[Project for the Creation of a Medical or Hospital Ethical Committee at a Local Level in the San Miguel Arcangel Hospital, District of San Miguelito, Province of Panama. Year 2013]. / Proyecto Para la Creación de un Comité de Ética Médica u Hospitalaria de Nivel Local en el Hospital San Miguel Arcángel, Distrito de San Miguelito, Provincia de Panamá. Año 2013.

The next project was based on the design on the creation of a medical ethical Committee at a hospital. It was developed at the San Miguel Arcangel Hospital, District of San Miguelito, Province of Panama, in 2013. Insomuch as the creation of social projects requires unified international parameters, format is taken from the Unesco's guides for the establishing and working of bioethics committees; adapted to the socio-economic, political and cultural context of the San Miguelito District, Panama Province. Furthermore to adapting to socio-ecological aspect where the research project is carried out, the theoretical aspect includes from the ontological personalistic bioethics, where the cornerstone is the dignity of the human person. A study of perceptions of medical staff and nursing was developed on the management of the most common ethical dilemmas in the Hospital San Miguel Arcángel. The instrument used was a previously validated perception survey through a pilot test. Reliability was measured using Cronbach's alpha coefficient, and validity was obtained from the content. Satisfactory statistical results, that verify the working hypotheses on the recognition of the importance of autonomy, confidentiality, protection of vulnerable population, occupational health staff welfare and integration of bioethics at the institutional agenda, were obtained. However, there were particular aspects that indicate some doubt as to the management of some realities that are presented in the context of health care.

Proyecto para la creación de un comité de ética médica u hospitalaria de nivel local en el hospital San Miguel Arcángel, distrito de San Miguelito, provincia de Panamá. Año 2013 / Project for the creation of a medical or hospital ethical committee at a local level in the San Miguel Arcangel Hospital, district of San Miguelito, province of panamá. Year 2013

El siguiente proyecto se basa en el diseño para la creación de un comité de ética médica asistencial a nivel hospitalario. Se elaboró en el Hospital San Miguel Arcángel, Distrito de San Miguelito, Provincia de Panamá, durante el año 2013. Dado que la creación de proyectos sociales requiere parámetros unificados a nivel internacional, se toma como formato las guías de creación y funcionamiento de los comités de bioética de la Unesco, adaptadas al contexto socioeconómico, político y cultural del Distrito de San Miguelito, Provincia de Panamá. Además de adaptarlo al aspecto socio-ecológico donde se realiza el proyecto de investigación, se abarca el aspecto teórico desde la bioética ontológica personalista, donde el eje fundamental es la dignidad de la persona humana. Se elaboró un estudio de percepción del personal médico y de enfermería, sobre el manejo de los dilemas éticos más frecuentes en el Hospital San Miguel Arcángel. El instrumento de medición utilizado fue una encuesta de percepción previamente validada a través de una prueba piloto. La confiabilidad se midió con el coeficiente alfa de Cronbach y la validez se obtuvo del contenido. Se obtiene resultados estadísticos satisfactorios que comprueban las hipótesis de trabajo sobre el reconocimiento de la importancia de la autonomía, confidencialidad, protección a la población vulnerada, bienestar laboral del personal de salud e integración de la bioética en la agenda institucional. Sin embargo, hubo aspectos particulares que indican algunas dudas en cuanto al manejo de algunas realidades que se presentan en el contexto de la atención sanitaria

