Treatment with Natalizumab in Relapsing–Remitting Multiple Sclerosis Patients Induces Changes in Inflammatory Mechanism

Natalizumab is a widely accepted drug for the relapsing–remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow cytometry was used to determine cytokines and regulatory T cell frequency while regulatory T cell suppressor function was assayed in vitro at different time-points after starting with natalizumab. Results showed serum levels of pro-inflammatory interferon gamma and interleukin (IL)-12p70, as well as anti-inflammatory IL-4 and IL-10, were elevated just a few hours or days after first IV infusion of natalizumab. Interestingly, other cytokines like IL-5 or IL-13 were also elevated while pro-inflammatory IL-17, IL-2, and IL-1β increased only after a long-term treatment, suggesting different immune mechanisms. In contrast, we did not observe any effect of natalizumab treatment on regulatory T cell frequency or activity. In conclusion, these results suggest natalizumab has other immunological effects beyond VLA-4 interaction and inhibition of CNS extravasation, the relevance of which is as yet unknown and warrants further investigation

Analysis of chemokine and chemokine receptor expression in squamous cell carcinoma of the head and neck (SCCHN) cell lines

The purpose of this work was to analyze chemokine and chemokine receptor expression in untreated and in irradiated squamous cell carcinoma of the head and neck (SCCHN) tumor cell lines, aiming at the establishment of assays to test for the relevance of chemokine and chemokine receptor expression in the response of SCCHN to radiotherapy and radiochemotherapy. Five low passage and 10 established SCCHN lines, as well as two normal cell lines, were irradiated at 2 Gy or sham-irradiated, and harvested between 1 and 48 h after treatment. For chemokines with CC and CXC structural motifs and their receptors, transcript levels of target and reference genes were quantified relatively by real-time PCR. In addition, CXCL1 and CXCL12 protein expression was analyzed by ELISA. A substantial variation in chemokine and chemokine receptor expression between SCCHN was detected. Practically, all cell lines expressed CCL5 and CCL20, while CCL2 was expressed in normal cells and in some of the tumor cell lines. CXCL1, CXCL2, CXCL3, CXCL10, and CXCL11 were expressed in the vast majority of the cell lines, while the expression of CXCL9 and CXCL12 was restricted to fibroblasts and few tumor cell lines. None of the analyzed cell lines expressed the chemokines CCL3, CCL4, or CCL19. Of the receptors, transcript expression of CCR1, CCR2, CCR3, CCR5, CCR7, CCXR2, and CCXR3 was not detected, and CCR6, CXCR1, and CXCR4 expression was restricted to few tumor cells. Radiation caused up- and down-regulation with respect to chemokine expressions, while for chemokine receptor expressions down-regulations were prevailing. CXCL1 and CXCL12 protein expression corresponded well with the mRNA expression. We conclude that the substantial variation in chemokine and chemokine receptor expression between SCCHN offer opportunities for the establishment of assays to test for the relevance of chemokine and chemokine receptor expression in the response of SCCHN to radiotherapy and radiochemotherapy

HISTOLOGICINVESTIGATION OF PULPAL INFLAMMATION AND NECROSIS ON TRUMATIZED OPEN APEX CAT CANINE TEETH

Interoduction. Treatment of trumatized crown fractured teeth with open apex is a major problem in endodontic treatment. Long term stability of such teeth depends upon the maintainace of pulp vitality. The time period between the accident and the treatment affects the pulp vitality as well as the type of treatment and prognosis.
 The objective of this study was to provide a rough time table of pulpal inflammation and necrosis after the exposure of crow - fractured teeth to oral Environment.
 Methods. Fourty eight canine teeth in 12 young cats were used in this experiment. To make sure the teeth apecies were all open, they were checked by radiograph. The crown of all the teeth were cut 2mm from the CEJ and the pulps were left open to oral inviornment for periods of 1, 3, 7, 14, 28, 90 days. Animals were then sacrificed by vital perfusion fixation technique.
 Results. The mean depth of pulpal inflammation and necrosis for periods of 1, 3, 7, 14, 28 and 90 days were 1.98, 3.3, 2.39, 2.84, 3.92 and 8.57, respectively. There was no statistically significant difference between the time periods of 1, 7 and 14 days. Where as, time periods of 14 and 28 days showed significant difference. In 90 day time period, all the teeth showed total pulpal necrosis and was significantly different from all the other groups.
 Discussion. It appears that, trumatized open apex teeth exposed to oral Enviornment for less than 28 days could be well treated by apexogenesis. Considering the sufficient blood supply to open apex teeth in cases of deep inflammation and necrosis the teeth could be saved by partial pulpectomy. Only cases of total pulp necrosis should be treated by apexification technique

Assessment of Helicobacter Pylori Prevalence by Scorpion Real-Time PCR in Chronic Tonsillitis Patients

Background: Occasionally, bacteria or viruses enter the tonsils and these organs become overwhelmed by bacterial or viral infection leading to inflammation. Some studies confirmed the presence of Helicobacter pylori in tonsillar specimens of patients suffering from chronic tonsillitis and some others did not. The difference in results in various studies might be due to different laboratory methods. The aim of this study was to investigate the presence of H. pylori Deoxynucleic acid (DNA) in archival tonsillar tissues of patients with chronic tonsillitis by a rapid, sensitive, and specific technique of Scorpion real-time polymerase chain reaction (PCR). Materials and Methods: Scorpion real-time PCR and modified McMullen′s staining was performed on 103 archival paraffin-embedded tonsillar samples collected from patients with chronic tonsillitis following tonsillectomy operation. Results: Our findings showed that H Cell and Molecular Research Center. pylori DNA was present in 21.35% of total specimens by using Scorpion real-time PCR. Modified McMullen′s staining of paraffin-embedded sections was positive in 19 patients. Out of our 103 samples, 50 samples showed positive a rapid urease test whereas 53 samples demonstrated negative results, 20 produced positive PCR results, and 83 were negative for H. pylori. There was no significant relationship between the presence of H. pylori, sex, age, and place of residence. Conclusion: Although the existence of H. pylori in tonsillar tissue samples of patients with chronic tonsillitis is controversial, however, our results showed that in our studied specimens, a significant number of patients with chronic tonsillitis had H. pylori colonization