Evaluation of therapeutic use of a combination of pentoxifylline and vitamin E in radiation-induced renal fibrosis.

Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness. We used four groups, each with six rats: radiation therapy alone (RT-only), radiation therapy plus drug treatment (RT + drug), drug treatment alone (drug-only), and a control group. Rats were monitored for three months, with weight measurements every four weeks. Afterward, rats were analyzed biochemically and histologically, with blood and tissue samples taken for statistical comparison. No significant differences in serum creatinine levels and body weight were observed. RT-only group had more severe kidney tubule effects. Histomorphological, immunohistochemical, and TUNEL analyses showed significant RIRF mitigation in the RT + drug group. Our study highlighted molecular pathways (SMAD, TGF-beta, VEGF) and histological markers (collagens, a-SMA, fibronectin, metalloproteinases) associated with RIRF. PTX and vitamin E reduced ionizing radiation's impact on renal cells and mitigated radiation-induced kidney fibrosis. Further human studies are needed to confirm these findings.

Hypomagnesemia May Predict Better Survival and Reduced Nonrelapse Mortality in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

BACKGROUND: Magnesium (Mg) is an essential element that is required as a cofactor for many cellular reactions, including immunologic pathways. The aim of this study was to investigate the potential impact of serum Mg levels on allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. METHODS: Medical records of 340 alloHSCT recipients (median age: 45 [18-71] years; M/F: 210/130) were reviewed for this retrospective study. Serum Mg levels on days -28, -7, 0, +7, +14, +21, +30, +60, and +90 were included in the analysis. RESULTS: Serum Mg+14 levels predicted nonrelapse mortality (NRM) (P = .025) and had a significant impact on the development of mucositis (P = .027), fungal infection (P = .006), engraftment syndrome (P < .001), sinusoidal obstruction syndrome (SOS) (P = .001), cytomegalovirus (CMV) reactivation (P = .039), and acute graft vs host disease (GvHD) (P < .001). Based on the optimal threshold of serum Mg+14 level (1.33 mg/dL; area under the curve: 0.581 [0.515-0.648]; P = .018), the study group was divided into 2 subgroups as low- and high-Mg+14. The incidence of acute GvHD (P = .002), SOS (P = .013), engraftment syndrome (P = .013), CMV reactivation (P = .001), and Epstein Barr virus reactivation (P = .005) was significantly lower in low-Mg+14 group. The probability of overall survival (OS) was significantly better (P = .002), whereas NRM was lower in the low-Mg+14 group (P = .001). CONCLUSION: Hypomagnesemia seems to provide a considerable advantage for the post-transplant outcome, which may confirm its potential role in the immunologic microenvironment and adaptive immunity.

Lipopolysaccharide, VE-cadherin, HMGB1, and HIF-1α levels are elevated in the systemic circulation in chronic migraine patients with medication overuse headache: evidence of leaky gut and inflammation.

OBJECTIVE: Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation. MATERIALS AND METHODS: The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels. RESULTS: Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores. CONCLUSION: We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH.

Detecting the interferences in adrenocorticotropic hormone measurement - three cases reinforcing the efficiency of the complementary clinical and laboratory audit.

Accurate measurement of adrenocorticotropic hormone (ACTH) is crucial in the evaluation of pituitary and adrenal disorders. Although great progress has been achieved in ACTH measurement with immunometric assays, interference may occur and adversely affect the clinical management. The report contributes to compiling the evidence on the clinical challenges with the management of the interferences in the ACTH measurement by presenting three cases: two with clinically overt hypercortisolism and discrepant ACTH concentrations within the reference interval; the third case describes the falsely elevated ACTH in a patient with secondary adrenal insufficiency. In all patients, the results obtained with the two immunometric platforms, chemiluminescence (CLIA) immunoassay (Siemens, Immulite) and electrochemiluminescence (ECLIA) immunoassay (Roche, Cobas), were discordant. Serial dilution of plasma samples revealed nonlinearity. After polyethylene glycol (PEG) precipitation recoveries were less than 22%, 26%, and 3%, respectively, supporting interference. Moreover, a decrease in ACTH concentration after incubation in a heterophile antibody-blocking tube was observed in the second case. In the first case, misinterpretation of ACTH led to inferior petrosal sinus sampling (IPSS), whereas timely detection of assay interference prevented further investigations in other cases. Increasing awareness regarding ACTH interference and comprehensive approach in evaluation could allow timely detection, helping to prevent unnecessary testing and perplexing clinical outcomes.