The next project was based on the design on the creation of a medical ethical Committee at a hospital. It was developed at the San Miguel Arcangel Hospital, District of San Miguelito, Province of Panama, in 2013. Insomuch as the creation of social projects requires unified international parameters, format is taken from the Unesco’s guides for the establishing and working of bioethics committees; adapted to the socio-economic, political and cultural context of the San Miguelito District, Panama Province. Furthermore to adapting to socioecological aspect where the research project is carried out, the theoretical aspect includes from the ontological personalistic bioethics, where the cornerstone is the dignity of the human person. A study of perceptions of medical staff and nursing was developed on the management of the most common ethical dilemmas in the Hospital San Miguel Arcángel. The instrument used was a previously validated perception survey through a pilot test. Reliability was measured using Cronbach’s alpha coefficient, and validity was obtained from the content. Satisfactory statistical results, that verify the working hypotheses on the recognition of the importance of autonomy, confidentiality, protection of vulnerable population, occupational health staff welfare and integration of bioethics at the institutional agenda, were obtained. However, there were particular aspects that indicate some doubt as to the management of some realities that are presented in the context of health care

Syntheses and biological evaluations of alpha-D-mannosyl [60]fullerenols.

[60]Fullerenols carrying mono- and bis-alpha-D-mannosyl linkages on the surface were prepared via a [3+2]-cycloaddition reaction between 2-azidoethyl alpha-D-mannoside and C(60) followed by polyhydroxylation with aqueous NaOH. Their biological activity was evaluated in terms of binding affinity to lectins by hemagglutination assay and surface plasmon resonance. [60]Fullerenols without the mannosyl linkage caused aggregation of erythrocytes and binding to a beta-D-galactopyranoside specific lectin (RCA(120)). In contrast, mono- and bis-mannosyl fullerenols were found to decrease the activity for both aggregating erythrocytes and binding to RCA(120), and mono-mannosyl fullerenols turned to binding to alpha-D-mannose specific lectin (Con A).

Acute-phase proteins and Chlamydia pneumoniae infection: which one is more important in acute coronary syndrome?

Elevated levels of acute-phase proteins, a systemic marker for inflammation, predict coronary events; Chlamydia pneumoniae (C. pneumoniae) infection is associated with coronary atherosclerosis. The present study investigated whether inflammation or infection is involved in the pathogenesis of acute coronary syndrome (ACS) and which one has the more important role. The study group comprised 49 patients with angiographically diagnosed ACS, 48 cases of chronic coronary heart disease (CCHD), and 44 subjects with a normal coronary profile. The levels of serum C-reactive protein (CRP), fibrinogen and anti-C. pneumoniae IgG antibody were measured. The IgG antibody against C. pneumoniae was higher in the ACS and CCHD groups compared with the control group after adjusting for age and gender. The levels of CRP and fibrinogen were significantly increased in patients with ACS compared with controls and CCHD patients. Multiple stepwise logistic regression analysis revealed that C. pneumoniae IgG antibody is an independent risk factor for both ACS and CCHD (odds ratio 2.3 and 2.1, respectively), but the CRP level is a risk factor only for ACS (odds ratio 6.9). The inflammatory response, as indicated by acute-phase proteins, especially CRP, rather than C. pneumoniae infection, may contribute more to the clinical course of ACS.

Chlamydia pneumoniae infection and accelerated development of coronary artery disease in patients with chronic renal failure.

