ABSTRACT
This study was undertaken to examine the effect of GH treatment during a pause in laying on (1) ovarian follicle formation, growth (folliculogenesis), and atresia; (2) follicle cell proliferation and apoptosis; and (3) mRNA expression of selected yolk-specific proteins in the chicken liver. A pause in egg laying was induced by food deprivation for 5 d, followed by feeding every other day, and then feeding daily from day 10 onward. Birds were divided into 3 groups: control (n = 18) fed ad libitum, subjected to a pause in laying (n = 18), and subjected to a pause in laying and injected every day with 200 µg/kg BW of chicken GH (chGH; n = 18). The liver, ovarian stroma, and follicles were isolated from the hens of each group on days 6 (ovary regression), 13 (ovary recrudescence), and 17 or 20 (ovary rejuvenated) of the experiment. The results showed that injection of chGH during fasting (1) increased the number of follicles <1 mm and proliferating cell nuclear antigen (PCNA)-positive (proliferating) cells in these follicles; (2) attenuated the expression of PCNA and survivin mRNA in the white follicles and the activity of caspases 3, 8, and 9 in the stroma and white follicles; (3) intensified the atresia of yellow hierarchical follicles; and (4) deepened the effect of starvation on egg yolk gene expression concomitantly with considerably increased IGF-1 transcription levels in the liver (P < 0.05 to P < 0.001). Prolongation of chGH injections into the refeeding period did not exert pronounced effects on the examined parameters. In summary, the results provide evidence that GH promotes the formation and development of prehierarchical follicles in the hen ovary during a pause in laying by regulating cell proliferation and apoptosis. Alterations in cell proliferation- and apoptosis-related gene expression or enzyme activity in ovarian follicles as well as the expression of egg yolk proteins in the liver after chGH treatment strongly suggest that this hormone is involved in determining the rate of regression and rejuvenation of the chicken ovary during a pause in laying.
Subject(s)
Chickens , Food Deprivation , Growth Hormone/pharmacology , Ovary/drug effects , Oviposition/physiology , Animals , Apoptosis , Caspases/metabolism , Cell Proliferation , Female , Gene Expression Regulation/drug effects , Ovary/cytology , Ovary/physiology , RNA/genetics , RNA/metabolism , Reverse Transcriptase Polymerase Chain Reaction/veterinaryABSTRACT
BACKGROUND: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. PATIENTS AND METHODS: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). RESULTS: Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. CONCLUSION: The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Dose Fractionation, Radiation , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/epidemiology , Rectal Neoplasms/therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Consolidation Chemotherapy/adverse effects , Consolidation Chemotherapy/methods , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Incidence , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoplasm Recurrence, Local/prevention & control , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Poland/epidemiology , Proctectomy , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Rectum/drug effects , Rectum/pathology , Rectum/radiation effects , Rectum/surgery , Time Factors , Young AdultABSTRACT
BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS), affecting approximately 40 to 70% of patients. We developed a psycho-educational program (ADACOG program) to allow patients to cope with cognitive deficits. The purpose of this exploratory study was to investigate the impact of the ADACOG program on subjective self-reported cognitive impairments, quality of life, anxiety, depression and self-esteem in MS patients. METHODS: ADACOG program is a psycho-educational program focusing on cognitive and emotional dysfunctions in MS consisting of three modules in small groups lasting two hours every two weeks. Forty-five MS patients with self-reported cognitive impairments and objective cognitive deficits were enrolled consecutively in two groups: (i) the ADACOG group (N=24) and (ii) the control group (N=21). Both groups of patients completed questionnaires evaluating self-reported cognitive impairments (Multiple Sclerosis Neuropsychological Screening Questionnaire), quality of life (Multiple Sclerosis Impact Scale), anxiety and depression (Hospital Anxiety and Depression Scale, HAD) and self-esteem (Rosenberg Scale) at inclusion (M0), one month later (M1) and seven months after inclusion (M7). The evolution of outcomes within ADACOG group and between both groups was analyzed. RESULTS: The analyses within the ADACOG group showed that patients reported better quality of life and fewer anxiety symptoms at M1 compared to M0 (respectively P=0.03 and P=0,04). Moreover, patients presented less subjective self-reported cognitive deficits at M7 compared to M0 (P=0.003). Score evolution for HAD depression and self-esteem were not significant within the ADACOG group. The change M1-M0 for MSIS-29 and HAD anxiety scores was significantly different between both groups (respectively P=0.04 and P=0.008), with improvement of quality of life and anxiety in the ADACOG group. The evolution of scores between groups was not significant for the other outcomes. DISCUSSION: This study showed a small effect of a psycho-educational program focusing on cognitive and emotional disorders in MS patients with subjective self-reported cognitive deficits and objective cognitive deficits. Interest of psycho-education focusing on cognition in MS patients is discussed.
