Ascorbate affects proliferation of guinea-pig vascular smooth muscle cells by direct and extracellular matrix-mediated effects

Proliferation of smooth muscle cells and deposition of extracellular matrix proteins are important events in the formation of atherosclerotic plaques. We have investigated the direct and matrix-mediated effects of ascorbate on the proliferation rate of vascular smooth muscle cells (VSMC) isolated from the guinea-pig aorta. In the presence of ascorbate, cells showed a bi-phasic growth pattern. At 125 microM ascorbate, -3H--thymidine incorporation was stimulated 25%. However, higher concentrations of ascorbate gradually decreased cell-incorporated radioactivity up to 50% at 2 mM ascorbate. These effects of ascorbate on DNA synthesis in VSMC were paralleled by the changes in cell number and were not due to ascorbate cytotoxicity. Alpha-tocopherol (0.1 mM), individually and in combinations with 1 mm ascorbate, also inhibited DNA synthesis in VSMC. Ascorbate also influenced proliferation of smooth muscle cells through matrix-mediated effect. New VSMC culture plated on extracellular matrices deposited by smooth muscle cells in the presence of 0.1-1 mM ascorbate had up to 50% lower proliferation rate than on matrices from ascorbate-deficient cells, as assessed by [3H]-thymidine incorporation. This effect was independent from alpha-tocopherol and specific inhibitors of collagen synthesis: L-azetidine-2-carboxylic acid and pyridine-2,4-dicarboxylic acid. An ascorbate-dependent matrix effect was specific for smooth muscle cells grown on VSMC and human skin fibroblast-originated matrices, but not for human vascular endothelial cells. The possible involvement of ascorbate in the regulation of smooth muscle cells proliferation by its antioxidant/pro-oxidant effects and regulation of extracellular matrix composition are discussed.     

Reduction and direct alloying of calcium vanadate

Based on the reduction law of calcium vanadate, which was explored in the laboratory, the experiments were carried out during direct alloying with calcium vanadate in a high-frequency induction furnace with a capacity of 25 kg. The average recovery ratio of vanadium was 83.4 %. The tests were also carried out for direct alloying with a briquette of calcium vanadate in a 0.51 electric arc furnace and with cold-bound pellets of calcium vanadate in a ladle to smelt the low alloy steel with mass contents of about 0.1 % vanadium. The recovery ratios of vanadium were 89.9 % and 86.0 %, respectively.     

Long-term therapeutic effects of ace inhibitor and calcium antagonists on hypertensive vascular lesions in M-SHRSP

1. Our results indicate that the drugs used in this study are very effective in malignant hypertension therapy. 2. For M-SHRSP treated with highly effective antihypertensive drugs, if blood pressure remains under 200 mmHg over the long-term, the structures of the small arteries and/or arterioles stay as well preserved as they do in WKY. 3. For M-SHRSP treated with drugs with a lower antihypertensive effect, the occurrence of cerebrovascular lesions and angionecrosis in the various organs are suppressed significantly, even though blood pressure remains over 250 mmHg over the long-term. Based upon effect alone, there is no difference between ACEI and a calcium antagonist. However, inhibition of the proliferation of vascular smooth muscle cells is more potent in the former than in the latter. 4. These results suggest that ACEI might have the potential to suppress smooth muscle cell proliferation independent of high blood pressure.     

Peripheral nerve vascular changes in spontaneously hypertensive rats

Circulation to the brain is affected by hypertension. Hypertension-dependent cerebrovascular changes were documented primarily in brain pial arteries, whereas no information is so far available concerning changes of peripheral nerve vascularization in hypertension. This study was designed to assess the occurrence of structural changes of interfascicular and intrafascicular arteries supplying peripheral nerves (the so called vasa nervorum) in spontaneously hypertensive rats (SHR). The investigation was performed in 8-month-old SHR, by using standard microanatomical techniques associated with quantitative image analysis. In SHR a significant increase of systolic pressure values accompanied by thickening of the arterial wall, narrowing of the lumen and increase of the wall-to-lumen ratio were observed in comparison with age-matched normotensive Wistar-Kyoto rats. Hypertension-related structural changes involved primarily interfascicular arteries and to a lesser extent intrafascicular arteries. These findings indicate that similarly as documented for cerebral arteries, the vascular supply to peripheral nerves is impaired in hypertension. Structural changes of interfascicular and intrafascicular arteries of SHR could lead to ischemia of peripheral nerves. Further work is in progress to evaluate the functional relevance of hypertensive changes to peripheral nerve vasculature.     

