Comparison of the effectiveness of cyclophosphamide and rituximab treatment in patients with systemic sclerosis–related interstitial lung diseases: a retrospective,observational cohort study

Clinical Rheumatology - To compare the effectiveness of cyclophosphamide and rituximab in the treatment of patients with systemic sclerosis with pulmonary involvement (SSc-ILD). Symptoms and the...     

Analysis of insulin like growth factor 1 and insulin like growth factor binding protein 3 levels in bronchoalveolar lavage fluid and serum of patients with lung cancer

OBJECTIVE: Insulin like growth factor 1 (IGF-1) is recognized as a potent mitogen for many cancer cell lines and there is good evidence that lung cancer cells produce both IGF-1 and insulin like growth factor binding protein 3 (IGFBP-3). The aim of this study was to investigate the clinical significance of IGF-1 and IGFBP-3 levels in serum and in bronchoalveolar lavage (BAL) fluid by comparing lung cancer patients with healthy controls. METHODS: BAL fluid and serum samples were obtained from 24 lung cancer patients and 12 healthy controls, and were analyzed for IGF-1 and IGFBP-3 levels by a two site immunoradiometric assay. The recovered BAL fluid was standardized by albumin to remove the variable of dilution and the data was expressed in epithelial lining fluid (ELF). RESULTS: Serum IGF-1 and IGFBP-3 levels were lower in lung cancer patients, but the difference between the groups did not reach a statistical significance. IGF-1/IGFBP-3 ratio in ELF was significantly lower in lung cancer patients (P=0.035). Mean IGF-1 level in ELF was determined to be significantly lower in patients with distant metastasis (P=0.04). Serum IGF-1/IGFBP-3 ratio was found to be significantly lower in patients with distant (P=0.04) and nodal metastasis (P=0.03). Tumor stage was negatively correlated with IGF-1 level in ELF (P=0.05, r=-0.4) and serum IGF-1/IGFBP-3 ratio (P=0.04, r=-0.4). CONCLUSION: IGF-1 and IGFBP-3 levels both in serum and ELF might serve a clinical significance in patients with lung cancer. However, further studies comprising more cases are needed to investigate the clinical significance of IGF-1 and IGFBP-3 in lung cancer.     

Ultrastructural Damage in Vascular Endothelium in Rats Treated with Paclitaxel and Doxorubicin

Endothelium is the first physiological barrier between blood and tissues and can be injured by physical or chemical stress, particularly by the drugs used in the cancer therapy. Paclitaxel and doxorubicin are frequently used anticancer drugs and their cardiac side effects are well observed in clinical setting. Their side effects on the endothelium are still not clear enough. There are few investigations assessing the damages elicited by the combination use of chemotherapy agents in animal experimental models. The purpose of this study was to examine and compare the side effects of doxorubicin and paclitaxel on endothelium in vivo. The drugs were administered weekly to rats via intraperitoneal injections singly or in combinations. Lastly, aorta endothelium was examined. The most familiar parts of the aorta endothelium are the nucleus, free ribosomes, Weibel-Palada granules, plasmalemmal vesicles, and clear basement membrane. Examination of the endothelium and the related structures revealed some clear degenerative findings. Notably, administration of a paclitaxel and doxorubicin combinations caused the most dramatic change in ultrastructure, which may disrupt many functions of the endothelium.     

Kv4.3 Channel Dysfunction Contributes to Trigeminal Neuropathic Pain Manifested with Orofacial Cold Hypersensitivity in Rats

