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PubMed1993

Immunoelectrophoresis and ELISA techniques for assay of plasma beta 2 glycoprotein-1 and the influence of plasma lipids.

Beta 2 glycoprotein-1 (beta 2GP1) has been identified as a cofactor for the binding of some antiphospholipid antibodies to anionic phospholipids and has been demonstrated to possess anticoagulant properties in vitro. We have investigated Laurell rocket immunoelectrophoresis (IEP) and ELISA techniques for measurement of beta 2GP1. Western blotting and crossed immunoelectrophoresis (CIE) of plasma demonstrated free beta 2GP1 and beta 2GP1 complexed with unidentified plasma constituents. The free and complexed forms were not distinguished in immunoelectrophoresis assays, allowing measurement of total beta 2GP1. Standard and detergent modified IEP and ELISA techniques were compared: significant correlation was demonstrated between unmodified and detergent modified IEP, detergent modified IEP and ELISA and unmodified IEP and ELISA. The intra-assay co-efficients of variation (CVs) of the unmodified and modified IEPs and ELISA were 7.5, 3.7 and 7.9%. Inter-assay CVs determined for the modified IEP and ELISA were 5.8 and 9.1% respectively. The purified beta 2GP1 used to standardise the assays was shown to have subfraction selectivity and different calibration values were obtained for pooled normal plasma by the unmodified IEP (242 mg/l) and modified IEP and ELISA (201 mg/l). We have also investigated the influence of some pre-test variables on beta 2GP1 levels and shown that heparin, citrate or EDTA plasma and serum samples are suitable for assay of this glycoprotein and that levels are unaffected by repeated freeze/thawing. The influence of plasma lipids on beta 2GP1 measurement was also examined and we demonstrated no significant differences between pre and postprandial samples, which suggests that fasting status is not an important consideration for assay of beta 2GP1 in healthy subjects.

Apolipoproteins↗
PubMed1995

Plasma pancreastatin-like immunoreactivity correlates with plasma norepinephrine levels in essential hypertension.

Pancreastatin (PST), a 49 amino acid peptide originally isolated from porcine pancreas, is derived from chromogranin A (Cg A), an acidic protein co-released with catecholamines from sympathetic nerve terminals and chromaffin cells. Extracellular processing of Cg A yields PST as well as other biological active peptides. Measurement of Cg A and PST-like immunoreactivity (PST-LI) has been used to investigate patients with pheochromocytoma and other neuroendocrine neoplasia. Some studies have found increased plasma norepinephrine (NE) levels in essential hypertension. We therefore measured venous plasma PST-LI and catecholamines in patients with essential hypertension. We employed a radioimmunoassay developed with commercially available reagents for measuring plasma PST-like immunoreactivity, and HPLC with electrochemical detection for measurement of plasma catecholamines. The correlation of PST-LI with epinephrine (E) was very weak. However, its correlation with NE was highly significant. Thus, venous plasma PST-LI immunoreactivity may reflect sympathetic nerve activity in essential hypertension.

Adult↗
PubMed1990

Topical application of the hypoglycemic agent glibenclamide and changes in blood glucose, plasma insulin (IRI) levels and plasma concentration of glibenclamide in normal rats.

This study was done to determine whether an oral hypoglycemic agent would be absorbed through the skin and consequently lower blood glucose levels. We applied 250 mg or 500 mg of 5% glibenclamide ointment (GO) to the cleanly shaved dorsa (5 x 10 cm) of overnight-fasted male Wistar rats, weighing 250-300 g. Blood samples were collected at 1, 3, 6, 12 and 24 h after the application of GO and blood glucose, plasma insulin (IRI) and the plasma concentration of glibenclamide were determined. The plasma concentration of glibenclamide reached a high level as early as 1 h after application and the level was maintained for 24 h. The plasma concentration of glibenclamide in the 500-mg GO group was higher than in the 250-mg GO group, but even 24 h after application the 250-mg GO group showed a mean value of 206 ng/ml. Mean blood glucose levels in both GO groups at every time point after application were significantly lower than in the control group; with respect to mean IRI levels the opposite was found. Thus, glibenclamide is absorbed through the skin and reaches a level of plasma concentration which induces significant changes in blood glucose and IRI levels. This may well be a new approach to controlling blood glucose levels in patients with diabetes mellitus.