Cost analysis of 25-hydroxy vitamin D tests in Turkiye with big data: A cross-sectional study.

OBJECTIVE: The high prevalence of vitamin D deficiency in the population causes physicians to request more vitamin D tests and increases laboratory costs. It is aimed at investigating the demanded numbers and cost analyzes of 25-hydroxyvitamin D (25(OH)D) tests with the big data obtained from the national information health system of the Turkish Ministry of Health. METHODS: Between 2017 and 2018, all inpatient and outpatient tests and 25(OH)D tests in all medical biochemistry laboratories in Turkiye were determined based on department and institution type. The cost amount, distribution among health institutions, and test request rates were calculated. In both years, the top ten most expensive tests, according to health institutions, were evaluated. RESULTS: The total number of medical biochemistry tests performed in 2017 and 2018 was 1.424.948.155 and 1.713.134.326, respectively. The number of 25 (OH)D tests analyzed in the same years was 8.698.393 and 13.919.127, respectively. When the data of the 2 years are compared, the consumption of 25 (OH)D tests increased by 37% in General hospital laboratories, whereas it increased by 115.09% in primary health laboratories. When all health institutions were evaluated, the increase rate in 25 (OH)D test demand was 60%, while the cost increase rate was 23%. CONCLUSION: This report showed that the demands for 25(OH)D testing are increasing steeply, especially in primary health-care facilities. In this direction, laboratory information system test demand restrictions in accordance with national and international guidelines are important issues for policymakers.

The Level of Inflammatory Markers and Their Relationship with Fat Tissue Distribution in Children with Obesity and Type 2 Diabetes Mellitus.

OBJECTIVE: This study aimed to determine the changes in proinflammatory and anti-inflam- matory markers in children aged 10-18, who were not diagnosed with type 2 diabetes mel- litus, were obese/overweight, and children with type 2 diabetes mellitus. In addition, we aimed to investigate whether these markers were associated with clinical and laboratory parame- ters, subcutaneous adipose tissue, preperitoneal adipose tissue, visceral adipose tissue, and hepatosteatosis. MATERIALS AND METHODS: Children between the ages of 10 and 18, obese/overweight, with type 2 diabetes mellitus, and with a normal body mass index were included. Fat tissue thick- ness was measured. Tumor necrosis factor-α, interleukin-1ß, interleukin-6, interleukin-18, and interferon-γ as proinflammatory markers and transforming growth factor-ß and interleukin-10 levels as anti-inflammatory markers were studied. RESULTS: Twenty-eight (31.8%) controls, 44 (50%) obese/overweight, and 16 (18.2%) patients with type 2 diabetes mellitus were included in our study. Age, sex, and puberty were similar between the groups. In the type 2 diabetes mellitus group, the subcutaneous fat tissue thick- ness was higher than that in the obese group, and the preperitoneal and visceral fat tissue thicknesses were similar to those in the obese group. Proinflammatory markers and interleu- kin-10 levels were similar in the obese/overweight, type 2 diabetes mellitus, and control groups. Transforming growth factor-ß levels were significantly lower in the type 2 diabetes mellitus group than in the control group (P = .039). Transforming growth factor-ß levels and other labo- ratory variables did not differ significantly in the type 2 diabetes mellitus group. CONCLUSION: While there was no change in all markers in the obese/overweight group com- pared with the control group, proinflammatory markers in the type 2 diabetes mellitus group were similar to those in the obese/overweight and control groups, and transforming growth factor-ß level, an anti-inflammatory marker, was lower in the type 2 diabetes mellitus group than in the control group.