AIMS: This study examined the relationship between Chlamydia pneumoniae (C. pneumoniae) infection and the accelerated development of coronary artery disease (CAD) in patients with chronic renal failure (CRF). METHODS: Two-hundred and fourteen patients undergoing coronary angiography, including 67 controls and 147 patients with CAD (97 without CRF and 50 with CRF), were enrolled in this study. Anti-C. pneumoniae specific IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Coronary artery disease (expressed as CAD score) was more severe in patients with than without CRF (14.9 +/- 6.0 vs. 11.3 +/- 6.0, p < 0.01). Seropositive rates of IgG and IgA antibodies against C. pneumoniae were higher in all CAD patients than in the controls (76.2% vs. 44.8%, p < 0.001 for IgG; 59.9% vs. 40.3%, p < 0.01 for IgA). In both CAD subgroups, IgG seropositive rates were similarly elevated (82.0% and 73.2% vs. 44.8% for control, p < 0.001, respectively), whereas those of IgA were significantly elevated only in CAD with CRF (68.0% vs. 55.7% for control, p < 0.01). The mean antibody index of IgG was elevated in all CAD patients compared with the controls (1.9 +/- 1.0 vs. 1.3 +/- 0.9, p < 0.0001), but that of IgA was not (1.5 +/- 1.0 vs. 1.2 +/- 0.9). Levels of IgG were elevated in all patients with CAD compared with the control (2.4 +/- 1.1 and 1.8 +/- 1.0 vs. 1.3 +/- 0.9, p < 0.001 and p < 0.001, respectively), whereas those of IgA were elevated only in CAD with CRF (1.8 +/- 1.1 vs. 1.2 +/- 0.9, p < 0.05). Stepwise logistic regression analysis revealed that the elevated IgG antibody index was an independent risk factor for CAD regardless of CRF (odds ratios 1.9, 1.8, and 2.3), whereas the IgA index was a risk factor only in CAD with CRF (odds ratio 1.7). CONCLUSIONS: Chlamydia pneumoniae infection may be related to the accelerated CAD in patients with CRF, which was specifically suggested by an elevated IgA level. In other words, the prevalence of active C. pneumoniae infection is higher in patients with CAD and CRF than that in those with CAD without CRF.

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells.

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO4 caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO4 for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression.

Atherogenic lipoproteins inhibit catecholamine secretion in cultured bovine adrenal medullary cells.

The effects of lipoproteins on ion channel-mediated catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Low density lipoprotein (LDL: 20-80 mg/dl) and lipoprotein(a) [Lp(a); 10-80 mg/dl] inhibited catecholamine secretion induced by carbachol, an activator of nicotinic acetylcholine receptor-ion channels. LDL and Lp(a) suppressed carbachol-induced 22Na+ influx as well as 45Ca2+ influx in a concentration-dependent manner similar to that of catecholamine secretion. The inhibition of catecholamine secretion by Lp(a) was not overcome by increasing the concentration of carbachol. On the other hand, high density lipoprotein (HDL; < 150 mg/dl) had no effect on 22Na+ influx, 45Ca2+ influx, and catecholamine secretion. Like LDL and Lp(a), a synthetic peptide homologous to human plasma apolipoprotein B (apoB), apoB fragment(3358-3372)-amide (3-60 microM), attenuated 22Na+ influx, 45Ca2+ influx, and catecholamine secretion caused by carbachol. The apoB fragment also suppressed 22Na+ influx induced by veratridine (an activator of voltage-dependent Na+ channels) and 45Ca2+ influx induced by 56 mM K+ (an indirect activator of voltage-dependent Ca2+ channels). These findings suggest that atherogenic lipoproteins such as LDL and Lp(a) suppress catecholamine secretion by interfering with Na+ influx through nicotinic acetylcholine receptor-ion channels, in which apoB, a structural component common to both LDL and Lp(a), plays an important role. The inhibition by atherogenic lipoproteins of catecholamine secretion may influence the progression of atherosclerosis induced by these lipoproteins.

Enhanced macrophage uptake of lipoprotein(a) after Ca2+-induced aggregate-formation.

We tested the hypothesis that aggregated lipoprotein(a) [Lp(a)] is avidly taken up by macrophages. Lp(a) was isolated by sequential centrifugations and gel chromatography from a patient with high plasma levels of Lp(a) who was being treated with low density lipoprotein (LDL)-apheresis. Aggregated Lp(a) was prepared by mixing native Lp(a) with 2.5 mmol/L CaCl2, and 54% of the 125I-Lp(a) aggregated after interacting with CaCl2. The binding and degradation of aggregated Lp(a) in macrophages were 4.6- and 4.7-fold higher than those of native Lp(a), respectively. An excess amount of LDL did not inhibit either increase. Cholesterol esterification in macrophages was markedly stimulated by aggregated Lp(a), and macrophages were transformed into foam cells. Cytochalasin B, a phagocytosis inhibitor, strongly inhibited the degradation and cholesterol esterification (78 and 83%, respectively). These findings suggested that aggregation may be partially involved in Lp(a) accumulation, thereby contributing to the acceleration of atherosclerosis.

