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Sensorineural Hearing Loss
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Linnea Cheung, David M. Baguley, Andrew McCombe
Intratympanic (IT) steroid therapy results in higher inner ear steroid levels than oral therapy. The main advantage is a reduction in systemic side effects; therefore, it can be valuable in diabetics or patients who cannot take systemic corticosteroids. Dexamethasone and methylprednisolone sodium succinate are the most frequently used preparations. There is no evidence on which steroid is superior; however, better hearing outcomes have been associated with higher doses and the cumulative effect of multiple administrations. Commonly this is administered via a grommet or injected intratympanically under local anaesthetic with the patient lying in a supine position and the injected ear facing towards the ceiling for approximately 30 minutes to facilitate diffusion of the drug across the round window membrane. Diffusion across the round window membrane is variable and leads to unpredictable intracochlear bioavailability. Risks of IT administration include pain, dizziness, and persistent tympanic membrane perforation at the site of injection. No comparative trials have shown superiority of primary IT steroid therapy over oral steroids with respect to hearing outcomes; however, combination therapy has been shown to improve overall hearing compared with oral treatment alone.
Carbohydrates
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
In 1935 Himwich and Fazekas reported that nicotine (14 mM) reduced the “no substrate” respiration of minced brain of rat, cat and dog and inhibited by 60% the increased oxygen uptake with added lactate, but it had no effect on the increase with added glucose or pyruvate.80,81 It was concluded that lactic dehydrogenase was inhibited. Oxidation of succinate was also inhibited. These observations led Himwich and Fazekas to suggest that glucose oxidation in brain might proceed directly without previous glycolysis, a suggestion based on the assumption that lactate was an intermediate in the oxidation of glucose via the glycolytic pathway of metabolism. The precise role of lactate in carbohydrate metabolism was a matter of debate at that time, and it was not then commonly realized that pyruvate is reduced to lactate in quantity only when there is insufficient oxygen for its complete oxidation. Nor was it always appreciated that an inhibitor of lactic dehydrogenase would inhibit the formation of lactate to the same extent that it inhibits its oxidation. It is however of interest that it was this early work with nicotine that inspired later research leading to the discovery of alternative metabolic pathways for the oxidation of glucose.
M
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
IV methylprednisolone sodium succinate (8 mg/kg given 1–4 hours prior to the first dose of OKT3) is strongly recommended to decrease the incidence and severity of reactions to the first dose. Paracetamol and antihistamines given concomitantly with OKT3 may also help to reduce some early reactions.
Dysregulated metabolism: A friend-to-foe skewer of macrophages
Published in International Reviews of Immunology, 2023
Keywan Mortezaee, Jamal Majidpoor
Increasing the production of succinate is important for regulation of macrophage polarization. Succinate is a known regulator of pro-inflammatory responses, mediated through HIF-1α stabilization and suppression of anti-inflammatory gene expression profile. Glutamine synthetase is an enzyme related to acid-base homeostasis and nitrogen metabolism. M2 macrophages under starvation induce the activity of glutamine synthase for production of glutamine. Blockade of glutamine synthase causes M2-to-M1 skewing of macrophages and the resultant tumor regression. Incubation of M2 macrophages with the glutamine synthase inhibitor methionine sulfoximine causes succinate accumulation and increased glucose utilization, thereby promoting metabolic rewiring toward attaining M1-like phenotype. Succinate is contributed to HIF-1α stabilization, so it is expected that blockade of glutamine synthase will cause HIF-1α activation, as it is attested [84]. Due to the interference between PKM2 activity with succinate accumulation and glycolysis for M1 polarization, a suggested strategy could be targeting PKM2.
Sweet syndrome and erythema nodosum in a young patient with ulcerative colitis
Published in Baylor University Medical Center Proceedings, 2023
Katherine Gonzalez, Janice Thomas, John Givler, Lindsey Stockton
On admission, the patient was started on methylprednisolone sodium succinate 81.25 mg intravenously every 8 hours. Gastroenterology was consulted for her UC flare and recommended the intravenous steroids be reduced to 40 mg every 8 hours. Infectious disease started the patient on vancomycin 750 mg intravenously every 8 hours. To rule out infectious causes of rash, Cryptococcus antigen, Histoplasma antigen, Blastomyces dermatitidis antibody, varicella zoster IgG serology, fungal culture, blood culture, and methicillin-resistant Staphylococcus aureus (MRSA) culture were ordered and came back negative. After MRSA came back negative, vancomycin was discontinued. Dermatology conducted a shave biopsy on a small subcentimeter lesion on the back. The epidermis showed a small erosion, mild spongiosis with exocytosis of a few neutrophils. The dermis was extensively infiltrated with numerous neutrophils with significant leukocytoclasis, consistent with SS. No overt vasculitis or ulceration was noted.
Microbiome therapeutics for the treatment of recurrent Clostridioides difficile infection
Published in Expert Opinion on Biological Therapy, 2023
Patricia P Bloom, Vincent B Young
Alterations in short-chain fatty acid (SCFA) composition can also contribute to rCDI and represent another potential treatment target. SCFA are the main fermentation products of dietary fibers [33,34]. Antibiotic-induced diarrhea is associated with a decrease in succinate-utilizing microbes, and a corresponding increase in succinate availability [35]. On the other hand, rCDI is associated with a loss of butyrate-producing Firmicutes species and low levels of many SCFAs [36]. C. difficile is able to utilize succinate as a carbon source, which can provide a nutrition advantage in an environment deficient in microbial competitors [37]. In one experiment, a defined consortium of 58 bacteria from a healthy donor (DEC58) was treated with ciprofloxacin [37]. The cell-free supernatant of DEC58, containing metabolites, and separately ciprofloxacin-treated DEC58 were applied to bioreactors containing C. difficile. Ciprofloxacin-treated DEC58 supernatant promoted vegetative cell growth of C. difficile, while DEC58 supernatant did not. The main metabolite responsible for this difference was succinate. The ciprofloxacin-treated DEC58 yielded higher concentrations of succinate, which C. difficile was able to utilize. In terms of the potential role of SCFA in recurrent CDI, it has been shown that successful treatment of rCDI with FMT has been associated with restoration of both bile acid profiles and normal levels of SCFAs [38].