Administration, Topical↗
PubMed1991

The transport of vitamin E in plasma and its correlation to plasma lipoproteins in non-insulin-dependent diabetes mellitus.

It is known that plasma low density lipoproteins (LDL) contain a great amount of vitamin E and that LDL enter cells via the specific receptor-mediated mechanism. In this study, we aimed to investigate the transport of alpha-tocopherol from plasma to tissues in subjects with non-insulin-dependent diabetes mellitus (NIDDM) with poor glycaemic control; and the relationships between alpha-tocopherol and plasma lipid and lipoprotein levels. alpha-Tocopherol determination was carried out by colorimetric assay according to the modified micromethod of Fabianek et al. The mean plasma alpha-tocopherol and (LDL + VLDL)-alpha-tocopherol levels increased significantly in the diabetic group as compared to control (P less than 0.05 and P less than 0.02), whereas the high density lipoprotein (HDL)-alpha-tocopherol level was significantly lower in the diabetic group than that in the controls (P less than 0.05). Correlations between plasma alpha-tocopherol levels showed close positive relationships (r = 0.87, r = 0.75 and r = 0.78, respectively, P less than 0.001). A strong positive correlation was also observed between alpha-tocopherol and the cholesterol content, either in the HDL or in the (LDL + VLDL) fractions (r = 0.75 and r = 0.77; P less than 0.001). These findings indicate that there is a direct positive relationship between lipid and alpha-tocopherol concentrations. The increased level of alpha-tocopherol in the LDL + VLDL fraction and decreased level in HDL in these patients could be attributed to the impairment of the cholesterol uptake of the cells by the receptor mediated mechanism.

Blood Glucose↗
PubMed1995

Pharmacoclinical correlations in schizophrenic patients treated with haloperidol decanoate: clinical evaluations, concentrations of plasma and red blood cell haloperidol and its reduced metabolite, and plasma homovanillic acid.

1. The aim of this open study was to determine whether a more rational therapeutic approach could be devised for psychotic patients (n = 11) treated for long periods with long-acting (LA) haloperidol. The mean multiplication factor for the transition from the oral formulation to the long-acting one was 12.8 (10.4, standard deviation), lower than the theoretically recommended factor of 20. 2. The best dose (mg/kg)-concentration correlations were found for haloperidol (HAL) and reduced HAL (RHAL) in the red blood cells (RBC) (representative of the free drug fraction) rather than in the plasma of patients that had attained the steady state (at the third cycle and afterwards) 3. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the BPRS and determinations of plasma levels of total, free and conjugated homovanillic acid (HVA), a marker of central dopaminergic activity. 4. A between groups comparison at the steady state (patients (n = 20) with oral administration and the above patients (n = 11) with long-acting form of HAL), showed that the plasma and RBC RHAL/HAL ratios of long-acting HAL decreased significantly (p < 0,005) in comparison with oral administration, at least by half. 5. Plasma HVA values complete the information provided by plasma and more especially RBC HAL and RHAL levels. All these results taken together, as substantiated by the clinical assessment scales (BPRS), assure a better pharmacoclinical surveillance and can be predictive of a patient's response.

Adult↗
PubMed1984

Plasma lipoprotein profiles and arylesterase activities in two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol.

