铸氩气保护浇铸效果的最优条件,以便指导现场操作,减少钢液的二次氧化,提升钢锭质量。     

Long-term effects of antihypertensive agents on proteinuria and renal function

BACKGROUND: Although many studies have examined the effects of antihypertensive agents on proteinuria and glomerular filtration rate in patients with kidney disease, many questions remain unresolved. These questions include whether the effects of agents differ, whether their effects are similar in diabetic and nondiabetic patients with renal disease, and whether the effects of any agents are independent of blood pressure reductions. METHODS: We conducted a meta-analysis of studies obtained with MEDLINE and bibliographies from comprehensive reviews but included only investigations with follow-up times of at least 6 months. We combined data (1) in an analysis of randomized controlled trials, (2) in a separate univariate analysis of controlled and uncontrolled trials, and (3) using weighted multiple linear regression. RESULTS: In 14 randomized controlled trials, angiotensin-converting enzyme inhibitors caused a greater decrease in proteinuria (pooled mean [95% confidence intervals], -0.51[-0.68 to -0.35], ln [treatment/control]), improvement in glomerular filtration rate (0.13 mL/min per month [0.10 to 0.16 mL/min per month]), and decline in mean arterial pressure (-4.0 mm Hg [-4.9 to -3.0 mm Hg]) compared with controls. In a multivariate analysis of controlled and uncontrolled trials, each 10-mm Hg reduction in blood pressure decreased proteinuria (regression coefficient [95% confidence interval] -0.14 [-0.22 to -0.06] ln [after/before]), but angiotensin-converting enzyme inhibitors (-0.45 [-0.58 to -0.32]) and nondihydropyridine calcium antagonists (-0.38 [-0.70 to -0.06]) were associated with additional declines in proteinuria that were independent of blood pressure changes and diabetes. Each 10-mm Hg reduction in blood pressure caused a relative improvement in glomerular filtration rate (0.18 mL/min per month [0.04 to 0.31 mL/min per month]), but among diabetic patients there was a tendency for dihydropyridine calcium antagonists to cause a relative reduction in glomerular filtration rate (-0.68 mL/min per month [-1.31 to -0.04 mL/min per month]). CONCLUSIONS: Long-term beneficial effects of antihypertensive agents on proteinuria and glomerular filtration rate are proportional to blood pressure reductions and are similar in diabetic and nondiabetic patients with renal disease. In addition, angiotensin-converting enzyme inhibitors, and possibly nondihydropyridine calcium antagonists, have additional beneficial effects on proteinuria that are independent of blood pressure reductions.     

The renal effects of melatonin in intact and epiphysectomized rats

Epiphysectomy in adult pubescent Wistar rats causes polyuria and Na uresis at the expense of the increased rate of the glomerular filtration and sodium filtration charge. Melatonin in a dose of 4.31 mkM/100 g of the body weight increased the glomerular filtration of both sodium and water and stimulated the sodium tubular transport in rats with intact epiphysis and did not normalize changes of the nephron excretory activity after epiphysectomy.     

Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with antioxidants was investigated. Adult female Sprague-Dawley rats were injected sc with 5 micromol CdCl2/kg/day, 5 times a week, for up to 22 weeks. Serum alanine amino transferase and lactate dehydrogenase activities were elevated after 9 weeks of Cd administration, indicating hepatic damage. Renal toxicity, indicated by elevation in urinary lactate dehydrogenase activity and protein, was also observed around this time. Chronic Cd administration resulted in a gradual rise in hepatic as well as renal cortex glutathione levels. In spite of this, lipid peroxidation increased in both tissues, particularly during the second half of the Cd exposure period. Depletion of glutathione following buthionine sulfoximine administration at the end of Week 5, or inhibition of catalase by aminotriazole at the end of Week 7, resulted in the development of acute nephrotoxicity within 6 h. Coadministration of antioxidants, N-acetylcysteine (50-100 mg/kg, sc), or vitamin E (100-150 mg/kg, sc) with Cd, starting from the early phases of Cd exposure, controlled Cd-induced lipid peroxidation and protected the animals against hepatic as well as renal toxicity. A Japanese hepatoprotective drug, Stronger Neo-Minophagen C, containing glycyrrhizin, glycine, and cysteine, was also effective in reducing the chronic Cd nephrotoxicity. In conclusion, oxidative stress appears to play a major role in chronic Cd-induced hepatic and renal toxicity since inhibition of components of the antioxidant defense system accelerated and administration of antioxidants protected against Cd toxicity.     

Self-worth protection in achievement motivation: Performance effects and attributional behavior.

Two experiments tested central assumptions of the self-worth theory of achievement motivation. This theory states that certain students, known as self-work protective students, will voluntarily withdraw effort in achievement situations in which poor performance is likely to be attributed to low ability. Thereby, a sense of self-worth is protected. Self-worth theory also states that these students will perform well in situations in which a mitigating excuse allows poor performance to be attributed to a factor that is unrelated to ability. Experiment 1 confirmed that self-worth protective students perform well following failure that allows a face-saving opportunity but perform poorly following failure that does not allow face-saving. The results of Experiment 2 confirmed that the poor performance of self-worth protective students following failure is associated with a lesser tendency to assume personal responsibility for failure. These findings are discussed in terms of strategies for modifying the achievement-limiting behaviors of self-worth protective students. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Haemodynamic and renal effects of felodipine in young and elderly subjects

OBJECTIVE: To study the influence of age on renal and haemodynamic effects of the calcium antagonist felodipine. METHODS: Eight young (mean age 27 years) and eight elderly (mean age 75 years) healthy normotensive subjects were given felodipine intravenously for 120 min aiming at close to therapeutic plasma level concentration. Renal blood flow (RBF) and renal vascular resistance (RVR) was estimated from para-aminohippuric acid (PAH) clearance 51CrEDTA clearance was used to measure glomerular filtration rate (GFR) and used in the calculations of fractional excretion (FE) of electrolytes. Impedance cardiography was performed to assess stroke volume and for the calculation of cardiac output and ejection fraction. RESULTS: At the end of felodipine infusion, the concentration of felodipine was on average 10.0 nmol x l(-1) in young and 12.0 nmol x l(-1) in elderly subjects (NS). During felodipine infusion blood pressure (BP) decreased from 138/76 to 120/68 in elderly subjects. The BP in young subjects was 126/74 at basal and 125/70 after infusion of felodipine. The systemic and renal vascular resistance decreased to a similar extent in young and elderly subjects after felodipine infusion. Felodipine caused a decrease in systemic vascular resistance from 25.6 to 23.3 in elderly and from 23.8 to 21.8 in the young subjects. Mean values for RVR at baseline and during infusion of felodipine were significantly higher in the elderly (10.1-15.1) than in the young subjects (5.4-6.7). Felodipine reduced RVR by 10% in the young and by 12% in the elderly at the end of infusion. The young subjects had 31% higher GFR than the elderly subjects at the start of infusion. Felodipine infusion did not affect GFR. There were no effects on stroke volume and ejection fraction. An initial natriuretic effect was found after infusion of felodipine in the young subjects. The fractional excretion of all electrolytes tended to increase after both felodipine and placebo, more in the elderly than in the young subjects. CONCLUSION: The effects of felodipine on central and renal haemodynamics previously observed in young and middle-aged subjects also seem to exist in the elderly. Volume expansion seems to increase the excretion of electrolytes more in elderly than in young people, and therefore the effect of felodipine on natriuresis is more evident in young subjects.