The effects of vitamin D on acute viral respiratory infections: A rapid review.

BRIEF OVERVIEW: Current evidence suggests vitamin D replacement may reduce risk for acute respiratory tract infections (ARTI) in people with deficiency or insufficiency, although the effects of supplementation on incidence and severity of ARTI in the general population remain unknown. Oral vitamin D supplemzentation taken at routine doses appears to be generally safe and well tolerated. VERDICT: Current experimental evidence remains inconclusive regarding the effects of vitamin D supplementation in the general population for the prevention and treatment of acute respiratory tract infections (ARTI). There is also insufficient evidence to draw conclusions regarding the impact of vitamin D supplementation on the severity or duration of ARTI, nor on outcomes related to lung injury or hospitalization from ARTI. Based on this rapid review, sources of significant heterogeneity in published clinical trials include: differences study populations, inconsistent assessment of serum status at baseline, dosing variability, varying routes of administration, and/or inconsistent definitions of outcome measures. Experimental evidence and observations in large cohorts are generally consistent that vitamin D deficiency (<50 nmol/L [<20 ng/mL]) and insufficiency (<75 nmol/L [<30 ng/mL]) of serum 25-hydroxycholecalciferol (25-OHD) concentration is associated with increased risk of ARTI, and supplementation for those with deficiency/insufficiency may lead to clinically meaningful reductions in the incidence of ARTI. In this rapid review, vitamin D was primarily administered as oral supplementation, and findings suggested significant differences in daily oral dosing compared to periodic bolus dosing. Based on the available experimental evidence, vitamin D supplementation appears to have a high margin of safety with very few adverse events reported in children or adults from a variety of dosing strategies. Future clinical trials on vitamin D should consider the sources of heterogeneity in the existing experimental research and design trials that account for baseline status, evaluate the potential for prevention and treatment in at risk populations, standardize dosing strategies, assess product quality, assess outcomes according to gold standard definitions/diagnostic methods, and delineate viral ARTI from other causes when possible. The available mechanistic evidence related to immunological requirements for adequate vitamin D, the availability of observational and experimental evidence suggestive of clinically meaningful benefits (especially in deficient/insufficient participants), and the high margin of safety, should make vitamin D a high priority for additional clinical research during the current COVID-19 pandemic.

Persistent inactivation of macrophage cyclooxygenase-2 in mycobacterial pulmonary inflammation.

The induction of cyclooxygenase-2 (COX-2) in tissue macrophages (MØ) increases prostaglandin E(2) (PGE(2)) release, potentially down-regulating granulomatous inflammation. In response to Mycobacteria, local MØ express COX-2, which is either nuclear envelope (NE)-associated or NE-dissociated. Persistent mycobacterial pulmonary inflammation is characterized by alveolar MØ expressing NE-dissociated (inactive) COX-2 without release of PGE(2). In this study, we examined COX-2 in alveolar MØ after intranasal exposure to heat-killed Mycobacterium bovis BCG (HK-BCG). After administration, whole lungs of C57Bl/6 mice were lavaged with saline; COX-2 expression and PGE(2) release by alveolar MØ and tumor necrosis factor (TNF)-alpha and nitric oxide levels in the lung lavage were monitored. Normal alveolar MØ had undetectable levels of COX-2 on Western blots. However, 1 day after intranasal administration, almost all alveolar MØ had phagocytosed HK-BCG and expressed NE-dissociated COX-2 without any increase in the release of PGE(2). At 28 days after intranasal administration, 68% of alveolar MØ still contained both BCG and the NE-dissociated form of COX-2. NE-associated (active) COX-2 was not observed in alveolar MØ. In contrast, 7 days after intraperitoneal injection of HK-BCG, peritoneal MØ containing HK-BCG were no longer detected. At 28 days after intranasal administration, TNF-alpha and nitrite levels in the lung lavage fluid were significantly higher than those in controls. Our results indicate that mycobacterial pulmonary inflammation is associated with suppressed PGE(2) production by alveolar MØ, with expression of COX-2 dissociated from the NE.

