Induction of metallothionein in mouse cerebellum and cerebrum with low-dose thimerosal injection.

Thimerosal, an ethyl mercury compound, is used worldwide as a vaccine preservative. We previously observed that the mercury concentration in mouse brains did not increase with the clinical dose of thimerosal injection, but the concentration increased in the brain after the injection of thimerosal with lipopolysaccharide, even if a low dose of thimerosal was administered. Thimerosal may penetrate the brain, but is undetectable when a clinical dose of thimerosal is injected; therefore, the induction of metallothionein (MT) messenger RNA (mRNA) and protein was observed in the cerebellum and cerebrum of mice after thimerosal injection, as MT is an inducible protein. MT-1 mRNA was expressed at 6 and 9 h in both the cerebrum and cerebellum, but MT-1 mRNA expression in the cerebellum was three times higher than that in the cerebrum after the injection of 12 microg/kg thimerosal. MT-2 mRNA was not expressed until 24 h in both organs. MT-3 mRNA was expressed in the cerebellum from 6 to 15 h after the injection, but not in the cerebrum until 24 h. MT-1 and MT-3 mRNAs were expressed in the cerebellum in a dose-dependent manner. Furthermore, MT-1 protein was detected from 6 to 72 h in the cerebellum after 12 microg/kg of thimerosal was injected and peaked at 10 h. MT-2 was detected in the cerebellum only at 10 h. In the cerebrum, little MT-1 protein was detected at 10 and 24 h, and there were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1 and MT-3 mRNAs but not MT-2 mRNA are easily expressed in the cerebellum rather than in the cerebrum by the injection of low-dose thimerosal. It is thought that the cerebellum is a sensitive organ against thimerosal. As a result of the present findings, in combination with the brain pathology observed in patients diagnosed with autism, the present study helps to support the possible biological plausibility for how low-dose exposure to mercury from thimerosal-containing vaccines may be associated with autism.

Incidence and risk factors for aspiration pneumonia after cardiovascular surgery in elderly patients.

OBJECTIVE: Pneumonia after cardiovascular surgery is the leading cause of mortality. Postoperative aspiration pneumonia becomes a critical issue in the management of cardiovascular surgery in the aging society. The aim of this study was to investigate the incidence and risk factors of aspiration pneumonia after cardiovascular surgery for elderly patients. METHODS: This study consisted of 123 elderly patients (>65 years old) who survived their final extubation following cardiovascular surgery at Kinan Hospital. Patients were divided into aspiration pneumonia and no pneumonia groups. Postoperative aspiration pneumonia was diagnosed by two independent physicians according to the nursing- and healthcare-associated pneumonia guidelines by the Japanese Respiratory Society. RESULTS: Among the patients, 12 (9.8 %) had aspiration pneumonia. There were no differences in patients' characteristics between the groups except for a history of cerebral vascular disorder (aspiration pneumonia 42 % vs no pneumonia 15 %, p = 0.04) and ejection fraction (EF) (aspiration pneumonia 56 ± 21 % vs no pneumonia 66 ± 13 %, p = 0.02). Only six (5 %) patients needed more than 12 h intubation. There was no difference in the operative factors between the groups. Neurological deficit was more frequently observed in the aspiration pneumonia group (33 vs 5 %, p = 0.005). Multivariable logistic regression analysis showed that the history of cerebral vascular disorder and neurological deficit after surgery was independent risk factors for aspiration pneumonia after cardiovascular surgery. CONCLUSIONS: Our results could assist in screening elderly patients who should be more carefully evaluated before oral nutrition to minimize morbidity and mortality after cardiovascular surgery.

Expression of metallothionein mRNAs on mouse cerebellum microglia cells by thimerosal and its metabolites.

Effects of thimerosal and its metabolites, ethyl mercury and thiosalicylate, on the expression of metallothionein (MT) mRNAs in mouse cerebellum microglia cell line, C8-B4 cells, were studied. The level of MT-1 mRNA significantly decreased at early hours and recovered time-dependently 24h after thimerosal was added to the C8-B4 cells. However, MT-2 and MT-3 mRNA expressions did not change from the control group. In contrast, the expression of MT-1 mRNA increased in a mouse neuroblastoma cell line 6h after incubation with thimerosal. In addition, the level of MT-1 mRNA decreased in C8-B4 cells 6h after the addition of thiosalicylate, but ethyl mercury induced MT-1 mRNA expression. When cell viability was compared with thimerosal, thiosalicylate, and ethyl mercury, the viability of C8-B4 cells decreased dose-dependently 24h after either thimerosal or ethyl mercury was added; however, the viability increased dose-dependently until 15 microM thiosalicylate was added. From the present results, it is concluded that the expression of MT-1 mRNA may be mediated by different factors than the expression of MT-2 mRNA in C8-B4 cells. The reduction of MT-1 mRNA level by thiosalicylate may affect the proliferation of C8-B4 cells.