Background To study the relationship of Vitamin D with innate and adaptive immune response parameters in chronic hepatitis B and C patients.

Hintergrund: Phosphatidylcholin ist ein essenzieller Bestandteil des Darmschleims und dient als Schutzschild gegen das Eindringen von Bakterien aus dem Stuhl. Im Darmschleim von Patienten mit Colitis ulcerosa ist Phosphatidylcholin um 70% vermindert, welches den Darm anfällig gegenüber bakteriell ausgelösten Entzündungen macht. Lokale Applikation durch Gabe von darmlöslichem Phosphatidylcholin könnte diesen Mangel ausgleichen. Methode: Es wurde eine zusammenfassende Analyse der drei bisher veröffentlichten klinischen Studien mit 160 eingeschlossenen Colitis-ulcerosa-Patienten durchgeführt. Ergebnisse und Schlussfolgerung: Die Metaanalyse zeigte, dass mit Phosphatidylcholin angereichertes und mit Eudragit S-100 mikroverkapseltes Lecithin die Remissionsrate sowie das klinische und endoskopische Bild deutlich verbessert. Auch in Bezug auf Histologie und Lebensqualität war eine Besserung festzustellen. Gegenüber Placebo waren alle Parameter signifikant überlegen. Die erreichte Remission blieb unter darmlöslichem Lecithin deutlich länger erhalten als unter Placebo. Das Nebenwirkungsprofil war identisch zur Placebogruppe, was für die Patienten besonders wichtig ist. Phosphatidylcholin ist damit komplementärmedizinisch als Schutz für den Darm anzusehen. Eingereicht am 22.10.2021 - Revision akzeptiert am 16.12.2021

Background: Phosphatidylcholine (PC) is intrinsically missing in intestinal mucus of patients with ulcerative colitis. Topical supplementation with delayed intestinal release PC formulations is assumed to compensate this lack. Three monocenter randomized controlled trials (RCTs) with a 30% PC-containing lecithin were successful, whereas 1 trial with >94% PC-containing lecithin failed. Objectives: Evaluation of 30% PC-containing lecithin provided in a delayed intestinal release formulation for treatment efficacy of ulcerative colitis was evaluated by meta-analysis of 3 RCTs. Methods: Meta-analysis of 3 studies was performed using RevMan 5.3 software. Odds ratio (OR) and 95% Cl were calculated for remission, clinical and endoscopic improvement, histology, and life quality. p values <0.05 were accepted as significant. Results: The meta-analysis of 3 RTCs with 160 included patients with ulcerative colitis verified that PC improved the rate of remission (OR = 9.68), as well as clinical (OR = 30.58) and endoscopic outcomes (OR = 36.73). Within the available patient population, also histology and quality of life became better. All effects were significant over placebo. Achieved remission was maintained in a higher percentage of patients under intestinal-release PC formulation than placebo. The profile of adverse events was identical to the placebo population. Conclusions: A 30% PC-containing lecithin in delayed intestinal release formulation improves clinical and endoscopic outcomes, histologic activity, and quality of life in patients with ulcerative colitis. For the patients, lack of adverse events is an important consideration.

Background: The increased secretion of anti-Mullerian hormone (AMH) by the growing follicles has been supposed as a determinative feature of polycystic ovary syndrome (PCOS). The diagnostic performance of AMH in PCOS is superior compared to the free androgen index (FAI) and luteinizing hormone (LH)/follicle-stimulating hormone (FSH) quotient. We established age-dependent reference ranges to further improve the diagnostic performance of AMH. Methods: In a cross-sectional study, in samples of 4712 reproductive age patients, ranging from 14 to 50 years, BMI, AMH and other reproductive hormones were determined by immunoassay or tandem mass spectrometry (LC-MS/MS) to calculate age-specific reference ranges and the diagnostic performance. Results: Age-specific diagnostic performances for Elecsys (R) AMH, FAI and LH/FSH ratio were established in the reference group. No significant difference in BMI was found between the groups. AMH values were significantly negatively correlated with age (r = -0.628, p < 0.001) in patients with normal ovarian function, but there was no correlation between age and AMH levels in PCOS patients (r = -0.041, p < 0.174). In all the study groups, AMH showed a weak correlation between FAI and LH/FSH ratio (r = 0.302, p < 0.001 and r = 0.434, p < 0.001, respectively). The sensitivity/specificity for AMH, FAI and LH/FSH ratio were 89/96%, 71/69% and 75/72%, respectively, according to the Youden index. Conclusions: We determined the age-dependent reference ranges for serum AMH levels in a large population-based study and calculated the age-specific diagnostic performance of FAI and LH/FSH ratio, which allows physicians to evaluate patients with PCOS who have normal AMH levels. AMH is suggested as the strongest diagnostic marker in patients with PCOS compared to FAI and LH/FSH ratio.

