Evaluation of the therapeutic action of original antiviral drug in SARS-CoV-2.

Purpose of this article is to study the possible direct antiviral effect of "Armenikum" on SARS-CoV-2, conduct an in vitro study on the SARS-CoV-2 encephalomocarditis virus, and an in vivo study on the Syrian hamster model. Human coronavirus SARS-CoV-2 (delta strain) was used as the virus. Two groups of four-specimen hamsters were used to study the therapeutic activity of the drug during 48 h after infecting. One group of hamsters served as positive control and was infected with the virus at a similar dose as experimental one and was used as a control of pathology induced by the viral infection till the end of the experiment. Another group of hamsters (four of them) was injected physiological solution and was used as a control. The Syrian hamsters underwent a clinical blood test and computed tomography. "Armenikum" in the form of an injection has a significant antiviral effect on the human coronavirus SARS-CoV-2, credibly reducing the titers of the virus and the time of its elimination from the Syrian hamsters, significantly mitigating the viral infection. "Armenikum" in the form of an injection drug almost completely removes the pathological effect of the virus in the lungs of the hamsters.

Long-term effectiveness of UV functionalised short (≤ 6 mm) dental implants placed in the posterior segments of the atrophied maxilla: controlled case series.

This study evaluated long-term effectiveness UV functionalised short implants (≤ 6 mm) placed in the posterior segments of the atrophied maxilla. The study included 47 patients from 2018 to 2023 (aged 27 to 56 years, 24 women and 23 men) without any systemic diseases, with unilateral/bilateral missing teeth and vertical atrophy of the posterior maxillary area. Total installed were 64 short UV-functionalized implants and 62 standard implants over 10 mm in length in segments maxilla with sufficient bone parameters. Clinical, laboratory and cone beam computed tomography (CBCT) methods were used to plan implant therapy. The clinical indices included the following parameters: ISQ, MBL, OHIP-G scale. For short implants, the median ISQ at placement was 62.2 for primary stability and the median ISQ at 5 months was 69.6 ISQ. For standard implant, the mean ISQ at placement was 64.3 ISQ, and ISQ after 5 months was 71.6 ISQ. After 6 months mean MBL short implants 0.87 mm, after 1 year 1.13 mm, after 5 years was 1.48 mm. After 6 months mean MBL standard implants 0.84 mm, after 1 year 1.24 mm, after 5 years was 1.58 mm. Mean OHIP-G scores-patients satisfaction with the implant at 4.8 ± 0.3, satisfaction with the operation 4.6 ± 0.4; satisfaction with prosthetics 4.7 ± 0.5. Cumulative success rate 5 years short implants was 96.7%, standard implants was 97.4%, and prosthesis cumulative survival rate was 97.2%. Short ultraviolet functionalized implants used in the posterior resorbed segment of maxilla have been shown to be a reliable alternative to sinus lift, demonstrating fewer complications, reduction in the number of additional surgical interventions and showed satisfactory long-term survival.

Corrigendum: Evaluation of the survival rate of short implants placed in the posterior atrophic mandible: 5-year clinical study.

The following amendments are made to the published article: Quintessence Int 2022;53:690-696; First published 17 August 2022; doi: 10.3290/j.qi.b3095013.

Efficacy of the transcutaneous electrostimulation in treatment dysfunctions of the TMJ associated with occlusion distortions.

