Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study.

BACKGROUND: Clinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. METHODS: This was a post hoc analysis of the 24-month Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. RESULTS: Of the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49-0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. CONCLUSIONS: Tiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry.

Rhizoma Alismatis (RA) was wildly used for treatment of dysuria, pyelonephritis, hyperlipidemia, enteritis diarrhea, diabetes, inflammation, and cancer. Triterpenoids are the major active components of RA, and its extract is mainly composed of alisol A (ALA), alisol B (ALB), alisol C 23-acetate (ALC-23A), alisol A 24-acetate (ALA-24A), and alisol B 23-acetate (ALB-23A). In this study, a simple, reliable, and sensitive ultra high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was created and validated for the quantification of the five major triterpenoids in rat plasma and various tissues biosamples (including intestine, stomach, liver, kidney, fat, muscle, brain, heart, lung, spleen, and testes). The plasma and tissues biosamples were pretreated by direct precipitation deproteinization method with acetonitrile. 17α-Hydroxyprogesterone was used as internal standard (IS). The chromatography was performed on a Phenomenex C8 column (30×2.00mm, 1.8µm) at room temperature with gradient elution. Compounds were quantified by selected multi-reactions monitoring (SRM) scanning with positive electric spray ionization mode. The linearity of detection for each triterpene was respectively from 1 to 1000ng/mL for ALC-23A and ALA, from 4 to 4000ng/mL for ALA-24A, from 10 to 10,000ng/mL for ALB, and from 2 to 2000ng/mL for ALB-23B (r>0.99) with low quantification limits of 1-10ng/mL for all analytes. All of the other validation parameters were also in an acceptable range. The validated UHPLC-MS/MS method subsequently applied for the pharmacokinetic and tissue distribution studies of RA extract. After orally given 100mg/kg of RA extract, ALA was the most exposed component, followed by ALB and ALA-24A. Whereas significant gender difference was observed for ALB, ALA, and ALA-24A between female and male rats. The AUC(0-∞) of ALA, ALB, and ALA-24A in female rats were approximately 2-5 fold larger than that in male rats. These triterpenoids also displayed approximately 1.5-2 times longer half-life (t1/2) in female rats. Appearant Km, Vmax and Clint of ALA, ALB, and ALA-24A were calculated by substrate depletion approach, rat P450 CYP3A2 plays an important role in the metabolism of ALA, ALB, and ALA-24A, which is an important factor leading to the different exprosures of ALA, ALB, and ALA-24A between the male rats and the female rats. Furthermore, results from tissue distribution in male rats showed that the main tissue depots of five triterpenoids were the stomach/intestine, followed by the liver, brain, and fat. However, ALA was still measured in the kidney after a long elimination time. ALB and ALB-23B exhibited lower elimination rate in the testis. These results provide a fundamental support for further pharmacological development and clinical safety application of RA.

Application of COI barcode sequence for the identification of snake medicine (Zaocys).

Counterfeits in the medicine market make the authentication of snakes used for Chinese medicine a challenge to Chinese drug regulatory control agencies. This paper explores existing methods that can be used to quickly and accurately distinguish Zaocys (Z. dhumnades) from its counterfeits for routine identification of snake meats in food and drug control laboratories. In this research, the Cytochrome Oxidase I (COI) fragments of 51 samples from 17 species of snakes were amplified using Polymerase Chain Reaction (PCR) and sequenced. The inter- and intra-specific variations of COI sequences were analyzed and compared based on Kimura-2-parameter (K-2P) distances; the minimal interspecific K-2P distance was 0.0934, which was bigger than the maximum intraspecific K-2P distance in Z. dhumnades (0.0523), indicating that Zaocys can be separated from its counterfeits. The Neighbor-Joining (N-J) tree of the snakes was constructed and the results show that snakes of the same species cluster with 100% bootstrap values. Since the Zaocys and its counterfeits are of different species, they can be distinguished using the N-J tree method. Another 10 samples of Zaocys from markets and drug stores were identified at the species level, among which 5 samples were proven to be the counterfeits--Ptyas korros.

[Complication analysis of endorectal pull-through radical operation for Hirschsprung disease].

