The effects of TNF-α inhibitors on carbon tetrachloride-induced nephrotoxicity.

OBJECTIVES: Carbon tetrachloride (CCl4), employed in various industrial fields, can cause acute damage in renal tissues. This study investigated the therapeutic effect of the TNF-alpha inhibitor Infliximab on TGF-ß and apoptosis caused by acute kidney image induced by CCl4. METHODS: Twenty-four male Sprague-Dawley rats were assigned into control, CCl4, and CCl4+ Infliximab groups. The control group received an isotonic saline solution, and the CCl4 group 2 mL/kg CCl4 intraperitoneally (i.p). The CCl4+ Infliximab group was given 7 mg/kg Infliximab 24 hours after administration of 2 mL/kg CCl4. Kidney tissues were removed at the end of the experiment and subjected to histopathological and biochemical analysis. RESULTS: The application of CCl4 led to tubular necrosis, inflammation, vascular congestion, and increased Serum BUN and creatinine values. An increase in caspase-3 activity also occurred in the CCl4 group. However, Infliximab exhibited an ameliorating effect on kidney injury by causing a decrease in the number of apoptotic cells. Tissue ADA and TGF-ß values of the CCL4 group were significantly higher than the values of the control group (p = .001, p < .001 respectively) and CCL4+ Inf group (p = .004, p = .015, respectively). CONCLUSIONS: This study shows that Infliximab ameliorates nephrotoxicity by reducing lipid peroxidation, oxidative stress, and apoptosis in acute kidney damage developing in association with CCl4 administration. These findings are promising in terms of the ameliorating role of TNF-alpha inhibitors in acute kidney injury.

Proprotein convertase subtilisin/kexin type 9 is associated with atherosclerosis in patients with Behcet's disease.

OBJECTIVES: The incidence of cardiovascular disease is increased in patients with Behcet's disease (BD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) causes the acceleration of atherosclerosis. We aimed to investigate whether there is a relationship between PCSK9 with carotid artery intima-media thickness (cIMT), a marker of subclinical atherosclerosis, and BD disease activity. METHODS: Fifty-eight patients with BD and 58 age-, gender-, and body mass index (BMI)-matched healthy control subjects were included in the study. The disease activity of the patients was estimated. Individuals' cIMT values were measured, and PCSK9 levels were studied. RESULTS: Patients with BD' cIMT (0.51 ± 0.1 vs 0.41 ± 0.1 mm, p < .001) and PCSK9 (623.2 ± 101.7 ± 10.1 vs 528.3 ± 242.7 ng/ml, p = .007), values were significantly higher than the control group. In stepwise regression analysis, there was an independent relationship between cIMT with PCSK9 (ß = 0.179, p < .050). There was no independent relationship between disease activities with PCSK9. Based on the ROC curve analysis, the PCSK9 optimal cutoff value for cIMT was 595.1 ng/ml, sensitivity 66.7%, specificity 64.7% (AUC = 0.672; 95% CI: 0.530-0.815, p = .040). CONCLUSION: There is a strong independent association between subclinical atherosclerosis and PCSK9 in patients with BD. There may be no independent association between PCSK9 and disease activity.

Strong relationship between cholesterol, low-density lipoprotein receptor, Na+/H+ exchanger, and SARS-COV-2: this association may be the cause of death in the patient with COVID-19.

