Toxins
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Review
Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization.
Chronic kidney disease (CKD) affects more than 10% of the world population and leads to excess morbidity and mortality (with cardiovascular disease as a leading cause of death). Vascular calcification (VC) is a phenomenon of disseminated deposition of mineral content within the media layer of arteries preceded by phenotypic changes in vascular smooth muscle cells (VSMC) and/or accumulation of mineral content within the atherosclerotic lesions. Medial VC results in vascular stiffness and significantly contributes to increased cardio-vascular (CV) morbidity, whereas VC of plaques may rather increase their stability. ⋯ All mentioned toxins promote VC by several mechanisms, including: Transdifferentiation and apoptosis of VSMC, dysfunction of endothelial cells, oxidative stress, interaction with local renin-angiotensin-aldosterone system or miRNA profile modification. Several attractive methods of gut microbiota manipulations have been proposed in order to modify their metabolism and to limit vascular damage (and VC) triggered by uremic toxins. Unfortunately, to date no such method was demonstrated to be effective at the level of "hard" patient-oriented or even clinically relevant surrogate endpoints.
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Botulinum neurotoxin type A (BoNT/A) injections have to be administered repeatedly to achieve a rather stable, high level of improvement. This study aimed to take a look at changes in the daily routine of a BoNT/A outpatient clinic due to the SARS-CoV-2 pandemic lockdown, analyze the impact of SARS-CoV-2-induced re-injection delay on outcomes in patients with cervical dystonia (CD) (n = 36) and four other disease entities (n = 58), and study the influence of covariables, including previous injections and doses. For the present observational study, the first 100 patients who were scheduled to have an appointment between April 20 and May 18 during the partial lockdown and also had been treated regularly before the lockdown were recruited. ⋯ In CD patients, the physician´s rating of CD worsening by the TSUI score (ATUSI-PTSUI) was significantly correlated with general worsening (DwP) and the TSUI at the last visit (PTSUI). A small delay of a few weeks led to a similar worsening of symptoms in CD and all other disease entities and to relapse on a higher level of severity. This relapse can only be compensated by continuous treatment up to at least 1 year until patients reach the same level of treatment efficacy as that before the SARS-CoV-2 pandemic.
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The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. ⋯ The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.
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The mammary gland of the cow is particularly susceptible to infections of a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative bacteria. The endotoxins of these pathogenic bacteria include peptidoglycan (PGN), lipoteichoic acid (LTA) and lipopolysaccharide (LPS), and they are the pathogen-associated molecular patterns (PAMPs) to induce mastitis. LPS can directly inhibit proliferation and milk fat synthesis of bovine mammary epithelial cells (BMECs) while inducing mastitis, but it is unclear whether PGN and LTA also have such effects. ⋯ Co-stimulation with PGN, LTA and LPS significantly increased the expression of fat acid synthesis-related genes and the intracellular NEFAs, but decreased intracellular TG, compared with sole LPS stimulation. Collectively, PGN, LTA and LPS showed an additive effect on inhibiting proliferation of BMECs. The promoting role of LTA in fatty acid synthesis might offset the negative effects of LPS in this regard, but co-stimulation with PGN, LTA and LPS significantly decreased intracellular TG content.
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Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. ⋯ A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone-vascular axis may open avenues for novel therapeutics, including nutriceuticals.