The Effect of Continuous Positive Airway Pressure (CPAP) Therapy on Serum Caspase-3 Level in Patients with Obstructive Sleep Apnea (OSA).

INTRODUCTION: Intermittent hypoxemia has an important role in the physiopathogenesis of obstructive sleep apnea (OSA) complications. Increased apoptosis due to intermittent hypoxemia may be an important clinical entity in OSA. In this study, we aimed to evaluate caspase-3 enzyme level, which is an indirect marker of increased apoptosis in patients with OSA and to evaluate the effect of OSA treatment with continuous positive airway pressure on caspase-3 enzyme level. MATERIALS AND METHODS: This study included 141 consecutive patients admitted to the sleep-disordered breathing laboratory within 6 months. Caspase-3 was measured in routine blood samples obtained on the morning of polysomnography (PSG) performed at night. The compliance of the patients to CPAP treatment was evaluated and caspase-3 levels were checked again after treatment. RESULTS: A total of 141 patients, 39 females (27,7%) and 102 males (72,3%) were included in the study. The mean age of the patients was 49 ± 12 years (min-17, max-77). According to PSG results, OSA was detected in 95.7% (135/141) of the cases. Mild OSA was 35 (24.8%), moderate OSA 39 (27.7%) and severe OSA 61 (43.3%) cases. Median caspase-3 enzyme levels were similar in men and women in the study group. There was no statistically significant difference in hemogram parameters and caspase-3 enzyme levels between the groups divided according to the presence and severity of OSA. It was determined that caspase-3 enzyme level did not change significantly after 3 months of CPAP treatment in OSA compared to pretreatment. Caspase-3 was found to have a negative correlation with both the percentage of daily use of CPAP therapy and the percentage of CPAP device use for more than 1 h per night. It was found that the control caspase-3 level decreased statistically significantly as the percentage of daily use of CPAP therapy increased (r = -0.397, p = 0.030). It was found that the control caspase-3 level decreased statistically significantly as the percentage of CPAP therapy use for more than 1 h per night increased (r = -0.411, p = 0.024). CONCLUSION: The results of this study did not reveal a relationship between the severity of OSA and caspase-3 levels. However, blood caspase-3 levels decreased as treatment compliance increased, suggesting that CPAP treatment may correct increased apoptosis in OSA. There is a need for more comprehensive studies on this issue.

The predictive role of laboratory parameters in cardiovascular risk assessment in obese.

The significance of cardiovascular diseases in mortality is indisputable. It is well-established that cardiovascular diseases are more prevalent among individuals with obesity. This study aimed to determine the predictive value of easily accessible hematological and biochemical parameters in assessing cardiovascular risk among obese patients. The study was designed as an observational retrospective. Department of Family Medicine, study was carried out between 25/06/2022 to 30/10/2022. The data of 439 obese patients were analyzed retrospectively. Using the online Heart Score system, the patients were classified into low, medium, high, and very high cardiovascular risk categories. The hemogram and certain biochemistry values of the patients at the time of admission were examined. Receiver operating characteristic (ROC) analyses were conducted to discriminate cardiovascular risk classes based on laboratory values. Markers with high diagnostic value, including a high area under the curve (AUC) value, sensitivity, and specificity, were presented. Significant differences were observed between the groups in terms of age, systolic blood pressure, diastolic blood pressure, total cholesterol, low-density lipoprotein, glucose, HbA1c, hemoglobin, platelet count, neutrophil (NEU) count, and platelet-lymphocyte ratio parameters (P < .05). The white blood cell count and NEU count of patients in the high-risk groups were found to have significantly higher AUC values compared to the moderate-risk group (AUC values of .737 and .779, respectively). The white blood cell and NEU parameters were found to have a positive predictive value in estimating the degree of cardiovascular risk. These parameters can potentially serve as biomarkers in identifying individuals at high risks for cardiovascular diseases.

Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells.

Glioblastoma (GBM) is classified as a stage-IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)-binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron-dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87-MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase-3/7 activity were determined. We found that borax reduced U87-MG cell viability in a concentration- and time-dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87-MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87-MG cells. The result showed that borax in U87-MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87-MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.

The Use of Predictive Laboratory Tests in Rapid Triage of COVID-19 Pandemic Outpatient Clinic Patients.

