Role of pentraxin-3 in risk assessment of patients with metabolic syndrome.

BACKGROUND: Inflammation plays a major role in the development of metabolic syndrome (MetS) and its progression. Recent studies have shown that pentraxin-3 (PTX-3), osteoprogerin (OPG), and tumor necrosis factor-alpha (TNF-α) are key factors in MetS pathophysiology, but evidence for endorsing their clinical use is currently unclear and insufficient. AIM: The study aimed to evaluate the association between the inflammatory biomarkers' levels and the severity of MetS. METHODS: The study was observational, transversal, prospective, cohort, and analytical type. We enrolled 80 patients (M:F = 1, mean age = 55 ± 10.77 years) who met MetS criteria. The study protocol included: medical history, physical examination, 6-min walk test distance (6MWTD), biochemical tests, electrocardiogram, echocardiography, and carotid ultrasonography. We also performed plasmatic measurement of PTX-3, OPG, and TNF-α, in addition to standard biochemical tests. RESULTS: Subjects with severe MetS had higher values of body mass index (BMI) and waist circumference (p < 0.001, p = 0.001). PTX-3 levels were significantly higher in patients with severe MetS (p = 0.03) and the values were not influenced by age or gender. OPG positively correlated with BMI (r = 0.264, p = 0.018). 6MWTD was lower in patients with severe MetS (p = 0.005), whereas CCA-IMT was higher in this group of patients (p = 0.005). In addition, the receiver operating characteristic (ROC) curve analysis for PTX-3 identified a cut-off value of 10.7 ng/dl that differentiates between mild and severe MetS [AUC 0.656; sensitivity =47.1% (95% CI = 36.1%-62.3%); specificity = 78.9% (95% CI = 54.4%-93.9%)]. CONCLUSION: PTX-3 was correlated with the severity of MetS, with other inflammatory parameters and cardiovascular tests. CCA-IMT and 6MWTD are useful in differentiating between mild and severe MetS.

Factors that influence the severity of post-stroke depression.

AIM: The aim of this paper was to investigate whether the extent of neurological impairment, the location of ischemic lesions due to stroke are associated with the severity of post-stroke depression. MATERIALS AND METHODS: The study included 82 patients, who were diagnosed with acute ischemic stroke and post-stroke depression and were admitted to the Neurology Clinic of Cluj-Napoca County Emergency Hospital between 2009 and 2011. A head MRI was performed with a 1.5 Tesla. Psychometric assessment was performed by using several scales, including the Beck Depression Inventory and the Mini-Mental State Examination. The National Institutes of Health Stroke Scale (NIHSS) and the Barthel Index of Activities of Daily Living were used to produce a complete neurological assessment. RESULTS: Patients with severe depression had a lower score on the Quality of Life Scale (QOLS) and higher scores for the Barthel index, NIHSS and MMSE. A stroke located in the basal nuclei increased the probability of severe depression. The patients with fewer lesions (1-2) had a greater chance of developing mild or moderate depression compared to the patients with 3-4 lesions. A frontal localization of the stroke was almost twice as common in patients with severe depression. If the stroke affected the left hemisphere, there was a higher probability of severe depression. In multivariate analysis, a basal nuclei lesion, a left hemisphere stroke location, and an NIHSS score >11 were all independently associated with severe depression. CONCLUSION: The location of the stroke and the NIHSS score could be related to the severity of post-stroke depression. Abbreviations: NIHSS = The National Institutes of Health Stroke Scale; QQL = Quality of life Scale; BDI = Beck Depression Inventory; MMSE = Mini-Mental State Examination; PSD = Post-stroke depression; MRI = Magnetic resonance imaging.

Pharmacogenetics aspects of oral anticoagulants therapy.

