Covid-19 infection and the host genetic predisposition: does it exist?

Knowledge of genomic interindividual variability could help us to explain why different manifestation of clinical severity of Covid-19 infection as well as modified pharmacogenetic relations can be expected during this pandemic condition.

MicroRNAs in pathophysiology of acute myocardial infarction and cardiogenic shock.

AIM: Levels of circulating miRNA are considered to be potential biomarkers of acute myocardial infarction and disease progression. METHODS: In this study, the expression levels of circulating miRNA-1, miRNA-133 and miRNA-124a were investigated in a group of patients with acute myocardial infarction (STEMI) and cardiogenic shock (CS) compared to controls. RESULTS: During the hospitalization period, miRNA-133 showed a significant up-regulation in the serum of STEMI and CS patients compared to controls, while the expression of miRNA-1 was significantly different only in CS. The expression of miRNA-124 was significantly higher in STEMI and CS. Furthermore, miRNA-1 expression was related to the level of circulating glucose in patients with STEMI. We also found a negative correlation between miRNA-133 and MMP-9 levels. MiRNA-124 expression was significantly related to the level of soluble ST2; the marker correlated to cardiac damage. CONCLUSION: All selected miRNAs are potential markers of cardiac injury in cardiogenic shock, whereas miRNA-124a and -133 are markers of injury in STEMI. MiRNA-1 expression is related to circulating glucose in STEMI. None of miRNAs could be correlated to the extent of injury, progress of the disease, or prognosis of patient outcome. Therefore, the levels of circulating miRNA have no potential for becoming a biomarker of myocardial damage and as such would bring no further benefit compared to current markers (Tab. 4, Fig. 1, Ref. 47).

Genetic predisposition for chronic venous insufficiency in several genes for matrix metalloproteinases (MMP-2, MMP-9, MMP-12) and their inhibitor TIMP-2.

OBJECTIVE: The project was scheduled as a case-control study to investigate the correlation between MMP-2 (rs243864), MMP-9 (3918242), MMP-12 (rs7123600) and TIMP-2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP-2 genotypes and phenotypes of CVD. MATERIAL AND METHODS: 150 patients with CVD and 227 controls were enrolled into the study. The MMPs and TIMP-2 genotypes were identified by the PCR method and restriction analysis according to standard protocols. RESULTS: The G allele of MMP-2 -790 T/G was 1.85 times more frequent in men with CVD than in the control group (P = 0.008). The T allele of MMP-9 -1562 C/T was observed 2.571 times more frequently in patients with CVD than in the control individuals (both in men and women) with clinically significant specificity (P = 0.0000009). The G allele of MMP-12 rs7123600 was determined 2.082 times more frequently in female patients with CVD than in the control group with clinically significant specificity (P = 0.02). No significant result in TIMP-2 rs8176329 polymorphism in the case-control study was observed. CVD women with G allele in MMP-2 -790 T/G in the genotype-phenotype study are seen to develop ulceration 2.539 times more frequently (P = 0.003). The G allele of MMP-12 rs7123600 was detected 3.167 times more frequently in CVD women with ulceration compared with CVD women without ulceration (P = 0.007). In CVD men in C6 stage, the incidence of AG genotype in rs7123600 MMP-12 polymorphism was found to be 4.675 times higher compared to CVD women with C6 staging (P = 0.005). The AG genotype in TIMP 2 rs8176329 polymorphism was found to be associated with higher risk of tumour (P = 0.01). CONCLUSION: Studying these polymorphisms can contribute to better identification of patients at higher risk of developing CVD, while providing the most appropriate prevention and treatment strategies for limiting the progression and complications of CVD.

Central pulse pressure and variability in matrix metalloproteinases genes and their inhibitors in patients with ischemic heart disease.

