The pulmonary involvement in rheumatic diseases: pulmonary effects of ankylosing spondylitis and its impact on functionality and quality of life

Rheumatic diseases are chronic inflammatory diseases which cause mild to severe functional loss and disability due to articular and extra-articular manifestations. One common form -ankylosing spondylitis (AS)- affects mainly the axial skeleton and sacroiliac joints, and certain extra-articular organs. The pulmonary involvement is a known manifestation of AS and emerges either in the form of interstitial lung disease or in the form of restricted pulmonary functions. The aim of this study is to determine the pulmonary functions in AS patients and to assess its relationship with quality of life, functionality and disease activity. Thirty-six AS patients and 34 healthy volunteers were recruited for the study. A detailed examination, pulmonary function tests, smoking inquiry and quality of life questionnaire were performed on all participants. Also patients were requested to complete functionality and disease activity indexes. The outcomes showed that 15 (41.7%) AS patients had pulmonary involvement: twelve patients with restrictive patterns, one with obstructive pattern, and two with both restrictive and obstructive patterns. Decreased forced expiratory volume in one second was associated with deteriorated functionality (p < 0.05). Decreased chest expansion was also accompanied with decreased forced vital capacity (p < 0.05). There was no statistically significant difference between the smoking and non-smoking patients in regard to disease activity, functionality and pulmonary function test variables (p > 0.05). In conclusion, the pulmonary involvement is common in AS and might have disturbed functionality and the quality of life in AS patients.     

Heterogeneity of Coronary Plaque Morphology and Natural History: Current Understanding and Clinical Significance

Purpose of Review

Despite the important progress in identifying high-risk atherosclerotic plaques, many key elements are elusive. Advanced imaging modalities provide valuable information about the anatomic and functional plaque characteristics and underscore the presence of multiple plaque morphologies. However, how the heterogeneity of atherosclerotic plaque can alter our current understanding of coronary artery disease is not fully understood.

Recent Findings

Along the length of an individual plaque, the morphology patterns display marked heterogeneity. Contrary to previous beliefs, plaque morphology is also highly dynamic over time, with the vast majority of high-risk plaques becoming quiescent and mild plaques becoming severely obstructive in a short period of time. Endothelial shear stress, a local hemodynamic factor known for its critical effects in plaque initiation and progression, also displays longitudinal heterogeneity contributing to the arterial wall response in all time points.

Summary

Risk stratification of plaques based on the morphological characteristics at one region of the plaque, usually the minimal lumen diameter, and at one point in time may be misleading. The evaluation of both morphological and hemodynamic characteristics along the length of a plaque will improve the risk assessment of individual plaques.

     

L-carnitine alleviates sciatic nerve crush injury in rats：functional and electron microscopy assessments

Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.     

Antioxidant effects of vitamin D on lacrimal glands against high dose radioiodine-associated damage in an animal model

Purpose: To evaluate antioxidant effects of active vitamin D (calcitriol) against high-dose radioiodine (RAI) therapy-associated damage of lacrimal gland.

Materials and methods: Wistar albino rats were used and divided into three groups randomly (n?=?12/group). The first group was appointed as the negative control group and received no RAI or medication. The second group was appointed as the positive control group that only received 3?mCi/kg (111 MBq/kg) RAI via gastric gavage and the last group was the treatment group that received 3?mCi/kg RAI via same method and calcitriol (200?ng/kg/day) via intraperitoneal administration. Seven days after RAI administration, bilateral intraorbital (IG), extraorbital (EG) and Harderian (HG) glands were removed for the evaluations of histopathologic, tissue cytokine, total oxidant status (TOS) and total antioxidant status (TAS).

Results: RAI led to significant increase in tissue TOS, TNF-α, IL-6 levels and significant decrease in IL-10 and TAS levels (p?p?p?p?=?0.049), periductal fibrosis in EG and HG (p?=?0.049 and 0.038, respectively), abnormal cell outlines in EG and HG (p?=?0.020 and 0.011, respectively) and variation in cell size in the IG and the HG (p?=?0.003 and 0.049 respectively).

Conclusions: RAI caused significant oxidative stress and inflammation in lacrimal glands. Vitamin D demonstrated potent anti-inflammatory, antioxidant and radio-protective effects on lacrimal glands in histopathologic, tissue cytokine and oxidant/antioxidant level evaluations.     

Are trauma and dissociation related to treatment resistance in patients with obsessive–compulsive disorder?

Objective

Previous research has indicated a relation between obsessive–compulsive disorder (OCD), childhood traumatic experiences and higher levels of dissociation that appears to relate to negative treatment outcome for OCD. The aim of the present study is to investigate whether childhood trauma and dissociation are related to severity of OCD in adulthood. We also intend to examine the association between treatment resistance, dissociation, and each form of trauma.

Methods

Participants included 120 individuals diagnosed with OCD; 58 (48.3 %) of them met the criteria for treatment-resistant OCD (resistant group), whereas the other 62 (51.7 %) were labeled as responder group. The intensity of obsessions and compulsions was evaluated using Yale-brown obsessive–compulsive scale (Y-BOCS). All patients were assessed with the traumatic experiences checklist, dissociative experiences scale, beck depression inventory, and beck anxiety inventory.

Results

Controlling for clinical variables, resistant group had significantly higher general OCD severity, anxiety, depression, trauma, and dissociation scores than the responders. Correlation analyses indicated that Y-BOCS scores were significantly related to severity of dissociation, anxiety, depression, and traumatic experiences. In a logistic regression analysis with treatment resistance as a dependent variable, high dissociation levels, long duration of illness, and poor insight emerged as relevant predictors, but gender, levels of anxiety, depression, and traumatic experiences did not.

Conclusions

Our results suggest that dissociation may be a predictor of poorer treatment outcome in patients with OCD; therefore, a better understanding of the mechanisms that underlie this phenomenon may be useful. Future longitudinal studies are warranted to verify if this variable represents predictive factors of treatment non-response.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).