Munekazu Gemba

Bio: Munekazu Gemba is an academic researcher from Osaka University of Pharmaceutical Sciences. The author has contributed to research in topics: Nephrotoxicity & Kidney. The author has an hindex of 19, co-authored 65 publications receiving 1280 citations. Previous affiliations of Munekazu Gemba include Mitsubishi.

Purification of docosahexaenoic acid by selective esterification of fatty acids from tuna oil with Rhizopus delemar lipase

Abstract: To purify docosahexaenoic acid (DHA), we attempted the selective esterification of fatty acids originating from tuna oil with lipases. Tuna oil was hydrolyzed in NaOH-ethanol solution, and the resulting fatty acid mixture [DHA, 23.2%; named tuna-free fatty acid (FFA)] was used as a starting material. Rhizopus delemar which acted lightly on DHA, was a suitable catalyst for the selective esterification of tuna-FFA, and lauryl alcohol was the best substrate. The reaction proceeded most effectively when a mixture of 2.4 g lauryl alcohol/tuna-FFA (2:1, mol/mol), 0.6 g water, and 600 U Rhizopus lipase was incubated at 30°C for 20 h with stirring at 500 rpm. Under these conditions 72% of tuna-FFA was esterified, and 84% of DHA was recovered in the unesterified fatty acid fraction. The DHA content in the fatty acid fraction rose from 23 to 73% with this reaction. To further elevate the DHA content, the unesterified fatty acids were extracted, and then esterified again under the same conditions. By this repeated esterification, DHA was purified to 89% with a recovery of 71% of its initial content.

Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation.

Abstract: Nedaplatin is known to exhibit antitumor activity similar to that of cisplatin. However, concerning side effects, nedaplatin causes renal toxicity less frequently than cisplatin. In this study, we compared the incidence of renal toxicity between cisplatin and nedaplatin by investigating the difference in kidney tissue accumulation. Kidney tissue accumulation of cisplatin administered at 3.75 mg/kg was similar to that of nedaplatin administered at 24 mg/kg. At these doses, the plasma creatinine level and urinary excretion of glucose and N-acetyl-beta-D-glucosaminidase (NAG) similarly increased. There was a correlation between kidney accumulation of cisplatin and nedaplatin and the increases in plasma creatinine level and urinary excretion of NAG. Therefore, our results suggest that nedaplatin less frequently causes renal toxicity in comparison to cisplatin due to lower kidney accumulation.

Cell Biology of Ischemia/Reperfusion Injury

Abstract: Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues.

The status of platinum anticancer drugs in the clinic and in clinical trials.

Abstract: Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin™ and ProLindac™). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.