Adverse effects of calcium binding contrast agents in diagnostic cardiac angiography. A comparison between formulations with and without calcium binding additives

RATIONALE AND OBJECTIVES: The authors compared complications and hemodynamic and electrophysiologic effects of two formulations of diatrizoate, one with additives that bind calcium and one without, in diagnostic cardiac angiography. METHODS: Two hundred twenty-three consecutive low-risk patients alternately received Hypaque 76 (group 1, little calcium binding effect), and MD 76 (group 2, significant calcium binding). Electrocardiographic and hemodynamic changes related to coronary angiography and left ventriculography were measured, and complications requiring treatment were recorded. RESULTS: There were more complications in patients in group 2 than in group 1 (18 versus 8, P = 0.04). Arterial pressure fell more, the QT interval increased more, and the heart rate fell more in group 2 after coronary angiography. CONCLUSIONS: Formulations of diatrizoate that minimize calcium binding are advocated for cardiac angiography when using high osmolality contrast media. The more detrimental effects that calcium binding has on myocardial function and cardiac conduction may lead to the higher incidence of complications.     

Peripheral vascular disease evaluated with reduced-dose gadolinium-enhanced MR angiography

OBJECTIVE: To examine the effect of oxygen on apneas and sleep quality in patients with frequent central apneas during sleep. DESIGN/SUBJECTS: Prospective intervention study of 20 consecutive patients with predominant central apnea identified from 570 patients referred for suspected sleep apnea syndrome. Sixteen patients had congestive heart failure and seven of them had a previous stroke. Three of the remaining four patients without heart failure had experienced a previous stroke, and one was being treated with morphine. SETTING: The Department of Pulmonary Medicine at Ume? (Sweden) University Hospital. INTERVENTIONS: The patients were investigated for one night receiving nasal oxygen and one night without it. MEASUREMENTS: Overnight polysomnography with transcutaneous PCO2 and arterial blood gases. RESULTS: Central apneas occurred during Cheyne-Stokes respiration in 18 of 20 patients and two patients had idiopathic central apneas. Without oxygen, the median number of all central apneas and hypopneas was 33.5 (range, 8.0 to 52.0) per hour of sleep. These episodes decreased to 5.0 (range, 0.0 to 31.0)(p < 0.01) during oxygen therapy. In 17 of 20 patients, the frequency of central apneas was reduced by more than 50%. Central apneas were reduced by oxygen irrespective of the presence or absence of heart failure or Cheyne-Stokes respiration. The arousal frequency was reduced during oxygen treatment. Daytime sleepiness, difficulty falling asleep, snoring, and self-scored awakenings were reduced in seven patients who were given nocturnal oxygen at home. Obstructive and mixed apneas were unaffected by oxygen. CONCLUSIONS: Oxygen effectively reduces central sleep apnea in eucapnic patients.     

Expression of calcium channels in adult cardiac myocytes is regulated by calcium

In addition to playing a significant role in cardiac excitation-contraction coupling, intracellular Ca2+ ([Ca2+]i) can regulate gene expression. While the mechanisms regulating expression of Ca2+ channels are not entirely defined, some evidence exists for Ca2+-dependent regulation. Using an adult ventricular myocyte culture system, we determined the effects of Ca2+ on: (1) abundance of mRNA for L-type Ca2+ channel alpha1 subunit (DHP receptor); (2) amount of DHP receptors; and (3) whole-cell Ca2+ current (ICa). Rat ventricular myocytes were cultured for 1-3 days in serum-free medium containing either normal (1.8 mM) or high (4.8 mM) Ca2+. Exposing myocytes to high Ca2+ rapidly elevated [Ca2+]i as determined by fura-2. Northern blot analysis revealed that culturing cells in high Ca2+ produced 1.5-fold increase in mRNA levels for the DHP receptor. The abundance of DHP receptors, determined by ligand binding, was two-fold greater in myocytes after 3 days in high Ca2+. Moreover, peak ICa was larger in myocytes cultured for 3 days in high Ca2+ (-17.8+/-1.5 pA/pF, n=26) than in control cells (-11.0+/-1.0 pA/pF, n=23). Voltage-dependent activation and inactivation, rates of current decay, as well as percent increases in ICa elicited by Bay K8644 were similar in all groups. Therefore, larger ICa is likely to represent a greater number of functional channels with unchanged kinetics. Our data support the conclusion that transient changes in [Ca2+]i can modulate DHP receptor mRNA and protein abundance, producing a corresponding change in functional Ca2+ channels in adult ventricular myocytes.     

