EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Kinetic properties of erythrocyte membrane Ca2+ ATPase and effects of peroxides on the activity of the enzyme

Hayvansal organizmaların hücre içi ve hücre dışı kalsiyum- iyonlarının fizyolojik sınırlar içerisinde sabit tutulmasından sorumlu olan Ccr+ ATPaz enziminin aktivitesi insan eritrosit zarlarında farklı inkübasyon ortamları kullanılarak ölçülmüş, enzimin aktivatörü olduğu bildirilen kalmodulinin (CaM) enzim aktiyitesine etkisi incelenmiştir. Enzimatik reaksiyonun maksimum hızı (Vm), 16 fimol Pilmg prot. saat, Michaelis Menten hız sabiti (Km), 1,9 mM ve aktivasyon enerjisi (Ea), 4,5 kkal/mol olarak bulunmuştur. Aktif oksijen bileşiklerinden hidrojen peroksit (H2O2) ve tersiyer butil hidroperoksitin (t-BHP) enzim aktivitesini azalttığı ancak t-BHP'in H2Û2'ye göre daha fazla inhibisyon etkisine sahip olduğu saptanmıştır.Activity of human erythrocyte membrane Ca^+ ATPase which is responsible for maintaining the inside and outside Ca concentration of the cell within physiological limits, was measured by using different incubation mediums. The effect of calmodulin (CaM) on the activity of the enzyme was investigated. Maximum velocity of the reaction (specific activity) (Vm), Michaelis-Menten Coefficient (Km) and activation energy (Ea) were determined as 16 [xmol Pilmg prot.h, 1.9 mM and 4.5 kcallmol, respectively. Effects of two activated oxygen species, tert-butyl hydroperoxide (t-BHP) and hydrogen peroxide (H2O2) on the enzyme activity were also determined. Both peroxides inhibited the enzyme activity, however their effects were different and t-BHP has more inhibitory effect than H2ö2

HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population

Increased Gastric Cancer Risk with PTEN IVS4 Polymorphism in a Turkish Population

We aimed to investigate the association of the phosphatase and tensin homolog (PTEN) IVS4 polymorphism with a gastric cancer (GC) risk in the Turkish population. A hospital-based case-control study was conducted in 93 patients with GC, and 113 healthy controls. The PTEN IVS4 (rs no: 3830675) polymorphism was determined by using polymerase chain reaction-restriction fragment length polymorphism analysis. The PTEN IVS4 (-/-) genotype exhibited a significantly elevated risk for GC compared to controls (p 0.05). In conclusion, the PTEN IVS4 polymorphism might contribute to the development of GC in a Turkish population. Further studies, including comparison of the PTEN IVS4 polymorphism with plasma and tissue expressions of PTEN in larger study size groups will provide a further assessment of the PTEN IVS4 polymorphism in GC patients

Interactive Effects of Common Haplotypes of Two Leukocyte Diapedesis-Related Genes, LFA-1 and JAM-A on Breast Cancer Risk

Leukocyte diapedesis is an important process in breast cancer etiopathogenesis. Therefore, Junctional adhesion molecule-A (JAMA) and lymphocyte function-associated antigen-1 (LFA-1) genes are among potential candidate genes involved in breast cancer development. In the present study, JAM-A rs790056 (T > C), LFA-1 rs8058823 (A > G) and LFA-1 rs2230433 (C > G) gene variations and their associations with breast cancer risk were investigated in breast cancer patients and healthy subjects. The JAM-A and LFA-1 genotypes were determined in 108 breast cancer patients and 63 healthy controls with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. LFA-1 rs8058823 common AA genotype (x(2) = 6.062, p = 0.014) and A allele frequency (p = 0.001) and LFA-1 rs2230433 rare GG genotype frequency (p = 0.048) was higher in the patient group compared with controls. The TA haplotype (JAM-A rs790056-T, LFA-1 rs8058823-A alleles) frequency was significantly increased in the patient group compared with controls (p = 0.0173), while the TG haplotype (JAM-A rs790056-T, LFA-1 rs8058823-G alleles) and CG haplotype (LFA-1 rs2230433-C, LFA-1 rs8058823-G alleles) frequencies were significantly lower in the patient group compared with controls (p = 0.0051 and p = 0.002, respectively). In addition, the TCG haplotype (JAM-A rs790056-T, LFA-1 rs2230433-C, LFA-1 rs8058823-G alleles) frequency was significantly lower in the patient group compared with controls (p = 0.0096). Haplotype analysis confirmed that the LFA-1 rs8058823 is more effective in breast cancer risk than LFA-1 rs2230433 and JAM-A rs790056. LFA-1 rs8058823 A allele may be related to breast cancer risk, influencing leukocyte diapedesis. Our findings indicate that functional gene variations associated with leukocyte diapedesis may affect breast cancer risk

