IL-33 is associated with allergy in children sensitized to the cat.

BACKGROUND: Several studies suggest that early-life exposure to animal allergens constitutes a relevant risk factor for the development of allergic sensitization. OBJECTIVES: The aim of the present study was to determine the role of interleukin-33 in children sensitive to cat allergen with allergic rhinitis and/or asthma. METHODS: The study included 51 children aged 5-18 years, both sexes, allergic to cats. Sensitization to cat allergen was confirmed by skin prick tests or specific IgE. Children were evaluated for the presence of bronchial asthma, atopic dermatitis, allergic rhinitis. A questionnaire evaluating the occurrence of allergic symptoms in children after contact with the cat and dog was performed. Mothers completed a questionnaire regarding cat exposure: during pregnancy and having a cat at home. A blood sample was taken from all children to measure the level of IL-33 in the serum. RESULTS: Keeping a cat in the home, once in the past, or having a cat in the home during the mother's pregnancy, revealed a statistically significant relationship with IL-33 levels in the studied patients. Also, daily contact with a cat during pregnancy affected the level of IL-33. Higher levels of IL-33 were shown in people with hypersensitivity to cat and pollen allergens and cat and other animals. In patients with bronchial asthma higher levels of IL-33 were found than in patients without bronchial asthma. CONCLUSIONS: Increased serum levels of IL-33 is related with keeping cats during pregnancy and in early childhood and can be associated with the development of asthma in children.

Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype.

This corrects the article DOI: 10.1038/ijo.2016.228.

Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype.

BACKGROUND/OBJECTIVE: Futile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (de novo lipogenesis (DNL)), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis. METHODS: Male obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days. In epididymal WAT (eWAT), TAG synthesis and DNL were determined using in vivo 2H incorporation from 2H2O into tissue TAG and nuclear magnetic resonance spectroscopy. Quantitative real-time-PCR and/or immunohistochemistry and western blotting were used to determine the expression of selected genes and proteins in WAT and liver. RESULTS: The mass of WAT depots declined during cold exposure (CE). Plasma levels of TAG and non-esterified FA were decreased by day 2 but tended to normalize by day 7 of CE. TAG synthesis (reflecting TAG/FA cycle activity) gradually increased during CE. DNL decreased by day 2 of CE but increased several fold over the control values by day 7. Expression of genes involved in lipolysis, glyceroneogenesis, FA re-esterification, FA oxidation and mitochondrial biogenesis in eWAT was induced during CE. All these changes were more pronounced in obesity-resistant A/J than in B6 mice and occurred in the absence of uncoupling protein 1 in eWAT. Expression of markers of glyceroneogenesis in eWAT correlated negatively with hepatic FA synthesis by day 7 in both strains. Leptin and fibroblast growth factor 21 plasma levels were differentially affected by CE in the two mouse strains. CONCLUSIONS: Our results indicate integrated involvement of (i) TAG/FA cycling and DNL in WAT, and (ii) hepatic very-low-density lipoprotein-TAG synthesis in the control of blood lipid levels and provision of FA fuels for thermogenesis in cold. They suggest that lipogenesis in WAT contributes to a lean phenotype.

Subclinical Inflammation and Endothelial Dysfunction in Patients with Chronic Pancreatitis and Newly Diagnosed Pancreatic Cancer.

