PubMed - Herbal

High-performance liquid chromatography and LC-ESI-MS method for the identification and quantification of two biologically active isomeric coumarinolignoids cleomiscosin A and cleomiscosin B in different extracts of Cleome viscosa.

Biomed Chromatogr. 2008 Jul 23;

Authors: Chattopadhyay SK, Kumar S, Tripathi S, Kaur R, Tandon S, Rane S

A rapid, sensitive and simple reverse-phase high-performance liquid chromatographic-electrospray ionization-mass spectrometry method for simultaneous determination of cleomiscosin A and cleomiscosin B has been developed and validated. The isomeric coumarinolignoids cleomiscosin A (1) and cleomiscosin B (2) were separated on a Waters symmetry C(18) column with a solvent system composed of acetonitrile-methanol (1:2) and acetic acid-water (0.5 : 99.5) in a gradient elution mode. The absorption at 326 nm was chosen as the measuring wavelength in which resolution and baseline separation of compounds 1 and 2 could be obtained. The identity of the two isomeric compounds 1 and 2 in the samples were determined on a triple quadrupole mass spectrometer with ESI interface operating in the positive mode. Calibration curves were linear (r(2) > 0.993) over the concentration range 20-200 microg/mL for cleomiscosin A and 10-200 microg/mL for cleomiscosin B with acceptable accuracy and precision, respectively. The intra-day and inter-day precision were 1.13 and 0.82% for cleomiscosin A and 1.78 and 1.28% for cleomiscosin B, respectively. The validated method was successfully applied for the analysis of the above two compounds in different extracts of Cleome viscosa. Copyright (c) 2008 John Wiley & Sons, Ltd.

PMID: 18651599 [PubMed - as supplied by publisher]

Corrigendum: Recent advances in plant hepatoprotectives: A chemical and biological profile of some important leads.

Med Res Rev. 2008 Jul 23;

Authors: Negi AS, Kumar JK, Luqman S, Shanker K, Gupta MM, Khanuja SP

PMID: 18651581 [PubMed - as supplied by publisher]

Phytotoxic effects of sewage sludge extracts on the germination of three plant species.

Ecotoxicology. 2008 Jul 24;

Authors: Ramírez WA, Domene X, Andrés P, Alcañiz JM

In order to evaluate the ability of three types of extracts to explain the ecotoxicological risk of treated municipal sewage sludges, the OECD 208A germination test was applied using three plants (Lolium perenne L., Brassica rapa L., and Trifolium pratense L.). Three equivalent batches of sludge, remained as dewatered sludge, composted with plant remains and thermally dried, from an anaerobic waste water treatment plant were separated. Samples from these three batches were extracted in water, methanol, and dichloromethane. Plant bioassays were performed and the Germination Index (GI) for the three plants was evaluated once after a period of 10 days. Germination in extracts was always lower than the respective controls. The germination in composted sludge (GI 40.9-86.2) was higher than the dewatered (GI 2.9-45.8), or thermally dried sludges (GI 24.6-64.4). A comparison of the germination between types of extracts showed differences for dewatered sludge with the three plants, where the water and methanol extracts had significantly lower germination than the dichloromethane extract. A higher half maximal effective concentration (EC50) in composted extracts was established, mainly in the water extract (EC(50) 431-490 g kg(-1)). On the contrary, the germination was strongly inhibited in the water extract of the dewatered sludge (EC(50) 14 g kg(-1)). The germination was positively correlated with the degree of organic matter stability of the parent sludge, and an inverse correlation was detected for total nitrogen, hydrolysable nitrogen and ammonium content. It is concluded that the phytotoxic effect of the water extract is more closely related to hydrophilic substances rather than lipophilic ones, and care must be taken with dewatered sludge application, especially with their aqueous eluates. Results obtained in this work show the suitability of the use of sludge extracts in ecotoxic assays and emphasize the relevance of sewage sludge stabilization by post-treatment processes.

PMID: 18651217 [PubMed - as supplied by publisher]

Mechanisms of combined action of different chemopreventive dietary compounds: a review.