Matrix metalloproteinases (MMPs) as well as their inhibitors (TIMPs) play a crucial role in controlling extracellular matrix turnover and have recently been associated with atherosclerosis, myocardial and vascular injury. Moreover, the genetic variability of MMP genes has been suggested to play an important role in vascular remodeling and age-related arterial stiffening. This study aims to describe associations of 14 selected polymorphisms in genes for MMPs and TIMPs with selected cardiovascular parameters (including central pulse pressure), clinical conditions and drug treatment profiles in 411 stable ischemic patients with preserved systolic function of the left ventricle. The genotyping of 14 single-nucleotide polymorphisms in 8 genes was carried out either using 5´ exonuclease (TaqMan®) reagents or by restriction analysis. Numerous associations of the investigated polymorphisms with systolic and diastolic blood pressure, maximum left ventricular end diastolic pressure and ejection fraction were observed. While some of the observed effects were found to be age-dependent, associations with clinical conditions (hypertension, diabetes mellitus, angina pectoris) were only observed in women and associations with four groups of drugs (statins, nitrates, calcium channel blockers, anti-aggregation drugs) were only observed in men. The results of this study indicate that the genetic variability of MMPs and TIMPs is an important factor which influences cardiovascular functions and may have important consequences for individual therapy customization in the future.

Relation of IL-6, IL-13 and IL-15 gene polymorphisms to the rheumatoid factors, anti-CCP and other measures of rheumatoid arthritis activity.

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

Brain-derived neurotrophic factor and ciliary neurotrophic factor in maternal plasma and umbilical cord blood from pre-eclamptic and physiological pregnancies.

The aim of the study was to investigate the circulating levels of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in maternal serum and umbilical cord blood from respective pregnancies in pre-eclampsia (PE) cases and a control cohort. A total of 12 pre-eclampsia cases and 34 healthy controls were enrolled and the maternal peripheral blood - umbilical cord blood duos, were examined for BDNF and CNTF levels. BNDF levels were significantly higher in umbilical cord blood from pre-eclamptic pregnancies; there was also significant difference between maternal plasma and umbilical cord blood levels of BDNF (p < 0.001) in the controls. The CNTF levels in umbilical cord blood (CNTF-UCB) were significantly higher in PE cases than in the controls (p = 0.03). Significant differences were observed in expression of BDNF and CNTF proteins in maternal peripheral blood and umbilical cord blood between pre-eclampsia cases and healthy controls.

Association between three single nucleotide polymorphisms in eotaxin (CCL 11) gene, hexanucleotide repetition upstream, severity and course of coronary atherosclerosis.

The impact of three single-nucleotide polymorphisms in eotaxin (SCYA11) gene promoter (-426C>T and -384A>G) and first exon (67G>A) and recently described hexanucleotide (GAAGGA)(n) 10.9 kb upstream on coronary atherosclerosis was investigated. Elective coronary angiography of 1050 consecutive subjects was performed. All patients were genotyped for the three SNPs. In a subset of the first 472 samples, the number of (GAAGGA)(n) repetitions was determined. For further evaluation, short and long variants were distinguished; the borderline corresponded with the median value of all alleles: ≤8 repetitions were considered as short sequence, ≥9 repetitions as long. Patients with bronchial asthma or insignificant atherosclerosis were excluded; the remaining group of 933 subjects was further investigated. Patients were grouped according to the form of CAD (ACS vs. stable angina) and the number of diseased vessels. The GG variant of 67 G>A polymorphism was associated with acute form of CAD compared to stable angina (p=0.0011, p(corr.)=0.013). The number of (GAAGGA)(n) repetitions in our set of patients ranged from 3 to 12. There were no subjects with 4 or 5 repetitions. The frequency of short repetition alleles increased with the number of affected vessels (1 vs. 3 diseased vessels: p=0.0043, p(corr)=0.034). In our study, the (GAAGGA)(n) hexanucleotide was associated with the severity of CAD. The 67 GG was associated with acute form of CAD. None of the two SNPs in eotaxin promoter had any relation to CAD. The number of (GAAGGA)(n) repetitions can thus be a novel genetic marker of the extent of CAD.

[Adrenocorticotropin hormone--possible marker of pregnancy pathologies]. / Kortikotropin-releasing hormon a adrenokortikotropní hormon--mozné markery nekterých tehotenských patologií.