Lipids have a wide variety and vital functions. Lipids play roles in energy metabolism, intracellular and extracellular signal traffic, and transport of fat-soluble vitamins. Also, they form the structure of the cell membrane. SARS-CoV-2 interacts with lipids since its genetic material contains lipid-enveloped ribonucleic acid (RNA). Previous studies have shown that total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) levels are lower in patients with severe novel coronavirus disease 2019 (COVID-19) compared to patients with non-severe COVID-19.Na+/H+ Exchanger (NHE) is an important antiport that keeps the intracellular pH value within physiological limits. When the intracellular pH falls, NHE is activated and pumps H+ ions outward. However, prolonged NHE activation causes cell damage and atherosclerosis. Prolonged NHE activation may increase susceptibility to SARS-CoV-2 infection and severity of COVID-19.In COVID-19, increased angiotensin II (Ang II) due to angiotensin-converting enzyme-2 (ACE2) dysfunction stimulates NHE. Lipids are in close association with the NHE pump. Prolonged NHE activity increases the influx of H+ ions and free fatty acid (FFA) inward. Ang II also causes increased low-density lipoprotein receptor (LDLR) levels by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9). Thus, intracellular atheroma plaque formation is accelerated.Besides, SARS-CoV-2 may replicate more rapidly as intracellular cholesterol increases. SARS-CoV-2 swiftly infects the cell whose intracellular pH decreases with NHE activation and FFA movement. Novel treatment regimens based on NHE and lipids should be explored for the treatment of COVID-19.

Effects of the COVID-19 pandemic on psychology and disease activity in patients with ankylosing spondylitis and rheumatoid arthritis

Background/aim: The COVID-19 outbreak is known to increase stress levels of most patients with chronic diseases. Patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are highly susceptible to environmental stress. In the current study, we aimed to determine how the COVID-19 pandemic psychologically affected patients with chronic progressive diseases such as AS and RA and the effects of these psychological factors on disease activity. Materials and methods: Age and sex-matched patients with AS (n = 80), RA (n = 80), and healthy controls (n = 80) were included in the study. All participants were evaluated with the "Perceived COVID-19 Threat Form (PCTF)", "Suicide-Ideation Scale (SIS)", "Hospital Anxiety and Depression Scale (HADS)", "The Ability to Cope with Trauma (PACT)", and "Psychological General Well-Being Index (PGWB)" scales. BASDAI was used in patients with AS, and DAS28 was used in patients with RA to assess disease severity. Results: Compared to healthy individuals, patients with RA and AS had lower PGWB scores and higher HADS depression and anxiety subscale scores. Almost all psychometric assessment test scores were worse in AS patients with high-disease activity compared to those in low-disease activity. PACT scores were higher in patients with moderate RA compared to patients with mild RA (p = 0.006). While a positive correlation was identified between BASDAI and most of the psychometric assessment test scores (r = 0 .36 for PCTF, r = 0.53 for depressive scores, r = 0.54 for anxiety scores, r = 0.57 for suicidal ideation), DAS28 scores were found to be associated only with PACT total and PACT perceived forward-focused subscale scores (r = ­.26 and r = .33, respectively). Conclusion: Psychologically, AS and RA patients were found to be worse off compared to healthy controls. The perceived COVID threat and psychological status were associated with disease activity in AS, but not RA patients. Patients with chronic illnesses may be more vulnerable to the psychological effects of the pandemic, which can worsen disease activity.

The relationship of serum visfatin levels with clinical parameters, flow-mediated dilation, and carotid intima-media thickness in patients with ankylosing spondylitis

Background/aim: Atherosclerotic heart diseases can occur at an early age in patients with ankylosing spondylitis (AS). Flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) values are reliable markers for early detection of subclinical atherosclerosis in patients with AS. We aimed to investigate the relationship between visfatin levels and indirect markers of subclinical atherosclerosis and endothelial dysfunction in patients with AS. Materials and methods: Forty-two patients diagnosed with AS and 42 age, sex, and body mass index (BMI)-matched controls were included in the study. Visfatin levels, FMD, and cIMT were measured using appropriate methods. Results: Visfatin levels of the patients were significantly higher than controls (p < 0.001). FMD values in patients with AS were significantly lower (p = 0.007) whereas cIMT were significantly higher than the controls (p = 0.003). There was a negative relationship between FMD with visfatin levels (p = 0.004), BASDAI (p = 0.010), and BASFI (p = 0.007). There was a positive relationship between cIMT with visfatin (p = 0.005), BASDAI (p < 0.001), and BASFI (p < 0.001). There was a positive relationship between visfatin with BASDAI (p < 0.001), and BASFI (p < 0.001). Conclusion: Visfatin levels are increased and associated with impaired FMD and increased cIMT in patients with AS. Increased visfatin levels may be associated with subclinical atherosclerosis in AS.