Eur J Nutr. 2008 May;47 Suppl 2:51-9

Authors: de Kok TM, van Breda SG, Manson MM

Consumption of fruits and vegetables has generally been associated with a decrease in cancer incidence and cardiovascular disease. Over the years, numerous bioactive compounds have been identified that contribute to these beneficial health effects. More recently, evidence is emerging that specific combinations of phytochemicals may be far more effective in protecting against cancer than isolated compounds. Combinatorial effects have been observed where any one of the single agents is inactive. Apart from interactions among dietary micronutrients, drug-phytochemical interactions have also been observed, indicating possibilities for improved cancer therapeutic strategies. Our understanding of the molecular mechanisms underlying such synergistic effects is still limited, but it appears that different combinations of complementary modes of actions are involved. In this review, we discuss the molecular mechanisms that are likely to be involved in cancer chemoprevention and summarize the most important findings of those studies that report synergistic chemopreventive effects of dietary compounds.

PMID: 18458834 [PubMed - indexed for MEDLINE]

[Evaluation of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia with persistent symptoms following treatment with alpha1-adrenoceptor blocker]

Hinyokika Kiyo. 2008 May;54(5):341-4

Authors: Naruoka T, Suzuki Y, Furuta A, Endo K, Sugaya S, Egawa S

We examined the effectiveness of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia (BPH) whose lower urinary tract symptoms (LUTS) caused by BPH were not adequately relieved by an alpha1-adrenoceptor blocker. Twenty-nine patients with insufficient improvement in the International Prostate Symptom Score (IPSS) and quality of life (QOL) score after administration of 50 mg naftopidil for 4 weeks or more received 6 tablets of Eviprostat in addition to naftopidil for another 2 weeks or more. With supplemental administration of Eviprostat, significant improvement was observed in the symptoms of incomplete emptying, daytime frequency, intermittency, weak stream, total IPSS, sum of the IPSS subscores for voiding symptoms (intermittency, weak stream and straining), sum of the IPSS subscores for storage symptoms (daytime frequency, urgency and nocturia), and QOL score. Supplemental administration of Eviprostat is therefore effective for the improvement of LUTS and QOL in BPH patients resistant to an alpha1-adrenoceptor blocker.

PMID: 18546857 [PubMed - indexed for MEDLINE]

[Six-year review of cigarette ingestion in children--gastric lavage versus medical observation]

Chudoku Kenkyu. 2008 Apr;21(2):115-22

Authors: Kubo K, Chishiro T

During 2006, the Japan Poison Information Center received 2583 inquiries about ingestion of cigarette, which is the most frequent household products ingested by children in Japan. During 2001-2006, two hundred and seventy-six children under seven years of age ingesting cigarettes and its related substances presented to the emergency department in Japan Red Cross Hospital Wakayama Center. The peak age was one year and younger, so-called "ingestion age". Patients were frequently detected chewing cigarettes and the situation of cases varied individually. It was impossible to estimate the amount of ingested cigarette based on the medical interview. Eighty-three percent of the patients were asymptomatic. Treatment strategy has been changed into a noninvasive one. Gastric lavage has not been performed by emergency physicians since 2001, and by pediatricians since 2006. After the medical observation for two hours following ingestion, all the children except one (who was hospitalized because of his family's request) were discharged from the emergency department. Independent of doing gastric lavage, all the 276 children had good prognosis. We conluded that ingestion of cigarette in children is generally benign. No gastric lavage, but medical observation for two hours following ingestion in emergency department is our recommendation of management.

PMID: 18516935 [PubMed - indexed for MEDLINE]

The willow as a Hottentot (Khoikhoi) remedy for rheumatic fever.

J R Soc Med. 2008 Jun;101(6):321-3

Authors: Volmink J

PMID: 18515781 [PubMed - indexed for MEDLINE]

Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial.

