A massive natural disaster, the Great East Japan Earthquake, and the incidence of dialysis due to end-stage kidney disease.

BACKGROUND: Disaster-related stress can increase blood pressure and the incidence of cardiovascular diseases. However, the role of massive disasters in the development of end-stage kidney disease (ESKD) remains unknown. We investigated the incidence and different causes of dialysis initiation in patients with chronic kidney disease in a city affected by the Great East Japan Earthquake. METHODS: This was a single-center, retrospective observational study. All patients who initiated or were treated with dialysis at Kesennuma City Hospital between 2007 and 2020 were enrolled. The year of dialysis initiation was retrospectively determined based on the initiation date. The causative renal diseases that led to the need for dialysis initiation were divided into four groups: diabetic nephropathy, hypertensive renal disease, glomerulonephritis, and others. RESULTS: Age at dialysis initiation differed significantly among the four groups (p = 0.0262). There was a significant difference in the numbers of the four groups before and after the Great East Japan Earthquake (p = 0.0193). The age of hypertensive renal disease patients was significantly higher than those of patients with diabetic nephropathy (p = 0.0070) and glomerulonephritis (p = 0.0386) after the disaster. The increasing number of dialysis initiations after the Great East Japan Earthquake appeared to be associated with changes in hypertensive renal diseases; the number peaked after 10 years. CONCLUSIONS: There was an increase in the number of dialysis initiations, especially caused by hypertensive renal diseases, for up to 10 years after the Great East Japan Earthquake.

Efficacy and safety of atovaquone-proguanil compared with mefloquine in the treatment of nonimmune patients with uncomplicated P. falciparum malaria in Japan.

Malaria treatment is becoming increasingly difficult due to the widespread drug resistance of Plasmodium falciparum. In Japan, only three antimalarials are approved for treatment: oral quinine, sulfadoxine-pyrimethamine, and mefloquine. Recently, however, the Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil for treating drug-resistant P. falciparum malaria. This research group had also introduced mefloquine before it was licensed nationally. Using data obtained from the research group, we analyzed the efficacy and safety of atovaquone-proguanil, as compared with mefloquine, in nonimmune patients with uncomplicated P. falciparum malaria. Cures were attained in all (100%) of 20 atovaquone-proguanil-treated and 49 (98%) of 50 mefloquine-treated adults. The mean fever clearance time (FCT) and parasite clearance time (PCT) appeared to be longer in the atovaquone-proguanil group than in the mefloquine group, but the differences were not statistically significant. Three (15%) of the 20 atovaquone-proguanil-treated adults had adverse events (AEs), all of which were transient elevations of liver enzymes, while 19 (38%) of the 50 mefloquine-treated adults had AEs, including dizziness in 8 (16%) and nausea/vomiting in 7 (14%). All 3 children treated with atovaquone-proguanil were cured without developing AEs. Despite the limitations of this study in not being a formal clinical trial, atovaquone-proguanil seemed to be at least equal to, or even better than, mefloquine for the treatment of uncomplicated P. falciparum malaria in nonimmune patients, including children. Its marketing in Japan could be beneficial in offering an alternative therapeutic option. However, vigilance should be maintained on the possible occurrence of rare but severe AEs, and also of the possible spread of drug resistance.

Oral ivermectin treatment in two cases of scabies: effective in crusted scabies induced by corticosteroid but ineffective in nail scabies.

We report two cases of scabies treated with oral ivermectin (200 micro g/kg). Case 1, a 72-year-old man, developed crusted scabies with the use of oral corticosteroids due to a misdiagnosis by an earlier physician. The patient was successfully treated with two doses of oral ivermectin at a 7 day interval with concomitant topical use of crotamiton and keratolytic agents. However, the nail scabies in this patient failed to respond to these treatments. Live mites were detected from all his toenails two weeks after the second dose of ivermectin. A complete cure of the nail scabies was achieved by occlusive dressing of 1% gamma-BHC on all toenails for one month. Case 2, a 52-year-old woman, had been treated with oral corticosteroid for mesangial nephritis. She developed common scabies, but a topical scabicide, crotamiton, was not effective. Two weeks after treatment with a single dose of oral ivermectin, eggs were still detected from a burrow on her trunk. Her treatment was completed after a further two doses of oral ivermectin were administered at 7 day intervals. In both patients, the administration of oral ivermectin did not induce any clinical or laboratory side effects. Oral ivermectin is effective for crusted scabies, but not effective for nail scabies. Two doses of oral ivermectin, administered with a one-week interval, is an appropriate treatment regimen.

Effect of jasplakinolide on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum.

The effect of jasplakinolide (JAS), an actin-polymerizing and filament-stabilizing drug, on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum was examined. Jasplakinolide markedly decreased the parasitemia in a synchronized culture of P. falciparum strain FCR-3 in a time- and concentration-dependent manner. The decrease became evident at day 2 at concentrations of 0.3 micro M and above, and parasites finally disappeared at day 4. Giemsa-stained smears of P. falciparum-infected erythrocytes demonstrated that there was no effect on the development of schizonts from ring forms. Merozoites were released from the infected erythrocytes in a normal manner with and without JAS. However, there were no ring form-infected erythrocytes when JAS was administered, even after the release of merozoites. This indicates that the merozoites exposed to JAS failed to invade erythrocytes. The inhibitory effect of JAS on the parasitemia was reversed by the removal of the drug after exposure to 1 micro M of JAS for 1 day. Electron microscopy revealed that the merozoites treated with JAS showed a protrusion of the apical end which contained the microfilament structure. Immunoblot analysis indicated that the JAS treatment increased F-actin filaments of merozoites but had no effect on those of the trophozoites and schizonts. Therefore, this study demonstrated that JAS has an antimalarial activity.

Effect of proteasome inhibitors on the growth, encystation, and excystation of Entamoeba histolytica and Entamoeba invadens.

The effect of three proteasome inhibitors, lactacystin, clasto-lactacystin beta-lactone, and MG-132, on the growth, encystation, and excystation of Entamoeba histolytica and Entamoeba invadens was examined. All of these drugs blocked E. histolytica growth in a concentration-dependent manner; lactacystin was most potent for the inhibition and MG-132 showed the inhibitory effect only at higher concentrations. E. invadens was more resistant to these drugs than E. histolytica. Encystation of E. invadens was also inhibited and was more sensitive to the drugs than was growth. Beta-lactone was the most potent encystation inhibitor. The inhibitory effect of lactacystin and the beta-lactone on encystation was slightly and little abrogated by the removal of the drug, respectively. Multinucleation occurred in E. histolytica trophozoites treated with these drugs, being most marked with lactacystin. In contrast, no multinucleation was observed in E. invadens treated with the drugs. Electron microscopy revealed that the treatment of E. histolytica trophozoites with lactacystin led to an increase in the number of cells with many glycogen granules in the cytoplasm. Lactacystin, beta-lactone and MG-132 had no or little effect on the excystation and metacystic development of E. invadens. These results suggest that proteasome function plays an important role for Entamoeba growth and encystation, but has no obvious effect on excystation or metacystic development.