BACKGROUND: The study evaluation of the effectiveness the method of electrostimulation in treatment TMJ associated with occlusion disorders with the use of a patches by the company "Aganyan''. METHODS: The study included 54 patients with temporomandibular dysfunction syndrome who had previously undergone endodontic dental treatment. In patients temporomandibular disorders (TMD) determined on the basis of Diagnostic criteria for temporomandibular disorders(DC/TMD).All patients had occlusion disorders due to errors after dental filling restoration. To diagnose the TMJ, a CT scan was used. The complex therapy also included therapy and with the use of a patches by the company "Aganyan''. The wearable patch includes a flexible substrate, a binder an adhesive layer, with an electrode foil attached to it. Patients applied one patch behind each TMJ. The patches were applied for eight hours every third day for three months. All the patients were given full-fledged endodontic treatment and restoration of the crown part, taking into account anatomical features. RESULTS: The dynamics of the complex treatment of patients diagnosed with TMJ dysfunction syndrome showed that after treatment, the clinical symptoms gradually decreased and disappeared at the end of treatment. CT scan a year after treatment showed a normal ratio of TMJ elements. Сomplex treatment was effective in 87% of patients, after 3-5 months gradually decreased pain, noise in the joints, restriction of opening and closing of the mouth disappeared. Patients recovered their chewing functions, psycho-emotional state. CONCLUSION: The results of the studies revealed a positive effects for the complex treatment dysfunctions syndrome TMJ the using the patches by the company "Aganyan" through electrical stimulation with low intensity.

Vitamin C supplementation alleviates hypercortisolemia caused by chronic stress.

The aim of this study was to determine whether ascorbic acid (AA) supplementation can lower plasma levels of Cortisol and dehydroepiandrosterone-sulphate (DHEA-S) in patients diagnosed with functional hypercortisolemia due to unspecified chronic stress. Study includes data from 69 female with elevations in the cortisol and DHEA-S levels. Duration of follow-up was 2 months. Patients were divided into 3 groups. Group I included patients 23 with elevated cortisol, Group II-patients 24 with elevated levels of both hormones, Group III- patients 22 with normal cortisol and increased DHEA-S. Each group was randomly divided into two subgroups. The first subgroup was prescribed 1000 mg daily oral dose of AA. The diet of the second subgroup were left unaltered. All patients have their hormones levels re-examined 2 months later. After 2 months of AA supplementation the mean levels of elevated plasma cortisol and DHEA-S decreased. In Group I the level of cortisol fell from 780 ± 57-446 ± 26 nmol/L, p = 0.000065 in Group II from 657 ± 47-515 ± 29 nmol/L, p = 0.005. The elevated levels of DHEA-S have also declined in patients from AA-treated subgroups (from 13.9 ± 1.6-9.9 ± 1.2, p = 0.0007 in Group II, and from 12.8 ± 1.0-7.8 ± 1.4, p = 0.003 in Group III). In untreated subgroups changes in hormone levels were insignificant. The study shows that female patients with functional hypercortisolemia or elevated levels of DHEA-S can be treated with AA to bring level of these hormones closer to a normal range.

Diagnostic and prognostic value of indicators of markers of bone metabolism in type 2 diabetes mellitus patients with UV functionalised dental implants.

BACKGROUND: Diabetes mellitus affects many organ systems, including bone tissue.In diabetic patients, the activity of osteoblasts is suppressed and the activity of osteoclasts in the bone matrix increases, bone formation decreases, which can disrupt the process of osseointegration and ultimately lead to disintegration and failed implants. Based on the foregoing, with diabetes, it is very important to study bone metabolism to predict and dynamically control dental implants. OBJECTIVES: To assess the indicators of bone metabolism markers Osteocalcin and ß-Cross-Laps in blood serum in patients with type 2 diabetes mellitus with intraosseous dental implants. METHODS: The study included 86 patients, diagnosed type 2 diabetes mellitus in period 2018 - 2023 with partially or complete edentulous. Implant surgery was performed after periodontal therapy using 367 UV functionalized dental implants in patients 1 group. Patients 2 group was performed implant surgery using 54 dental implants that were not UV functionalization. Final dental prosthetics was performed 4-5 months. UV functionalization of the implant surface was carried out using a UV Activator YWJ-QSY001 (Foshan, Wenjian Medikal Enstriman) for 20 s. The content biochemical markers of bone Osteocalcin and ß-Cross-Laps serum was determined by enzyme-linked immunosorbent assay ELISA (ELISA, IFA Roche Diagnostics, Basel, Switzerland) before and after dental implantation according to the manufacturers' protocols. Outcomes assessed included; implant survival, men MBL, PPD, BOP, RFA, prosthetic success. RESULTS: There were no clinical examinations of serious biological or prosthetic complications. There is a correlation between different concentrations of Osteocalcin or ß-Cross- Laps and the success rate of implants. Implants were shown to be unsuccessful low concentrations of Osteocalcin and high concentrations ß-Cross- Laps in serum compared with average mean biochemical markers of bone in 2 group patients. In patients of the 2nd group, the indicators of biochemical bone markers were within the normal range; no correlation was found between osseointegration failers and the complication of peri-implatitis. Short implants success rate was 96,7 %, standart implants success rate was after 97,5 after 5 years. CONCLUSION: Implant therapy can be successfully used in diabetic patients with UV photofunctionalized implants, blood glucose levels should be constantly maintained at a normal level. Monitoring of bone metabolism markers in patients with type 2 diabetes mellitus may have prognostic value for implants and will encourage the practitioner to apply corrective drug therapy in case of violation of markers.

