Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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Pathogenesis of diabetic retinopathy and the renin-angiotensin system.

Despite the beneficial effects of good glycaemic control, loss of vision because of diabetic retinopathy (DR) still occurs. Recent studies have suggested that hypertension is a risk factor for the development and progression of DR and that blood pressure reduction can delay the progression of retinopathy. The renin-angiotensin system is activated by chronic hyperglycaemia, and the vitreous fluid level of angiotensin II (AII) is elevated in patients with proliferative diabetic retinopathy and diabetic macular oedema. AII increases vascular permeability and promotes neovascularization. It has been suggested that an autocrine-paracrine relationship may exist between AII and vascular endothelial growth factor in the ocular tissues. Accordingly, angiotensin-converting enzyme inhibitors or AII Type 1 (AT1) receptor blockers may be useful therapeutic agents for preventing the progression of DR.     

Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of major depressive disorder. A number of studies have shown that this dysregulation is correlated with impaired forebrain glucocorticoid receptor (GR) function. To determine whether a primary, acquired deficit in forebrain GR signaling is an etiologic factor in the pathogenesis of depression, we generated a line of mice with time-dependent, forebrain-specific disruption of GR (FBGRKO). These mice develop a number of both physiological and behavioral abnormalities that mimic major depressive disorder in humans, including hyperactivity of the HPA axis, impaired negative feedback regulation of the HPA axis and, increased depression-like behavior. Importantly, a number of these abnormalities are normalized by chronic treatment with the tricyclic antidepressant, imipramine. Our findings suggest that imipramine's proposed activities on forebrain GR function are not essential for its antidepressant effects, and that alteration in GR expression may play a causative role in disease onset of major depressive disorder.     

Rare Complication of Takotsubo Cardiomyopathy: Ventricular Septal Perforation with Septal Dissection

We describe a rare case of takotsubo cardiomyopathy complicated by acute ventricular septal perforation with ventricular septal dissection. The ventricular perforation was successfully closed by repairing the dissecting site with a bovine pericardial patch. doi: 10.1111/jocs.12676 (J Card Surg 2016;31:150–153)     

Present status of ophthalmological care for diabetic patients in Japan

PURPOSE: To investigate the present status of diabetic care provided by ophthalmologists working in hospitals and private clinics in Japan. METHODS: Questionnaires were mailed to 315 ophthalmologists. There was a return rate of 73%. RESULTS: Problems identified in the clinics were: (1) many diabetic patients who complain chiefly of ophthalmological symptoms voluntarily request their first ophthalmological examination; (2) appropriate cooperation between ophthalmologists and physicians is not established; (3) assessing the level of blood glucose control is difficult; and (4) scheduling of appointments is inadequate. Moreover, (1) inadequate handling of patients who discontinue their ophthalmological examinations, and (2) the lack of an established patient education program were seen as problems common to both hospitals and clinics. CONCLUSIONS: For the resolution of these problems, comprehensive countermeasures should be developed urgently by medical associations, medical administrators, and other relevant entities.     

High metabolic function of primary human and porcine hepatocytes in a polyurethane foam/spheroid culture system in plasma from patients with fulminant hepatic failure

It has been demonstrated that plasma from patients with fulminant hepatic failure (FHF) interferes extensively with cellular function. We placed primary human and primary porcine hepatocytes in a polyurethane foam (PUF)/spheroid culture system and compared the metabolic functions in the plasma of patients with FHF in a 24-h stationary culture to those in a monolayer culture. The PUF/spheroid culture system using primary human and primary porcine hepatocytes significantly decreased ammonia content during 28-day culture. Fisher's ratio significantly increased at culture days 3 and 7. Tauroursodeoxycholic acid significantly increased and glycochenodeoxycholic acid and taurochenodeoxycholic acid decreased in the FHF patients' plasma at culture day 3. During at least a 24-h culture in the FHF patients' plasma, metabolic functions of primary human and primary porcine hepatocytes were almost identical. The present results indicate that the PUF/spheroid culture system using primary human or primary porcine hepatocytes demonstrated more advantageous metabolic functions in the plasma from patients with FHF than the monolayer culture.     

Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell source for hybrid artificial liver

The aim of this study was to investigate the feasibility of human hepatoblastoma cell line (Hep G2), which differentiates by spheroid formation, and treatment with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL). Hep G2 spontaneously formed spheroids in polyurethane foam (PUF) within 3 days of culture and restored weak ammonia removal activity. Treatment with SB, which is a histone deacetylase inhibitor, further increased the ammonia removal activity of Hep G2 spheroids in a concentration-dependent manner. The activation of ornithine transcarbamylase--a urea cycle enzyme--was significantly related to the upregulation of ammonia removal by spheroid formation, but scarcely contributed to the further upregulation following SB treatment. In contrast with ammonia removal, treatment with SB reduced the albumin secretion of Hep G2 spheroids in a concentration-dependent manner. In the PUF-HAL module in a circulation culture, the ammonia removal rate and albumin secretion rate (per unit volume of the module) of Hep G2 spheroids treated with 5 mM SB were almost the same as those of primary porcine hepatocyte spheroids. These results suggest that simultaneous use of spheroid formation and SB treatment in Hep G2 is beneficial in enhancing the functions of human hepatocytes with potential applications in regenerative medicine and drug screening.