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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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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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.
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Chronic pelvic pain (CPP) is defined as chronic pain and inflammation in the pelvic organs for more than six months. There are wide ranges of clinical presentations, including pelvic pain, painful intercourse, irritable bowel syndrome, and pain during urinating. Chronic pelvic pain syndrome (CPPS) is a subdivision of CPP, and the pain syndrome may be focused within a single organ or more than one pelvic organ. ⋯ Due to the reversible effect of BoNT-A, repeated injection appears to be necessary and effective in reducing symptoms. Adverse effects of BoNT-A may worsen the preexisting conditions, including constipation, stress urinary incontinence, and fecal incontinence. This review summarizes the evidence of BoNT-A treatment for CPPS in animal studies and clinical studies regarding the therapeutic effects of BoNT-A for CPPS in female patients.
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Treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is always challenging for urologists. The main mechanism of the botulinum toxin A (BoNT-A) is inhibition of muscle contraction, but the indirect sensory modulation and anti-inflammatory effect in the bladder also play important roles in treating patients with IC/BPS. Although current guidelines consider BoNT-A injection to be a standard treatment, some practical issues remain debatable. ⋯ For IC/BPS patients with Hunner's lesion, the efficacy of BoNT-A injection remains controversial. Most patients with IC/BPS experience symptomatic relapse at six to nine months after a BoNT-A injection, although repeated injections exhibit a persistent therapeutic effect in long-term follow-up. Further randomized placebo-controlled studies with a larger number of patients are needed to support BoNT-A as standard treatment for patients with IC/BPS.