Piotr Wacinski

Volatile Anesthetics Reduce Biochemical Markers of Brain Injury and Brain Magnesium Disorders in Patients Undergoing Coronary Artery Bypass Graft Surgery

OBJECTIVES Neuropsychological disorders are some of the most common complications of coronary artery bypass graft (CABG) surgery. The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers. The aim of this study was to analyze the effects of volatile anesthesia (VA) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation (a-vtMg and a-viMg), plasma matrix metalloproteinase-9 (MMP-9), and glial fibrillary acidic protein (GFAP) in adult patients undergoing CABG surgery. DESIGN An observational study. SETTING The Department of Cardiac Surgery in a Medical University Hospital. PATIENTS AND METHODS Studied parameters were measured during surgery and in the early postoperative period. Patients were assigned to 3 groups: group O, patients who did not receive VA; group ISO, patients who received isoflurane; and group SEV, patients who received sevoflurane. RESULTS Ninety-two patients were examined. CABG surgery increased MMP-9 and GFAP. The highest MMP-9, GFAP, and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS Cardiac surgery increased plasma MMP-9 and GFAP concentrations. Changes in MMP-9, GFAP, and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics, such as ISO or SEV, reduced plasma MMP-9, GFAP concentrations, and disturbances in a-vtMg and a-viMg.

Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma

The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented. The TDL regimen was safe and well tolerated. The incidence of side effects was comparable in both groups. Plasma cells have been cultured in vitro with thalidomide and lovastatin to assess the impact of both drugs on the apoptosis rate of plasma cells. In vitro experiments revealed that the combination of thalidomide and lovastatin induced higher apoptosis rate than apoptosis induced by each drug alone. Our results suggest that the addition of lovastatin to the TD regimen may improve the response rate in patients with relapsed or refractory myeloma.

Common polymorphism in the cannabinoid type 1 receptor gene (CNR1) is associated with microvascular complications in type 2 diabetes

Endocannabinoids exert their biological effects via interaction with G-protein coupled cannabinoid receptors CB1 and CB2. Polymorphisms in the CNR1 gene (encoding CB1 receptor) were previously found to be associated with dyslipidemia and cardiovascular diseases. We investigated a role of the polymorphism in CNR1 gene in type 2 diabetes and its complications. The study involved 667 T2DM patients and 450 healthy individuals. All subjects were genotyped for G1359A polymorphism by PCR-RFLP procedure. Genotype frequencies did not differ significantly between patients and controls. The statistically significant differences were seen between T2DM patients with diabetic nephropathy (DN) and those without it (OR for risk allele 2.84, 95% CI 2.04-3.94, p<0.0001). There were also differences between patients with diabetic retinopathy (DR) and those without DR (OR for risk allele 1.81, 95% CI 1.30-2.53, p=0.0005). No differences were observed in diabetic neuropathy. The A allele was more frequent in patients with coexisting cardiovascular disease (CVD) compared to patients without CVD (p=0.0044). The novel finding of our study is the association of the G1359A polymorphism with diabetic nephropathy and diabetic retinopathy in patients with T2DM. This polymorphism was also associated with cardiovascular disease in the patient group.

Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

AIMS To investigate the effect of the microRNA-196a2 gene polymorphism (rs11614913) on risk of cardiovascular disease in type 2 diabetes patients. METHODS We examined 920 patients with diabetes and 834 healthy controls. All subjects were genotyped for the miRNA-196a2 SNP by polymerase chain reaction (PCR) and restriction analysis. RESULTS The genotype distribution among controls and patients was in Hardy-Weinberg equilibrium (p=0.227 and 0.308, respectively). The frequency of the T allele was lower in patients than in controls (p=0.044). The odds ratio 0.66 (95% CI 0.54-0.79) suggests an association of the T allele with decreased risk of T2DM. For the main purpose of the study, T2DM patients were stratified into patients with CVD and those without it. The T allele and TT genotype were significantly more frequent in patients with CVD compared to those without CVD (p=0.013, p<0.001, respectively). The odds ratio for the T allele in the CVD+subgroup vs. CVD- was 1.76 (1.35-2.30), p<0.0001, mostly due to the overrepresentation of TT homozygotes. The highest risk of development of CVD was observed in the additive model for TT homozygotes (OR 3.33, 95% CI 2.05-5.42, p<0.0001). CONCLUSION Our findings suggest that miRNA-196a2 T/C polymorphism (rs11614913) is associated with an increased risk of CVD in type 2 diabetes patients. This provides further insights on pathogenesis of cardiovascular disease in type 2 diabetes patients.

