YokoCo

Hesperidin possesses myriads of pharmacological benefits, including anti-inflammatory and antioxidant properties. Herein, we speculated that the described pharmacological benefits of hesperidin might be due to its potentiating action on SIRT1; thereby, inhibition of NOX4. We developed diabetic neuropathy in Sprague-Dawley rats by feeding them a high-fat diet (HFD) for 12 weeks. We checked the effect of hesperidin on the level of oxidative stress, inflammatory markers, NOX4, and SIRT1 by biochemical analysis, histopathology, immunoblotting, immunocytochemistry, and real-time qPCR in HFD-fed rats and Palmitate (Pal) encountered rat glial C6 cells. Hesperidin administration improved mechanical, thermal allodynia, and glucose homeostasis. There was a decrease in oxidative stress and inflammation and an enhanced level of antioxidant enzymes. Besides, the expression of NOX4 was down-regulated, while SIRT1 was upregulated. Interestingly, hesperidin treatment protected them from oxidative and inflammatory damage by upregulating SIRT1 and inhibiting NOX4 expression.

Traumatic fractures of the thoracolumbar spine are common. Their management considers the fracture type according to the various classifications in existence, as well as the patient's background and age. In some cases, the occurrence of a fracture on a spine with an unoperated scoliotic deformity can be observed. This entity, not described in the literature, can pose a therapeutic challenge and is not present in any existing treatment algorithm. The main objective of this work was to describe the characteristics and management of vertebral fractures in patients with unoperated idiopathic scoliosis.

There is considerable clinical evidence that topiramate (TPM) has a high potential in the treatment of refractory and super-refractory status epilepticus (RSE, SRSE). Because TPM is only approved for oral administration, it is applied as suspension via a nasogastric tube for SE treatment. However, this route of administration is impractical in an emergency setting and leads to variable absorption with unpredictable plasma levels and time to peak concentration. Thus, the development of an intravenous (i.v.) solution for TPM is highly desirable. Here we present data on two parenteral formulations of TPM that are currently being developed. One of these solutions is using sulfobutylether-β-cyclodextrin (SBE-β-CD; Captisol®) as an excipient. A 1% solution of TPM in 10% Captisol® has been reported to be well tolerated in safety studies in healthy volunteers and patients with epilepsy or migraine, but efficacy data are not available. The other solution uses the FDA- and EMA-approved excipient amino sugar meglumine. Meglumine is much more effective to dissolve TPM in water than Captisol®. A 1% solution of TPM can be achieved with 0.5-1% of meglumine. While the use of Captisol®-containing solutions is restricted in children and patients with renal impairment, such restrictions do not apply to meglumine. Recently, first-in-human data were reported for a meglumine-based solution of TPM, indicating safety and efficacy when used as a replacement for oral administration in a woman with epilepsy. Based on the multiple mechanisms of action of TPM that directly target the molecular neuronal alterations that are thought to underlie the loss of efficacy of benzodiazepines and other anti-seizure medications during prolonged SE and its rapid brain penetration after i.v. administration, we suggest that parenteral (i.v.) TPM is ideally suited for the treatment of RSE and SRSE. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Gelsemiumelegans(Gardner. & Chapm.) Benth. has long been considered a traditional Chinese medicine effective against rheumatoid pain, cancer, cirrhosis, and skin diseases. Koumine (KM), the most abundant alkaloid in G.elegans Benth., demonstrates a variety of biological effects, including antitumor, analgesic, anxiolytic, anti-inflammatory, antidepressant, antioxidant, immunoregulatory, and hepatoprotective effects. Furthermore, the relatively low toxicity of KM makes it a promising drug candidate. This study aimed to investigate the protective effects of KM and its possible mechanisms using a concanavalin A (Con A)-induced autoimmune hepatitis (AIH) model in mice. Mice were orally administered different doses of KM for 14 d before Con A tail vein injections. The effects of KM on serum biochemical markers and liver histopathology were then evaluated 12 h after Con A exposure. The Nrf2 and NF-κB signaling pathways and alterations in gut microbiota were determined using western blotting, immunohistochemistry, and 16S rRNA sequencing to explore the underlying mechanisms of KM exposure. KM pretreatment dose-dependently decreased serum liver injury markers (Alanine aminotransferase, and aspartate aminotransferase) and cytokine levels (Tumor necrosis factor-α and interleukin-6), as well as the liver pathological damage triggered by Con A. Furthermore, the results of the multi-technique analysis indicated that KM activated the Nrf2 pathway, upregulated the expression of anti-oxidation factors HO-1 and Nrf2, and downregulated the expression of Keap1. Moreover, the NF-κB signaling pathway was inhibited. Interestingly, pre-treatment with KM also significantly improved the composition of the gut microbiota probably because it increases the richness of probiotics. Our findings suggest that KM pretreatment could attenuate Con A-induced AIH, the Nrf2 and NF-κB signaling pathways, and that gut microbiota are involved in the process of the hepatoprotective effect. This study provides a theoretical basis for the development of KM as an effective agent against AIH.