BACKGROUND: Patients who come to the emergency pandemic outpatient clinic with a pre-diagnosis of COVID-19 are still a burden on the health system. Rapid triage of patients is important to reduce transmission. The aim of this study is to evaluate the biochemistry and hemogram results of real-time reverse transcription-polymerase chain reaction (RT-PCR) positive and negative patients in the emergency pandemic outpatient clinic and to investigate predictive values of the initial tests that will help to make rapid diagnosis. METHODS: Patients who applied to the emergency pandemic outpatient clinic with the suspicion of COVID-19 between November 01, 2020 and January 01, 2021 were evaluated with RT-PCR and laboratory examinations. RESULTS: A total of 551 patients were included in the study. The mean age of the patients was 50.31 ± 18.47 (min. 18 - max. 94), and 47.2% (n = 260) of the patients included in the study were male and 52.8% (n = 291) were female. In the comparison of hemogram parameters, we found that mean platelet volume (MPV) was significantly higher (p = 0.023), whereas white blood cell (WBC), platelet counts (PLT), lymphocyte and neutrophil values were significantly lower in RT-PCR positive patients (p < 0.001). There were no significant differences between the PCR positive and negative patients in terms of other parameters. In the comparison of biochemical parameters, we found that lactate dehydrogenase LDH (p = 0.001), creatinine (p = 0.002), and AST (p < 0.001) values were significantly higher in PCR positive patients, while there were no significant differences in terms of other biochemical parameters (p > 0.05). CONCLUSIONS: Our study results show that the practical quick-look hemogram and MPV can be used as a specially evaluated parameter in the rapid management of the first application COVID-19 patients. In addition, biochemically high levels of LDH and creatinine can be used to guide the clinician in terms of early hydration of the patient with a pre-diagnosis of COVID-19 to alleviate acute kidney damage.

The evaluation of both the expression and serum protein levels of Caspase-3 gene in patients with different degrees of SARS-CoV2 infection.

To evaluate the effects of Caspase-3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 41 individuals (male: 21; female: 20) with SARS-CoV-2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3  2-ΔΔCt (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 2-ΔΔCt levels and hemoglobin (p = 0.023), between CASP3 2-ΔΔCt levels and C-reactive protein (CRP) (p = 0.001), between CASP3 2-ΔΔCt levels and ferritin (p = 0.003), between CASP3 2-ΔΔCt levels and lactate dehydrogenase (p = 0.001), and between CASP3 2-ΔΔCt levels and SpO2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS-CoV-2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease.

Association of interleukin 18-607A/C and -137C/G polymorphisms with oxidative stress in renal transplant recipients.

Objectives IL-18 mediates various inflammatory and oxidative responses including renal injury, fibrosis, and graft rejection. It has been reported that the promoter -607 and -137 polymorphisms of IL-18 influence the level of IL-18. This prospective observational study investigated the association between oxidative stress with IL-18-607 and -137 polymorphisms in renal transplant recipients. Patients and methods This study included 75 renal transplant recipients (28 female, 47 male) from living-related donors. Blood samples were collected immediately before and after transplantation at day 7 and month 1. Serum IL-18, creatinine, cystatin C, CRP, and oxidative stress markers (TOS, TAC) were measured. The Oxidative Stress Index (OSI) was calculated. Polymorphisms of the promoter region of the IL-18 gene, IL18-607A/C, and -137C/G were determined by analysis of a "real-time PCR/Melting curve". Results Serum creatinine, cystatin C, CRP, IL-18, TOS, and OSI levels significantly decreased after transplantation. Post-transplant levels of serum TAC and estimated GFR demonstrated consistent significant increases. Serum IL-18 levels were significantly higher in patients with IL-18-137 GG and IL-18-607 CC genotypes before transplantation. Conclusion Our results indicate that the IL-18-137 GG and -607 CC genotypes contribute to higher IL-18 levels; however, the influence of these polymorphisms on oxidative stress has not been observed.

The association of serum-free light-chain levels with markers of renal function.

BACKGROUND: The kidney is often affected in plasma cell dyscrasias, usually due to the effects of nephrotoxic monoclonal-free light chains. Renal failure due to a monoclonal gammopathy may be detected by the highly sensitive serum-free light-chain (sFLC) ratio yet missed by electrophoretic assays. The aim of this study was to assess sFLC levels in relation to markers of renal function. METHODS: Five-hundred thirteen patients were included in this study. sFLC levels were measured by Freelite® (The Binding Site Group Ltd, Birmingham, UK) assay using the BNII nephelometer (Siemens Diagnostics, Germany). Kappa/lambda (κ/λ) sFLC ratio was calculated. Serum creatinine levels were analyzed by modified Jaffe method in Cobas 8000 analyser. GFR was estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Patients were assigned to two groups depending on their eGFR values: ≤ 60 mL/min/1.73 m(2) (Group 1, n = 103) and > 60 mL/min/1.73 m(2) (Group 2, n = 410). Data were expressed as median and min-max. All the statistical analyses were done with SPSS version 20.0 and a significance level of 0.05 was considered. RESULTS: Serum κ-FLC median value was 36.4 (5.62-16,000) mg/L, serum λ-FLC was 21.7 (4.91-8770) mg/L, κ/λ sFLC ratio was 1.33 (0.01-3258) and serum creatinine was 1.56 (0.63-7.21) mg/dL in Group 1. Both λ sFLC and κ/λ sFLC ratios were correlated with eGFR (r = -0.318, r = 0.198, p < 0.05, respectively). We did not find any significant correlation between κ/λ sFLC ratio and eGFR in Group 2. CONCLUSIONS: We examined the association between sFLC concentrations and renal function. Our preliminary findings suggest that serum λ-FLC might be considered as a useful marker for predicting renal function. Prospective studies are needed to clarify the usefulness of these parameters for identifying renal failure due to a monoclonal gammopathy.

