Did diet compliance and remission reduce oxidative stress in celiac patients?

SUMMARY OBJECTIVE: We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet. METHODS: Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year. RESULTS: While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 μmol/L vs. 365.3±44.0 μmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 μmol/L down to 8.9±4.2 μmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001). CONCLUSION: Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.

Evaluation of serum semaphorin 3A and interleukin 6 levels in patients with pseudoexfoliation syndrome.

PURPOSE: To evaluate serum semaphorin 3A (Sema3A) and interleukin 6 (IL-6) levels in pseudoexfoliation syndrome (PXS) patients to determine whether these mediators play a role in the systemic manifestations of PXS. METHODS: This prospective case-control study included 70 patients divided into PXS (n = 30) and a control group (n = 40). Serum Sema3A and IL-6 levels were analyzed using the enzyme-linked immunosorbent assay. RESULTS: The PXS group had a statistically higher IL-6 level [3.6(0.64-100) pg/mL], compared to the control group [2.1(0.41-39.93) pg/mL] (p < 0.05). On the other hand, the Sema3A level of the PXS group was lower at [21.55(13.2-67.5) ng/mL] compared to the control group at [29.05(11.5-103.3) ng/mL] (p < 0.05). In the PXS group, there was no correlation between the participants' IL-6 values and Sema3A, age, and body mass index (BMI) (r = 0.153, 0.000, - 0.103, respectively, all, p > 0.05), and between Sema3A values and age and BMI values (r = 0.048, - 0.133, respectively, all, p > 0.05). In the control group, there was no correlation between the participants' IL-6 values and Sema3A, age, and BMI values (r = 0.138, - 0.001, - 0.145, respectively, all, p > 0.05) and between the Sema3A and age and BMI values (r = - 0.078, - 0.281, respectively, all, p > 0.05). CONCLUSIONS: Decreased levels of the anti-inflammatory mediator Sema3A and increased levels of inflammatory mediator IL-6 detected in PXS suggest that these molecules may play a role in systemic manifestations of this syndrome, such as inflammation, atherosclerosis, heart arrhythmia, and Alzheimer's disease.

What does the Procalcitonin Level Tell us in Patients with Acute Pancreatitis?

OBJECTIVE: To determine the factors affecting the procalcitonin level, and its association with the severity of pancreatitis in patients with acute pancreatitis (AP). STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Division of Gastroenterology, University of Health Sciences, Diyarbakir Gazi Yasargil Education and Research Hospital and Department of Gastroenterology, Dicle University School of Medicine, Diyarbakir, Turkey, between April 2017 and June 2021. METHODOLOGY: The study included 214 patients diagnosed with AP according to Atlanta criteria. By checking the PCT and CRP values of the patients in the first 12 hours, the relationship with these scales that predict the severity of pancreatitis was statistically examined. RESULTS: Hundred and fifty-two patients (71.0%) had mild, while 62 patients (29.0%) had severe pancreatitis. According to the Atlanta criteria, the mean PCT level of patients with mild pancreatitis was 1.4±0.7 ng/mL, while the mean PCT level of patients with severe pancreatitis was 9.0±12.3 ng/mL (p<0.001). The diagnostic performance of PCT was better for predicting severe AP. For the 0.94 ng/mL cut-off, PCT had 86.9% sensitivity and 50.7% specificity. (AUC=0.731[95% CI: 0.669-0.811]; p<0.001; LR: 1.7). In patients with severe pancreatitis, the PCT level was 4.7±18.5 ng/mL in patients without concomitant infection and 15.8±8.1 ng/mL in patients with concomitant infection (p<0.001). CONCLUSION: High PCT value measured at the time of the first admission to the hospital may predict severe pancreatitis. In addition, a high PCT value at the time of admission to the hospital in patients with pancreatitis may indicate another concomitant infection. KEY WORDS: Acute pancreatitis, Coinfection, Procalcitonin, Severity of pancreatitis.