RATIONALE: Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or intra-individual variability in response to the treatment. OBJECTIVE: to establish the influence of several genetic factors on VKA efficacy and adverse reactions. METHODS AND RESULTS: The metabolism of VKA differs depending on their chemical structure: indandiones derivatives (fluindione) or coumarin derivatives (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants being associated with differences in the enzymatic activity of CYP2C9. The most important in terms of their frequency in the general population are CYP2C9*2 and CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK metabolism. Various polymorphisms in the VKORC1 gene have been described. VKORC1*2 haplotype seems to be the most important in relation to the variability in response to VKA. DISCUSSIONS: Various studies have shown a relationship between the genotype and the mean warfarin maintenance dosing: in patients carrying 2C9*1/*2 alleles, the dose is reduced by 18-40% in patients carrying 2C9*2/*2 alleles, by 21-49% in patients carrying 2C9*1/*3 alleles. The A allele of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for a lower dose of acenocoumarol in patients on anticoagulant therapy. ABBREVIATIONS: SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists, C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International Normalized Ratio.

GSTM1, GSTT1 and GSTP1 in patients with multiple breast cancers and breast cancer in association with another type of cancer.

INTRODUCTION: breast cancer has the highest incidence in women.Glutathione S-transferases (GSTs) are a large group of enzymes involved in the metabolism of xenobiotics. The members of this gene superfamily are involved in the development of multiple cancers. OBJECTIVES: the aim of the study was to see whether the GSTM1, GSTT1 and GSTP1 genetic polymorphisms are risk factors for patients diagnosed with multiple malignancies, of which at least one is located in the breast. MATERIALS AND METHODS: in the period between 2005 and 2012,of the 520 patients diagnosed with breast cancer, 69 had multiple primitive malignant tumors, of which at least one was localized in the breast. The research on GSTM1, GSTT1 and GSTP1 genotypes consisted of 59 patients diagnosed with multiple breast cancers or with breast cancer in association with another type of cancer, compared with a group of healthy controls. RESULTS: in the subgroup of patients with breast cancer in association with another type of cancer, the GSTM1 null genotype was present in 61.2% of patients, compared to 29% of controls; the subgroup of metachronous breast cancers, the presence of any of the GSTT1 or GSTM1 null genotypes was statistically significantly different from that of controls (65.2%vs. 28.5%); in the subgroup with synchronous cancers, the GSTM1 null genotype was found in 66.6% of patients compared to 9% for the controls, and the presence of any null genotype (GSTM1 and GSTT1) was also statistically significant in the case group. CONCLUSIONS: the GSTM1 null genotype is a risk factor for synchronous breast cancers and for breast cancer associated with extramammary cancer; the presence of null genotypes(GSTM1 or GSTT1) is a risk factor for multiple breast cancer(bilateral or synchronous); the GSTT1 null genotype and the heterozygous variant allele (Ile105Val) and homozygous variant allele (Val105Val) of GSTP1 are not risk factors for the cases studied.

The relationship between the metabolic syndrome and its components and bone status in postmenopausal women.

UNLABELLED: The association between metabolic syndrome (MS) and bone status remains controversial. We aimed to study the relationships between MS, bone mineral density (BMD), and bone metabolism in postmenopausal women. MATERIAL AND METHODS: MS was assessed in 218 white postmenopausal women. BMD (lumbar spine and hip) was measured by dual energy X-ray absorptiometry (DXA). Serum carboxyterminal cross-linked telopeptide of type 1 collagen (CTX), undercarboxylated osteocalcin (uOC), bone alkaline phosphate (BAP) and vitamin D were assayed. RESULTS: Postmenopausal women with MS had a significantly higher lumber spine BMD than women without MS (p < 0.05). A progressive increase of the BMD at both sites with the number of MS components was observed. Bone turnover markers and vitamin D levels were not significantly influenced by the presence of MS. BMD at both sites positively correlated with body mass index (BMI), waist circumference (WC) and glucose in unadjusted analysis. In multiple regression analysis, WC was independently associated with BMD at both sites, while hypertension was associated only with lumbar spine BMD. CONCLUSIONS: In postmenopausal women, MS is associated with increased lumbar spine BMD and this relation is explained mainly by the higher BMI and WC in the MS group.

