Determination of Oxyphylla A Enantiomers in the Fruits of Alpinia oxyphylla by a Chiral High-Performance Liquid Chromatography-Multiple Reaction Monitoring-Mass Spectrometry Method and Comparison of Their In Vivo Biological Activities.

(R)-Oxyphylla A, a natural product isolated from Alpinia oxyphylla Miquel as a food and medicinal plant, has been reported previously as a novel chiral compound that possesses a potential therapeutic value for Parkinson's disease (PD). A chiral high-performance liquid chromatography-multiple reaction monitoring-mass spectrometry method was developed to separate oxyphylla A enantiomers and to identify the presence of natural (S)-oxyphylla A for the first time. Twelve samples of dried A. oxyphylla fruits were analyzed in which a large variation in the abundance of enantiomers was observed. Moreover, (S)-oxyphylla A was less abundant in all tested samples, whereas fruits harvested from Hainan and Guangdong tended to have relatively higher total concentrations of enantiomers. Additionally, enantiomers exhibited comparable neuroprotective effects in the zebrafish model of PD without observed toxicity phenotype. The optimized enantioseparation method will be crucial for the quality control of A. oxyphylla and research on bioactivities facilitates the development of oxyphylla A as a potential therapeutic for neurodegenerative diseases.

Bioavailability of the Phenolic Antioxidant 4-Methyl-2,6-Diisobornylphenol After Oral Administration.

We compared bioavailability of 4-methyl-2,6-diisobornylphenol after single intragastric administration to rats in a dose of 200 mg/kg in starch suspension and in almond oil. Absorption of 4-methyl-2,6-diisobornylphenol in the gastrointestinal tract after administration in almond oil was much more efficient than after administration in aqueous starch mucus.

Cost-effectiveness analysis of solifenacin versus oxybutynin immediate-release in the treatment of patients with overactive bladder in the United Kingdom.

OBJECTIVE: To carry out a cost-utility analysis comparing initial treatment with solifenacin 5 mg/day vs oxybutynin immediate-release (IR) 15 mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the U.K. National Health Service (NHS). METHODS: A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5 mg to 10 mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a U.K. database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios. RESULTS: Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs. 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY. CONCLUSION: Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.

Protective effect of Cyperi rhizoma against 6-hydroxydopamine-induced neuronal damage.

Cyperi rhizoma, the rhizome of Cyperus rotundus L. (Family Cyperaceae), is a well-known functional food and traditional herbal medicine in Korea. It has been reported that Cyperi rhizoma has antioxidant and free radical scavenging activities that play a major role in protection of neurodegenerative disorders, such as Parkinson's disease (PD). In the present study, the neuroprotective effects of a water extract of Cyperi rhizoma (CRE) against 6-hydroxydopamine (6-OHDA)-induced neuronal damage were evaluated in an experimental model of PD. In PC12 cells, CRE showed a significant protective effect on cell viability at 50 and 100 microg/mL. CRE inhibited generation of reactive oxygen species and nitric oxide, reduction of mitochondrial membrane potential, and caspase-3 activity, which were induced by 6-OHDA. CRE also showed a significant protective effect against damage to dopaminergic neurons in primary mesencephalic culture. These results suggest that CRE has neuroprotective effects against 6-OHDA-induced toxicity through antioxidant and anti-apoptotic activities in an in vitro PD model.

5-FU for genital warts in non-immunocompromised individuals.

BACKGROUND: Genital warts are common and usually are harmless but can be painful and psychologically burdensome. Several local treatments can be used, including topical 5-Fluorouracil (5-FU). OBJECTIVES: To determine the effectiveness and safety of 5-FU topical treatment for genital warts in nonimmunocompromised individuals. SEARCH STRATEGY: Databases searched were Cochrane Central Register of Controlled Trials (The Cochrane Library 2009 Issue 3), MEDLINE (1966 to August 2009), EMBASE (until August 2009), LILACS (1982 to August 2009). The search had no language or publication restrictions. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) among women, men, or both sexes, aged 18 years and older, comparing: 5-FU versus placebo or no treatment; 5-FU in any dose versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus placebo; 5-FU in any dose associated with other treatment versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus other associated treatment, topical or systemic. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from the original publications. MAIN RESULTS: Six trials involving 988 patients (645 women and 343 men) and reporting eight comparisons were found. Two studies reported withdrawals and dropouts, but none mentioned analysis by intention to treat (ITT). 5-FU presented better results for cure than placebo or no treatment (relative risk (RR) 0.39, 95% confidence interval (CI) 0.23 to 0.67), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% CI 0.83 to 5.37), Podophylin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82). There were no statistical differences for treatment failure for 5-FU versus CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) versus 5-FU + INFalpha-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119). Worse results were found for 5-FU versus 5-FU + INFalpha-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser INFalpha-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13). AUTHORS' CONCLUSIONS: The reviewed trials were highly variable in methods and quality, and the evidence provided by these studies was weak. Cure rates with several treatments were variable, and although 5-FU presents therapeutic results that are inferior to those seen with 5-FU + Inf alpha-2a (high dose) and 5-FU + CO2 Laser + Inf alpha-2a (high dose), the treatment should not be abandoned. Topical treatment with 5-FU has a therapeutic effect; however, the benefits and risks have not been determined clearly and further studies are needed.