Subject(s)
Affective Symptoms/therapy , Cognitive Dysfunction/therapy , Adult , Affective Symptoms/etiology , Aged , Cognitive Dysfunction/etiology , Efficiency, Organizational , Female , Humans , Male , Middle Aged , Multiple Sclerosis/complications , Prospective Studies , Young AdultABSTRACT
This study was undertaken to examine the effect of growth hormone (GH) treatment during pause in laying on (1) the concentration of steroids in blood plasma and oviduct tissues, (2) the expression of mRNA of steroid receptors, and (3) the mRNA expression of selected egg-specific proteins in the chicken oviduct. A pause in egg laying was induced by food deprivation for 5 d, followed by feeding every other day, and then feeding daily from Day 10 onward. Birds were divided into three groups: control (n = 18) fed ad libitum, subjected to pause in laying (n = 18), and subjected to pause in laying and injected every day with 200 µg/kg BW of chicken GH (chGH; n = 18). The oviduct was isolated from hens of each group on Days 6 (when the oviduct was regressed), 13 (during oviduct recrudescence), and 17 or 20 (rejuvenated oviduct) of the experiment. Fasting caused a decrease in plasma concentrations of progesterone (P4), testosterone, and estradiol on Day 6 and a reduction in tissue concentrations of these steroids on Days 6 and 13. Fasting also caused an increased relative expression of estrogen receptor α and ß (ERα, ERß) and progesterone receptor (PR) in the magnum and shell gland on Day 6, increased ERα and PR in the magnum on Days 13 and 17 or 20, and increased androgen receptor (AR) mRNA in the magnum on Days 6 and 13 and in the shell gland on Day 13. A fasting-induced elevation in ovocalyxin-36 mRNA expression on Day 6 and a decrease in avidin mRNA on Days 6 and 13 and in ovocleidin-116 on Day 13 were also observed (P < 0.05 to P < 0.001). Administration of chGH abolished the fasting-induced decrease in the concentration of steroids in plasma and tissues. Furthermore, chGH enhanced the effect of fasting on mRNA expression of PR, ERα, and avidin in the magnum on Day 6, and ERα in the shell gland on Day 13. The gene expression of ovalbumin on Days 6 and 13, ovocalyxin-36 and ovocleidin-116 on Day 6 was decreased in chGH-treated chickens. In contrast, the expression of ovalbumin on Day 17 or 20 was increased (P < 0.05 to P < 0.001). The results obtained indicate that, by alterations in the concentration of steroid hormones and their receptor expression in the chicken oviduct, GH determines the rate of regression and rejuvenation of this organ during molting. Moreover, changes in the expression of selected egg proteins indicate that GH might be the regulator of the secretory activity of the hen oviduct.