Topiramate Reduces Aortic Cross-Clamping-Induced Lung Injury in Male Rats.

BACKGROUND: Topiramate (TPM) decreases cytokine release and generation of reactive oxygen species (ROS). Cytokine and endothelin-1 (ET-1) secretion and ROS formation play an important role in ischemia-reperfusion (I/R) injury. We aimed to evaluate whether TPM prevents damage occurring in lung tissue during I/R. MATERIALS AND METHODS: A total of 27 Wistar albino rats were divided into three groups of nine. To the I/R group, two hours of ischemia via infrarenal abdominal aorta cross-ligation and then two hours of reperfusion process were applied. TPM (100 mg/kg/day) orally for seven days was administered in the TPM treatment group. After the last dose of TPM treatment, respectively, two hours of ischemia and two hours of reperfusion were applied in this group. RESULTS: Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group's lung tissue were significantly lower than for the I/R group. Caspase-3 and histopathological damage were rather lower than that of the I/R group. CONCLUSIONS: During I/R, lung damage occurs due to excessive TNF-α and ET-1 release and ROS generation. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced.

Soluble Tumor Necrosis Factor (TNF)-Like Weak Inducer of Apoptosis (Tweak) Independently Predicts Subclinical Atherosclerosis in Behcet's Disease.

BACKGROUND: Vasculopathy is a major cause of mortality and morbidity in Behcet's Disease (BD). Subclinical atherosclerosis can even be detected in the early stage of BD. Soluble tumor necrosis factor-like (TNF) weak inducer of apoptosis (TWEAK) is known as a good marker of the inflammation in vascular tree. The aim of this study is to examine the relationship between carotid artery intima-media thickness (cIMT) and serum TWEAK levels in patients with BD. MATERIALS AND METHODS: In line with International BD Study Group criteria, 48 BD, and 30 controls were included in our study. Disease activity was evaluated according to BD current activity form (BDCAF). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lipid parameters, serum TWEAK levels, and cIMT were measured. RESULTS: Disease activity score of BD patients was found as 2 (range 0-7). cIMT, serum TWEAK, CRP and ESR levels of BD patients were significantly higher comparing to cIMT (0.62 ± 0.13 mm vs. 0.43 ± 0.09 mm, p < 0.001), serum TWEAK (667.5 ± 130.6 vs. 603.4 ± 89.6 pg/ml, p = 0.015), CRP (3.9 ± 4.3 vs. 1.4 ± 1.0 mg/dl, p < 0.001) and ESR (10.2 ± 10.0 vs. 5.6 ± 3.7 mm/h, p = 0.005) levels of the control group. There was a positive correlation between serum TWEAK level and disease activity (r = 0.251, p = 0.030) and cIMT (r = 0.463, p < 0.001). Our study also revealed an independent correlation between cIMT and serum TWEAK levels (beta = 0.354, p < 0.001). CONCLUSION: Increased serum TWEAK levels can play a part in the development of atherosclerotic heart disease in BD. Due to their liability to atherosclerosis, patients with BD must followed closely.

The evaluation of cochlear functions in Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) is a progressive disease characterized by chronic inflammation, which also has negative effects on cochlear functions and hearing levels. We investigated whether the cochlear functions and hearing levels of FMF patients were different than healthy controls and also evaluated the relationship of hearing levels with the age at diagnosis, duration without treatment, and inflammation and lipid parameters in this study. A total of 60 patients diagnosed with FMF and 48 age, gender and body mass index (BMI)-matched healthy controls were included in the study. The hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid parameters of the subjects were studied and they all underwent pure tone audiometry and Transient evoked otoacoustic emission tests after an otologic examination. The hearing levels of the FMF group were significantly higher than those of the control group. The TEOAE signal/noise (S/N) ratios were similar in both groups. A positive relationship was present between the audiometric test results and the age, BMI, low-density lipoprotein and triglyceride levels and a negative relationship with the high-density lipoprotein levels. A negative relationship was present between the TEOAE S/N ratios and the age of the patients, duration without treatment, lipid parameters, inflammation markers and the creatinine level. FMF patients are exposed to chronic inflammation and this can influence their hearing levels. The age at diagnosis, duration without treatment, chronic inflammation, unfavorable lipid parameters, and obesity can affect hearing tests negatively.

