Glycosaminoglycan-induced proinflammatory cytokine levels as disease marker in mucopolysaccharidosis.

Recently, it has been shown disturbances in oxidant/antioxidant system and increases in some inflammatory markers in animal studies and in some Mucopolysaccharidoses (MPSs) patients. In this study, we aimed to determine the oxidative stress/antioxidant parameters and pro-inflammatory cytokine levels in the serum of MPS patients, in order to evaluate the possible role of inflammation in these patient groups regarding to accumulated metabolites. MPS I (n = 3), MPS II (n = 8), MPS III (n = 4), MPS IVA (n = 3), MPS VI (n = 3), and VII (n = 1) patients and 20 age-matched healthy subjects were included into the study. There was no statistically significant change in activities of SOD, Catalase, GSH-Px and lipid peroxidation levels in erythrocytes between the MPS patients and healthy controls. While IL-1alpha (p = 0.054), IL-6 (p = 0.008) levels, and chitotriosidase activity (p = 0.003) elevated in MPS3 patients, IL1α (p = 0.006), IL-1ß (p = 0.006), IL-6 (p = 0.006), IFNγ (p = 0.006), and NFκB (p = 0.006) levels increased in MPS-6 patients. Elevated levels of IL-6, IL1α and chitotriosidase activity demonstrated macrophage activation in MPSIII untreated with enzyme replacement. Our study showed for the first time that high levels of IL1α, IL-6, IL1ß and NFκB were present in MPSVI patients, demonstrating the induction of inflammation by dermatan sulphate. The low level of paraoxonase in MPSVI patients may be a good marker for cardiac involvement. Overall, this study provides important insights into the relationship between lysosomal storage of glycosaminoglycan and inflammation in MPS patients. It highlights possible pathways for the increased release of inflammatory molecules and suggests new targets for the development of treatments.

Development, optimization and validation of LC-MS/MS method for the determination of DBS GALT enzyme activity.

Galactosemia is a carbohydrate metabolism disorder often caused by galactose-1-phosphate uridyl transferase (GALT) deficiency. Detecting GALT deficiency involves measuring intra-erythrocyte enzyme activity. We aimed to create a robust liquid chromatography-mass spectrometry (LC-MS/MS) method to assess GALT activity in dried blood spot (DBS) samples. We validated this method and compared it to the fluorometric approach. We investigated the impact of K2EDTA and lithium heparin tubes on enzyme activity to identify the best sample collection tube. We also assessed the reaction-stopping method. The developed approach employed [13C6]-galactose-1-phosphate as a substrate and UDP-N-acetylglycosamine as an internal standard (IS). The mean ± SD value for GALT activity of DBS samples was determined as 6.37 ± 1.96 µmol/gHb/hour. The linear range was 0.4-50 µM (2.4-310% of normal) in the DBS method. The % coefficient of variation (%CV) values were less than 15 for intra-day and inter-day repeatability studies. Over 90% recovery was achieved in recovery studies, and no ion suppression from matrix was detected. DBS samples were quite stable for 31 days under different storage conditions. Enzyme activity results reported as <3.5 U/g Hb by fluorometric method, were quantitatively determined for even very low concentrations by LC-MS/MS method.

Effects of vitrification solution supplemented with platelet-rich plasma in rat ovarian tissue cryopreservation.

Background/aim: The subject of this study was to investigate the utility of platelet-rich plasma (PRP) in the cryopreservation process to reduce cryodamage and increase tissue viability. Materials and methods: Twenty-one female Wistar rats were randomly allocated to three groups. In Group 1 (G1), rats were not subjected to vitrification (n = 7). Group 2 (G2) was the vitrification group in which PRP was added to the basic vitrification solution (n = 7). Group 3 (G3) was the vitrification group in which fetal bovine serum was added to the basic vitrification solution (n = 7). Warmed tissues were evaluated with histochemical (HC) and immunohistochemical (IHC) staining, the TUNEL method, immunofluorescence (IF) staining, and biochemical analyses. Results: The percentages of IHC staining, TUNEL method positivity, and IF staining were significantly higher in G2 compared to both G1 and G3 (P < 0.05). G2 ovaries exhibited a significant increase in both malondialdehyde and catalase values in comparison to G1 (P < 0.05). In HC staining, degenerations in primary and secondary follicles and in ovarian tissue were more common in the PRP-supplemented group. The calcium used in PRP activation was suspected to have increased the degeneration and prevented the possible positive effects of PRP. Conclusion: To the best of our knowledge, PRP-supplemented vitrification solution was used for the first time in the literature in this study in whole rat ovarian tissue vitrification. If PRP is to be used as a component in vitrification solution for rat ovarian tissue, the use of lower amounts of calcium or different methods in PRP activation, or the use of nonactivated PRP, should be considered from the beginning.