Plasma nitrite/nitrate level is inversely correlated with plasma low-density lipoprotein cholesterol level.

BACKGROUND: Plasma nitrite/nitrate (NOx) is a stable end product of the vasodilator nitric oxide (NO). However, there are few reports about plasma NOx levels in humans. HYPOTHESIS: The purpose of this study was to assess the availability of plasma NOx for evaluating basal endogenously-synthesized or endothelium-derived NO, and to examine whether NOx levels are lowered in patients with coronary artery disease (CAD) or its risk factors. METHODS: Plasma NOx levels were measured using an automated system based on the Griess reaction. NOx levels for a 24-h period reproducibly became lowest at 6 A.M. in restricted healthy volunteers, and became stable in inpatient volunteers at 6 A.M. within 4 days after admission. RESULTS: Based on these findings, NOx levels at 6 A.M. in inpatients can be considered as the basal levels. In 40 inpatients suspected of CAD (28 men, 12 women; mean age 60 +/- 11 years), the basal levels of NOx were not related to CAD and its risk factors, except for hypercholesterolemia. The NOx level of patients with hypercholesterolemia was significantly lower than that of patients with normal cholesterol (n = 16,34 +/- 16 mumol/l vs. n = 24, 49 +/- 23 mumol/l, p < 0.03). Furthermore, the NOx levels correlated negatively with the total cholesterol and low-density lipoprotein cholesterol levels (r = -0.40, p < 0.01; r = -0.47, p < 0.003, respectively), but not with other lipid fraction levels. CONCLUSION: The results suggest that the quantity of basal endothelium-derived NO synthesis may be decreased in the presence of hypercholesterolemia.

Simvastatin increases plasma NO2- and NO3- levels in patients with hypercholesterolemia.

In this study, plasma NO2- and NO3- (NOx-) levels were studied after lowering cholesterol with simvastatin in 26 outpatients with hypercholesterolemia (male, 9; female, 17; mean age, 59 +/- 12 years; cholesterol level > 220 mg/dl). Simvastatin (5 mg) was orally administered once daily, and blood samples were collected before, and after 4 and 12 weeks of treatment. Total, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol were lowered (total, 254 +/- 44 mg/dl to 209 +/- 34 mg/dl; VLDL, 48 mg/dl [5-126 mg/dl] to 34 mg/dl [10-67 mg/dl]; LDL, 171 +/- 41 mg/dl to 133 +/- 37 mg/dl), but high-density lipoprotein (HDL) cholesterol was elevated (33 +/- 9.5 mg/dl to 39 +/- 11 mg/dl) at 12 weeks after starting simvastatin. Although the effects of simvastatin on the lipid levels nearly reached their maximum levels at 4 weeks, NOx- was elevated in a linear fashion with simvastatin (before; 8 +/- 17 mumol/l, at 12 weeks; 57 +/- 32 mumol/l). The % changes in the NOx- correlated directly with those in HDL-cholesterol at 12 weeks (P < 0.002) but not with other lipoprotein cholesterol fractions. These results suggest that simvastatin lowers cholesterol levels and elevates HDL while increasing the plasma NOx- levels.

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.

Increased susceptibility of angiographically smooth left anterior descending coronary artery to an impairment of vasoresponse to acetylcholine, and the relation between impaired vasoresponse and low-density lipoprotein cholesterol level.

In the present study, we demonstrated that the angiographically smooth LAD is more susceptible than the LC to an impairment of vasoresponse to acetylcholine, suggesting the more severe endothelial dysfunction in the LAD. We also showed that levels of LDL play a partial but important role on endothelial dysfunction.