Subject(s)
Chickens , Egg Proteins/metabolism , Food Deprivation/physiology , Gonadal Steroid Hormones/metabolism , Growth Hormone/pharmacology , Oviposition/physiology , Animals , Egg Proteins/genetics , Estradiol/blood , Female , Gene Expression Regulation/drug effects , Gonadal Steroid Hormones/genetics , Oviducts/metabolism , Progesterone/blood , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Steroid/genetics , Receptors, Steroid/metabolism , Testosterone/bloodABSTRACT
PURPOSE: To identify the main difficulties in postoperative clinical target volume (CTV) delineation in gastric cancer (GC). METHODS: Before and after a training course, 20 radiation oncology residents were asked to delineate the CTV for the postoperative GC case on four computed tomography scans: dome of the diaphragm, anterior abdominal wall, duodenal stump and porta hepatis level, and to determine the lower CTV border. CTV volume was reconstructed from requested planar contours. Area of intersection (AI) for each requested scan and volume of intersection (VI), defined as the overlap of delineated area/volume with respective reference area (RA)/reference volume (RV) proposed by the senior radiation oncologist, were computed. The degree of agreement between the reference and participants' contours was quantified using the Concordance Index (CI): AI/RA × 100% or VI/RV × 100%. The lower CTV border was analyzed separately. Pre- and post-training CIs were compared. A questionnaire investigated the difficulties with contouring. RESULTS: Mean CI value was the lowest for the dome of the diaphragm (24% pre-training, 35 % post-training) and for the duodenal stump (49% pre-training, 61% post-training). Mean CI for the CTV volume was 49% pre-training and 59% post-training, p = 0.39. Mean distance from the reference to the participants' lower CTV borders was 2.73 cm pre-training and 2.0 cm post-training, p = 0.71. In a questionnaire, 75% of respondents indicated the elective nodal area as the main difficulty. CONCLUSIONS: Delineation of the dome of the diaphragm and the duodenal stump, as yet not recognized as the source of variation, should be addressed in the international consensus guidelines and clarified.
Subject(s)
Adenocarcinoma/pathology , Observer Variation , Practice Guidelines as Topic/standards , Radiotherapy Planning, Computer-Assisted/methods , Stomach Neoplasms/pathology , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Gastrectomy , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Care , Prognosis , Radiotherapy Dosage , Stomach Neoplasms/radiotherapy , Stomach Neoplasms/surgery , Tumor BurdenABSTRACT
Transmission of hepatitis B virus (HBV) infection from donors negative for hepatitis B surface antigen (HBsAg) but positive for antibody to hepatitis B core antigen (anti-HBc) have been reported. The aim of our study was to evaluate the outcomes of recipients who received liver grafts from living related donors with serological evidence of previous exposure to hepatitis B virus (HBsAg-negative/anti-HBc-positive) after recipient vaccination against HBV before and after liver transplantation.
Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines , Hepatitis B/prevention & control , Liver Transplantation/immunology , Child , Child, Preschool , Hepatitis B/immunology , Humans , Infant , Living DonorsABSTRACT
Organ transplantation is a risk factor for atherogenesis that may be related to immunosuppressive therapy. Increased free radical generation may even aggravate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors for atherogenesis as well as carbohydrate metabolism and antioxidant status among children after liver transplantation. We studied 35 children at 3 to 5 years after liver transplant in whom the following parameters were assessed: total cholesterol; triglyceride; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol; apolipoproteins B, AI, E, lipoprotein (a); vitamin E; glutathione; glucose; insulin; and glutathione peroxidase activity. Three subgroups of patients were assessed according to the immunosuppressive therapy: cyclosporine (CsA), tacrolimus (Tac), or mycophenolate mofetil (MMF) in combination with low-dose CsA or Tac. We observed differences among the subgroups only in total cholesterol (CsA: 131.6 to 285.6; Tac: 144.0 to 181.61; MMF: 132.1 to 181.2) and LDL-C (CsA: 79.4 to 126.9; Tac: 42.2 to 118.8; MMF: 74.2 to 117.3). Lipid metabolism was not significantly disturbed among children after liver transplantation, an observation that does not point to a high risk of atherogenesis. CsA seems to have the strongest untoward effect on cholesterol metabolism. Decreased GSH concentration after liver transplantation may be related to slightly impaired liver function, but GPx activity and vitamin E concentrations remained normal.
