OBJECTIVETo explore the in vitro anti-platelet effects of Ginsenoside -2A,a purified extract from Panax notoginseng.

METHODSPlatelet rich plasma (PRP) was prepared routinely from venous blood samples of patients with essential hypertension and normal persons. PRP was incubated with different concentrations of Nifedipine, Ginsenoside-2A ,and SK&F96365. Maximal platelet aggregation rate[ PAG (M) ] induced by 2 micromol/L ADP was taken as the observed index. Five-minute PAG( M) was determined for 5 consecutive times.

RESULTS(1) PAG (M) in essential hypertension group was 0. 89 +/- 0. 06, which was higher than that in the normal group (0. 68 +/-0. 07 ) with significant difference (P <0.01). (2)Nifedipine of two concentrations (10 p.mol/L,20 pVmol/L) had no effect on PAG(M) in either essential hypertension group or normal group(P >0. 05). (3)Different concentrations of SK&F96365 (2.5 micromol/L,5 micromol/L,10 micromol/L and 20 micromol/L) could inhibit the PAG(M) in essential hypertension group; (4) Differen concentrations of Ginsenoside -2A (2. 5 micromol/L, 5 micromol/L, 10 micromol/L and 20 micromol/L) could inhibit PAG ( M) in essential hypertension group; three concentrations of Ginsenoside -2A (5 micromol/L, 10 micromol/L, 20 micromol/L) could inhibit the PAG(M) in the normal group (all P <0.05).

CONCLUSIONPlatelet aggregating function in essential hypertension patients was obviously higher than that in the normal persons and platelets was in the high reactive status. Nifedipine had no inhibitive effect on platelet aggregation. SK&F96365 could inhibit the platelet aggregation. Ginsenoside-2A could inhibit platelet aggregation, and had the definite anti-platelet action.

Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ginsenosides ; administration & dosage ; pharmacology ; Humans ; Imidazoles ; administration & dosage ; pharmacology ; Nifedipine ; administration & dosage ; pharmacology ; Platelet Aggregation Inhibitors ; administration & dosage ; pharmacology

BACKGROUND: The selective unilateral administration of drugs into a single lung of a rat is difficult because of the small airway diameter. Therefore, a simple method for unilateral administration into rat lung is needed. METHODS: Rats were assigned to 1 of 2 groups according to the direction of the catheter used for drug administration. Anesthetized rats were intubated, and curved epidural catheters were rotated up to a maximum of 90degrees toward the left lung (group L) or right lung (group R). Bronchial catheters were then inserted via a tracheal tube and fixed. Methylene blue (0.3 ml) was injected via the epidural catheter. Additionally, to compare survival rates, rats were assigned to one of two groups according to the drug administration route. In group T, bleomycin hydrochloride (20 mg/kg) in 0.3 ml of phosphate-buffered saline (PBS) was administrated into the lung intratracheally via a tracheal tube. In group B, the same dose of bleomycin was administrated into the lung intrabronchially via a bronchial catheter, targeting the left lung. RESULTS: Gross examination revealed that targeted administration was 100% successful. Methylene blue was observed in the right lung of all rats in the R group and in the left lung of all rats in the L group. The survival rate was higher in group B than in group T. CONCLUSIONS: The intrabronchial method offers an advantage over tracheal administration as it decreases mortality and allows the administration of a drug unilaterally into a single lung or into a localized area without the need for double-lumen tubes or more invasive procedures.
Animals ; Bleomycin ; Catheters ; Drug Administration Routes ; Imidazoles ; Lung ; Methylene Blue ; Nitro Compounds ; Rats ; Survival Rate

