Effects of the Chemokine Receptor 5 (CCR5)-Delta32 Mutation on Hepatitis C Virus-Specific Immune Responses and Liver Tissue Pathology in HCV Infected Patients

Background:

The specific antiviral T cells provide CC chemokine receptor 5 (CCR5) for the immune response during the hepatitis C virus (HCV) infection. Heterogenous and/or homozygous 32 base pair deletion in CCR5 gene (CCR5Δ32 bpdel) leads to reduced protein expression.

Objectives:

In the current case control study, we aimed to compare the histopathological findings of liver to the CCR5Δ32 bpdel mutation profiles, expression and some other clinical findings in patients with chronic HCV infection.

Materials and Methods:

Multiple Strip Assay reverse hybridisation and Real Time PCR techniques were used to determine the germline CCR5 mutations and immunohistochemical technique was used to evaluate the gene expression in targer tissue biopsies.

Results:

Target CCR5 WT/WT, WT/Δ32, and Δ32/Δ32 genotypes were observed in 91.4%, 8.6% and 0.0% for HCV positive patients and 98.3%, 1.7% and 0.0% for control group respectively. The histologic activity index (HAI) was significantly lower (4.0 ± 1.0) in the mutated group than the non-mutated group (5.7 ± 1.0). Decreased fibrosis levels were detected in HCV positive mutated group.

Conclusions:

Results showed that CCR5 polymorphism was more frequent in HCV positive patients than in healthy population in Turkish population. Current results also showed that mutated CCR5 signalling pathway due to CCR5-Delta32 may potentially result in subtle reduction of HCV specifity to the drug responses due to the positive impact on liver inflammation, fibrosis levels and liver destruction in HCV infection.     

Fracture resistance of roots filled with three different obturation techniques

Objectives: The aim of this study was to compare in vitro root fracture resistance following root canal filling with AH 26 using lateral condensation, BeeFill, and Thermafil techniques. Study Design: Eighty extracted human mandibular premolars with similar dimensions were selected. In order to standardize the roots, measurements were taken in two separate regions of the teeth—at the cemento-enamel junction and 8 mm apically from the junction—buccolingual as well as mesiodistal for every tooth. Teeth were then randomly divided into five groups (n=16). With the exception of the non-prepared group (Group 1), instrumentation was done in all groups. In group 2, instrumentation but no filling was performed; in group 3, the obturation was done with AH 26 + gutta-percha; in group 4, with AH 26 + BeeFill and in group 5, AH 26 + a Thermafil obturator was used. All the roots were mounted vertically in copper rings and filled with acrylic resin, exposing 8 mm of the coronal part. A universal testing machine was used for the strength test. Results: The results were analyzed using the one-way ANOVA test. The significance between the groups was tested with Temhane’s T2 test. The results indicate that instrumentation of root canals had a significant effect on fracture resistance (p<0.05). In addition, there were no differences between the root canal obturation techniques; furthermore, these techniques did not create a statistically important resistance to vertical fracture (p>0.05). Conclusions: The results suggest that instrumentation of root canals significantly weakens the tooth structure to fracture and the root canal obturation techniques that are used are not able to form reinforcement. Key words:AH 26, obturation technique, vertical fracture.     

Minimal intervention concept: a new paradigm for operative dentistry

The current treatment philosophy is to prevent and detect dental disease at the earliest stage in order to avoid invasive treatment. With the current understanding of the nature of dental disease and its process, the treatment philosophy is now changing to a more conservative approach and the concept of minimal intervention is gaining popularity in modern dentistry throughout the world. It is now established that demineralized but non-cavitated enamel and dentine can be healed and traditional surgical approach of drilling and filling may no longer be necessary as this only treats the symptoms of the disease and not the cause. However, when surgical intervention is indicated, the least invasive techniques such as preventive resin restoration and minimal cavity preparation are utilized. The aim of this article is to give dental professionals an overview of the concepts of minimal intervention dentistry and recent innovations in dental technology in both the diagnosis and treatment of dental caries.     

Increased carotid intima-media thickness is associated with higher SYNTAX score

The main purpose of this study was to investigate the relation between carotid intima-media thickness (CIMT) and coronary artery disease (CAD) complexity. Consecutive patients (n = 360) with CAD confirmed by coronary angiography were enrolled. Mean CIMT and the overall SYNTAX score (SXscore) were 0.87 ± 0.12 mm and 15 ± 9, respectively. In univariate analysis, there was a significant correlation between the overall SXscore and CIMT (r = .42, P < .001), age (r = .23, P < .001), hypertension (r = .27, P = 0.001), diabetes (r = 0.11, P = 0.02), smoking (r = .24, P = .01), dyslipidemia (r = .2, P = 0.03), and β-blocker use (r = .19, P < .001). In multivariate analysis, CIMT (β = .34, P < .001) and age (β = .11, P < .019) were independently associated with SXscore. We have demonstrated a significant relation between CIMT and SXscore. Although this study is correlative and no causative conclusions can be drawn, our findings suggest that increased CIMT could reflect complex coronary artery lesions.     

