Olivio Perković

The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P = 0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P = 0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P = 0.017). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS.

MMP-2 -1575G/A polymorphism modifies the onset of optic neuritis as a first presenting symptom in MS?

Previous studies show altered activities of matrix metalloproteinase (MMP)-2 and MMP-9 in serum and cerebrospinal fluid of multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. Optic neuritis (ON) is a common symptom of both disorders. Here we investigated the impacts of MMP-2 -1575G/A and MMP-9 -1562 C/T gene polymorphisms on disease phenotype in 100 MS patients with ON as a first symptom and 376 MS patients with other initial symptomatology. The MMP-2 -1575G/A polymorphism led to a 5-year-earlier age of disease onset in MS patients with ON as a first symptom (p=0.009).

A Case of Lichen Ruber Planus in a Patient with Familial Multiple Sclerosis

Multiple sclerosis and lichen ruber planus are clinically and histologically distinct complex disorders of putative autoimmune aetiology that are fairly commonly observed in isolation but rarely found in combination. Only two previous reports have described lichen skin disorders in association with multiple sclerosis. The present report describes the case of a 51-year old Caucasian woman exhibiting both familial multiple sclerosis and lichen ruber planus. This combination may have occurred by chance or it might imply that these disorders share common mechanisms in their pathogenesis.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and interferon-β treatment response in multiple sclerosis patients: a preliminary report

We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-&bgr; (IFN-&bgr;) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-&bgr; treated MS patients [162 responders (Rs) and 113 nonresponders (NRs)] were genotyped by PCR. The ACE I/D genotype distribution and allele frequencies did not differ between female Rs and NRs. However, male NRs tended to have a greater prevalence of the DD genotype (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91–7.60) and a significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95% confidence interval: 1.13–5.20) than male Rs. Multiple forward stepwise regression analysis indicated that the negative response to IFN-&bgr; therapy was associated with the ACE-DD genotype in men (&bgr;=0.371; multiple R2 change: 0.132; P=0.009) and a higher pretreatment relapse rate in both men (&bgr;=−0.438; multiple R2 change: 0.135; P=0.015) and women (&bgr;=−0.208; multiple R2 change: 0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted for ∼26.7% of the IFN-&bgr; response variability among the men in the sample. Further studies of a larger number of MS patients from different populations are necessary to evaluate these preliminary findings.

Tihi infarkt mozga

BACKGROUND AND OBJECTIVE. Although previous studies have provided new information on bone repair, there are still gaps in knowledge about resorptive and formative processes during bone repair at the electron microscopic level. The aim of this study was to compare bone repair after the internal fracture, osteotomy, and bicortical perforation of the tibia by means of electron microscopy. MATERIAL AND METHODS. An electron microscopic study of bone repair after the internal fracture, osteotomy, and bicortical perforation of the tibia was performed on 72 male Wistar rats. Rats undergoing osteotomy and perforation were further subdivided into the control and immobilization subgroups. Bone repair was observed during the first posttraumatic weeks. RESULTS. Although bone repair in general had similar bone healing stages in all the groups, the repair process depended on the mode and degree of injury thus being different in the experimental groups. After the internal fracture, indirect ossification was observed; after osteotomy, primary periosteal, secondary endosteal ossification was noted; and after perforation, primary endosteal, secondary periosteal ossification was documented. Immobilization had an inhibitory effect on bone repair. CONCLUSIONS. The results of the present study gave new information at the electron microscopic level about intracellular changes and intercellular matrix synthesis during different types of posttraumatic bone repair and confirmed our previous reports on similar posttraumatic bone repair in histomorphometric and immunohistochemical studies.