Surgical Treatment in Patients with Toxic Phosphorus Osteonecrosis of Facial Skull Middle Zone.

During the last few years, in the territory of the Russian Federation, the number of cases of toxic phosphoric osteonecrosis of the jaws has increased against the background of taking drugs of "artisanal" production (pervitin, desomorphin). The aim of our study was to increase the effectiveness of surgical treatment of patients with a diagnosis of toxic phosphorus necrosis of the maxilla. We performed a comprehensive treatment of patients with a history of drug addiction and the above diagnosis. Surgical intervention in the volume of complete resection of pathologically altered tissues and reconstructive techniques using local tissues and a replaced flap made it possible to achieve good aesthetic and functional results in the early and late postoperative period. Thus, our proposed method of surgical treatment can be used in similar clinical situations.

Clinical Outcome of Immediate Loading UV-Photofunctionalized Implants in Patients with Completely Edentulous Mandible, Placed with Guided Surgery.

Objectives: The purpose of this study was to evaluate clinical results of immediate loading UV-photofunctionalized dental implants placed using guided surgery in patients with completely edentulous mandible. Material and Methods: In this study, 58 fully edentulous patients were treated with immediate loading implant-supported mandibular prostheses. All patients underwent a thorough clinical examination according to the generally accepted scheme; qualitative and quantitative parameters of the jaw bones patients were diagnosed with cone beam computerized tomography (CBCT). Surgical templates modeled in the 3 Shape software were made from biocompatible polymeric materials and provided with depth-calibrated drill sleeves for preparing osteotomies using a 3D printer (Stratasys). Before short implant placement, ultraviolet functionalization of implant surfaces was performed by UV Activator YWJ-QSY001 (Foshan, Wenjian Medikal Enstriman) in the device for 20 s. After flapless surgery, implant sockets were prepared with guided surgery and implants were placed through the sleeves of the surgical template tightening torque of 35-45 Ncm. An implant-supported temporary prosthesis made of acrylic resin was installed 6 h after implantation. Final dental prosthetics was performed 2 months after implant placement.The patients had 128 short (length 5-6 mm, diameters 4,5-5 mm) and 256 implants with length greater than 10 mm in bone segments with sufficient bone parameters. The following parameters were assessed: implant success, prosthetics survival and changes in peri-implant marginal bone loss (MBL). Results: During a clinical examination, no serious biological or prosthetic complications have been reported. The esthetic result evaluated from patients was excellent. The mean ISQ of short implants was 69.2 ± 8 for primary stability at implant placement and 73.6 ± 4 ISQ after 3 months. The mean of implants with length greater than 10 mm was 71,2ISQ at implant placement, respectively, and 75,6 ISQ after 3 months. After 3 months of prosthetic loading for short implants marginal bone loss (MBL) 0.74 mm, after 1 year of MBL 11.21 mm, after 5 years of MBL 1,37 mm, for implants with length greater than 10 mm after 3 months of MBL 0.72 mm, after 1 year of MBL 1.19 mm and after 5 years of MBL 1.35. There was no statistically significant difference in clinical indices between short and standard implants. After 5 years of follow-up, stable levels of bone tissue around the implants and healthy tissues around the implants were recorded, and postoperative occlusal function was favorable. The success rates of the short implants in maxilla were 95.5%, and the success rates of the short implants in mandible were 98.7%. The success rates of the implants with length greater than 10 mm in maxilla were 97.8%, and the success rates of the implants with length greater than 10 mm in mandible were 98.8%. Conclusion: Computer-guided implant surgery and immediate loading of UV-photofunctionalized implants in patients with completely edentulous mandible are a predictable and effective method with a minimum rehabilitation period.