Obstet Gynecol. 2008 Jun;111(6):1371-9

Authors: Tatti S, Swinehart JM, Thielert C, Tawfik H, Mescheder A, Beutner KR

OBJECTIVE: To estimate the clinical efficacy of topical sinecatechins, a defined green tea extract, in the treatment of external genital and perianal warts. METHODS: This was a randomized, double-blind, vehicle-controlled trial involving 502 male and female patients aged 18 years and older, with 2-30 anogenital warts ranging from 12 to 600 mm(2) total wart area. Patients applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily for a maximum of 16 weeks or until complete clearance of all warts, followed by a 12-week treatment-free follow-up to assess recurrence. RESULTS: Complete clearance of all baseline and newly occurring warts was obtained in 57.2% and 56.3% of patients treated with sinecatechins ointment 15% and 10%, respectively, compared with 33.7% for vehicle (both P<.001). Significance was observed at weeks 4 and 6 and all subsequent visits. Numbers needed to treat were 4.3 and 4.4. Partial clearance rates of at least 50% were reported for 78.4% and 74.0% of patients in the sinecatechins ointment 15% and 10% groups compared with 51.5% of vehicle patients. During follow-up, recurrence of any wart was observed in 6.5%, 8.3%, and 8.8% in the sinecatechins ointment 15% group, sinecatechins ointment 10% group, and vehicle patients, respectively. A total of 3.7%, 8.3%, and 0.0% developed new warts, respectively. A total of 87.7% and 87.3% of patients in the sinecatechins ointment 15% and 10% groups, and 72.1% of vehicle patients experienced application site reactions; 49.2%, 46.2%, and 65.4% of those, respectively, were mild or moderate. CONCLUSION: Topical sinecatechins ointments 15% and 10% are effective and well-tolerated in the treatment of anogenital warts. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00449982. LEVEL OF EVIDENCE: I.

PMID: 18515521 [PubMed - indexed for MEDLINE]

Effects of Parietaria judaica pollen extract on human microvascular endothelial cells.

Biochem Biophys Res Commun. 2008 Aug 8;372(4):644-9

Authors: Taverna S, Flugy A, Colomba P, Barranca M, De Leo G, Alessandro R

Pollinosis from Parietaria judaica is one of the main causes of allergy in the Mediterranean area. The present study is designed to assess if P. judaica pollens contain bioactive compounds able to elicit a functional response in endothelial cells. We have demonstrated that addition of pollen extract to human lung microvascular endothelial cells (HMVEC-L) induces a modification of cell morphology, actin cytoskeletal rearrangements and an increase in endothelial cell permeability. We further showed that the treatment of endothelial cells with pollen extract causes an increase of E-selectin and VCAM-1 protein levels as well as an increase of IL-8 production. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of polymorphonuclear cells (PMNs) to HMVEC-L monolayer. Our results suggest for the first time that pollen affect directly endothelial cells (EC) modulating critical functions related to the inflammatory response.

PMID: 18515075 [PubMed - indexed for MEDLINE]

[Neuroprotective features of phytoadaptogens]

Vestn Ross Akad Med Nauk. 2008;(4):47-50

Authors: Bocharov EV, Kucherianu VG, Bocharova OA, Karpova RV

In the article the authors demonstrated that phytoadaptogens (Panax ginseng, Eleutherococcus senticosus, Rhodiola rosea) take part in protecting brain neurons from various injuries. Ability of phytoadaptogens to have influence on neurodegenerative mechanisms at Parkinson's disease is discussed. Phytoadaptogens should be proposed for study or use as therapeutic modulators in neurodegenerative disorders including Parkinson's disease.

PMID: 18488457 [PubMed - indexed for MEDLINE]

Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the Chinese herb Ligusticum wallichi.