Subject(s)
Antioxidants/metabolism , Dietary Carbohydrates/metabolism , Dietary Fats/metabolism , Liver Transplantation/physiology , Atherosclerosis/epidemiology , Child , Child, Preschool , Cyclosporine/therapeutic use , Drug Therapy, Combination , Follow-Up Studies , Glutathione/blood , Glutathione Peroxidase/blood , Humans , Immunosuppressive Agents/therapeutic use , Lipoproteins/blood , Postoperative Complications/epidemiology , Retrospective Studies , Tacrolimus/therapeutic use , Time FactorsABSTRACT
Liver transplantation is recognized as the appropriate treatment for end-stage liver disease. Four patients undergoing liver transplantation for classical end-stage liver disease developed de novo autoimmune hepatitis (AIH) in the graft. Recurrence of AIH after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in one other patient. Markedly elevated serum transaminases were observed, together with an elevated serum IgG and/or globulin fraction and histological feature typical of AIH on liver biopsy.
Subject(s)
Hepatitis, Autoimmune/pathology , Liver Transplantation/pathology , Adolescent , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Liver Transplantation/immunology , Male , ReoperationABSTRACT
We describe the case of successful delivery in a 21-year-old woman who became pregnant 3 years after liver transplantation and who received sirolimus during the first 6 weeks of gestation. Sirolimus was discontinued when ultrasonography revealed a pregnancy, she was switched to tacrolimus and prednisone was continued. The course of pregnancy was uneventful; there were no signs or symptoms of graft rejection. Due to fetal intrauterine threatening asphyxia the pregnancy was concluded by cesarean section in the 39th gestational week, delivering a healthy, 2950 g, Apgar 10, female infant.
Subject(s)
Liver Transplantation/immunology , Pregnancy Complications/immunology , Sirolimus/therapeutic use , Adult , Apgar Score , Female , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infant, Newborn , Pregnancy , Pregnancy Outcome , Sirolimus/adverse effects , TeratogensABSTRACT
The aim of this study was to examine whether liver transplantation reverses the abnormal distribution of lymphocyte subsets previously observed in biliary atresia children, namely a selective decrease in the naive CD4/CD45RA+ T cell subset and an increase in the B and natural killer cell subpopulations. Eight biliary atresia children aged 1.08 to 6 years were studied before and 1 year after LTx for comparison with 15 age-matched healthy controls. The posttransplant immunosuppressive regimens included prednisone [0.1 mg/kg] and tacrolimus (level range: a 10-12 microg/dL). The percentage, absolute cell number, and receptor density were assessed by the use of double color flow cytometry (EPICS-XL MCL fluorocytometer). Biliary atresia patients were compared after LTx with subjects before LTx, essentially showing no statistically significant changes in lymphocyte subsets. We conclude that LTx of biliary atresia children does not reverse the abnormal lymphocyte subset distribution present before transplantation. Hence, these changes may reflect either their independence from the liver status or may result from immunosuppressive treatment that contributes to defective CD4+ T cell regeneration reflected by a deficiency in CD4/CD45RA+ naive T cells.
Subject(s)
Biliary Atresia/surgery , CD4-Positive T-Lymphocytes/immunology , Leukocyte Common Antigens/blood , Liver Transplantation/immunology , T-Lymphocytes/immunology , Antigens, CD/blood , Biliary Atresia/blood , Biliary Atresia/immunology , Child , Child, Preschool , Humans , Immunosuppressive Agents/therapeutic use , Infant , Lymphocyte Count , Reference Values , T-Lymphocyte Subsets/immunologyABSTRACT
The effect of human recombinant growth hormone (hrGH) on intestinal adaptation in rats subjected to massive small bowel resection has been followed by monitoring changes in the tissue polyamine system and in red blood cell (RBC) polyamine levels. In parallel, the activities of monoamine oxidase A and B and diamine oxidase, the enzymes that catalyse one of the major routes of biogenic amine metabolism, oxidative deamination, were also examined. The results suggest that whilst hrGH treatment accelerates adaptive intestinal hyperplasia evoked by the resection, it has no significant effect on RBC polyamine level or gut mucosal DNA concentration as measured 3 weeks post surgery. hrGH treated operated rats exhibited significantly lower amine oxidase activities which implies that GH may alter biogenic amine systems.