Is blue light exposure a cause of precocious puberty in male rats?

Purpose: Our study aimed to examine the effects of blue light exposure on prepubertal male rats' puberty and testis tissue. Methods: Eighteen 21-day-old male Sprague Dawley rats were divided into three groups consisting of six rats in each group: Control Group (CG), Blue Light-6 hours (BL-6), and Blue Light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The rats of BL-6 and BL-12 were exposed to blue light (450-470nm/irradiance level 0.03uW/cm2) for 6 hours and 12 hours, respectively. Rats were exposed to blue light until the first signs of puberty. The ELISA method was used to analyze the serum levels of FSH, LH, testosterone, DHEA-S, leptin, ghrelin, melatonin, glutathione, glutathione peroxidase, and malondialdehyde. Testes were dissected for histomorphological examination. Results: The medians of the pubertal entry days of the CG, BL-6, and BL-12 were 38th, 30th, and 28th days, respectively. (p:0.001) The FSH, LH, and testosterone concentrations of all groups were similar. The FSH concentration increased as the LH concentration increased (r: 0.82 p: 0.001). The serum LH concentration increased as serum testosterone, and DHEAS decreased, respectively (r: -0.561, p: 0.01) (r:-0.55 p:0.01). Testicular lengths and weights of the BL groups were smaller compared to CG (p: 0.03),(p: 0.04). GPx was higher for BL-6 and BL-12 than the CG (p:0.021, p:0.024). Testis tissue was compatible with the pubertal period in all groups. As the blue light exposure time increased, spermatogenesis was suppressed, and capillary dilatation and edema in the testis tissue increased. Conclusion: Our study is the first to show the effects of blue light exposure on male rats' puberty process. And we showed that exposure to blue light and the duration of exposure lead to precocious puberty in male rats. The blue light exposure suppressed spermatogenesis, marked vasodilatation in the interstitial area of the testis, and disrupted the integrity of the basement membrane. These findings intensified with increasing exposure time.

Effects of Blue Light on Puberty and Ovary in Female Rats

Objective: This study was designed to examine the effect of blue light exposure and exposure time on puberty in an animal model. Methods: Eighteen 21-day-old female Sprague Dawley rats were divided into three equal groups which were: control group (CG); blue light-6 hours (BL-6); and blue light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The animals in BL-6 and BL-12 were exposed to blue light of wavelength 450-470 nm and intensity of 0.03 uW/cm2 for 6 and 12 hours, respectively. Exposure to blue light continued until the first signs of puberty. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), leptin and melatonin were measured. Subsequently the ovaries and uterus were examined histomorphologically. Results: The median day of puberty start was 38, 32 and 30 for the CG, BL-6, and BL-12 groups, respectively (p=0.001). FSH, testosterone, DHEA-S, and leptin concentrations of all groups were similar. However, LH and estradiol concentrations in BL-6 were higher compared to CG (p=0.02). There was a negative correlation between blue light exposure, exposure time, and melatonin concentrations (r=-0.537, p=0.048). Ovarian tissue was compatible with puberty in all groups. As blue light exposure time increased, capillary dilatation and edema in the ovarian tissue increased. Prolonged exposure was associated with polycystic ovary-like (PCO) morphological changes and apoptosis in granulosa cells. Conclusion: These results suggest that exposure to blue light and the duration of exposure induced earlier puberty in female rats. As the duration of blue light exposure increased, PCO-like inflammation, and apoptosis were detected in the ovaries.

Relationship Between Appetite-Related Peptides and Frailty in Older Adults.

