Disruption of the gut microbiota, termed gut dysbiosis, has been described in animal models of hypertension and hypertensive patients. We have shown that gut dysbiosis plays a causal role in the development of hypertension in a rat model of obstructive sleep apnea (OSA). Functional analysis of the dysbiotic microbiota in OSA demonstrates a loss of short chain fatty acid (SCFA) producing bacteria. However, measurements of SCFA concentrations and testing of their role in blood pressure regulation is lacking. We hypothesized that reduced SCFAs in the gut are responsible for OSA-induced hypertension. OSA significantly increased SBP at 7 and 14 days (p<0.05), an effect that was abolished by the probiotic Clostridium butyricum or the prebiotic Hylon VII. 16S rRNA analysis identified a number of SCFA producing bacteria that were significantly increased by C.butyricum and Hylon treatment. Acetate concentration in the cecum was decreased by 48% following OSA (p<0.05), an effect that was prevented by C.butyricum and Hylon. C.butyricum and Hylon reduced OSA-induced dysbiosis, epithelial goblet cell loss, mucus barrier thinning, and activation of brain microglia (p<0.05 for each). To examine the role of acetate in OSA-induced hypertension, we chronically infused acetate into the cecum during 2 weeks of sham or OSA. Restoring cecal acetate concentration prevented OSA-induced gut inflammation and hypertension (p<0.05). These studies identify acetate as a key player in OSA-induced hypertension. We demonstrate that various methods to increase cecal acetate concentrations are protective from the adverse effects of OSA on the microbiota, gut, brain, and blood pressure.

No abstract

No abstract

Effective pain management is essential in the treatment of musculoskeletal pathology. Corticosteroid injections have long been used both locally and systemically for their analgesic and anti-inflammatory properties in orthopedic conditions. Opioids have long been used in the perioperative setting to optimize pain control, however both corticosteroids and opioids are not without harm. Ketorolac, a nonsteroidal anti-inflammatory (NSAID) has shown to be effective as an anti-inflammatory and analgesic agent in and outside the perioperative setting with less risk of local and systemic side effects. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant publications were identified searching the PubMed database and EMBASE. The initial search totaled 3,978 articles. After thorough review, 21 full text manuscripts were included (Fig. 1 – PRISMA Chart). 21 full text manuscripts were reviewed assessing over 3,100 who received a local injection of Toradol. Overall, the studies reviewed universally demonstrated an excellent safety profile for ketorolac both systemically and locally. Clinical studies have shown that local application of ketorolac demonstrated decreased postoperative pain, decreased lengths of hospital stays, and decrease postoperative opioid use. This is the first ever study to assess the efficacy, safety profile, and postoperative outcomes with local use of ketorolac injections in musculoskeletal pathology. The local use of ketorolac in the intra-articular and peri-articular setting provides a safe and effective adjunct or alternative treatment in patients with musculoskeletal ailments.

No abstract