Myocardial torsion and cardiac fulcrum.

OBJECTIVE: The development of the myocardial band shows that it starts and ends at the origin of the great vessels and that the myocardium joins to these rings but does not inserted into them. We always considered that there should be a fixed end of the muscle band that would allow it a helical rotation to fulfill its fundamental movements of shortening-torsion (systole) and elongation-distortion (suction). MATERIAL AND METHODS: Seven young-bovine hearts (800-1000g) and seven human hearts (one embryo, 4g; one 10 years, 250g and five adult, 300g/average) were used for a detailed macrocoscopic and microscopic study. RESULTS: We have found in all the bovine and human hearts studied a nucleus underlying the right trigone, whose osseus, chondroid or tendinous histological structure depends on the specimen analyzed. The microscopic analysis revealed in the hearts a trabecular osteochondral matrix (fulcrum) with segmental lines in bovines and in the ten-year-old human. In the fetus, it was found pre-chondroid areas in a myxoid stroma. In the adult human hearts, the histological analysis revealed a matrix similar to that of a tendon. All the hearts studied presented myocardial attachment to the rigid structure of the fulcrum. Myocardiocytes were not found neither at the left or rigth trigonous nor at the base of the valves. CONCLUSIONS: The finding of the fulcrum gives support to the spiral myocardial band being the point of fixation that allows the helicoidal torsion.

Renormalizable two-parameter piecewise isometries.

We exhibit two distinct renormalization scenarios for two-parameter piecewise isometries, based on 2π/5 rotations of a rhombus and parameter-dependent translations. Both scenarios rely on the recently established renormalizability of a one-parameter triangle map, which takes place if and only if the parameter belongs to the algebraic number field K=Q(5) associated with the rotation matrix. With two parameters, features emerge which have no counterpart in the single-parameter model. In the first scenario, we show that renormalizability is no longer rigid: whereas one of the two parameters is restricted to K, the second parameter can vary continuously over a real interval without destroying self-similarity. The mechanism involves neighbouring atoms which recombine after traversing distinct return paths. We show that this phenomenon also occurs in the simpler context of Rauzy-Veech renormalization of interval exchange transformations, here regarded as parametric piecewise isometries on a real interval. We explore this analogy in some detail. In the second scenario, which involves two-parameter deformations of a three-parameter rhombus map, we exhibit a weak form of rigidity. The phase space splits into several (non-convex) invariant components, on each of which the renormalization still has a free parameter. However, the foliations of the different components are transversal in parameter space; as a result, simultaneous self-similarity of the component maps requires that both of the original parameters belong to the field K.

Near-critical behavior of the Zhong-Zhang model.

The Zhong-Zhang (ZZ) model is a one-degree-of-freedom dynamical system describing the motion of an insulating plate of length d floating on the upper surface of a convecting fluid, with locking at the boundaries. In the absence of noise, the system away from the boundaries is described by linear differential equations with a delay time τ. The d,τ plane consists of two domains separated by a critical curve. For asymptotically long times, subcritical orbits approach a nontrivial periodic attractor, while the supercritical ones tend to a stationary state at the origin. We investigate near-critical behavior using a modified fourth-order Runge-Kutta integration scheme. We then construct a piecewise analytic decomposition of the periodic attractor, which makes possible a far higher level of accuracy. Our results provide solid evidence for an asymptotic power-law approach to criticality of several observables. The power laws are fed back to determine the piecewise-analytic structure deep into the near-critical regime. In an Appendix, we explore the effect of introducing noise using modified order-3/2 Kloeden-Platen-Schurz stochastic integration, following several observable quantities through the near-critical parameter domain.

Flights in a pseudo-chaotic system.