BACKGROUND: Frailty, is a geriatric syndrome that reduces the resistance to stress situations caused by activities of daily living and increases morbidity and mortality. We hypothesized that a decrease in orexigenic peptides or an increase in anorexigenic peptides might be associated with frailty. We aimed to investigate the relationship between frailty and six appetite-related peptides: ghrelin, neuropeptide Y (NPY), agouti-related peptide (AgRP), cocaine-amphetamine-associated peptide (CART), peptide YY, and alpha MSH (α-MSH). METHODS: This cross-sectional study was conducted on 85 older adults who visited the outpatient clinic. All patients underwent comprehensive geriatric assessment. Frailty status was assessed using the Fried frailty index. Plasma levels of six appetite-related peptides were studied. RESULTS: The mean age was 73.7 ± 5.4 years, 27 (31.8%) of the patients were male, and 32 of the patients (37.6%) were frail. While plasma levels of ghrelin, NPY and AgRP were significantly lower in frail patients, CART and α-MSH levels were higher compared to non-frail patients (p < .05 for all). Peptide YY was found to be higher in the frail group, however, the difference did not reach statistical significance (p = .052). In multivariate logistic regression analysis, the ghrelin, AgRP, CART, and α-MSH levels were independent predictors of frailty. Moreover, a weak correlation was found between all peptides(except NPY) and handgrip strength and Lawton-Brody score. CONCLUSION: Ghrelin, AgRP, CART, and α-MSH levels were found to be independent predictors of frailty. Our results suggest that appetite-related peptides might be playing roles in the pathogenesis of frailty. Further larger prospective studies are needed to test this hypothesis.

Evaluation of The Effects of Carob (Ceratonia siliqua L.) Fruits on the Puberty of Rats

Objective: This study was planned to determine the effects of carob use on puberty because of the observation of early puberty or pubertal variants due to the long-term use of carob in our clinic. Methods: Forty-eight Wistar albino rats, on postnatal day 21, were assigned into two groups female (n=24) and male (n=24). Groups were divided into four groups Control, and Carob-150, Carob-300, and Carob-600. Ceratonia siliqua L. extract was given to rats in a 0.5% carboxymethylcellulose (CMC) solution. CMC (0.5%) was given to the control, Ceratonia siliqua L. extract was given 150 mg/kg/day to the Carob-150, 300 mg/kg/day to the Carob-300, 600 mg/kg/day to the Carob-600 by oral gavage. The treatments were performed once daily until the first sign of puberty. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, total testosterone, leptin, glutathione, glutathione peroxidase (GPx), and malondialdehyde were measured by commercial rat-specific ELISA kits. Testis, uterus and ovarian tissue were examined histologically. Results: The median time of preputial separation in male rats was 38th, 31st, 31st, and 31st days in the Control, Carob-150, Carob-300, and Carob-600 groups, respectively (p=0.004). The median day of vaginal opening day was the 39th, 31st, 34th, and 31st days in the Control, Carob-150, Carob-300, and Carob-600 groups, respectively (p=0.059). FSH, LH, testosterone (male), estradiol (female) and leptin levels of the groups were similar. However, GPx levels were higher in male and female animals given C. siliqua extract compared to the Control (male p=0.001 and female p=0.008). Testicular and ovarian tissues were concordant with the pubertal period in all groups. As the dose of Ceratonia siliqua extract increased, it induced spermatogenesis and spermiogenesis, causing abnormal changes, such as ondulation in the basement membrane, capillary dilatation, and increased congestion in males. In females, edema in the medulla gradually increased with increased dosage, and granulosa cell connections were separated in Carob-300 and Carob-600 groups. Conclusion: This study demonstrated that C. siliqua caused early puberty and increased spermiogenesis and folliculogenesis. Antioxidant mechanisms were impaired with increasing dose, possibly leading to tissue damage at high doses.

Modafinil attenuates the neuroinflammatory response after experimental traumatic brain injury.