Cholesterol feeding for 4 weeks of female and male rabbits of two inbred strains increased plasma cholesterol concentrations by about 11 and 48 mmole/1 in the hypo- and hyperresponsive strain, respectively. On the low-cholesterol pre-experimental diet, the hyporesponsive animals had significantly higher plasma HDL (high density protein) cholesterol levels than hyperresponders. In both strains, cholesterol feeding caused elevations of cholesterol in all lipoprotein classes, the difference between the hypo- and hyperresponsive strains in essence only being observed in the VLDL (very low density lipoprotein) fraction. Basal plasma total arylesterase activity was significantly higher in the hypo- than in the hyperresponsive rabbits. Dietary cholesterol caused an increase in plasma esterase activity in both We suggest that in rabbits a low plasma arylesterase activity and a low concentration of HDL cholesterol are associated with an increased sensitivity to dietary cholesterol.

Animals↗
PubMed1994

Simultaneous determination of plasma haloperidol and its metabolite reduced haloperidol by liquid chromatography with electrochemical detection. Plasma levels in schizophrenic patients treated with oral or intramuscular depot haloperidol.

A simple and highly sensitive liquid chromatographic method with electrochemical detection for the simultaneous determination of haloperidol and its metabolite reduced haloperidol in human plasma has been developed. The sample preparation for the analysis involves a simple one-step extraction procedure with 10% methylene chloride in pentane. The compounds were separated on a cyano column maintained at a temperature of 40 degrees C and were detected electrochemically by a flow-through analytical cell kept at +0.95 V. The standard curve is linear over the range of 0.1 to 15 ng/ml and the lower limit of quantitation is 0.1 ng/ml for haloperidol and 0.25 ng/ml for reduced haloperidol which is equivalent to approximately 40 pg on column when 1 ml of plasma was used for the analysis. The lower limit of quantitation for reduced haloperidol can be extended to 0.1 ng/ml if 2 ml of plasma is used in the analysis. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%. Commonly co-administered drugs and other neuroleptics used in conjunction with haloperidol did not interfere in the determination of either haloperidol or reduced haloperidol. This method has been successfully used for the determination of haloperidol and reduced haloperidol in plasma and their levels in patients treated with various doses oral haloperidol or intramuscular haloperidol decanoate are reported.

Administration, Oral↗
PubMed2004

Liquid chromatographic-tandem mass spectrometric assay for the simultaneous determination of didanosine and stavudine in human plasma, bronchoalveolar lavage fluid, alveolar cells, peripheral blood mononuclear cells, seminal plasma, cerebrospinal fluid and tonsil tissue.

We have developed a sensitive, high-pressure liquid chromatographic-tandem mass spectrometric (LC/MS/MS) method for the simultaneous determination of didanosine (ddI) and stavudine (d4T) in human plasma, bronchoalveolar lavage fluid (BALF), alveolar cells (AC), peripheral blood mononuclear cells (PBMC), seminal plasma, cerebrospinal fluid (CSF), and tonsil tissue. Plasma, AC, PBMC and CSF were run with an isocratic HPLC method, while BALF supernatant, semen, and tonsil tissue utilized a gradient elution. Samples were prepared by solid phase extraction. Detection was by electrospray positive ionization with multiple reaction monitoring mode. The lower limits of quantitation for both ddI and d4T were 2.0 ng/ml in plasma; 0.5 ng/ml in CSF; 0.4 ng/ml in AC, PBMC, and BALF; 1.0 ng/ml in seminal plasma; and 0.01 ng/mg in tonsil tissue.

Bronchoalveolar Lavage Fluid↗
PubMed2006

Determination of ziprasidone in human plasma by liquid chromatography-electrospray tandem mass spectrometry and its application to plasma level determination in schizophrenia patients.