Development of hepatocellular carcinoma in patients with chronic hepatitis C who had sustained viral response following direct-acting antiviral therapy.

Background and Aim: Several studies have suggested that treatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) may be associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the incidence and risk factors of HCC in HCV patients who achieved a sustained virologic response (SVR) following DAA therapies. Materials and Methods: The medical data of patients who were diagnosed with HCV and received DAA therapy in two tertiary centers in Turkey were retrospectively collected. Results: Among them, 75 patients (52.4%) were noncirrhotic and 68 patients (47.6%) were cirrhotic. The overall SVR rate was 97.2% (139/143). It was 100% in noncirrhotic and 94.1% in cirrhotic patients. HCC was developed in 5 (7.4%) patients, all of whom had baseline cirrhosis. The annual rate of HCC occurrence was 2.94%, and the 5-year cumulative incidence of HCC was 7.3%. The mean Child-Pugh score (CPS) and Model for End-Stage Liver Disease (MELD) score significantly decreased after DAA treatment (CPS 7.0 vs 5.9, p=0.001; MELD 10.8 vs 9.5, p=0.003). Conclusion: There was no significant increase in the rate of HCC in cirrhotic HCV patients treated with DAAs. This treatment led to a remarkably high SVR rate and lowered CPS and MELD scores in cirrhotic HCV patients.

Oxidative stress and the importance of H. pylori eradication in patients with functional dyspepsia.

Background: To investigage the thiol and disulphide levels in Helicobacter pylori-positive patients with non-ulcer dyspepsia and investigate the change in these levels with eradication therapy. Methods: This is a prospective observational study. A total of 320 patients diagnosed with dyspepsia according to Rome IV criteria were included in the study. First, blood samples were drawn from patients to determine their serum thiol and disulphide levels. Endoscopic biopsy was performed on all patients and the biopsy specimens obtained were examined pathologically. Patients positive for H. pylori were administered eradication therapy. Blood samples were drawn from these patients for the second time, and their serum thiol and disulphide levels were measured. The thiol-disulfide levels of the patients who were successful in H. pylori eradication treatment, with those who were not, were compared before and after the treatment. Results: The mean plasma disulphide level decreased significantly from 14.0 ± 6.6 to 10.9 ± 5.9 µmol/L in H. pylori-positive patients that responded to the H. pylori eradication treatment (P = 0.033). On the other hand, there was an insignificant increase in the mean serum thiol level (341.4 ± 30.5 vs. 342.6 ± 29.8 µmol/L; P = 0.273) and an insignificant decrease in the mean serum disulphide level (15.2 ± 2.5 vs. 14.8 ± 2.3 µmol/L; P = 0.163) in H. pylori-positive patients that did not respond to the H. pylori eradication treatment. Conclusion: The inflammation caused by H. pylori shifted the thiol-disulphide equilibrium in the cell redox system towards the direction of disulphide. The study findings suggest that the restoration of the said hemostatic balance with eradication therapy relieved the organism from oxidative stress.

The protective effects of trimetazidine against ovary ischemia-reperfusion injury via the TLR4/Nf-kB signal pathway.

Late diagnosis and treatment of ovarian ischemia can lead to worsening of ischemia, irreversible damage to ovarian functions and infertility. In this process, there is no approved medical treatment that can reduce the negative effects of ischemia and contribute positively to ovarian functions during reperfusion after detorsion. Rats were randomly assigned into one of six groups of eight animals each. The groups were designed as follows: The control group, The ischemia(I) group, The Ischemia + Trimetazidine (I + TMZ) (20 mg/kg) group, and The ischemia-reperfusion group (I/R). The Ischemia-Reperfusion + Trimetazidine (I/R + TMZ) (20 mg/kg) group, and The Sham + Trimetazidine (Sham + TMZ) (20 mg/kg) group. In this study performed thiobarbituric acid reactive substances (TBARS), total thiol (-SH), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), toll-like receptor 4 (TLR4), and nuclear factor-kappa B(NF-κß). Increased oxidative stress and inflammation were as a result of ovarian I and I/R application. Trimetazidine (TMZ), was sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-κß, which were upregulated by oxidative stress and inflammation, were regressed by TMZ. TMZ should be considered as a potential therapeutic agent in addition to surgery in the clinical treatment of ovarian torsion.