Adrenocorticotropin hormone (ACTH) is produced from the anterior pituitary gland and can be considered as one of the main elements of the hypothalamic-pituitary-adrenal axis. ACTH secretion is controled by corticotropin-releasing hormone (CRH) from hypothalamus. ACTH stimulates the adrenal cortex. It's affects synthesis and releasing of glucocorticoids, precursors of aldosterone, which affects the synthesis of mineralocorticoids. Preeclampsia and intrauterine growth retardation (IUGR) is one of the major pregnancy pathologies. The aetiology of these states are not clearly known, it is assumed that factors pathogenetic chain has been operating in early pregnancy. These factors are generally similar for both diseases. It is assumed that these pathologies will activate the hypothalamic-pituitary-adrenal stress axis both for mother and fetus. In research studies, mathernal plasma CRH concentrations are elevated in complicated pregnancies. Etiopathogenesis of severe pregnancy pathologies such as IUGR, or preeclampsia is still unclear. Therefore, the research focuses on finding new markers that contribute to early diagnosis of serious states.

Visfatin is secreted into the breast milk and is correlated with weight changes of the infant after the birth.

INTRODUCTION: Visfatin is a recently identified adipokine with numerous metabolic and immunoregulatory properties that has been implicated in the regulation of the white adipose tissue (WAT) and significant changes in visfatin levels were reported during pregnancy. The aim of the study was to investigate dynamics of visfatin levels in maternal serum and human breast milk during a 180-d period after the delivery. MATERIALS AND METHODS: : Breast milk and venous blood samples were obtained from 24 healthy lactating women with uncomplicated, physiological pregnancy and appropriate-for-gestational age neonates and serum-milk sample duos were collected at the time of birth, at the 1-3, 12-14, 28-30, 88-90 and 178-180 postpartum. RESULTS: Our study demonstrates that (1) visfatin is abundantly secreted into breast milk in humans, reaching approx. 100× higher concentrations compared to maternal serum; (2) visfatin concentrations in maternal serum show significant variations after the delivery and (3) visfatin concentration in colostrum could be used for prediction of the subsequent weight development (less/more severe weight loss during first 3 days after the birth) of the infant. DISCUSSION: Our data suggest that visfatin could play an important role in regulation of adiposity of the infant after the birth.

Relationship of resistin levels with endometrial cancer risk.

Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p <001). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects.

Association of eNOS gene polymorphisms T-786C and G894T with blood pressure variability in man.

The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) T-786C and G894T in the gene encoding eNOS with blood pressure variability (BPV) in man. Blood pressure was recorded beat-to-beat at rest three times in periods of one week (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years). Systolic (SBPV(0.1r)/SBPV(0.1a)) and diastolic (DBPV(0.1r)/DBPV(0.1a)) blood pressure variabilities in relative (r.u.) and absolute (mm Hg(2)/Hz) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz. Genotypes of both polymorphisms were detected using polymerase chain reaction and restriction analysis using enzymes Msp I and Ban II. Significant differences were observed in BPV among genotypes of T-786C SNP (p<0.05; Kruskal-Wallis), and among haplotypes of both SNPs (p<0.05; Kruskal-Wallis) as well. In T-786C SNP, carriers of less frequent allele (CC homozygotes and TC heterozygotes) showed significantly greater SBPV(0.1r) and SBPV(0.1a) compared to TT homozygotes (Mann-Whitney; p<0.05). The G894T variant showed no significant differences, but, both SNPs were in linkage disequilibrium (D'=0.37; p<0.01). Carriers of haplotype CT/CT (CC homozygotes of -786C/T and TT homozygotes of G894T) displayed significantly greater SBPV(0.1r), SBPV(0.1a) and DBPV(0.1a) compared to carriers of other haplotype combinations (Kruskal-Wallis; p=0.015, p=0.048, and p=0.026, respectively). In conclusion, the haplotype formed by less frequent alleles of both eNOS variants was associated with increased systolic and diastolic BPV in this study.

Difference in angiotensinogen haplotype frequencies between chronic heart failure and advanced atherosclerosis patients - new prognostic factor?

