The positive effects of preoperative chlorhexidine rinse to reduce postoperative pneumonia after kidney transplantation surgery.

BACKGROUND: Postoperative pneumonia is one of the most observed hospital-acquired infections and increases the postoperative mortality rate. Further, it drives the healthcare systems under a severe financial burden. Preventing postoperative pneumonia is an incredibly challenging issue for clinicians. Since immunosuppression therapy, the patients who had kidney transplants are more vulnerable to postoperative infections. There is no data in the scientific literature focusing on the effects of preoperative oral care with chlorhexidine antiseptic solutions on postoperative pneumonia in kidney transplantation surgery cases. In the present research, we studied this topic. METHODS: A prospective, randomized clinical trial was conducted at our institution between August 2020 and August 2022. Group A: Received 0.12 % chlorhexidine oral rinse preoperatively; Group B: Not received 0.12 % chlorhexidine oral rinse preoperatively. We analyzed the differences between the two trial groups using a chi-square or t-test. The Mann-Whitney U test was used for the categorical data. RESULTS: Nine patients (17.6 %) were diagnosed with postoperative pneumonia in Group A and fourteen (25.9 %) in Group B (p < 0.05). Hospitalization time of Group B was prolonged (p < 0.05). In multivariate analysis, significant risk factors associated with postoperative pneumonia were advanced age, diabetes mellitus, smoking, delayed graft function and not gargling with 0.12 % chlorhexidine (p < 0.05). CONCLUSIONS: To reduce postoperative pneumonia risk in patients undergoing kidney transplantation surgery, an oral health protocol including 0.12 % chlorhexidine mouth rinse seems beneficial.

Nilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages.

In this study, we aimed to analyze the effects of first and second-generation Bcr-Abl tyrosine kinase inhibitors, imatinib and nilotinib on LPS/IFN gamma activated RAW 264.7 macrophages. Our data revealed that imatinib was less effective on nitrite levels and more toxic on macrophages compared to nilotinib. Therefore, we further analysed the effect of nilotinib on various inflammatory markers including iNOS, COX-2, NFkB, IL-6, p-ERK, p-p38 and p-JNK in LPS/IFN gamma activated RAW264.7 macrophages. Spectrophotometric viability test and Griess assay,western blot, RT-PCR and luciferase reporter assays were used to analyze the biological activity of nilotinib. Our findings revealed that nilotinib decreases nitrite levels, iNOS mRNA, iNOS and p-p38 protein expressions significantly whereas induces IL-6 mRNA and p-JNK protein expressions at particular doses. We did not find significant effect of nilotinib on COX-2, p-ERK and nuclear p65 proteins and NFkB transcriptional activity. In addition, the binding mode of nilotinib to iNOS protein was predicted by molecular docking. According to the docking analyses, nilotinib exhibited hydrophobic interactions between MET349, ALA191, VAL346, PHE363, TYR367, MET368, CYS194, TRP366 residues at the binding pocket and the molecule as well as van der Waals interactions at specific residues. In conclusion, our results reveal that, in addition to its anticancer activity, nilotinib can exhibit immune modulatory effects on macrophages through its effects on iNOS, IL-6, p-p38 and p-JNK.

Some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives overcome imatinib resistance by induction of apoptosis and reduction of P-glycoprotein activity.

Imatinib (IMA) is a tyrosine kinase inhibitor (TKI) introduced for the chronic myeloid leukemia (CML) therapy. Emergence of IMA resistance leads to the relapse and failure in CML therapy. Benzimidazole is a heterocyclic organic compound which is widely investigated for the development of anticancer drugs. In this study, we aimed to explore the anticancer effects of some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives on K562S (IMA-sensitive) and K562R (IMA-resistant) cells. To analyze the cytotoxic and apoptotic effects of the compounds, K562S, K562R, and L929 cells were exposed to increasing concentrations of the derivatives. Cytotoxic effects of compounds on cell viability were analyzed with MTT assay. Apoptosis induction, caspase3/7 activity were investigated with flow cytometry and BAX, BIM, and BAD genes expression levels were analyzed with qRT-PCR. Rhodamine123 (Rho-123) staining assays were carried out to evaluate the effect of compounds on P-glycoprotein (P-gp) activity. The hit compounds were screened using molecular docking, and the binding preference of each compounds to BCR-ABL protein was evaluated. Our results indicated that compounds triggered cytotoxicity, caspase3/7 activation in K562S and K562R cells. Rho-123 staining showed that compounds inhibited P-gp activity in K562R cells. Overall, our results reveal some benzimidazole derivatives as potential anticancer agents to overcome IMA resistance in CML.

Novel indole retinoid derivative induces apoptosis and cell cycle arrest and modulates AKT and ERK signaling in HL-60 cells.

Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high-risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL-60. Novel N-(1H-indol-1-yl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound 5, were determined in K562 chronic myeloid leukemia and HL-60 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound 5 more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound 5 induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0/G1 was also increased with compound 5 treatment. Important modulator proteins of cell proliferation p-ERK, p-AKT, and p-m-TOR were also found to be inhibited with compound 5 treatment. Collectively, our results reveal compound 5, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia.

Diagnostically challenging rupture of pancreaticoduodenal artery aneurysm: A case report.

Splanchnic artery aneurysms are rare vascular lesions with a high risk of rupture regardless of their size. Symptoms may vary from simple abdominal pain or vomiting to morbid conditions like haemorrhagic shock; however, most aneurysms are asymptomatic and difficult to diagnose. In this study, it was aimed to present the case of a 56-year-old female with a ruptured pancreaticoduodenal artery aneurysm treated by coil embolization.

Synthesis of Some Benzimidazole-derived Molecules and their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.

BACKGROUND: Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. OBJECTIVE: In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1Hbenzo[ d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer activities. METHODS: Compounds were tested by cell-free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer, and L929 fibroblast cell lines. RESULTS: Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells, whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. CONCLUSION: These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells, and further research will enlighten the underlying mechanisms of their effects.

Effect of Visceral, Subcutaneous and Retroperitoneal Adipose Tissue on Renal Function After Living Donor Nephrectomy: A Retrospective Analysis of 69 Cases.

PURPOSE: Recent studies reported that the presence of metabolic syndrome is closely correlated with impaired kidney function after living donor nephrectomy. Since the measurement of body mass index cannot differentiate the amount of body adipose tissue from total body weight, body mass index is not a reliable parameter for determining metabolic syndrome. In the present study, we investigated the correlation between body adipose tissue and kidney function recovery following living donor nephrectomy. MATERIALS AND METHODS: The patients who underwent living kidney donor nephrectomy consequently from July 2016 through December 2017 were enrolled in the study. We preoperatively measured the visceral (VAdT), retroperitoneal (RPAdT), and subcutaneous (SCAdT) adipose tissue volume by a computed tomography scan. Body mass index, adipose tissue measurements, and postoperative estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: The decrease between preoperative eGFR, and the first day, the first month and the sixth month eGFR after surgery were statistically significant (P = .001; P = .001; P = .001, respectively). The negative correlation between VAdT/SCAdT measurements and changes in eGFR at the first and the sixth postoperative month compared to preoperative eGFR were statistically significant (P = .049; P = .041, respectively). Additionally, RPAdT measurements and changes in eGFR at the first and the sixth postoperative month compared to preoperative eGFR (decreasing as RPAdT value increased) were statistically significant (P = .035; P = .026, respectively). CONCLUSION: According to a preoperative computed tomography scan, VAdT, RPAdT, and VAdT-to-SAdT ratio can predict impaired kidney function recovery. Furthermore, RPAdT measurement is a new variable to predict the impaired kidney function after living donor nephrectomy.

Evaluation of Male Circumcision: Retrospective Analysis of One Hundred and Ninety-eight Patients.

Introduction Circumcision is the oldest and most frequently used surgical procedure. It dates back to at least 10,000 years from today. The debate on the benefits and necessity of circumcision is ongoing. In this study, we aimed to determine the complications and complication rate of circumcisions occurring in our circumcision clinic and to compare these with the complication rates in the world. Methods A total of 198 male patients circumcised between 2011 at 2019 at Bursa State Hospital was enrolled in the presented retrospective study. Demographic data of the patients were assessed and the height and weight of the patients were evaluated according to the child growth standards and weight for age percentile charts for boys of the World Health Organization (WHO). All early or late complications were noted after circumcision. Results The mean age of the patients was 93.57±40.12 (2-248) months. The mean follow-up time was 16.32±9.24 (2-35) months. Sixteen patients had bleeding, four patients had a penile hematoma, and 108 patients had penile edema. There is no statistically significant difference in the penile edema occurrence according to the weight of the patients (p=0.58).  Conclusion Circumcision is a frequently applied procedure. Like any other surgery, perioperative and postoperative complications can be observed. More importantly, a significant number of these complications can be prevented by careful surgery and postoperative care.

Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors.

In this study, a series of benzimidazoles bearing thiosemicarbazide chain or triazole and thiadiazole rings were designed and synthesized. Crystal and molecular structure of the compound 5c has been characterized by single crystal X-ray crystallographic analysis. EGFR kinase inhibitory potencies of synthesized compounds were compared with erlotinib in vitro and most of the compounds exhibited significant activities. Cell culture studies were also carried out for selected compounds and 12b was found to be the most active compound. To understand the binding mode of synthesized benzimidazoles, three compounds (12b, 16, 16c) were selected and placed on the binding site of EGFR tyrosine kinase based on their kinase inhibitor potencies and cell culture studies. Docking study indicated that compound 12b showed two-hydrogen bonding interactions with residues of LYS721 and THR830 at the binding pocket.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.