Chemotactic cytokine receptor 5 gene polymorphism: relevance to microvascular complications in type 2 diabetes.

We investigated the involvement of chemotactic cytokine receptor 5 (CCR5) gene polymorphism in microvascular complications of T2DM. All subjects were genotyped with the 59029 SNP in the CCR5 gene. The genotype/allele frequencies did not differ between T2DM patients and controls. Genotype distribution was compared in patients with and without complications (nephropathy, retinopathy and neuropathy). The frequency of A allele was significantly higher in patients with complications (OR for A allele 3.07, 95% CI 2.49-3.77). The A allele carriage was associated with diabetic nephropathy (OR 6.17, 95% CI 3.28-11.6). An association was observed between 59029 polymorphism and age at T2DM onset. The A allele was more frequent in early onset than in late onset patients. For AA homozygotes OR was 2.38 (1.19-4.76) and 2.26 (1.12-4.58) in complicated and uncomplicated subgroups, respectively. These results suggest that CCR5 gene polymorphism is associated with diabetic nephropathy in T2DM.

The effect of Toll-like receptor 4 gene polymorphism on vascular complications in type 2 diabetes patients

OBJECTIVE The aim of our study was to assess the association between the TLR4 Asp299Gly polymorphism and vascular complications in patients with type 2 diabetes. METHODS We examined 1090 patients with T2DM and 716 healthy controls. All subjects were genotyped for the Asp299Gly polymorphism by polymerase chain reaction (PCR) and restriction analysis. RESULTS The genotype frequencies of the Asp299Gly polymorphism were similar in T2DM patients and controls (p=0.512 and 0.311, respectively). The polymorphism was analyzed in subgroups of patients with macro- and microvascular complications. The distribution of genotypes was significantly different between patients with CVD and those without CVD. A significant increase of G allele frequency was observed in CVD+ patients, with odds ratio 2.06 (1.27-3.34), p=0.0035. The same effect was found when patients with diabetic retinopathy were compared with those without it (OR for G allele 2.12, 95% CI 1.43-3.12, p=0.0002). There were no statistically significant differences in genotype distribution between patients with diabetic nephropathy or neuropathy and those without these complications. CONCLUSIONS The results of our study demonstrated that the G allele of the Asp299Gly polymorphism of the TLR4 gene is associated with increased risk of cardiovascular disease and diabetic retinopathy in type 2 diabetes patients.

Calpain-10 gene polymorphisms in type 2 diabetes and its micro- and macrovascular complications

Genetic variations in the calpain 10 gene (CAPN10) were previously implicated with increased risk of type 2 diabetes (T2DM). We studied the association of single nucleotide polymorphisms in the CAPN10 gene, SNP -43, SNP -19 and SNP -63, with T2DM and its complications. Overall, we examined 1440 individuals: 880 patients with diabetes and 560 healthy subjects, all Caucasians of Polish origin. All subjects were genotyped for the CAPN10 SNPs by polymerase chain reaction (PCR). The frequencies of alleles, genotypes and haplotypes at three studied loci were similar between the groups. However, the -43 SNP was significantly more frequent in T2DM patients with coexisting cardiovascular disease (CVD) than in patients without CVD (p=0.001). The -43 SNP was still significantly associated with the risk of CVD after adjusting for potential risk factors including male gender, age, BMI, dyslipidemia and hypertension. The odds ratio for G allele for CVD+ versus CVD- patients was 1.89, 95% CI 1.52-2.35. None of the studied SNPs was significantly associated with microvascular diabetic complications. There was a tendency to increased frequency of SNP -43 1/1 homozygotes in patients with diabetic retinopathy (p=0.057). The homozygous haplotype combination 121/121 was more frequent in T2DM patients than in non-diabetic controls (18.4% vs 10.5%, p=0.019). In conclusion, the results of our study suggest the significant association of SNP -43 with the risk of CVD coexisting with T2DM. We also observed that 121/121 haplotype was associated with T2DM in the studied population.