Numerous association studies have been involved in studying the angiotensinogen (AGT) variants, AGT plasma levels and relations to cardiovascular diseases, such as hypertension, myocardial infarction, coronary heart disease. To investigate a role of AGT G(-6)A and M235T genetic variants for chronic heart failure (CHF) and advanced atherosclerosis (AA), a total of 240 patients with CHF and 200 patients with AA of the Czech origin were evaluated for the study. The study shows the role of polymorphism AGT G(-6)A in genetic background among advanced atherosclerosis patients and chronic heart failure patients (Pg=0.001). This difference was also observed in comparison of AA patients with subgroup of CHF with dilated cardiomyopathy (Pg=0.02; Pa=0.009), and ischemic heart disease (Pg=0.007). The greatest difference between triple-vessel disease and chronic heart failure groups was observed in frequency of GT haplotype (P<0.001) and GGMT associated genotype (P<0.001). Retrospectively, we found the same trend when the subgroups of CHF were compared to AA group (AA vs. IHD with CHF P<0.001; AA vs. DCM P<0.001). These results suggest AGT genetic variants as a risk factor for chronic heart failure compared to advanced atherosclerosis disease without heart failure, with a strong difference between IHD patients and chronic heart failure patients with ischemic heart disease, especially in haplotypes and associated genotypes.

Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy.

AIM: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes-metalloproteinase-2 (MMP-2) and angiotensin converting enzyme (ACE)-with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. METHODS: The double centre study included 48 patients with a first acute myocardial infarction treated with primary coronary angioplasty, stent implantation and transplantation of MBMC. According to the changes in perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dSaMI) after cell therapy, the patients were retrospectively divided into group A (responders) and group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. RESULTS: Of the 48 patients who received MBMC transplantation, 17 responded to the therapy. There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGCCTT between responder/non-responder groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (p=0.933). Compared to patients with ACE genotype ID or DD, the patients with ACE II genotype significantly improved in regional systolic LV function of the infarcted wall after implantations of MBMC (dSaMI - 0.4 versus 1.4 cm/s, p=0.037). CONCLUSION: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene was not associated with clinical response to cell therapy.

Association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity.

The aim of this study was to evaluate the association of A1166C polymorphism in angiotensin II type 1 receptor (AT(1)R) gene with baroreflex sensitivity (BRS in ms/mm Hg; BRSf in mHz/mm Hg) in man. BRS and BRSf were determined by a spectral method in 135 subjects (19-26 years) at a frequency of 0.1 Hz. Genotypes were detected by means of polymerase chain reaction and restriction analysis using enzyme DdeI. We compared BRS and BRSf among genotypes of this polymorphism. The frequency of genotypes of AT(1)R A1166C polymorphism was: 45.9 % (AA, n=62), 45.9 % (AC, n=62), 8.2 % (CC, n=11). Differences in BRS (p<0.05) and BRSf (p<0.01) among genotypes of this single nucleotide polymorphism were found (Kruskal-Wallis: BRS - AA: 7.9+/-3.3, AC: 8.6+/-3.6, CC: 5.9+/-2.3 ms/mm Hg; BRSf - AA: 12.0+/-4.0, AC: 12.0+/-5.0, CC: 8.0+/-3.0 mHz/mm Hg). Compared to carriers of other genotypes (AA+AC) the homozygotes with the less frequent allele (CC) showed significantly lower BRSf (Mann-Whitney: BRSf - AA+AC: 12.0+/-4.0, CC: 8.0+/-3.0 mHz/mm Hg; p<0.01) and borderline lower BRS (BRS - AA+AC: 8.2+/-3.5, CC: 5.9+/-2.5 ms/mm Hg; p=0.07). We found a significant association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity. Homozygosity for the less frequent allele was associated with decreased baroreflex sensitivity.

Association of the eNOS 4a/b and -786T/C polymormphisms with coronary artery disease, obesity and diabetes mellitus.