Clinical advantages of improving the excessive gingival display (EGD) by surgical repositioning of the upper lip.

OBJECTIVES: The objective of this study is to minimize gingival display by surgical repositioning of the upper lip and to suggest this technique as an alternative treatment modality to orthognatic surgery for treatment of excessive gingival display. MATERIALS AND METHODS: Forty-eight patients were selected with gingival display of more than 2 mm during maximal smiling. All patients underwent surgical repositioning of the upper lip, aimed at limiting elevator muscle activity to treat excessive gum exposure. Patients were regathered in 1 week for the follow-up postoperative symptoms according to VAS scale to evaluate pain and swelling. Reference values were given to patients. RESULTS: The study has indicated good results and stability especially to patients with skeletal class I classification along with medium and thick biotype of attached gingiva without hypermobile upper lip. CONCLUSION: Surgical repositioning of the upper lip is an effective way to improve a patient's gingival smile caused by degree I and II VME in combination with HUL as an alternative treatment modality to orthognathic surgery. This method is less invasive and cost-effective, causes minimal postoperative complications, and provides faster recovery. CLINICAL RELEVANCE: Excessive gingival display (EGD) with various etiologies requires several proper treatment modalities. The proposed modified method of lip repositioning to reduce the degree of gingival display is less aggressive, reliable, and causes fewer postoperative complications compared to orthognathic surgery.

Evaluation of the survival rate of short implants placed in the posterior atrophic mandible: 5-year clinical study.

OBJECTIVE: The aim of the study was to assess the long-term prognosis of short implants (5 to 6 mm) placed in the posterior region of the atrophic mandible. METHOD AND MATERIALS: The study included 81 patients with severe vertical atrophy of the bone in the posterior region. The patients had 248 short implants (5 to 6 mm) implants placed in the mandibular posterior region and 256 implants with length greater than 10 mm in the mandibular anterior region. Analysis of implant and prosthesis failures, cumulative survival rate, and marginal bone loss was determined at 1 year and 5 years of follow-up (58 ± 7 months). RESULTS: Mean marginal bone loss after 1 year of prosthetic loading was 0.74 mm for short implants and 0.72 mm for implants with length greater than 10 mm; after 5 years of prosthetic loading this was 1.27 mm for short implants and 1.31 mm for implants with length greater than 10 mm. Of 248 short implants (5 to 6 mm), six failed: four due to peri-implantitis and two due to lack of osseointegration (early rejection). Of 256 implants with length greater than 10 mm, five failed: three due to peri-implantitis and two due to lack of osseointegration (early rejection). On average, over the observation period (58 ± 7 months), the 5-year cumulative implant survival rate was 97.8% in short implants, and 98.1% in longer implants; the prosthesis cumulative survival rate was 98.2%. CONCLUSIONS: Based on the results, it was concluded that the prognosis of the use of short implants for prosthetics in the posterior resorbed mandible can be considered favorable and reasonable.

Impact of supplemental essential phospholipids on treatment outcome and quality of life of patients with psoriasis with moderate severity.