Exp Biol Med (Maywood). 2008 Jul;233(7):891-6

Authors: Ali BH, Al-Moundhri M, Eldin MT, Nemmar A, Al-Siyabi S, Annamalai K

Nephrotoxicity of the anticancer drug, cisplatin (CP) involves enhanced renal generation of reactive oxygen metabolites and lipid peroxidation caused by decreased levels of antioxidants and antioxidant enzymes. Tetramethylpyrazine (TMP) is known to act as a strong antioxidant. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of TMP on CP nephrotoxicity in rats. TMP was given orally at a dose of 80 mg . kg(- 1) . day(- 1) for 7 days. Some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg on Day 6 of treatment. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained. Nephrotoxicity was assessed biochemically by measuring creatinine and urea in serum, reduced glutathione (GSH) concentration in renal cortex, by urinalysis, and histopathologically by light microscopy. CP significantly increased the concentration of urea and creatinine (P < 0.05) by about 128% and 170%, respectively; increased urine volume and N-acetyl-beta-D-glucosaminidase (NAG) activity; and significantly decreased osmolality and protein concentrations. CP treatment reduced GSH by about 34% (P < 0.05) and superoxide dismutase (SOD) and total antioxidant activity (TOX) by about 28% and 21%, respectively (P < 0.05). TMP pretreatment significantly mitigated all of these effects. Sections from saline- and TMP-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly reduced when CP was given after pretreatment with TMP. CP cortical concentration was not significantly altered by TMP treatment. The results suggest that TMP ameliorated the histological, physiological, and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, TMP may potentially be useful as a nephroprotective agent.

PMID: 18445776 [PubMed - indexed for MEDLINE]

[A clinical research of Jiawei simiaosan oral administration combined with the external application of Sihuangshuimi in the treatment of acute gouty arthritis]

Zhong Yao Cai. 2007 Sep;30(9):1196-8

Authors: Zhou HM, Chen SQ, Sun BG, Yin LR, Ye XY, Chen ZX

OBJECTIVE: To investigate the clinical curative effect in the treatment of acute gouty arthritis with Chinese traditional medicine. METHODS: All the 65 patients of acute gouty arthritis were randomly divided into two groups. The treatment group was treated by jiawei simiaosan and combined with the external application of Sihuangshuimi. The control group was treated by gclchicine. Then an evaluation was made on the clinical effect just referring to clinical symptoms and physical sign after a week. RESULTS: Two groups were therapeutic equivalence (P >0.05). The changes of the two groups in clinical symptoms physical signs and integral signs were so obviously after treatment (P <0.01), except for the UA of control group (P >0.05). Howerer, the level of UA of the treatment group had an advantage to the control group (P <0.05). CONCLUSION: The effect of using sihuangshuimi combined with Jiawei simiaosan to cure acute gouty arthritis is not only to improve joint function and cut down UA level obviously, but also to decline the body temperature and decrease swelling to relieve pain.

PMID: 18236765 [PubMed - indexed for MEDLINE]

[Randomized multicenter control clinical study on acute ischemic stroke treatment with traditional Chinese medicine]

Zhong Yao Cai. 2007 Sep;30(9):1192-5

Authors: Cai YF, Fu Y, Guo JW, You JS, Wang LX, Liang WX, Huang Y, Huang PX

OBJECTIVE: To observe the effect of a comprehensive protocol of integrated Chinese and Western medicine (ICWM) in treating with acute ischemic stroke. METHODS: A multi-center, prospective, random and control clinical trial was adopted with 606 patients of acute ischemic stroke. They were divided into the treatment group (274 cases) treated with ICWM protocol, and the control group (263 cases) treated with Western medicine plus placebe, and BI, mRS were assessed after treatment. RESULTS: Compared with the control group, the 90th day assessment showed that the severe disability rate was lower (BI <75) (P <0.05), the complete reabilitation and mild disability rate (BI> or =95, P < 0.05), and the disability level (modified Rankin scale mRS) were improved (P <0.05) in the treatment group than those in the control group. CONCLUSION: The ICWM protocol used in this study may improve neural function and quality of life of acute ischemic stroke patients, and reduce the severe disability rate in those after 90 days treatment.

PMID: 18236764 [PubMed - indexed for MEDLINE]

[Extract process of cyclic adenosinemonophosphate (cAMP) in Ziziphus jujuba]

Zhong Yao Cai. 2007 Sep;30(9):1143-5

Authors: Li M, Yang GL, Mi S, Gao XY, Wang Y, Li MR

OBJECTIVE: To study the extract process of Cyclic adenosinemonophosphate (cAMP) in Ziziphus jujuba. METHODS: CAMP was extracted with water, separated and purificated by ion exchange and silica gel G column chromatography. RESULTS: Thin layer chromatography (TLC) of the extracts and control cAMP showed the same Rf 0.75; The UV-absorption of the extracts and control cAMP had maximal absorb peak at 260 nm and the least absorb value at 230 nm; Infra-red spectrum of the extracts was indistinguishable from that of control cAMP; Retention time of the extracts by high-performance liquid chromatography (HPLC) determinate was 5.237 minute,unsettled impurity peak,content was 97%. Control cAMP was 5.350 minute,their retention time were of little difference. CONCLUSION: Chemistry structure of this extract with that of control cAMP is the same.