OBJECTIVE: To summarize the complications after endorectal pull-through radical operation, Soave procedure, for Hirschsprung disease. METHODS: Clinical data of 286 cases with Hirschsprung disease who received Soave procedure and were proved by postoperative pathology in our hospital from February 2003 to February 2010 were analyzed retrospectively. All the patients were diagnosed with barium enema and anorectal manometry. Among them, 233 cases(81.5%) were identified during neonatal period. All the patients underwent cleansing enema and anus dilation immediately after definite diagnosis. Radical operation with Soave endorectal pull-through procedure, including simple transanal endorectal pull-through in 251 cases(87.8%), transabdominal approach in 17 cases (5.9%), laparoscopy-assisted endorectal pull-through in 18 cases (6.3%). The operations were performed in 54 cases (18.9%) within 3 months of age, in 183 cases (64.1%) between 3 and 6 months, in 38 cases(13.3%) between 6 months and one year, in 10 cases (3.5%) older than 1 year. The rectosigmoid was resected in 259 cases. Subtotal colectomy was performed in 25 cases, and total colectomy in 2 cases. Postoperative regular anal dilation lasted for 6 months. A total of 286 cases (male:250, female:36) were followed up for 2 to 5 years. RESULTS: There was wound infection in 1 case, ileus in 1 cases, anastomotic stricture in 1 case, which was cured by continuous anal dilation. Two cases had constipation and received re-operation because of refractory to conservative therapy for 6 months. Perianal erosion was found in 63 cases(22.0%) and was healed within 3 months, except 2 children undergoing total colectomy. During follow-up, enterocolitis occurred in 11 cases(3.8%), including healing in 8 cases with conservative therapy, death in 1 case, and recurrent attacks in 2 cases. Soiling occurred in 45 cases(15.7%), among them, 5 cases presented in kindergarten and primary school. Morbidities of perianal erosion, enterocolitis and soiling were higher in infants undergoing operation within 3 months as compared to those more than 3 months [90.7%(49/63) vs. 6.0%(14/63), P=0.000; 9.3%(5/54) vs. 2.6%(6/232), P=0.022; 25.9%(14/54) vs. 13.4%(31/232), P=0.022]. Morbidity of perianal erosion enterocolitis was higher in infants undergoing subtotal or total colectomy as compared to those partial colon resection[51.9%(14/27) vs. 18.9%(49/259), P=0.000; 18.5%(5/27) vs. 2.3%(6/259), P=0.000]. CONCLUSIONS: Primary transanal endorental pull-through procedure can be performed in most children with Hirschsprung disease. Postoperative short-term complications are mainly perianal erosion and long-term ones are enterocolitis and soiling. Early diagnosis, colon irrigation, avoiding premature operation and anal dilation can decrease the morbidities of enterocolitis and soiling.

In vitro anti-coxsackievirus B(3) effect of ethyl acetate extract of Tian-hua-fen.

AIM: To investigation the anti-coxsackievirus B(3) (CVB(3m)) effect of the ethyl acetate extract of Tian-hua-fen on HeLa cells infected with CVB(3m). METHODS: HeLa cells were infected with CVB(3m) and the cytopathic effects (CPE) were observed through light microscope and crystal violet staining on 96-well plate and A(600) was detected using spectrophotometer. The protective effect of the extract to HeLa cells and the mechanism of the effect were also evaluated through the change of CPE and value of A(600). RESULTS: The extract had some toxicity to HeLa cells at a higher concentration while had a marked inhibitory effect on cell pathological changes at a lower concentration. Consistent results were got through these two methods. We also investigated the mechanism of its anti-CVB(3m) effect and the results indicated that the extract represented an inhibitory effect through all the processes of CVB(3m) attachment, entry, biosynthesis and assemble in cells. CONCLUSION: The results demonstrate that the ethyl acetate extract of Tian-hua-fen has a significant protective effect on HeLa cells infected with CVB(3m) in a dose-dependent manner and this effect exists through the process of CVB(3m) attachment, entry, biosynthesis and assemble in cells, suggesting that the ethyl acetate extract of Tian-hua-fen can be developed as an anti-virus agent.