Immunochemically detectable lipid-free apo(a) in plasma and in human atherosclerotic lesions.

Although Lp(a) is an independent risk factor for cardiovascular diseases in humans, the precise pathogenetic mechanisms are still unknown. We have shown that Lp(a) accumulates in human atherosclerotic lesions, and some particles undergo oxidation. Since, following agarose electrophoresis of both plaque extracts and plasma, a region close to the origin immunostained intensely for apo(a) but was lipid-free, we sought to identify whether such samples contained lipid-free apo(a), as previously reported to occur in plaque extracts. Immunochemically identifiable apo(a) was found following density-gradient ultracentrifugation both in the 1.05 < d < 1.09 and the d > 1.21 density fraction from both plasma and plaque extracts. However, because in a competitive binding RIA, displacement curves of apo(a) in plasma and the d > 1.21 were not parallel, it is premature to ascribe a relative amount of total apo(a) to this fraction. Whereas apo(a) immunoblots of SDS-PAGE under reducing conditions of the d > 1.21 fraction of a plaque extract with high apo(a) content showed high molecular weight bands consistent with apo(a) isoforms, the corresponding d > 1.21 fraction showed multiple low molecular weight bands characteristic of fragmentation. Since the d > 1.21 of arterial extracts contained all the material immunostaining for apo(a) migrating towards the cathode, characteristic of immunoglobulins (IgG), we asked whether fragments of apo(a) might have associated with human IgG both in plasma and tissue extracts, or whether our anti-apo(a) reacted with epitopes on human IgG. Immunoblotting with our anti-apo(a) of samples of plasma and plaque extracts run on agarose electrophoresis or SDS-PAGE further demonstrated intense staining of multiple bands in the molecular weight range of human IgG. Furthermore, a fraction of plasma and tissue extracts that bound to a protein G affinity column demonstrated immunostaining for apo(a) and was in the size range of IgG. Although one polyclonal anti-apo(a) provided by another laboratory showed the same findings as our antibody, two other polyclonal anti-apo(a) failed to demonstrate immunostaining of human IgG, either on agarose electrophoresis or SDS-PAGE. We speculate that the Lp(a) immunogen used to prepare our anti-apo(a) may have undergone modest oxidation, thus exposing epitopes not normally expressed on apo(a) in native Lp(a). Either antibodies to these epitopes could be recognizing apo(a) fragments, possibly released during oxidation, which are then covalently bound to IgG, or oxidation of apo(a) creates epitopes on apo(a) that are homologous with IgG, thereby leading to cross-reactivity with IgG.(ABSTRACT TRUNCATED AT 400 WORDS)

Partial characterization of lipoproteins containing apo[a] in human atherosclerotic lesions.

Previously we quantified the amounts of immunoreactive apo[a] found in human atherosclerotic lesions extracted sequentially with phosphate-buffered saline (PBS) and guanidine hydrochloride (GuHCl). In this study we have attempted to characterize lipoproteins containing apo[a] in such PBS and GuHCl fractions, obtained from autopsy samples, in order to eventually determine their structure-function relationships critical for evaluating the mechanisms that make them atherogenic. Apo[a] in the PBS extracts migrated slightly ahead of plasma Lp[a] on agarose electrophoresis. Although apo[a] in extracts showed the same isoforms as in plasma in SDS-PAGE, it was also highly fragmented. When a d < 1.10 g/ml ultracentrifugation fraction of the PBS extract was subjected to gel filtration, a major part of the immunoreactive apo[a] in this fraction co-isolated with plasma Lp[a]. When the Lp[a]-sized fraction was further separated by density gradient ultracentrifugation, a subpopulation was isolated containing apo[a] in the 1.06 < d < 1.08 g/ml density range that was free of lesion-derived low density lipoprotein (LDL) (A-LDL). This fraction contained immunoreactive apo[a] and apoB, had a total cholesterol to protein ratio of about 1, and demonstrated increases in fluorescence (360 ex/430 em) and conjugated dienes that were even greater than values obtained for the corresponding A-LDL sample. The void volume fraction following gel exclusion chromatography of the d < 1.10 g/ml fractions contained both apo[a] and apoB that comigrated on nondenaturing PAGE, suggesting that they were present on the same particle. Apo[a] in GuHCl extracts comigrated with plasma Lp[a] on agarose electrophoresis and contained apo[a] isoforms of similar molecular weights as those found in corresponding plasma samples. When the GuHCl extract was subjected directly to gel filtration in the presence of 6 M GuHCl, two included peaks of apo[a] immunoreactivity were present, one eluting slightly ahead of plasma Lp[a], the other slightly ahead of plasma LDL. Collectively, these data indicate that apo[a] is present in human atherosclerotic lesions in forms resembling intact but oxidized plasma Lp[a], as larger particles possibly representing Lp[a] complexed to itself or other plaque components, and as slightly smaller particles possibly representing degraded Lp[a].