BACKGROUND: Modafinil has been proven to exert anti-inflammatory, anti-oxidative and neuroprotective effects on numerous neurological disorders. However, its effects after traumatic brain injury (TBI) have not been yet explored. The aim of this study was to explore if Modafinil can attenuate the neuroinflammatory phase of TBI and clarify the possible underlying mechanisms. METHODS: A weight drop model was used to induce experimental TBI on 30 Wistar albino rats. The treatment group received Modafinil on the day of the trauma and the following 5 days. Garcia Test was used to assess for neurological status and histopathological examination along with biochemical analysis of NSE, S-100B, CASP3, and TBARS levels were performed. RESULTS: Rats treated with Modafinil after the trauma had a statistically significant higher Garcia Test Score (P<0.001) and presented with increased evidence of anti-inflammatory and neuroprotective effect (P<0.05, P=0.005). Decreased levels of all biochemical parameters with NSE, CASP3, and TBARS having statistical significance was observed (P<0.05). CONCLUSIONS: The findings of this paper support the notion that a psychoactive drug Modafinil, traditionally used for sleep disorders and also known as a cognitive enhancer may prove beneficial in decreasing mortality and morbidity after TBI through anti-inflammatory, anti-oxidative and neuroprotective effects.

Does Venipuncture Increase Lymphedema by Triggering Inflammation or Infection? An Experimental Rabbit Ear Lymphedema Model Study.

Background: Recent guidelines recommend avoiding venipuncture to prevent lymphedema for breast cancer patients. This study investigated whether single or multiple sterile venipuncture procedures develop a systemic inflammation or infection and increase lymphedema in the rabbit ear lymphedema model. Methods and Results: Eighteen New Zealand white female rabbits were included. The right ear lymphedema model was created by surgical procedure; then, rabbits were divided into three randomized groups. Single and multiple venipuncture procedures were applied at least the 60th day after surgery for Group I and II, respectively. Group III was a control group. C-reactive protein (CRP) and procalcitonin (PCT) levels were analyzed to determine inflammation and infection. Ear thickness measurements were applied using a vernier caliper to assess the differences in lymphedema between the ears. All rabbits were euthanized on the 90th day after surgery. Histopathological analysis was performed to evaluate lymphedema by measuring tissue thicknesses. Ear thickness measurements showed that ear lymphedema was developed and maintained with surgical operation in all groups (p < 0.05). There was no difference in the ear thickness measurements between and within-groups results (p > 0.05). CRP and PCT levels were below the lower detection levels in all groups. According to the differences of histopathological ear distances, there were significant differences within-groups for all groups (p < 0.05), and no differences were identified between groups (p > 0.05). Conclusion: This experimental study demonstrated that single or multiple sterile venipuncture procedures did not trigger infection or inflammation and did not exacerbate ear lymphedema in the rabbit ear lymphedema model.

The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-ß1, FGF-2 in COVID-19 Patients.

Background: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-ß1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19. Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-ß1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed. Results: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis. Conclusions: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-ß1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.

25-hydroxyvitamin D (25-OHD) levels in Turkish geriatric population: A nationwide study.

Background: Across the world, 25-hydroxyvitamin D (25-OHD) deficiency is a major health problem associated with many chronic diseases in the geriatric population. Prior to this study, there were no data regarding 25-OHD levels among individuals over the age of 65 in Turkey. The aim of this study was to assess 25-OHD levels and seasonal variations in these values among people over the age of 65 in Turkey. Methods: This study included vitamin D measurements taken in 2016, 2017, and 2018 from the Turkish population over the age of 65. The age, gender, and seasonal average data of the study population were defined. The study data were obtained from the database of the Ministry of Health, and a Kolmogorov-Smirnov test was used to assess the distribution of the data. Medians and interquartile ranges (IQRs) were calculated for all categories, as the data were nonparametric. Results: The number of vitamin D measurements taken from the geriatric individuals included in this study was 305,329 for 2016, 576,452 for 2017, and 752,837 for 2018. The medians and IQRs of the 25-OHD levels in this population were 16 µg/L (IQR 7.45-24.55 µg/L) for 2016, 16.1 µg/L (IQR 7.8-24.4 µg/L) for 2017, and 16.4 µg/L (IQR 8.95-23.85 µg/L) for 2018. Conclusions: While the 25-OHD levels of older men tended to increase during the period of seasonal sunlight in Turkey, this variability was observed in elderly women. This suggests that older women tend to live more sedentary lives and have insufficient sun exposure. Overall, the median 25-OHD levels of individuals over the age of 65 tended to decrease each year.