We consider the problem of transport in a one-parameter family of piecewise rotations of the torus, for rotation number approaching 1∕4. This is a zero-entropy system which in this limit exhibits a divided phase space, with island chains immersed in a "pseudo-chaotic" region. We identify a novel mechanism for long-range transport, namely the adiabatic destruction of accelerator-mode islands. This process originates from the approximate translational invariance of the phase space and leads to long flights of linear motion, for a significant measure of initial conditions. We show that the asymptotic probability distribution of the flight lengths is determined by the geometric properties of a partition of the accelerator-mode island associated with the flight. We establish the existence of flights travelling distances of order O(1) in phase space. We provide evidence for the existence of a scattering process that connects flights travelling in opposite directions.

Ammonia production in muscle: the purine nucleotide cycle.

Experiments are reported which throw new light on the problem of ammonia production by muscle and, probably, by other tissues.

Mammoth albumin.

Serum albumin was detected immunologically in muscle from a mammoth that died about 40,000 years ago. Rabbits injected with ground mammoth muscle produced antibodies that react strongly with elephant albumin, weakly with sea cow albumin, and still more weakly or not at all with other mammalian albumins. Since elephant albumin elicited antibodies with the same specificity, some of the surviving mammoth albumin molecules evidently have antigenic sites identical to those on native elephant albumin. Much of the mammoth albumin has, however, undergone postmortem change. The small amount of soluble albumin extractable from mammoth muscle is heterogeneous in size, charge, and antigenic properties.

Metabolic control of the circulation. Effects of acetate and pyruvate.

Chloralose-anesthetized dogs were infused intravenously with either Tris-acetate or Tris-pyruvate at 0.0375, 0.075, and 0.15 mmol/kg per min successively, each for 20 min. Acetate infusion increased cardiac output, left ventricular dP/dt and dP/dt/P, and coronary blood flow, while pyruvate infusion did not. Infusions of either substance increased arterial blood and skeletal muscle concentrations of citrate and malate, but only acetate infusion increased the tissue AMP content and decreased the ATP:AMP ratio. The increase in cardiac output produced by acetate was accompanied by an increase in total body oxygen consumption and a decrease in the difference between arterial and mixed venous blood oxygen. Myocardial oxygen consumption increased during acetate infusion, but the decrease in myocardial oxygen extraction and the increase in coronary sinus blood oxygen saturation suggest that an active coronary vasodilation which was not a result of the increased cardiac work, occurred. The concentration of hypoxanthine in the coronary sinus and the content of myocardial adenosine increased, which suggests that the increase in coronary blood flow was caused by the vasodilator action of adenosine released from the myocardium, and that adenosine production is not necessarily tied to PO(2). These systemic and coronary hemodynamic changes also occurred when acetate (0.075 mmol/kg per min) was infused into conscious dogs. Acetate infusion also increased blood flow to the gastrointestinal tract, kidneys, intercostal muscle, and diaphragm. These changes were not affected by propranolol pretreatment, but were abolished by pretreatment with fluoroacetate which reduced acetate oxidation. These results suggest that the circulatory stimulation produced by acetate was not caused by increases in tricarboxylic acid cycle intermediates. Instead, it was probably related to the increased cleavage of ATP to AMP that accompanies activation of acetate to acetyl CoA, and was not mediated via beta-adrenergic receptors. It is speculated that hemodynamic changes may occur in patients who undergo hemodialysis with acetate-containing dialysate. Hemodynamic changes of ethanol may also be brought about by acetate, which is one of the intermediates that accumulates during ethanol metabolism.

The purine nucleotide cycle. A pathway for ammonia production in the rat kidney.

Particle-free extracts prepared from kidney cortex of rat catalyze the formation of ammonia via the purine nucleotide cycle. The cycle generates ammonia and fumarate from aspartate, using catalytic amounts of inosine monophosphate, adenylosuccinate, and adenosine monophosphate. The specific activities of the enzymes of the cycle are 1.27+/-0.27 nmol/mg protein per min (SE) for adenoylosuccinate synthetase, 1.38+/-0.16 for adenylosuccinase, and 44.0+/-3.3 for AMP deaminase. Compared with controls, extracts prepared from kidneys of rats fed ammonium chloride for 2 days show a 60% increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity, and a greater and more rapid synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate. Extracts prepared from kidneys of rats fed a potassium-deficient diet show a twofold increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity. In such extracts the rate of synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate is also increased. These results show that the reactions of the purine nucleotide cycle are present and can operate in extracts of kidney cortex. The operational capacity of the cycle is accelerated by ammonium chloride feeding and potassium depletion, conditions known to increase renal ammonia excretion. Extracts of kidney cortex convert inosine monophosphate to uric acid. This is prevented by addition of allopurinol of 1-pyrophosphoryl ribose 5-phosphate to the reaction mixture.

