Distress tolerance and special alcohol metacognitions behave differently in the association of negative affect with alcohol-related patterns in men with problematic alcohol use in the abstinence phase

Negative affect may be related to alcohol-related patterns (e.g., craving and problematic alcohol use). Distress intolerance and positive and negative alcohol-related metacognitions may be underlying mechanisms in this link. This study aimed to evaluate the effect of negative affect including depressive, anxious, and stress symptoms on alcohol craving and problematic alcohol use via the paths of distress tolerance and both positive and negative alcohol-related metacognitions. Three hundred men with problematic alcohol use during the abstinence phase completed psychological and clinical measures. Results showed that craving and negative alcohol metacognitions mediated the relationship between negative affect and problematic alcohol use. Negative affect had a direct and positive effect on craving and indirect effect via distress intolerance and positive alcohol metacognitions. In turn, distress intolerance and positive alcohol metacognitions indirectly and positively affected problematic alcohol use via craving. The study indicates that distress tolerance and distinct alcohol metacognitions may be differently related to various patterns of alcohol-related problems, such that alcohol drinkers with high levels of negative affect, distress intolerance, and positive alcohol metacognitions show higher levels of craving, while high negative affect in relation to high negative alcohol metacognitions and alcohol craving is related to the perpetuation of alcohol use or problematic alcohol use.     

Role of calcineurin in the regulation of human lung mast cell and basophil function by cyclosporine and FK506

BACKGROUND AND PURPOSE: Cyclosporine and FK506 are thought to act by targeting the Ca2+-dependent protein phosphatase, calcineurin. The aim of the present study was to determine whether cyclosporine and FK506 stabilize mast cells and basophils by interacting with calcineurin. EXPERIMENTAL APPROACH: The effects of cyclosporine and FK506 on the IgE-mediated release of histamine from mast cells and basophils were evaluated. The presence of calcineurin in cells was determined by Western blotting. Ca2+-dependent protein phosphatase activities were assessed in cell extracts using a synthetic phosphorylated peptide that is known to serve as a substrate for calcineurin. KEY RESULTS: FK506 was about 100-fold more potent than cyclosporine as an inhibitor of IgE-dependent histamine release from mast cells and basophils. Immunoblotting of solubilized preparations of purified cells demonstrated the presence of calcineurin in mast cells and basophils. In enzyme assays, mast cells expressed approximately 7-fold higher Ca2+-dependent protein phosphatase activity than basophils. Whereas cyclosporine effectively inhibited Ca2+-dependent protein phosphatase activity in cell extracts, FK506 was considerably less effective. CONCLUSIONS AND IMPLICATIONS: FK506 and cyclosporine inhibit the stimulated release of histamine from mast cells and basophils. However, the ability of cyclosporine, but not FK506, to inhibit Ca2+-dependent protein phosphatase activity questions whether FK506 stabilizes mast cells and basophils by interacting with calcineurin.     

Alexithymia influences craving through facets of emotion regulation in alcoholic patients

There is evidence that alexithymia is related to alcohol problems. However, no study has been conducted to show whether emotion regulation (ER) subscales such as reappraisal and suppression mediate the relationship between alexithymia and craving. The aim of this study was to evaluate the effects of ER subscales (i.e., reappraisal and suppression) as mediators on the relationships between alexithymia and subscales of craving (i.e., obsessive and compulsive subscales). A total of 205 alcoholic outpatients completed the Farsi version of the Toronto Alexithymia Scale (FTAS-20), the Emotion Regulation Questionnaire (ERQ), the Obsessive Compulsive Drinking Scale (OCDS), the Alcohol Use Disorders Identification Test (AUDIT), and the Beck Depression Inventory-II (BDI-II). Results revealed that alexithymia indirectly influenced obsessive and compulsive cravings through both paths of ER decreased reappraisal and increased suppression subscales. Also, the relations of alexithymia to obsessive and compulsive cravings through the mediation pathway of decreased reappraisal were stronger than the path of suppression. It was concluded that low reappraisal and high suppression seem to be important in predicting obsessive and compulsive cravings for alcoholics with alexithymia. This suggests that the efforts based on increasing reappraisal and decreasing suppression may be important in reducing craving in alcoholic patients.     