The aim was to assess the relationship between eNOS 4a/b and -786T/C polymorphisms with coronary artery disease (CAD), obesity and diabetes mellitus. Total number of 1313 patients underwent coronary angiography, 939 had significant CAD (stenosis of > or = 1 coronary artery > or = 50%), 222 had smooth coronary arteries. Patients with insignificant atherosclerosis were excluded, the study finally comprised 1161 patients. The analysis of eNOS 4a/b and -786T/ C polymorphisms was performed by polymerase chain reaction. No significant interaction was found between -786T/C polymorphism and solitary CAD or CAD with diabetes and obesity. For 4a/b polymorphism, genotypes aa+ab were almost three times more frequent in diabetic patients without CAD versus patients without CAD and without diabetes--OR 2.79; P = 0.009, Pcorr = 0.03. In 4a/b polymorphism and CAD with obesity and diabetes: bb genotype was significantly more frequent: in patients with CAD, diabetes and obesity in comparison with obese diabetic patients without CAD (OR = 3.63, Pcorr = 0.05); in non-diabetic non-obese patients with CAD, versus diabetic and obese patients without CAD (OR = 3.38, Pcorr = 0.05); in obese non-diabetic patients without CAD vs. obese diabetic patients without CAD (OR = 5.91, Pcorr = 0.01); in patients without CAD, obesity and diabetes vs. obese diabetic patients without CAD (OR = 3.59, Pcorr = 0.05). The eNOS 4a/b polymorphism has significant association with diabetes mellitus in CAD-negative patients, and with CAD in combination with obesity and diabetes mellitus. No association between 4a/b or -786T/C polymorphism and solitary CAD was found.

[Comparison of contact and immersion techniques of ultrasound biometry in terms of target postoperative refraction]. / Srovnání kontaktní a imerzní ultrazvukové biometrie s ohledem na cílovou pooperacní refrakci.

The success of cataract surgery in terms of the postoperative refractive result depends on the calculation of optimal intraocular lens (IOL) power. The accuracy of preoperative measurements (keratometry, biometry) is of a great importance due to the increasing patients' demands on final refractive results. The purpose of this study was to compare the accuracy of contact and immersion techniques of A - scan ultrasound biometry in terms of target postoperative refraction while using the SRK/T formula. The accuracy of the applied biometric techniques was compared by means of the postoperative spherical equivalent (SE). The prospective longitudinal study included 111 non-paired eyes, and the preoperative biometry was performed by means of an OcuScan ultrasound machine (Alcon).The contact technique was used in 48 eyes whereas the immersion technique was employed in 63 eyes.The mean SE in the group measured by the contact technique was -0.13 D, compared to 0.25 D in the group with the applied immersion technique. No statistically significant difference was found in postoperative spherical equivalents while using both biometric techniques (p > 0.1). In this study the choice of a biometric technique had therefore no influence on the predicted postoperative refraction. The results have indicated that the biometric techniques (contact and immersion) are interchangeable in terms of postoperative refractive results.

The efficacy of magnesium sulfate on resolving surgically provoked vasospasm of the flap pedicle in an experiment.

BACKGROUND: Vasospasm frequently accompanies manipulation of small vessels during free flap surgeries and replantations. The purpose of this experimental study was to evaluate the effect of magnesium sulphate on vasospasm provoked by surgical manipulation (axial tension) on the flap pedicle. This kind of surgical manipulation of the vessel cannot be studied in a clinical environment without putting flap viability into risk. MATERIAL AND METHODS: Forty male Wistar rats weighing around 300 g each were classified in two experimental groups (n=20 in each). In the treatment group (group A) Magnesium Sulphuricum 10% (Biotika, Czech Republic) was applied; the second group (group B) served as a control. The vasopasm was provoked by pulling the pedicle of the right groin flap of the rat. The peripheral blood perfusion of the flap was continuously measured using laser-Doppler recording. In the study group, magnesium sulphate was applied topically on the flap pedicle to relieve vasospasm, and duration of the vasospasm was compared to the control group. RESULTS: A statistically significant difference (p=0.01) between the groups was found. The duration of vasospasm was significantly shorter in the treatment group A. CONCLUSIONS: We conclude that in an experimental environment magnesium sulphate is effective in relieving surgically provoked vasospasm of the flap pedicle. This finding is in accordance with our clinical observations.

The effect of blood around a flap pedicle on flap perfusion in an experimental rodent model.

