The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity.

AIMS/HYPOTHESIS: Chemical and biological characteristics of LDL(-) from type 1 diabetic subjects were analysed. The diabetic patients were studied during poor and optimised glycaemic control. MATERIALS AND METHODS: Total LDL was subfractionated into electropositive LDL(+) and electronegative LDL(-) by anion exchange chromatography and the lipid and protein composition of the two determined. RESULTS: LDL(-) differed from LDL(+) in that it had higher triglyceride, non-esterified fatty acids, apoE, apoC-III and platelet-activating factor acetylhydrolase (PAF-AH), as well as lower apoB relative content. No evidence of increased oxidation was observed in LDL(-). LDL(-) increased two-fold the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells, suggesting an inflammatory role. Optimisation of glycaemic control after insulin therapy decreased the proportion of LDL(-), but did not modify the composition of LDL subfractions, except for a decrease in PAF-AH activity in LDL(-). The possibility that LDL(-) could be generated by non-enzymatic glycosylation was studied. Fructosamine and glycated LDL content in LDL subfractions from type 1 diabetic patients was greater than in LDL subfractions isolated from normoglycaemic subjects, and decreased after glycaemic optimisation in both subfractions. However, no difference was observed between LDL(+) and LDL(-) before and after insulin therapy. CONCLUSIONS/INTERPRETATION: These results provide evidence that LDL(-) is not produced by glycosylation. Nevertheless, LDL(-) from diabetic patients displays inflammatory potential reflected by the induction of chemokine release in endothelial cells. This proatherogenic effect could be related to the high PAF-AH activity in LDL(-).

Emerging cardiovascular risk factors in subclinical hypothyroidism: lack of change after restoration of euthyroidism.

Subclinical hypothyroidism (SH) is a frequent condition that may be associated with increased cardiovascular risk. There is current interest in determining the effect, if any, of substitutive therapy with l-thyroxine (L-T4) on cardiovascular risk factors in SH and, particularly, on those associated with emerging cardiovacular risk, such as apolipoprotein (apo) B, lipoprotein (Lp) (a), total homocysteine (t-Hcy), and C-reactive protein (CRP). Thus, the aim of this study was to assess the impact of euthyroidism restoration on these emerging risk factors in SH. Forty-two patients diagnosed with SH were consecutively recruited before treatment. These patients were treated with L-T4 for 3 to 6 months with the dose necessary to restore euthyroidism. Lp(a), fasting and postmethionine (n = 28) t-Hcy, and CRP did not change with substitutive therapy, regardless of the respective baseline values, and the decrease in apo B paralleled that of low-density lipoprotein (LDL) cholesterol. Similarly, no treatment effect was observed on homocysteine or CRP in patients with thyrotropin-stimulating hormone (TSH) >10 mIU/L. Monitoring of emerging risk factors did not offer additional arguments for treating patients with SH and, thus, is not justified in their clinical management.

Comparison of the Abbott IMx and a high-performance liquid chromatography method for measuring total plasma homocysteine.

The determination of the total concentration of plasma homocysteine is of interest in a variety of clinical circumstances, especially, in the evaluation of the risk of cardiovascular disease. However, most of the methods available to date, many of them chromatographic, are not well suited for the majority of clinical laboratories. Several automated methods are now or will be, shortly, commercially available. We have compared one of them, the fluorescence polarization immunoassay (FPIA) adapted to the IMx analyzer (Abbott Laboratories), with the high-performance liquid chromatography (HPLC) method with fluorescent detection currently used in our laboratory. The results show that the FPIA-IMx method is less imprecise and slightly more sensitive than the HPLC. The comparison of 67 clinical plasma specimens indicated that there is a proportional error disagreement between FPIA-IMx and HPLC (FPIA=1.19 HPLC + 0.92; confidence region for slope and y-intercept were, respectively, from 1.06 to 1.31 and from -0.06 to 2.32). The nature of this error is not explained by the experiments performed to study the inaccuracy of both methods, which included the investigation of dilution parallelism, analytical recovery and cross-reactivity. The different results of homocysteine concentration obtained with FPIA-IMx and HPLC must be taken into account when a change of methodology is under consideration.

Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome.

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.

Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?

The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.

Levodopa does not aggravate postural tremor in Parkinson's disease.

Characterization of postural tremor in Parkinson's disease (PD) is incomplete. It was suggested to be an exaggerated physiological tremor and to be enhanced by the action of levodopa. We compared the magnitude of postural tremor to the magnitude of rest tremor and to plasma levodopa levels in 20 PD patients, 10 with stable motor response to oral levodopa, and 10 with the wearing-off phenomenon. Tremor assessment included motor scores of the Unified Parkinson's Disease Rating Scale and accelerometric measurements. Accelerometric data showed that the absolute power of both rest and postural basal dominant tremor frequencies significantly diminished with the increase in plasma levodopa levels and increased with their decrease. Tremor frequencies were also significantly changed by levodopa, which slowed rest tremor and increased postural tremor dominant frequency. This latter, however, did not reach the 8- to 12-Hz frequency band said to be typical of exaggerated physiological tremor. No significant differences between groups were found in their tremor response to levodopa. This study shows that the net postural tremor exhibited by PD patients is improved by levodopa, that levodopa does not augment tremor in the 8- to 12-Hz range, and that this effect is independent of the patient's motor response pattern of oral levodopa.

Dipyrone interference on several common biochemical tests.

We studied the effect in vitro and in vivo of dipyrone on the determination of several biochemical tests in two analyzers, a Hitachi 747 and a Kodak Ektachem 700. From studies in vitro, we found significant interference by dipyrone (P < 0.05) in the determination of creatine kinase (CK), lactate dehydrogenase (LD), uric acid, triglycerides, cholesterol, aspartate aminotransferase, alanine aminotransferase, and urea nitrogen with both instruments, and in the determination of creatinine in the Ektachem analyzer. We also studied the effect of intravenously administered dipyrone in 14 patients. Dipyrone interfered significantly (P < 0.05) in the determination of CK, LD, uric acid, triglycerides, and cholesterol with both instruments, and creatinine only with the Ektachem analyzer. Using high-performance liquid chromatography (HPLC), we measured concentrations of dipyrone in the serum of patients who had received the drug and observed a negative correlation between the concentrations of dipyrone in the blood and the percentage of each analyte concentration.

[Effectiveness of rectal metromidazole in acute infantile appendicitis]. / Eficacia del metronidazol rectal en la apendicitis aguda infantil.

Thirty two consecutive children who underwent surgery for suspected acute appendicitis, were treated with prophylactic metronidazole suppositories. A serum sample was taken at surgery to determine the serum concentration of the drug. After a preoperative dose of 15-20 mg/kg the minimal bactericidal concentration was achieved in almost all cases at the time of anesthetic induction. This drug showed an optimal biodisponibility when used rectally and no side-effects was noted. Neither a wound-infection, nor a wound-sepsis was reported and a satisfactory outcome was registered. We conclude that rectal dosing with metronidazole is effective for prophylactic wound infection in acute appendicitis.