Coenzyme Q10 levels increase with embryonic development in medaka.

Coenzyme Q10 is an important molecule for mitochondrial respiration and as an antioxidant. Maintenance of the ovum in a good condition is considered to be important for successful fertilization and development, which has been reported to be promoted by coenzyme Q10. In this study, we investigated the level of coenzyme Q10 during ovum fertilization and maturation. We attempted to analyze coenzyme Q10 levels during ovum development in species that use coenzyme Q10 but not coenzyme Q9. It was shown that medaka produces coenzyme Q10. We then measured the amount of coenzyme Q10 after fertilization of medaka ovum and found that it increased. The amount of free cholesterol biosynthesized from acetyl CoA as well as coenzyme Q10 increased during development, but the increase in coenzyme Q10 was more pronounced. The mRNA expression level of coq9 also increased during embryonic development, but the mRNA expression levels of other coenzyme Q10 synthases did not. These results suggest that the coq9 gene is upregulated during the development of medaka ovum after fertilization, resulting in an increase in the amount of coenzyme Q10 in the ovum. Medaka, which like humans has coenzyme Q10, is expected to become a model animal for coenzyme Q10 research.

Direct Comparison of Therapeutic Effects on Diabetic Polyneuropathy between Transplantation of Dental Pulp Stem Cells and Administration of Dental Pulp Stem Cell-Secreted Factors.

Stem cell transplantation is a potential novel therapy for diabetic polyneuropathy. Dental pulp stem cells (DPSCs) are attractive stem cell sources because DPSCs can be isolated from extracted teeth and cryopreserved while retaining viability. In this study, we directly compared the efficacy of the transplantation of DPSCs and the administration of the secreted factors from DPSCs (DPSC-SFs) on diabetic polyneuropathy. Eight weeks after streptozotocin injection, DPSCs (1.0 × 106 cells/rat) or DPSC-SFs (1.0 mL/rat) were administered into the unilateral hindlimb skeletal muscles of diabetic Sprague-Dawley rats. DPSC transplantation and DPSC-SF administration did not affect blood glucose levels and body weights in the diabetic rats. Both DPSC transplantation and DPSC-SF administration significantly ameliorated sciatic nerve conduction velocity and sciatic nerve blood flow, accompanied by increases in muscle bundle size, vascular density in the skeletal muscles and intraepidermal nerve fiber density in the diabetic rats, while there was no difference between the results for DPSCs and DPSC-SFs. These results suggest that the efficacy of both DPSC transplantation and DPSC-SF administration for diabetic polyneuropathy four weeks after transplantation/administration was mainly due to the multiple secretomes secreted from transplanted DPSCs or directly injected DPSC-SFs in the early phase of transplantation/administration.

Comparison of severe hyponatremia in patients with and without psychiatric diseases: A single-center retrospective study.

Aims: Hyponatremia is a common electrolyte disorder. The severe hyponatremia has a mortality rate of 4%-40%. Psychiatric patients are likely to develop the condition because of polydipsia or the adverse effects of antipsychotics. We investigated the characteristics of patients with and without psychiatric diseases who developed severe hyponatremia. Materials and Methods: We retrospectively investigated cases admitted to our hospital (all departments) between October 2012 and November 2015 with a serum sodium concentration of ≤125 mmol/l on admission. We compared patient characteristics, etiology, and clinical course between psychiatric and nonpsychiatric patients. Results: In total, 123 cases (62 female) were analyzed. Psychiatric disorders were present in 69 cases (56%), including schizophrenia (n = 19), anorexia (n = 16), mood disorders (n = 14), and organic mental disorders (n = 9). The mean patient age was 63 years. The mean serum sodium concentration on admission was 119 mmol/l, and the main causes of hyponatremia were polydipsia (20%), insufficient sodium intake (18%), and syndrome of inappropriate antidiuretic hormone secretion (16%). Compared with the nonpsychiatric group, the psychiatric group was significantly younger (55 vs. 74 years), was more likely to have polydipsia (30% vs. 6%), and had a lower in-hospital mortality (0% vs. 17%). Conclusions: Our study found differences in the clinical picture between psychiatric and nonpsychiatric patients with severe hyponatremia. Clinicians need to monitor serum sodium because the symptoms of hyponatremia can mimic those of psychiatric diseases.

Transplantation of human dental pulp stem cells ameliorates diabetic polyneuropathy in streptozotocin-induced diabetic nude mice: the role of angiogenic and neurotrophic factors.