An accurate, rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS-MS) assay method was developed for the determination of ziprasidone (ZIP) in the plasma of schizophrenia patients. A simple one step liquid-liquid extraction with 20% methylene dichloride in pentane was used to isolate ZIP and the internal standard from the plasma matrix. The compounds were separated on a C-18 column by an isocratic elution and the eluted compounds were analyzed by a triple quadrupole mass spectrometer with a TurboIon spray interface using the positive ion atmospheric pressure electrospray ionization method and detected using multiple reaction monitoring mode. The ZIP standard calibration curve was linear over the range of 0.25-500ng/ml when 0.5ml of plasma was used for the analysis (r(2)>0.998). The intra-assay (within-day) and inter-assay (between-day) variations were less than 12% for the spiked standard curve and quality control samples. The absolute extraction efficiency was 82% for ZIP and 68% for INS-RSP. The analysis time for each sample was less than 3min and useful for high turnaround plasma level determinations. This LC-MS-MS assay method for ZIP is highly specific, sensitive, accurate and rapid and is currently being used for the plasma level determination of ZIP in schizophrenia patients treated with various daily oral doses of ZIP. The data showed large inter-individual variations.

Adult↗
PubMed2004

Vascular endothelium is the organ chiefly responsible for the catabolism of plasma asymmetric dimethylarginine--an explanation for the elevation of plasma ADMA in disorders characterized by endothelial dysfunction.

Plasma levels of asymmetric dimethylarginine (ADMA), an endogenously produced competitive inhibitor of nitric oxide synthase (NOS), have been found to be elevated in a large number of disorders characterized by endothelial dysfunction; this remarkable phenomenon has yet to receive a plausible explanation. ADMA arises by proteolysis of methylated proteins throughout the body; the majority of this ADMA is catabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), found in many tissues, including those that express NOS. Since the production of ADMA can be considered constitutive, and little intact ADMA emerges in the urine, impaired catabolism is most likely responsible for elevations of plasma ADMA. The association of elevated ADMA with endotheliopathy is readily explained if we assume that vascular endothelium is the organ chiefly responsible for the catabolism of plasma ADMA--a view that is credible owing to the privileged access of endothelium to plasma, the capacity of endothelium for active transport of arginine (and methylated arginines), and the ample DDAH activity of healthy endothelial cells--and further assume that endothelial dysfunction is often attended by a loss of DDAH activity and/or an impairment of arginine transport, reducing the efficiency of ADMA catabolism. Indeed, there is recent evidence that DDAH is inhibited by endothelial oxidative stress, a typical feature of endotheliopathy; there is also some reason to suspect that arginine transport may be less efficient in dysfunctional endothelium. From this perspective, increased plasma ADMA is not the primary cause of the endothelial dysfunction in various disorders, but rather its effect--though the rise in ADMA can then exacerbate this dysfunction by inhibiting endothelial NOS. Supplemental arginine should be of some clinical benefit in disorders characterized by elevated ADMA, since it can offset that adverse impact of ADMA on NOS activity, and possibly exert other beneficial effects on endothelium--but it cannot be expected to reverse the primary cause of the endothelial dysfunction. Whether or not ADMA plays an important pathogenic role, it seems likely to emerge as a potent risk factor for adverse vascular events, since it may be viewed as a barometer of endothelial health.

Amidohydrolases↗
PubMed2006

Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma.

Dietary or pharmacological manipulation of plasma lipids markedly influences amyloid deposition in animal models of Alzheimer's Disease (AD). However, it is not known whether baseline plasma lipids in AD models differ from wild-type littermates throughout the natural history of disease. To address this question, we measured plasma total cholesterol and triglyceride levels over time in three transgenic AD mouse models in the absence of dietary or pharmacological treatments. Total cholesterol levels were not significantly different between transgenic and wild-type mice during the development of AD neuropathology in all models tested. In contrast, elevated very-low-density lipoprotein (VLDL) triglyceride levels preceded amyloid deposition in two AD models with abundant plasma A beta. Elevated triglycerides were not accompanied by increased inflammatory markers nor decreased lipase activity, but were associated with a significant 30% increase in VLDL-triglyceride secretion rate. Our results suggest that the presence of A beta in plasma may affect peripheral lipid metabolism early in AD pathogenesis.

