Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1

Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88-/- mice, but not macrophages from TRL2-/- or from wild-type mice, were unable to produce tumor necrosis factor-alpha in response to HSV-1 exposure. Additionally, although TLR2-/- mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88-/- mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs.     

DNA immunization efficiently targets conserved functional domains of protease and ATPase/helicase of nonstructural 3 protein (NS3) of human hepatitis C virus

Nonstructural protein 3 (NS3) of human hepatitis C virus (HCV) is a conserved multi-functional protein essential for replication and translation of viral RNA and polyprotein processing. Early T-cell response against NS3 is capable of restricting viremia. We aimed at characterizing the immunogenicity in gene immunization of the conserved regions of NS3 critical for protein folding and activity. C57BL/6 mice were injected with NS3 gene of Russian HCV 1b isolate 274933RU. Immunization did not exert any overt histological changes and had no long-term effects on the immune status of NS3 gene-recipients. The immune response in NS3 gene-recipients was screened by antibody ELISA, T-cell proliferation test and immune assays for specific cytokine production. T-lymphocytes of NS3 gene-recipients proliferated in response to peptides representing conserved regions of protease and ATPase/helicase. Stimulated T-lymphocytes produced IL-2, and in response to protease-derived peptides, also IFN-gamma. Potent and long-lasting antibody response was raised against conserved NS3 regions including "Greek-key" motif of protease, motifs II, V and polynucleotide-binding domains of ATPase/helicase. Thus, gene immunization effectively targeted conserved regions critical for NS3 protease and helicase function. In type and specificity, immune response of NS3 gene-immunized mice mimicked immunity achieved in the acute self-limiting HCV infection of human and primates and in virus-exposed healthy individuals, indicating promiscuity of NS3 as immunogen.     

Psoas abscess: diagnostic and therapeutic considerations in six patients

Psoas abscess (PA) is an infrequent clinical entity and presents diagnostic and therapeutic challenges. Six cases are reported concerning diagnostic and therapeutic considerations. Clinical diagnosis is difficult because of non-specific symptoms. The primary psoas abscess has no definite etiology and is spread by hematogeneous route from a distant occult site. The PA can also be secondary to gastrointestinal pathology through direct infection of adjacent structures. The most common causes are Crohn's disease, appendicitis, diverticulitis and carcinoma. Routine laboratory evaluation is seldom useful for localizing the disease process. Conventional radiological techniques are often unhelpful. Modern imaging diagnosis techniques such as ultrasound and computerized tomography have allowed for a refinement in both the etiologic diagnosis and the treatment by means of CT-guided or ultrasound-guided percutaneous drainage of the abscess, thus avoiding surgical drainage in many cases. Immediately on diagnosis of PA prompt treatment is necessary. Percutaneous drainage should be performed whenever possible and in case of failure, surgical drainage should be practiced as well as intestinal resection, whenever indicated.     

Low eradication rate of Helicobacter pylori with triple 7-14 days and quadriple therapy in Turkey

AIM:The eradication rate of Helicobacter pylori (H pylon) shows variation among countries and regimens of treatment.We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication.METHODS:One hundred and sixty-four Hpylori positivepatients (68 males, 96 females; mean age:48±12 years)with duodenal or gastric ulcer without a smoking history were included in the study. The patients were divided into three groups according to the treatment regimens. Omeprazole 20mg, clarithromycin 500mg, amoxicillin 1g were given twice daily for 1 week (Group I) and 2 weeks (Group Ⅱ).Patients in Group Ⅲ received bismuth subsitrate 300mg,tetracyline 500 mg and metronidazole 500mg four times daily in addition to Omeprazole 20mg twice daily.Two biopsies each before and after treatment were obtained from antrum and corpus, and histopathologically evaluated.Eradication was assumed to be successful if no Hpylorus was detected from four biopsy specimens taken after treatment. The effects of factors like age, sex, Hpyloridensity on antrum and corpus before treatment, the total Hpylori density, and the inflammation scores on the rate of Hpylori eradication were evaluated.RESULTS:The overall eradication rate was 42%. The rates in groups Ⅱ and Ⅲ were statistically higher than that in group I (P<0.05). The rates of eradication were 24.5%,40.7% and 61.5% in groups Ⅰ, Ⅱ and Ⅲ, respectively. The eradication rate was negatively related to either corpus Hpylori density or total Hpyloridensity (P<0.05).The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55yr vs 39yr, P<0.001). No correlation between sex and Hpylori eradication was found.CONCLUSION: Our rates of eradication were significantly lower when compared to those reported in literature.We believe that advanced age and high Hpyloridensity are negative predictive factors for the rate of Hpylorieradication.     

