We performed a prospective study to determine the effects of introducing low-load muscular training with moderate restriction of blood flow during the first 16 weeks after reconstruction of the anterior cruciate ligament. 44 subjects (average age 29 (18-52) years) were randomized into a group that trained restriction of blood flow (group R, n = 22) and a group that trained without restriction (group N, n = 22). Both groups followed the same training schedule. Evaluations of knee extensor and flexor torques before surgery and 16 weeks after it showed a significant increase in muscular strength in group R as compared to group N. The preoperative/16-week postoperative ratio of the crosssectional area of the knee extensor muscles showed a statistically significant enlargement in group R as compared to group N. 16 weeks after surgery, the short diameters of type 1 and type 2 fibers of M. vastus lateralis tended to be larger in group R (n = 8) than in group N (n = 8), although the differences were not significant. These findings show that low-load resistance muscular training during moderate restriction of blood flow is an effective exercise for early muscular training after reconstruction of the anterior cruciate ligament. Recently, many studies have reported stable postoperative results of ligament reconstruction by autologous tendon grafting of the anterior cruciate ligament (ACL), a procedure which permits early rehabilitation according activities of daily living and sports. However, an important issue is how early the patients can return to athletic activities. Currently, several techniques of ACL reconstruc
The effects of dietary administration of 1H, 1H, 2H, 2H-perfluorodecanol (8-2 telomer alcohol), on peroxisome proliferation in the liver of mice were studied. Male ddY mice were fed on a diet containing 8-2 telomer alcohol at concentrations of 0, 0.025, 0.05, 0.1, and 0.2% (w/w) for 7, 14, 21, and 28 days. These treatments with 8-2 telomer alcohol caused liver enlargement in a dose- and duration-dependent manner. Peroxisome proliferation in the liver of mice was confirmed by electron microscopic examination. Peroxisomal acyl-CoA oxidase was induced by these treatments with 8-2 telomer alcohol in a dose- and time-dependent manner. The concentration of perfluorooctanoic acid (PFOA) and related compounds were determined in the liver and plasma, since PFOA had been shown to be a possible metabolite of 8-2 telomer alcohol and to cause significant peroxisome proliferation in rodents. Five metabolites, namely, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), 2H, 2H-perfluorodecanoic acid (8-2 telomer acid), and two unidentified metabolites, were present in the liver and serum. PFOA was confirmed to be accumulated in the liver of mice following the administration of 8-2 telomer alcohol in a dose- and duration-dependent manner. A linear relationship was observed between the concentration of PFOA and the activity of peroxisomal acyl-CoA oxidase in the liver of mice. These results strongly suggest that PFOA, but not 8-2 telomer alcohol itself, caused peroxisome proliferation in the liver. The present study provided evidence that 8-2 telomer alcohol is converted into PFOA in vivo and that the PFOA formed produces biological effects in the liver of mice.
The presence of a higher level of sIL-6 and the varus alignment of the joint is associated with pain in early- and advanced-stage knee OA patients, respectively.
Everolimus has demonstrated antitumor efficacy for various cancers as a result of its inhibition of the mammalian target of rapamycin (mTOR) signaling cascade, which activates cell growth and cell proliferation. However, the low water solubility and low bioavailability of everolimus have prevented its clinical development as an anticancer drug. Therefore, to address the unsuitable characteristic of everolimus, we attempted to prepare liposomal everolimus as a viable drug delivery system, and then evaluated the anticancer efficacy of this system against a medullary thyroid carcinoma cell line (TT cells), a breast cancer cell line (MCF-7 cells) and a small lung carcinoma cell line (NCI-H446 cells). The particle size and entrapment efficacy of liposomal everolimus was ca. 80 nm and more than 90%, respectively. Liposomal everolimus showed higher cytotoxicity against NCI-H446 cells compared with TT cells. Against NCI-H446 tumors, significant suppression of the tumor volume was observed in liposomal everolimus-treated mice by intravenous injection, compared with free everolimus-treated mice by intraperitoneal injection, at a dose of 5 mg/kg without body weight loss. This study showed that liposomal everolimus could be a powerful formulation with anticancer efficacy for some cancers.
Medullary thyroid carcinoma (MTC) is a rare endocrine tumor that frequently metastasizes, but treatment with irinotecan (CPT-11) is limited because of side effects. MTC is known to overexpress the somatostatin receptor subtype 2 (SSTR2). Octreotide (Oct) is a somatostatin analogue that has a high binding affinity for SSTR and can be used as a tumor-targeting ligand. We prepared Oct-targeted liposomes loaded with CPT-11 using Oct-poly (ethylene glycol) (PEG)-lipid and evaluated Oct-mediated association and cytotoxicity of the liposomes with an MTC cell line TT. The association of higher concentrations of modified Oct-targeted liposomes with TT cells was significantly higher than PEGylated liposomes and was significantly inhibited by empty Oct-targeted liposomes but not by free Oct. With exposure for 96 h, the cytotoxicity of Oct-targeted liposomal CPT-11 (IC50: 1.05 ± 0.47 μM) was higher than free CPT-11 (IC50: 3.76 ± 0.61 μM) or PEGylated liposomal CPT-11 (IC50: 3.05 ± 0.28 μM). In addition, empty Oct-targeted liposomes showed significantly higher cytotoxicity than empty nontargeted liposomes at a concentration where free Oct did not show cytotoxicity, suggesting that Oct as a ligand showed cytotoxicity. Moreover, Oct-targeted liposomal CPT-11 led to significantly higher antitumor activity and prolonged the survival time compared with nontargeted liposomal and free CPT-11 at a one-third dose and lower administration times with free CPT-11. These findings indicated that Oct-targeted liposomes loaded with CPT-11 may offer considerable potential for MTC chemotherapy because cytotoxicity of both CPT-11 and Oct was enhanced by effective cellular uptake via SSTR2.
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