BACKGROUND: Recent studies have suggested that various cytokines may be important players in the development and progression of chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC). AIMS: We studied endothelial dysfunction and subclinical inflammation in patients with newly diagnosed pancreatic adenocarcinoma and CP. METHODS: A total of 45 patients were included in the present investigation, 27 with CP and 18 with PC. In addition, the study included 13 age- and body weight-matched healthy subjects served as controls. In all subjects, plasma adiponectin, TNF-alfa, interleukin 6 (IL-6), interleukin 1beta (IL-1ß), E-selectin, thrombomodulin, adhesion molecules ICAM and VCAM, and endothelin-1 were assessed. RESULTS: PC and CP patients as compared with controls had significantly greater plasma adiponectin (13,292 and 12,227 vs 5408 ng/ml; p < 0.0003), TNF-alfa (22.1 and 23.1 vs 13 pg/ml; p < 0.0002), and IL-6 (6.6 and 7.3 vs 3.3 pg/ml; p < 0.0001). Moreover, there was significantly higher concentration of ICAM (931 and 492 vs 290 ng/ml; p < 0.005) and VCAM (1511 and 1080 vs 840 ng/ml; p < 0.01) in PC and CP patients. When PC and CP patients with and without diabetes were considered separately, there was no difference in adiponectin, cytokines, and parameters of endothelial dysfunction. CONCLUSION: In summary, our data indicate that patients with CP and PC express high levels of several cytokines compared with healthy individuals, especially adiponectin, TNF-α and IL-6. Serum TNF-α and ICAM concentrations coordinately increase in advanced CP. Furthermore, especially in PC subjects, elevated markers of endothelial dysfunction are present. This study provides additional evidence that changes in inflammatory cytokine and adhesion molecules in PC and CP are not likely related to endocrine disorders.

The effect of a 10-week Nordic walking training program on the level of GH and LH in elderly women.

OBJECTIVE: The aim of this study was to determine the effect of a 10-week Nordic walking training program on resting growth hormone (GH) and luteinizing hormone (LH) blood concentrations and their relationships to the values of inflammatory, metabolic, and muscle injury parameters in postmenopausal women with overweight and obesity. METHODS: Thirty-two postmenopausal women with overweight or obesity (body mass index 30.5 ± 4.1 kg/m(2)), aged 59.6 ± 5.9 years were included in the investigation. Concentrations of GH, LH, C-reactive protein, total cholesterol, low density (LDL) and high density lipoprotein (HDL) cholesterol, triglycerides and albumin, as well as the plasma activity of muscle enzymes such as creatine kinase and lactate dehydrogenase, were examined before and after the participants finished a 10-week Nordic walking rehabilitation program. RESULTS: After a 10-week rehabilitation period in accordance with a Nordic walking program, significant increases in blood concentrations of GH (median 47.5%) and HDL cholesterol (on average by 0.1%) as well as a decrease in LH values (on average by 19%), total cholesterol, LDL cholesterol and triglycerides (all on a similar average by between 0.1 and 0.2%), creatine kinase (on average by 14%), lactate dehydrogenase (on average by 4%), C-reactive protein (on average by 24%), and body mass index (on average by 5.7%) were found. CONCLUSIONS: Nordic walking for postmenopausal women with overweight and obesity led to favorable hormonal responses, as well as improvement in muscle integrity and nutritional and inflammatory states, suggesting chronic, regular exercise as an effective tool in protecting against menopause-related catabolic processes.

Evolutionary neutrality of mtDNA introgression: evidence from complete mitogenome analysis in roe deer.

Introgressive hybridization offers a unique platform for studying the molecular basis of natural selection acting on mitogenomes. Most of the mtDNA protein-coding genes are extremely conserved; however, some of the observed variations have potentially adaptive significance. Here, we evaluated whether the evolution of mtDNA in closely related roe deer species affected by widespread mtDNA introgression is neutral or adaptive. We characterized and compared 16 complete mitogenomes of European (Capreolus capreolus) and Siberian (C. pygargus) roe deer, including four of Siberian origin introgressed into European species. The average sequence divergence of species-specific lineages was estimated at 2.8% and varied across gene classes. Only 21 of 315 fixed differences identified in protein-coding genes represented nonsynonymous changes. Only three of them were determined to have arisen in the C. pygargus lineage since the time to the most recent common ancestor (TMRCA) of both Capreolus species, reflecting a decelerated evolutionary ratio. The almost four-fold higher dN /dS ratio described for the European roe deer lineage is constrained by overall purifying selection, especially pronounced in the ND4 and ND5 genes. We suggest that the highly divergent C. capreolus lineage could have maintained a capability for genomic incorporation of the well-preserved and almost ancestral type of mtDNA present in C. pygargus. Our analyses did not indicate any signs of positive selection for Siberian roe deer mtDNA, suggesting that the present widespread introgression is evolutionarily neutral.

