Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity

Leptin is a peptide hormone with the tertiary structure of a cytokine, which not only regulates body weight by inhibiting food intake, but also modulates inflammatory and immune responses. The aim of the study was to investigate if there are connections between leptin concentrations and parameters of nutritional status and disease activity in a group of rheumatoid arthritis (RA) patients. The study group consisted of 37 patients. The mean leptin serum concentration was significantly higher in women than in men. The leptin concentrations correlated positively with BMI only in women with RA. The leptin concentrations were significantly higher in patients with erosive RA. Assessing the group of patients with long-standing RA (duration > 10 years), we found that leptin levels were significantly higher in patients with higher disease activity than in those with DAS28 ≤ 5,1; there was also a positive correlation between serum leptin concentration and the value of DAS28, ESR and the number of tender joints. The results suggest that some important dependence exists between the risk of aggressive course of RA and increased leptin levels.     

Differentiative potential of human metanephric mesenchymal cells

OBJECTIVE: To evaluate the ability of mesenchymal cells derived from nonhematopoietic organs to form blood and other tissues in vitro and in vivo. MATERIALS AND METHODS: Because of its mesodermic derivation, human fetal kidney was used as a source of mesenchymal cells. Two populations of kidney cells were studied at a nonclonal level: a crude preparation, and an adherent fraction that was derived from the first by propagation in vitro (MNMC). Both populations were transplanted into sheep fetuses and analyzed at intervals for the presence of human cells in different organs by flow cytometry, PCR, immunohistochemistry, and in situ hybridization. Secondary transplantation studies were performed using human hematopoietic cells obtained from the bone marrow (BM) of primary recipients. RESULTS: MNMC were Thy-1(+), CD51(+), CD44(+), CD45(-), and vimentin(+), a phenotype consistent with that of metanephric mesenchyme. The crude population displayed the same phenotype but was contaminated with 0.4% CD34(+)CD45(+) cells. Cells with hepatocyte-like morphology and phenotype were obtained from the MNMC after culture in specific inducing media. After transplantation, both populations of cells produced multilineage hematopoietic engraftment and gave rise to CD34(+) cells. Successful hematopoietic engraftment in secondary recipients demonstrated the generation of long-term engrafting hematopoietic stem cells from MNMC. PCR analysis confirmed human hematopoietic engraftment and revealed that human cells were also present within other organs. Liver sections of transplanted animals contained human albumin-producing hepatocyte-like cells. CONCLUSION: A human metanephric mesenchymal cell population simultaneously gave rise to human blood and liver-like cells, suggesting that mesenchymal cells may represent a broad population of putative stem cells in multiple adult organs.     

Immunomagnetic bone marrow (BM) and peripheral blood progenitor cell (PBPC) purging in follicular lymphoma (FL)

Twenty-nine B cell follicular lymphoma (FL) patients had their BM (n = 12) or PBPC (n = 17) purged using a panel of monoclonal antibodies and immunomagnetic beads (IMB). The median recovery of nucleated cells (NC) and CD34+ cells was 59.3% (40.5-74) and 56.1% (30.8-82.9) in BM and 77.2% (64.7-88.3) and 73.5% (61.5-98.6) in PBPC (P<0.0005). A median of >1.62 and >1.02 log of target cell depletion was achieved as judged by flow cytometry analysis in BM and PBPC, respectively. Of 29% of initial harvests that had a bcl2 PCR-amplified signal, 37.5% became PCR negative in the final purged products. Absorbed cells containing IMB-target cell complexes gave bcl2 rearrangement signal in 20% of samples in which the start and final purged components were negative. Twenty-three of 26 patients receiving an autologous purged product are evaluable for engraftment. Median time to reach an ANC >0.5x10(9)/l and platelet count >20x10(9)/l was 21 (11-43) and 41 days (13-70) for BM (n = 9) and 14 (10-31) and 14 (8-37) for PBPC (n = 14) autografted patients (P = 0.01 and 0.001). One patient did not engraft and was rescued with a back-up BM. These data demonstrate that this indirect immunomagnetic technique is able to achieve a high grade of lymphoma cell depletion in BM and PBPC and that these purged products are capable of rapid engraftment after autologous transplantation.     

IL-17F gene polymorphism is associated with susceptibility to acute myeloid leukemia

Purpose

Recent studies have suggested that Th17 cells may play a role in the pathogenesis of acute myeloid leukemia (AML). This subset of CD4+ cells is characterized by interleukin (IL)-17A and IL-17F production, which share strong homology, and surface expression of the IL-23 receptor (IL-23R). The present study aimed to determine the association between the polymorphic features located within the IL-17A, IL-17F and IL-23R genes and disease susceptibility, progression and response to therapy. In addition, the relationship between the polymorphic variants and the plasma IL-17 levels in patients was analyzed.

Methods

For this purpose, 187 individuals of Polish origin including 62 AML patients and 125 healthy controls were typed for IL-17A (rs2275913; G-197A), IL-17F (rs763780; A7488G; His161Arg) and IL-23R (rs11209026, G1142A; Arg381Gln) alleles.

Results

The rs763780 IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the minor (G) variant (RR = 4.76, p < 0.001) and its homozygosity (RR = 23.02, p < 0.005) was more frequent among patients than healthy individuals. No significant association was observed for either other polymorphisms studied or IL-17 levels.

Conclusions

Thus, the rs763780 IL-17F polymorphism was found to be associated with predisposition to AML in the Polish population.     

Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis—a prospective randomized study

Background

Microencapsulated sodium butyrate (MSB) has been previously associated with anti-inflammatory and regenerative properties regarding large bowel mucosa. We aimed to examine a role of MSB in patients with diverticulosis, hypothesizing its potential for reduction of diverticulitis episodes and diverticulitis prevention.

Methods

Seventy-three patients with diverticulosis (diagnosed in colonoscopy or/and barium enema or/and CT colography) were recruited for the study and randomized. The investigated group was administered MSB 300 mg daily; the control group was administered placebo. After 12 months, a total of 52 patients completed the study and were subject to analysis (30 subjects and 22 controls). During the study, the number of episodes of diverticulitis (symptomatic diagnosis with acute pain, fever, and leukocytosis), hospitalizations, and surgery performed for diverticulitis were recorded. Additionally, a question regarding subjective improvement of symptoms reflected changes in quality of life during the analysis.

Results

After 12 months, the study group noted a significantly decreased number of diverticulitis episodes in comparison to the control group. The subjective quality of life in the study group was higher than in the control group. There were no side effects of the MSB during the therapy.

Conclusions

MSB reduces the frequency of diverticulitis episodes, is safe, and improves the quality of life. It can play a role in the prevention of diverticulitis.     

The Relationship Between Limit of Dysphagia and Average Volume Per Swallow in Patients with Parkinson’s Disease

The goal of this study was to obtain the limit of dysphagia and the average volume per swallow in patients with mild to moderate Parkinson’s disease (PD) but without swallowing complaints and in normal subjects, and to investigate the relationship between them. We hypothesize there is a direct relationship between these two measurements. The study included 10 patients with idiopathic PD and 10 age-matched normal controls. Surface electromyography was recorded over the suprahyoid muscle group. The limit of dysphagia was obtained by offering increasing volumes of water until piecemeal deglutition occurred. The average volume per swallow was calculated by dividing the time taken by the number of swallows used to drink 100 ml of water. The PD group showed a significantly lower dysphagia limit and lower average volume per swallow. There was a significantly moderate direct correlation and association between the two measurements. About half of the PD patients had an abnormally low dysphagia limit and average volume per swallow, although none had spontaneously related swallowing problems. Both measurements may be used as a quick objective screening test for the early identification of swallowing alterations that may lead to dysphagia in PD patients, but the determination of the average volume per swallow is much quicker and simpler.     

RANKL/RANK/OPG system and bone status in females with anorexia nervosa

Minimal data exist concerning the relationship between osteokines of the RANKL/RANK/OPG system, especially RANKL, and bone status in females with anorexia nervosa (AN). For this reason we investigated the relationship between bone metabolism (as assessed based on serum levels of OC and CTx), and OPG and sRANKL concentrations in females with AN. Ninety-one female patients with AN and 29 healthy female subjects aged 13 to 18 years of age participated in the study. Serum OC, CTx, OPG and sRANKL were measured by ELISA. The female patients with AN demonstrated an essential suppression of OC and CTx, increased OPG and sRANKL levels, and a reduced OPG/sRANKL ratio. OC, CTx and the OPG/sRANKL ratio correlated positively with body mass and BMI in these patients, whereas in the case of OPG and sRANKL the relationship was negative. A significant positive correlation was observed between OPG and sRANKL and also between bone markers and the OPG/sRANKL ratio, and negative between CTx and sRANKL. In female patients with AN, the OPG/RANKL ratio was a significant and independent predictor of osteocalcin, a bone formation marker — OC (R² = 0.065, p = 0.012) whereas the OPG/sRANKL ratio and BMI were significant and independent predictors of a bone resorption marker — CTx (R² = 0.095; p = 0.012). In conclusion, the body mass, BMI values, and bone markers suppression observed in female patients with AN might be associated with an increase in OPG and sRANKL levels and a significant decrease of the OPG/sRANKL ratio. Although higher OPG levels may compensate for excessive bone resorption in female patients with AN, the lower OPG/sRANKL ratio seems to indicate that some inadequacies exist regarding this compensation effect, which might contribute to low bone density in these patients. The OPG/sRANKL ratio might prove a more relevant marker to predict bone metabolism in female patients with AN than sRANKL and/or OPG alone.     

Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years

Background/PurposeThe aim of the study was to analyze changing management and survival of children with hepatoblastoma (HBL) treated in one center.Materials and MethodsOver the last 20 years, 51 children with HBL were treated. Surgery was performed in 48 children (94.1%), conventional liver resection in 38 (of those, 2 received a rescue liver transplantation [LTx] for relapse), and total hepatectomy and primary LTx in 10 patients. The remaining 3 patients received only palliative treatment. Patient data were analyzed for survival with respect to PRETreatment EXTent of disease (PRETEXT), metastases, histopathology, conventional resection, and LTx.ResultsSurvival of children with HBL treated with liver resection is 71% and 80% for primary LTx. Favorable prognostic factors for patient survival was tumor histology as epithelial-fetal subtype and mixed epithelial and mesenchymal type, without teratoid features, and good response to chemotherapy (necrosis, fibrosis). Unfavorable prognostic factors were small cells undifferentiated, transitional liver cell tumor, α-fetoprotein level above 1,000,000 IU/mL and below 100 IU/mL at diagnosis, lung metastases, and local recurrence after initial resection. Survival was related to PRETEXT stage. However, among patients with PRETEXT III and IV, LTx resulted in better survival.ConclusionLiver transplantation is a good option for children with advanced HBL. Early referral of children with potentially unresectable tumors to centers where combined treatment (chemotherapy, surgery including LTx) is available is crucial.