1-Acyl-2-lysophosphatidylcholine transport across the blood—retina and blood—brain barrier

The transport of lysophospholipids through the rat blood—retina and blood—brain barrier was determined by using radioactive 1-palmitoyl-2-lysophosphatidylcholine (Pam-lysoPtdCho) and by measuring the uptake of this labeled compound into the retina and various brain regions after short in situ carotid perfusion. The transport was not affected by probenecid (0.25 mM), but it was inhibited, in a dose-dependent manner, by circulating albumin which is able to bind tightly to lysophosphatidylcholine and lowered the availability of the latter for tissue extraction. Radiotracer transfer in the retina was higher than in brain regions. The permeability-surface area products (PS) changed with the inclusion of unlabeled Pam-lysoPtdCho, showing that transport across retinal and brain microvessels is mainly saturable. The data provided an estimate of transport constants (V_max, K_m and non-saturable constant K_d). However, we could not distinguish whether this saturable process represents the saturation of a transport carrier or simple passive diffusion followed by the saturation of enzymatic reactions. In brain tissue lipid extract, 20 s after carotid injection, radiolabel was associated by 45% to unmetabolized Pam-lysoPtdCho. Partial acylation to phosphatidylcholine, as well as hydrolysis and redistribution of the fatty acyl moiety into main phospholipid classes also occurred. The present results, compared to our previous data, indicate that PamlysoPtdCho is transported faster and/or in greater amounts than unesterified fatty acids.     

Hawthorn special extract WS? 1442 increases red blood cell NO-formation without altering red blood cell deformability

WS(?) 1442 is a special extract of hawthorn leaves with flowers used for the treatment of mild cardiac failure. The activation of endothelial nitric oxide synthase (eNOS) has been shown to contribute to its vasodilating properties. Quite recently it has been demonstrated that red blood cells (RBCs) express a functional NO-synthase (rbcNOS) and rbcNOS activation has been associated with increased RBC deformability. The aim of the present study was to determine whether WS(?) 1442 is able to activate rbcNOS, to induce NO-formation in RBC and to alter RBC-deformability. Blood from healthy volunteers was incubated with WS(?) 1442 (25-100 μg/ml) for up to 30 min. RbcNOS activation was detected by immunohistochemical staining of phosphorylated rbcNOS and NO-formation was examined by diaminofluorescein (DAF) fluorescence. RBC deformability was measured by a laser assisted optical rotational cell analyzer. Serine 1177 of RbcNOS (rbcNOS Ser(1177)) was time- and concentration-dependently phosphorylated by WS(?) 1442. Rates of rbcNOS Ser(1177) phosphorylation were up to 149% higher in RBCs treated with WS(?) 1442 in comparison to control (DMSO 0.05%). WS(?) 1442 induced a time-dependent increase in NO-formation in RBCs which reached its maximum after 5 min. An increase in shear stress (0.3-50 Pa) caused an increase in RBC deformability. WS(?) 1442 did not change either basal or maximal RBC-deformability or shear stress sensitivity of RBC at normoxia. CONCLUSION: WS(?) 1442 activates rbcNOS and causes NO-formation in RBCs. WS(?) 1442-dependent NO-formation however does not affect RBC-deformability at normoxia.     

Low blood pressure,low mood?

OBJECTIVE--To determine whether a set of physical symptoms is associated with low blood pressure and to investigate the possible role of psychological factors in their occurrence. DESIGN--Analysis of data collected by questionnaire and physical screening from the first phase of the Whitehall II study, a cohort study of an employed population. SETTING--23 civil service departments in London. SUBJECTS--10,314 male and female London based civil servants aged between 35 and 55. MAIN OUTCOME MEASURES--Symptoms of dizziness-giddiness and unexplained tiredness; psychological functioning as measured by the 30 item general health questionnaire in which the response "no more than usual" to an item about disease was scored as indicating chronic illness. RESULTS--Dizziness-giddiness in men and unexplained tiredness in both men and women were significantly related to low systolic blood pressure. There was a highly significant inverse relation between general health questionnaire score and systolic blood pressure for both men and women, which persisted after controlling for potentially confounding variables, including age, body mass index, drug treatment, physical illness, and exercise. This association of low blood pressure with physical symptoms was no longer significant when general health questionnaire score was controlled for. CONCLUSIONS--There seems a strong relation between low systolic blood pressure and minor psychological dysfunction. Associated physical symptoms seem to be secondary to the primary disturbance in mental state.     

Does sodium restriction lower blood pressure?

Data from 13 randomised trials on the effect of sodium restriction on blood pressure were analysed. The hypotensive effect of sodium restriction was found to be small and restricted largely to systolic blood pressure, which fell by an average of 3.6 mm Hg (range 0.5-10.0 mm Hg). The reduction increased with age and in those with higher blood pressure. Sodium restriction therefore seems to be of limited use in those who are most eligible for non-pharmacological treatment of high blood pressure--namely, young patients with mild hypertension.     

Does dietary magnesium modulate blood lipids?