Comparison of calcium phosphate cement mixture and pure calcium hydroxide as direct pulp-capping agents

This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins.     

Phospholamban-dependent effects of C12E8 on calcium transport and molecular dynamics in cardiac sarcoplasmic reticulum

We have studied the effects of the nonionic detergent C12E8 on Ca-ATPase enzymatic activity and oligomeric state (detected by time-resolved phosphorescence anisotropy, TPA) in skeletal and cardiac sarcoplasmic reticulum (SR). In skeletal, SR, C12E8 inhibits the CA-ATPase, both at high (micromolar and above) and low (submicromolar) Ca. In cardiac SR, C12E8 inhibits at high Ca but activates at low Ca. Thus C12E8 activates enzymatic activity only in cardiac SR and only under conditions (submicromolar Ca) where phospholamban (PLB) regulates (inhibits) the enzyme [Lu, Y.-Z., & Kirchberger, M.A. (1994) Biochemistry 33, 5056-5062]. TPA of skeletal SR at low and high Ca demonstrates that C12E8 induces aggregation of ATPase monomers and small oligomers. C12E8 also aggregates the Ca-ATPase in cardiac SR at high Ca. In cardiac SR at low Ca, the Ca-ATPase is already highly aggregated, and C12E8 partially dissociates these aggregates. Thus the TPA results provide a simple physical explanation for the functional effects: C12E8 inhibits the ATPase when it aggregates the enzyme (skeletal SR at high and low Ca; cardiac SR at high Ca), and the detergent activates when it dissociates ATPase oligomers (cardiac SR at low Ca). C12E8 stabilizes the E2P conformation of the Ca-ATPase with respect to the E2 conformation, and this stabilization is PLB-dependent. Both the physical and functional effects of C12E8 on the Ca-ATPase are PLB-dependent, with C12E8 reversing the effects of PLB. The results provide insight into the mechanism by which PLB regulates the Ca-ATPase in cardiac SR.     

Steady-state calcium fluxes: membrane versus mitochondrial control of ionized calcium in axoplasm

Squid axons appear in a steady state with respect to ionized Ca when [Ca]o is ca. 3 mM and [Ca]i is ca. 30 nM. A membrane pump energized by the Na gradient across the membrane is capable of maintaining this ratio of ionized Ca if four Na enter per Ca extruded. Empirically, it is noted that if the difference between the electrochemical gradient for Na+ and that for Ca2+ is large and positive, Ca efflux is large; for a large but negative difference in the gradient, Ca influx is large. Net fluxes of Ca into the fiber are induced by Na-free solutions or stimulation. These are buffered in axoplasm principally by a high affinity Ca buffer. Mitochondria apparently do not contain large amounts of stored Ca as CN poisoning does not increase ionized Ca in axoplasm if the seawater is Ca-free.     

Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers

Members of the new class of antimigraine compounds, 5HT1B/1D agonists, as well as ergotamine, may cause vasoconstriction through stimulation of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig, formerly 311C90), 2 mg oral ergotamine and the combination were assessed in a randomized double-blind, placebo-controlled crossover study in 12 healthy subjects. Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degrees of peripheral vasoconstriction, including increases in diastolic blood pressure and blood flow velocity and decreases in arterial diameter and toe-arm systolic pressure gradient. These effects were generally additive with the combination but of no clinical importance. There were no significant changes in cardiac output, stroke volume heart rate or ECG. Zolmitriptan, at eight times the likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamine. Ergotamine had no clinically important effects on zolmitriptan pharmacokinetics.     

Self-esteem and direct versus indirect forms of self-enhancement.