Aim of this study was to evaluate effect of supplemental of essential phospholipids (EPL) on the treatment efficacy in patients with moderate psoriasis. One hundred and thirty-two subjects over 18 years of age with diagnosed psoriasis participated in this study. Patients were randomly assigned two treatment groups. Two types of treatment were used for the treatment of the patients. First group of patients received conventional treatment which included systemic immunosuppressant, antihistamine, calcium gluconate, and topical salicylic acid. Second group (n = 67) received same treatment with supplemental EPL. Data was comprised of age, gender, psoriasis area and severity index (PASI) and dermatological life quality index (DLQI) scores, other clinical/laboratory characteristics including TNF-α, IL-1α, IL-2, INF-γ, IL-10, and TGF-ß. All measurements were done before and after treatments. After treatment in the treatment groups the PASI scores decreased to 4.5 (SD ± 2.66) and 2.09 (SD ± 1.09) respectively. The observed difference was statistically significant (p < 0.001). Change of PASI score was greater in group II on average by 2.81 (SD ± 0.38). After treatment in both groups the DLQI scores decreased to 4.42 (SD ± 1.23) and 3.91 (SD ± 0.34), respectively. The observed difference was statistically significant (p < 0.001). Change of DLQI score was greater in group II on average by 4.29 (SD ± 0.44). We can state that addition of EPL to the standard treatment can improve treatment outcomes and quality of life in patients with moderate psoriasis.

Coil embolization of arterioportal fistula complicated by gastrointestinal bleeding after Caesarian section: A case report.

BACKGROUND: Most intrahepatic arterioportal fistulae (IAPF) are acquired. The few cases of congenital fistulae are diagnosed in infants and children. CASE SUMMARY: We report a 31-year-old female patient presenting with haematemesis and melena three weeks after delivering her second child. The patient had a 20-year history of abdominal distention and nausea. IAPF, along with splenomegaly and ascites, was found by Doppler sonography and confirmed by computed tomography angiography. The patient was treated with endovascular coil embolization, resulting in occlusion of the fistula. CONCLUSION: This was an unusual case of possible congenital IAPF that manifested during a second pregnancy and was complicated by portal hypertension.

Prevalence of Helicobacter pylori infection and antibiotic resistance profile in Armenia.

BACKGROUND: The prevalence of Helicobacter pylori infection was never assessed in Armenia, nor was the prevalence of H. pylori resistance against the main antibiotics concerned, despite the fact that these data are fundamental to establish evidence-based recommendations for management of this infection. We aimed to fill this gap by assessing prevalence of H. pylori among adult population in Armenia and resistance of H. pylori strains to clarithromycin and levofloxacin. METHODS: Helicobacter pylori seroprevalence was determined in 217 asymptomatic adult subjects submitted to a health checkup using an ELISA. Molecular methods were used to detect H. pylori in gastric biopsies from 91 adult dyspeptic patients [55 (60.4%) were positive] as well as the mutations associated with clarithromycin resistance by real-time PCR and with levofloxacin by sequencing the gyrA QRDR. RESULTS: Helicobacter pylori seropositivity was found to be 41.5% globally and increased with age from 13.6% (age 18-25 years) to 83.3% (age > 65 years). Only two cases were found with a A2142/43G mutation causing clarithromycin resistance, and 6 cases showed mutations associated with levofloxacin resistance. CONCLUSIONS: Helicobacter pylori infection is estimated to be about 42% among adults in Armenia and the low clarithromycin resistance allows the use of the standard triple therapy as a first line therapy.

Simultaneous endoscopic endonasal sinus surgery and sinus augmentation with immediate implant placement: A retrospective clinical study of 23 patients.

OBJECTIVE: The aim of this study was to evaluate the efficacy of simultaneous endoscopic endonasal sinus surgery and sinus augmentation with immediate implant placement. PATIENTS AND METHODS: The study patients (n = 23) were partially or completely edentulous in the posterior maxilla and required maxillary sinus augmentation. All included patients had a sinus pathology confirmed clinically and radiographically. The technique of simultaneous endoscopic endonasal sinus surgery and sinus augmentation was used in 15 patients, with eight endonasal sinus surgery procedures being performed 2-3 months before sinus augmentation. Where possible, implants were placed during the same surgical procedure (with a ridge bone height of at least 4 mm). RESULTS: There were no any major intraoperative complications. Implants placed in the reconstructed areas were shown to integrate normally, and postoperative occlusal function and aesthetics were favorable. Of the 95 implants placed in these 23 patients, two failed to osseointegrate. CONCLUSION: The method of simultaneous endoscopic endonasal sinus surgery and sinus augmentation with immediate implant placement leads to a reduction in postoperative complications, significantly shortening the rehabilitation period for patients with maxillary sinus diseases and insufficient bone tissue.

