GC-MS analysis of organic fractions of Chrozophora tinctoria (L.) A.Juss. and their prokinetic propensity in animal models.

Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 3-5 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.

Investigation of using pectin and chitosan as natural excipients in pellet formulation.

This study aimed to evaluate the potential of applying pectin and chitosan polysaccharides in pellet formulation. These biopolymers have advantages such as biocompatibility, low toxicity, low price and easy processing which make them interesting candidates for drug delivery purposes. Careful control of pellet porosity is essential to achieve an appropriate drug release profile. Replacing microcrystalline cellulose (MCC) with polysaccharides, especially pectin, leads to increased pellet porosity. Theophylline, dimenhydrinate and ibuprofen were chosen as model drugs. Investigation of possible ionic interactions between drugs and excipients is crucial to optimize the formulation of pellets with acceptable drug release. Differential scanning calorimetry of chitosan showed an endothermic peak; however, this peak was not observed in thermograms of the pectin, implying the lack of interaction between polysaccharides. Fourier transform infrared analysis did not indicate any interaction between drugs and polymers. Incorporation of MCC into the pellet formulation significantly increased the mean dissolution time while substitution of MCC with polysaccharides led to a faster release for each of the three drugs - that were different in their net charges - in both acidic and buffer media. These results highlight the potential value of polysaccharides in improving drug delivery characteristics of pharmaceutical pellets.

Antivertiginous drug therapy does not hinder the efficacy of individualized vibrotactile neurofeedback training for vestibular rehabilitation - a randomized trial.

Vestibular rehabilitation using individualized vibrotactile neurofeedback training (IVNT) can lead to significant improvement in the postural stability of patients with vestibular symptoms of different origins. However, some of these patients have complex, severe dizziness, meaning that a pharmacological pretreatment or parallel (to vestibular rehabilitation) treatment can help them perform the rehabilitation exercises. Hence, the present study investigated the influence of a pharmacological treatment on the efficacy of vibrotactile neurofeedback training in patients with chronic, noncompensated vestibulopathies. All participants performed IVNT for ∼10 min each day for 2 weeks. In addition, every second participant was selected randomly to receive oral medication (20 mg cinnarizine and 40 mg dimenhydrinate per tablet), taking three tables per day. Trunk and ankle sway and postural stability were measured. In addition, the dizziness handicap inventory was evaluated immediately before training on the last day of training and 6 months after training. After the 10-day period of IVNT, both groups showed a statistically significant improvement in all parameters tested. A follow-up analysis after 6 months showed a long-term efficacy for the IVNT, that is, the patients remained significantly improved in their postural stability. The antivertiginous therapy did not hinder the efficacy of the IVNT. The present results indicate that IVNT even in combination with an antivertiginous drug therapy is an effective treatment regime for patients with disabling vertigo of different origins.

Anti-Oxidative Effect of Myrtenal in Prevention and Treatment of Colon Cancer Induced by 1, 2-Dimethyl Hydrazine (DMH) in Experimental Animals

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.

Direct standard-free quantitation of Tamiflu and other pharmaceutical tablets using clustering agents with electrospray ionization mass spectrometry.

Accurate and rapid quantitation is advantageous to identify counterfeit and substandard pharmaceutical drugs. A standard-free electrospray ionization mass spectrometry method is used to directly determine the dosage in the prescription and over-the-counter drugs Tamiflu, Sudafed, and Dramamine. A tablet of each drug was dissolved in aqueous solution, filtered, and introduced into solutions containing a known concentration of l-tryptophan, l-phenylalanine, or prednisone as a clustering agent. The active ingredient(s) incorporates statistically into large clusters of the clustering agent where effects of differential ionization/detection are substantially reduced. From the abundances of large clusters, the dosages of the active ingredients in each of the tablets were determined to typically better than 20% accuracy even when the ionization/detection efficiency of the individual components differed by over 100x. Although this unorthodox method for quantitation is not as accurate as using conventional standards, it has the advantages that it is fast, it can be applied to mixtures where the identities of the analytes are unknown, and it can be used when suitable standards may not be readily available, such as schedule I or II controlled substances or new designer drugs that have not previously been identified.

Multimodal therapy for chronic tinnitus.

From 2001 to 2006, we performed a retrospective study of patients suffering from chronic unilateral or bilateral tinnitus that was previously ineffectively treated by oral drugs [betahistine (Betaserc), extract of Ginkgo biloba (EGb 761), tanakan (Tebokan), and cinnarizine-dimenhydrinate (Arlevert), singly or in combination]. We divided 150 tinnitus patients (80 men, 70 women) into seven treatment groups. Treatments consisted of application of intravenous pentoxifylline, lidocaine, or vinpocetine (Cavinton) and combination of these agents with physiotherapy and soft laser. Mean duration (+/- standard deviation) of tinnitus in these patients was 7.4 +/- 6.0 years; their mean age was 55.6 +/- 12.5 years. The aim of our study was to compare treatment modalities and define their effectiveness for tinnitus relief. The most effective treatment was defined as a combination of Cavinton and physiotherapy. We evaluated pure lidocaine infusion therapy as ineffective. None of the treatment modalities had an objective correlate of improvement, though improvement was reported by a visual analog scale.

