Anti-SPAG16 antibodies in primary progressive multiple sclerosis are associated with an elevated progression index.

BACKGROUND AND PURPOSE: Sperm-associated antigen 16 (SPAG16), a sperm protein which is upregulated in reactive astrocytes in multiple sclerosis (MS) lesions, has recently been identified as a novel autoantibody target in MS. The aim of this study was to investigate whether anti-SPAG16 antibody levels differ between MS subtypes (relapsing-remitting, RR; primary or secondary progressive, PP, SP) and whether antibody positivity is associated with clinical characteristics. METHODS: Plasma anti-SPAG16 antibody levels were determined by recombinant protein enzyme-linked immunosorbent assay (ELISA) in 374 MS patients (274 RRMS, 39 SPMS and 61 PPMS) and 106 healthy controls. RESULTS: Significantly elevated anti-SPAG16 antibodies were found in 22% of MS patients with 93% specificity. Anti-SPAG16 seropositivity was associated with an increased Expanded Disability Status Scale (EDSS) in overall MS. A higher proportion of PPMS patients showed anti-SPAG16 antibody reactivity (34%) compared to RRMS (19%) and SPMS (26%), and presented with higher anti-SPAG16 antibody levels. Seropositive PPMS patients had a significantly increased progression index compared to seronegative patients. CONCLUSIONS: Anti-SPAG16 antibodies are associated with an increased EDSS in overall MS, indicating that they are linked to a worse MS disease outcome. Moreover, the presence of anti-SPAG16 antibodies may be a biomarker for a more severe disease in PPMS patients, as indicated by an increased progression index.

The mycotoxin T-2 inhibits hepatic cytochrome P4503A activity in pigs.

Mycotoxins are toxic metabolites produced by fungi that readily colonize crops. After ingestion, these mycotoxins can compromise intestinal health, and once entering the blood stream, even affect the liver and its metabolizing enzymes. It was therefore the aim of the present study to investigate the effect of T-2 toxin, an emerging and potent Fusarium mycotoxin, on the enzymatic activity of cytochrome P4503A (CYP3A) metabolizing enzymes in the liver of pigs. In addition, a yeast-derived feed additive that claims to bind T-2 toxin was included in the study to evaluate its efficacy. Our results demonstrated that a 14-days intake of T-2 toxin contaminated feed at a dose of 903 µg/kg feed, whether or not combined with the mycotoxin binder, results in a substantial inhibition of the CYP3A activity in the liver of pigs. This result may be of importance for animal health, the pharmacokinetics and the withdrawal time of drugs that are substrate of CYP3A enzymes, and consequently can be a threat for public health with respect to tissue residues of these drugs.

Toxic effects of dietary exposure to T-2 toxin on intestinal and hepatic biotransformation enzymes and drug transporter systems in broiler chickens.

The effects of the mycotoxin T-2 on hepatic and intestinal drug-metabolizing enzymes (cytochrome P450) and drug transporter systems (MDR1 and MRP2) in poultry were investigated during this study. Broiler chickens received either uncontaminated feed, feed contaminated with 68µg/kg or 752µg/kg T-2 toxin. After 3weeks, the animals were euthanized and MDR1, MRP2, CYP1A4, CYP1A5 and CYP3A37 mRNA expression were analyzed using qRT-PCR. Along the entire length of the small intestine no significant differences were observed. In the liver, genes coding for CYP1A4, CYP1A5 and CYP3A37 were significantly down-regulated in the group exposed to 752µg/kg T-2. For CYP1A4, even a contamination level of 68µg/kg T-2 caused a significant decrease in mRNA expression. Expression of MDR1 was not significantly decreased in the liver. In contrast, hepatic MRP2 expression was significantly down-regulated after exposure to 752µg/kg T-2. Hepatic and intestinal microsomes were prepared to test the enzymatic activity of CYP3A. In the ileum and liver CYP3A activity was significantly increased in the group receiving 752µg/kg T-2 compared to the control group. The results of this study show that drug metabolizing enzymes and drug transporter mechanisms can be influenced due to prolonged exposure to relevant doses of T-2.

Hepatic and intestinal CYP3A expression and activity in broilers.

Cytochrome P450 is involved in drug metabolism. Subfamily CYP3A shows a degree of similarity across different animal species. However, little information is available about its expression and activity in broiler chickens. A RT-PCR method was developed for the quantification of CYP3A37 expression in the liver and small intestine of broilers. A higher expression in the jejunum was observed compared with that in the ileum. In the liver, a significantly lower expression compared with that in the jejunum was noticed. Thus, the role of the small bowel in drug metabolism cannot be neglected in broilers. CYP3A activity was studied in vitro using midazolam as a substrate. Two protocols for the preparation of intestinal microsomes were compared. Mincing of the tissues before ultracentrifugation seemed to be more appropriate than a protocol based on ethylenediaminetetra-acetic acid separation. CYP3A activity revealed to be the highest in the duodenum with a decreasing trend towards the ileum. Activity in liver was comparable to duodenal activity.