BACKGROUND:Different polycystic ovary syndrome (PCOS) phenotypes are correlated with different clinical severity levels. Insulin resistance correlates with higher severity. In a retrospective study, 130 patients with polycystic ovary syndrome were examined for insulin resistance. The aim of the study was to investigate relationships between glucose metabolism and different PCOS phenotypes and to identify biomarkers or combinations thereof to obtain information on the type of metabolic disorder or the severity of PCOS.METHODS:A total of 130 patients with PCOS were included in the study. Biometric data such as weight, height, cycle day and cycle length were compared with glucose metabolism parameters such as fasting glucose, insulin before and 60 and 120 minutes after 75 g glucose intake, intact proinsulin, C-peptide and ovarian function parameters including Anti-Müllerian hormone (AMH) and the soluble AMH receptor (sAMHR2). The parameters were correlated, and their diagnostic performance with respect to different expressions of PCOS was evaluated.RESULTS:The biomarkers of impaired glucose metabolism showed strong significant difference in HOMA Index, adiponectin, proinsulin and body mass index (BMI) and Insulin levels in 0-60-120 minutes of glucose tolerance test but also with parameters of ovarian function as AMH, AMH z-score sAMHR2, and sAMHR2/AMH ratio. A strong correlation between sAMHR2 and adiponectin (r = .818, P < .0001) was found indicating a relationship between the degree of glucose metabolic impairment and ovarian function.CONCLUSIONS:The parameters glucose, insulin, insulin 60 minutes after intake of 75 g glucose and adiponectin or sAMHR2 enable a biochemical classification of PCOS patients that correlates with morphological PCOS phenotypes. By determining biomarkers, it is possible to classify PCOS patients into subgroups that correlate with different PCOS phenotypes and the clinical severity.

OBJECTIVES:Clinical decisions in patients with monoclonal gammopathies may be highly imprecise because of variations of parameters used in diagnosis. In this study, we aimed to calculate the variation in M-protein, free light chains (FLCs), and immunoglobulins in respective patients. DESIGN & METHODS:We analyzed the data of clinically stable patients with monoclonal gammopathy (MG), which were monitored for 7-years to determine the biological variations and reference change values (RCV) of serum M-protein, monoclonal serum FLCs and immunoglobulin (Ig) concentrations. Patients that were included in the study had no change in diagnosis and showed <5 g/L change in serum M-protein during the monitoring. From the patients included at least 3 consecutive samples were analyzed within 8 months and 7 years of initial diagnosis. RESULTS:The total coefficient of variations (CV) was calculated for M-protein and involved/uninvolved fractions of FLCs and immunoglobulins. From 38 patients and 456 samples that were included in the study, the total CVs were calculated for serial M-proteins (8.9%), serum involved FLCs (iFLC, 21.4%), involved Ig (i-Ig, 8.7%) and uninvolved Ig (u-Ig, 9.1%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-protein (8.4%), serum iFLC concentration (21.1%), i-Ig (8.6%) and u-Ig (9.0%). A significant correlation was found in multiple myeloma patients between the κ/λ light chain ratio (rFLC) with i-Ig, the difference between i-Ig level and u-Ig level (d-Ig) and ratio Ig (r-Ig) (r = 0.790, 0.703 and 0.711, respectively). These correlations were not found in patients suffering from MG of undetermined significance and smoldering multiple myeloma. CONCLUSIONS:i-Ig determinations may be an alternative to M-protein for MGs. The variations in serum FLC measurements during MG monitoring were greater than those observed in serum M-proteins and therefore need to be more rigorously revised for recommendations.