Alzheimer Disease↗
PubMed2001

The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)).

OBJECTIVES: To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FER(HDL)) and lipoprotein particle size. DESIGN AND METHODS: We analyzed previous data dealing with the parameters related to the FER(HDL) (an indirect measure of lipoprotein particle size). In a total of 1433 subjects from 35 cohorts with various risk of atherosclerosis (cord plasma, children, healthy men and women, pre- and postmenopausal women, patients with hypertension, type 2 diabetes, dyslipidemia and patients with positive or negative angiography findings) were studied. RESULTS: The analysis revealed a strong positive correlation (r = 0.803) between FER(HDL) and Log(TG/HDL-C). This parameter, which we propose to call "atherogenic index of plasma" (AIP) directly related to the risk of atherosclerosis in the above cohorts. We also confirmed in a cohort of 35 normal subjects a significant inverse correlation of LDL size with FER(HDL) (r = -0.818) and AIP (r = -0.776). CONCLUSION: Values of AIP correspond closely to those of FER(HDL) and to lipoprotein particle size and thus could be used as a marker of plasma atherogenicity.

Adult↗
PubMed1999

Plasma levels of the soluble fraction of tumor necrosis factor receptors 1 and 2 are independent determinants of plasma cholesterol and LDL-cholesterol concentrations in healthy subjects.

In the last few years, it has been demonstrated that tumor necrosis alpha (TNF-alpha) has important effects on whole-body lipid metabolism. TNF-alpha administration has been found to produce an increase in serum cholesterol levels and increased hepatic hydro-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase activity in mice. The purpose of this study was to test whether plasma levels of the soluble forms of the TNF-alpha receptors 1 and 2 (sTNFR1, sTNFR2) are associated with lipid abnormalities. A total of 36 healthy subjects (19 males, mean age 36.2 +/- 1.9, and 17 females, mean age 34.9 +/- 1.4) were studied. Plasma sTNFR1 levels correlated with total (r = 0.43, P = 0.01) and LDL-cholesterol (r = 0.52, P = 0.002) levels, but not with total or HDL2-HDL3 subfractions of HDL-cholesterol, total plasma triglycerides, VLDL-cholesterol or VLDL-triglycerides (all r < 0.11, P = NS). Plasma sTNFR2 levels also correlated with total (r = 0.44, P = 0.009) and LDL-cholesterol (r = 0.57, P < 0.0001) levels, and negatively with HDL2-cholesterol (r = -0.37, P = 0.029). A stepwise multiple linear regression was constructed to predict total cholesterol levels, with BMI, sex, age, sTNFR1 or sTNFR2 as independent variables. Both sTNFR1 and sTNFR2 were significantly associated with total cholesterol (P = 0.031 and 0.009), contributing to 26 and 19%, respectively, of its variance. In another model in which LDL-cholesterol was substituted for total cholesterol, sTNFR1 or sTNFR2 (P = 0.0084 and 0.0005) were significantly associated with LDL-cholesterol, contributing to 39 and 32% of its variance. In summary, plasma levels of sTNFR1 and sTNFR2 circulate in proportion to total and LDL-cholesterol in healthy subjects.

Adolescent↗
PubMed2000

Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels.

A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025 individuals with respect to the effect of the 68-bp insertion (844ins68 variant) of the cystathionine beta-synthase (CBS) gene, the A(2756)G transition of the B(12)-dependent methionine synthase (MS) gene and the C(677)T transition of the methylenetetrahydrofolate reductase (MTHFR) gene on fasting and 4 h PML tHcy. Of these individuals, 153 (14.9%) were heterozygous for the 68-bp insertion, 329 (32.1%) were heterozygous for the G(2756) allele and 122 (11.9%) were homozygous for the C(677)T transition. Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations, while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels. A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy, confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive. The effects are opposite but additive with the C(677)50% of all individuals in this study carried polymorphic traits, which predisposed them to either higher or lower plasma tHcy concentrations, thus providing new evidence of the importance of genetic influences as determinants of tHcy levels.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2003

Effect of spark plasma sintering on the microstructure and in vitro behavior of plasma sprayed HA coatings.

