Homocysteine levels and cardiovascular disease in migraine with aura

Clinical studies suggest that hyperhomocysteinemia could be considered an independent risk factor for premature cerebral, peripheral and vascular diseases. A number of authors found an epidemiological correlation between increased risk of cerebrovascular disease and migraine with aura. In this study, 34 patients suffering from migraine with aura and 36 healthy controls were evaluated with respect to total plasma homocysteine levels, measured with FPIA immunoassay in the fasting state and after methionine load. Moreover, vitamin B12, folate and other classic biochemical indicators of atherosclerosis disease were evaluated. In this study, homocysteine levels, both at basal and after load, and other cardiovascular risk factors such as vitamin B12 and apo-LpA were within the normal range. Other multicentric randomised trials are needed to carry on and confirm these data

Trend of drug detection in urine samples tested at the University Hospital of Modena, during a 10-year period

A retrospective analysis of data from 1997 to 2006 from over 30.000 urinalysis screening between 1997 and 2006 has been performed. Urine samples had been tested at the laboratory of the Clinical Pharmacology and Toxicology service of the University Hospital of Modena by enzyme-multiplied immunoassay. All tests have been requested by the departments of the hospital, included emergency department; urine specimens have been analysed for the presence of opiates, cocaine, cannabinoids, and amphetamines. Results: as a whole the percentage of samples positive declined over the 10-year period for all drugs tested. However the pattern changed in time: in the period 1997-1999 the drugs most often detected were opiates followed cannabinoids and in the period 2004-2006 the drugs most often detected were cannabinoids followed by opiates and cocaine at the same level. The detection of opiates peaked between 1997-1999 (mean 25.47%) then decreased over the following seven year to 5.2% in 2006. Detection of cannabis also decreased from a mean of 16% of all samples during 1997-1999 to 7.6% in 2006. The percentage of urine samples that were positive for amphetamine-class drugs decreased from a mean of 4.3% to 1.09% in 2006. The detection of cocaine and its metabolites peaked between 1998-2001 (mean 10.4%) then declined to a mean of 5.9% in the period 2004-2006.Conclusions: Since 1996 implementation at the drug services units of the province of Modena of harm reduction policies, mainly methadone maintenance treatment, has been followed by a reduction of drug addicts hospitalised for health damage associated with injection practices as shown by the substantial fall of samples positive for opiates from 1997 to 2006. However, in 2006, cannabis, opiates, cocaine, and amphetamines continued to be detected in percentages ranging from 1 to 7 % of urine samples ….

Plasma glutathione level in paracetamol daily abuser patients. Changes in plasma cysteine and thiol groups after reduced glutathione administration

Since plasma reduced glutathione (GSH) seems to reflect liver GSH content, we have assessed plasma GSH in patients using paracetamol daily. In these patients a significant lower plasma GSH concentration was found with respect to controls. After the i.v. administration of GSH free plasma cysteine was 12 fold higher than in basal condition and all the pattern of plasma thiol groups was modified. This work suggests that the possible protective effect of GSH administration is due to the availability of plasma thiol compounds that enter the cell rather than GSH itself

Dopaminergic control of renal tubular function in patients with compensated cirrhosis

In normal humans, plasma dopamine levels rise during head-out water immersion or saline intravenous infusion. Dopamine inhibits NA(+),K+-ATPase activity in the proximal tubule and blunts aldosterone secretion leading to increased diuresis and natriuresis. The aim of this study is to evaluate the role of endogenous dopaminergic activity in the intrarenal sodium handling in patients with compensated liver cirrhosis. We studied nine healthy controls and 12 patients with Child-Pugh A cirrhosis during a normosodic diet for (1) dopaminergic activity, as measured by the incremental aldosterone responses 30 and 60 min after intravenous metoclopramide administration; (2) basal plasma levels of active renin and aldosterone; (3) 4-hr renal clearance of lithium (an index of fluid delivery to the distal tubule), creatinine, sodium, and potassium, first without and then with dopaminergic blockade with intravenous metoclopramide. The patients displayed greater endogenous dopaminergic activity, evidenced by higher incremental aldosterone responses compared with controls (+30 min: 160.2 68.8 vs 83.6 +/- 35.2 pg/ml, P < 0.01; +60 min: 140.5 +/- 80.3 vs 36.8 +/- 39.1 pg/ml, P < 0.01, respectively). In spite of this, patients and controls did not show significantly different basal aldosterone plasma levels, delivery of sodium to the distal nephron, or urinary excretion of sodium. In both groups the dopaminergic blockade with metoclopramide determined no change in sodium and potassium urinary excretion, but it caused a fall of the fluid and sodium delivery from the proximal tubule to the distal nephron among the patients (from 30.7 +/- 9.3 to 14.4 +/- 4.5 ml/min, P < 0.001; and from 4.25 +/- 1.30 to 2.00 +/- 0.64 meq/min, P < 0.001, respectively). In this group the natriuresis was maintained due to a reduction of the reabsorbed fraction of the distal sodium delivery (from 97.5 +/- 1.9% to 89.8 +/- 12.4%, P < 0.05). In conclusions, compensated cirrhotic patients display an increased endogenous dopaminergic activity compared with controls. This function is critical in maintaining the delivery of sodium to the distal nephron

Switching from HPLC/UV to MEIA for whole blood sirolimus quantitation: Comparison of methods

Sirolimus is a immunosuppressive agent for renal transplant recipients. Monitoring of whole blood sirolimus concentration is necessary in order to improve clinical outcomes. An increasing number of clinical laboratories (4-14% during 2005) are using microparticle enzyme immunoassay (MEIA) for sirolimus quantitation but previous reports indicated a high variability, with a mean difference of 17% for MEIA method vs. high-performance liquid chromatography/ultraviolet (HPLC/UV). This study was aimed at comparing the reliability of MEIA with the HPLC/UV method. Blood samples from transplant patients were processed using both HPLC/UV and MEIA assays. Comparison and Bland-Altman plots, as well as regression analysis and paired t-test were used to compare results of the assays. Concentrations were stratified into three groups and used to investigate whether any observed difference between methods could be influenced by sirolimus concentration. Regression analysis yielded a coefficient of correlation R of 0.9756, the line of best fit being y = 0.9832x + 0.1976. The statistical analysis showed no difference between the two sets of experimental data. The average percentage difference between the two methods was found to be -0.2 +/- 19.2%. On the basis of our present results, the tested MEIA assay is able to quantify sirolimus concentration with a clinically acceptable imprecision, similar to that of HPLC/UV method

Automated Antibody De Novo Sequencing and Its Utility in Biopharmaceutical Discovery

Applications of antibody de novo sequencing in the biopharmaceutical industry range from the discovery of new antibody drug candidates to identifying reagents for research and determining the primary structure of innovator products for biosimilar development. When murine, phage display, or patient-derived monoclonal antibodies against a target of interest are available, but the cDNA or the original cell line is not, de novo protein sequencing is required to humanize and recombinantly express these antibodies, followed by in vitro and in vivo testing for functional validation. Availability of fully automated software tools for monoclonal antibody de novo sequencing enables efficient and routine analysis. Here, we present a novel method to automatically de novo sequence antibodies using mass spectrometry and the Supernovo software. The robustness of the algorithm is demonstrated through a series of stress tests. Graphical Abstract ᅟ