SummaryObjectiveAnti‐Mullerian hormone (AMH) together with luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) plays crucial roles in gonadal functions. However, the possible effects of GnRH on AMH via the hypothalamic‐pituitary‐gonadal (HPG) axis remain unexplored. We aimed to explore the changes in AMH levels after bolus GnRH stimulation and understand the relationship of AMH with FSH and LH in healthy subjects.MethodsThirty‐one prepubertal children (15 males/16 females) and 78 adults (36 males/42 females) were included. We collected basal (0 minute) samples for determining levels of hormones. After GnRH treatment at a dose of 2.5 μg/kg body weight (maximum of 100 μg/kg body weight) intravenously, blood was collected at 30 minutes intervals for 120 minutes. Serum LH, FSH and AMH were measured by electrochemiluminometric assays.ResultsAfter injection of GnRH, AMH levels were significantly decreased in 30 minutes (P < 0.001) in all groups with parallel increase of FSH and LH. In the second 30 minutes, all hormones levels reversed. There was also a moderate correlation between AMH and FSH (r = −0.430, P < 0.001).ConclusionsGnRH lowers serum AMH levels, which have a negative correlation with the increase in gonadotrophins. These data pinpoint GnRH as an important factor of the AMH regulation, leading new opportunities for the understanding of AMH role in reproductive function and dysfunction.

The continuing development of nanotechnology necessitates the reliable assessment of potential adverse health consequences associated with human exposures. The physicochemical properties of nanomaterials can be responsible for unexpected interactions with components of classical toxicity assays, which may generate erroneous interpretations.In this paper, we describe how particle interference can be observed in in vitro toxicity tests (CellTiter Blue, CyQUANT, WST-1 and CellTiter-Glo assay) and in cell biology tests using flow cytometry (cell cycle analysis). We used cobalt oxide (Co3O4) particles as an example, but these assays can be performed, in principle, regardless of the nanoparticle considered. We have shown that cobalt particles interfere with most of these tests. We adapted the protocol of the CellTiter-Glo assay to circumvent this interference and demonstrated that, using this protocol, the toxicity level is consistent with results obtained using the clonogenic assay, which is considered to be the reference test.Before assessing particle toxicity using in vitro toxicity tests, interference testing should be performed to avoid false interpretations. Furthermore, in some cases of interference, protocol adaptation can be considered to allow the reliable use of these quick and convenient in vitro tests.

Background: For screening for monoclonal gammopathies, their prognostic stratification and therapy monitoring, the quantitative determination of free immunoglobulin light chains is a significant component.Nephelometric and turbidimetric test methods have so far been associated with analytical limitations and pitfalls.The new quantitative s-FLC ELISA (Sebia) was tested for its suitability for use in routine clinical diagnostics in an application study in a supraregional laboratory center in Germany.Materials and Methods: 510 samples in which the free light chains had previously been determined with the Freelite assays (The Binding Site) were compared with the new ELISA.Furthermore, the M-protein peak concentrations from 25 serum protein electrophoresis (SPE) were compared with the results of free light chain measurements of Freelite and Sebia FLC.Results: Only moderate correlations for the κ and λ light chains between the two methods, Sebia FLC ELISA and Freelite, were found.The concordance correlation coefficients (CCC) were only r=0.68 and r=0.67, respectively.There were significant quantitative differences between the two methods, which were particularly pronounced in samples with high FLC concentrations.The agreement between the immune fixation, which is considered the gold standard, and the Sebila FLC determination was 92.6%, but only 83.0% for the Freelite tests.The Sebia monoclonal FLC concentrations were consistent with the M protein concentrations determined with the SPE.Compared to this, the Freelite monoclonal FLC concentrations were consistently higher.The average overestimation was 10-fold compared to the SPE. Conclusion:The Sebia FLC Assay proved to be a robust platform for the sensitive and accurate determination of free light chains in serum.Due to the good agreement with the SPE and the conformity to the immunofixation as well as the low rerun rate resulting from the larger measuring range of the Sebia sFLC ELISA, these assays are suitable alternatives for the determination of free light chains for screening on monoclonal gammopathies as well as for the follow-up of patients with multiple myeloma.