BACKGROUND: Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. In our previous study, we demonstrated that cryopreserved rat DPSCs improved diabetic polyneuropathy and that the efficacy of cryopreserved rat DPSCs was equivalent to that of freshly isolated rat DPSCs. The present study was conducted to evaluate whether transplantation of cryopreserved human DPSCs (hDPSCs) is also effective for the treatment of diabetic polyneuropathy. METHODS: hDPSCs were isolated from human impacted third molars being extracted for orthodontic reasons. Eight weeks after the induction of diabetes in nude mice, hDPSCs (1 × 105/limb) were unilaterally transplanted into the hindlimb skeletal muscle, and vehicle (saline) was injected into the opposite side as a control. The effects of hDPSCs were analyzed at 4 weeks after transplantation. RESULTS: hDPSC transplantation significantly ameliorated reduced sensory perception thresholds, delayed nerve conduction velocity, and decreased the blood flow to the sciatic nerve in diabetic mice 4 weeks post-transplantation. Cultured hDPSCs secreted the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) proteins. A subset of the transplanted hDPSCs was localized around the muscle bundles and expressed the human VEGF and NGF genes at the transplanted site. The capillary/muscle bundle ratio was significantly increased on the hDPSC-transplanted side of the gastrocnemius muscles in diabetic mice. Neutralizing antibodies against VEGF and NGF negated the effects of hDPSC transplantation on the nerve conduction velocity in diabetic mice, suggesting that VEGF and NGF may play roles in the effects of hDPSC transplantation on diabetic polyneuropathy. CONCLUSIONS: These results suggest that stem cell transplantation with hDPSCs may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors.

Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti-inflammatory, neuroprotective and angiogenic actions: Cell-free regenerative medicine for diabetic polyneuropathy.

AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) can be easily obtained from teeth for general orthodontic reasons. We have previously reported the therapeutic effects of DPSC transplantation for diabetic polyneuropathy. As abundant secretomes from DPSCs are considered to play a central role in the improvement of diabetic polyneuropathy, we investigated whether direct injection of DPSC-conditioned media (DPSC-CM) into hindlimb skeletal muscles ameliorates diabetic polyneuropathy in diabetic rats. MATERIALS AND METHODS: DPSCs were isolated from the dental pulp of Sprague-Dawley rats. Eight weeks after the induction of diabetes, DPSC-CM was injected into the unilateral hindlimb skeletal muscles in both normal and diabetic rats. The effects of DPSC-CM on diabetic polyneuropathy were assessed 4 weeks after DPSC-CM injection. To confirm the angiogenic effect of DPSC-CM, the effect of DPSC-CM on cultured human umbilical vascular endothelial cell proliferation was investigated. RESULTS: The administration of DPSC-CM into the hindlimb skeletal muscles significantly ameliorated sciatic motor/sensory nerve conduction velocity, sciatic nerve blood flow and intraepidermal nerve fiber density in the footpads of diabetic rats. We also showed that DPSC-CM injection significantly increased the capillary density of the skeletal muscles, and suppressed pro-inflammatory reactions in the sciatic nerves of diabetic rats. Furthermore, an in vitro study showed that DPSC-CM significantly increased the proliferation of umbilical vascular endothelial cells. CONCLUSIONS: We showed that DPSC-CM injection into hindlimb skeletal muscles has a therapeutic effect on diabetic polyneuropathy through neuroprotective, angiogenic and anti-inflammatory actions. DPSC-CM could be a novel cell-free regenerative medicine treatment for diabetic polyneuropathy.

Acute toxicity of pierisin-1, a cytotoxic protein from Pieris rapae, in mouse and rat.

To investigate the toxicity of pierisin-1, a cytotoxic protein present in the cabbage butterfly, Pieris rapae, pierisin-1 was administered via intraperitoneally in mice and rats and the effects examined. Common findings in these experiments were hypoactivity with a gradual decrease in body weight due to decreased food intake, relative polycythemia with low serum albumin concentration and atrophy of the thymus, spleen, seminal vesicles and adipose tissue. Characteristic findings were diarrhea, fusion and atrophy of the villi and dilatation of the crypts in the small intestine at 6-100 microg/kg in BALB/c mice as well as elevation of LDH activity and creatinine value, hemolysis and renal and hepatic injuries at 1,000 and 10,000 microg/kg in BALB/c mice. In the case of ICR mice, severer renal injury was observed. On the other hand, in Fischer 344/Du rats, sudden stop of food intake, elevation of both AST and ALT activities, interlobar adhesion of the right hepatic lobe, capsular thickening, septal fibrosis and single cell necroses of subcapsular hepatocytes in the liver and basophilic tubules in the kidneys were observed. Oral administration of pierisin-1 at a dose of 10,000 microg/kg in BALB/c mice did not exert any obvious effects. Thus, existence of species and strain differences in toxicity of pierisin-1 to animals was demonstrated.