Indoor air quality at the Correr Museum, Venice, Italy.

Two multidisciplinary field surveys, one in winter and the other in summer have monitored the indoor microclimate, air pollution, deposition and origin of the suspended particulate matter and microorganisms of the Correr Museum, Venice. In addition, this study was focused to identify the problems caused by the heating and air conditioning system (HAC) and the effects due to the presence of carpets. Heating and air conditioning systems (HACs), when chiefly designed for human welfare, are not suitable for conservation and can cause dangerous temperature and humidity fluctuations. Improvements at the Correr Museum have been achieved with the assistance of environmental monitoring. The carpet has a negative influence as it retains particles and bacteria which are resuspended each time people walk on it. The indoor/outdoor pollutants ratio is greater in the summertime, when doors and windows are more frequently open to allow for better ventilation, illustrating that this ratio is mainly governed by the free exchange of the air masses. The chemical composition, size and origin of the suspended particulate matter have been identified, as well as the bacteria potentially dangerous to the paintings. Some general suggestions for improving indoor air quality are reported in the conclusions.

Applications of micro-analysis to individual environmental particles.

An overview is given of the recent applications of micro-analytical techniques to single particle environmental research performed at the University of Antwerp since 1990. Automated electron probe X-ray micro-analysis, laser microprobe mass spectrometry and micro-particle induced X-ray emission are the techniques most used for aerosol, aqueous suspension and sediment characterisation. Other techniques like scanning transmission electron microscopy, electron energy loss spectroscopy, Fourier transform infra red microscopy and secondary ion mass spectrometry have only recently been implemented into environmental research.

Limited acute dissections of the abdominal aorta. Report of five cases.

Within a two year period, the diagnosis of acute dissection of a segment of the abdominal aorta was made in five cases without aneurysmal dilation or leakage and with virtually no ischaemia. All patients presented with an atypical painful abdominal syndrome and the diagnosis was made by computed tomography. Only one patient, suffering persistent pain was treated by resection and graft interposition of the infrarenal aorta. All the others were treated conservatively and kept under close follow-up. Two of them died from intercurrent disease. The remaining three patients are doing well after 30 and 42 months conservative treatment and 43 months after surgery respectively. A non-complicated dissection of the abdominal aorta must be considered in the differential diagnosis of atypical painful abdominal syndromes. In cases of persistent pain, progression, ischaemia, aneurysmal dilatation or leakage, surgical treatment is mandatory. In uncomplicated cases conservative treatment is recommended, similar to the principles of management for dissections of the descending thoracic aorta.

Pseudoaneurysm of the posterior tibial artery as an early complication after Fogarty catheter thrombectomy.

After angioplasty of the superficial femoral artery at Hunter's canal in a 65-year-old woman thrombosis developed and femoropopliteal bypass grafting was necessary. Four weeks later the graft occluded, successful thrombectomy was performed with a Fogarty catheter and the patient heparinised. Three days later a pseudoaneurysm developed on the posterior tibial artery which was excised and the artery which was longitudinally torn repaired with a vein graft giving good functional results. Complications after Fogarty balloon catheter thrombectomy are relatively rare but Pseudoaneurysms can occur after perforation or rupture of smaller vessels.

Acute aortic dissection confined to the infrarenal segment.

A case of acute infrarenal aortic dissection is presented. The diagnosis was confirmed by ultrasonography, CT-scan, arteriography, and at operation. A successful aortobifemoral graft replacement was performed.

Selective embolization in the treatment of severe blunt renal injury.

About 10-15 percent of all blunt abdominal trauma is associated with blunt renal injury; 85 percent of these renal injuries are minor contusions and can successfully be treated conservatively. Injuries of the pedicle account for 5 percent and require surgical intervention. Serious lacerations and disruptions of renal parenchyma associated with bleeding, account for the remaining 10 percent. The treatment of these major injuries is more difficult and controversial. Surgical treatment is associated with few complications, but nephrectomies are indicated in 15 to 60 percent of cases. A conservative approach is associated with many early and late complications (up to 60 percent) and in 13 to 68 percent surgery is still necessary. Selective embolization of one or more bleeding segmental renal arteries is an attractive alternative. The advantages are evident. The chance that the bleeding can be successfully stopped is high (more than 90 percent). The treatment is relatively easy and can be repeated, as much as possible renal parenchyma can be saved and arteriovenous fistula can also be treated. Early complications are minor and rare and late complications e.g. hypertension, are also very rare. Two patients are presented who were successfully treated with selective embolization for severe renal bleeding after blunt trauma.

The importance of two-dimensional echocardiography in the location of a bullet embolus to the right ventricle.

Bullets which enter a sufficiently large vein may embolize to the right ventricle. This finding is usually determined after the bullet has been removed from the heart. A chest x-ray study cannot, however, differentiate with certainty between localization in the right ventricular cavity, the right ventricular wall, or the pericardium. We recommend echocardiography to document bullet localization in the right ventricular cavity prior to surgical removal.