Effect of omega 3 and omega 6 fatty acids on transformation of cultured cells by irradiation and transfection.

Mouse embryo fibroblasts (C3H 10T1/2) were exposed to 4 Gy of gamma-rays. The cells yielded 5-8 transformed foci per 10(4) surviving cells. Addition of 100 microM of either eicosapentaenoate or docosahexaenoate to the tissue culture medium reduced the number of transformed foci to 0-1.4. C3H 10T1/2 and NIH 3T3 cells were transfected with plasmid T24 containing the Harvey ras oncogene. C3H 10T1/2 cells yielded 0.85-1.1 foci/ng DNA, while NIH 3T3 cells yielded 0.12-0.14 foci/ng DNA. Foci formation was suppressed 65% in C3H 10T1/2 cells and 93% in NIH 3T3 cells when 100 microM eicosapentaenoate was present in the culture medium. Docosahexaenoate had a similar but somewhat weaker effect. Addition of arachidonate to the medium had little or no effect. Cells grown in the presence of added eicosapentaenoate or docosahexaenoate produced much less prostaglandin E when challenged with calcium ionophore A23187. This is a reflection of changes in arachidonate production or utilization that occur during transformation which are suppressed by the added omega 3 fatty acids. Addition of eicosapentaenoate or docosahexaenoate to the culture medium resulted in extensive remodeling of the molecular species of the four major phospholipid classes that were examined. In its simplest form, omega 3-fatty acid-containing species substantially replaced omega 6-fatty acid-containing species. However, many more subtle changes occurred, and the different phospholipids responded differently to different polyunsaturated fatty acids. A feature of C3H 10T1/2 cells was their preferential accumulation of molecular species of 22-carbon fatty acids such as docosapentaenoate (22:5 omega 3) and docosatetraenoate (22:4 omega 6) in preference to eicosapentaenoate (20:5 omega 3) and eicosapentaenoate (arachidonate, 20:4 omega 6). It is proposed that the protective effect of eicosapentaenoate and docosahexaenoate arises out of the changes in the composition of the fatty acids that are released from one or more phospholipids by the action of phospholipases. The changes consist of a reduced release of arachidonate, the normal substrate of cyclooxygenase and lipoxygenases, and a greatly increased release of eicosapentaenoate and docosahexaenoate, which inhibit one or more of these enzymes, or form oxygenated products which are not as active as the arachidonate-derived products. Other mechanisms are also considered.

Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND: Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS: Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS: The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS: In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia.

Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction. Echo Dobutamine International Cooperative (EDIC) Study.

OBJECTIVES: The aim of this multicenter, multinational, prospective, observational study was to assess the relative value of myocardial viability and induced ischemia early after uncomplicated myocardial infarction. BACKGROUND: Dobutamine-atropine stress echocardiography allows evaluation of rest function (at baseline), myocardial viability (at low dose) and residual ischemia (peak dose, up to 40 micrograms with atropine up to 1 mg) in one test. METHODS: Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/- SD) after a first uncomplicated acute myocardial infarction in 778 patients (677 men; mean age 58 +/- 10 years) with technically satisfactory rest echocardiographic study results. Patients were followed-up for 9 +/- 7 months. RESULTS: Dobutamine-atropine stress echocardiographic findings were positive for myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24 (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for unstable angina. One hundred seventy-four patients (22%) underwent coronary revascularization (bypass surgery or coronary angioplasty). Spontaneous events occurred in 61 of 436 patients with positive and 40 of 342 patients with negative findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3). When only spontaneously occurring events were considered, the most important predictor was myocardial viability (chi-square 9.7). Using the Cox proportional hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0, p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously occurring events. When only hard cardiac events were considered, age was the strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi-square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was the best predictor (HR 9.2, p < 0.0001). CONCLUSIONS: During dobutamine stress, echocardiographic recognition of myocardial viability is more prognostically important than echocardiographic recognition of myocardial ischemia for predicting unstable angina, whereas WMSI at peak stress was the best predictor of cardiac-related death. Different events can be recognized with different efficiency by various stress echocardiographic variables.