Use of the Obstetric Quality-of-Recovery score (ObsQoR-11) to measure the impact of an enhanced recovery programme for elective caesarean section.

BACKGROUND: Enhanced recovery after caesarean (ERAC) has been shown to postoperatively reduce opioid consumption, reduce pain scores, and shorten hospital stay. Arguably, none of these measures provide for a patient-centred approach. We believe that patient-reported outcome measures (PROMs) represent a more holistic approach to the reporting of outcomes. One such PROM is the Obstetric Quality-of-Recovery Score (ObsQoR-11). This has been shown to be a valid and reliable assessment of recovery after elective caesarean section. METHODS: This before-and-after quality improvement programme studied consecutive patients undergoing elective caesarean section. We implemented an ERAC pathway with the aim of improving quality of recovery and patient satisfaction. Our primary outcome was the change in the ObsQoR-11 score. RESULTS: A total of 318 medical records were reviewed (n = 93 before ERAC, n = 225 after ERAC). There was a significant improvement in ObsQoR-11 score in ERAC patients compared with pre-ERAC patients (85.0 vs 82.3, P < 0.001). Morphine consumption (MMEQ) was reduced by 10% overall in the ERAC group, with no increase in pain scores at day 1 postoperatively and a decrease in pain scores on day 2 in the ERAC group (P = 0.02). The length of hospital stay was significantly shorter in ERAC patients (63.1 h vs 79.9 h, P < 0.001). CONCLUSIONS: Our study demonstrated an improved ObsQoR-11 score after ERAC implementation. This is the first example in the literature of using ObsQoR-11 in ERAC. We believe this is a more comprehensive way to assess patient recovery and the impact of an ERAC programme.

Clinical significance of activin A and myostatin in patients with pancreatic adenocarcinoma and progressive weight loss.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. Several cytokines, such as activin A and myostatin, ligands of the transforming growth factor-ß superfamily, have been shown to influence the pathogenesis of muscle wasting and tumor progression. The aim of our study was to assess the clinical significance of these cytokines in patients with different stages of PDAC. The study included 93 patients: 73 with newly diagnosed PDAC and 20 healthy volunteers as the control group. PDAC patients included 42 diagnosed with non-metastatic pancreatic cancer (stage I - III) and 31 patients with metastatic cancer (stage IV). The peripheral venous blood samples were collected from each patients at the time of cancer diagnosis and plasma concentrations of activin A and myostatin have been measured with an enzyme-linked immunoassay. Forty five patients (61.6%) presented weight loss > 5%, including 24 (57.1%) with stage I - II and 21 (67.7%) with metastatic PDAC (P > 0.05). Plasma levels of activing A were significantly higher in metastatic PDAC patients compared with stage I - III PDAC patients and control group (P < 0.01). The relationship between higher activin A levels and weight loss was also observed (P < 0.05). On the other hand, myostatin was not associated with weight loss in analysed group of patients. In conclusion, the current study demonstrates that high activin A plasma levels at the time of PDAC diagnosis is associated with unintentional weight loss and may be an useful biomarker for identifying patients with metastatic disease. However, further prospective studies are needed to fully explore the clinical significance of myostatin in pathogenesis of progressive weight loss in PDAC patients.

NADH-generating substrates reduce peroxyl radical toxicity in RL-34 cells.