Preparation, characterization and evaluation of Marsupsin-phospholipid complex.

The aim of this research was to formulate Marsupsin-phospholipid complex (M-P Complex) in attempt to increase the bioavailability of marsupsin and to characterize this new formulation along with its evaluation. Marsupsin-phospholipid complex was formulated by mechanical dispersion method. In this new formulation, complex formation was confirmed by carrying out transmission electron microscopy (TEM), IR, (1)H-NMR and RP-HPLC analysis. TEM showed M-P Complex diameter range of 0.05-0.5 microm. The entrapment efficiency of M-P Complex was found to be 44%. In vitro release study revealed its first order release profile. Mean blood serum concentration vs time curve of marsupsin was of first order after oral administration of M-P Complex in albino rabbits which clearly showed remarkably increased bioavailability of M-P Complex than standardized marsupsin. The average value of C(max) and T(max) of M-P Complex were found to be 3.02 mg/ml and 10.2 h, respectively. Hence the findings demonstrate that complexing marsupsin with phospholipids results in better oral bioavailability and improved biological response than free form of standardized marsupsin.

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes.

The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003-9 nmol per mouse intracerebroventricularly [i.c.v.]) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001-1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was then evaluated by inhibiting the expression of the three RyR proteins in the mouse brain. A selective knockdown of the RyR isoforms was obtained by the i.c.v. administration of antisense oligonucleotides (aODNs) complementary to the sequence of RyR1, RyR2 and RyR3 proteins, as demonstrated by immunoblotting experiments. RyR1 (5-9 nmol per mouse i.c.v.) knockdown mice did not show any memory dysfunction. Conversely, RyR2 (1-7 nmol per mouse i.c.v.) and RyR3 (1-7 nmol per mouse i.c.v.) knockdown animals showed an impairment of memory processes. This detrimental effect was temporary and reversible, disappearing 7 d after the end of the aODN treatment. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous mobility and inspection activity, as revealed by the hole-board test. In conclusion, the lack of any involvement of cerebral RyR1 was demonstrated. These findings also showed the involvement of type 2 and type 3 RyR in the modulation of memory functions identifying these cerebral RyR isoforms as critical targets underlying memory processes.

Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways.

OBJECTIVES: To investigate the potential of antimuscarinic agents for sensory mechanisms in overactive bladder using intravesical instillation. METHODS: Antimuscarinic agents were instilled intravesically in rats using two protocols. In the high-dose protocol, 5 mg atropine, oxybutynin, and dimethindene (M2-selective muscarinic receptor antagonist) were instilled into the bladder, and cystometric parameters, such as bladder capacity, intercontraction interval, pressure threshold, and maximal voiding pressure were monitored. In the low-dose protocol, 0.1 and 0.5 mug/mL oxybutynin, trospium, tolterodine, and dimethindene were continuously infused into the bladder. The doses chosen were based on the calculated urine-excreted concentrations of trospium typically achieved from human oral treatment of 40 mg/day. The effect of carbachol with and without the low-dose agents was then assessed. RESULTS: With the high-dose protocol, bladder capacity, intercontraction interval, and pressure threshold were increased when atropine and oxybutynin were instilled, but not when dimethindene was used. The maximal voiding pressure was not affected by any of the agents tested. In the low-dose protocol, none of the cystometric parameters were altered with antimuscarinic agents alone. The intercontraction interval decreased with intravesical carbachol (65% +/- 0.1% compared with baseline), but this was prevented with concomitant antimuscarinic agents. CONCLUSIONS: We have separated the local inhibitory effects of antimuscarinic agents during the storage phase from a decrease in voiding pressure. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating overactive bladder, not only by suppression of muscarinic receptor-mediated detrusor muscle contractions, but also by blocking muscarinic receptors in bladder-afferent pathways.

[Management of neuropathic bladder in multiple sclerosis]. / Management della vescica neurologica nella sclerosi multipla.

It is estimated that almost 70% of patients affected by multiple sclerosis (MS) suffer from urinary symptoms, with devastant impact on Quality of Life (QoL). The major aims of management should be to ameliorate the patients quality of life and to prevent the frequent complications of bladder dysfunction such as infention and renal damage. Therapy can usually eliminate or reduce the symptoms of neuropathic bladder. In the following pages is discussed the complex management of urinary symptoms in MS patients.

Lispro insulin: adsorption and stability in selected intravenous devices.