The effects of vitamin B12 on the TLR-4/NF-κB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation.

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factorkappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1ß, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue.

Evaluation of Thiol/Disulfide Homeostasis in Bronchiectasis.

PURPOSE: Thiols are sulfhydryl-containing organic compounds that have an important role in preventing cellular oxidative stress. This study compares the blood oxidative stress marker levels in bronchiectasis cases during their stable periods with healthy controls. MATERIALS AND METHODS: Seventy-seven patients (49 patients with stable bronchiectasis/28 healthy controls), followed up by the chest disease clinic, were included in the study. Peripheral blood thiol-disulfide parameters (NT: native thiol (-SH); TT: total thiol (-SH + SS); SS: disulfide (-SS); SS-SH: disulfide/native thiol index; SS-TT: disulphide/total thiol index; SH-TT: native thiol/total thiol index), and ischemia-modified albumin (IMA) levels were examined in the stable bronchiectasis group and the control group. Thiol-disulfide homeostasis was evaluated using a novel and automated assay. Findings and Result. Blood native thiol levels in patients with stable bronchiectasis were found to be significantly higher compared with healthy controls. A positive correlation between the total airway disease score and IMA levels was present. Our findings revealed that native thiol levels, which constitute a part of the antioxidant defense system, are increased in patients with stable bronchiectasis.

Total thiol can contribute to differentiating prostate cancer from BPH: Prostate Thiol Index as a new player.

To assess the distinctiveness of serum native thiol (NT), total thiol (TT) and disulfide (SS) levels in PCa patients, we created a new parameter, prostate thiol index (PTI) [tPSA (TTxPVxAge) -1/2 ]. We determined the performance of the PTI on PCa diagnosis. A total of 107 male patients (PCa:65; BPH:42) who were separated according to their Gleason scores, ISUP grades and EAU risk groups and 20 healthy subjects were included. The performances of the tests were determined. The PCa and BPH groups had lower NT and TT levels and higher SS levels than the control group. PCa patients had higher PTI, tPSA, fPSA, PSAD levels, lower fPSA%, PV and PSA-AV levels than BPH patients. TT, PTI, tPSA, fPSA, fPSA%, PSA-AV, PSAD and PV had significant diagnostic performances. PTI had the highest AUC value and accuracy, PSA-AV had the highest specificity, and fPSA had the lowest sensitivity. The performance of the PTI was the best in distinguishing PCa from BPH. PTI, tPSA and PSAD positively and PSA-AV negatively correlated with ISUP grades and EAU groups. TT can contribute to the discrimination of PCa from BPH and PTI may decrease unnecessary biopsies in clinical practice.

Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters.

BACKGROUND AND OBJECTIVE: Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases. MATERIALS AND METHODS: 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed. RESULTS: We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis. CONCLUSION: Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.

Increased serum concentration of netrin-1 after intravitreal bevacizumab injection: is it a compensatory mechanism to counteract drug side effects?