Prognostic Value of Serial Measurement of Serum Des-Arg(9)-Bradykinin Levels in Severe COVID-19 Patients.

BACKGROUND: Excessive inflammatory immune response during SARS-CoV-2 infection contributes to severe disease in COVID-19 patients. Recently, some researchers hypothesized that dysregulation of the bradykinin (BK) system may also play a role in the pathogenesis of severe disease. Des-Arg(9)-bradykinin (DABK), an active metabolite of BK, is responsible for vasodilatation and increased permeability in the lungs and regulated by angiotensin converting enzyme 2 (ACE-2). Viral inhibition of ACE-2 by SARS-CoV-2 increases DABK levels. Serum levels of this metabolite may be linked to disease severity in COVID-19 patients. In this study, it is aimed to investigate the prognostic value of serial measurement of serum DABK levels in severe COVID-19 patients. METHODS: This prospective cohort study was conducted in hospitalized severe COVID-19 patients. Serum DABK levels of patients were serially measured on day 0, day 3 and day 5. Patients were categorized as cases with poor or good prognosis and critical or non-critical cases. Serum DABK levels of these patient groups were compared with paired sample t-test. Serum DABK levels on different days in the same patients were compared with repeated measures ANOVA tests. RESULTS: There was no statistically significant difference in serum DABK levels measured at day 0, day 3, and day 5 between good and poor prognosis groups. DABK levels in critical and non-critical COVID-19 patients also did not show any significant difference. CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.

Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress.

Coronavirus disease 2019 (COVID-19) has resulted in long-term psychiatric symptoms because of the immunologic response to the virus itself as well as fundamental life changes related to the pandemic. This immune response leads to altered tryptophan (TRP)-kynurenine (KYN) pathway (TKP) metabolism, which plays an essential role in the pathophysiology of mental illnesses. We aimed to define TKP changes as a potential underlying mechanism of psychiatric disorders in post-COVID-19 patients. We measured plasma levels of several TKP markers, including KYN, TRP, kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), as well as the TRP/KYN, KYNA/3-HK, and KYNA/QUIN ratios, in 90 post-COVID-19 patients (on the first day of hospitalization) and 59 healthy controls (on the first admission to the Check-Up Center). An online questionnaire that included the Depression, Anxiety and Stress Scale-21 (DASS-21) was used 6 months after the initial assessment in both groups. A total of 32.2% of participants with COVID-19 showed depressive symptoms, 21.1% exhibited anxiety, and 33.3% had signs of stress at follow-up, while 6.6% of healthy controls exhibited depressive and anxiety symptoms and 18.6% had signs of stress. TRP and 3-HK were negative predictors of anxiety and stress, but KYN positively predicted anxiety and stress. Moreover, TRP negatively predicted depression, while KYNA/3-HK was a negative predictor of anxiety. The correlation between depression, anxiety, and stress and TKP activation in COVID-19 could provide prospective biomarkers, especially the reduction in TRP and 3HK levels and the increase in KYN. Our results suggest that the alteration of TKP is not only a potential biomarker of viral infection-related long-term psychiatric disorders but also that the therapy targets future viral infections related to depression and anxiety.

Serum ciliary neurotrophic factor levels in children with attention deficit hyperactivity disorder.