The Effect of Foot Reflexology Applied Before Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty on Anxiety, Stress, and Cortisol Levels of Individuals: A Randomized Controlled Trial.

BACKGROUND: Coronary angiography and percutaneous transluminal coronary angioplasty procedures cause anxiety and stress in individuals. OBJECTIVE: The aim of this study was to determine the effect of foot reflexology applied before coronary angiography and percutaneous transluminal coronary angioplasty on the anxiety, stress, and cortisol levels of individuals. METHODS: A simple randomized trial design was used. The patients who met the inclusion criteria were divided into 4 groups including experimental and control groups of coronary angiography patients (30 patients in each group) and percutaneous transluminal coronary angioplasty (26 patients in each group) by randomization method. Data were collected with the State-Trait Anxiety Inventory and Distress Thermometer 90 minutes before coronary angiography and percutaneous transluminal coronary angioplasty and the laboratory samples were taken. After these procedures, foot reflexology was applied to both feet of the patients in the experimental group for 30 minutes, and the control group received only standard care. The inventories were reapplied 30 minutes after the reflexology application and after coronary angiography and percutaneous transluminal coronary angioplasty. RESULTS: Whereas there was no statistically significant difference (P > .05) between the coronary angiography and percutaneous transluminal coronary angioplasty experimental and control groups in Anxiety Inventory and stress median scores before reflexology, a significant difference was found (P < .001) 30 minutes after reflexology application and after coronary angiography and percutaneous transluminal coronary angioplasty. After the reflexology, anxiety and stress scores were significantly lower in the experimental group compared with the control group (P < .001). Whereas there was a significant difference (P < .001) in the within-group cortisol values of both reflexology groups, no significant difference was found in the control groups (P > .05). CONCLUSIONS: The application of reflexology before coronary angiography and percutaneous transluminal coronary angioplasty reduces the levels of anxiety, stress, and cortisol without any side effects.

Can urinary biomarkers predict acute kidney injury in newborns with critical congenital heart disease?

BACKGROUND: Congenital heart disease (CHD) is the most common congenital malformation group and is the leading cause of newborn mortality in developed countries. Most of the infants with CHD develop preoperative or postoperative acute kidney injury (AKI). Acute kidney injury may develop before the serum creatinine rise and oliguria. Urinary biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, and cystatin C may predict AKI in patients with critical CHD (CCHD) before the serum creatinine rise. In this study, we aimed to determine the AKI incidence among newborn patients with CCHD and investigate the predictivity of urinary biomarkers for AKI. METHODS: Newborns with a gestational age >34 weeks and birth weight >1500 g with a diagnosis of CCHD were enrolled in the study. Blood and urine samples were collected at birth, during the first 24-48 h, and in the preoperative and postoperative periods. RESULTS: A total of 53 CCHD patients requiring surgery during the neonatal period were enrolled in the study. The 24-48 h KIM-1 levels of the cases with exitus were higher (P = 0.007). The 24-48 h cystatin C and preoperative NGAL levels were higher in patients with postoperative AKI (P = 0.02). DISCUSSION: In newborns with CCHD, high KIM-1 levels may predict mortality, whereas high cystatin C and preoperative NGAL levels may be indicative of AKI. These biomarkers deserve further investigation in larger study populations.

A novel marker of systemic inflammation in psoriasis and related comorbidities: chitotriosidase

Background/aim: Chitotriosidase (ChT) is an enzyme secreted by activated macrophages and neutrophils in response to proinflammatory signals. There is growing evidence indicating that ChT activity reflects the systemic inflammatory status. This study aimed to investigate whether serum ChT activity increased in patients with psoriasis and related comorbidities. Materials and methods: This cross-sectional study included 53 (28 with associated comorbidities and 25 without comorbidities) patients with psoriasis and 52 healthy volunteers. All participants underwent laboratory investigations for serum ChT levels, complete blood count, erythrocyte sedimentation rate, C-reactive protein, and serum lipid levels. Results: The patients with psoriasis showed significantly higher levels of ChT activity as compared to the healthy controls (23.5 ± 11.4 vs. 17.5 ± 10.4 µmol/mL/hour; p = 0.015). Additionally, the ChT activity was significantly higher in patients with comorbidities than in those without (p = 0.042). Conclusion: Our data support the pathogenetic role of inflammatory processes induced by macrophage activation in patients with psoriasis and related comorbidities. We believe that high ChT activity in patients with psoriasis may serve as an early prediction of the possible related comorbidities.

