Diagnostic value of synovial fluid anti-cyclic citrullinated peptide antibody for rheumatoid arthritis

Early and accurate diagnosis and treatment of rheumatoid arthritis (RA) improves disease outcome. Anti-cyclic citrullinated peptide antibody (anti-CCP) which is highly specific for RA is produced locally from inflamed synovium. The present study was designed to assess the diagnostic performance of synovial fluid anti-CCP (sf-CCP) for RA. A total of 128 patients consisted of 37 RA confirmed by the American College of Rheumatology revised criteria, 91 non-RA (50 non-RA inflammatory arthritis and 41 osteoarthritis) entered the study. Serum anti-CCP (sm-CCP) and Sf-CCP were measured by the ELISA method. Receiver operating characteristics curves were constructed to determine the optimal cutoff point levels for sf-CCP and sm-CCP to discriminate RA from non-RA. Diagnostic characteristics of both variables were determined by comparison of RA patients with non-RA controls. Mean levels of sf-CCP and sm-CCP were significantly higher in RA than in non-RA (P < 0.001). Sf-CCP discriminated RA from non-RA at the optimal cutoff value of 10 U/mL with high accuracy at AUC value of 0.897 ± 0.039, P < 0.001) sensitivity of 83.7% and specificity of 95.6%. Sm-CCP diagnosed RA at optimal cutoff level of 14.6 U/mL with respective sensitivity, specificity and AUC values of 84.8, 94.3% and 0.895 ± 0.049, P < 0.001). Sm-CCP was strongly correlated with sf-CCP (r = 0.75, r ² = 0.57, P < 0.0001). Two of 5 sm-CCP negative RA and 25.7% of serum rheumatoid factors negative RA were sf-CCP positive. These findings indicate that sf-CCP yields diagnostic ability as comparable as sm-CCP for RA. Respecting to local production of sf-CCP prior to disease onset, therefore sf-CCP determination may offer earlier as well as additional diagnostic information which may be more helpful in recognizing RA particularly among recent onset arthritis.     

Long-term response in advanced bladder cancer involving the use of temsirolimus and vinflunine after platin resistance

Relapse after initial first-line chemotherapy shows a poor prognosis in metastatic urothelial cancer. Currently, several chemotherapeutic agents and targeted drugs are under evaluation for platin-resistant advanced urothelial carcinoma. Vinflunine has been approved for second-line treatment in this indication. We present a patient with initial T4 advanced and subsequently metastasized bladder cancer, who has shown prolonged survival of 44 months after radical cystectomy. During her clinical course, the patient received two different platinum-containing therapies, temsirolimus within a phase II protocol and subsequent vinflunine chemotherapy. Treatment duration was 15 weeks with temsirolimus and 9 weeks with vinflunine, respectively, with a stable disease period of 3.8 months under temsirolimus therapy. This case is an example of how patients can derive a survival benefit from adequate sequencing of surgery and medical treatment including the newest therapies, even in advanced disease.     

Genetic polymorphism at the C-terminal domain (region III) of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum in isolates from Iran

The knob-associated histidine-rich protein (KAHRP) plays a major role in the virulence of Plasmodium falciparum and is one of the targets for molecular therapy. The primary structure of KAHRP of P. falciparum consists of three domains (regions I–III), of which the C-terminal domain (region III) is the most polymorphic segment of this protein. One of the main obstacles is genetic diversity in designing and developing of malaria control strategies such as molecular therapy and vaccines. The primary objective of the present study was to investigate and analyze the extent of genetic polymorphism at the region III of KAHRP of P. falciparum in isolates from Iran. A fragment of the kahrp gene spanning the C-terminal domain was amplified by nested PCR from 50 P. falciparum isolates collected from two malaria endemic areas of Iran during 2009 to August 2010 and sequenced. In this study, three allelic types were observed at the C-terminal domain of KAHRP on the basis of the molecular weight of nested PCR products and the obtained sequencing data. The presence of multiple alleles of the kahrp gene indicates that several P. falciparum strains exist in the malaria endemic areas of Iran. Our findings will be valuable in the design and the development of the molecular therapeutic reagents for falciparum malaria.     

A lupus-susceptibility C57BL/6 locus on chromosome 3 (Sle18) contributes to autoantibody production in 129 mice

Epistatic interactions between the non-autoimmune strains 129 and C57BL/6 (B6), used for generating gene-targeted animals, can induce a lupus-like disease. Genome-wide scan analyses of testcross progeny between these two strains have identified several lupus susceptibility loci, with the strongest linkage to the production of autoantibodies (auto-Abs) displayed by an interval on chromosome 1 of 129 origin (Sle16). However, the contribution of B6 loci to the lupus phenotype remained unknown. We used a congenic approach to deduce the contribution to the autoimmune traits of the B6 genomic interval on chromosome 3 (Sle18), previously shown to be linked to antinuclear Ab production. This interval, when transferred on a 129 background (a strain termed 129.B6-Sle18), promoted auto-Ab production targeting a broad spectrum of autoantigens, expansion of activated CD4(+)T and B cells and mild glomerulonephritis. Surprisingly, these immunological and serological defects were accompanied by a significant increase in the percentage of regulatory T cells (Tregs; CD4(+) Foxp3(+)). However, these cells, that expressed lower levels of Foxp3, had no impaired regulatory function when tested in vitro. These findings illustrate further the efficacy of congenic dissection for functional characterisation of individual lupus susceptibility loci and highlight the contribution of loci derived from non-autoimmune strains to the disease pathogenesis.     