PURPOSE: The adsorption characteristics and stability profile of an insulin analog, lispro insulin, were evaluated against a recombinant human regular insulin using intravenous infusion sets and syringes. METHODS: Studies were performed using either 0.9% NaCl or 5% dextrose intravenous injection solution. Effects of container type, infusion rate, product concentration, presence-absence of an in-line filter, and storage condition on release profiles of lispro and human regular insulin infusion solutions were determined. RESULTS: Lispro insulin and m-cresol were chemically stable. Release rates of insulin (both types) were steady after an initial lag time. The lag time was much longer with intravenous bag infusion than with intravenous syringe infusion. A higher product concentration, faster flow rate, and prewash of the infusion tubing were shown to substantially decrease the lag time. CONCLUSIONS: The adsorption profile of lispro insulin was the same as that of human regular insulin in both syringes and bags. Use of a load-and-sit prewash scheme may shorten or nearly eliminate the lag time, which in turn may be used to make a more accurate calculation of a patient's dose.

[Ointment treatment of 1st degree hemorrhoids. Comparison of the effectiveness of a phytogenic preparation with two new ointments containing synthetic drugs]. / Salbenbehandlung von Hämorrhoiden ersten Grades. Wirksamkeitsvergleich eines Präparats auf pflanzlicher Grundlage mit zwei nur synthetische Wirkstoffe enthaltenden Salben.

OBJECTIVES: Investigation of the usefulness of a vegetable-based hemorrhoid ointment in comparison with two other ointments containing synthetic substances, one of which additionally contained corticoid. STUDY DESIGN: Treatment of 90 patients with first-degree hemorrhoids in the surgical department of a University Polyclinic, within the framework of a double-blind three-limb study of 21 days duration. Follow-up examinations on the third, seventh, fourteenth and twenty-first day of treatment. TARGET CRITERIA: Four typical symptoms--pruritus, bleeding, burning sensation, sore sensation--graded by both physician and patient. RESULTS: All three ointments proved highly effective. Both during the course of treatment and at the final examination carried out on the 21st day, no major differences were to be found between the three treatment groups. In the case of some of the test parameters, a positive tendency in favor of the herbal ointment was observed.

[A comparative study of methods of preparing the colon for a double-contrast study: Prepacol versus ricinus capsules with a cleansing enema]. / Vergleichende Studie zur Vorbereitung der Doppelkontrastuntersuchung des Kolons: Prepacol versus Rizinuskapseln mit Reinigungseinlauf.

In a controlled study, we analyzed the efficiency of cleansing out the colon and the best contrast medium of two different regimens (total n = 237) for preparing the colon for double-contrast examination. The recommendations regarding diet and liquid intake, contrast medium and examination technique were identical in both groups. The combination laxative Prepacol without cleansing enema resulted in a more thoroughly cleaned colon that ricinol with cleansing enema (very good/good cleanliness: Prepacol, 92.4%; ricinol, 83.2%, p less than 0.05). However, the quality of contrast medium (good: Prepacol 71.2% as opposed to ricinol 74.8%) was (independent of the preparation method) below standard regarding cleansing of the colon. Better patient compliance was accomplished by Prepacol because the medication was easier to take, and omitting the cleansing enema was a reduction in burden for both patients and medical staff. Written instructions for diet is essential and was of help to the patients.

[Comparative evaluation of a new colon preparation method prior to a double-contrast barium enema: toward discontinuation of the cleansing enema]. / Evaluation comparée d'une nouvelle méthode de préparation du côlon pour le lavement baryté en double contraste: vers la suppression du lavement évacuateur.

Evaluation of the efficacy and adequacy for double contrast barium enema of a recently described oral lavage solution associated with bisacodyl (Prepacol) and its comparison with a traditional method of colon cleansing (low-residue diet, cathartics and water enema) are reported. Two similar groups of 100 outpatients were compared. The new cleansing method presents several interesting advantages: time saving for the nurse of the radiology department and the patient himself (cleansing enema is no longer required), better patient acceptance, equal evacuation of fecal residue but significantly better evacuation of residual liquid resulting in better mucosal coating.

Effect of bisacodyl on gut lavage cleansing for colonoscopy.

The effect of 10 mg oral bisacodyl (n = 19) or placebo (n = 26) on colon cleansing with polyethylene glycol electrolyte lavage solution was studied during colonoscopy. Patient tolerance was evaluated by questionnaire. During colonoscopy endoscopists graded adequacy of cleansing and subjective amounts of residual fluid and recorded the actual amount of fluid suctioned. Patient tolerance and adequacy of cleansing were not different between bisacodyl and placebo. There was no difference in subjective and measured residual fluid between the two groups. Compared to placebo, 10 mg oral bisacodyl does not influence adequacy of cleansing, patient tolerance, or residual fluid following polyethylene glycol electrolyte lavage solution for colonoscopy. This suggests that the beneficial cleansing effects with bisacodyl for barium enema may occur by mechanisms other than simple fluid evacuation.

[Comparison of mannitol and traditional methods in the preparation of the large intestine for barium enema]. / Confronto tra mannitolo e metodica tradizionale nella preparazione del grosso intestino al clisma opaco.

The authors point-out the importance of a good bowel preparation for radiological researches. After an evaluation of the results of so-called "traditional methods" and an oral Mannitol method, the Authors conclude that a mannitol preparation is easily accepted by the patient for his effectiveness and tolerance and should be widely used.