Acute left main coronary artery occlusion following inadvertent delivery of radiofrequency energy during ventricular tachycardia ablation successfully treated by rescue angioplasty with stenting: A two-year follow-up

Radiofrequency catheter ablation (RFCA) is a treatment mode in patients with recurrent, symptomatic, ventricular arrhythmias. A rare but potentially life-threatening complication of RFCA includes injury to the coronary arteries, which leads to acute occlusion and myocardial infarction. In the few reported cases, the most frequently affected vessel has been the left main coronary artery. We present the case of a 28 year-old female. During the RFCA procedure, an acute occlusion of the left main coronary artery occurred, which was treated successfully with emergency angioplasty.

Increase in intra-abdominal pressure raises brain venous pressure, leads to brain ischaemia and decreases brain magnesium content.

BACKGROUND Intra-abdominal hypertension (IAH) may increase brain venous pressure, which may lead to brain injury. The aim of the present study was to analyse the effect of IAH on brain venous pressure and brain total and ionised magnesium (tMg and iMg), calcium (Ca) and zinc (Zn) contents in rats. MATERIAL AND METHODS Forty four adult Wistar rats were examined. Animals were divided into two groups: control, and IAH: rats with intra-abdominal pressure (IAP) elevated to 25 mmHg. IAP was measured directly in the abdominal cavity. After retrograde cannulation of the jugular vein, the jugular venous pressure (JVP) was measured as the brain venous pressure. JVP and IAP were noted after induction of anaesthesia, immediately following induction of IAH and 90 min after induction of IAH. In all rats, brains were removed for biochemical and histological analysis. RESULTS Biochemical analysis was performed in 30 rats, histological visualisation in 14. IAP elevated to 25 mmHg increased JVP in the IAH group. After 90 min, JVP decreased; however, its value was still higher compared with pre-IAH. In the IAH group, tMg and iMg were significantly lower than in the control group. Moreover, Ca and Zn levels were higher in the IAH group compared with the control group. The histological examination showed changes indicative of ischaemic neuronal cell stress. CONCLUSIONS Firstly, increase in IAP elevates JVP. Secondly, raised JVP decreases tMg and iMg. Thirdly, raised JVP increases the Ca and Zn content in the rat brain. Fourthly, IAH leads to changed characteristics of brain ischaemia.

Complement receptor 1 gene polymorphism and cardiovascular disease in dialyzed end-stage renal disease patients.

Inflammation plays an important role in cardiovascular disease (CVD). The complement system is a critical component of innate and acquired immunity. We investigated whether the polymorphisms in the complement receptor 1 (CR1) gene are associated with CVD in end-stage renal disease (ESRD) patients. The study groups of 1200 patients with ESRD, 360 patients with type 2 diabetes and 924 healthy individuals were genotyped. The GG genotype of the C5507G polymorphism was significantly more frequent in ESRD patients with CVD than in patients without CVD and controls (odds ratio [OR] = 3.44, 95% confidence interval [CI] = 2.23-5.3, and OR = 5.46, 95% CI = 3.72-8.0, respectively). The GG genotype was observed in 62% of patients with a history of myocardial infarction. The frequency of the G allele was also higher in patients with CVD (OR = 2.24, 95% CI = 1.93-2.61 vs controls, and OR = 1.97, 95% CI = 1.63-2.36 vs patients without CVD). In the multivariate logistic regression analysis the carrier status of G allele of C5507G polymorphism was an independent risk factor of CVD in ESRD patients (p < 0.001). In conclusion, our results suggest strong association between the CR1 gene polymorphism and CVD in ESRD patients.