Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague-Dawley rats.

Platycodi radix is widely used in traditional herbal medicine for the treatment of bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. This study aimed to investigate cell proliferation (Ki-67) and apoptosis (Caspase-3) potential in squamous cell hyperplasia of the stomach induced by a Platycodi radix water extract in a subchronic toxicity study. One hundred formalin-fixed, paraffin-embedded stomach tissues of rats treated with Platycodi radix at doses of 0, 500, 1,000, and 3,000 mg/kg body weight/day were used for the analysis. They were conventionally stained using hematoxylin and eosin (H&E) and immunohistochemically (IHC) stained using caspase-3 and Ki-67 antibodies. The incidence of squamous cell hyperplasia was significantly increased in the 3,000 mg/kg b.w./day treatment group in both sexes (p<0.01). However, the hyperplastic change was completely repaired after 4 weeks of recovery period. Ki-67 expression was similar in all groups, with no statistically significant differences among the groups. Caspase-3 expression was significantly increased in both sexes in the 3,000 mg/kg b.w./day treatment group (p<0.01), compared with the vehicle control groups, and then reduced to normal levels in the recovery groups in both sexes. In conclusion, this study showed that squamous cell hyperplasia induced by the Platycodi radix water extract in the limiting ridge of the stomach is not considered to be abnormal proliferative change; as a result, squamous cell hyperplasia is considered to be a non-adverse effect when induced by the oral administration of the Platycodi radix water extract once daily for 13 weeks in rats.

Safety studies on intravenous infusion of a potent angiogenesis inhibitor: taurocholate-conjugated low molecular weight heparin derivative LHT7 in preclinical models.

CONTEXT: As a class of angiogenesis inhibitors, heparin conjugates have shown significant effectiveness in several studies. OBJECTIVES: The purpose of our current study is to evaluate the effectiveness and safety of infusing the conjugate of low molecular weight heparin and taurocholate (LHT7), which has been developed as a potent angiogenesis inhibitor. METHODS: To evaluate its safety, the method of intravenous infusion was compared with its i.v. bolus administration. Intravenous infusion was administered at a rate of 400 µl/min/kg of body weight for 30 min. Pharmacokinetic (PK) analysis, organ accumulation, and plasma concentration profiles of LHT7 were measured. The anticancer effect of LHT7 was evaluated in murine and human xenograft models, and preclinical studies were performed in SD rats and beagle dogs. RESULTS: The results of the PK studies showed reduced organ accumulation in mice and the AUC(0-96 h) (area under the curve) was increased up to 1485 ± 125 h × µg/ml. The efficacy, at dose 1 mg/kg/2 d was higher for i.v. infusion than for i.v. bolus administration in both murine and human cancer models. The preclinical studies showed the safety dose of LHT7 is less than 20 mg/kg in SD rats and in the next safety analysis in beagle dogs showed that there were no organ-specific adverse effects in higher doses, such as, 12 mg/kg. LHT7 showed sustained effects with minimized adverse events when administered through i.v. infusion. CONCLUSIONS: LHT7 (i.v. infusion) could be safely used for further clinical development as a multi-targeting anti-angiogenic agent.

Prediction of bone mineral density and content from measures of physical activity and sedentary behavior in younger and older females.

BACKGROUND: Little is known regarding the extent to which physical activity (PA) and sedentary behavior (SB) influence bone mineral content (BMC) and bone mineral density (BMD) in females across the lifespan. METHODS: Data from 2232 females aged 12 years and older collected as part of the 2007-2008 National Health and Nutrition Examination Survey were analyzed. Categories of PA and SB were used to predict femoral and spinal BMD and BMC in four age groups (G1: 12-17; G2: 18-39; G3: 40-64; G4: ≥ 65 years). Self-reported PA categories included sufficient moderate-to-vigorous recreational PA (S-MVRPA) and insufficient MVRPA (I-MVRPA). RESULTS: G1 females who accumulated S-MVRPA displayed greater femoral and spinal BMC and BMD compared to G1 females who displayed I-MVRPA. For G4 females, higher levels of SB were associated with lower femoral BMC and BMD. CONCLUSIONS: These findings highlight the importance of engaging in sufficient moderate-to-vigorous physical activity during adolescence and reducing sedentary behavior in older adults to improve bone health in females.

Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague-Dawley rats.

Fermented Rhus verniciflua stem bark (FRVSB) extract, an urushiol-free extract of Rhus verniciflua Stokes (RVS) fermented with Fomitella fraxinea, has various biological activities. The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repeated oral administration to Sprague-Dawley rats. In the single dose toxicity study, the FRVSB extract was administered orally to male and female rats at single doses of 0, 2500, 5000, and 10,000mg/kg. No animals died and no toxic changes were observed in clinical signs, body weight, and necropsy findings during the 15-day period following administration. In the repeated dose toxicity study, the FRVSB extract was administered orally to male and female rats for 90days at doses of 0, 556, 1667, and 5000mg/kg/day. There were no treatment-related adverse effects in clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any dose tested. The approximate lethal dose of the FRVSB extract was >10,000mg/kg in both genders, the oral no-observed-adverse-effect level of the FRVSB extract was >5000mg/kg/day in both genders, and no target organs were identified.

Comparative study on the effects of bee venom pharmacopuncture according to the treatment method for knee osteoarthritis.

OBJECTIVES: The purpose of this study is to compare the effects of bee venom pharmacopuncture (BVP) therapy according to the methods used to treat knee osteoarthritis (OA): intra-acupoint combined with intra-articular injection, intra-acupoint injection, and intra-articular injection. METHODS: A total of 69 patients were recruited by the Department of Acupuncture & Moxibustion at Dong- Eui Oriental University Hospital from February 1 to July 23, 2012. The patients were assigned to 3 groups: the first group with intra-acupoint combined with intraarticular BVP Injection (the experimental group), the 2nd group with intra-acupoint BVP injection (control groupⅠ), and the 3rd group with intra-articular BVP injection (control groupⅡ). The participants were assigned in the order in which they were recruited. Treatments were done twice a week, for a total of 9 times. The effectiveness was assessed by using the visual analouge scale (VAS) and the Korea Western Ontario and McMaster Universities Osteoarthritis Index (KWOMAC). RESULTS: All three groups exhibited significant VAS and KWOMAC effects. Moreover, the 4 week follow-up after the final treatment showed a persistence of BVP effects. However, when the groups were compared, no statistically significant differences in VAS and KWOMAC were noted, but when improvement was considered, the results showed that intra-articular injection was more effective than intra-acupoint injection. Especially, intra-acupoint combined with intra-articular injection was the most effective among the three treatments. CONCLUSIONS: Combining intra-acupoint with intraarticular injection, depending on the patient's symptoms, may produce better results when conservatively treating knee OA.