Purpose/aim of the study: The study aimed to highlight the possible role of ciliary neurotrophic factor (CNTF) in the pathophysiology of attention deficit hyperactivity disorder (ADHD) and determine whether CNTF can be used as a biomarker for ADHD.Materials and methods: Patients with a diagnosis of ADHD and neurotypical subjects aged 6-12 years were recruited prospectively. The study applied Conners' Teacher Rating Scale (CTRS) to determine the patients' ADHD predominance and severity. Serum CNTF levels were measured with an enzyme-linked immunosorbent assay (ELISA) kit.Results: A total of 43 ADHD patients and 33 healthy controls were included in the study. A significant difference was found between the serum CNTF levels of the ADHD patients (22.17 pg/ml) and the controls (22.80 pg/ml). Correlations between the CNTF levels and CTRS scores were not significant.Conclusions: The study identified an alteration of serum CNTF levels in ADHD patients and thus asserted a link between CNTF and ADHD pathophysiology; children with ADHD had significantly lower serum CNTF levels compared to the neurotypical controls. Further research is needed to understand the mechanisms of CNTF.

Serum Heat Shock Protein 70 Level in Children with Attention Deficiency Hyperactivity Disorder.

Introduction: Attention deficit hyperactivity disorder (ADHD) have quite complicated etiology. The relationship between ADHD and immune and oxidative imbalances is discussed in current researches investigating the pathophysiology of ADHD. The aim of the study is to determine whether heat shock protein 70 (HSP70) has a potential role in pathophysiologic mechanisms of attention deficit hyperactivity disorder. Methods: This study included 41 children that were diagnosed with ADHD and 32 typically developing children. Conners' Teacher Rating Scale (CTRS) was used to evaluate ADHD presentation and severity. Additionally, an enzyme-linked immunosorbent assay (ELISA) kit was used to evaluate serum HSP70 level. Results: We have detected that the serum HSP70 levels of children with ADHD were lower than the typically developing group (p<0.01). No relationship was determined between HSP70 levels and either the severity of ADHD or predominantly ADHD presentations (p>0.05). Conclusion: With these findings, it can be proposed that HSP70 might have a crucial role in the etiological mechanisms of ADHD. Moreover, these changes in peripheral blood may have therapeutic and/or diagnostic value. However, more detailed prospective studies are needed to explain the link between ADHD and heat shock proteins.

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition.

BACKGROUND/AIM: Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. METHODS: Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. RESULTS: Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. CONCLUSION: Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.

The Relationship Between Myostatin, Inflammatory Markers, and Sarcopenia in Patients With Chronic Kidney Disease.

OBJECTIVE: To determine the prevalence of sarcopenia in patients with chronic kidney disease (CKD), investigate the relationship of the serum myostatin level with sarcopenia and inflammatory markers. METHODS: The study was conducted with four patient groups: renal transplantation (TX), stage 3-5 non-dialysis-dependent CKD (NDD-CKD), hemodialysis (HD), and peritoneal dialysis (PD). Laboratory parameters, serum myostatin, C-reactive protein, and interleukin-6 levels were studied. Body composition was estimated using a multifrequency bioimpedance analysis. Handgrip strength (HGS) was evaluated with a handgrip dynamometer. The HGS and appendicular skeletal muscle index measurements were used to determine sarcopenia presence. RESULTS: The study included 130 patients (72 [55%] male patients). The patient distribution in groups was as follows: 37 in HD, 28 in PD, 37 in renal TX, and 28 in NDD-CKD. The highest level of myostatin was measured in the HD group, and the lowest in the TX group (P < .001). The HGS measurement in the PD group was significantly lower than that in the TX group (P = .025). The myostatin was negatively correlated with HGS, albumin, estimated glomerular filtration rate, and Kt/Vurea. However, myostatin had no correlation with inflammatory markers or appendicular skeletal muscle index. Sarcopenia was present in 37 (29%) patients: 15 (40%) in the HD group, nine (32%) in NDD-CKD, seven (25%) in PD, and six (16%) in TX. When the patients with and without sarcopenia were compared, only myostatin was higher in the former (P = .045). As a result of multivariate analysis, myostatin was the only independent factor which predicts sarcopenia (odds ratio: 1.002, 95% confidence interval: 1.001-1.005, P = .048). CONCLUSION: To prevent devastating events associated with sarcopenia in patients with CKD, renal transplantation seems to be the best treatment solution. For the early recognition of sarcopenia, the measurement of the serum myostatin level may be a promising diagnostic approach.