The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study

Hypovitaminosis D in the elderly causes falls and fractures as a result of impaired neuromuscular functions and also may be a reason for nonspecific musculosceletal pain. The aim of this study is to investigate the benefits of a single dose per os or parenterally administrated vitamin D on increasing the quality of life and functional mobility and decreasing the pain in the elderly. The community-dwelling elderly subjects over 65?years age were included in the study. The subjects were given 300.000?IU Vitamin D via per os and parenteral route and assessed after 4?weeks. The serum creatinine, calcium, phosphorous, ALT, ALP, 24-h urine calcium excretion, PTH, and vitamin D levels, as well as VAS (visual analog scale) for pain assessment, functional mobility with TUG (timed up and go test) and quality of life with SF-36 before and after the treatment were evaluated. The serum vitamin D levels were measured by the RIA method. The subjects were divided into four groups each consisting of 30 subjects. The 1st group took i.m. vitamin D, the 2nd group took i.m. placebo, the 3rd group took p.o. vitamin D, and the 4th group took p.o. placebo. The mean age of all the participants was 70.1?±?4.3?years. There was no difference in the age and gender between the groups (P?>?0.05). After treatment, the PTH level of first group was decreased (P?=?0.0001) and the vitamin D level increased (P?=?0.0001) significantly. In the third group, the PTH level of first group was decreased (P?=?0.0001) and the vitamin D level increased (P?=?0.004) and the 24-h calcium excretion in urine (P?=?0.015) increased significantly. When the pain, the functional mobility, and the quality of life were evaluated, in the first group, the TUG (P?=?0.0001) and the VAS (P?=?0.0001) decreased significantly, whereas the SF-36 subtitles: physical functioning (P?=?0.0001), role physical (0.006), bodily pain (P?=?0.0001), general health (P?=?0.007), social functioning (P?=?0.05), and mental health (P?=?0.048) increased significantly. In group two, the VAS (P?=?0.001) decreased, the role physical (P?=?0.009), and role emotional (P?=?0.034) increased significantly; In group three, the TUG (P?=?0.0001) and the VAS (P?=?0.002) decreased, whereas the physical function (P?=?0.0001) and role physical (0.001) increased significantly; In group four, the VAS (P?=?0.007) decreased significantly. The megadose vitamin D administration increases quality of life, decreases pain, and improves functional mobility via po or im route in the elderly.     

A case of primary Sjögren’s syndrome presenting primarily with central nervous system vasculitic involvement

Sjögren’s syndrome is primarily a chronic systemic autoimmune disease that affects exocrine organs. Neurologic symptoms frequently present as peripheral neuropathy due to small vessel vasculitis. Type and prevalence of central nervous system involvement are still controversial. In this report, we present a 35-year-old woman with primary Sjögren’s syndrome with central nervous system vasculitic involvement.     

DRESS syndrome with fatal results induced by sodium valproate in a patient with brucellosis and a positive cytoplasmic antineutrophilic cytoplasmic antibody test result

DRESS syndrome is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunctions. DRESS syndrome related to valproic acid use is very rarely observed. We present a case of DRESS syndrome induced by sodium valproate, which developed and progressed fatally in a brucellosis patient with a positive c-ANCA test. A 19-year-old female patient presented with fever, cough, jaundice, and rash all over her body. Brucella Coombs test was positive at 1:1280 titers, and the Rose Bengal test was also positive. The involuntary movements were thought to be due to chorea, and the patient was started on sodium valproate 500 mg 2*1, as well as streptomycin 1?g flk 1*1 and tetradox capsules 2*1 for the brucellosis and was discharged. DRESS syndrome was suspected in the patient, and she was taken off sodium valproate and tetradox; N-acetylcysteine, ceftriaxon, prednizolone, and support treatment were started. When sodium valproate is used on its own, it carries no risk of inducing DRESS syndrome. However, in the case presented, another co-morbidity such as brucellosis and c-ANCA positivity was present. We believe that the presence of further co morbidity not yet reported in literature is important from the perspective of the risk of valproate-induced DRESS syndrome. Therefore, if sodium valproate treatment is to be started in patients, especially those with co morbidity, they must be closely monitored with clinical and laboratory observations. At the slightest suspicion of DRESS syndrome, all medication should be ceased immediately and the patient should be placed under continuous observation.