Subject(s)
Amines/metabolism , Human Growth Hormone/administration & dosage , Intestine, Small/injuries , Animals , Humans , Rats , Rats, Wistar , Recombinant Proteins/administration & dosageABSTRACT
Gastroenterology has emerged from paediatrics as a separate discipline after 1978, due to the development of basic sciences, i.e., biochemistry, immunology, pathomorphology and introduction of miniaturized endoscopic and radiological equipment. This paper describes the most significant achievements in the areas of gastroenterology, hepatology, and nutrition in children in particular medical centres in Poland. It also discusses the role of the Polish Society for Paediatric Gastroenterology, Hepatology and Nutrition, the role of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and the role of other Scientific Societies and Foundations supporting the development of science and education. The emphasis has been placed upon utilitarian research and education with regard to the management of children with gastrointestinal and hepatic disease.
Subject(s)
Gastroenterology/history , Nutritional Sciences/history , Pediatrics/history , Child , Gastroenterology/methods , Gastroenterology/trends , Gastrointestinal Diseases/history , History, 20th Century , History, 21st Century , Humans , Nutritional Sciences/trends , Pediatrics/methods , Pediatrics/trends , PolandABSTRACT
AIM: To determine the content of trans fatty acids in human milk in relation to breastfeeding mothers' diet. METHODS: Samples of milk were collected from 100 breastfeeding mothers and 7-d dietary records and anthropometry from 69 mothers were obtained. RESULTS: The following total trans fatty acids contents (median (lower-upper quartile); % wt/wt) in milk samples were determined: 1) data for Spring: colostrum--1.37 (1.00-2.00), mature milk at 5-6 wk of lactation--2.59 (1.49-3.34) and at 9-10 wk of lactation--2.36 (1.55-3.92); 2) data for Autumn: colostrum--1.80 (1.42-2.48), mature milk at 5-6 wk of lactation--2.41 (1.79-4.31) and at 9-10 wk of lactation--2.77 (1.53-4.18). The major sources of trans fatty acids in mothers' diets were bakery products, confectionery and snacks. Mothers who had high level of trans isomers in their milk consumed significantly higher amounts of these products. CONCLUSIONS: Bakery products, confectionery and snacks are a major source of trans fatty acids in maternal diet in Poland. The levels of trans fatty acids in human milk may reflect the current diet of the mother as well as the diet consumed early in pregnancy.
Subject(s)
Diet , Milk, Human/chemistry , Mothers , Trans Fatty Acids/analysis , Adult , Breast Feeding , Colostrum/chemistry , Female , Humans , PolandABSTRACT
UNLABELLED: Magnesium deficiency has been reported in patients with classical coeliac disease. Classical coeliac disease has been recently very rare, but the frequency of the silent or latent form has increased. The aim of the study was to evaluate the magnesium status in patients with coeliac disease diagnosed according to ESPGAN criteria. 41 GFD(+) patients aged 6-18 years, who were on a gluten-free diet (GFD) for 2.8 to 17.3 years (mean 11 years); with normal villous structure and IgAEmA(-), and 32 GFD(-) patients aged 5-17 years, with villous atrophy and IgAEmA(+): 8--after 7/12-13/12 of gluten challenge, 4--with late onset of coeliac disease, 20--with silent coeliac disease. All of the children did not have any other disorders. Magnesium status was examined by using: an i.v. Mg-loading test (30 mmol/1.73 m2); Mg urinary excretion and Mg concentration in serum, erythrocytes, and in hair. Abnormal values in GFD(+) and GFD(-) patients were found in: Mg i.v. loading test (retention > 40%) in 20 vs 34%, serum Mg (< 0.7 mmol/l) in 7 vs 3%, erythrocytes Mg (< 1.8 mmol/l) in 20 vs 25%. The reversed statistically significant correlation was found between Mg retention and Mg urinary excretion (R = -0.293, p = 0.009). No other statistically significant correlations were found. CONCLUSION: The magnesium deficiency was present in all patients with classical coeliac disease, but only in 1/5 of patients with coeliac disease on a gluten-free diet and in 1/5 of patients with silent coeliac disease.