BACKGROUND: To evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME). METHODS: This prospective case-control study included a total of 50 participants assigned to one of three groups, including 10 individuals with DME and non-proliferative diabetic retinopathy (NPDR), 13 with DME, and proliferative diabetic retinopathy (PDR), and 27 healthy individuals as a control group. Serum VEGF and netrin-1 concentrations were measured by enzyme-linked immunosorbent assays (ELISAs) immediately before, as well as 1 week and 1 month after, intravitreal BCZ injection. RESULTS: The mean VEGF serum concentrations in the PDR and NPDR groups were 388.4 and 196.9 pg/mL at baseline, respectively. After 1 week, these concentrations changed to 193.41 and 150.23 pg/mL, respectively (P = 0.001 and P = 0.005, respectively); after 1 month, the concentrations were 97.89 and 76.46 pg/mL, respectively (P = 0.001 and P = 0.009, respectively). The mean netrin-1 serum concentrations in the PDR patients and NPDR groups were 318.2 and 252.7 pg/mL at baseline, respectively. After 1 week, these concentrations increased to 476.6 and 416.3 pg/mL, respectively (P = 0.033 and P = 0.005, respectively), and after 1 month, they were 676.6 and 747.5 pg/mL, respectively (P = 0.001 and P = 0.005, respectively). The correlation analysis revealed a significant inverse relationship between changes in serum VEGF and netrin-1 concentrations in both the PDR and NPDR groups (r = - 0.685, P = 0.029). CONCLUSIONS: Intravitreal BCZ injections work systemically to significantly decrease serum VEGF levels, leading to a significant upregulation in the concentration of another angiogenic mediator, netrin-1.

A comparison study of dual-energy spectral CT and 18F-FDG PET/CT in primary tumors and lymph nodes of lung cancer.

PURPOSE: We aimed to investigate whether there is a correlation between dual-energy spectral computed tomography (DESCT) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters in primary tumor and metastatic lymph nodes in patients with newly diagnosed lung cancer. METHODS: Primary tumor and metastatic lymph nodes of 68 patients diagnosed with lung cancer were evaluated retrospectively with 18F-FDG PET/CT and DESCT imaging. The histologic subtypes were adenocarcinoma (n=29), squamous cell carcinoma (SCC) (n=26), small cell lung cancer (SCLC) (n=11), and large cell neuroendocrine cancer (LCNEC) (n=2). In terms of PET parameters, SUVmax, SUVmean, SULmax, SULmean, SULpeak, and normalized SUL values were obtained for primary tumors and metastatic lymph nodes. In terms of DESCT parameters, maximum and mean iodine content (IC), normalized IC values, iodine enhancement (IE) and normalized IE values were calculated. RESULTS: We found no correlation between DESCT and 18F-FDG PET/CT parameters in primary tumors and metastatic lymph nodes. In addition, no correlation was found in the analysis performed in any of the histologic subgroups. In patients with a primary tumor <3 cm, there was a moderate negative correlation between the parameters SUVmax-ICmax (r= -0.456, p = 0.043), SUVmean-ICmax (r= -0.464, p = 0.039) SULmean-ICmax (r= -0.497, p = 0.026), SUVmax-ICmean (r= -0.527, p = 0.020), SULmean-ICmean (r= -0.499, p = 0.025), and SULpeak-ICmean (r= -0.488, p = 0.029). CONCLUSION: We consider that DESCT and 18F-FDG PET/CT indicate different characteristics of the tumors and should not supersede each other.

PET-CT and MR Imaging in the Management of Axillary Nodes in Early Stage Breast Cancer.

OBJECTIVE: To discriminate between malignant or benign axillary lymph nodes in breast cancer using MRI, PET-CT, and sentinel lymph node biopsy. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of General Surgery, Recep Tayyip Erdogan University School of Medicine, from January 2014 to March 2019. METHODOLOGY: Sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) was carried out on 102 patients, who had locally advanced cases and had not previously received neoadjuvant therapy. Axillary lymph nodes pathology results were evaluated and compared with PET-CT and MRI findings. RESULTS: PET-CT specificity was 93.18%, MRI specificity was 93.75%, and combined PET-CT and MRI specificity was 97.67%. PET-CT sensitivity was 81.03%, MRI sensitivity was 68.57%, and combined PET-CT and MRI sensitivity was 83.05%. For detecting the presence of axillary lymph node metastasis, there was a good correlation between histopathological results and the combined evaluation with PET-CT and MRI (kappa: 0.785, p <0.001). In combined PET-CT and MRI, short diamater mean values of lymph nodes in 10 patients, which could not detect lymph node metastases, were determined to be 5.2 ±0.9 mm. CONCLUSION: Combining PET-CT and MRI is superior to PET-CT or MRI imaging alone in distinguishing benign and malignant axillary lymph node; and contributes to deciding the approach to axillary lymph node surgery. Lymph node size is also important for this imaging method to determine benign and malignant nodes correctly. Key Words: Breast cancer, PET-CT, MRI, Sentinel lymph node biopsy, Axilla.