Research question: The ectodomain of the anti-Mullerian hormone (AMH) type 2 receptor is shed by proteases under certain conditions, which makes it measurable in the blood. The aim of this study was to identify correlations of soluble anti-Mullerian hormone receptor type 2 (sAMHR2) with other sex hormone concentrations and to assess whether sAMHR2 may serve as a new biomarker in fertility disorders. Design: In a retrospective cross-sectional study of women (n = 186) with different gynaecological-endocrinological disorders, mixed-effect models were used to analyse the correlation with established diagnostic hormone tests. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance. Results: There was a strong correlation of sAMHR2 with LH (r = 0.898) and FSH (r = 0.846) and a moderate correlation of AMH with testosterone (r = 0.666) and androstenedione (r = 0.696) (all P < 0.001). In diagnoses of polycystic ovary syndrome (PCOS), AMH showed the best performance (area under the curve [AUC] 0.981, cut-off 4 ng/ml) with 96% sensitivity and 94% specificity. sAMHR2 concentrations and sAMHR2/AMH ratios were elevated in women with ovarian insufficiency, compared with all other study groups, including post-menopausal women on hormone replacement therapy. Highest sensitivity and specificity (100% and 98.2%, respectively) were achieved with sAMHR2/AMH ratio for the diagnosis of post-menopausal status (cut-off 68.85). The sAMHR2/AMH ratio (AUC 0.997) had a better performance than sAMHR2 (AUC 0.947), FSH (AUC 0.989) and LH (AUC 0.967). Conclusions: The sAMHR2/AMH ratio may serve as a useful biomarker for infertility diagnostics to identify postmenopausal women.

Objective: We aimed to contribute to the literature by determining deflection point of parathyroid hormone (PTH) level compared to 25-hydroxy vitamin D-3 (25(OH)D-3) level for determining the cut-off value of vitamin D deficiency level in Turkish adults. Methods: The levels of 25(OH)D-3 and intact parathyroid hormone (iPTH) which were requested simultaneously in 1 year of 1684 adults were evaluated retrospectively. 25(OH)D-3 levels were first classified as 80-50, 50-30, 30-25, 25-20, 20-15, 15-10, 10-5, 5-0 ng/mL and iPTH levels among those groups were compared. Results: First significant difference in iPTH levels was determined between 25(OH)D-3 groups of 80-50 and 50-30 ng/mL (p = 0.007). Second and third significant differences were determined between 25(OH)D-3 groups of 15-10 and 10-5 ng/mL and between 10-5 and 5-0 ng/mL, respectively (p = 0.006 and p = 0.035, respectively). There were no differences in iPTH levels among seasons (p = 0.11). Conclusion: In the light of these findings; we can state that iPTH levels are suppressed when 25(OH)D-3 over 50 ng/mL, remains stable when 25(OH)D-3 levels in between 50-10 ng/mL and gives the first increase response when 25(OH)D-3 falls below 10 ng/mL. We believe that cut-off value for vitamin D deficiency in Turkish adults at all seasons depending on PTH response should be used as 10 ng/mL.

Objective To describe the reference intervals of folate, vitamin B12, vitamin B6, and vitamin B1 by sex and age. Methods The study was performed by gathering data on 55,811 subjects from 57 medical centers. Groups were categorized based on age and grouped according to statistical significance values. The reference values for the different groups were determined using the Bhattacharya and Hoffmann methods. Results Vitamin B1 and B6 values and folate (vitamin B9) levels between the sexes were statistically significantly increased in the group aged 0 to 10 years. Likewise, we witnessed a similar increase in vitamin B12 levels in the group aged 0 to 5 years. However, low vitamin B6 levels (P <.001) were detected in nongeriatric patients (aged 0-60 years), and the reference intervals (3.4-41.9 mu g/L) also were significantly different from those in the geriatric group (aged 61-100 years; 2.0-29.4 mu g/L). Conclusion A lower vitamin B6 reference limit allows detection of subclinical vitamin deficiency more precisely in the geriatric group; respective reference intervals should be revised accordingly.