The Treatment of Lower Jaw Defects Using Vascularized Fibula Graft and Dental Implants.

This study is based on an analysis of the results of treatment of 21 patients with mandibular defects of different localization and etiology who underwent reconstruction with fibula free flap. Postoperative clinical and radiographic controls were made regularly, the criteria for implant success were assessed.The postoperative evolution of the patients was favorable, with the integration of the fibula vascularized grafts. Complete engraftment of bone autografts and wound healing was obtained in all observations. In all 21 patients, fibula flaps provided adequate conditions for implant placement. The coefficient of osteointegration of implants 3 years after bone grafting was 97%.Using a vascularized autograft from the fibula to replace the defects of the lower jaw provides the conditions for a full rehabilitation of patients. The methods of reconstructive surgery and implantation make it possible to successfully perform the replacement of defects in the maxillofacial region, being one of the methods medical and social rehabilitation of patients with this pathology.

Long-term familial Mediterranean fever remission on successful hepatitis C virus treatment in a patient not responding to colchicine: a case report.

BACKGROUND: Familial Mediterranean fever is an autosomal recessive disorder characterized by periodic febrile attacks of aseptic serositis and/or arthritis. The main treatment is colchicine which prevents attacks in the majority of patients except for a group of colchicine-resistant cases. Chronic hepatitis C is a viral infection causing chronic inflammation of liver tissue (hepatitis) which ultimately progresses to fibrosis and liver cirrhosis with a high chance of hepatocellular carcinoma. However, we found no data in the literature concerning the impact of hepatitis C on the course of attacks of familial Mediterranean fever. CASE PRESENTATION: We report a case of a 21-year-old white woman with familial Mediterranean fever who had not been responding to a high dose of colchicine (2 mg/day). She presented to our clinic with a finding of chronic hepatitis C genotype 3 infection. After successful antiviral therapy with peginterferon and ribavirin, she became attack-free for 2 years and went on to a lower dose of colchicine. CONCLUSIONS: This unusual case illustrates complete resolution of attacks of autoinflammatory disease after drug-induced clearance of chronic hepatitis C infection. Coexisting infections should be viewed as potentially altering the course of autoinflammatory disorders, and any attempt to cure the infections should be made in order to gain an added value of benefiting the chronic disease. This case highlights the interrelation of external pathogen-related and genetically inherited alterations in immunity and the importance of considering the whole spectrum of possible causative factors rather than implementing separate guidelines in order to achieve best quality of medical care in any given patient.

Structure, Energetics, and Dynamics of Screw Dislocations in Even n-Alkane Crystals.

Spiral hillocks on n-alkane crystal surfaces were observed immediately after Frank recognized the importance of screw dislocations for crystal growth, yet their structures and energies in molecular crystals remain ill-defined. To illustrate the structural chemistry of screw dislocations that are responsible for plasticity in organic crystals and upon which the organic electronics and pharmaceutical industries depend, molecular dynamics was used to examine heterochiral dislocation pairs with Burgers vectors along [001] in n-hexane, n-octane, and n-decane crystals. The cores were anisotropic and elongated in the (110) slip plane, with significant local changes in molecular position, orientation, conformation, and energy. This detailed atomic level picture produced a distribution of strain consistent with linear elastic theory, giving confidence in the simulations. Dislocations with doubled Burgers vectors split into pairs with elementary displacements. These results suggest a pathway to understanding the mechanical properties and failure associated with elastic and plastic deformation in soft crystals.

Accelerated apoptosis of neutrophils in familial mediterranean Fever.

