Toxins
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Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common pathogens of mastitis, and S. aureus generally causes subclinical mastitis which is more persistent and resistant to treatment. Peptidoglycan (PGN) and lipoteichoic acid (LTA) are cell wall components of S. aureus. Although the roles of PGN and LTA in causing inflammation are well studied, the epigenetic mechanisms of the effects of PGN and LTA on the inflammation and lactation remain poorly understood. ⋯ LTA and PGN + LTA induced hypomethylation of global DNA by suppressing DNA methyltransferase (DNMT) activity. PGN and LTA, alone or combined, decreased the mRNA expression of casein genes (CSN1S1, CSN2, and CSN3) and the expression of two caseins (CSN2 and CSN3), and reduced histone H3 acetylation by suppressing histone acetyltransferase (HAT) activity and promoting histone deacetylase (HDAC) activity. Collectively, this study revealed that PGN and LTA induced inflammation probably due to decreasing DNA methylation through regulating DNMT activity, and decreased lactation possibly through reducing histone H3 acetylation by regulating HAT and HDAC activity in bovine mammary epithelial cells.
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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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Comparative Study
Botulinum Toxin Injection in Children with Hemiplegic Cerebral Palsy: Correction of Growth through Comparison of Treated and Unaffected Limbs.
Botulinum toxin type A (BoNT-A) injections in children with cerebral palsy (CP) may negatively affect muscle growth and strength. We injected BoNT-A into the affected limbs of 14 children (4.57 ± 2.28 years) with hemiplegic CP and exhibiting tip-toeing gait on the affected side and investigated the morphological alterations in the medial head of the gastrocnemius muscle (GCM). We assessed thickness of the GCM, fascicle length, and fascicle angle on the affected and unaffected sides at baseline at 4 and 12 weeks after BoNT-A injections. ⋯ However, the percentage of fascicle length and angle in treated limbs showed no significant change from baseline 4 and 12 weeks after the injection. BoNT-A injections might reduce muscle thickness in children with spastic hemiplegic CP. Fascicle length and angle might not be affected by BoNT-A injections after correction of normal growth of the children.
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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.
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Review
Promise and the Pharmacological Mechanism of Botulinum Toxin A in Chronic Prostatitis Syndrome.
Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) has a negative impact on the quality of life, and its etiology still remains unknown. Although many treatment protocols have been evaluated in CP/CPPS, the outcomes have usually been disappointing. ⋯ Animal studies demonstrated that BoNT-A, a potent inhibitor of neuroexocytosis, impacts the release of sensory neurotransmitters and inflammatory mediators. This pharmacological action of BoNT-A showed promise of relieving the pain of CP/CPPS in placebo-controlled and open-label BoNT-A and has the potential to serve as an adjunct treatment for achieving better treatment outcomes in CP/CPPS patients.