The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND: In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS: Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS: No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS: Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Molecular preservation in Late Cretaceous sauropod dinosaur eggshells.

Exceptionally preserved sauropod eggshells discovered in Upper Cretaceous (Campanian) deposits in Patagonia, Argentina, contain skeletal remains and soft tissues of embryonic Titanosaurid dinosaurs. To preserve these labile embryonic remains, the rate of mineral precipitation must have superseded post-mortem degradative processes, resulting in virtually instantaneous mineralization of soft tissues. If so, mineralization may also have been rapid enough to retain fragments of original biomolecules in these specimens. To investigate preservation of biomolecular compounds in these well-preserved sauropod dinosaur eggshells, we applied multiple analytical techniques. Results demonstrate organic compounds and antigenic structures similar to those found in extant eggshells.

Rebound hypertension after sodium nitroprusside-induced hypotension.

Patients undergoing surgical procedures using sodium nitroprusside-induced hypotension were studied to determine the role of the renin-angiotensin system in the pathogenesis of rebound hypertension (RH) after discontinuing sodium nitroprusside (SNP) infusion. Retrospective observations documented RH in 9 of 12 patients (group I) with a systolic blood pressure (SBP) increase from 112 +/- 3.92 before SNP to 144 +/- 5.60 torr 10 min after SNP (p less than 0.001). In 12 patients (group II), plasma renin activity (PRA) rose from 950 +/- 432 to 3,611 +/- 1.874 pg/ml/hr (p less than 0.0005) during SNP and remained elevated (2,504 +/- 792 pg/ml/hr) 30 min after cessation of SNP. SBP rose from a control (pre-SNP) value of 112 +/- 5.24 to 129 +/- 8.52 torr after discontinuation of SNP (p less than 0.05). Significant PRA and SBP changes did not occur in a matched group of patients (group III) who did not receive SNP. That RH after cessation of SNP infusion was associated with persistent elevation of PRA leads us to suggest that RH may be attributable to the unopposed effects of the renin-angiotensin system after the rapid plasma disappearance of SNP.

A multifunctional vector system for heterologous expression of proteins in Escherichia coli. Expression of native and hexahistidyl fusion proteins, rapid purification of the fusion proteins, and removal of fusion peptide by Kex2 protease.

Vectors have been constructed for the general purpose of expressing foreign proteins in E. coli. These vectors allow the production in high yield of either native proteins or of fusion proteins which contain, at their amino terminus, the peptide Met Gly His6 Ser Gly Leu Phe Lys Arg/, where Leu Phe Lys Arg/ is the recognition site for Kex2 protease which cleaves at the site indicated by /. The His6 sequence is used as a ligand for the one-step affinity purification of the expressed proteins on columns containing Ni or Zn ions chelated to iminodiacetic acid-agarose. After affinity chromatography, the purification peptide is cleaved off with Kex2 protease from Saccharomyces cerevisiae. The vectors also allow site-directed mutagenesis and sequencing of the cloned gene to be expressed without any intermediate subcloning. For practical examples of over-expression, affinity purification, and removal of the purification peptide, we chose a high-molecular-weight protein, phospholipase C gamma 1 (PLC gamma 1, M(r) 148,000) and a low-molecular-weight protein, Hit-1 (M(r) 16,000). Both were obtained pure and in high yield. PLC gamma 1 was fully active; the function of Hit-1 is not known. A set of companion vectors for co-expression of additional proteins has also been developed. These allow expression of proteins which enhance the production or activity of the protein of primary interest and of proteins which exhibit trans-interactions.

