Serotonin and Serotoninergic Agents Affect Proliferation of Normal and Transformed Lymphoid Cells

Blastogenic transformation of murine spleen cells elicited with concanavalin A was suppressed by serotonin 10^--¹² to 10^--⁶ M, and marginally stimulated by its antagonists ketanserin and propranolol in low concentrations (10^--¹⁵ to 10^--¹¹ M). Ketanserin (5-HT₂ receptor ligand) and propranolol (5-HT_1A and beta-adrenergic ligand) did not block the suppressive effect of serotonin if used along with it in equimolar concentrations (10^--⁹ M). Ergot-alkaloid dihydroergosine suppressed, whereas dihydroergotoxin stimulated the bldstogenic transformation. Opposite effects of the agents were obtained in experiments with mouse myeloma X63/Ag 8.653 and hybridoma SHV 125 cell lines, which unlike normal lymphoid cells, are homologous cell populations and proliferate spontaneously. The data indicate that serotonin and its antagonists interfere directly with mitosis and/or autocrine stimulation of target cells.     

Immunogenicity of peptides of measles virus origin and influence of adjuvants

Epitope-based peptide antigens have been under development for protection against measles virus. The immunogenicity of five peptides composed of the same B cell epitope (BCE) (H236-250 of the measles virus hemagglutinin), and different T cell epitopes of measles virus fusion protein (F421-435, F256-270, F288-302) and nucleoprotein (NP335-345) was studied in mice (subcutaneous immunisation). The adjuvant effects of peptidoglycan monomer (PGM), Montanide ISA 720 and 206 were also investigated. Results showed basic differences in peptide immunogenicity that were consistent with already described structural differences. PGM elevated peptide-specific IgG when applied together with four of five tested peptides. A strong synergistic effect was observed after co-immunisation of mice with a mixture containing all five chimeric peptides in small and equal amounts. Results revealed for the first time that immunisation with several peptides having the common BCE generated significantly higher levels of both anti-peptide and anti-BCE IgG in comparison to those obtained after immunisation with a single peptide in much higher quantity. Further improvement of immune response was obtained after incorporation of such a peptide mixture into oil-based adjuvants.     

Tumor-derived Cyr61(CCN1) promotes stromal matrix metalloproteinase-1 production and protease-activated receptor 1-dependent migration of breast cancer cells

Matrix metalloproteinases (MMPs) play a central role in remodeling the tumor-stromal microenvironment. We recently determined that stromal-derived MMP-1 also acts as a signaling molecule by cleaving protease-activated receptor 1 (PAR1) to cause breast cancer cell migration and invasion. Here, we show that ectopic PAR1 expression induces expression of the angiogenic factor Cyr61(CCN1) in breast cancer cells. The tumor-derived Cyr61 acts as an invasogenic signaling molecule that induces MMP-1 expression in adjacent stromal fibroblasts. Gene silencing of Cyr61 in breast cancer cells suppresses MMP-1 induction in stromal fibroblasts resulting in a major loss in migration of the cancer cells toward the fibroblasts. Cyr61-dependent loss of migration was complemented by exogenous MMP-1 and required the presence of the functional PAR1 receptor on the breast cancer cells. These results suggest that interrupting tumor-stromal cell communication by targeting Cyr61 may provide an alternative therapeutic approach for the treatment of invasive breast cancer.     

Colon carcinoma in a child treated with oxaliplatin and antiangiogenic treatment regimens

Colorectal carcinoma is an extremely rare tumor in childhood. Therefore, the role of adjuvant chemotherapy has not been adequately evaluated in children leading to limited data on safety profile and treatment response after application of novel drugs and novel targeted agents. In this report, we describe a case of colon adenocarcinoma in a 13-year-old girl treated with standard adult treatment as well as novel targeted therapy. This case report illustrates initial good disease control with FOLFOX therapy. On the other hand, targeted therapy revealed no improvement in disease control and good safety profile without significant adverse effects.     