The crystalline phases and degree of crystallinity in plasma sprayed calcium phosphate coatings on Ti substrates are crucial factors that influence the biological interactions of the materials in vivo. In this study, plasma sprayed hydroxyapatite (HA) coatings underwent post-spray treatment by the spark plasma sintering (SPS) technique at 500 degrees C, 600 degrees C, and 700 degrees C for duration of 5 and 30 min. The activity of the HA coatings before and after SPS are evaluated in vitro in a simulated body fluid. The surface microstructure, crystallinity, and phase composition of each coating is characterized by scanning electron microscopy and X-ray diffractometry before, and after in vitro incubation. Results show that the plasma sprayed coatings treated for 5 min in SPS demonstrated increased proportion of beta-TCP phase with a preferred-orientation in the (214) plane, and the content of beta-TCP phase corresponded to SPS temperature, up to 700 degrees C. SPS treatment at 700 degrees C for 30 min enhanced the HA content in the plasma spray coating as well. The HA coatings treated in SPS for 5 min revealed rapid surface morphological changes during in vitro incubation (up to 12 days), indicating that the surface activity is enhanced by the SPS treatment. The thickest apatite layer was found in the coating treated by SPS at 700 degrees C for 5 min.

Biomimetic Materials↗
PubMed2002

Translocation of pyrene-labeled phosphatidylserine from the plasma membrane to mitochondria diminishes systematically with molecular hydrophobicity: implications on the maintenance of high phosphatidylserine content in the inner leaflet of the plasma membrane.

To study the translocation of phosphatidylserine (PS) from plasma membrane to mitochondria, dipyrene PS molecules (diPyr(n)PS; n=acyl chain length) were introduced to the plasma membrane of baby hamster kidney cells (BHK cells) using either cyclodextrin-mediated monomer transfer or fusion of cationic vesicles. Translocation of diPyr(n)PS to mitochondria was assessed based on decarboxylation by mitochondrial PS decarboxylase (PSD). It was found that the rate of translocation diminishes systematically with acyl chain length (molecular hydrophobicity) of diPyr(n)PS. Using an in vitro assay, it was shown that the spontaneous translocation rates of long-chain diPyr(n)PS species are similar to those of common natural PS species, thus supporting the biological relevance of the data. These results, and other data arguing against the involvement of vesicular traffic and lipid transfer proteins, imply that spontaneous monomeric diffusion via the cytoplasm is the main mechanism of PS movement from the plasma membrane to mitochondria. This finding could explain why a major fraction of PS synthesized by BHK cells consists of hydrophobic species: such species have little tendency to efflux from the plasma membrane to mitochondria where they would be decarboxylated. Thus, adequate molecular hydrophobicity seems to be crucial for the maintenance of high PS content in the inner leaflet of the plasma membrane.

Animals↗
PubMed2002

Plasma profiles of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1.

