Solid lipid nanoparticles of lutein with improved dissolution behavior and oral absorption.

The present study aimed to develop solid lipid nanoparticles of lutein (SLN/LT) with improved dissolution behavior and oral absorption. SLN/LT were prepared by a flash nanoprecipitation method using a multi-inlet vortex mixer, and their physicochemical, photochemical, and pharmacokinetic properties were evaluated. The mean particle size of SLN/LT re-dispersed in water was 237 nm, and small spherical particles with no significant aggregation were observed. LT significantly generated singlet oxygen upon exposure to pseudo-sunlight (250 W/m2, 1 h), suggesting its high photoreactivity. The remaining LT in LT solution, crystalline LT, and SLN/LT after irradiation with pseudo-sunlight (250 W/m2, 2 h) were 56.3, 86.7, and 101%, respectively. SLN/LT showed improved dissolution behavior of LT in simulated intestinal fluid, and the dissolved amounts of LT at 2 h were at least 50 times higher than that of crystalline LT. Orally administered SLN/LT (100 mg-LT/kg) exhibited enhanced oral absorption of LT, as evidenced by a relative bioavailability of 3.7 to crystalline LT in rats. SLN/LT may be a promising dosage form for orally available LT supplements, possibly leading to enhanced nutritional functions of LT.

Asymmetric Total Synthesis of Indole Alkaloids Containing an Indoline Spiroaminal Framework.

The total synthesis of the indole alkaloids, neoxaline, oxaline and meleagrin A, all containing a unique indoline spiroaminal framework, was accomplished through the stereoselective introduction of a reverse prenyl group to the congested benzylic carbon of furoindoline, a two-pot transformation of indoline (containing three nitrogen atoms at appropriate positions) to the featured indoline spiroaminal framework, and elimination of carbonate assisted by the adjacent imidazole moiety to construct the (E)-dehydrohistidine. The absolute stereochemistry of neoxaline was elucidated through our total synthesis. In addition, we evaluated the bioactivity, especially the anti-infectious properties, of neoxaline and oxaline, and of some synthetic intermediates.

Pu-erh tea hot-water extract activates Akt and induces insulin-independent glucose transport in rat skeletal muscle.

Skeletal muscle is a major organ that is important for whole-body glucose metabolism. We found that when isolated rat epitrochlearis muscle was incubated with a Pu-erh tea hot-water extract (PTE) for 30 min, the rate of 3-O-methyl-D-glucose (3MG) transport increased in the absence of insulin. This activation was associated with an increase in Ser(473) phosphorylation of Akt, a signaling intermediary leading to insulin-dependent glucose transport, but not Tyr(458) phosphorylation of phosphoinositide 3-kinase p85, an upstream molecule of Akt. PTE-stimulated 3MG transport was also not accompanied by Thr(172) phosphorylation of the catalytic α-subunit of 5'-AMP-activated protein kinase (AMPK). Gallic acid, a water-soluble ingredient in Pu-erh tea, stimulated Akt phosphorylation, but not AMPK phosphorylation. These results suggest that Pu-erh tea potentially promotes skeletal muscle glucose transport at least in part by activating Akt.

[A case of skin cancer diagnosed 21 days after renal transplantation].

The patient was a 67-year-old man who was started on peritoneal dialysis for treatment of diabetic nephropathy in March 2010. He received an ABO-compatible living-donor kidney transplant from his wife in October 2010. The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, steroid and basiliximab. Before the operation, a bump on his forehead/temple region that was increasing in size for years was noted. The bump had a scaly surface and the top of the bump was sloughed on postoperative day 14. Histological examination suggested malignancy. On postoperative day 21, a skin biopsy was performed by dermatologists and squamous cell carcinoma was confirmed. On postoperative day 36, wide excision and transposition flap procedures were performed by the plastic surgeon. At 15 months after transplantation, the kidney graft was functioning well with a serum creatinine level of 0.84 mg/dl and there was no sign of recurrence of the squamous cell carcinoma.

Risk factors for major limb amputations in diabetic foot gangrene patients.

We analyzed the clinical picture of diabetic foot lesion patients to investigate the risk factors for major limb amputations. The subjects were 210 diabetic foot lesion patients treated at our department over the past 9 years. The mean follow-up period was 604.5 [standard deviation (S.D.) 451.2] days with a median value of 492 days. There were 113 men and 97 women. By the final follow-up day, 18 underwent bypass surgeries (9%) and 13 skin grafts (6%), while 110 patients (52%) finally required limb amputation. The breakdown was 45 major amputations above or below the knee and 65 minor amputations of the toes or metatarsals. The outcomes of the major amputations were retrospectively analyzed by group. The blood glucose control was poor in all 45 major amputees, and their mean HbA1c (8.80%) was higher than that in the minor or non-amputation group (7.79%, P = 0.035). In the major amputation group, two patients had loss of vision due to retinopathy, and 30 patients received long-term hemodialysis due to nephropathy. The rate of arteriosclerosis obliterans (ASO) was higher in the major amputation group than in the minor or non-amputation group, and arteriography showed significantly high rates of multiple stenosis. Multivariate analysis of these results by the proportional hazard model showed that ASO with multiple stenosis (hazard ratio 3.23, 95% CI: 1.12-5.10), hemodialysis (2.14, 95% CI: 1.17-3.44), and HbA1c (1.20, 95% CI: 1.03-1.41) were independent risk factors for major amputation. The 3-year survival rate was 24.1% in the major amputation group and 93.0% in the minor or non-amputation group, and the life expectancy was significantly lower for the major amputees than the minor or non-amputees (P<0.0001). Together with early detection and treatment of foot lesions, good blood glucose control and early management of systemic complications such as nephropathy and arteriosclerosis are considered important to avoid major amputations.