Although it is known that diabetic nephropathy is accelerated by hypertension, the mechanisms involved in this process are not clear. In this study we aimed to clarify these mechanisms using male Wistar fatty rats (WFR) as a type 2 diabetic model and male Wistar lean rats (WLR) as a control. Each group was fed a normal or high sodium diet from the age of 6 to 14 weeks. We determined the blood pressure and urinary albumin changes in the kidney, including glomerular hyperfiltration and glomerular hypertension (1). These changes are accompanied by structural changes such as glomerular hypertrophy, basement-membrane thickening or mesangial expansion (2). Accumulating evidence suggests that the metabolic pathway associated with hyperglycemia plays a pivotal role in the pathogenesis of diabetic nephropathy in part via the en-

Clarithromycin (CAM), a semisynthetic macrolide antibiotic, is a widely used antibacterial drug. Recently, the efficacy of CAM as an add-on drug for treating multiple myeloma (MM) has been noted. Its effect on treating MM has been confirmed in combination chemotherapies that include CAM. However, a single treatment of CAM has no efficacy for treating MM. Many myeloma growth factors (MGFs) including interleukin (IL)-6 are known to be closely involved in the development of MM. CAM has been shown to suppress many MGFs, particularly IL-6. The possible mechanisms of action of CAM in treating MM have been suggested to include its immunomodulatory effect, autophagy inhibition, reversibility of drug resistance, steroid-sparing/enhancing effect and suppression of MGFs. In addition, MM is characterised by uncontrolled cell growth of monoclonal immunoglobulin (Ig)-producing neoplastic plasma cells. Large quantities of unfolded or misfolded Ig production may trigger considerable endoplasmic reticulum stress. Thus, MM is originally a fragile neoplasm particularly susceptible to autophagy-, proteasomeand histone deacetylase 6-inhibitors. Taken together, CAM plays an important role in MM treatments through its synergistic mechanisms. In addition, CAM with its pleiotropic effects on cytokines including IL-6 and indirect antiviral effects might be worth a try for treating COVID-19.

BackgroundIn general, dexamethasone is a required component drug in various combination chemotherapies for treating multiple myeloma, and its efficacy has been widely recognized. However, administration of dexamethasone is known to cause various adverse effects including hyperglycemia which requires insulin therapy. During the course of treatment, we developed a novel effective dexamethasone-free combination regimen and evaluated it for its effect in multiple myeloma.Case presentationWe report a case of 68-year-old Japanese woman with refractory advanced Bence-Jones-λ type multiple myeloma associated with diabetes mellitus. Various combination regimens were carried out, but the response to some regimens was insufficient or others containing dexamethasone, although effective, were inappropriate to continue due to aggravation of diabetes mellitus. Thus, we developed a dexamethasone-free, short dosing-period regimen consisting of bortezomib, lenalidomide, and clarithromycin. This regimen was found to be highly effective and succeeded in achieving stringent complete response.ConclusionsThe successful dexamethasone-free regimen clearly shows that dexamethasone is not a requisite component in treating multiple myeloma, and it can be substituted with clarithromycin. This regimen is particularly useful for treating patients with multiple myeloma associated with diabetes mellitus.

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