CD40 ligand and interferon‐γ induce an antimicrobial response against Mycobacterium tuberculosis in human monocytes

The ability of T cells to activate antimicrobial pathways in infected macrophages is essential to host defence against many intracellular pathogens. Here, we compared the ability of two T‐cell‐mediated mechanisms to trigger antimicrobial responses against Mycobacterium tuberculosis in humans, CD40 activation and the release of interferon‐γ (IFN‐γ). Given that IFN‐γ activates a vitamin D‐dependent antimicrobial response, we focused on induction of the key components of this pathway. We show that activation of human monocytes via CD40 ligand (CD40L) and IFN‐γ, alone, and in combination, induces the CYP27b1‐hydroxylase, responsible for the conversion of 25‐hydroxyvitamin D (25D) to the bioactive 1,25‐dihydroxyvitamin D (1,25D), and the vitamin D receptor (VDR). The activation of the vitamin D pathway by CD40L and IFN‐γ results in up‐regulated expression of the antimicrobial peptides, cathelicidin and DEFB4, as well as induction of autophagy. Finally, activation of monocytes via CD40L and IFN‐γ results in an antimicrobial activity against intracellular M. tuberculosis. Our data suggest that at least two parallel T‐cell‐mediated mechanisms, CD40L and IFN‐γ, activate the vitamin D‐dependent antimicrobial pathway and trigger antimicrobial activity against intracellular M. tuberculosis, thereby contributing to human host defence against intracellular infection.     

Network remodeling of intramural coronary resistance arteries in the aged rat: A statistical analysis of geometry

AimsTo identify the geometrical alterations in the age-remodeled rat coronary artery network and to develop a useful technique to analyze network properties in the rat heart.Methods and resultsWe analyzed the networks of the left anterior descendent coronary arteries on in situ perfused hearts of young (3 months) and old (18 months) male rats. All segments and branching over >80 μm diameter were analyzed using 50 μm long cylindrical ring units of the networks. Arterial widening and paucity, increased tortuosity were typical features in the old network. In addition, axis angles deviated more from the mother branches in the old, whereas the diameters of daughter branches fit the Murray law in both groups. The detected changes in the old network resulted in a longer blood flow route for the same direct distance.ConclusionWe developed a useful method to investigate arterial network property changes in the rat heart. Ageing resulted in longer, more tortuous flow route in the LAD network that might be hemodynamically disadvantageous.     

Lithium-associated hyperparathyroidism and hypercalcaemia: A case-control cross-sectional study

Background

Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium.

Methods

112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8±74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels.

Results

PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels.

Limitations

Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism.

Conclusions

Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.     

VEGF Production by Osteoarthritic Chondrocytes Cultured in Micromass and Stimulated by IL-17 and TNF-α

We compared the secretion of vascular endothelial growth factor (VEGF) by chondrocytes isolated from cartilage of patients with osteoarthritis (OA) and maintained in monolayer or in three-dimensional culture. Chondrocytes, immediately after isolation, or after one passage in monolayer culture (subculture), were seeded in monolayer or pelleted in micromasses. Cells cultured differently were immunoassayed for the secretion of VEGF in basal conditions or after stimulation with IL-17, TNF-α or B IL-17+TNF-α. Chondrocytes cultured in micromasses secreted lower levels of VEGF in comparison with those in monolayer culture. In micromass cultures TNF-α was more stimulating than IL-17 and their combined effect was additional. On the basis of alkaline phosphatase/cathespin B activities, primary cultures in micromass, characterized by low VEGF secretion, represented the best condition for maximal cell differentiation. Our results suggest that the culture of chondrocytes in micromasses represents a good condition to study the physiology of these cells to a maximum degree when micromasses are obtained with freshly isolated chondrocytes.     

Proteoglycans in the Control of Tumor Growth and Metastasis Formation

Proteoglycans (PGs) as a whole, or when considering their GAG chains as single entities, are emerging as key regulators of tumor progression. Expectations on using them as putative prognostic markers and potential therapeutic targets are increasing coincidentally. Due to the multitude of biological roles that they may invest and the ample spectrum of cellular processes that they may control, we still need to learn better how they regulate phenomena such as intracellular signaling, proliferation, apoptosis, motility, and drug resistance. Depending on the type, their expression pattern, and the accessibility of their molecular ligands, PGs can either promote or inhibit tumorigenesis. The structural and functional diversity of PGs coupled with their ubiquitous abundance place them at the crossroads of many critical steps within the metastatic cascade. As this phenomenon is the pivotal factor for patient survivals, particular attention should be given to the understanding of how PGs govern metastasis formation.     

Young Adults with Autism Spectrum Disorder and the Criminal Justice System

Journal of Autism and Developmental Disorders - This study describes charges, outcomes, and recidivism in both the juvenile and adult criminal justice systems (CJS) for young adults aged 17 to...     

Anti-thyroid antibodies and thyroid dysfunction in rheumatoid arthritis: Prevalence and clinical value

Objectives: The aim of this study was to assess thyroid function as well as the prevalence and clinical value of anti-thyroid antibodies in patients with rheumatoid arthritis (RA).

Methods: Seventy patients with active RA (ACR criteria), 9 males and 61 females, mean age 47 years (range 15–77) were analyzed. Anti-thyroperoxidase (TPOAb) and anti-thyroglobulin antibodies (TgAb) were tested using radioimmunoassay. Free thyroxine (FT4) and free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) serum levels were measured using electro-immunochemiluminescence (ECLIA, Elecsys Roche). Clinical variables, including tender and swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP) and antinuclear antibodies (ANA) were also evaluated. Statistics were performed by the SPSS statistical software for Windows.

Results: Twenty-six patients (37%) with RA were positive for TPOAb and 16 (23%) for TgAb. In 5 (7.1%) patients TSH level was slightly elevated, ranging between 4.52 and 15.65 UI/ml. The increase of TSH levels was associated with normal FT4 in 3 cases (4.2%) and with reduced FT4 in 2 cases (2.8%). One patient (1.5%) had low TSH serum value along with normal FT4. No differences in clinical and serological data between anti-thyroid positive and negative patients were observed.

Conclusion: Our study shows an increased prevalence of anti-thyroid antibodies in RA patients with a low prevalence of hormonal alterations. However, anti-thyroid antibodies do not seem to identify any peculiar RA phenotype.     

Beneath the surface: hyper-connectivity between caudate and salience regions in ADHD fMRI at rest

European Child & Adolescent Psychiatry - Attention-Deficit/Hyperactivity Disorder (ADHD) comprises disturbances in attention, emotional regulation, and reward-related processes. In spite of the...