Two studies explored the relation between self-esteem and self-enhancement biases. It was proposed that people with high self-esteem engage in forms of self-enhancement in which the self is directly linked to positive identities and outcomes, whereas people with low self-esteem engage in forms of self-enhancement in which the self is indirectly linked to positive identities and outcomes. To test the hypothesis, we examined group favoritism as a function of self-esteem and group involvement. As expected, high self-esteem subjects were most apt to display favoritism when they were directly involved in group processes, whereas low self-esteem subjects were most apt to display favoritism when they were not directly involved in group processes. Furthermore, consistent with the view that these tendencies reflect a motivated desire to enhance self-worth, these effects were less evident after subjects had received positive feedback than after they had received negative feedback. The discussion centers on the nature of high and low self-esteem and the influence of self-enhancement and self-consistency motives in social behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Home- versus clinic-based treatment of vascular headache.

Contrasted the efficacy of a traditional clinic-based relaxation training and thermal biofeedback treatment to a comparable home-based program with minimal therapist contact in the treatment of 40 vascular-headache sufferers (mean age 37 yrs). The home-based condition was at least as efficacious as the clinic-based treatment in terms of reduction of headache intensity and frequency and medication usage, and was clearly more cost-effective. Findings suggest that a minimal-therapist-contact condition may be a viable, low-cost alternative to more expensive clinic-based programs in the treatment of vascular headache. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spasm in cardiac and vascular pathology. Conclusion

The values of blood rheological and coagulation properties were studied in stages of operative treatment in 30 patients operated on for grade III-IV mitral stenosis. Complex statistical models of the inter-relationship of the blood coagulation and rheological properties were complied which allow for the substantiation of the optimum transfusion tactics in preventing complications in the operative and postoperative periods.     

Activation of calcium sparks by angiotensin II in vascular myocytes

Contraction in smooth muscle is triggered by an increase in cytoplasmic free calcium ([Ca2+]i) which depends on both Ca2+ influx through L-type Ca2+ channels and Ca2+ release from the sarcoplasmic reticulum (SR). Two mechanisms have been shown to be involved in SR Ca2+ release, one is stimulated by Ca2+ and involved ryanodine-sensitive Ca2+-release channels; the other is stimulated by an increase in inositol 1,4,5-trisphosphate (InsP3) generation induced by various mediators and involved InsP3-sensitive Ca2+ release channels. Here, we examined the effects of angiotensin II on [Ca2+]i in single rat portal vein myocytes using both the whole cell patch-clamp method and a laser scanning confocal microscope. Elementary Ca2+ release events (Ca2+ sparks) were obtained spontaneously or in response to L-type Ca2+ channel current activation, and resulted from activation of ryanodine-sensitive Ca2+-release channels in the SR. We show that angiotensin AT1 receptors stimulate Ca2+ sparks through activation of L-type Ca2+ channels without involving InsP3-induced Ca2+ release. This novel transduction pathway may be a common mechanism for vasoconstrictors which do not stimulate generation of chemical second messengers.     

Peripheral nerve regeneration: the effects of postoperative irradiation

Our purpose is to review recent data and provide a clinical opinion on the use of antibiotics to prevent preterm birth or related maternal-neonatal complications. A literature review and a synthesis of opinion are provided. During prenatal care, standard practices should be applied regarding Neisseria gonorrhoeae, Chlamydia trachomatis, and bacteriuria. In addition, screen for and treat bacterial vaginosis in patients at high risk for preterm birth but do not treat Ureaplasma urealyticum or group B streptococci genital colonization. With preterm labor and intact membranes, standard practices should be applied regarding group B streptococci prophylaxis. Do not give antibiotics routinely to prolong pregnancy, but in patients with bacterial vaginosis and Trichomonas vaginalis specific treatment should be given. With preterm premature rupture of membranes, standard practices should be applied regarding group B streptococci prophylaxis, but additional antibiotics should also be given to prolong pregnancies at 24 to 32 weeks' gestation. Reported adverse effects have been few to date. However, increased diligence is needed for resistant organisms. In selected clinical settings antibiotic therapy is now indicated to prolong pregnancy and prevent maternal-neonatal complications associated with preterm birth.     

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants

The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)