Safety Evaluation of Curcumol by a Repeated Dose 28-Day Oral Exposure Toxicity Study in Rats.

Curcumol, a natural product isolated from the traditional Chinese medicine Rhizoma curcumae, possesses various potential therapeutic values in many diseases. However, evidence of its toxicological profile is currently lacking. In this study, a repeated toxicity study of curcumol was conducted for the first time. SD rats were exposed to doses of 250, 500, 1000 mg/kg in a selected dose formulation for 28 days through oral administration. The potential toxic effects of curcumol on the blood system were observed and further validated in vivo and in vitro. Moreover, other hematology and biochemistry parameters as well as the weight of organs were altered, but no related histopathological signs were observed, indicating these changes were not regarded as toxicologically relevant. Our current findings provide a complete understanding of the safety profile of curcumol, which may contribute to its further study of investigational new drug application.

Epidemiological Investigation of 387 Individuals Over 65 Years Old With Osteoporotic Fractures.

Context: With the rapidly aging population globally, osteoporosis (OP) has become a major public health problem, and fracture is a common complication of OP. Older adults, especially postmenopausal women, have a higher incidence of OP. Objective: The study intended to analyze the clinical information, epidemiological characteristics, treatments, and follow-up results of patients with osteoporotic fractures (OPFs) in adults over 65 years old, to provide data support for the prevention, treatment, and use of OPF focus groups in clinical practice. Design: The research team performed a retrospective analysis using electronic medical records and related imaging data of patients. Setting: The study took place at Hebei General Hospital in Hebei, China. Participants: Participants were 387 patients over 65 years old with osteoporotic fractures who had been admitted to the hospital between July 2012 and July 2018. Outcome Measures: The research team recorded participants' ages, genders, fracture causes, and fracture sites. The team performed a follow-up analysis on refractures, treatment with anti-osteoporotic drugs, exercise, and survival status within the 3 years after surgery. Results: The study's male-to-female ratio was 1:3.1, and the rate of osteoporotic fracture for females was significantly higher than that of males. The mean age of participants with fractures was 75.6 ± 8.5 years, and most fractures occurred in participants 78 to 85 years old. Of the 387 participants, 169 participants had hip fractures (43.67%); 98 had vertebral compression fractures (25.32%); 51 had distal radius and ulna fractures (13.18%); 42 had proximal humerus fractures (10.85%); and 27 had other fractures (6.98%). The number of women with fractures at each site was greater than the number of men, but the differences weren't statistically significant (P > .05). The main causes of injury were falls (71.58%), and the main place of the occurrence of injury was at home (65.6%). Of the 387 participants, 346 had surgical treatment (89.41%), and the effective rate of surgical treatment was 99.42%. Three years after surgery, the research team followed up with 235 participants, for a follow-up rate of 60.72%. Within the 3 years of the follow-up period, 61 participants had refractures (25.63%), 29 received treatment with regular anti-osteoporotic drugs (12.34%), 36 exercised twice or more a week (15.32%), and 32 had died for various reasons (13.62%). Conclusions: The study preliminarily described the epidemiological characteristics of 387 osteoporotic fractures in adults over 65 years old. More women had fractures than men; the hip was the most common fracture site, and falls were the main cause of injury. Most of the fractures occurred in the place of residence, and the refracture rate was 25.96% at three years after surgery.

Pharmacokinetics, tissue distribution, and plasma protein binding rate of curcumol in rats using liquid chromatography tandem mass spectrometry.

