Medicina, Volume 48, Issue 10 (October 2012) – 8 articles

Background and Objective. The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery.
Material and Methods. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/ PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery.
Results. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups.
Conclusions. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis. Full article

Background and Objective. Cerebral gliomas have a tendency to infiltrate the surrounding brain tissue for several centimeters from the core of tumor. The usefulness of structural magnetic resonance (MR) sequences is limited because of their insensitivity for the detection of tumor cells outside the visible tumor border. The aim of this study was to investigate the validity and the repeatability of 2 functional MR methods: fractional anisotropy (FA) and spectroscopy in the assessment of the peritumoral area of cerebral gliomas.
Material and Methods. Forty-five patients with histologically verified brain gliomas underwent diffusion tensor imaging (DTI) and MR spectroscopy (MRS). Metabolic ratios were calculated from choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lactate/lipids (LL), myo-inositol (MI) spectroscopic values obtained within the tumor center, perifocal edema, and distant and contralateral normal-appearing white matter. DTI maps of FA were calculated at the same locations.
Results. A significant gradual increase of FA and a decrease of LL/Cr ratios from the tumor center to the normal-appearing white matter were observed. The Cho/Cr ratio was significantly lower in the distant normal-appearing white matter than in the perifocal edema and the tumor center. The NAA/Cr ratio was significantly reduced in the tumor center, perifocal edema, and distant normal-appearing white matter compared with the contralateral hemisphere. MRS and DTI measurements of glioma and peritumoral area had a high degree of repeatability.
Conclusions. Our study shows that MRS and DTI measurements are reproducible. The combined use of Cho/Cr, LL/Cr, and FA measurements is a promising MR technique that provides valuable additional information about the location of glioma potential border. Full article

Background and Objective. The basis of substance use disorders (SUD) is formed with regard to biopsychosocial aspects. By following the SUD biological model exclusively, the effectiveness of treatment is limited since all the formation aspects of SUD are not taken into account. By using the psychosocial model, however, the understanding and treatment of a substance use illness becomes enhanced and is more effective. A key role in this model is played by self-help groups and psychotherapy. The aim of this study was to determine the viewpoint of patients with substance use disorders in terms of the number of visits, duration of treatment, efficacy of self-help groups, and individual and group psychotherapy in different treatment methods.
Material and Methods. The participants were approached by researchers at two drug and alcohol services in Latvia. In total, 587 patients received questionnaires developed by the authors of the study.
Results. All the 587 questionnaires of both outpatient respondents (n=200, 34.1%) and inpatient respondents (n=387, 65.9%) were analyzed. Of all the outpatient department respondents, 41.5% (n=83) attended self-help groups, 28.5% (n=57) individual psychotherapy, and 14.5% (n=29) group psychotherapy; the inpatient department respondents were 2 to 4 times less often involved in the measures.
Conclusions. The outpatient respondents were more frequently employed. They attended selfhelp groups and psychotherapy and obtained longer remission comparing with inpatient respondents. This study has shown that patients had a greater success rate in staying in remission, maintaining outpatient care and shedding the need of inpatient care. Full article

Background and Objective. Studies on decompressive craniectomy (DCE) after a malignant middle cerebral artery (MCA) stroke in selected population show an increased probability of survival without increasing the number of very severely disabled. Cerebral infarct volume (CIV) as a triage criterion for performing surgery has not been discussed in literature. The aim of this study was to investigate the value of CIV and initial National Institutes of Health Stroke Scale (NIHHS) and Glasgow Coma Scale (GCS) scores as possible triage criteria in the surgical treatment of patients with “malignant” MCA stroke.
Material and Methods. According to the study protocol, 28 patients with a malignant MCA stroke were included and analyzed prospectively. The patients were randomly divided either into the DCE plus best medical treatment (BMT) group or BMT alone group. CIV and NIHHS and GCS scores were measured at time of enrollment in every case. Clinical outcome was evaluated 1 year after the treatment.
Results. Six patients survived: 5 in the DCE group (none of them was older than 60 years) and 1 in the BMT group (P=0.03/0.06). Among survivors, none had a cerebral infarct volume of more than 390 cm3 (P=0.05). All survivors in the DCE group had favorable outcomes. There was no significant difference in the NIHSS and GCS scores between the groups and survivors/nonsurvivors (P>0.05).
Conclusions. Decompressive surgery in the selected patients is likely to increase the probability of survival with a favorable outcome without increasing the number of severely disabled survivors. Patients with CIV of more than 390 cm3 may be bad candidates for DCE, and the prognosis is likely to be bad regardless the treatment strategy. The initial NIHHS and GCS scores did not prove any prognostic value in outcome. Full article