There is general agreement that oxidative stress may induce apoptotic and necrotic cell death. Recently it has been shown that NADH can be considered an important antioxidant as it reacts with peroxyl and alkoxyl radicals under in vitro conditions. Therefore, in the present study we hypothesized that an increase in intracellular NADH using specific substrates will protect RL-34 cells against cytotoxicity of 2'-azobis (2-amidinopropane) dihydrochloride (AAPH), which is a peroxyl radical generating compound. Cells treated for 24 hours with 6.0 mM AAPH were severely damaged: mitochondria were vacuolated, and the level of free radicals significantly increased. Both apoptotic and necrotic cells were detected (11.1% and 11.4%, respectively) even after 5 hours of treatment. Pretreatment of the cells with substrates which increase the intracellular level of NADH, such as lactate, beta-hydroxybutyrate, and ethanol, distinctly inhibited AAPH-induced reactive oxygen species (ROS) formation and cell death. On the other hand, acetoacetate (AcA), which decrease the intracellular level of NADH, had opposite effects. Interestingly, NADH-generating substrates augment, while AcA reduced superoxide radical formation induced by AAPH. These results may suggest that although NADH generating substrates may exert some deleterious effects within a cell by inducing reductive stress, they diminish alkoxyl or peroxyl radical cytotoxicity. The protection is associated with a decrease in ROS formation measured by dichlorofluorescein, but with an increase in superoxide radical formation.

Do protons and X-rays induce cell-killing in human peripheral blood lymphocytes by different mechanisms?

PURPOSE: Significant progress has been made in the technological and physical aspects of dose delivery and distribution in proton therapy. However, mode of cell killing induced by protons is less understood in comparison with X-rays. The purpose of this study is to see if there is any difference in the mode of cell-killing, induced by protons and X-rays in an ex vivo human peripheral blood lymphocyte (HPBL) model. MATERIALS AND METHODS: HPBL were irradiated with 60 MeV proton beam or 250-kVp X-rays in the dose range of 0.3-4.0 Gy. Frequency of apoptotic and necrotic cells was determined by the Fluorescein (FITC)-Annexin V labelling procedure, 1 and 4 h after irradiation. Chip-based DNA Ladder Assay was used to confirm radiation-induced apoptosis and necrosis. Chip-based DNA Ladder Assay was used to confirm radiation-induced apoptosis. RESULTS: Ex vivo irradiation of HPBL with proton beams of 60 MeV or 250 kVp X-rays resulted in apoptotic as well as necrotic modes of cell-killing, which were evident at both 1 and 4 h after irradiation in the whole dose and time range. Generally, our results indicated that protons cause relatively higher yields of cell death that appears to be necrosis compared to X-rays. The analysis also demonstrates that radiation type and dose play a critical role in mode of cell-killing. CONCLUSION: Obtained results suggest that X-rays and protons induce cell-killing by different modes. Such differences in cell-killing modes may have implications on the potential of a given therapeutic modality to cause immune modulation via programmed cell death (X-rays) or necrotic cell death (proton therapy). These studies point towards exploring for gene expression biomarkers related necrosis or apoptosis to predict immune response after proton therapy.

The effect of a single intravitreal implantation of dexamethasone on the fellow eye in bilateral non-infectious uveitis - case report.

OBJECTIVE: To present the influence of dexamethasone intravitreal implant due to macular edema in non-infectious uveitis in the fellow eye. PATIENTS AND METHODS: A 25-year-old patient with a long history of juvenile arthritis with concomitant recurrent bilateral uveitis, complicated with increases of intraocular pressure and macular edema was treated with a single intravitreal dexamethasone implant into the eye with lower visual acuity. RESULTS: During a 36-month follow-up, the patient's bilateral visual acuity improved. The retinal thickness in both maculae decreased. CONCLUSIONS: Treating macular edema in the course of recurrent uveitis accompanying a systemic disease with dexamethasone depot in vitreous may play a beneficial role also in the fellow eye, when affected. This therapeutic effect in the fellow eye may suggest that the medication can penetrate into the circulatory system and reach such other organs as the fellow eye.