A comparison of self-reported and record-linked blood donation history in an Australian cohort

BACKGROUND: Questionnaire‐based studies investigating blood donation history rely on the accurate recall of information from participants for results to be valid. This study aimed to retrieve electronic records from a national blood donation service and link them to self‐reported history of donation to assess agreement between the two sources. STUDY DESIGN AND METHODS: Between 2004 and 2006, a sample of participants of northern European descent was selected from the Melbourne Collaborative Cohort Study (n = 31,192) to participate in the “HealthIron” study (n = 1438). A total of 1052 participants completed questionnaires that included questions about blood donation history. In 2009, consenting participants' records were linked to the Australian Red Cross Blood Service (ARCBS) to provide information on blood donations made between 1980 and follow‐up (2004‐2006). Those who commenced blood donation before 1980 were excluded. RESULTS: A total of 718 participants were available for analysis. Of these, 394 (55%) provided signed consent, including 182 (82%) of the 227 participants who self‐reported ever donating blood. The two data sources were concordant for 331 (87%) of participants, with a κ statistic of 0.74 (SE, 0.05) indicating a high level of agreement. Participants tended to overstate by a factor of 2.0 (95% confidence interval, 1.7‐2.2) the number of donations they had made when compared with ARCBS records. CONCLUSION: Participants in studies assessing self‐reported blood donation history are likely to correctly indicate whether or not they have ever donated blood. Quantitative estimates are potentially inaccurate and could benefit from validating a sample of records to quantify the bias.     

Detection of gelatinase B activity in serum of gastric cancer patients

AIM:To determine the proteolytic activity andexpression of gelatinase B in serum of gastric cancerpatients and their correlation with the stage of thetumor.METHODS:Sera from 23 patients who underwentsurgery for primary gastric cancer as the experimentalgroup and from 11 as the control group were used todetermine the proteolytic activity and its inhibition byEDTA and 1,10-phenanthroline.Gelatinase B activitywas detected by SDS polyacrylamide gel electrophoresis(SDS-PAGE) and SDS-PAGE zymography.RESULTS:Proteolytic enzyme activity was increased ingastric cancer patients when compared to the controlgroup (P<0.05).The proteinases were determined tobe metalloproteinases upon inhibition test with specificmetalloproteinase inhibitors 1,10-phenanthroline(P<0.05) and EDTA (P<0.01).SDS-PAGE and SDS-PAGEzymography revealed gelatinase 13 (proMMP-9) activityand its molecular mass of 92 ku.CONCLUSION:Proteinase activity is overexpressedin serum of gastric cancer patients.Gelatinase B inserum plays an important role in the progression ofgastric cancer.ProMMP-9 can be used as a marker forinvasiveness of gastric cancer.     

Correlation between uroflowmetry parameters and treatment outcome in children with dysfunctional voiding

PurposeTo investigate the correlation between subjective (clinical) treatment outcome and objective uroflowmetry parameters and curve pattern in children with dysfunctional voiding.MethodSeventy-five children were randomly allocated to two urotherapy programs. Group A was submitted to standard urotherapy and pelvic floor exercises while group B received conservative treatment. Constipation and recurrent urinary tract infections (UTIs) were treated in both groups. Selected children from both groups received pharmacotherapy (anticholinergics or desmopressin). Uroflowmetry with electromyography of the pelvic floor and ultrasound post-void residual (PVR) urine volumes were obtained before and at the end of the 12-month treatment period. Uroflowmetry findings were stratified into two categories based on clinical treatment outcome: ‘cured’ and ‘unchanged’. Uroflowmetry findings were compared between categories at the beginning and the end of the investigation.ResultsVoided volume, average and peak flow rates were significantly increased while PVR urine was decreased in children with cured urinary incontinence and nocturnal enuresis compared with ‘unchanged’ category. Significant decrease of PVR urine was noted in children with cured UTIs. The frequency of a bell-shaped curve was significantly higher compared to other curve patterns in children with cured urinary incontinence and UTIs.ConclusionPost-treatment improvement in clinical symptoms correlated with improvement in uroflowmetry parameters and curve pattern. Correction of voiding phase is necessary for urinary continence achievement and resolution of UTIs.     

Short report: dual infections with Puumala virus and Leptospira interrogans serovar lora in a bank vole (Clethrionomys glareolus)

Leptospirosis and hemorrhagic fever with renal syndrome are public health problems in Croatia. Diagnosis and epidemiology of these diseases are complicated because these two diseases are sympatric in certain areas. We describe a natural dual infection of Puumala virus and a leptospire in a bank vole (Clethrionomys glareolus).     

Correlation and regression

Correlation and regression are statistical methods that help us determine interactions of variables. Both are being used in statistical analysis of basic and clinical research. Correlation (r) is a measure of linear relationship between two numerical measurements made on the same set of subjects and it is represented by correlation coefficient. Values of correlation coefficient range between -1 and 1. Pearson's and Spearman's coefficients of correlation are the most often used correlation coefficients. Correlation can be linear and non-linear. We calculate the significance of correlation (P) in an effort to determine significance of correlation coefficient. Regression is a statistical method that allows us to predict values of one variable from another. The simplest regression is linear regression. The success of regression equation is valued by analysis of residuals. Multiple regression is used to predict one variable from several known variables.