PMID: 18236762 [PubMed - indexed for MEDLINE]

[Study on extraction technology of Mosla chinensis volatile oil]

Zhong Yao Cai. 2007 Sep;30(9):1135-9

Authors: Jiang HM, Lu XY, Fang J, Xu XL, Yi K, Ge B

OBJECTIVE: To study the techniques of organic solvent extraction method and supercritical CO2 extraction for extracting Mosla chinensis Maxim volatile oil (MCMVO), and to analyze its chemical compositions. METHODS: Organic solvent extraction method and supercritical CO2 extraction were used to extract the oil and GC-MS was used to analyze its chemical compositions. RESULTS: The best extraction techniques of organic solvent method to extract volatile oil should be divided into two steps, total time was 210 minutes, the total proportions of input of the solvent and raw materials was 8:1 (ml:g), and temprature was 65 degrees C, its extraction rate was 1.83%. The MCMVO was extracted by supercritical CO2, and its extraction rate was 3.4%. GC-MS was used to analyze volatile oil, the results suggested MCMVO contain thymol, carvacrol, P-cycmene, humulene etc. The thymol had the highest content accounts for 56.25%, and the carvacrol was 19.21%. The content of thymol and carvacrol of MCMVO extracted by organic solvent was 58.33% and 22.54%. CONCLUSION: the content of thymol and carvacrol extracted by organic solvent extraction method is higher than that extracted by supercritical CO2 extraction method. Chemical compositions extracted by organic solvent extraction method are less than extracted by supercritical CO2 extraction method. 10 compositions are firstly extracted by supercritical CO2 extraction method.

PMID: 18236760 [PubMed - indexed for MEDLINE]

[Optimization of the polymerization conditions of vinblastine imprinted polymer by uniform design]

Zhong Yao Cai. 2007 Sep;30(9):1131-4

Authors: Zhu QH, Feng JY

OBJECTIVE: To optimize the polymerization conditions of vinblastine (VLB) imprinted polymer. METHODS: The conditions were optimized by the method of uniform design. The major factors investigated included the amount of functional monomer (MAA) and the cross-linker (EDMA) and the progenic solvent (toluene or acetonitril). The adsorption rate of VLB on the solid-phase extraction (SPE) column packed with MIP was adopted as the response value. RESULTS: The optimal conditions were MAA 0.4 mmol, EDMA 1.6 mmol and using acetonitrile as the solvent. Under the conditions,the VLB imprinted polymer was synthesized and the absorption rate of VLB was 88.20%. The characterizations of the optimal MIP were determined by IR spectrometry and scanning electron microscope (SEM) analysis. CONCLUSION: It is possible to furtherly improve the nature of the polymer by optimizing the polymerization parameters with uniform design. The polymer synthesized under the optimal conditions exhibited high affinity to the target molecule VLB.

PMID: 18236759 [PubMed - indexed for MEDLINE]

[Determination of contents of amygdalin in traditional and granular decoctions of Maxingshigan decoction by HPLC]

Zhong Yao Cai. 2007 Sep;30(9):1128-30

Authors: Wu KY, Liang GY, He ZY, Jin FY, Li X, Feng H

OBJECTIVE: To determine the contents of amygdalin in traditional and granular decoctions of Maxingshigan decoction. METHODS: The determination was carried out by HPLC with an ODS column and a mobile phase of water-methanol (23:77) at 215 nm. RESULTS: The content of amygdalin in traditional decoction of Maxingshigan Decoction was 17.74 mg/g and 24.80 mg/g in granular one. CONCLUSION: The content of glycyrrhizic acid in traditional decoction of Maxingshigan decoction is obviously higher than that in granular one.