Trigeminal neuropathic pain is the most debilitating pain disorder but current treatments including opiates are not effective. A common symptom of trigeminal neuropathic pain is cold allodynia/hyperalgesia or cold hypersensitivity in orofacial area, a region where exposure to cooling temperatures are inevitable in daily life. Mechanisms underlying trigeminal neuropathic pain manifested with cold hypersensitivity are not fully understood. In this study, we investigated trigeminal neuropathic pain in male rats following infraorbital nerve chronic constrictive injury (ION-CCI). Assessed by the orofacial operant behavioral test, ION-CCI animals displayed orofacial cold hypersensitivity. The cold hypersensitivity was associated with the hyperexcitability of small-sized trigeminal ganglion (TG) neurons that innervated orofacial regions. Furthermore, ION-CCI resulted in a reduction of A-type voltage-gated K⁺ currents (IA currents) in these TG neurons. We further showed that these small-sized TG neurons expressed Kv4.3 voltage-gated K⁺ channels, and Kv4.3 expression in these cells was significantly downregulated following ION-CCI. Pharmacological inhibition of Kv4.3 channels with phrixotoxin-2 inhibited IA-currents in these TG neurons and induced orofacial cold hypersensitivity. On the other hand, pharmacological potentiation of Kv4.3 channels amplified IA currents in these TG neurons and alleviated orofacial cold hypersensitivity in ION-CCI rats. Collectively, Kv4.3 downregulation in nociceptive trigeminal afferent fibers may contribute to peripheral cold hypersensitivity following trigeminal nerve injury, and Kv4.3 activators may be clinically useful to alleviate trigeminal neuropathic pain.SIGNIFICANCE STATEMENT Trigeminal neuropathic pain, the most debilitating pain disorder, is often triggered and exacerbated by cooling temperatures. Here, we created infraorbital nerve chronic constrictive injury (ION-CCI) in rats, an animal model of trigeminal neuropathic pain to show that dysfunction of Kv4.3 voltage-gated K⁺ channels in nociceptive-like trigeminal ganglion (TG) neurons underlies the trigeminal neuropathic pain manifested with cold hypersensitivity in orofacial regions. Furthermore, we demonstrate that pharmacological potentiation of Kv4.3 channels can alleviate orofacial cold hypersensitivity in ION-CCI rats. Our results may have clinical implications in trigeminal neuropathic pain in human patients, and Kv4.3 channels may be an effective therapeutic target for this devastating pain disorder.     

Investigation of perfusion defects by Q-SPECT/CT in patients with mild-to-moderate course of COVID-19 and low clinical probability for pulmonary embolism

Annals of Nuclear Medicine - Pulmonary embolism is a severe source of mortality and morbidity in patients with severe and critical coronavirus disease 2019. It is not yet clear whether the tendency...     

Correlation of molecular biomarker concentrations between synovial fluid and saliva of the patients with temporomandibular disorders

Objectives

The synovial membrane and fluid are involved in the pathogenesis of temporomandibular joint (TMJ) disorders. This study aims to assess the relationship between matrix metalloproteinase-2 (MMP-2), chemerin and prostaglandin (PGE₂) levels in the synovial fluid (SF) and saliva of patients with TMJ disorder regarding their role in inflammation and the value of being a candidate for predictive biomarkers in the disease. Also, it is aimed to find out whether chemerin’s main function triggers the formation inflammatory cytokine markers in the associated area.

Materials and methods

Thirty-two samples of SF and saliva were obtained from patients with disc displacement without reduction with limited opening (DDWORwLO). Mann-Whitney-U test was used for the comparisons of the biomarker levels in SF and saliva. The correlation between chemerin and BMI (Body Mass Index) is analyzed by non-parametric Spearman’s rho correlation coefficient.

Results

For all of the three biomarkers, statistically significant differences were found between SF and saliva. An unexpectedly high level expression of chemerin was observed in SF. A statistically significant, positive correlation was observed between PGE₂ -MMP-2, and chemerin-PGE₂ in saliva, chemerin and MMP-2 in SF, respectively (p = 0.031, r = 0.382 / p = 0.039, r = 0.366 / p = 0.032, r = 0.379). A positive correlation was determined between saliva and SF levels of PGE₂ (p = 0.016, r = 0.421).

Conclusions

Chemerin, MMP-2, and PGE₂ can play a role as an inflammatory factor for the development of TMJ disorder.

Clinical relevance

The search for molecular markers in TMJ and the inhibition of the associated molecular signaling mechanism is important to reduce joint inflammation and cartilage degradation.