Propolis prevents inhibition of apoptosis by potassium bromate in CCD 841 human colon cell.

Previously, we demonstrated that biotransformation of propolis by some special strains of Lactobacillus plantarum might decrease the allergenic molecules in propolis. In this study, we aimed to investigate the effect of biotransformation of propolis on its antioxidant effect and its protective effect against potassium bromate-induced cancer in human colon cell line. Propolis samples were treated with different solutions (ethanol, polyethylene glycol, and water), and ultrasonication was applied at 40 Hz (5, 10, and 15 minutes) in order to facilitate solvation of solid samples. Fermentations were performed by L. plantarum strains (ISLG-2, ATCC-8014, and Visbyvac). The phenolic content of propolis was determined with liquid chromatography-mass spectrometry/mass spectrometry (LCMS/MS). The antioxidant activity (antioxidant enzymes, lipid peroxidation) and apoptosis markers (caspase 3,8,9, cytochrome-c, tumour necrosis factor-related apoptosis-inducing ligand-R1 and R2 [TRAIL], and apoptosis protease activating factor-1 [APAF-1] levels) were determined in CCD 841-human colon cell line after induction of oxidative stress by potassium bromate. All propolis samples in different solvents induced apoptosis and 4 biotransformed (by L. plantarum ISL-2 strain and L. plantarum ATCC 8014 strain) propolis samples with low allergenic molecules demonstrated similar inductions of apoptosis in CCD841 cell line. In conclusion, reduction of allergenic molecules in propolis via biotransformation did not change the antioxidant and protective effects of propolis, and it is suggested as a potential therapeutic molecule in prevention of colon cancer caused by oxidative stress for all patients. SIGNIFICANCE OF THE STUDY: This study is the first investigation that shows protective effect of propolis against potassium bromate toxicity by means of decreasing lipid peroxidation and reversing the main molecule levels in intrinsic and extrinsic pathway of apoptosis. Biotransformed propolis samples by L. plantarum ISL-2 and ATCC 8014 strain with low allergen molecule content has also the same effect in potassium bromate toxicity in CCD841 colon cell. Our data contributed that propolis as a natural compound might be a good candidate due to its minimal toxicity and lack of any adverse effects to prevent carcinogenic effect of potassium bromate.

Coexistence of Gaucher Disease and severe congenital neutropenia.

Gaucher Disease (GD) is the most common lysosomal storage disorder has traditionally been classified into three clinical phenotypes. Type 3 GD is characterized by neurological involvement but neurological symptoms generally appear later in life than in type 2 disease. Neutropenia is much rarer than other hematological manifestations in GD and has not been scrutinized adequately. Severe congenital neutropenia (SCN) is a rare disease entity which is characterized by a paucity of peripherally circulating neutrophils with arrest of neutrophil maturation at the promyelocyte stage and consequent increased susceptibility to severe and recurrent infections. We report a patient who presented in the first year of life with visceral involvement and severe neutropenia in whom the propositus had a unique coexistence of Gaucher Disease and severe congenital neutropenia associated with a mutation in HAX1. In contrast to his expired siblings he had experienced no severe infections. These clinical observations suggest that enzyme replacement therapy may display a modulating factor with respect to the clinical course of SCN. SYNOPSIS: Our patient is the only report of the combination of Gaucher Disease and Kostmann Syndrome in the literature. The clinical course of our patient is not severe when comparing with exitus siblings and other Kostmann Syndrome patients. But when considering the patient's only clinical difference is ERT, this case is very important to emphasise the role of enzyme replacement therapy in bone marrow.

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey.

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.

An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation.

