Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway

BACKGROUND: Leaves of the natural plant lotus are used in traditional Chinese medicine and tea production. They are rich in flavonoids. METHODS: In this study, lotus leaf flavonoids (LLF) were applied to human lung cancer A549 cells and human small cell lung cancer cells H446 in vitro to verify the effect of LLF on apoptosis in these cells through the ROS/p38 MAPK pathway. RESULTS: LLF had no toxic effect on normal cells at concentrations up to 500 µg/mL, but could significantly inhibit the proliferation of A549 cells and H446 cells. Flow cytometry showed that LLF could induce growth in A549 cells. We also found that LLF could increase ROS and MDA levels, and decrease SOD activity in A549 cells. Furthermore, qRT-PCR and western blot analyses showed that LLF could upregulate the expression of p38 MAPK (p-p38 MAPK), caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9 and Bax and downregulate the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1, and Bcl-2 in A549 cells. Results of HPLC showed that LLF mainly contain five active substances: kaemp-feritrin, hyperoside, astragalin, phloridzin, and quercetin. The apoptosis-inducing effect of LLF on A549 cells came from these naturally active compounds. CONCLUSIONS: We have shown in this study that LLF is a bioactive substance that can induce apoptosis in A549 cells in vitro, and merits further research and development.

The effect of food intake on the pk of rhein released from diacerein

Diacerein is a symptomatic slow-acting drug used for treating osteoarthritis. This drug is completely metabolized into the active metabolite rhein before reaching the systemic circulation. This study evaluated the effects of food on the pharmacokinetics of rhein released from diacerein in healthy Chinese subjects. This was a single-center, randomized, single-dose, open-label, two-period, cross-over study. Twenty-four healthy subjects were randomly selected to receive a single oral dose of 50 mg diacerein capsule in either fasted or fed state on two separate visits. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters were calculated using WinNonlin software. In the fasted and fed states, the main pharmacokinetic parameters of diacerein capsule were as follows: Cmax were (4471 ± 936), (3225 ± 755) ng/mL, t1/2 were (4.22 ± 0.42), (4.19 ± 1.05) h, tmax were (2.61 ± 1.25), (3.81 ± 1.29) h, AUC0-24 h were (24223 ± 4895), (24316 ± 5856) h·ng/mL, and AUC0-∞ were (24743 ± 5046), (25170 ± 6415) h·ng/mL. The absorption rate of diacerein capsule was obviously delayed by food intake but the absorption degree remained unaffected.

Analysis of clinicopathological characteristics and survival of 1 915 oral cavity squamous cell carcinoma patients: 24-year experience from a single institution / 口腔疾病防治

Objective @#To investigate the clinicopathological features and survival rate of oral squamous cell carcinoma patients in China.@*Methods@#The clinicopathological characteristics, stage, treatment modality, and 5-year disease-specific survival (DSS) rate of 1 915 OCSCC patients who received initial treatment at the Sun Yat-sen University Cancer Center from 1990 to 2013 were collected and analyzed. The clinicopathological characteristics, stage, treatment modality, and 5-year disease-specific survival (DSS) rate of OCSCC patients treated during the successive decades of 1990-1999, 2000-2009, and 2010-2013 were analyzed retrospectively to show the trends over time.@*Results @#The average age of all OCSCC patients who received initial treatment at this cancer center from 1990 to 2013 was 54.8 years (SD, 12.6 years). The sex ratio was approximately 2:1. The oral tongue was the site most prone for OCSCC, accounting for 63.6% of all cases. The proportions of early-stage (Ⅰ-Ⅱ) and advanced-stage (Ⅲ-Ⅳ) cases were approximate. Regarding the treatment modality, surgery-based treatment accounted for 80.4%. Survival analysis showed that the 5-year DSS rate of all cases was 57%. Survival decreased with age. The survival of females, nonsmokers, and nondrinkers was higher than that of males, smokers, and drinkers. The 5-year DSS rates of patients with squamous cell carcinoma of the lips, oral tongue, and other sites of the oral cavity were 81%, 63%, and 42%, respectively. The 5-year DSS rates of patients who received surgery-based treatment and nonsurgical treatment were 66% and 19%, respectively. The analysis of trends over time showed that in the period of 1990-1999 and 2010-2013, the age and sex ratio were relatively stable. The proportion of patients with squamous cell carcinoma of the lips and oral tongue gradually decreased, while the proportion of those with squamous cell carcinoma of the other sites of the oral cavity gradually increased. The proportion of surgery-based treatment increased from 77.7% to 91.3%. The 5-year DSS rate gradually increased from 53% in 1990-1999 to 64% in 2010-2013. The 5-year DSS rate of female patients increased significantly from 55% to 78%. However, the 5-year DSS rate of male patients was relatively stable. The 5-year DSS rate of patients who received surgery-based treatment gradually increased from 62% to 69%. @*Conclusion@#The 5-year DSS rate has steadily improved for OCSCC patients at this cancer center from 1990-2013, especially in female patients. The 5-year DSS rate of patients with squamous cell carcinoma of the oral tongue has reached the rate in developed countries worldwide. The proportion and survival rate of patients who received surgery-based treatment gradually increased. The survival rate of patients with squamous cell carcinoma of the other sites of the oral cavity was significantly lower than that of patients with squamous cell carcinoma of the lips and oral tongue, suggesting that more effort should be put into the treatment of patients with squamous cell carcinoma of the other sites of the oral cavity to improve the survival rate in the future.

