Interleukin-1 receptor antagonist and tumour necrosis factor-alpha gene polymorphisms in Turkish patients with allergic contact dermatitis

Background: It has been shown that the family of interleukin-1 receptor antagonist (IL-1 RA) and tumour necrosis factor-alpha (TNFα) genes are polymorphic and related to some inflammatory diseases. Allergic contact dermatitis is the classic presentation of delayed-type hypersensitivity responses to exogenous agents. A number of genes playing role in inflammatory response may be associated with allergic contact dermatitis.
Objectives: To investigate whether there is an association between IL-1RA and TNFα gene polymorphisms and allergic contact dermatitis in Turkish patients with allergic contact dermatitis.
Methods: This study was performed by the collaboration of Departments of Dermatology and Medical Genetics, Ege University, Faculty of Medicine. A total of 50 patients (31 females and 19 males) with allergic contact dermatitis, and 100 age- and sex-matched controls (58 females and 42 males) were included in the study. IL-1RA Variable Number of Tandem Repeats (VNTR) polymorphism in intron 2 and TNFα-308G-A polymorphism were genotyped by using polymerase chain reaction and agarose gel electrophoresis.
Results: The frequency of IL-1RA 1/2 (48%) genotype was significantly higher ( P = 0.002) in patient group than that is found in control group (22%). The frequency of TNFα (TNF G-308A) G/G genotype was significantly higher in patient group (68%) than that is found in control group (31%) ( P = 0.008).
Conclusions: Our findings suggest that TNFα (G/G) gene polymorphism may play role in susceptibility to allergic contact dermatitis in Turkish patients.     

Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model

Through a whole-cell panning approach, we previously identified a panel of antibodies that bound to prostate cancer cell surface antigens. One such antigen, CUB domain-containing protein 1 (CDCP1), was recognized by monoclonal antibody 25A11 and is a single transmembrane molecule highly expressed in several metastatic cancers as well as on CD34(+)CD133(+) myeloid leukemic blast cells. We show CDCP1 expression on prostate cancer cell lines by real-time quantitative PCR (RT-qPCR), flow cytometry, and immunohistochemistry and on prostate cancer patient samples by RT-qPCR and immunohistochemical staining. In cell-based assays, antibody 25A11 inhibited prostate cancer cell migration and invasion in vitro. Further characterization showed that CDCP1 is internalized on antibody binding. When 25A11 was coupled to the cytotoxin saporin either directly or via a secondary antibody, both resulted in prostate cancer cell killing in vitro. In vivo targeting studies with an anti-CDCP1 immunotoxin showed significant inhibition of primary tumor growth as well as metastasis in a mouse xenograft model. These data provide support for continued evaluation of anti-CDCP1 therapy for potential use in cancer in primary and metastatic disease.     

Evidence of an association between mannose binding lectin codon 54 polymorphism and adenoidectomy and/or tonsillectomy in children

Mannose binding lectin (MBL) is a calcium-dependent lectin that plays an important role innate immunity by activating the complement pathway. There have been a number of studies describing an association between the MBL genotype and disease susceptibility. MBL deficiency has been described as one of the factors leading to a number of infections in children with recurrent upper respiratory tractus infections (URTI). We hypothesized that MBL deficiency may be associated with recurrent URTI, which requires adenoidectomy and/or adenotonsillectomy. In this study to clarify this hypothesis we investigated whether there may be an association between two low producing MBL variants and adenoidectomy and/or tonsillectomy due to recurrent URTI in children. Blood samples were collected, adenoidectomy and/or tonsillectomy due to recurrent URTI and 50 controls (mean age 80.53 +/- 32.62 months). In all patients and controls codon 54 and codon 57 polymorphisms of the MBL gene were analyzed. None of the subjects from the patient group and control group carried codon 57 polymorphism of the MBL gene. The frequency of low-level MBL genotypes (AB and BB) for codon 54 polymorphism in the patient group was found to be significantly higher compared to the control subjects (55.7% versus 14%) (p<0.001). This study shows that the presence of low-level MBL alleles is associated with adenoidectomy and/or tonsillectomy caused by recurrent URTI in children.     