Background and Objective. Glucose transport via GLUT1 protein could be one of additional mechanisms of the antidiabetic action of sulfonylureas. Here, the GLUT1 gene and the protein expression was studied in rats in the course of severe and mild streptozotocin-induced diabetes mellitus and under glibenclamide treatment.
Material and Methods. Severe and mild diabetes mellitus was induced using different streptozotocin doses and standard or high fat chow. Rats were treated with glibenclamide (2 mg/kg daily, per os for 6 weeks). The therapeutic effect of glibenclamide was monitored by measuring several metabolic parameters. The GLUT1 mRNA and the protein expression in the kidneys, heart, and liver was studied by means of real-time R T-PCR and immunohistochemistry.
Results. The glibenclamide treatment decreased the blood glucose concentration and increased the insulin level in both models of severe and mild diabetes mellitus. Severe diabetes mellitus provoked an increase in both GLUT1 gene and protein expression in the kidneys and the heart, which was nearly normalized by glibenclamide. In the kidneys of mildly diabetic rats, an increase in the GLUT1 gene expression was neither confirmed on the protein level nor influenced by the glibenclamide treatment. In the liver of severely diabetic rats, the heart and the liver of mildly diabetic rats, the GLUT1 gene and the protein expression was changed independently of each other, which might be explained by abortive transcription, and pre- and posttranslational modifications of gene expression.
Conclusions. The GLUT1 expression was found to be affected by the glucose and insulin levels and can be modulated by glibenclamide in severely and mildly diabetic rats. Glibenclamide can prevent the liver damage caused by severe hyperglycemia. Full article

Background and Objective. Ischemic stroke may initiate a reperfusion injury leading to brain damage cascades where inflammatory mechanisms play a major role. Therefore, the necessity for the novel stroke-protecting agents whose the mechanism of action is focused on their anti-inflammatory potency is still on the agenda for drug designers. Our previous studies demonstrated that cerebrocrast (a 1,4-dihydropyridine derivative) and mildronate (a representative of the aza-butyrobetaine class) possessed considerable anti-inflammatory and neuroprotective properties in different in vitro and in vivo model systems. The present study investigated their stroke-protecting ability in an endothelin-1 (ET-1)-induced ischemic stroke model in rats.
Material and Methods. Male Wistar rats were pretreated (for 7 days, per os) with cerebrocrast (0.1 mg/kg), mildronate (100 mg/kg), or their combination, followed by the intracerebral injection of ET-1. Functional and behavioral tests were carried out up to 14 days after the ET-1 injection. Ex vivo, the number of degenerated neurons and the infarction size in the cerebral cortical tissue were assessed histologically.
Results. Cerebrocrast and mildronate effectively normalized ET-1-induced disturbances in neurological status, improved the muscle tone, and decreased the number of degenerated cortical cells. Both drugs also reduced the infarction size, and cerebrocrast showed at least a 2-fold higher activity than mildronate. The combination of both drugs did not cause a more pronounced effect in comparison with the action of drugs administered separately.
Conclusions. The 1,4-dihydropyridine and aza-butyrobetaine structures may serve for the design of novel stroke-protecting agents to prevent severe neurological poststroke consequences. Full article

Background and Objective. Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease.
Material and Methods. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study. Immunohistochemical and Western blot methods were used to analyze sirtuin expression in the airways.
Results. The obtained results showed the nonuniform sirtuin expression throughout the bronchial tree. Smokers both with and without chronic obstructive pulmonary disease had decreased sirtuin expression in large airways. However, in small airways, sirtuin expression was decreased only in patients with chronic obstructive pulmonary disease. In addition, a correlation between airflow limitation, smoked pack-years and the number of sirtuin-positive cells in airways was found.
Conclusions. Smoking is characterized by suppressed sirtuin expression in large airways, whereas chronic obstructive pulmonary disease is characterized by more severe suppression of sirtuin expression both in large and small airways. Full article

Background and Objective. Distinction between benign and malignant thyroid tumors is essential for proper clinical management. The aim of this study was to evaluate the diagnostic potential of a set of 3 molecular markers in the differential diagnosis of thyroid tumors.
Material and Methods. Immunohistochemistry for HBME-1, E-cadherin (E-CAD), and CD56 was carried out in 36 follicular adenomas, 77 colloid goiters, 36 papillary thyroid carcinomas, and 14 follicular carcinomas. Sixty-eight thyroid fine needle aspiration (FNA) cases confirmed by subsequent surgical resection specimens were selected. Immunocytochemistry for HBME-1, E-CAD, and CD56 was performed in these cases, including 25 papillary thyroid carcinomas, 1 follicular carcinoma, 22 follicular adenomas, and 20 colloid goiters.
Results. PTC was characterized by a decreased expression of E-CAD and CD56 contrary to the surrounding benign thyroid tissues. There was no HBME-1 expression in benign thyroid tissues, but it was high in papillary thyroid carcinomas and weak in follicular adenomas. The expression of E-CAD and CD56 was significantly higher in follicular adenomas than in the surrounding thyroid tissues. Analyzing the FNA material, HBME-1 expression was documented in 96% of papillary thyroid carcinomas, but there was no expression in the benign lesions. E-CAD and CD56 expression was significantly weakened in papillary thyroid carcinomas, but enhanced in follicular adenomas.
Conclusions. HBME-1 was found only in malignant lesions and can be considered the most sensitive, specific single marker in papillary thyroid carcinomas. CD56 and E-CAD can assist in the decision-making on the benign and malignant nature of the nodule. Immunocytochemistry is of value as an ancillary test to enhance the diagnostic accuracy of thyroid FNA samples. Full article