Effects of extracts from Italian medicinal plants on planktonic growth, biofilm formation and adherence of methicillin-resistant Staphylococcus aureus.

AIM OF STUDY: One-third of botanical remedies from southern Italy are used to treat skin and soft tissue infection (SSTI). Staphylococcus aureus, a common cause of SSTI, has generated increasing concern due to drug resistance. Many plants possess antimicrobial agents and provide effective remedies for SSTI. Our aim was to investigate plants from different ethnobotanical usage groups for inhibition of growth and biofilms in methicillin-resistant Staphylococcus aureus (MRSA). MATERIALS AND METHODS: Three groups were assessed: plant remedies for SSTI, plant remedies not involving the skin, and plants with no ethnomedical application. We screened 168 extracts, representing 104 botanical species, for activity against MRSA (ATCC 33593). We employed broth dilution methods to determine the MIC after 18 h growth using an optical density (OD 600 nm) reading. Anti-biofilm effects were assessed by growing biofilms for 40 h, then fixing and staining with crystal violet. After washing, 10% Tween 80 was added and OD 570 nm readings were taken. RESULTS: Extracts from 10 plants exhibited an IC50

Depletion of cellular cholesterol enhances macrophage MAPK activation by chitin microparticles but not by heat-killed Mycobacterium bovis BCG.

When macrophages phagocytose chitin (N-acetyl-d-glucosamine polymer) microparticles, mitogen-activated protein kinases (MAPK) are immediately activated, followed by the release of Th1 cytokines, but not IL-10. To determine whether phagocytosis and macrophage activation in response to chitin microparticles are dependent on membrane cholesterol, RAW264.7 macrophages were treated with methyl-beta-cytodextrin (MBCD) and stimulated with chitin. These results were compared with the corresponding effects of bacterial components including heat-killed (HK) Mycobacterium bovis bacillus Calmette-Guèrin (BCG) and an oligodeoxynucleotide (ODN) of bacterial DNA (CpG-ODN). The MBCD treatment did not alter chitin binding or the phagocytosis of chitin particles 20 min after stimulation. At the same time, however, chitin-induced phosphorylation of cellular MAPK was accelerated and enhanced in an MBCD dose-dependent manner. The increased phosphorylation was also observed for chitin phagosome-associated p38 and ERK1/2. In contrast, CpG-ODN and HK-BCG induced activation of MAPK in MBCD-treated cells at levels comparable to, or only slightly more than, those of control cells. We also found that MBCD treatment enhanced the production of tumor necrosis factor-alpha (TNF-alpha) and the expression of cyclooxygenase-2 (COX-2) in response to chitin microparticles. In neither MBCD- nor saline-treated macrophages, did chitin particles induce detectable IL-10 mRNA synthesis. CpG-ODN induced TNF-alpha production, and COX-2 expression were less sensitive to MBCD treatment. Among the agonists studied, our results indicate that macrophage activation by chitin microparticles was most sensitive to cholesterol depletion, suggesting that membrane structures integrated by cholesterol are important for physiological regulation of chitin microparticle-induced cellular activation.

Panax ginseng.

The herbal remedies referred to as "ginseng" are derived from the roots of several plants. One of the most commonly used and researched of the ginsengs is Panax ginseng, also called Asian or Korean ginseng. The main active components of Panax ginseng are ginsenosides, which have been shown to have a variety of beneficial effects, including anti-inflammatory, antioxidant, and anticancer effects. Results of clinical research studies demonstrate that Panax ginseng may improve psychologic function, immune function, and conditions associated with diabetes. Overall, Panax ginseng appears to be well tolerated, although caution is advised about concomitant use with some pharmaceuticals, such as warfarin, oral hypoglycemic agents, insulin, and phenelzine. Panax ginseng does not appear to enhance physical performance. Products with a standardized ginsenoside concentration are available.