BACKGROUND: An unexpectedly detected prolonged activated partial thromboplastin time (APTT) can be a harmless laboratory finding, but can also reflect a thrombotic tendency or a bleeding disorder. The assistance of laboratory professionals in the interpretation of an unexpectedly detected prolonged APTT (uAPTT) is often required. The way in which uAPTTs are evaluated in laboratories was assessed in this international study with the aim of determining whether laboratory professionals are able to fulfill this need. METHODS: Postanalytical practices after uAPTT were investigated and the mixing study methodology (if used) was studied by circulating a case report with a questionnaire to staff in the invited laboratories. In addition, the interpretations of those staff regarding the presence or absence of inhibitors in three APTT mixing study scenarios were examined. RESULTS: Large within- and between-country variations were detected in both postanalytical practices and mixing study methodologies among the 990 responding laboratories, 90% of which were in 13 countries. Shortcomings regarding the investigation of uAPTTs leading to potentially incorrect or delayed clinical diagnoses were found in 88% of the laboratories. Of the laboratories to which the interpretative questions were sent, 49% interpreted all mixing study scenarios correctly. uAPTTs were investigated appropriately and all mixing study scenarios interpreted correctly in parallel in only 9.6% of the participating laboratories. CONCLUSIONS: The clinical requirement for the assistance of laboratory professionals in the interpretation of uAPTTs cannot be met at most of the participating laboratories. Laboratory professionals should be trained in the evaluation of ordinary laboratory tests, such as that for uAPTTs.

Cord blood and consecutive chitotriosidase activity: Relationship to prematurity and early prognosis.

BACKGROUND: The aim of this study was to investigate the relationship between plasma chitotriosidase activity, an inflammatory protein secreted mainly from macrophages, and neonatal morbidity and mortality in premature infants. METHODS: Cord blood chitotriosidase activity was studied in healthy control infants (53 term, group 1; 26 late preterm [33-37 gestational weeks], group 2) and 35 preterm infants (≤ 32 weeks; group 3). In group 3, consecutive samples at 3 h, 24 h, 72 h, 7 days, 14 days, and 36 weeks after conception were also analyzed. Group 3 was also evaluated for mortality, respiratory treatment and bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). RESULTS: Cord blood chitotriosidase activity was positively correlated with gestational age and birthweight. SNAPPE-II score was correlated with chitotriosidase activity at 24 h. Consecutive chitotriosidase activity for group 3 was non-significantly higher in infants who died in the early neonatal period. Higher chitotriosidase activity was observed in mechanically ventilated infants than infants treated with non-invasive assisted ventilation. BPD, PDA, IVH and ROP, but not NEC, were related to higher chitotriosidase activity, being significant at some of the time points. CONCLUSION: Neonatal stress such as invasive ventilation may create a risk for the development of BPD, PDA, IVH, and ROP by increasing macrophage activation in preterm infants as reflected in the higher chitotriosidase activity. High chitotriosidase activity may also be associated with disease severity and mortality.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery.

BACKGROUND: Currently, the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors, but they are not a cure, and some patients don't respond well or refuse long-term use. Therefore, alternative therapies are needed to understand the disease and develop better treatments. Laparoscopic anti-reflux surgery (LARS) can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects. Successful LARS improves typical gastroesophageal reflux symptoms in most patients, mainly by reducing the exposure time to gastric contents in the esophagus. Amelioration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack. AIM: To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery. METHODS: Of 22 patients with LARS (pre- and post/5.8 ± 3.8 months after LARS) and 25 healthy controls (HCs) were included. All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy, during which esophageal biopsy samples were collected using endoscopic techniques. Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay. RESULTS: Post-LARS samples showed significant increases in proinflammatory cytokines [interleukin (IL)-1ß, interferon-γ, C-X-C chemokine ligand 2 (CXCL2)], anti-inflammatory cytokines [CC chemokine ligand (CCL) 11, CCL13, CCL17, CCL26, CCL1, CCL7, CCL8, CCL24, IL-4, IL-10], and homeostatic cytokines (CCL27, CCL20, CCL19, CCL23, CCL25, CXCL12, migration inhibitory factor) compared to both HCs and pre-LARS samples. CCL17 and CCL21 levels were higher in pre-LARS than in HCs (P < 0.05). The mRNA expression levels of AKT1, fibroblast growth factor 2, HRAS, and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS. CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs (P < 0.05). CONCLUSION: The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium. Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS. The anti-inflammatory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

Ocular Manifestations of Fabry Disease: Report from a Tertiary Eye Care Center in Türkiye.