BACKGROUND: This study investigates the plasma activity of inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), C-C chemokines and soluble adhesion molecules, produced by monocyte-endothelial cell adhesive interaction, in patients with arterial hypertension. METHODS: We studied 66 untreated patients with mild to moderate arterial hypertension (hypercholesterolemic: 34, normocholesterolemic: 32) and 30 sex- and age-matched normocholesterolemic normotensive controls. Plasma concentrations of GM-CSF, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES (regulated on activation normally T-cell expressed and secreted), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), as well as plasma endothelin-1 (ET-1), were determined in study population by ELISA and RIA, respectively. RESULTS: Hypertensives exhibited significantly higher levels of GM-CSF (6.5+/-1.3 vs. 2.3+/-0.7 pg/ml, P=0.099), MCP-1 (175+/-31 vs. 120+/-24 pg/ml, P=0.0093), MIP-1alpha (23+/-4 vs. 15+/-2 pg/ml, P=0.0089), RANTES (17+/-4 vs. 14+/-3 ng/ml, P=0.047), sICAM-1 (235+/-39 vs. 187+/-21 ng/ml, P=0.0041), sVCAM-1 (684+/-42 vs. 589+/-23 ng/ml, P=0.0045) and ET-1 (6.1+/-1.5 vs. 2.4+/-0.3 pg/ml, P=0.0095) than those of normotensives. The normocholesterolemic hypertensives had significantly lower levels of GM-CSF, MCP-1, MIP-1alpha, sICAM-1 and sVCAM-1 than hypercholesterolemic hypertensives but higher than normotensives. In hypertensives, ET-1 levels were significantly correlated with mean arterial pressure (r=0.51, P=0.028), MCP-1 values (r=0.45, P=0.047) and sICAM-1 levels (r=0.64, P=0.0090). Significant correlations were also found between LDL cholesterol values and plasma inflammatory factors GM-CSF (r=0.58, P=0.0088), MCP-1 (r=0.49, P=0.040) and sICAM-1 (r=0.53, P=0.034) in the hypercholesterolemic sub-group of hypertensives. CONCLUSIONS: Inflammatory markers of monocyte-endothelial cell adhesive interaction are elevated in hypertensives in comparison to normotensives and may be related to plasma ET-1 activity. The coexistence of hypercholesterolemia may enhance this inflammatory process induced by arterial hypertension.

Biomarkers↗
PubMed2002

Long-term pharmacoclinical follow-up in schizophrenic patients treated with risperidone. Plasma and red blood cell concentrations of risperidone and its 9-hydroxymetabolite and their relationship to whole blood serotonin and tryptophan, plasma homovanillic acid, 5-hydroxyindoleacetic acid, dihydroxyphenylethyleneglycol and clinical evaluations.

The aim of the study was to establish a relationship between the clinical efficacy of risperidone (Risp), the biological levels of Risp and its metabolite, 9-hydroxyrisperidone (9-OH-Risp), and the turnover of blood biogenic amines during a long-term treatment (1 year). Risp is one of the newer atypical antipsychotic drugs with potent serotonin (5HT2), moderate D2 and real alpha 1-alpha 2 adrenoreceptor antagonistic effects. The study has been performed in an open setting and included 17 patients, but only 15 were followed-up from 3 to 12 months. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI), the Global Assessment of Functioning Scale (GAF), the Quality of Life Scale (QLS) and the Extrapyramidal Symptoms Rating Scale (ESRS) and the determinations of plasma and red blood cell (RBC) Risp and 9-OH-Risp, whole blood 5HT and tryptophan (Trp), plasma homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5HIAA) and dihydroxyphenylethyleneglycol (DHPG). The therapeutic drug monitoring needed oral Risp daily dose of 4.5 +/- 2.3 mg (range 2-8) and the stabilized concentrations (ng/ml) at endpoint in plasma and RBC were 10 +/- 8 (range 1-23) and 3.5 +/- 2 (range 1-8) for Risp and 29 +/- 19 (range 8-70) and 11.5 +/- 6.6 (range 2.6-22.5) for 9-OH-Risp, respectively. 9-OH-Risp appears to be the major active metabolite compound at higher concentrations than Risp. Positive linear correlations were found only between plasma and RBC 9-OH-Risp and the daily dose and the score of the GAF. Statistically significant clinical results showed that Risp is a potent antipsychotic agent efficacious both on positive and negative symptoms and on quality of life. Positive symptoms decreased after about the second month and the negative symptoms improved secondly. Patients (n = 8) who responded to Risp were characterized, on the long-term, by a statistically significant decrease of whole blood 5HT and increase of plasma DHPG.

Adult↗