Comparison of Cystatin C and ß-Trace Protein Versus 99mTc-DTPA Plasma Sampling in Determining Glomerular Filtration Rate in Chronic Renal Disease.

UNLABELLED: Glomerular filtration rate (GFR) is the best indicator of renal function. The gold standard for GFR measurement is inulin clearance. However, its measurement is inconvenient, time-consuming, and costly. Thus, in both scientific studies and routine clinical practice nuclear medicine methods ((99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA] and (51)Cr-ethylenediaminetetraacetic acid [(51)Cr-EDTA]) are preferred, and they correlate strongly with inulin clearance. In addition, cystatin C and ß-trace protein have also recently been used for this purpose. In the literature, however, data are limited about the clinical value of cystatin C and ß-trace protein in GFR measurement in chronic renal disease (CRD), and the results have been inconclusive. In this study, we aimed to determine the efficiency of cystatin C and ß-trace protein in the determination of GFR in CRD patients. METHODS: Eighty-four patients with CRD were included in the study (59 men and 25 women; age range, 21-88 y; mean age, 61 y). GFR was calculated using the gold-standard (99m)Tc-DTPA 2-sample plasma sampling method (TPSM) and 2 alternative methods: a formula using cystatin C and a formula using ß-trace protein. The correlation between TPSM and the cystatin C and ß-trace protein methods was assessed, and Bland-Altman analysis was used to graph scatterplots of the differences at a confidence interval of 95% (mean difference ± 1.96 SDs). RESULTS: GFRs calculated using both alternative methods correlated strongly with those calculated using the gold standard. However, the correlation was stronger for the cystatin C method than for the ß-trace protein method, and neither method produced reliably consistent GFRs. CONCLUSION: This study demonstrated that cystatin C and ß-trace protein do not reflect GFR with sufficient accuracy.

Clinical value of cystatin C and beta-trace protein in glomerular filtration rate in renal transplant cases with stable renal graft functions: comparison by the 99mTc-DTPA plasma sample method.

AIM: The aim of this study was to investigate the value of cystatin C and beta-trace protein (BTP) levels in determination of the glomerular filtration rate (GFR) by accepting the technetium-99m diethylenetriamine pentaacetic acid (Tc-DTPA) method as the gold standard for GFR measurement in renal transplant patients with stable renal functions and to investigate the value of cystatin C and BTP levels in the determination of GFR in cases with or without renal tubular injury. METHODS: A total of 89 (60 men and 29 women) renal transplant patients aged 19-67 years (mean 38.15 years) with stable graft functions were included in the study. GFR was calculated using three different methods: (a) the Tc-DTPA two plasma sample method; (b) eight different formulas containing cystatin C; and (c) three different formulas containing BTP. In addition, the cases were divided into two groups on the basis of N-acetyl-ß-D-glucosaminidase and ß2 microglobulin levels showing tubular damage. RESULTS: GFR values obtained with cystatin C had a better correlation with the gold standard method compared with those obtained with BTP, and the GFR value obtained with cystatin C had the most reliable consistency. We found that cystatin C provided more accurate results in GFR follow-up in renal transplant patients with no tubular injury compared with those with tubular injury. CONCLUSION: Cystatin C is a good marker of GFR in renal transplant patients, especially in those with no tubular injury; however, BTP is not as good as cystatin C in that regard.

The effects of luteolin on the intestinal ischemia/reperfusion injury in mice.