Objectives: The aims of this study were to underline the interpretation of vitamin B-1 and to evaluate whether differences in hemoglobin (Hb) levels and sex effect vitamin B-1 results. Methods: Simultaneously, whole blood vitamin B-1 and complete blood count were determined in 2238 individuals. Groups were categorized on the basis of sex and Hb levels. Significance and correlation between groups and reference intervals of the study group were determined. Results: There was an 8.4% (P < 0.001) difference between vitamin B-1 levels of men and women, whereas the ratio of vitamin B-1 to Hb showed a 0.12% (P=0.921) difference. The reference interval for the ratio of vitamin B-1 to Hb was 268 to 675 ng/g Hb. Conclusion: Vitamin B-1 concentrations >48 mu g/L should be interpreted with Hb levels to avoid postanalytical errors that mask deficiency. Therefore, in comparative studies, researchers need to pay attention to eliminate the effect of Hb on whole blood vitamin B-1 levels. (C) 2018 Elsevier Inc. All rights reserved.

Aim: We aimed to measure the extent of oxidative stress experienced during labor by the neonates of pregnant women undergoing induced or spontaneous birth and to compare the effects of induced labor on fetalwell-being.Methods: Sixty-four healthy pregnant women referring to the Department of Gynecology and Obstetrics, Dicle University Medical Faculty between October 2010 and May 2011 were included in this comparative study. Pregnant women undergoing induced labor by oxytocin were group 1 and those without labor induction were group 2. Post-partum Apgar score was calculated at 1 and 5 min and measurements of weight and height of the neonateswere carried out. After the fetal cordwas clamped, 5 cm(3) blood was drawn into a plain tube without anticoagulant. The samples were centrifuged at 5000 r.p.m. for 5 min. Separated sera were transferred to Eppendorf tubes and were stored at -80 C degrees until the analysis time.Results: The complete blood counts and biochemistry results indicated that there were no statistically significant differences in regards to diseases between the two groups. Nitric oxide and asymmetrical dimethylarginine values of the two groups were not significantly different; however, there were statistically significant differences in the malondialdehyde, paraoxonase, total antioxidative status, and total oxidative status values of the two groups (respectively, P = 0.005, P = 0.006, P = 0.008, and P = 0.007).Conclusion: We observed that oxytocin-induced labor increases stress markers but does not affect Apgar scores. Oxidative stress in pregnant women may trigger antioxidative mechanisms. Prospective studies in larger cohorts are needed to better understand the impact of oxytocin-induced labor on pregnant women and neonates.

Objective: The primary aim of our study was to investigate the usefulness of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in the differential diagnosis of causative gram-positive (Gram+) or gram-negative (Gram-) bacteria in patients with sepsis to facilitate decisions concerning the initial choice of an empiric antibiotic regimen. Methods: Between February 2014 and February 2016, 47 patients who had sepsis diagnosed on the basis of positive blood cultures and clinical examination results were retrospectively enrolled. Serum CRP and PCT levels of 15 gram+ and 32 gram-bacterial sepsis groups were compared using the Mann-Whitney U test. The correlation between CRP and PCT levels was calculated using the Spearman's test. Results: Among patients with bacterial sepsis, the median CRP level was 91.42 mg/L and the median PCT level was 0.46 ng/mL. There were no significant difference in CRP and PCT levels between the gram+ and gram-sepsis groups (p=0.98 and p=0.21, respectively). There was good correlation between the CRP and PCT levels (r=0.64, p<0.001). Conclusion: Considering the changes and the status of proinflammatory/anti-inflammatory responses in the pathogenesis of sepsis, we believe that CRP and PCT levels alone are insufficient for predicting the type of causative bacteria in sepsis.