Low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression

Objectives

To investigate the low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression.

Methods

Cross-sectional study with 180 women aged between 19 and 60 years who admitted to our outpatient clinic. Sexual function was assessed by female sexual function index and clinically significant depression was measured by Beck depression inventory test.

Results

The rate of low sexual function was 85.9% in postmenopausal (OR 2.9, 95% CI 1.8–4.8) and 47.7% in premenopausal women (OR 0.4, 95% CI 0.3–0.5) (p < 0.0001). The postmenopausal group reported significantly lower desire, arousal, lubrication, orgasm, satisfaction and pain scores than controls (p < 0.0001, for all of them). Low sexual function was positively correlated with age (r = 0.37, p < 0.0001), menopausal status (r = 0.40, p < 0.0001), gravidity (r = 0.44, p < 0.0001), parity (r = 0.43, p < 0.0001), abortion rates (r = 0.27, p = 0.001) and marriage period (r = 0.40, p < 0.0001). There were also significant negative correlations between low sexual function and education (r = −0.39, p < 0.0001) and family income (r = −0.29, p < 0.0001). However, multivariate regression analysis demonstrated that education, family income and menopausal status were the only independent variables for low sexual function after adjusted for age, gravidity, parity, abortion, marriage period and menopausal status.

Conclusion

Low sexual function was relatively high in postmenopausal women without clinically significant depression. Education, family income and menopausal status were the independent risk factors for low sexual function. Investigation of female sexuality was essential for these patients.     

Effect of low level laser therapy and zoledronate on the viability and ALP activity of Saos-2 cells

A limited number of clinical studies indicate the supportive role of low level laser therapy (LLLT) on medical and/or surgical approaches carried out in treatment modalities for bisphosphonate related necrosis of jaws (BRONJ), the most common side effect of bisphosphonates used to inhibit bone resorption. The purpose of this study was to investigate the effects of LLLT on cell proliferation and alkaline phosphatase (ALP) activity of human osteoblast-like cells (Saos-2) treated with different doses of zoledronate, the most potent bisphosphonate. Saos-2 cells were treated with different concentrations of zoledronate and were irradiated with diode laser (wavelength 808 nm, 10 s, 0.25 or 0.50 W). Cell numbers and ALP activity of the cells were determined. LLLT mildly increased the proliferation rate or ALP activity, while zoledronate reduced both. When applied together, LLLT lessened the detrimental effects of zoledronate and improved cell function and/or proliferation. Based on the results of this study, it was concluded that LLLT has biostimulative effects on Saos-2 cells, even after treatment with zoledronate. LLLT may serve as a useful supportive method for BRONJ treatment through enhancement of healing by osteoblasts.     

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease‐causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate‐to‐severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease‐specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)‐13 and IL‐4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti–IL‐4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate‐to‐severe AD. The anti–IL‐13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL‐13 epitopes with potentially different effects, are currently in advanced‐stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine.     

A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease

Interstitial lung disease (ILD) is a condition affecting the lung parenchyma by inflammation and fibrosis and can be caused by various exposures, connective tissue diseases (CTD), and genetic disorders. In this report, a family with five patients having progressive respiratory failure that begins with coughing in adolescence, followed by dyspnea and recurrent spontaneous pneumothorax, and death in early adulthood is presented. The patients were diagnosed to have ILD through clinical and radiological evaluations. Molecular genetic analyses of the family provided two homozygous rare variants in the WRN and SFXN5 genes, co-segregating with the phenotype. The network analyses pointed out that the variant in the WRN, rather than that in the SFXN5 gene, could be the main factor in the existence of the ILD phenotype, putatively through the altered DNA repair and telomere maintenance pathways. In silico analyses suggested that the variant could affect the exonuclease activity or the stability of the WRN protein. Moreover, the adolescent-onset pulmonary phenotype described in the case has not been reported in Werner Syndrome, the only disease known to be associated with biallelic WRN pathogenic variants. Thus, the present phenotype could be either a very atypical presentation of Werner syndrome or a new clinical entity associated with the WRN gene.