Kei Fujioka

Effect of royal jelly ingestion for six months on healthy volunteers

BackgroundRoyal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans.MethodsWe conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention.ResultsThirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x106 /μL for the RJ group vs. -0.01x106 /μL for the control group, P = 0.0134), hematocrit (+0.9% vs. -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. -0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log μg/dL vs. +0.20 log μg/dL, P = 0.0483), log testosterone (T) (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental health (MH) (+4 vs. -7, P = 0.0276).ConclusionsSix-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.

TAFRO syndrome: 2 cases and review of the literature

Recently, more than ten cases of thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome or Castleman–Kojima disease exhibiting such symptoms as thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly have been reported in Japan. We have found two cases of TAFRO syndrome and have reviewed another eighteen previously reported cases. Histological findings of the lymph nodes and levels of interleukin 6 (IL-6) and vascular endothelial growth factor in both serum/plasma and effusions are important characteristics for diagnosing this syndrome.

Effects of phorbol ester‐sensitive PKC (c/nPKC) activation on the production of adiponectin in 3T3‐L1 adipocytes

PPARγ plays a key role in adipocyte specific gene expression. In this study, we assessed the effects of phorbol ester (TPA)‐sensitive PKC (c/nPKC) activation on the expression of adipocyte specific genes and inflammation related genes. Treatment with both TPA and TNFα decreased mRNA levels of PPARγ, aP2, LPL and adiponectin. TNFα, but not TPA, increased IL‐6 and MCP‐1 mRNA levels, Next, we investigated the effects of ligands which activate c/nPKC. Insulin and angiotensin II (AII), but not high glucose, reduced PPARγ, aP2 and adiponectin mRNA levels. AII‐induced suppression of these genes was restored in the presence of Go6976, a specific c/nPKC inhibitor, and candesartan, an AII receptor blocker. The effect of reduced insulin was prevented by Go6976 and LY294002, a specific PI 3‐kinase inhibitors. Our results indicate that activation of c/nPKC could debilitate and/or might deteriorate insulin sensitivity in vivo, through the reduction of PPARγ and adiponectin expression in adipocyte.

Anti-p155/140 antibody-positive dermatomyositis with metastasis originating from an unknown site.

Dermatomyositis (DM) is a systemic inflammatory myopathy with characteristic cutaneous manifestations (a heliotrope rash, Gottrons papules, paronychial erythema and nailfold bleeding) and is often associated with interstitial lung disease and internal malignancy. Thus far, some autoantibodies specific for myositis have been discovered, including antibodies to aminoacyl-tRNA synthetases (ARS), anti-Mi-2 antibodies, anti-CADM 140 antibody, anti-p155/140 antibody and others (1-3). The various autoantibody-positive subgroups of DM vary in their clinical features. Of these myositis-specific autoantibodies, the anti-p155/140 antibody is a 155-kDa reactive nuclear protein relevant to cancer-associated DM (1, 4-8). However, the frequency of malignancies in patients with anti-p155/140 antibody is undefined because no large epidemiological studies have been undertaken. We describe here a patient with anti-p155/140 antibody-positive DM who had a poorly differentiated metastatic adenocarcinoma; however, the primary tumour could not be identified despite comprehensive examination.

Effect of Dehydroepiandrosterone on Insulin Sensitivity and Adipocyte Growth in Otsuka Long-Evans Tokushima-Fatty Rats

Dehydroepiandrosterone (DHEA) (1) is the major adrenal androgen of young adults. However, serum concentration of DHEA in 60 yearold men shows a gradual decrease, when compared with young men aged 25-30 years old. This decrease occurs as the incidence of atherosclerosis (2), obesity (3), and diabetes increases (4), suggesting that administration of DHEA may protect against the development of these disorders. Previously, we reported that in vitro DHEA treatment increased glucose uptake and activation of PI 3-kinase in native rat adipocytes (5). Protein kinase C (PKC) is a family of serine/threonine kinases, which play key functions in cellular signal transduction. Three categories of PKC, conventional, novel, and atypical PKCs, have been described depending on their mechanisms of activation. Moreover, it is known that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is the hub of many signaling pathways, which phosphorylate many downstream kinases of phosphatidylinositol 3-kinase (PI 3-kinase), such as Akt kinase, S6 kinase and PKC. Previous studies suggested that atypical PKC (aPKC/) isoforms are required for insulin stimulation of glucose uptake (6), and PDK1 is necessary for activation of aPKCs (7). It has been reported that DHEA treatment reduces fat accumulation and protects against insulin resistance via an increase in PI 3-kinase after immunoprecipitation with insulin receptor substrate-1 (IRS-1) in male rats (8). We have investigated the in-vitro and in-vivo effects of DHEA on insulin-induced glucose uptake in adipocytes of Otsuka Log-Evans Tokushima fatty (OLETF) (9) and LETO rats. Moreover, we have shown the DHEA-induced glucose uptake by activation of PI 3-kinase/atypaical PKC siganlling without association with IRS-1 (10). In vivo treatment with DHEA affects on a decrease of adipose tissue via downregulation of peroxisome proliferator-activated receptor  (PPAR) expression (11). Based on above results, we have searched more precise mechanism of DHEA-induced amelioration of insulin sensitivity and clinical application of DHEA in diabetic animal models and human male adults.