Gross cystic disease fluid protein in nipple aspirates of breast fluid of Asian and non-Asian women.

Gross cystic disease fluid protein 15 (GCDFP-15) is universally present in the apocrine metaplastic epithelium of cystic breast disease and breast cancer, but it is rarely found in normal breast epithelium. Therefore GCDFP-15 detected in nipple aspirates of breast fluid (NAF) could serve as a biochemical marker of the presence and possibly extent of apocrine metaplasia within the breast. GCDFP-15 levels were measured in NAF from 37 Asian and 78 non-Asian women using radioimmunoassay. GCDFP-15 (range, 0-81,643 micrograms/ml) was found in the NAF of all but 1 woman and was highly correlated between right and left breasts. Mean concentrations of GCDFP-15 were significantly lower in NAF from Asian compared with non-Asian women. Markedly reduced levels of GCDFP-15 were found in the 17 women who had been parous in the previous 2 years. In women not parous within the prior 2 years, no relationship was found between GCDFP-15 levels and age, weight, age at menarche, first-degree family history of breast cancer, parity, oral contraceptive use, or smoking history. High concentrations of GCDFP-15 were found in the NAF of women with a history of a benign breast biopsy. Because similarly high levels of GCDFP-15 were found in NAF in over 40% of women without a history of benign breast biopsy, and because GCDFP-15 in the breast is produced only by apocrine metaplastic epithelium, we infer that the breasts of these women likely contain a significant degree of apocrine metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women.

Soy foods have been reported to have protective effects against premenopausal breast cancer in Asian women. No studies have been reported on potential physiological effects of dietary soy consumption on breast gland function. We evaluated the influence of the long-term ingestion of a commercial soy protein isolate on breast secretory activity. We hypothesized that the features of nipple aspirate fluid (NAF) of non-Asian women would be altered so as to resemble those previously found in Asian women. At monthly intervals for 1 year, 24 normal pre- and postmenopausal white women, ages 30 to 58, underwent nipple aspiration of breast fluid and gave blood and 24-h urine samples for biochemical studies. No soy was administered in months 1-3 and 10-12. Between months 4-9 the women ingested daily 38 g of soy protein isolate containing 38 mg of genistein. NAF volume, gross cystic disease fluid protein (GCDFP-15) concentration, and NAF cytology were used as biomarkers of possible effects of soy protein isolate on the breast. In addition, plasma concentrations of estradiol, progesterone, sex hormone binding globulin, prolactin, cholesterol, high density lipoprotein-cholesterol, and triglycerides were measured. Compliance was assessed by measurements of genistein and daidzein and their metabolites in 24-h urine samples. Excellent compliance with the study protocol was obtained. Compared with NAF volumes obtained in months 1-3, a 2-6-fold increase in NAF volume ensued during months 4-9 in all premenopausal women. A minimal increase or no response was found in postmenopausal women. No changes were found in plasma prolactin, sex hormone binding globulin, cholesterol, high density lipoprotein cholesterol, and triglyceride concentrations. Compared with concentrations found in months 1-3 (no soy), plasma estradiol concentrations were elevated erratically throughout a "composite" menstrual cycle during the months of soy consumption. No significant changes were seen in plasma progesterone concentrations. No significant changes were found in plasma estrogen levels in postmenopausal women. A moderate decrease occurred in the mean concentration of GCDFP-15 in NAF in premenopausal women during the months of soy ingestion. Of potential concern was the cytological detection of epithelial hyperplasia in 7 of 24 women (29.2%) during the months they were consuming soy protein isolate. The findings did not support our a priori hypothesis. Instead, this pilot study indicates that prolonged consumption of soy protein isolate has a stimulatory effect on the premenopausal female breast, characterized by increased secretion of breast fluid, the appearance of hyperplastic epithelial cells, and elevated levels of plasma estradiol. These findings are suggestive of an estrogenic stimulus from the isoflavones genistein and daidzein contained in soy protein isolate.