Estrogen receptor alpha and beta gene polymorphisms are not risk factors for recurrent miscarriage in a Brazilian population.

The aim of this study was to determine the prevalence of alpha (ESR1: c.454-397T>C and c.454-351A>G) and beta (ESR2: 1082G>A and 1730G>A) estrogen receptor gene polymorphisms in 2 Brazilian ethnic groups (Caucasian, African Brazilian) and to investigate their association with recurrent miscarriage (RM) in 75 women with a history of 3 or more consecutive pregnancy losses and 139 controls with at least 2 live births and no history of pregnancy loss. Polymerase chain reaction and restriction fragment length polymorphism were used to identify gene polymorphisms. Coagulation methods were used to measure protein C, protein S, and fibrinogen, and a chromogenic method was used for antithrombin quantification. Significantly higher prevalences of 1082G>A and 1730G>A polymorphisms were seen in African Brazilian and Caucasian controls, respectively. There was no association between RM and ESR polymorphisms. There was a difference in the genotype prevalence in the c.454-39T>C polymorphism between RM and control Caucasians, but this finding was not associated with an increased risk of miscarriage. There was no synergistic or additive effect between ESR polymorphisms and thrombophilia in RM patients. A difference in the prevalence of ESR polymorphisms was observed, according to ethnic origin. ESR polymorphisms could not be considered a risk factor for RM.     

Determinants of Functional and Structural Properties of Large Arteries in Healthy Individuals

Background

Changes in the properties of large arteries correlate with higher cardiovascular risk. Recent guidelines have included the assessment of those properties to detect subclinical disease. Establishing reference values for the assessment methods as well as determinants of the arterial parameters and their correlations in healthy individuals is important to stratify patients.

Objective

To assess, in healthy adults, the distribution of the values of pulse wave velocity, diameter, intima-media thickness and relative distensibility of the carotid artery, in addition to assessing the demographic and clinical determinants of those parameters and their correlations.

Methods

This study evaluated 210 individuals (54% women; mean age, 44 ± 13 years) with no evidence of cardiovascular disease. The carotid-femoral pulse wave velocity was measured with a Complior^® device. The functional and structural properties of the carotid artery were assessed by using radiofrequency ultrasound.

Results

The means of the following parameters were: pulse wave velocity, 8.7 ± 1.5 m/s; diameter, 6,707.9 ± 861.6 μm; intima-media thickness, 601 ± 131 μm; relative distensibility, 5.3 ± 2.1%. No significant difference related to sex or ethnicity was observed. On multiple linear logistic regression, the factors independently related to the vascular parameters were: pulse wave velocity, to age (p < 0.01) and triglycerides (p = 0.02); intima-media thickness, to age (p < 0.01); diameter, to creatinine (p = 0.03) and age (p = 0.02); relative distensibility, to age (p < 0.01) and systolic and diastolic blood pressures (p = 0.02 and p = 0.01, respectively). Pulse wave velocity showed a positive correlation with intima media thickness (p < 0.01) and with relative distensibility (p < 0.01), while diameter showed a positive correlation with distensibility (p = 0.03).

Conclusion

In healthy individuals, age was the major factor related to aortic stiffness, while age and diastolic blood pressure related to the carotid functional measure. The carotid artery structure was directly related to aortic stiffness, which was inversely related to the carotid artery functional property.     

Canalicular adenoma of the palate

ABSTRACT: Canalicular adenomas are uncommon, benign epithelial neoplasm of the salivary glands that usually involve the upper lip and the buccal mucosa of elderly people. Differential diagnosis of the canalicular adenoma versus adenocarcinoma is important because it may result in unjustified radiotherapy or extensive and aggressive surgery. Despite the benign nature of canalicular adenomas, complete surgical removal and a regular clinical follow-up are recommended. The current study describes the diagnostic procedures, surgical management, and follow-up of a canalicular adenoma involving the palate of a 79-year-old man.