Subject(s)
Celiac Disease/complications , Magnesium Deficiency/complications , Magnesium/metabolism , Adolescent , Celiac Disease/metabolism , Child , HumansABSTRACT
Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by defective intestinal electrolyte absorption, resulting in voluminous osmotic diarrhea with high chloride content. A variety of mutations in the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or DRA) are responsible for the disease. Since the identification of the SLC26A3 gene and the determination of its genomic structure, altogether three founder and 17 private mutations have been characterized within miscellaneous ethnic groups. We screened for mutations in seven unrelated families with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven novel mutations including two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two previously identified mutations were also found. This is the first report of rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for the two rearrangements may include repetitive elements and palindromic-like sequences. The increasingly wide diversity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene may not be rare events.
Subject(s)
Antiporters , Carrier Proteins/genetics , Chlorides/metabolism , Diarrhea/genetics , Gene Deletion , Membrane Proteins/genetics , Base Sequence , Chloride-Bicarbonate Antiporters , Codon, Nonsense , DNA/chemistry , DNA/genetics , DNA Mutational Analysis , Diarrhea/congenital , Family Health , Humans , Mutagenesis, Insertional , Mutation , Mutation, Missense , Polymorphism, Genetic , Polymorphism, Single-Stranded Conformational , Sequence Deletion , Sulfate TransportersABSTRACT
The immunological background of the pathological changes that appear in infantile cholestasis (infections, inflammatory process in the liver) is largely unknown. With the use of double color flow cytometry, we assessed the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 29 infants with extra and intra-hepatic cholestasis (12 and 17 patients, respectively), aged from 1 to 8.6 months. Control group consisted of 15 age-matched, healthy infants. We examined: (1) the expression of CD3, CD4, CD8, CD19 lymphocyte surface receptors; and (2) the distribution of lymphocyte subsets with distinctive surface Ag characteristics of 'naive' (CD45RA+) and 'memory' (CD45RO+) cells in both CD4+ and CD8+ cell populations. The surface markers expression was evaluated in terms of percentage of positive cells and receptor density. The following changes in the expression of lymphocyte surface markers are described: (1) a decrease in the percentage of total CD3+, CD4+ cells but normal percentage of CD8+ cells and elevated proportion of CD19+ B cells; (2) a reduction of the proportion of 'naive' CD4+ lymphocytes but normal percentage of 'naive' CD8+ as well as 'memory' CD4+ and CD8+ cell subsets; (3) a decrease in density of CD3, CD4+, CD8 receptors, and D45RA isoform in a subset of 'naive' CD4+ cells. We conclude that deficiency of 'naive' CD4+ T cell subset which possess important effector and immunoregulatory functions, and low expression of certain lymphocyte receptors known to be engaged in T cell activation, possibly reflect a defect of cell mediated immunity that may account for viral and bacterial infections, often observed in infants with cholestasis.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cholestasis, Extrahepatic/immunology , Cholestasis, Intrahepatic/immunology , Leukocyte Common Antigens/metabolism , CD4-Positive T-Lymphocytes/metabolism , Flow Cytometry , Humans , Infant , Phenotype , Protein Isoforms/metabolism , T-Lymphocyte Subsets/immunologyABSTRACT