BACKGROUND: The vasospasm has been studied to a considerable extent in the neurosurgical literature. Little experimental and basic scientific literature about vasospasm of flap pedicle is available in the field of reconstructive microsurgery. The purpose of the study was to investigate the effect of presence of blood around the pedicle on a flap perfusion. MATERIAL AND METHODS: Blood flow through a right groin flap was continuously measured using Laser Doppler flowmetry on 40 male Wistar rats. A segment of the flap's pedicle was surgically cleared of adventitia and bathed in blood. The blood used was either collected from the tail of the rat (group A) or from the bleeding branch of the pedicle itself (group B). The differences between the signal amplitudes before and after exposure of the pedicle to blood were recorded. RESULTS: The presence of blood around the pedicle resulted in a significant decrease in perfusion of the flap in both groups. However, no significant differences in the duration of impaired blood flow between the groups were observed. CONCLUSIONS: In conclusion, the presence of blood around the vascular pedicle may cause a significant decrease in the perfusion of a flap, while the origin of the blood does not appear to be an important factor.

Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis.

BACKGROUND: Matrix metalloproteinases are notable contributors to neuroinflammation and blood-brain barrier disruption in multiple sclerosis (MS). OBJECTIVE: The goal of this study was to determine the serum levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), and their tissue inhibitors (TIMP-1) and (TIMP-2), and to investigate their possible relations to type, disability, and severity of MS. MATERIALS AND METHODS: Eighty-seven patients with definite MS according to the McDonald criteria and 50 healthy controls were enrolled in the study. Their clinical status was evaluated with the Expanded Disability Status Scale. Serum levels were analyzed by enzyme-linked immunoassay. RESULTS: A significant elevation in MMP-9 serum levels and in the MMP-9/TIMP-1 ratio was found in the whole MS group (P<0.001), in the relapsing-remitting MS (RRMS) (P<0.001), and secondary-progressive MS (SPMS) (P<0.001) groups when compared with the controls. A significant elevation in MMP-2 serum levels and in the MMP-2/TIMP-2 ratio was observed in the primary progressive (P<0.001) and the SPMS (P<0.002) groups when compared with the RRMS group, and this increase was also associated with the disability (P<0.001) and severity (P<0.05) of the disease. CONCLUSION: We confirmed that metalloproteinases are useful biological markers in MS, providing information about the clinical type, disability, and severity of the disease.

Nuclear receptors gene polymorphisms and risk of restenosis and clinical events following coronary stenting.

INTRODUCTION: Hereditary factors connected with inflammation and fibroproliferation may play important role in restenotic process after coronary stenting. Peroxisome proliferator-activated receptors (PPAR) and retinoic X receptors (RXR) regulate the transcription of crucial genes involved in the glucose and lipid metabolism, inflammation and cell differentiation. METHODS: In our angiographic and clinical study we assessed the association of gene polymorphisms of L162V for PPAR-alpha, C161T for PPAR-gamma and A(39526)AA for RXR-alpha with the risk of restenosis and cardiac events after coronary stenting. Primary endpoint was diameter stenosis > or = 50% at follow-up angiography. Secondary endpoints were death, myocardial infarction and/or target lesion revascularisation at 12 months, and clinical restenosis. The results were adjusted for known predictors of restenosis. The genotypes were analysed by polymerase chains reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. RESULTS: Control angiography was performed in 477 of 565 patients (84.4%) with following restenosis rates in genotype subgroups: CC 29.0% vs GC/GG 22.6% (p = 0.33) in L162V, CC 29.9% vs TC/TT 24.6% (p = 0.24) in C161T and A/A 26.9% vs A/AA + AA/AA 35.0% (p = 0.14) in A(39526)AA polymorphisms. The T allele ofC161T polymorphism was associated with lower frequency of clinical restenosis (p = 0.015). CONCLUSION: We could not find an association of L162V PPAR-alpha, C161T PPAR-gamma and A(39526)AA RXR-alpha gene polymorphisms with angiographic in-stent restenosis or major cardiac events. However, we found the relationship between C161T PPAR-gamma polymorphism and clinical restenosis deserving further study.