Trigeminal neuralgia (TN) is a stubborn head and face neuropathic pain with complex pathogenesis. Patients with TN have a significantly increased risk of central neurodegeneration, which manifests as cognitive impairment and memory loss, but the specific mechanism underlying central nervous degeneration is still unclear. This study aimed to explore central neurodegeneration and its possible mechanism of action in TN rats based on changes in the brain fatty acid content and microglia-related neuroinflammation. Using a TN neuropathic pain model established by us, we found that TN rats have obvious cognitive impairment. Furthermore, changes in the brain fatty acid content were analyzed using gas chromatography-mass spectrometry (GC-MS). It was found that the docosahexaenoic acid (DHA) content in the central nervous system (CNS) of TN rats was significantly decreased compared to that in the CNS of Sham rats. An important component in maintaining brain cognition, DHA also plays a key role in regulating central neuroinflammation. Here, by continuous supplementation of DHA, the CNS DHA content was increased to a certain extent in TN rats. The cognitive impairment of TN rats was improved after restoring the central DHA level; this may be related to the improvement of neuroinflammation through the DHA-mediated regulation of microglial polarization. Overall, this study provides a theoretical basis for explaining the pathogenesis of central neurodegeneration in TN. It also suggests DHA as a target for protecting the CNS of patients with TN from damage.

Dementia is an urgent public health problem worldwide, and the determination of the contribution of pain to cognitive decline or dementia is significant for the prevention of dementia.

This review synthesizes recent findings related to the biopsychosocial processes that underlie racial disparities in chronic pain, while highlighting opportunities for interventions to reduce disparities in pain treatment among BIPOC.

Multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis. Hospital care represents the costliest portion of health services. We found public hospital bed days for fragility fractures in Ireland increased by 43% between 2008 and 2017 which exceeded those for other common diseases.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising non-pharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST).

A primary spontaneous pneumothorax (PSP) is caused by rupture of subpleural emphysematous blebs, without inciting event or pre-existing co-morbidity. A previously healthy 16-year-old male presented with upper chest pain. As expected, chest radiographs (CXR) demonstrated a 13 mm pneumothorax. Additionally, a 4.7 cm apical bleb was identified. After six-hours of observation and non-rebreather oxygen mask therapy, follow-up CXR confirmed stable findings. The patient was subsequently discharged home after symptoms improved. Follow-up CXR at 2-weeks confirmed persistent visible apical bleb. After lengthy discussion addressing patient and parental concerns, elective surgical management was pursued. Current literature suggests blebs are not routinely identified on CXR. While there is no universally accepted management algorithm for PSP in children, visible apical blebs on CXR may influence the decision to pursue surgical intervention. Shared decision making should involve counseling regarding the recurrence risk following surgery, and consideration of patient-specific factors including patient and parental anxiety.