Unraveling the parahormetic mechanism underlying the health-protecting effects of grapeseed procyanidins.

Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against a spectrum of inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric and dimeric PACs undergo some absorption within the gastrointestinal tract, their larger oligomeric and polymeric counterparts are not bioavailable. However, higher molecular weight PACs engage with the colonic microbiota, fostering the production of bioavailable metabolites that undergo metabolic processes, culminating in the emergence of bioactive agents capable of modulating physiological processes. Within this investigation, a GSE enriched with polymeric PACs was employed to explore in detail their impact. Through comprehensive analysis, the present study unequivocally verified the gastrointestinal-mediated transformation of medium to high molecular weight polymeric PACs, thereby establishing the bioaccessibility of a principal catabolite termed 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL). Notably, our findings, encompassing cell biology, chemistry and proteomics, converge to the proposal of the notion of the capacity of VL to activate, upon oxidation to the corresponding quinone, the nuclear factor E2-related factor 2 (Nrf2) pathway-an intricate process that incites cellular defenses and mitigates stress-induced responses, such as a challenge brought by TNFα. This mechanistic paradigm seamlessly aligns with the concept of para-hormesis, ultimately orchestrating the resilience to stress and the preservation of cellular redox equilibrium and homeostasis as benchmarks of health.

Vitamin D: a steroid hormone with progesterone-like activity.

OBJECTIVE: This review is aimed at demonstrating the progesterone-like activity exerted by the active form of vitamin D, or calcitriol (1,25(OH)2D). To achieve this outcome, we compared the effects in vivo and in vitro exerted by progesterone and vitamin D, with a special focus on the female reproductive system and pregnancy. MATERIALS AND METHODS: This is a literature review of the most important articles published in English on vitamin D as a hormone, mainly found by MEDLINE. Furthermore, a section of our review contains some unpublished data, concerning the analysis in silico of the similarities between the steric structure of progesterone and calcitriol, based on the availability of the experimental structures of progesterone and vitamin D3 receptors in complex with their physiological ligands in the RCSB Protein Data Bank. RESULTS: Vitamin D was shown to exert many physiological activities during the very early stages of gestation in perfect synchrony with progesterone. Both the molecules mutually help and reinforce the activity exerted by each one. A little bit later than progesterone is released, vitamin D secretion rises, but only if pregnancy occurs. Calcitriol contributes to prepare the endometrium to be receptive. Moreover, it supports the implantation process and the course of pregnancy through different but similar pathways to those used by progesterone, giving rise to a significant synergy of action. It is increasingly evident that vitamin D gives an essential support from the luteal phase onwards. CONCLUSIONS: Based on the evidence displayed in this review we may define appropriately vitamin D as a steroid hormone with progesterone-like activity.

Peripheral neuropathy associated with primary Sjögren's syndrome.

Clinical and electrophysiological signs of peripheral neuropathy were found in 10 of 46 patients (21.7%) with primary Sjögren's syndrome, symmetric polyneuropathy in seven (mainly sensory in five, mainly autonomic in two), sensory neuronopathy in two patients, and mononeuropathy multiplex in one patient. Peripheral neuropathy was the presenting manifestation in five patients (10.9%). Onset of the disease after 50 years was significantly more common in the polyneuropathy group (six of seven) than in non-neuropathic patients with primary Sjögren's syndrome (14 of 36; p = 0.034). No other difference in clinical or laboratory variables between neuropathic and non-neuropathic patients with primary Sjogren's syndrome was found. Neurophysiological study showed variable findings predominantly suggesting an axonopathy. Nerve biopsy showed moderate remyelination and regeneration in four patients, and fibre loss, mainly of large size, in three. Necrotising vasculitis was not seen but alterations of the endoneurial microvessels were prominent.

Spondylodiscitis and ankylosing spondylitis: HLA typing and nosological implications.

Nine cases from among 64 patients with ankylosing spondylitis (AS) are described. In addition to bilateral sacroiliitis these cases had a peculiar type of spondylodiscitis characterised by quite diffuse and marked sclerosis of multiple vertebral bodies, with only minimal erosions of the adjacent vertebral plates while classical syndesmophytosis was absent. The antigen HLA-B27 was found only in 1 of these 9 cases. This type of spondylodiscitis could discriminate among all the patients with AS a subgroup with a peculiar clinical pattern and a probably distinctive pathological mechanism.