Multiple malignant tumors.

BACKGROUND: Due to the improvement in diagnosis and therapy for certain malignant tumors, we are now faced with patients who develop in time multiple malignancies. METHODS: We conducted a retrospective analysis of the patients diagnosed with at least two primary cancers that were admitted and treated in Cluj-Napoca Municipal Hospital. The study followed patients for a period of 7.5 years. RESULTS: We included in the present study 217 patients (4.33%) with two or more malignant primary tumors from 5003 cases diagnosed with a primary cancer. The most common sites for multiple malignant tumors were related to the breast, colorectum, urinary bladder, prostate and kidneys. CONCLUSIONS: We should always take into consideration the possibility of synchronous tumors and we have to keep in mind that a successful treatment of cancer might not prevent the onset of another primary mass.

GST gene variants in synchronous colorectal cancers and synchronous association of colorectal cancers with other cancers.

BACKGROUND: the present study evaluates genetic polymorphisms of three glutathione S-transferases (GSTM1, GSTT1and GSTP1) in patients with synchronous malignant colorectal tumors and the association of synchronous colorectal cancers with other cancers. MATERIAL AND METHODS: from 420 patients with a colorectal cancer admitted to our hospital between 2005-2012, we selected for genetic analysis 20 patients with multiple synchronous malignant colorectal tumors and 9 patients with asynchronous association of colorectal cancer with another cancer. We searched for GST genotypes, comparing the results with controls. RESULTS: the genetic analysis was possible only in 19 patients with colorectal synchronous cancers and 9 patients with asynchronous association of colorectal cancer with another cancer; we found a statistically significant difference for null GSTM1 genotype frequency between these patients and the control group; we found no differences regarding the frequency of null GSTT1 genotype and Ile105Val polymorphism of GSTP1 in patients with synchronous cancers compared with the control group. CONCLUSION: in our study we found the null GSTM1 genotype as a risk factor for multiple colorectal synchronous cancers and for an association of synchronous colorectal with other cancers

Epidemiology of documented viral respiratory infections and acute otitis media in a cohort of children followed from two to twenty-four months of age.

BACKGROUND: Viral upper respiratory infections (URIs) are considered major risk factors for acute otitis media (AOM) in young children. We studied the epidemiology and relative roles of different viruses in respiratory infections in a cohort of 329 Finnish children followed from 2 months to 2 years of age. METHODS: A nasopharyngeal aspirate (NPA) was collected whenever the child had signs and/or symptoms of URI and tested for the presence of common respiratory virus antigens or infectivity/nucleic acid (only rhinoviruses). Possible repeated detections of a given virus during a 30-day period were considered to represent a single designated virus-specific episode. AOM and URI episodes were defined in a similar way. RESULTS: At least one virus was detected in 837 (41.7%) of the 2005 NPA specimens examined. Rates of URI and virus-specific episodes showed expected seasonal variation with major peak occurrences coinciding with or preceding those of AOM. The proportions of rhinoviruses, respiratory syncytial (RS) virus, parainfluenza virus (PIV) type 3, influenza virus A and adenoviruses were 63.1, 14.7, 6.7, 6.7 and 6.2% of the total of 761 virus-specific episodes. Influenza virus B, PIV1 and PIV2 were each responsible for approximately 1% of the episodes. AOM was diagnosed in 870 URI cases (43.4%) and in 43.3% of cases associated with a virus-positive NPA. The latter figure was clearly higher (57.7%) for RS virus-positive specimens. CONCLUSIONS: The seasonal coincidence of URI and AOM demonstrated the obvious role of URI in the pathogenesis of AOM. The occurrence of rhinoviruses and RS virus in URI was strikingly more common than that of any other virus tested. Although rhinoviruses were definitely the most frequently found viruses in NPA specimens, the association of RS virus with concurrent AOM was relatively higher than that of any other virus.