Gallic and carnosic acids improve quality of frozen‐thawed ram spermatozoa

The objective was to determine effects of gallic acid (GA) and carnosic acid (CA), present in carob pods and rosemary extract respectively, on frozen‐thawed ram spermatozoa. Thirty ejaculates were collected from five Merino rams, pooled, diluted in Tris‐based extender and divided into five equal portions containing: 0.05 or 2 mM of GA; 0.05 or 0.2 mM of CA; or no additive (control). Extended semen was equilibrated at +4°C, loaded into straws, held 5 cm above liquid nitrogen for 12 min then plunged. Computer‐aided sperm analysis was used to assess motility, whereas flow cytometry was used to assess high mitochondrial membrane potential (HMMP) and percentages of spermatozoa with plasma membrane and acrosome integrity (PMAI). Spermatozoa supplemented with 2 mM GA had greater total motility than control spermatozoa (39.9 ± 3.01 vs. 29.2 ± 1.31%, mean ± SEM, p < .05). The PMAI was greatest in 0.2 mM CA (13.3 ± 0.68%), whereas HMMP was highest in 0.05 mM CA but lowest in control (22.9 ± 4.95 and 11.4 ± 3.64% respectively; p < .05). In conclusion, for cryopreservation of ram semen in Tris‐based extender, supplementation with 2 mM GA increased post‐thaw motility, whereas supplementation with 0.05 mM CA enhanced mitochondrial function.     

Effects of fostriecin on β2-adrenoceptor-driven responses in human mast cells

As part of the intracellular processes leading to mast cell and basophil activation, phosphorylation of key substrates is likely to be important. These processes, mediated by phosphatases, are responsible for regulating phosphorylation. The aim of the present study was to determine effects fostriecin – a selective inhibitor of PP2A (protein phosphatase-2) – on β₂-adrenoceptor-driven responses in human mast cells. Here, the effects of fostriecin (PP inhibitors) on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization were investigated. Long-term incubation (24?h) of mast cells with fostriecin (10^?6 M) resulted in a significant (p 2-adrenoceptors.     

The associations of obsessive–compulsive symptom dimensions and general severity with suicidal ideation in patients with obsessive–compulsive disorder: The role of specific stress responses to COVID-19

Suicidal ideation is prevalent in patients with obsessive–compulsive disorder (OCD); but, during COVID-19, it may be increased. The present study aimed to examine the effects of obsessive–compulsive (OC) symptom dimensions and OCD severity on suicidal ideation by considering the role of stress responses in reaction to COVID-19 in a clinical sample of patients with OCD. In a cross-sectional study, 304 patients with OCD completed measures of OC symptom dimensions, OCD severity, general mental health (depression and anxiety), and COVID-19-related stress. Results showed that after controlling for depression, anxiety, comorbidity, and lifetime suicide attempts, the OC symptom dimensions of responsibility for harm and unacceptable obsessional thoughts as well as general severity had indirect effects on suicidal ideation through the specific stress responses to COVID-19, including traumatic stress and compulsive checking. The study shows that OCD patients with specific OC symptom dimensions and severe OCD are more likely to have suicidal ideation during the pandemic. Further, the specific stress responses to COVID-19 may be an underlying mechanism. Clinicians should carefully assess suicidal ideation in patients with OCD who experience responsibility for harm and unacceptable thoughts, particularly during the pandemic.     

Treating acute ischemic stroke

Acute ischemic stroke (AIS) is a common disorder that has only one associated approved therapy: intravenous tissue plasminogen activator (iv t-PA). A limiting factor to the use of iv t-PA is that it must be initiated within 3 h of stroke onset. Efforts to expand the therapeutic time window are underway and include image evaluation of the ischemic penumbra to target those patients who are most appropriate for treatment. Intra-arterial t-PA is also used only in some treatment centers despite convincing proof of efficacy of this therapy. Devices to restore perfusion that have been approved in the US for recanalization exist, but these are not approved for use in stroke therapy. Many neuroprotective drugs have been evaluated as potential acute stroke therapies, but none have shown efficacy, hence the future of neuroprotection as a strategy for acute ischemic stroke therapy remains uncertain.     

Regulation of immunoglobulin E-mediated secretion by protein phosphatases in human basophils and mast cells of skin and lung.

A wide range of serine/threonine protein phosphatase (PP) inhibitors were studied for effects on the immunoglobulin E (IgE)-mediated release of histamine from human lung mast cells, human skin mast cells and basophils. Okadaic acid (OA) inhibited the release of histamine from all three cell types in a concentration-dependent manner. Two structural analogues of okadaic acid, okadaol and okadaone, known to be less active than the parent molecule as inhibitors of PP, were less active than okadaic acid as inhibitors of histamine release in these three cell types. A number of PP inhibitors, showing differences in selectivity for PP1 and PP2A, were also evaluated. Calyculin, which is roughly equipotent as a PP1 and PP2A inhibitor, attenuated the release of histamine from all three cell types. Similarly, tautomycin (TAU), which shows greater selectivity for PP1 over PP2A, was also effective at inhibiting histamine release in all three cell types. In contrast, fostriecin, which is very much more potent as an inhibitor of PP2A over PP1, was ineffective as an inhibitor in all three cell types. These data indicate that the regulation of mediator release by PPs is similar in lung mast cells, skin mast cells and basophils. Moreover, the data suggest that PP1 is important in the control of cellular activity.