Could immune cells be associated with nephropathy in Fabry disease patients?

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT. MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration. RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3-CD16+CD56+ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3+4+T-cells infiltration remained the same, whereas CD8+T cells, CD16+ and 56+NK-cells infiltration were significantly decreased. In contrast, CD20+B cells and CD138+plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20+B and CD138+ plasma cells and IF were positively correlated with proteinuria. CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

Sleep disturbances and affecting factors in young children with food allergy and their mothers.

OBJECTIVE: To examine sleep patterns and sleep disturbance of children with food allergy (FA) and their mothers. METHODS: The food allergy group included 71 children with mean age, 2.97±1.52 years, and 58 control children were recruited the study. Mothers of children completed the Childhood Sleep Habits Questionnaire (CSHQ) and The Pittsburgh Sleep Quality Index (PSQI) in order to evaluate sleep disturbance in both children and themselves. Depressive symptomatology of mothers of children with or without food allergy was assessed with Beck-Depression Inventory II (BDI-II). RESULTS: The mean total scores of CSHQ was 49.33±7.93 (range=31-68) in the FA and 42.39±6.43 (range=30-62) in controls. The total CSHQ scores were significantly higher in children with FA than in controls (p=0.002). The total PSQI score was significantly higher in mothers of children with FA than in mothers of children without FA (7.09±3.11 vs 5.15±2.59, p<0.001) indicating that the mothers of children with FA had worse sleep quality. The mothers of children with FA had more depressive symptoms than mothers of children without FA. The mean total scores of BDI-II were 10.10±6.95 in mothers of children with FA and 7.78±6.64 in mothers of children without FA (p=0.005). CONCLUSION: The presence of a food allergy in a child may be associated with a deterioration in sleep quality in children and mothers as well as increased depressive symptoms in mothers.

Risk factors for postoperative nausea and vomiting in pediatric patients undergoing ambulatory dental treatment.

AIM: This study aimed to determine the risk factors for postoperative nausea and vomiting (PONV) in children receiving dental treatment under general anesthesia and to identify the subcategories leading to risk formation. MATERIALS AND METHODS: The study comprised of 100 American Society of Anesthesiologists I patients aged 2-7 years who were administered dental treatment under general anesthesia. Patients were evaluated with regard to PONV risk. Eight different independent risk factors were identified as follows: age, gender, weight, duration of anesthesia, duration of recovery, postoperative pain, rescue analgesia, and type of dental treatment. Classification and regression trees method was used to choose the best predictor for PONV. RESULTS: The incidence of PONV was 25%. No significant difference was found between those with PONV and those without PONV with regard to gender, weight, duration of anesthesia, duration of recovery, or the type of dental treatment (P > 0.05). However, postoperative pain level and use of rescue analgesia with tenoxicam were both predictors of PONV (P < 0.05). For the postoperative pain (≤1.5) subgroup, age proved to be the best predictive variable. CONCLUSION: The risk limit for PONV was determined to be ≥5.5 years for children who underwent dental procedures under general anesthesia. Postoperative pain and rescue analgesia constituted risks for PONV.

The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.

Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies. Although GATA factors bind DNA motifs harboring the sequence GATA, only a very small subset of these abundant motifs are occupied in genomes. Mechanistic studies revealed a unique configuration of a GATA factor-regulated cis-element consisting of an E-box and a downstream GATA motif separated by a short DNA spacer. GATA-1- or GATA-2-containing multiprotein complexes at these composite elements control transcription of genes critical for hematopoietic stem cell emergence in the mammalian embryo, hematopoietic progenitor cell regulation, and erythroid cell maturation. Other constituents of the complex include the basic helix-loop-loop transcription factor Scl/TAL1, its heterodimeric partner E2A, and the Lim domain proteins LMO2 and LDB1. This chapter reviews the structure/function of E-box-GATA composite cis-elements, which collectively constitute an important sector of the hematopoietic stem and progenitor cell cistrome.

Clinical features of potato sensitivity in children with allergic disease.

BACKGROUND AND OBJECTIVE: Although potato is greatly consumed all over the world, adverse reactions to potato are uncommon. Our aim is to describe the clinical features of potato sensitivity in allergic children. MATERIALS AND METHODS: Forty children with sensitivity to potato were followed up in the Pediatric Immunology and Allergy Clinic of our hospital were included in the study. These patients were retrospectively evaluated from January 2012 to December 2013. RESULTS: Forty children aged between 6 months and 10 years (mean 2.9±3.2, median:1.5 years) were enrolled of whom 26 were male (65%). Thirty three of these children had presented eczema, nine wheezing, seven urticaria and/or angioedema, six rhinitis, four subjects had experienced anaphylaxis, and two vomiting or other gastrointestinal complaints. In 38 (95%) patients, skin prick tests detected sensitivity to other allergens besides potato. The most frequently identified sensitivities were to food sensitivities (82.5%). In addition sensitivity to house dust mite, cat dander, pollens, A. Alternata and cockroaches in skin prick tests were documented in nine, six, five, four and four patients, respectively. Latex sensitivity was not detected in any patient. Five (38.5%) out of 13 patients over the age of three showed sensitivity to pollen. CONCLUSIONS: Potatoes sensitivity is mostly seen in children with atopic dermatitis. In children with atopic eczema should be asked whether the increase in complaints with potatoes. Mostly potato sensitivity is combined with other food allergies. Therefore potato should be included in the test in patients with atopic eczema and food allergy.