The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates of systemic neutrophil apoptosis as well as the levels of proteins involved in apoptosis were investigated ex vivo in patients with FMF using flow cytometry and RT-qPCR. The freshly collected neutrophils from the patients in FMF remission displayed a significantly larger number of cells spontaneously entering apoptosis compared to control (6.27 ± 2.14 vs. 1.69 ± 0.18%). This elevated ratio was retained after 24 h incubation of neutrophils in the growth medium (32.4 ± 7.41 vs. 7.65 ± 1.32%). Correspondingly, the mRNA level for caspase-3 was also significantly increased under these conditions. In response to the inducing agents, the neutrophils from FMF patients also displayed significantly elevated apoptotic rates compared to control. The elevated rates, however, can be largely explained by the higher basal ratio of apoptotic cells in the former group. Monitoring of several proteins involved in apoptosis has not revealed any conventional mechanisms contributing to the enhanced apoptotic rate of neutrophils in FMF. Although the exact molecular mechanisms of accelerated neutrophil apoptosis in FMF remain unknown, it may provide a protection against excessive inflammation and tissue damage due to a massive infiltration of neutrophils in the acute period of the disease.

Neutrophil F-actin dynamics in Familial Mediterranean Fever: the unequal effect of colchicine on activated neutrophils.

In the innate immune system, cellular adaptation regulates neutrophil activation and chemotaxis, which have a pivotal role in Familial Mediterranean Fever (FMF) pathogenesis. We investigated neutrophil F-actin, phagocytosis and macropinocytosis dynamics during neutrophil chemoattractant-dependent activation in FMF patients carrying mutations in the MEFV locus. We found that while a non-stimulated neutrophil shows an increased overall F-actin content in patients with FMF, the activation-dependent F-actin dynamics in the presence of chemoattractant peptide is significantly reduced. Neither overall F-actin content nor F-actin dynamics was changed in FMF patient's neutrophils in the presence of double doses of chemoattractant, while in healthy donors it occurred with significant reduction of F-actin content and dynamics. The neutrophil shows increased phagocytosis and macropinocytosis dynamics for a relatively short period, which may contribute to the decreasing of plasticity of the cellular cytoskeleton during FMF. Colchicine causes reduction of overall F-actin content and shows a distinctively unequal effect on chemoattractant-activated neutrophil F-actin dynamics in FMF patients compared with healthy donors. These data suggested that mutations in MEFV cause the dissolution of cellular adaptation to chemoattractant stimuli due to alterations in neutrophil F-actin and phagocytosis dynamics, which could serve as a major target for FMF treatment.

The 1F7 idiotype is selectively expressed on CD5+ B cells and elevated in chronic hepatitis C virus infection.

Antibodies against different chronic viruses, including hepatitis C virus (HCV), express a public cross-reactive idiotype (Id) designated as 1F7. The prominence of this Id may reflect selective engagement of B1 B cells by chronic pathogens. We investigated this by comparing 1F7 Id expression on CD5(+) and CD5(-) B cells, total IgG, total IgM and anti-HCV core antibodies in different HCV exposure settings. By flow cytometry, we observed a selective increase in 1F7 Id(+)CD5(+) B cells in chronic HCV infection. 1F7 Id levels in different immunoglobulin compartments were measured by enzyme-linked immunosorbent assay. 1F7 Id expression was prominent in anti-HCV core antibodies of approximately 90% of 141 HCV-exposed individuals tested. In the Canadian and Armenian study groups, participants who spontaneously cleared HCV infection had lower median 1F7 Id levels on total plasma IgG and anti-HCV core antibodies. Armenian spontaneous clearers, who were younger and more recently infected than their Canadian counterparts, also had had lower median 1F7 Id levels on total plasma IgM. Engagement by HCV of B-cell receptors within, or overlapping with the CD5(+) B1 B-cell repertoire is reflected in the production of 1F7 Id(+) anti-HCV antibodies and expansion of 1F7 Id(+)CD5(+) B cells. Higher 1F7 Id expression levels are associated with chronic infection.