PMID: 18236758 [PubMed - indexed for MEDLINE]

[Protective effects of extract of Ginkgo biloba on vascular endothelial dysfunction induced by AGEs-BSA in vivo]

Zhong Yao Cai. 2007 Sep;30(9):1109-13

Authors: Li XX, Chen SX, Ye QS, Yu LP, Cao W

OBJECTIVE: To explore the effect of extract of Ginkgo biloba (EGb) on vascular endothelial dysfunction induced by AGEs and to investigate the potential mechanisms. METHODS: Exogenous glycosylated bovine serum Albumin (AGEs-BSA) was prepared according to the methods of article. Vascular endothelial dysfunction was induced by tail vein injection of AGEs-BSA. The treatment group rats were given tail vein injections with AGEs-BSA followed by immediate intragastric of EGb (15,30 mg/kg/day, respectively) for 30 days. At the end of 30 days period, rats were anaesthetized with an intraperitoneal injection of sodium pentobarbital. Blood samples were collected from the carotid artery for biochemical assay of NO, MDA, SOD, DDAH, ADMA. The thoracic aorta was immediately isolated and cut into rings of 3 - 4 mm. Then ACh-induced EDR response and sodium SNP-induced endothelium-independent relaxation of aortic rings were examined. RESULTS: Results from in vivo experiments showed that the injection of AGEs-BSA significantly inhibited ACh-induced EDR response, but had no effect on SNP-induced endothelial-independent relaxation. The injection of AGEs-BSA decreased concentration of serum NO, activity of serum SOD and elevated serum MDA and ADMA level. Egb markedly attenuated AGEs-BSA induced inhibition of EDR response, increase of serum MDA and ADMA level, reduction of both NO level and activity of serum SOD.

PMID: 18236757 [PubMed - indexed for MEDLINE]

[Protective effect of total flavonoid of Herba Pyrolae on acute myocardial ischemic injury in rats]

Zhong Yao Cai. 2007 Sep;30(9):1105-9

Authors: Ding CJ, Liu JT, Wang JX, Wang CJ, Ji YY, Li XK, Gou W, Li TX

OBJECTIVE: To investigate the protective effect of Total Flavonoid of Herba Pyrolae(TFHP) on acute myocardial ischemic injury in rats. METHODS: Acute myocardial ischemic models were established by i. v. injection of pituitrin and the ligation of left descending coronary artery in rats. ECG of the rat was recorded, myocardial ischemic size was evaluated, and activites of creatine phosphokinase( CK), lactate dehydrogenase (LDH) and superoxide dismutase (SOD), level of malondialdehyde (MDA) in the rat serum were determined. RESULTS: In comparison with the model control, TFHP significantly reduced the incidence of ischemic arrhythmia induced by pituitrin, size of myocardial infarction, release of myocardial CK and LDH caused by the ligation of left descending coronary artery in rats. The primary study of action mechanism showed that TFHP decreased MDA level and increased SOD activity in the rat serum. Conclusion: TFHP provide a protective effect on acute myocardial ischemic injury via antioxidation.

PMID: 18236756 [PubMed - indexed for MEDLINE]

[Pharmacokinetics of pueraria for intranasal on spray in rabbits]

Zhong Yao Cai. 2007 Sep;30(9):1102-5

Authors: Lu Y, Zhang T, Tao JS, Xu LY

OBJECTIVE: To explore pharmacokinetic features of puerarin in pueraria spray and calculate pharmacokinetic parameters according to puerarin of drug-time curve in rabbits. METHODS: The concentration of puerarin in plamsa was determined by HPLC. The methanol was used to sediment protine. The 3P87 program was used to calculate the pharmacokinetic parameters. RESULTS: The vivo course of pueraria in spray could be described by the two compartment model. The main pharmacokinetic parameters of Pueraria spray were: t(l/2(beta)) =0.93 h, CL =44.23 mg x L(-1), AUC = 16.28 mg x h x L(-1), Cmax =5.9 mg x L(-1) and tmax = 0.975 h. CONCLUSION: The study will provide some scientific basises for the quality evaluation and pharmaceutics reformation of pueraria for intranasal.

PMID: 18236755 [PubMed - indexed for MEDLINE]