Insoluble complex formation of lipoprotein (a) with low density lipoprotein in the presence of calcium ions.

We investigated whether apolipoprotein B-containing lipoproteins could bind to the insoluble complexes of lipoprotein (a) (Lp(a)) induced by Ca2+. Lp(a), but not low density lipoprotein (LDL), very low density lipoprotein (VLDL), or high density lipoprotein3 (HDL3) formed insoluble complexes at physiologic Ca2+ concentrations. Desialylation of Lp(a) dramatically decreased the ability of Lp(a) to aggregate, suggesting that sialic acids on Lp(a) were responsible for forming Ca2+ cross-bridges. Since a reduction of only 30% of the sialic acids on Lp(a) inhibited Ca(2+)-induced complex formation, it appears that only a small percentage of sialic acids on Lp(a) is involved in Ca(2+)-induced cross-bridging of Lp(a) particles. To determine whether other lipoproteins would complex to Lp(a) in the insoluble complexes, we mixed Lp(a) with LDL, VLDL, or HDL3 in the presence of Ca2+. Although both LDL and VLDL bound to the Lp(a) in the insoluble complexes, HDL3 not only did not bind, but it also prevented Lp(a) from forming insoluble complexes. LDL bound to Lp(a) in the insoluble complexes in a concentration-dependent manner, eventually reaching saturation at a molar ratio of 5:4 (LDL to Lp(a)). The interaction between LDL and Lp(a) appeared to be ionic, since increases in the positive charge on LDL by desialylation increased this interaction, whereas decreases in positive charge on LDL reduced this interaction. At higher Ca2+ concentrations, the binding of acetyl LDL to Lp(a) in the insoluble complexes was greater than that of LDL. Since more Ca2+ was required for concentration-dependent saturation of acetyl LDL binding, it is likely that Ca2+ cross-bridging was responsible for this binding. Thus, LDL, especially its modified forms, could contribute to the formation of insoluble complex of Lp(a) with Ca2+ in atherosclerotic lesions and help explain its preferential accumulation there.

Heparin-releasable platelet factor 4 in patients with coronary artery disease.