Objective: Curcumol is one of the major active ingredients isolated from the traditional Chinese medicine Curcumae Rhizoma and is reported to exhibit various bioactivities, such as anti-tumor and anti-liver fibrosis effects. However, studies of curcumol pharmacokinetics and tissue distribution are currently lacking. This study aims to characterize the pharmacokinetics, tissue distribution, and protein binding rate of curcumol. Methods: Pharmacokinetics properties of curcumol were investigated afte doses of 10, 40, and 80 mg/kg of curcumol for rats and a single dose of 2.0 mg/kg curcumol was given to rats via intravenous administration to investigate bioavailability. Tissue distribution was investigated after a single dose of 40 mg/kg of orally administered curcumol. Plasma protein binding of curcumol was studied in vitro via the rapid equilibrium dialysis system. Bound and unbound curcumol in rat plasma were analyzed to calculate the plasma protein binding rate. A UHPLC-MS/MS method was developed and validated to determine curcumol in rat plasma and tissues and applied to study the pharmacokinetics, tissue distribution, and plasma protein binding in rats. Results: After oral administration of 10, 40, and 80 mg/kg curcumol, results indicated a rapid absorption and quick elimination of curcumol in rats. The bioavailability ranging from 9.2% to 13.1% was calculated based on the area under the curves (AUC) of oral and intravenous administration of curcumol. During tissue distribution, most organs observed a maximum concentration of curcumol within 0.5-1.0 h. A high accumulation of curcumol was found in the small intestine, colon, liver, and kidney. Moreover, high protein binding rates ranging from 85.6% to 93.4% of curcumol were observed in rat plasma. Conclusion: This study characterized the pharmacokinetics, tissue distribution, and protein binding rates of curcumol in rats for the first time, which can provide a solid foundation for research into the mechanisms of curcumol's biological function and clinical application.

[Study on the cholelitholytic effect and safety of the preparation of Chinese medicine compound].

OBJECTIVE: To study the cholelitholytic effect and safety of the preparation of Chinese medicine compound. METHOD: Experiments were performed to study the efficacy of gallstones dissolution of the preparation of Chinese medicine compound in vitro and in vivo. The toxicity was studied by pathological and blood biochemical changes. RESULT: The preparation of Chinese medicine compound dissolved cholesterol and mixing gallstones in 7 days in vitro and in vivo, no influence on the blood biochemistry and the other organs of the rabbits. CONCLUSION: The preparation of Chinese medicine compound is effective and safe for treatment of chololithiasis.

[Laboratory and clinical study of levofloxacin against Helicobacter pylori].

OBJECTIVE: To assess antibacterial activity of levofloxacin to Helicobacter pylori (Hp) strains In Vitro and In Vivo. METHODS: The Minimum inhibitory concentration (MIC) for 52 clinical isolates was detected by agar dilution method and was compared with those of amoxicillin and clarithromycin. To examine the effects of pH variation on the susceptibility of Hp to levofloxacin, Mueller-Hinton agar with 7% defibrinated sheep blood was adjusted to a pH range of 4.0, 5.0, 7.0 by adding hydrochloric acid. 85 Hp-positive Patients with chronic active gastritis or active peptic ulcer disease were consecutively recruited in a prospective, open-label study. The enrolled patients were randomised to receive a seven-day course of omeprazole 20 mg bid plus amoxicillin 1000mg bid and levofloxacin 200mg bid. Their Hp status was assessed by (13)C-urea breath test and/or endoscopy 4 - 6 weeks after the end of treatment. RESULTS: The resistant rates of strains to levofloxacin, amoxicillin and clarithromycin were 1.9%, 11.5% and 25%, respectively. A dual-resistance to amoxicillin and clarithromycin was demonstrated in five Hp strains (9.6%), which were all susceptible to levofloxacin. The prevalence of strains with resistance to levofloxacin was lower than that of strains with resistance to clarithromycin (P < 0.01), and was no statistically different with amoxicillin (P > 0.05). The activity of levofloxacin was diminished under acidic environment (P < 0.01). 84 enrolled patients completed the study. 76 patients (PP and ITT analysis, 91.7%; 90.6%) become Hp-negative. Slight side-effects occurred in 5 patients (5.9%). CONCLUSION: In the present study, we report a high rate of resistance to amoxicillin and clarithromycin in this region. Omeprazole/levofloxacin-based triple therapy, including amoxicillin, is attractive because they combine a high eradication efficacy with an excellent tolerability and safety profile.