The effect of different molecular species of sphingomyelin on phospholipase C delta 1 activity.

Bovine brain sphingomyelin was separated into different molecular species using a reverse phase column. PLC delta 1 was inhibited by all molecular species of sphingomyelin. The extent of this inhibition was dependent on the hydrophobicity. Based on fatty acid analysis, we conclude that the inhibition of PLC delta 1 depends on the chain length and degree of unsaturation of the fatty acid moiety of SM. N-palmitoyl-D-sphingomyelin and N-stearoyl-D-sphingomyelin inhibited PLC delta 1 less then N-oleoyl-D-sphingomyelin. In the absence of Ca2+ (1 mM EGTA) all tested molecular species of SM inhibited weakly the enzyme. The sensitivity of PLC delta 1 to inhibition by SM increased with increasing Ca2+ concentration. The shape of calcium curve differed for molecular species with saturated and unsaturated fatty acids. Inhibition of PLC delta 1 by N-palmitoyl-D-sphingomyelin and N-stearoyl-D-sphingomyelin reached a maximum at 0.2 microM Ca2+, while inhibition by N-oleoyl-D-sphingomyelin reached maximum at 2 microM Ca2+. PLC delta 1 is more sensitive to inhibition by SM when it is maximally activated by spermine and calcium and the extent of this inhibition depends on the length and degree of fatty acid unsaturation of the molecular species.

Effects of prazosin, atenolol, and thiazide diuretic on plasma lipids in patients with essential hypertension.

The effects of prazosin and atenolol monotherapy on plasma lipid concentrations were compared in 51 patients with mild to moderate essential hypertension. Prazosin monotherapy (mean dose 5.4 +/- 5.3 mg per day) resulted in a significant decrease in total and low-density lipoprotein cholesterol concentrations; these changes were evident at three months and at six to 12 months. Atenolol monotherapy (mean dose 66 +/- 23 mg per day) resulted in a significant increase in plasma triglyceride concentration that persisted during one year of treatment. The deletion of thiazide from the regimen of prazosin plus thiazide resulted in a small stepwise decrease in plasma triglyceride concentration over 12 months of observation. The addition of polythiazide (0.5 mg two to three times weekly) to the regimen of patients in whom acceptable blood pressure was not attained with prazosin or atenolol monotherapy resulted in a decrease in blood pressure, averaging 18.8 mm Hg for systolic and 10.3 mm Hg for diastolic, and a small, though significant, increase in the concentration of low-density lipoprotein cholesterol. It is suggested that the effects of prazosin on plasma lipid composition may be mediated, at least in part, by blocking an action of either the sympathetic nervous system or circulating catecholamines that normally modulate lipoprotein metabolism and might mediate the lipid alterations induced by thiazide diuretics.

Effects of prazosin and propranolol on serum lipids in patients with essential hypertension.

The effects of prazosin and propranolol on total serum cholesterol concentration, low-density lipoprotein and high-density lipoprotein cholesterol fractions, and serum triglyceride concentration were compared in a crossover study in 29 patients with mild to moderate essential hypertension. All patients received polythiazide at a constant dose throughout control and drug treatment periods. Comparable blood pressure reduction was achieved with prazosin (9.3 +/- 7.1 mg per day) and propranolol (183.6 +/- 154.5 mg per day). Prazosin administration was associated with a significant reduction in the concentrations of total serum cholesterol (-5.5 percent), triglyceride (-20.0 percent), and low-density lipoprotein cholesterol (-10.1 percent). High-density lipoprotein cholesterol concentration increased (+8.0 percent) as did the ratio high-density lipoprotein: total cholesterol (+14.1 percent). No significant changes in any of the serum lipid fractions were observed during propranolol administration.