A rare variation of suprascapular artery originated from the axillary artery / Una rara variación de la arteria supraescapular originada de la arteria axilar

SUMMARY: The suprascapular artery (SSA) has been identified to be of clinical relevance to clavicular fracture, suprascapular neuropathy and surgical intervention of shoulder. Thus its origin and course have been intensively studied. In this case, we found a unilateral variation of the suprascapular artery, originating from the 1st segment of axillary artery, and sequentially penetrating the upper trunk of brachial plexus, passing through the suprascapular notch under the superior transverse scapular ligament. This case will be helpful to clinical management in cervical and shoulder region.

RESUMEN: Se ha identificado que la arteria supraescapular (ASS) tiene relevancia clínica en la fractura clavicular, la neuropatía supraescapular y la intervención quirúrgica del hombro. En consecuencia, su origen y su curso han sido ampliamente estudiados. En este caso, encontramos una variación unilateral de la arteria supraescapular, originada en el primer segmento de la arteria axilar, y que penetraba secuencialmente en el tronco superior del plexo braquial, pasando a través de la incisura supraescapular debajo del ligamento escapular transverso superior. Este caso será útil para el manejo clínico en la región cervical y del hombro.

Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

ABSTRACT Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.

Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

L-3-n-butilftalida (L-NMP) é um antioxidante natural, que pode ser utilizado para o tratamento do acidente isquêmico agudo e demência vascular. Este estudo avaliou segurança, tolerância e farmacocinética de comprimidos de L-NBP em chineses voluntários sadios. Este foi um estudo monocêntrico, randomizado, duplo cego, com controle por placebo e doses única e múltipla. Os indivíduos receberam dose única de comprimido de L-NBP de 80, 160, 320 ou 480 mg (n=40) e doses múltiplas de 160 mg duas vezes ao dia, por sete dias (n=12). Amostras de plasma foram analisadas com LC-MS/MS. Os parâmetros farmacocinéticos do L-NBP foram calculados utilizando análise não compartimental, com o programa WinNonlin. A análise estatística foi realizada utilizando-se o programa SPSS. Todos os eventos adversos (EAs) foram moderados e de duração limitada. EAs nesse estudo ocorreram menos frequentemente e mais moderadamente do que os EAs relacionados para cápsulas moles de DL-NBP. Não se observaram eventos adversos graves (EAG), morte ou abandono do estudo. Com dose única, atingiu-se o Cmax em cerca de 1 hora e o t1/2 médio foi de, aproximadamente, 13,76 h. A área sob a curva (ASC) e o Cmax aumentaram com o aumento da dose, mas não se observou proporcionalidade na faixa acima de 160 a 480 mg. No estudo de dose múltipla, o equilíbrio foi alcançado em três dias, com pequeno acúmulo. Em resumo, o comprimido de L-NMP foi bem tolerado em indivíduos chineses saudáveis. O acúmulo pequeno apareceu após doses repetidas.

Influence of hypoxia on apoptosis and glucose intake in bone marrow derived mesenchymal stem cells in rats / 中国实验血液学杂志

To investigate the effects of hypoxia on the apoptosis and glucose intake of mesenchymal stem cells (MSCs), MSCs derived from bone marrow of rats were incubated in the atmosphere of 1% O(2) for a series of time points and their glucose-intaking capacity, ultrastructural changes and apoptotic proportions were analyzed by (3)H-labeling assay, electron microscopy and flow cytometry, respectively. The results showed that the cultured cells took the fibroblast-like morphology and could be induced into osteoblasts and adipocytes under appropriate conditions. The proportions of apoptotic cells after hypoxia treatment for 1, 4 and 8 hours were 13.7 +/- 2.26%, 14.1 +/- 2.78% and 14.7 +/- 4.01%, respectively, all of which were significantly higher than that observed in normoxic counterparts (0.09 +/- 2.03%, p < 0.05). Also, cell death occurred after hypoxia treatment and the death rates were 3.11 +/- 2.14%, 4.72 +/- 2.05% and 4.91 +/- 3.72% for 1, 4 and 8 hours incubation respectively. Under hypoxia culture in vitro, cell membrane microvillus began to fall off and the mitochondrias became swelling at 1 hour, and the above changes increasingly aggravated along with hypoxia time prolongation. The (3)H-glucose intaking ratios of MSCs at different hypoxia time points significantly decreased than those in normoxic cells (p < 0.01). It is concluded that the acute hypoxia can induce down-regulation of glucose-intaking capacity, ultrastructural changes and apoptosis of MSCs.