Cytokines Genes Polymorphisms and Risk of Multiple Sclerosis

Association studies of proinflammatory and anti-inflammatory cytokines single nucleotide polymorphisms with multiple sclerosis (MS) in population with different ethnic background have shown inconsistent results. To study the possible role of tumor necrosis factor-α G-308A, interleukin-6 G-174C, interleukin-10 C-592A, C-819 T, G-1082A, transforming growth factor (TGF)-β (codons 10 and 25), and interferon-γ T + 874A polymorphisms in susceptibility to MS in Iranian population, DNA samples from 98 patients and 97 healthy controls were genotyped using polymerase chain reaction- sequence-specific primers. Analysis of the genotypes revealed a significant lower frequencies of tumor necrosis factor-a GA and TGF β C/C G/G genotypes and higher frequency of TGF β T/C G/C genotype in patients (P < 0.05). Our data suggest that these polymorphisms play a role in susceptibility to MS, which is possibly mediated by dysregulated production of these cytokines.     

Antiproliferative Effect of H2O2 against Human Acute Myelogenous Leukemia KG1 Cell Line

It has clearly been established that oxidative stress leads to perturbation of various cellular processes resulting in either inhibition of cell proliferation or cell death. In addition, there is a growing body of evidence indicating that reactive oxygen species (ROS) are required as signal molecules that regulate different physiological processes including survival or death. Free radicals, particularly ROS, have been proposed as general mediators for apoptosis and recent studies have established that the mode of cell death depends on the severity of the oxidative damage. In this study, we determined the effect of oxidative stress on cell proliferation and characterization of cell death in human KG1 cells treated with H₂O₂. Our results indicated that oxidative stress leads to a significant decrease in cell proliferation and induction of apoptosis. Moreover, our study suggests that antiproliferative and apoptotic cell death effects of H₂O₂ took place via activation of caspase-3, affecting the expression of Bcl-2 and Bax (an antiapoptotic and a proapoptotic factor, respectively), and through deactivation of catalase enzyme, leading to accumulation of intracellular ROS and depletion of intracellular ATP level.     

3D Cell Culturing and Possibilities for Myometrial Tissue Engineering

Research insights into uterine function and the mechanisms of labour have been hindered by the lack of suitable animal and cellular models. The use of traditional culturing methods limits the exploration of complex uterine functions, such as cell interactions, connectivity and contractile behaviour, as it fails to mimic the three-dimensional (3D) nature of uterine cell interactions in vivo. Animal models are an option, however, use of these models is constrained by ethical considerations as well as translational limitations to humans. Evidence indicates that these limitations can be overcome by using 3D culture systems, or 3D Bioprinters, to model the in vivo cytological architecture of the tissue in an in vitro environment. 3D cultured or 3D printed cells can be used to form an artificial tissue. This artificial tissue can not only be used as an appropriate model in which to study cellular function and organisation, but could also be used for regenerative medicine purposes including organ or tissue transplantation, organ donation and obstetric care. The current review describes recent developments in cell culture that can facilitate the development of myometrial 3D structures and tissue engineering applications.     

Risk Factors for Portal Vein Thrombosis in Patients With Cirrhosis Awaiting Liver Transplantation in Shiraz,Iran

Background:

Portal vein thrombosis is a fairly common and potentially life-threatening complication in patients with liver cirrhosis. The risk factors for portal vein thrombosis in these patients are still not fully understood.

Objectives:

This study aimed to investigate the associations between various risk factors in cirrhotic patients and the development of portal vein thrombosis.

Patients and Methods:

In this case-control study performed at the Shiraz organ transplantation center, Iran, we studied 219 patients (> 18 years old) with liver cirrhosis, who were awaiting liver transplants in our unit, from November 2010 to May 2011. The patients were evaluated by history, physical examination, and laboratory tests, including factor V Leiden, prothrombin gene mutation, Janus Kinase 2 (JAK2) mutation, and serum levels of protein C, protein S, antithrombin III, homocysteine, factor VIII, and anticardiolipin antibodies.

Results:

There was no statistically significant difference in the assessed hypercoagulable states between patients with or without portal vein thrombosis. A history of previous variceal bleeding with subsequent endoscopic treatment in patients with portal vein thrombosis was significantly higher than in those without it (P = 0.013, OR: 2.526, 95% CI: 1.200 - 5.317).

Conclusions:

In our population of cirrhotic patients, treatment of variceal bleeding predisposed the patients to portal vein thrombosis, but hypercoagulable disorders by themselves were not associated with portal vein thrombosis.     

A survey on causes of amputation in a 9-year period in Iran

Background

Limb loss occurs as a result of different causes and has been increasing in many countries. This study determines the demography of amputees in one of the relatively large cities of Iran.

Methods

This retrospective study was undertaken on all of the amputees between 2003 and 2011. Patients’ demographics including age, sex, the limb that had undergone amputation, etiology of limb loss and side and level of amputation were recorded. Also, the level of amputation was recorded as minor (below wrist or ankle) or major (above wrist or ankle).

Results

In total, 624 patients were enrolled in the study. The number of amputees was from 53 to 118/year. Of the patients, 508 were male (81.4?%) and 118 were female (18.6?%). The men with amputation were younger on average than women; 61.9?% of the amputations (386) were major and 38.1?% were minor (238). Overall, the most common cause of amputation was trauma and the most common level was transmetatarsal. The most common level for major amputations was below knee.

Conclusion

In contrast to similar studies in developed countries, trauma was found to be the major cause of all types of amputations and in all age groups, which emphasizes the need for preventive measures in the country.