Virulence of major periodontal pathogens and lack of humoral immune protection in a rat model of periodontal disease

Oral Diseases (2010) 16 , 686–695 Objective: This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis are synergistic in terms of virulence potential using a model of mixed‐microbial infection in rats. Materials and methods: Three groups of rats were infected orally with either T. forsythia or P. gingivalis in mono‐bacterial infections or as mixed‐microbial infections for 12 weeks and a sham‐infected group were used as a control. This study examined bacterial infection, inflammation, immunity, and alveolar bone loss changes with disease progression. Results: Tannerella forsythia and P. gingivalis genomic DNA was detected in microbial samples from infected rats by PCR indicating their colonization in the rat oral cavity. Primary infection induced significantly high IgG, IgG2b, IgG1, and IgG2a antibody levels indicating activation of mixed Th1 and Th2 immune responses. Rats infected with the mixed‐microbial consortium exhibited significantly increased palatal horizontal and interproximal alveolar bone loss. Histological examinations indicated significant hyperplasia of the gingival epithelium with moderate inflammatory infiltration and apical migration of junctional epithelium. The results observed differ compared to uninfected controls. Conclusion: Our results indicated that T. forsythia and P. gingivalis exhibit virulence, but not virulence synergy, resulting in the immuno‐inflammatory responses and lack of humoral immune protection during periodontitis in rats.     

Impact of cigarette smoking on response to interferon therapy in chronic hepatitis C Egyptian patients

AIM: Smoking may affect adversely the response rate to interferon-α. Our objective was to verify this issue among chronic hepatitis C patients. METHODS: Over the year 1998, 138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into: group I which comprised 38 smoker patients (>30 cigarettes/d) and group II which included 84 non-smoker patients. Irregular and mild smokers (16 patients) were excluded. Non eligible patients for interferon-~ therapy were excluded from the study and comprised 3/38 (normal ALT) in group I and 22/84 in group II (normal ALT, advanced cirrhosis and thrombocytopenia). Group I was randomly allocated into 2 sub-groups: group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy. In sub-group Ia, 3 patients with normal ALT after repeated phlebotomies were excluded from the study. Interferon-α2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia, 17 patients in group Ib and 62 patients in group II. Biochemical, virological end-of- treatment and sustained responses were evaluated.RESULTS: At the end of interferon-α treatment, ALT was normalized in 3/15 patients (20%) in group Ia and 2/17 patients (11.8%) in group Ib compared to17/62 patients (27.4%) in group II (P=0.1). Whereas 2/15 patients (13.3%) in group Ia. and 2/17 patients (11.8%) in group Ib lost viraemia compared to 13/62 patients (26%) in group II(P=0.3). Six months later, ALT was persistently normal in 2/15 patients (13.3%) in group la and 1/17 patients (5.9%) in group Ib compared to 9/62 patients (14.5%) in group Ⅱ (P= 0.47). Viraemia was eliminated in 1/15 patients (6.7%) in group Ia and 1/17 patients (5.9%) in group Ib compared to 7/62 patients (11.3%) in group Ⅱ, but the results did not mount to statistical significance (P = 0.4). CONCLUSION: Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers. Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group.     

Reduced levels of T-cell subsets CD4+ and CD8+ in homozygous sickle cell anaemia patients with splenic defects

T-lymphocyte subsets were studied in two patient groups: (1) 50 patients with homozygous sickle cell anaemia (SCA) (mean age 12 (range 3-32) years old) in good health at the time of the study who showed no infectious complication. (2) 50 patients (mean age 13 (range 4-29) years old) with normal haemoglobin rate. The global response revealed a significant increase in levels of CD3+ (P=0.04) and CD8+ (P=0.04) cells when compared with the control group, there was no significant difference in levels of CD4+ cells (P=0.05) between the two groups. However, there was a relationship between T-cell subpopulation levels and spleen status. The average values of T-cell subsets (CD4+ and CD8+) in patients with SCA-induced splenic defects (asplenic, splenomegaly or splenectomized patients) were significantly reduced when compared to SCA patients with normal spleens and the control groups. These data show that T-cell activity was reduced in patients with splenic defects. A correlation between splenic status and a perturbed host defence system in patients with SCA suggests that monitoring T-cell subsets might have prognostic value in the course of sickle cell disease.     

The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction

P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable angina. We investigated the P-selectin gene as a possible candidate for myocardial infarction (MI). The P-selectin gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17 exons. The sequences of the 5'-flanking region and exons of 40 alleles from patients with MI were screened for polymorphisms using polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing. Thirteen polymorphisms were identified: five in the 5'-flanking and eight in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp, Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of the P- selectin protein. All P-selectin polymorphisms as well as a common E- selectin polymorphism, Ser128Arg which has been reported as being associated with an increased risk of premature coronary heart disease (CHD), and is in tight linkage disequilibrium with several P-selectin polymorphisms, were investigated in 647 patients with MI and 758 control subjects from four regions of France and Northern Ireland (the ECTIM study). The entire set of P-selectin polymorphisms provided a heterozygosity of 91%. The polymorphisms were tightly associated with one another and displayed patterns of linkage disequilibrium suggesting the existence of highly conserved ancestral haplotypes. The five polymorphisms in the 5'-flanking region of the gene were unrelated to MI or any relevant phenotype measured in the ECTIM study. We inferred that the four missense variants identified in the coding region predicted eight common forms of the P-selectin protein. The Pro715 allele which characterizes one of these forms was less frequent in France than in Northern Ireland ( P < 0.002) and in cases than in controls ( P < 0.002; P < 0.02 after correction for the number of tests). We conclude that the P-selectin gene is highly polymorphic and hypothesize that the Pro715 variant may be protective for MI. Whether this variant affects the properties of the P-selectin protein in a way which is compatible with this hypothesis needs to be checked experimentally.      

Progression of primary APS (Hughes syndrome) into serological SLE: case report

An Arab woman presented with a history of multiple foetal losses and spontaneous venous thromboembolism, which recurred on several occasions. The presence of antiphospholipid antibodies in the absence of other clinical and serological features of systemic lupus erythematosus (SLE), including negative antinuclear antibodies (ANA), confirmed the diagnosis of primary antiphospholipid syndrome (PAPS). More than 15 years after the beginning of clinical events and 10 years after diagnosis, she progressed into the immunological domain of SLE without concurrent clinical features. The patient exhibited weakly positive ANA of a speckled pattern, strongly positive anti (ds) DNA antibodies and false positive VDRL. Lymphopenia has not been observed at any stage of the follow-up. Although the evolution of PAPS into SLE has been infrequently reported, this seems to be another case suggesting that PAPS in some patients may be an early manifestation of lupus. Received: 10 April 2000 / Accepted: 15 June 2000