Evaluation of aortic stiffness in Gilbert syndrome patients: a protective effect of elevated bilirubin levels.

OBJECTIVE: Gilbert's syndrome (GS) is an autosomal recessive disease that is characterized by an increase in indirect bilirubin (IB). The incidence of atherosclerotic heart disease is decreased in GS. This study aimed to investigate the relation between pulse wave velocity (PWV) and the presence of GS. METHODS: The study included 58 GS patients (32 females, age; 27.12 ± 7.27 years, 26 males, age; 26.63 ± 5.84 years) admitted to the internal medicine clinic of the hospital. The control group included 58 healthy individuals (35 females [27.33 ± 8.06 years old, p=0.716] and 23 males [27.38 ± 6.91 years old, p=0.923]). PWV of both groups was measured from the right carotid and femoral arteries. RESULTS: Mean age of the GS group was 26.03 ± 8.22 years, while that of the healthy group was 26.60 ± 5.84 years. The GS group's diastolic blood pressure and PWV were significantly lower than those of the control group: 67.76 ± 8.59 mmHg vs 71.72 ± 7.28 mmHg; p=0.008, and 5.63 ± 1.12 m/s vs 6.18 ± 1.22 m/s; p=0.014 respectively. The GS group's high density lipoprotein (HDL) level was significantly higher than that of the control group: 1.4 ± 0.3 mmol/L vs 1.2 ± 0.3 mmol/L, p=0.029. CONCLUSION: This study found PWV among GS patients to be lower than that among non-smoking and aged-matched healthy controls.

Molecular characterisation and control of Acinetobacter baumannii isolates resistant to multi-drugs emerging in inter-intensive care units.

BACKGROUND: A nosocomial outbreak of Acinetobacter baumannii (AB) infections occurred among intensive care units (ICU) (surgery, medical, cardiovascular surgery, coronary unit) of Recep Tayyip Erdogan University Medical School (Rize, Turkey) between January 2011 and May 2012. The identification of isolates and clonal relation among them were investigated by molecular techniques. METHODS: A total of 109 AB isolates were obtained from 64 clinical materials from 54 ICU patients and 3 from the hands of healthcare workers (HCWs) of 42 environmental samples. The isolates were identified by 16S rDNA sequencing and OXA- specific PCR. The clonal relation between isolates was investigated by PFGE methods using ApaI restriction enzyme. RESULTS: All isolates were determined as AB by 16S rDNA sequencing and OXA-spesific PCR. While the blaOXA-51-like gene was amplified in all isolates, the blaOXA-23-like gene was amplified from 103 isolates. The PFGE pattern generated 9 pulsotypes and showed that the isolates from patients, HCWs, and the environment were genetically related. In 7 of these pulsotypes, there were 107 strains (98%) showing similar PFGE profiles that cannot be distinguished from each other, ranging from 2 to 53. The remaining 2 pulsotypes were comprised of strains closely associated with the main cluster. Two major groups were discovered with similarity coefficient of 85% and above. The first group consisted of 97 strains that are similar to each other at 92.7% rate, and the second group consisted of 12 strains that are 100% identical. CONCLUSIONS: The common utilization of the blood gas device among ICU was the reason for the contamination. AB strains can remain stable for a long period of time, although due to the disinfection procedures applied in hospitals, there is a small chance that the same clone might reappear and cause another epidemic. For that reason, the resistance profiles of the strains must be continuously followed with amplification-based methods, and these methods should be used to support the PFGE method in the short term.