Objectives: To report ocular manifestations in patients with Fabry disease (FD) from a tertiary eye care center in Türkiye. Materials and Methods: This prospective, cross-sectional study included 30 eyes of 15 patients with FD. The diagnosis of FD was made based on a combination of clinical findings, genetic analysis, and biochemical evaluation. All participants underwent a detailed ophthalmic examination with special focus on the typical ocular features of FD (cornea verticillata, conjunctival aneurysms, cataract, retinal vessel tortuosity). Results: The mean age was 45±17 years (range: 22-75 years), with a female/male ratio of 2:3. All patients had tortuous conjunctival vessels and 12 patients (80%) had conjunctival aneurysms. Cornea verticillata was present in 10 patients (66.6%), lens opacification in 4 patients (26.6%), and retinal vascular tortuosity in 8 patients (53.3%). All patients had at least two different ocular findings; most (3 heterozygotes/7 hemizygotes) had a combination of corneal verticillata and conjunctival vessel abnormality. The conjunctiva, cornea, and retina were affected together in 5 hemizygous patients (33.3%). One hemizygous patient had all FDrelated ocular manifestations in both eyes. Conclusion: To our knowledge, this study is the first to describe the ocular manifestations of FD in the Turkish population. Although cornea verticillata is considered a hallmark of FD, it was absent in approximately one-third of patients. Moreover, cataract, another well-known feature of FD, was present in only 26.6% of the patients. Conjunctival vascular abnormality alone seems to be quite rare in FD, although it often accompanies other ocular manifestations. Therefore, recognition of other mild findings and special consideration of their associations may increase the diagnostic value of ocular findings in FD.

Development of a New Amperometric Biosensor for Measurement of Plasma Galactose Levels.

Galactosemia is an inherited disease that occurs as a result of insufficient or no synthesis of some enzymes (GALT, GALK, and GALE) in galactose metabolism. Failure to make an early diagnosis, especially in newborns, can lead to severe clinical and even fatal consequences. The aim of this study is to develop a biosensor for measuring free galactose in plasma. The immobilization components of the developed free galactose biosensor are screen printed carbon electrode (SCPE), Prussian blue (PB), chitosan (CHIT), Nafion (NAF), gold nanoparticle (GNP), and galactose oxidase (GaOX). The CHIT/GaOX/NAF-GNP/GaOX/CHIT-GNP/SCPE-PB electrode showed a sensitive amperometric response to detect galactose. While the surface characterization of the biosensor was performed with cyclic voltammetry and scanning electron microscopy, the optimization and performance characterizations were made by applying an amperometry technique. The amperometric operating potential for the free galactose biosensor was determined as -0.05 V. The linear detection range for the free galactose biosensor is between 0.025 and 10 mM. This range includes galactose levels in plasma of both healthy and patients. The percent coefficient of variation values calculated for intraday and interday repeatability of the developed biosensor are below 10%. The practical use of the biosensor, for which optimization and characterization studies were carried out, was tested in 10 healthy 11 patients with galactosemia, and the results were compared with the colorimetric method. In conclusion, the unique analytical properties and effortless preparation of the new galactose biosensor developed in this study make them serious candidates for point-of-care diagnostic testing.

Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model.

INTRODUCTION: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. METHODS: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. RESULTS: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. CONCLUSIONS: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

Reference intervals of α-glycosidase, ß-glycosidase, and α-galactosidase in dried blood spot in a Turkish newborn population.

Inherited lysosomal storage diseases (LSDs) are rare, and diagnosis is often delayed for 7-10 years. Since the therapies have become available for a limited number of LSDs, (Fabry, Gaucher, Pompe, and MPS-1), early diagnosis of treatable LSDs can be lifesaving or ameliorating and allows timely treatment before irreversible damage occurs. Recently, the use of dried blood spot test (DBS) for newborn screening of LSDs has been proposed for newborn screening tests. They are noninvasive, sensitive, and specific assays with the further advantage of a fast turnaround time compared to measurement in leukocyte and/or fibroblast culture. We aimed to determine the reference intervals for lysosomal enzyme activities of newborn babies in our population and to investigate the effect of gestational week on enzyme activity. One hundred thirty healthy newborn babies (70 girls, 60 boys) were included into the study. α-Glycosidase, ß-glycosidase, and α-galactosidase activities in DBS samples of newborns were determined fluorometrically. Reference intervals were calculated using Dixon's rule and percentiles of 2.5-97.5. Cutoff limits (5 %) for α-glycosidase, ß-glycosidase, and α-galactosidase activities were 0.57, 0.92, and 2.18, respectively. α-Galactosidase activity was higher in girls compared to boys (p < 0.05). Interestingly, α-glycosidase and ß-glycosidase activities of newborns who were delivered before 38 weeks were significantly lower than those who were delivered at 39-40 weeks. Conclusion It is of utmost importance to define the reference intervals for lysosomal enzyme activities as well as cutoff limits for newborn babies with regard to gestational age and sex. More studies to clarify the reason for the change in enzyme activity by gestational week will be required.

