Generalized myasthenia gravis with acetylcholine receptor antibodies: A guidance for treatment.

BACKGROUND: Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research. METHODS: MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings. RESULTS: Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended. CONCLUSIONS: Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.

Unravelling Effects of Rosemary (Rosmarinus officinalis L.) Extract on Hepatic Fat Accumulation and Plasma Lipid Profile in Rats Fed a High-Fat Western-Style Diet.

The objective of the study was to investigate the preventive effect on obesity-related conditions of rosemary (Rosmarinus officinalis L.) extract (RE) in young, healthy rats fed a high-fat Western-style diet to complement the existing knowledge gap concerning the anti-obesity effects of RE in vivo. Sprague Dawley rats (71.3 ± 0.46 g) were fed a high-fat Western-style diet (WD) or WD containing either 1 g/kg feed or 4 g/kg feed RE for six weeks. A group fed standard chow served as a negative control. The treatments did not affect body weight; however, the liver fat percentage was reduced in rats fed RE, and NMR analyses of liver tissue indicated that total cholesterol and triglycerides in the liver were reduced. In plasma, HDL cholesterol was increased while triglycerides were decreased. Rats fed high RE had significantly increased fasting plasma concentrations of Glucagon-like peptide-1 (GLP-1). Proteomics analyses of liver tissue showed that RE increased enzymes involved in fatty acid oxidation, possibly associated with the higher fasting GLP-1 levels, which may explain the improvement of the overall lipid profile and hepatic fat accumulation. Furthermore, high levels of succinic acid in the cecal content of RE-treated animals suggested a modulation of the microbiota composition. In conclusion, our results suggest that RE may alleviate the effects of consuming a high-fat diet through increased GLP-1 secretion and changes in microbiota composition.

Mucopenetrating polymer - Lipid hybrid nanovesicles as subunits in alginate beads as an oral formulation.

Crossing the intestinal mucus layer remains a great hurdle in oral drug delivery. The viscous mucus gel protects the body from pathogens but simultaneously traps many types of delivery vehicles, limiting their therapeutic efficacy. We report the assembly of mucopenetrating PEG-based polymer-lipid hybrid vesicles encapsulated in mucoadhesive alginate carriers aiming to increase their residence time in the intestine. The stability of the formulations was evaluated in simulated gastrointestinal conditions, showing negligible subunit leakage in the gastric fluid but a substantial release in the intestinal fluid. Mucopenetration of the free and encapsulated subunits was first demonstrated in vitro in a microfluidic set-up filled with reconstituted porcine mucus and in a mucus-covered co-culture of Caco-2 cells and HT29-MTX-E12 cells. Finally, the free and encapsulated subunits remained adhered in close proximity to the intestinal epithelium after oral administration to rats while the alginate carriers were washed away. In conclusion, the double-encapsulated system with combined mucoadhesive and mucopenetrating properties is a promising alternative drug carrier for oral delivery.

[Analgesic management of acute pain in patients receiving methadone or buprenorphine]. / Akut smertebehandling af stofbrugere i substitutionsbehandling med metadon eller buprenorfin.

In Denmark, approximately 7,600 patients receive maintenance therapy with methadone or buprenorphine because of opioid addiction. These patients have an increased risk of inadequate pain treatment during hospitalization, among others because of tolerance to opioids and poor communication with the staff. The present article describes four common misconceptions among health-care providers that underlie inadequate pain treatment and provides practical recommendations for the analgesic management of acute pain in patients receiving methadone or buprenorphine.