Effect of the 5-HTTLPR polymorphism on affective temperament, depression and body mass index in obesity.

BACKGROUND AND AIM: Many studies show high prevalence of affective disorders in obese patients. Affective temperament is a subclinical manifestation of such conditions. The 5-HTT gene encoding the serotonin transporter may be involved in both mood and eating dysregulation. The aim of this study was to investigate the influence of a polymorphism in the 5-HTT gene on affective temperament types, depressive symptoms and Body Mass Index (BMI) in obese patients. METHODS: This study involved 390 patients (237 females, and 153 males) with obesity. The TEMPS-A questionnaire, Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) were used to evaluate affective temperaments and prevalence of depression. DNA was obtained for serotonin transporter gene-linked polymorphism (5-HTTLPR) genotyping. RESULTS: In obese patients S/S genotype was associated with depressive and L/L with cyclothymic temperament. Subjects with L/L genotype presented significantly higher BMI and greater intensity of depressive symptoms in BDI and HDRS. Females scored higher in anxious and depressive, while males in hyperthymic, cyclothymic and irritable temperaments. Females scored higher in BDI (subjective depression) while males in HDRS (objective depression). LIMITATIONS: TEMPS-A, BDI and HDRS are frequently used in studies on affective disorders. However, these methods do not examine all dimensions of mood and personality. CONCLUSIONS: In obese patients S allele of 5-HTTLPR was associated with development of depressive temperament while L allele corresponded with greater obesity and prevalence of depression. Different mechanisms may be involved in manifestation of depression in males and females with obesity.

[Cognitive deficits in the bipolar affective disorder]. / Zaburzenia czynnosci poznawczych w chorobie afektywnej dwubiegunowej.

Cognitive deficits have been viewed as being characteristic features of schizophrenia. Neuropsychological impairment has been also identified in depression and mania. Recent studies have suggested that patients with bipolar disorder do not make full recovery between episodes of illness and that neuropsychological dysfunction may persist beyond these episodes. Remitted bipolar patients performed worse on Wisconsin Card Sorting Test, Verbal fluency and Stroop Test than healthy controls, the results of the patients with affective disorders with psychotic features were comparable with those of schizophrenics. Some studies suggest an association between the course of illness and the intensity of cognitive deficits, this link was not confirmed in other reports. Imaging studies have shown the presence of white matter lesions and other abnormalities in the brains of bipolar patients. The relative reduction in cerebral tissue may contribute to neuropsychological impairment in subgroup of bipolar patients. Results of studies on the role of white matter lesions are inconsistent. Recent studies point to an association between decreased prefrontal cortex volume and cognitive disturbances. Attention is focused on hippocampus volume as well, since it is associated with cognitive deficits in bipolar disorder. Further studies are needed to elucidate whether a severe course of illness is associated with more pronounced cognitive disorders and whether presence of psychotic symptoms during the acute phase of the illness is a predictor of the occurrence of cognitive deficits in patients with bipolar affective disorder.

[The case of central pontine myelinolysis in an alcohol dependent male]. / Przypadek mielinozy srodkowej mostu u mezczyzny uzaleznionego od alkoholu.

Long-term alcohol abuse can lead to numerous central nervous system lesions, among them central pontine myelinolysis. In this paper, the first in Polish literature case of central pontine myelinolysis in an alcohol dependent male, clinically diagnosed, and confirmed by nuclear magnetic resonance with one year follow-up has been presented. The patient, 49 years old, was admitted to Addiction Treatment Unit, Department of Psychiatry in Bydgoszcz. After admission he manifested clouded consciousness, dysphasia, hyponatremia and neuropsychological abnormalities which showed brain stem lesion. He had no significant abnormalities in CT. Nuclear magnetic resonance revealed triangular hypointensive lesion 10 x 5 mm in central pontine region. One year after admission to Addiction Treatment Unit he still has troubles with walking and swallowing. He has bilateral pyramidal symptoms and emotional lability. He was treated with vinpocetine (0.075 g per day), piracetam (4.8 g per day) and chlorprotixen (0.09 g per day). He was admitted to Psychiatric Ward because of a suicidal attempt as a manifestation of mood disorder due to general medical condition.