Objective: To investigate the protective effects of caffeic acid phenethyl ester (CAPE) against isoniazid (INH)- and rifampicin (RFP)-induced hepatic and pancreatic damage. Methods: Eighty adult rats were randomly divided into eight groups: control, INH, RFP, INII+RFP, INII+CAPE, RFP+CAPE, INII+RFP+CAPE, and CAPE. Both _MI and RFP were orally administered for 30 days at a dose of 50 mg/kg/day. Caffeic acid phenethyl ester was intraperitoneally injected for 30 days (10 mu mol/kg). Blood samples, hepatic and pancreatic tissues were obtained on day 30. Results: Total oxidant status levels were significantly higher in MI and/or RFP-treated groups than those of control and CAPE groups, while total antioxidant status and paraoxonase levels were significantly reduced in INH-RFP groups compared with the group receiving CAPE. Histopathological deterioration was observed in RFP and INH groups in pancreatic and hepatic tissue. However, significant amelioration was observed in CAPE-treated groups. Conclusion: Our findings suggest that CAPE may be a promising agent to prevent the side effects of INH and RFP treatment on hepatic and pancreatic tissues.

ABSTRACT Aim: Our aim was to evaluate the serum prolidase activity, total antioxidant capacity (TAC) and total oxidant status (TOS) in patients with keratoconus. Material and method: A total 69 keratoconus patients and 72 control subjects with similar age and gender were evaluated within the scope of this study. The keratoconus group was divided into four stages with the modified Krumeich classification. Serum prolidase activity, TAC and TOS were measured and compared between the patient and control groups. Results: The median serum prolidase enzyme activity value was 528.3 (684.1–416.7) U/L in the keratoconus group and 606.2 (812.9–482.3) U/L in the control group. The difference between the groups was statistically significant (p = 0.027). The median TAC value was 1.24 (1.37–1.05) mmol/L in the keratoconus group and 1.29 (1.38–1.18) mmol/L in the control group. The median TOS value was 2 (4–1) μmol/L in the keratoconus group and 3 (4–2) μmol/L in the control group. There was no statistically significant difference between the two groups in terms of TAC or TOS (p = 0.113 and p = 0.366, respectively). There was a positive correlation between TAC and TOS in keratoconus group but not in the control group (r = 0.670, p = 0.001 and r = 0.141, p = 0.241, respectively). No significant relationship was seen between the keratoconus group stages and serum prolidase activity, TAS or TOS (p = 0.894, p = 0.155 and p = 0.381, respectively). Conclusion: In conclusion, a significant relationship was found between decreased serum prolidase activity and keratoconus but there was no significant relationship between keratoconus and serum TAC or TOS.

Materials & Methods: Group Sham (n=15); the rats non exposed CO gas in air or to ambient air at a rate of 4L/min for 30 min in 16-L Plexiglas chamber. Group TQ (n= 15); TQ was given at a triple dose (at 0, 12 and 24 hrs) 8mg/kg TQ intraperitoneally in (3 ml DMSO). Group CO (n=15); CO poisoning was performed according to the published protocol in Plexiglas chambers. Rats breathed 1000 ppm CO for 40 min and then 3000 ppm for up to 20 min, until they lost consciousness; then they were removed to breathe room air and regain consciousness. Group CO+TQ (n=15); CO poisoning was performed according to the published protocal in Plexiglas chambers.

Aim: The aim of this study was to evaluate the relationship between hemoglobin A1c (HbA1c) and 25-hydroxyvitamin D levels and to investigate the difference in this relationship between genders.Methods: In this study, we retrospectively evaluated fasting blood glucose, HbA1c, 25-hydroxyvitamin D and parathyroid hormone levels in 3675 subjects (660 male, 3015 female). The subjects were divided into two groups according to sex and into three groups according to HbA1c levels as pre-diabetics (5.7-6.4%), diabetics (6.5-8.0%) and uncontrolled diabetics (>8.1%). Individuals with an HbA1c value between 4.0% and 5.6% who had no history of diabetes mellitus constituted the control group.Results: Significantly low levels of 25-hydroxyvitamin D were detected in female uncontrolled diabetics (p<0.001). However, no difference found in males between the groups A downward trend in 25-hydroxyvitamin D levels was observed to start in prediabetes period. There was no significant difference in parathyroid hormone levels between the groups.Conclusion: In addition to HbA1c levels, 25-hydroxyvitamin D levels should be investigated and considered especially in follow-up of diabetic female patients.