The impact of diurnal variation of PSA on timing of measurement in prostate biopsy.

BACKGROUND: Prostate-specific antigen (PSA) synthesis is related to testosterone, which has a diurnal rhythm. PSA might have a diurnal variation and the timing of measurement could change the clinical practice for prostate biopsy. METHODS: Male patients complaining of lower urinary tract symptoms (group 1) and diagnosed with prostate cancer (group 2) were recruited into the study. Morning fasting blood samples were withdrawn between 9.00 and 11.00 am for the determination of biochemical parameters, PSA (PSA1), total testosterone (T1), and estradiol (E1) levels. In the afternoon, between 15.00 and 15.30 pm, blood samples were again obtained from the same participants at the same day and the serum concentration of PSA (PSA2), total testosterone (T2), and estradiol (E2) were measured. RESULTS: A total of 160 and 30 patients were enrolled in groups 1 and 2, respectively. One hundred forty (87.5%) and 26 (86.6%) patients had a decrease in the PSA levels when measured in the afternoon. The Wilcoxon signed-rank test determined a statistically significant difference between the PSA levels measured in the morning and in the afternoon in each group. An analysis of covariance test revealed no statistically significant difference in PSA concentration between the groups after adjustment for baseline concentration (F(1.187) = 0.203, P = .653). There was a weak positive correlation between PSA1/PSA2 and T1/T2, rs (160) = 0.163, P = .034. An extra unit increase in PSA1 concentration leads to a 0.805 (95% confidence interval [CI], 0.781-0.830) and 0.828 (95% CI, 0.807-0.849) ng/mL increase in PSA2 concentration in groups 1 and 2, respectively, that is, patients with and without prostate cancer had a similar decrease in the PSA levels. When measured in the afternoon, 66.6% and 50% patients with a morning PSA level over 3 or 4 ng/mL had a PSA drop below these levels, respectively. CONCLUSIONS: PSA has a diurnal variation and the timing of measurement may alter the decision of the clinician for transrectal ultrasound prostate biopsy.

Radioprotective effect of endogenous melatonin secretion associated with the circadian rhythm in irradiated rats.

Purpose: We investigated the radioprotective effect of endogenous melatonin release at different times associated with the circadian rhythm on head and neck radiotherapy. Materials and methods: Two groups of animals were subjected daily to 8 Gy single fraction radiotherapy in the head and neck region from 5:00 to 6:00 (the morning group) or from 19:00 to 20:00 (the evening group). Corresponding untreated groups served as controls. Submandibular glands from rats sacrificed on the seventh day after irradiation were assessed biochemically and histopathologically. Melatonin, malondialdehyde and superoxide dismutase levels in blood collected immediately prior to irradiation were measured with rat-specific ELISA kits. Results: In irradiated rats, melatonin, malondialdehyde and superoxide dismutase levels were significantly higher in the evening group than in the morning group. In nonirradiated rats, melatonin and superoxide dismutase levels were significantly higher in the evening group than in the morning group. The areas of seromucous acinar cells were similar between the irradiated and nonirradiated evening groups, but the area was higher in the evening irradiated group than in the morning irradiated group. Conclusion: Consideration of endogenous melatonin secretion associated with the circadian rhythm may offer new therapeutic solutions for the complications of head and neck radiotherapy.