The purpose of this study is to investigate the potential protective effect of the flavonoid Luteolin on ischemia-reperfusion (IR) injury in mouse intestine, which has not previously been studied. Twenty-four female C57BL/6 mice were randomly assigned to four groups, each consisting of 6 mice: a sham group (laparotomy, but no IR injury), a sham + Luteolin group (no IR, and Luteolin was administered intraperitoneally 30 min after laparotomy), IR group (30 min occlusion of the superior mesenteric artery (SMA) then 2 hr' reperfusion), IR + Luteolin (30 min occlusion of the SMA then 2 hr' reperfusion; Luteolin was administered intraperitoneally before reperfusion). Intestine tissues were harvested from the mice for histopathological and biochemical analysis. Total oxidant status (TOS) and total antioxidant capacity (TAC) of the intestinal tissues were measured using Erel's method. Oxidative stress index (OSI) was calculated using the TOS/TAC ratio. Intestinal histological changes were significantly decreased in the IR + Luteolin group compared with the IR group (p = .037). TOS tissue levels were also significantly decreased in the IR + Luteolin group compared with the IR group (p = .005). TAC levels did not increase significantly in the IR treatment group and were not affected by Luteolin treatment (p > .05). The results of this study show that Luteolin administration provides considerable protection against IR injury in the mouse intestine.

Levels of TNF-α, soluble TNF receptors (sTNFR1, sTNFR2), and cognition in bipolar disorder.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-α) may play an important role in bipolar disorder (BD) pathogenesis. There is only one study about a relationship between TNF-α levels and cognitive impairments in BD. The aim of the present study was to see whether TNF-α, soluble P55 TNF receptor (sTNFR1), and soluble P75 TNF receptor (sTNFR2) levels in BD patients are different from controls and to investigate the relationships between the levels of TNF-α, sTNFR1, and sTNFR2 and the cognitive functions in euthymic BD patients and controls. METHODS: We assessed 54 BD type I patients and 18 controls by using a battery of neuropsychological tests. Serum TNF-α levels were measured using a commercially available enzyme-linked immunosorbent assay, whereas serum sTNFR1 and sTNFR2 levels were measured using a commercially enzyme-amplified sensitivity immunoassay kit. RESULTS: We found that levels of sTNFR1 and sTNFR2 in BD patients were different from controls. No difference was detected between the BD group and the control group for levels of TNF-α. TNF-α level was found to have a negative correlation with the delayed recall in RAVLT. CONCLUSIONS: High levels of sTNFR1 and sTNFR2 in euthymic patients showed that it may support that proinflammatory process continues in euthymic period. This is the first study which showed increased sTNFR2 levels in euthymic period, which could be interpreted as a compensatory mechanism and again the first which deals with verbal memory.

The assessment of carotid intima media thickness and serum paraoxonase-1 activity in Helicobacter pylori positive subjects.

BACKGROUND: The role of inflammation in the pathogenesis and progression of atherosclerosis has been increasingly discussed. Although the seroepidemiological studies have suggested a relationship between Helicobacter pylori (H. pylori) infection and atherosclerosis; the issue is still controversial. It is well known that abnormal lipid profil is related to atherosclerosis and the measurement of carotid-intima media thickness (CIMT) is one of the surrogate marker of atherosclerosis. The serum concentration of high-density lipoprotein (HDL-C) has been known to have an inverse correlation with the development of atherosclerosis. Paraoxonase-1 (PON1) is a major anti-atherosclerotic component of HDL-C. PON1 activity is related to lipid peroxidation and prospective cardiovascular risk. The aim of this study was to investigate CIMT and serum PON1 activities along with lipid parameters in H. pylori positive and negative subjects. METHODS: Thirty H. pylori positive subjects and thirty-one negative subjects were enrolled. H. pylori infection was diagnosed by the presence of positivity of stool H. pylori antigen test or Carbon 14 labeled urea breath test. Serum PON1 activity was measured spectrophotometrically. Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C). We assessed CIMT by high-resolution ultrasound of both common carotid arteries. RESULTS: We found that the mean and maximum values of right and overall CIMT in H. pylori positive subjects were significantly thicker than those of H. pylori negative subjects. There was no significant differences in serum HDL-C, LDL-C, TC levels and TC/HDL-C ratios between two groups. Serum TG levels of H. pylori positive subjects were significantly higher than those of H. pylori negative subjects (p = 0.014). We found that PON1 activities were significantly lower in H. pylori positive subjects compared with negative subjects. No significantly correlation was observed between PON1 and CIMT values. CONCLUSIONS: There is an increase in CIMT values in patients with H. pylori positive compared to H. pylori negative subjects. PON1 activity decrease significantly in H. pylori positive subjects. However, an association between PON1 and CIMT was not found. These data indicated that H. pylori may have a role in atherosclerotic processes, however, further studies are needed to evaluate the exact mechanisms.