Combined Effect of CYP1B1 Codon 432 Polymorphism and N-Acetyltransferase 2 Slow Acetylator Phenotypes in Relation to Breast Cancer in the Turkish Population

Background: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated. Patients and Methods: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Results and Conclusion: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004)

Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case–Control Study

© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Breast cancer (BC) has a high incidence rate among women worldwide, and the mechanisms and etiology of this disease are not yet fully understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that plays important roles in energy metabolism and cellular differentiation, is also suggested to be effective in cancer development. However, the results of studies investigating the cancer association with PPARgamma are inconsistent, creating a need for further investigation of the effects of this transcription factor on BC risk. We have examined the Pro12Ala-(rs1801282) and C161T-(rs3856806) polymorphisms of the PPARgamma gene in Turkish patients with BC in this case–control study. A total of 95 women diagnosed with BC as cases and 119 controls were genotyped for PPARgamma polymorphisms by polymerase chain reaction and restriction fragment length polymorphism techniques. The ProPro genotype and T161 allele were associated with an increased risk of BC comparing with the Ala12 allele and CC161 genotype, respectively (p 60 years) (p = 0.007) are risk factors for breast cancer. We also found that the PPARgamma Pro12Ala and C161T polymorphisms were in linkage disequilibrium (D’:0.511, r2:0.099). It was determined that carrying ProPro-T161 risky PPARgamma haplotype was associated with a higher risk of BC compared to protective Ala12-CC161 haplotype (p < 0.01, OR:7.797, 95% CI:3.521–17.263). We concluded that PPARgamma Pro12Ala and C161T polymorphisms are associated with increased BC risk, and ProPro-T161 risky haplotype, which is in linkage disequilibrium, increases this effect

Anatolian Propolis Prevents Oxalate Kidney Stones: Dramatic Reduction of Crystal Deposition in Ethylene-Glycol-Induced Rat Model

One of the many properties of propolis, a gift of nature, is that it is a potent antioxidant agent, which has been shown to be a miracle-worker in many different diseases. In this study, its possible protective and reversing effects against hiperoxaluria was investigated in a rat model in comparison with verapamil In all 5 groups (Total n=76), aside from the control, hiperoxaluria was induced with continuous ethylene glycol (EG) administration. The others received EG only, 50 mg/kg propolis, 100 mg/kg propolis and 1 mg/kg verapamil To estimate the antioxidant/oxidant status in the tissue and serum samples, catalase (CAT), superoxide dismutase (SOD), total glutathione (GSH), nitric oxide (NO), malonyl dialdehyde (MDA) and total anti-oxidant capacity (T-AOC) were measured after 7 and 28 days. In the early phase, serum T-AOC levels were significantly elevated in the EG+P100 (p=0.0062) compared to the control, while in the late phase, it was elevated in the EG+P50 (p=0.037) and EG+V (p=0.009) compared to the EG only group. Propolis administration was observed to dramatically decrease crystal deposition (p<0.0001) and was more effective in the prevention of oxalate-induced renal injury than verapamil Propolis being a natural product with almost none adverse effects elevates its value as a future approach to urolithiasis