Changes in skeletal muscle iron metabolism outpace amyotrophic lateral sclerosis onset in transgenic rats bearing the G93A hmSOD1 gene mutation.

OBJECTIVE: Recently, iron and the adaptor protein "p66Shc" have been shown to play an important role in the development of amyotrophic lateral sclerosis (ALS) in rats. We hypothesized that changes in muscle p66Shc activity and iron metabolism would appear before visible symptoms of the disease occurred. METHODS: In the present study, we used transgenic rats bearing the G93A hmSOD1 gene mutation and their non-transgenic littermates to test this hypothesis. We examined muscle p66Shc phosphorylation and iron metabolism in relation to oxidative stress in animals at three disease stages: asymptomatic (ALS I), disease onset (ALS II), and end-stage disease (ALS III). RESULTS: Significant changes in iron metabolism and markers of lipid and protein oxidation were detected in ALS I animals, which manifested as decreased levels of ferritin H and ferroportin 1 (Fpn1) and increased levels of ferritin L levels. Muscles of ALS I rats possessed increased levels of p66Shc phosphorylated at Ser(36) compared with muscles of control rats. During disease progression, level of ferritin H significantly increased and was accompanied by iron accumulation. CONCLUSIONS: This study showed that multiple mechanisms may underlie iron accumulation in muscles of ALS transgenic rats, which include changes in blood hepcidin and muscle Fpn1 and increased level of muscle ferritin H. These data suggest that impaired iron metabolism is not a result of changes in motor activity.

Diagnosis of gastroesophageal reflux and anti-reflux procedures among Polish children with gastrostomies: a 10-year nationwide analysis.

BACKGROUND/OBJECTIVES: To analyse the approach to diagnose gastroesophageal reflux (GER) and the qualification criteria for anti-reflux (AR) procedures in Polish children fed via gastrostomy between 2000 and 2010. SUBJECTS/METHODS: An electronic questionnaire containing questions on the demographic and clinical data of patients with gastrostomies was distributed to six Polish centres of nutritional therapy. The portion pertaining to GER included data on clinical exponents, diagnostic procedures (pH-metry, pH-impedance, scintigraphy and upper gastrointestinal (GI) series) and AR. RESULTS: In total, 348 children (M199/F149; age at gastrostomy 5.78±5.49 years) were included. Data on the diagnosis of GER and the AR criteria were available for 343 and 336 subjects, respectively. Percutaneous endoscopic gastrostomy was performed in 258/348 patients (74.1%), while surgery was performed in 80/348 patients (23%). The data from 10/348 (2.9%) cases were unavailable. At least one of the tests for GER was conducted in 177/343 (51.6%) of patients: pH-metry in 74/343 (21.6%), pH-impedance in 17/343 (5.0%), scintigraphy in 60/343 (17.5%) and upper GI series in 102/343 (29.7%). GER was reported in 114/343 cases (33.2%), and fundoplication was performed in 87 children (76.3% of patients with GER). The highest congruence between a positive test result and the decision to perform fundoplication was documented in cases of scintigraphy and upper GI series (P=0.00000 and P=0.00191, respectively). A significant increase in the prevalence of simultaneous gastrostomy and AR was observed over the decade analysed (r=0.8, P=0.009). This study revealed a centre-specific attitude towards the diagnosis of GER and the assessment of qualifications for fundoplication in Polish gastrostomy-fed children. CONCLUSIONS: The unified diagnostic algorithm of GER and the universal qualification criteria for AR procedures need to be defined for gastrostomy-fed children.