Roles of Cytokines in Pathological and Physiological Gastroesophageal Reflux Exposure.

Background/Aims: Gastroesophageal reflux disease is frequently observed and has no definitive treatment. There are 2 main views on the pathogenesis of gastroesophageal reflux disease. The first is that epithelial damage starts from the mucosa by acidic-peptic damage and the inflammatory response of granulocytes. The other view is that T-lymphocytes attract chemoattractants from the basal layer to the mucosa, and granulocytes do not migrate until damage occurs. We aim to investigate the inflammatory processes occurring in the esophageal epithelium of the phenotypes at the molecular level. We also examined the effects of these changes on tissue integrity. Methods: Patients with mild and severe erosive reflux, nonerosive reflux, reflux hypersensitivity, and functional heartburn were included. Inflammatory gene expressions (JAK/STAT Signaling and NFKappaB Primer Libraries), chemokine protein levels, and tissue integrity were examined in the esophageal biopsies. Results: There was chronic inflammation in the severe erosion group, the acute response was also triggered. In the mild erosion group, these 2 processes worked together, but homeostatic cytokines were also secreted. In nonerosive groups, T-lymphocytes were more dominant. In addition, the inflammatory response was highly triggered in the reflux hypersensitivity and functional heartburn groups, and it was associated with physiological reflux exposure and sensitivity. Conclusions: "Microinflammation" in physiological acid exposure groups indicate that even a mild trigger is sufficient for the initiation and progression of inflammatory activity. Additionally, the anti-inflammatory cytokines were highly increased. The results may have a potential role in the treatment of heartburn symptoms and healing of the mucosa.

High chitotriosidase and AGE levels in acromegaly: a case-control study.

PURPOSE: Acromegaly is associated with oxidative stress and inflammation parameters. Chitotriosidase (CHITO) is a marker of macrophage activation and plays a pivotal role in the activation of inflammatory and immunological responses. Our study aimed to determine CHITO,YKL-40, advanced glycation end product (AGE), and high-sensitivity C-reactive protein (hsCRP) levels to investigate malondialdehyde (MDA), catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and to evaluate any association of these parameters with carotid intima media thickness (cIMT) in patients with controlled acromegaly. METHODS: Thirty controlled acromegaly patients and 41 age- and sex-matched control cases were studied. We obtained demographic data, hormonal and metabolic parameters, and cIMT. CHITO activity was measured with the fluorometric method of Chamoles et al. YKL-40 and hsCRP levels were measured using ELISA. AGEs were measured based on spectrofluorimetric detection. GSH-Px activity was determined by a colorimetric assay. MDA, SOD, and catalase activities were determined in hemolysis. RESULTS: Higher CHITO, AGE, and hsCRP concentrations were observed in patients with acromegaly compared to controls. SOD levels were non-significantly higher in the acromegaly group, while catalase activities were lower in patients with acromegaly. Correlation analyses of CHITO, AGEs, YKL-40, hsCRP, MDA, catalase, GSH-Px, and SOD with metabolic, anthropometric, and laboratory parameters did not demonstrate any significant correlation (p > 0.05). There was no significant difference between groups with regard to cIMT levels. CONCLUSION: This is the first study investigating CHITO and AGE levels in patients with acromegaly. Serum CHITO, AGE, and hsCRP levels in acromegalic patients were significantly increased. It may be important to evaluate CHITO, AGE, and hsCRP levels in acromegalic patients who are already under cardiometabolic surveillance due to risk of developing cardiovascular disease.

Perspective on pros and cons of microlearning in health education.

Recently, digital technology and digital materials have started to be widely used in education from primary school to college worldwide. Microlearning is one of the innovative teaching techniques that use digital technologies. In this review, benefits and disadvantages of microlearning is discussed. Many studies show that microlearning facilitated learning by dividing into smaller pieces encourages students to study. A wide range of activities might be used in this technique and it can be easily integrated into daily routine, it allows on-demand learning for the students. On the other hand, the success of microlearning techniques is closely related to the personal characteristics of learners, teachers' prone to use digital technology and the external factors such as access to learning materials. Its effectiveness on behavior and outcome which were defined in the third and fourth levels of Kirkpatrick's learning model is still obscure. In the light of the literature, it should be decided which microlearning method will be used for which educational subjects.