In a randomized, single-blind, controlled study (400 patients aged 25-63 yr; 374 males, 26 females), 206 subjects were administered a magnesium-rich diet, and 194 subjects their usual diet, for 6 wk. Age, sex, body weight, hypertension, hyperlipidemia, smoking, obesity, diuretic therapy, and diabetes were comparable between the two groups, as were laboratory data at entry to the study. Intervention-group A received a significantly higher amount of dietary magnesium and potassium compared to group B, which received its usual diet. After 6 wk, there was a significant fall in total serum cholesterol (228.5 +/- 46.2 mg/dL), LDL cholesterol 146.5 +/- 75.5 mg/dL), and triglyceride (143.8 +/- 40.5 mg/dL) in group A compared to serum cholesterol (242.5 +/- 58.2 mg/dL), LDL cholesterol (157.0 +/- 78.4 mg/dL), and triglyceride (156.5 +/- 60.0 mg/dL) at entry to study, but no such changes in group-B subjects. HDL cholesterol showed a marginal mean decrease of 0.8 mg/dL in group B and a 2.5 mg/dL increase in group A. The changes in blood lipids were consistent with an increased intake of magnesium and with a rise in serum levels. Although a general blood-lipid-reducing effect of such a diet cannot be excluded, it is possible that dietary magnesium may have contributed to the reduction of total serum cholesterol, LDL cholesterol, and triglyceride, and the marginal rise in HDL cholesterol. More studies with longer follow-up periods are needed to confirm this observation.     

Cord blood stem cell transplantation. Why it is necessary to establish a Bulgarian cord blood bank?

The allogenic transplantation of hemopoietic stem cell from bone marrow and peripheral blood is limited due to the necessity to identify HLA matched donor within the family or in bone marrow donor registries. Although, more than 10 million donors are available worldwide, completely HLA matched donors could be found only for 75% of the patients. It is well known that transplantations of hematopoietic stem cell from cord blood are characterized with a lower risk of GvHD and therefore do not require so strict criteria for HLA matching, and less time for search of matched donor is needed. The necessity to establish a National cord blood bank in Bulgaria is emphasized further by the heterogeneity of HLA allele and haplotype distribution in the Bulgarian population. That could be explained by the ethnic diversity of the population. As a result some alleles are more frequent in Bulgarians compared to other populations. The organization, accreditation, and development of a strategy for a National cord blood bank will be discussed.     

Folate nutrition and blood–brain barrier dysfunction

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Mercury in blood cells—Altered elemental profiles

The study was composed of 27 persons that displayed vague symptoms similar to those of the victims of Minamata and Iraq. Skew distributions of mercury were observed in individual erythrocytes and neutrophil granulocytes when measured by PIXE. Mercury could not be detected in the platelets. The erythrocytes also displayed lowered concentrations of magnesium and zinc, together with increased concentrations of calcium and strontium. The neutrophils displayed decreased concentrations of magnesium and zinc and increased concentrations of calcium, strontium, and iron. The presence of mercury and the altered elemental profiles in the erythrocytes and the neutrophil granulocytes are suggested as early signs of exposure.     

Is exercise good for high blood pressure?

Ten men with uncomplicated essential hypertension (mean standing blood pressure 165/109 mm Hg) and 10 normal controls matched for age and weight were studied for the hypotensive potential of moderate exercise. Tests were conducted on a treadmill set to induce a steady heart rate of 120 beats/min and performed over five 10-minute periods separated by three minutes'' rest and finishing with 30 minutes'' sitting quietly in a chair.During exercise the mean systolic pressures were identical in the hypertensive patients and controls (175±SEM 5 mm Hg), the controls therefore sustaining an appreciably greater increase in pressure. During the 30-minute rest period after the tests both the control and hypertensive groups showed a significant and sustained fall in absolute systolic pressures as compared with pre-exercise values (p <0·001), the mean percentage reductions being 22% and 25% respectively.If a fall in blood pressure after exercise is maintained for four to 10 hours, then a “good walk” twice a day might be reasonable treatment for mild hypertension. Studies are continuing to determine the amount of exercise needed and the duration for which the reduction in blood pressure is maintained.     

How does salt retention raise blood pressure?

A critical question in hypertension research is: How is long-term blood pressure controlled? Excessive NaCl ingestion or NaCl retention by the kidneys and the consequent tendency toward plasma volume expansion lead to hypertension. Nevertheless, the precise mechanisms linking salt to high blood pressure are unresolved. The discovery of endogenous ouabain, an adrenocortical hormone, provided an important clue. Ouabain, a selective Na+ pump inhibitor, has cardiotonic and vasotonic effects. Plasma endogenous ouabain levels are significantly elevated in approximately 40% of patients with essential hypertension and in animals with several forms of salt-dependent hypertension. Also, prolonged ouabain administration induces hypertension in rodents. Mice with mutant Na+ pumps or Na/Ca exchangers (NCX) and studies with a ouabain antagonist and an NCX blocker are revealing the missing molecular mechanisms. These data demonstrate that alpha2 Na+ pumps and NCX1 participate in long-term regulation of vascular tone and blood pressure. Pharmacological agents or mutations in the alpha2 Na+ pump that interfere with the action of ouabain on the pump, and reduced NCX1 expression or agents that block NCX all impede the development of salt-dependent or ouabain-induced hypertension. Conversely, nanomolar ouabain, reduced alpha2 Na+ pump expression, and smooth muscle-specific overexpression of NCX1 all induce hypertension. Furthermore, ouabain and reduced alpha2 Na+ pump expression increase myogenic tone in isolated mesenteric small arteries in vitro, thereby tying these effects directly to the elevation of blood pressure. Thus, endogenous ouabain, and vascular alpha2 Na+ pumps and NCX1, are critical links between salt and hypertension. New pharmacological agents that act on these molecular links have potential in the clinical management of hypertension.