BACKGROUND: Vardenafil is a phosphodiesterase type 5 inhibitor, used in erectile dysfunction. This study aimed to evaluate the pharmacokinetics and tolerability of vardenafil following a single oral administration in healthy male subjects. METHODS: A randomized, double-blind, placebo-controlled, single dosing, dose-escalation study was conducted in 30 healthy subjects. A single oral dose of vardenafil or placebo was given to 10 subjects (8 active + 2 placebo) in each dose group of 5, 10 and 20 mg. Serial blood and urine samples were obtained up to 48 hours for pharmacokinetic analysis. Vardenafil and its metabolite were detected by high performance liquid chromatography tandem mass spectrometry assay. RESULTS: A total of 45 adverse events (AE) were reported in 22 subjects, including 5 AEs from placebo treatment, and all the AEs were mild, except one case of moderate nasal stuffiness. Vardenafil was absorbed after a single oral dose, with the tmax of 0.5-1.0 hours. The Cmax and AUClast were 10.21 +/- 3.68 ug/L(mean +/- SD) and 18.08 +/- 7.44 ugxh/L in 5 mg dose group, 19.79 +/- 12.13 ug/L and 38.61 +/- 21.04 ugxh/L in 10 mg dose group and 53.16 +/- 37.01 ug/L and 110.05 +/- 69.65 ugxh/L in 20 mg dose group. Dose-linearity on AUClast and Cmax of vardenafil were observed in three dose groups. In all dose groups, the fraction excreted in urine was less than 1%. CONCLUSION: The vardenafil was tolerable over a single dose range of 5 - 20 mg. The pharmacokinetics of vardenfil after a single oral dose was explored and linear pharmacokinetic characteristics were observed over the dose range of 5 - 20 mg in healthy subjects.
Administration, Oral ; Chromatography, Liquid ; Erectile Dysfunction ; Humans ; Imidazoles ; Male ; Piperazines ; Sulfones ; Tandem Mass Spectrometry ; Triazines

Vulvo-vaginal candidiasis (VVC) is a common infection among women. 5% of women with acute infection experience recurrent vulvo-vaginal candidiasis (RVVC). There is currently no optimal or recommended regime for RVVC. Although antifungal agents, such as imidazoles, have been successfully used as a first-line treatment for acute VVC, its effectiveness is limited in RVVC. This could be due to patient factors, drug application (such as leakage) or dosing factors. A sustained-release (SR) bioadhesive vaginal cream (2% butoconazole nitrate) has incorporated VagiSite technology, a topical drug delivery system that allows SR of the drug. We describe its efficacy and the successful use of a butoconazole-SR formulation in the treatment of two cases of RVVC.
Adult ; Antifungal Agents ; administration & dosage ; Candidiasis, Vulvovaginal ; drug therapy ; Female ; Humans ; Imidazoles ; administration & dosage ; Middle Aged ; Pessaries ; Recurrence

BACKGROUNDSystemic administration of bisphosphonates has shown promising results in the treatment of osteonecrosis of the femoral head (ONFH). However, few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH. The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH.

METHODSThis experimental study was conducted between October 2014 and June 2015. Forty-five rabbits underwent simulated ONFH surgery. Immediately following surgery, they were divided into three groups: model (untreated, n = 15), HA (treated with HA alone, n = 15), and HA + ZOL (treated with HA soaked in a low-dose ZOL solution, n = 15). Histological, immunohistochemical, and quantitative analyses were performed to evaluate bone formation and resorption 2, 4, and 8 weeks after surgery.

RESULTSGross bone matrix and hematopoietic tissue formation were observed in the HA + ZOL group 4 weeks after surgery. The immunohistochemical staining intensities for 5-bromodeoxyuridine, runt-related transcription factor 2, osteocalcin, osteopontin, and osteoprotegerin were significantly higher in the HA + ZOL group than that in the model (P < 0.001, P< 0.001, P< 0.001, P< 0.001, and P = 0.018, respectively) and HA groups (P = 0.003, P = 0.049, P< 0.001, P = 0.020, and P = 0.019, respectively), whereas receptor activator of the nuclear factor-κB ligand staining intensity was significantly lower in the HA + ZOL group than that in the model and HA groups (P = 0.029 and P = 0.015, respectively) 4 weeks after surgery. No significant differences in bone formation or bone resorption marker expression were found between the three groups 2 or 8 weeks after surgery (P > 0.05).