UNLABELLED: Magnesium (Mg) deficiency is often noted in patients with coeliac disease (CD). The aim of the study was the analysis of the reasons of this deficiency in children with CD, diagnosed according to ESPGAN criteria. MATERIAL: The study was performed on 41 patients aged 6-18 years adhering to strict gluten-free diet GFD(+) for mean 11 years, with normal small intestine mucosa, and IgAEmA(-), and on 32 patients aged 5-17 years on gluten containing diet, with classical CD, silent CD or after gluten challenge--GFD(-). In this group the villous atrophy of the small intestine and IgAEmA(+) were observed. In 18 of these patients Mg deficiency was found using Mg-loading test (30 mmol/1.73 m2). METHODS: The following parameters were analysed: type of the disease, observance of gluten-free diet, sex, and living place. Mg, Ca, Na, protein, fat, and dietary fiber intake was assessed using food frequency questionnaire method, and steatorrhea using faecal fat excretion (g/24 h). RESULTS: The frequency of Mg deficiency was similar in both sexes, occasionally in children from small towns (4.5%), and more often in children from big cities (31.5%), and village (34.4%). Dietary Mg intake below RDA was observed in 23% of children from GFD(+) group, in 19% from GFD(-) one, and in 17.6% in children with Mg deficiency. Insufficient Mg intake was found in 18.2% of children from small towns, in 17.6% from big cities, and in 12.5% from villages; Ca in 36.6%, 58.8%, and 59.3%, and protein in 18.2%, 35.3%, and in 34.4% respectively. In all groups of children high intake of fat and Na was observed. Dietary fiber intake was within the recommended values. All children with classical CD had increased fat excretion (mean 25.9 g/24 h), in other patients it was within normal values [GFD(+) mean 1.95 g/24 h, in GFD(-) without diarrhoea 1.7 g/24 h. CONCLUSIONS: Magnesium deficiency in children with CD depends on the form of the disease, adhering to GFD, diarrhoea with steatorrhea, and/or low Mg intake with the diet.
Subject(s)
Celiac Disease/metabolism , Magnesium Deficiency/epidemiology , Magnesium Deficiency/metabolism , Magnesium/metabolism , Adolescent , Case-Control Studies , Celiac Disease/diet therapy , Child , Diet Records , Feces/chemistry , Female , Humans , Magnesium Deficiency/diagnosis , Male , Poland/epidemiology , Sex Factors , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
Since orthotopic liver transplantation is the treatment of choice for bilary atresia, the role of nutritional support preceding this procedure is significant. The aim of this study was to assess the selected parameters of both humoral and cellular immunity before and after nutritional support. Eight children aged 1.08-7 years. with biliary atresia, qualified to LTx, received high-calorie standard diet supplemented with MCT oil. The distribution of functionally different lymphocyte subpopulations in the peripheral blood was evaluated using double color flow cytometry (EPICS-MCL, Coulter). The concentrations of total serum immunoglobulins were measured by nephelometry (Beckman Array 360) and concentrations of IgG subclasses by ELISA. Abnormalities in the expression of lymphocyte surface markers as well as in immunoglobulin synthesis were as follows: 1) decrease in the percentage of total CD3+ (4/8), CD4+ (5/8), CD8+ (3/8) cells and markedly elevated percentage of CD19+ B cells (4/8); 2) reduction of the proportion of 'naive' CD4+ and CD8+ lymphocytes but normal percentage of 'memory' CD4+ and CD8+ cell subsets; 3) hypergammaglobulinemia with especially high levels of IgG (16.0-3.05 g/l) and IgA (2.6-6.66 g/l) was found in 6 out of 8 children. Treatment with hypercaloric diet did not improve the immunological parameters. We conclude that lymphopenia and possibly also hypergammaglobulinemia observed in BA children resulted mainly from the deficiency of the so-called 'naive', suppressor-inducer CD4+ T cell subset (CD4+/CD45RA+) that is known to maintain the proper level of immunoglobulin synthesis by inhibition of B cell differentiation into plasma cells.