CD3G gene defects in familial autoimmune thyroiditis.

The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRαß+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.

Eccentric/concentric training of ankle evertor and dorsiflexors in recreational athletes: muscle latency and strength.

The aim of this study was to investigate the effects of a combined eccentric-concentric exercise program of the ankle evertors and dorsiflexors on the latency time of the peroneus longus and tibialis anterior muscles. Twenty-four healthy male recreational athletes were admitted to this study and were randomly assigned to either the exercise group (n = 12) or the control group (n = 12). Subjects in the exercise group performed an isokinetic exercise program of the ankle evertors and dorsiflexors in a combined eccentric-concentric mode for 3 days per week for 6 weeks. Before and after the exercise program, muscle reaction times of the peroneus longus and tibialis anterior muscles to sudden supinating maneuvers on a tilting platform, and isokinetic strength of the ankle joint musculature were evaluated. The peroneus longus and tibialis anterior reaction times showed significant (P < 0.01-0.05) reductions following six weeks of intervention in the exercise group. Additionally, eccentric peak torques for the ankle evertor and dorsiflexors represented significant (P < 0.05) increases in the exercise group compared with the control group. The results of this study suggest that it is possible to reduce peroneal and anterior tibial reaction times following a six week eccentric/concentric isokinetic training program in healthy ankles.

Temperature changes in the pulpal chamber and the sealing performance of various methods of direct pulp capping of primary teeth.

AIM: To compare changes in pulpal chamber temperature during the visible-light curing of direct pulp capping compounds and various modes of diode laser irradiation without prior placement of a pulp capping compound and the resultant seals. MATERIALS AND METHODS: Pulp exposure holes were made in 100 extracted human primary first molars, which were randomly assigned to ten equal groups. The holes were sealed by (a= Group 1, 2, 3, 4, 5, 6 and 7) different pulp capping compounds which were cured using various types of visible-light curing units or (b=Group 8, 9 and 10) diode laser irradiation without prior application of a pulp capping compound. Pulpal chamber temperatures were recorded during the procedure, and the resultant seals were examined under a scanning electron microscope. RESULTS: Visible-light curing of the pulp capping compounds and diode laser irradiation at a 0.7 W output power can cause non-injurious temperature rises in the pulpal chamber. At higher output powers of the diode laser, the temperature rises are sufficient to cause thermal injury. The seals were complete when pulp capping compounds were used for direct pulp capping, but were incomplete when laser irradiation without prior placement of a pulp capping compound was used for the identical purpose. CONCLUSION: The visible-light curing of pulp capping compounds is not harmful to vital pulp, and provides an effective seal of the pulp exposure hole. Laser irradiation is not an effective sealant, and can cause thermal injury to vital pulp at high output powers.

Comparison of the efficacy of articaine and prilocaine local anaesthesia for pulpotomy of maxillary and mandibular primary molars.

AIM: The aim of this study was to compare the local anaesthetic efficacy of articaine HCl and prilocaine HCl during an operative procedure after their administration by either mandibular nerve block or maxillary infiltration. STUDY DESIGN: The study was a double-blind clinical study which comprised 162 children (81 boys and 81 girls), who required a pulpotomy on their primary molars. Pain-related behaviours were used to assess the severity of pain during the injection of either prilocaine HCl or articaine HCl and the operative procedures following either a maxillary infiltration or mandibular nerve block of the two local anaesthetic agents. The frequencies of post-procedural adverse events in the prilocaine and articaine anaesthetised groups were also determined. RESULTS: Significantly more discomfort (p<0.05) was observed following maxillary infiltration compared to mandibular nerve block. There were no significant differences in the pain-related behaviours scores between the two local anaesthetic agents administered during the dental operative procedures, except for the removal of the coronal pulp. For this latter procedure, the pain-related behaviour score was 1.5- times higher in the prilocain-anaesthetised children than in the articaine-anaesthetised children. The frequencies of post- procedural adverse events in the prilocaine-treated children were similar to those found in the articaine-treated children. CONCLUSION: We concluded that local anaesthesia following mandibular nerve block is more effective than that following maxillary infiltration in 6-8-year-old children. However, the intensity of pain that was experienced by the children during administration of either prilocaine or articaine and some of the dental procedures after their administration were similar.

Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial.

BACKGROUND: In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. OBJECTIVES: To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). METHODS: In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n=16), SCIT (n=16) or pharmacotherapy alone (n=16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. RESULTS: SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. CONCLUSION: Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.

Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma.

Rhinovirus (RV) infections trigger asthma exacerbations. Genome-wide expression analysis of RV1A-infected primary bronchial epithelial cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of RV-induced gene expression. Virus replication rates were similar in cells from normal and asthmatic donors. Overall, RV downregulated 975 and upregulated 69 genes. Comparisons of transcriptional profiles generated from microarrays and confirmed by quantitative reverse transcription PCR and cluster analysis showed some up- and downregulated genes in asthma cells involved in immune responses (IL1B, IL1F9, IL24, and IFI44) and airway remodeling (LOXL2, MMP10, FN1). Notably, most of the asthma-related differences in RV-infected cells were also present in the cells before infection. These findings suggest that differences in RV-induced gene expression profiles of cells from normal and mild asthmatic subjects could affect the acute inflammatory response to RV, and subsequent airway repair and remodeling.

Albumin/creatinine ratio for prediction of 24-hour albumin excretion of > or =2 g in manifest preeclampsia.

PURPOSE OF INVESTIGATION: To compare whether albumin/creatinine ratios obtained from random or 8-hour urine collected in different periods of day differ in prediction of albumin excretion > or =2 g in 24-hour urine collection in preeclampsia. METHODS: From a total of 70 women, 24-hour urine collected by three consecutive periods of eight hours and three random urine samples were taken before each period. The variation of albumin-creatinine ratios in samples across the day was analyzed by the Friedman and inter-assay coefficient variation. For each sample, receiver operator characteristic (ROC) curves were constructed to determine an optimal albumin/creatinine ratio value in the prediction of albuminuria > or =2 g. RESULTS: The albumin/creatinine ratio did not vary significantly over time when all samples pooled. However, there was considerable intra-individual variation in both random and timed urine samples. On ROC analysis, the albumin/creatinine ratio in both random and timed urine samples predicted the 24-hour urine results and there was no difference between samples in prediction of albuminuria > or =2 g. A single optimal cut-off point was not available between samples. The positive and negative predictive values for optimal cut-offs ranged from 48%-88% and 94%-100%, respectively. CONCLUSIONS: The random urine albumin/creatinine ratio was a poor predictor for proteinuria a 2 g in patients with preeclampsia.

Hyperhomocysteinaemia as a risk factor for deep-vein thrombosis.

OBJECTIVE: Several studies have shown a relation between hyperhomocysteinaemia and vascular disease. To assess the risk of deep-vein thrombosis (DVT) associated with hyperhomocysteinaemia, we studied plasma homocysteine levels in patients with deep-vein thrombosis and in normal control subjects. MATERIALS AND METHODS: We measured plasma homocysteine levels in 48 patients with deep-vein thrombosis and in 33 healthy controls matched to the patients according to age and sex. Plasma homocysteine levels were measured with high performance liquid chromatography and fluorescence detection. Hyperhomocysteinaemia was defined as a plasma homocysteine level about 15 micromol/L in both groups. The diagnosis of all patients with deep-vein thrombosis (n=48) was verified by Doppler ultrasonography. RESULTS: Plasma homocysteine levels were found to be increased in the deep-vein thrombosis group compared the control group (p<0.001, t-test). The mean plasma homocysteine level in the patients was 17.1 SD 5.13 micromol/L (range 6.4-31.3), and that in the controls was 9.0 SD 1.27 micromol/L (range 6.0-11.5). The association between elevated homocysteine levels and venous thrombosis was stronger among men than among women. CONCLUSIONS: The increased plasma homocysteine levels we have observed may have a causative role in the development of deep-vein thrombosis.

The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis.

AIM: In some of the patients undergoing haemodialysis, (HD) resistance might develop against recombinant human erythropoietin (rHuEPO) used for treatment of anaemia. Recently, angiotensin-converting enzyme (ACE) inhibitors that are used to treat hypertension and congestive heart failure in HD patients have been suggested to contribute to anaemia as well by inhibiting erythropoiesis. Our purpose in this study is to investigate whether or not losartan, an angiotensin II (ATII) receptor antagonist, is causing rHuEPO resistance. METHODS: In this prospective study of 12 months, we compared the effects of high dose losartan (100 mg/day) and amlodipine (10 mg/day) on rHuEPO requirement in 40 hypertensive patients receiving rHuEPO for more than 12 months on maintenance HD. Twenty normotensive rHuEPO dependent patients served as control group. Iron deficiency, hyperparathyroidism, aluminium intoxication, infections and inflammations were excluded in all patients. RESULTS: The mean haemoglobin level was found >8 g/dl in all groups. The mean weekly rHuEPO dose increased in the losartan group (p<0.0001 vs before) and remained constant in the other groups. No significant differences were found with PTH, iron status, aetiologies of renal failure in all groups. CONCLUSION: High-dose losartan increases rHuEPO requirement and should be reserved for dialysis patients with hypertension uncontrollable with other antihypertensive medications.