CONCLUSIONSLocal administration of HA soaked in a low-dose ZOL solution increased new bone formation while inhibiting bone resorption in an animal model of ONFH, which might provide new evidence for joint-preserving surgery in the treatment of ONFH.

Animals ; Diphosphonates ; administration & dosage ; therapeutic use ; Durapatite ; administration & dosage ; therapeutic use ; Female ; Femur Head Necrosis ; drug therapy ; metabolism ; Imidazoles ; administration & dosage ; therapeutic use ; Immunohistochemistry ; Male

Repeated transcranial magnetic stimulation (rTMS) is a noninvasive treatment method recently approved by the U.S. Food and Drug Administration for the treatment of major depressive disorder in adults. Few clinical experiences with TMS or rTMS have been reported in children and adolescents. The clinical application of rTMS in children and adolescents should rest on data showing clinical efficacy and age-related safety. Despite these cautions, rTMS offers the advantage of noninvasive treatment and represents an alternative to classical drug treatment. We reviewed the effect of TMS and rTMS in child and adolescent psychiatric disorders.
Adolescent ; Adult ; Child ; Depressive Disorder, Major ; Humans ; Imidazoles ; Nitro Compounds ; Transcranial Magnetic Stimulation ; United States Food and Drug Administration

OBJECTIVEThe dermal absorption of Imidacloprid was studied to understand the effects of concentrations and skin reservoir on pesticide risk assessment in in vitro absorption studies.

METHODSBy using Franz diffusion cell and the transdermal barrier of viable Wistar rat abdomen skin or frozen ones, the imidacloprid content in the receptor fluid and skin was determined by LC/MS/MS method, and the absorption effects were compared between two concentrations of Imidacloprid solutions and two types of skin, respectively.

RESULTSAll percentages reported are % of applied dose. In vitro studies using viable skin, the Imidacloprid content in the receptor fluid of high and low concentration was 6.8%, 6.6% respectively; and 10.7%, 1.3% in skin, thus total absorption was 17.5% and 7.9%. And in vitro studies using both viable and frozen skin under the same concentration circumstances, the Imidacloprid content in the receptor fluid of viable and frozen skin was 6.6% and 0.7% respectively, in skin was 1.3% and 10.7%, and total absorption was 7.9% and 11.4%.

CONCLUSIONComparison of these in vitro results showed that either concentrations or skin reservoir had an effect on the dermal absorption. During 6h exposure, the high concentration in viable skin had the maximum dermal absorption value, which was the worst-case exposure estimate, also the best single estimate for pesticide risk assessment.

Administration, Cutaneous ; Animals ; Imidazoles ; pharmacokinetics ; In Vitro Techniques ; Male ; Neonicotinoids ; Nitro Compounds ; pharmacokinetics ; Rats ; Rats, Wistar ; Skin ; metabolism ; Skin Absorption

PURPOSE: We evaluated changes in bone mineral density and biochemical bone turn over markers resulting from intravenous administration of zoledronic acid for the purpose of increasing bone mineral density and decreasing bone turnover rate in patients who had received operative treatment after hip fracture. MATERIALS AND METHODS: We carried out a retrospective study of 34 patients who had received injections of zoledronic acid after surgical treatment for hip fracture from January 2009 to June 2010, with a follow up period of more than one year. We evaluated pre and post T-scores of DXA in spine, proximal femur and femoral neck along with biochemical bone metabolic markers, and we then analyzed each factor. RESULTS: T score was enhanced in all cases with pre T-score -4.2 and post T-score -3.3 revealing statistical significance (P<0.05). In addition, two biochemical bone turnover markers were observed to decrease in most patients. Three days after drug administration, 7 patients(20.6%) had minor adverse effects. There were no serious complications such as atrial fibrillation. CONCLUSION: No major adverse effects were observed, only minor ones in patients who had been injected with zoledronic acid for the prevention of osteoporotic fracture after surgical treatment for hip fracture. We confirmed the affirmative effects on changes in bone mineral density and biochemical bone turn over markers associated with the use of this drug.
Administration, Intravenous ; Bone Density ; Diphosphonates ; Femur ; Femur Neck ; Follow-Up Studies ; Hip ; Humans ; Imidazoles ; Osteoporosis ; Osteoporotic Fractures ; Retrospective Studies ; Spine