Recently, platelet factor 4 (PF4) release by heparin (heparin-releasable PF4) has been examined as a useful marker of the interaction between the substances liberated from circulating platelets and the vascular endothelium. We compared the plasma levels of PF4 and beta-thromboglobulin (beta-TG) after intravenous heparin injection in patients with coronary artery disease (CAD) and normal control subjects. We also studied the effects of low-dose aspirin (81 mg/day) on the plasma level of heparin-releasable PF4 in the CAD patients. Blood samples were obtained before and 5 min after the intravenous injection of heparin (1,000 IU) from 23 patients with CAD and 15 normal control subjects. Although the plasma beta-TG level remained unchanged after heparin injection, the plasma PF4 level markedly increased in both groups. There was a significant difference in plasma PF4 levels at 5 min after heparin injection between the CAD group (100.1 +/- 38.1) and the control group (61.0 +/- 24.0) (p less than 0.01). The PF4/beta-TG ratio after heparin injection was also higher in the CAD group than in the control group (p less than 0.01). There was a correlation between the PF4/beta-TG ratio after heparin and the Gensini CAD score, which defines the severity of coronary atherosclerosis (r = 0.489, n = 23, p less than 0.01). Low-dose aspirin was administered to 11 CAD patients for 246.0 +/- 28.8 days. Blood samples for the assay of PF4 and beta-TG were obtained as stated above, and platelet aggregation, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels were also measured before and during aspirin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained-release nifedipine (nifedipine-L) suppresses plasma thromboxane B2 and 6-keto prostaglandin F1 alpha in both young male smokers and nonsmokers.

Sustained-release nifedipine (nifedipine-L) (40 mg twice a day) was administered orally to healthy young adult male smokers and nonsmokers for 10 days, and its effects on platelet aggregation, beta-thromboglobulin and platelet factor 4 levels, and plasma thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-Keto-PGF1 alpha) concentrations were studied. The plasma nifedipine-L concentration in smokers (46.0 +/- 7.4 ng/ml) was significantly lower than that in nonsmokers (88.2 +/- 1.2 ng/ml). Nifedipine-L did not affect platelet aggregation induced by adenosine diphosphate, collagen, or epinephrine in either smokers or nonsmokers. The plasma beta-thromboglobulin level on the tenth day of nifedipine-L administration in nonsmokers was lower than that in smokers, but there were no significant differences either with or without nifedipine-L or between nonsmokers and smokers. Nifedipine-L had no effect on the concentration of platelet factor 4 in either smokers or nonsmokers. On the other hand, nifedipine-L significantly decreased the plasma TxB2 and 6-keto-PGF1 alpha concentrations in both smokers and nonsmokers. Thus we concluded that nifedipine-L suppressed the production of plasma TxB2 from platelets and also subsequently suppressed the production of 6-keto-PGF1 alpha and that this action was not affected by cigarette smoking.

Effects of polysulfated glycosaminoglycans obtained from bovine lung tissue on hypercholesterolemic rabbits.

Sixteen rabbits were fed a 1% cholesterol diet with an intraperitoneal injection of saline (n = 8) (cholesterol-diet group), or 50 mg glycosaminoglycans-polysulfate (GAG-PS) (n = 8) (GAG-PS group). After 10 weeks all rabbits were sacrificed and studied. Eight rabbits on a standard diet with an intraperitoneal injection of saline (n = 8) (standard-diet group) were processed in the same manner. After 10-weeks of feeding, the plasma total cholesterol of the GAG-PS group was significantly lower than that of lower than that of the control group (P less than 0.02). The VLDL cholesterol of the GAG-PS group was also significantly lower than that of the cholesterol-diet group. There were no differences in LDL-cholesterol, HDL-cholesterol or plasma triglycerides between the groups. Total lipoprotein lipase activity (T-LPL) (LPL + HTGL) of the GAG-PS group at 10 weeks was higher than that of the cholesterol-diet group. These elevated T-LPL levels were mainly due to an increase in the LPL from peripheral tissues. ADP-induced platelet aggregability of the GAG-PS group significantly decreased at 10 weeks when compared to the cholesterol-diet group, and antithrombin-III activity of the GAG-PS group was inversely increased when compared to the cholesterol-diet group. Although there were no differences in aortic levels of total cholesterol and uronic acid between the GAG-PS group and the cholesterol-diet group, the surface involvement of the aorta in the GAG-PS group was significantly lower than that in the cholesterol-diet group. The aortic levels of free cholesterol, hydroxyproline and calcium of the GAG-PS group were significantly decreased when compared to the cholesterol-diet group. These findings suggest that GAG-PS has antiatherosclerotic effects.