OBJECTIVETo study the inhibitory effect and toxicity of axitinib combined with 5-FU in nude mice bearing transplanted tumor of colon cancer LoVo cells.

METHODSNude mouse models bearing LoVo colon cancer xenograft were randomized into vehicle control group, untreated control group, axitinib-treated group, 5-FU-treated group and combined treatment group for corresponding treatments. The tumor dimensions, body weight and tumor weight were recorded, and the efficacy and toxicity were evaluated in terms of complete remission (CR), partial remission (PR), tumor growth delay (TGD), mortality rate and net body weight loss.

RESULTSThe combined treatment showed a significantly stronger efficacy than axitinib or 5-FU used alone. TGD of the combined treatment group was 16.73 days, longer than that of axitinib (8.53 days) and 5-FU (9.72 days) used alone. No mouse died during the treatments in the untreated control group, and 1 died in each of the other 4 groups. The mortality rate and weight loss were both less than 20%. One mouse had PR in axitinib-treated group and another in the combination treatment group. Axitinib, alone and in combination with 5-FU, reduced ABCG2 expression in the tumor tissue, and 5-FU has no such effect.

CONCLUSIONCombination of axitinib and 5-FU produces better antitumor effect than either drug used alone and is well tolerated in nude mice bearing colon cancer xenograft.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Colonic Neoplasms ; drug therapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Imidazoles ; administration & dosage ; Indazoles ; administration & dosage ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays

OBJECTIVETo survey the incidence of acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis and identify the related factors.

METHODSThirty-eight elderly patients with osteoporosis were hospitalized and treated with intravenous infusion of 5 mg zoledronic acid in 2010. The incidence of acute fever reaction was observed in these patients , and the time of fever onset, duration, average maximum temperature, and antipyretic drug used were recorded. The patients with and without acute febrile reaction were compared for age, duration of osteoporosis, sex ratio, use of parathyroid hormone before zoledronic acid treatment, β-fragment of collagen breakdown, calcitonin, osteocalcin, serum calcium, and use of anti-osteoporosis drugs before the treatment.

RESULTSAcute fever reaction occurred in 12 (31.6%) of the patients. Two of the patients had fever on the day of zoledronic acid treatment, and the other patients developed fever after the first day of treatment, with a mean duration of 1 day and a maximum temperature of (38.5∓0.84) degrees celsius;. The fever was treated with a mean of 3.55∓1.21 pseudoephedrine tablets. The patients with fever showed significantly higher parathyroid hormone levels before treatment than those without fever (P<0.05); osteocalcin, calcitonin, β-fragment of collagen breakdown, or serum calcium showed no significant difference between the two groups.

CONCLUSIONAcute febrile reaction, often moderate and transient, is common in elderly patients receiving intravenous zoledronic acid for osteoporosis, and its occurrence is possibly associated with parathyroid hormone levels before the treatment.

Aged ; Aged, 80 and over ; Bone Density Conservation Agents ; administration & dosage ; adverse effects ; China ; epidemiology ; Diphosphonates ; administration & dosage ; adverse effects ; Female ; Fever ; chemically induced ; Humans ; Imidazoles ; administration & dosage ; adverse effects ; Incidence ; Infusions, Intravenous ; Male ; Osteoporosis ; drug therapy ; Parathyroid Hormone ; blood