Identification of sinicuichi alkaloids in human serum after intoxication caused by oral intake of a Heimia salicifolia extract.

A 26-year-old male came to hospital around midnight complaining about muscle pain of the extremities as well as the tongue and slightly raised temperature. He reported the intake of an unknown amount of sinicuichi tea he had fermented over 24 h by adding yeast and sugar. The patient was treated with Vomex A (dimenhydrinate) and released from hospital the following afternoon. A blood sample taken shortly after submission and a small amount of the used plant material were available for analysis. Herbal drugs are widely used as stimulants as a legal alternative to illegal psychoactive drugs or in traditional context. Among many others like Sassafras officinalis, Salvia divinorum or Ephedra, Heimia salicifolia ("sinicuichi"), a species of the lythraceae family, is available via several online shops. Brewed up or fermented and consumed, the so-called sinicuichi tea may cause exhilarating feelings and an alteration of awareness accompanied by bradycardia, relaxation of the muscles and a pleasant faintness. Therefore Sinicuichi brew and heimia leaves are widely used for medication by the natives of Central and South America. After liquid extraction with acetone five different alkaloids were detected in the plant material by LC-MS/MS operated in the Q1 scan mode applying a TurboIonSpray source. Subsequently, Product Ion Spectra were recorded and after confirming the molecular formula by determining the accurate masses, possible structures of H. salicifolia alkaloids were assigned. The information of the Product Ion Spectra was then used to set up a sensitive multiple reaction monitoring (MRM) method. Applying the MRM method to the patient's serum sample after alkaline liquid-liquid extraction all of the five heimia alkaloids detected in the plant material were also detected qualitatively in the serum extract, confirming the ingestion.

A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy.

OBJECTIVE: To study the efficacy of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy. STUDY DESIGN: Double blind randomized controlled trial. SETTING: Department of Obstetrics and Gynecology, Thammasat Hospital, Faculty of Medicine, Thammasat University. MATERIAL AND METHOD: Between January 2005 and December 2005, 170 pregnant women who attended at antenatal clinic Thammasat University Hospital with the symptoms of nausea and vomiting in pregnancy were randomly allocated into group A (n = 85) and group B (n = 85). The patients in group A received one capsule of ginger twice daily (one capsule contained 0.5 gm of ginger powder) while the patients in group B received the identical capsule of 50 mg dimenhydrinate twice daily. The visual analogue nausea scores (VANS) and vomiting times were evaluated at day 0-7 of the treatment. RESULTS: There was no significant difference in the visual analogue nausea scores (VANS) between group A and group B in day 1-7 of the treatment. The vomiting episodes of group A were greater than group B during the first and second day of the treatment with statistically significant difference. No difference in vomiting episodes during the day 3-7 of treatment was found in both groups. There was a statistically significant difference in the side effect of drowsiness after treatment in group B greater (77.64%) than group A (5.88%) (p < 0.01). CONCLUSION: From the presented data, ginger is as effective as dimenhydrinate in the treatment of nausea and vomiting during pregnancy and has fewer side effects.

[Pharmacoprophylaxis of sea-sickness syndrome with the help of homeopathic drug "Avia-more"].

Anti-sea-sickness effect of a new homeopathic drug [see text] and its influence on operator's working capacity during Coriolis acceleration was evaluated in blind placebo-controlled investigation conducted in practically healthy volunteers with low vestibular resistance. For comparison "Dimenhydrinate" was used. The investigation has demonstrated that [see text] has rather strong anti-sea-sickness effect, is comparable with dimenhydrinate effectiveness and prevents the development of disorders in sensory-and-motor and cognitive functions during the influence of static-and- kinetic loads. According to the data obtained the protective action of [see text] is most likely connected with adaptive effect on organs and systems that form the functional protective system against sea-sickness. The negative influence of the drug on CNS complex functions was not observed that allows recommending its prophylactic use in subjects with low sea-sickness resistance including the operators.

[Treatment costs of otogenic vertigo]. / Die Kosten der Behandlung des otogenen Schwindels. Therapie mit einem Kombinationspräparat (Cinnarizin 20 mg und Dimenhydrinat 40 mg) im Vergleich zur Therapie mit Betahistin (12 mg).

PURPOSE: In this decision-tree analysis, the costs of otogenic vertigo treatment were investigated from the third-party payer's perspective. Either the combination preparation, with cinnarizine 20 mg and dimenhydrinate 40 mg as active substances, or betahistine (12 mg betahistinedimesilate) was administered. METHODS: A core model, based on clinical studies, was developed and a cost-effectiveness analysis was conducted. Both differences in effectiveness of the alternative treatments and adverse reactions and side effects were included. The number of cases, in which no more symptoms of dizziness were detected after 4 weeks of therapy, served as the effectiveness parameter. RESULTS: The effectiveness-adjusted costs amounted to 130.11 Euros for patients treated with the combination preparation and 629.28 Euros for treatment with betahistine. CONCLUSION: From the third-party payer's perspective, therapy of otogenic vertigo with the combination preparation is more cost-effective than a treatment with betahistine. From the patient's perspective, the higher effectiveness and the superior profile of side effects militate in favor of a therapy with the combination preparation.

Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials.

The increasing interest in alternative medical practices has led to a number of controlled studies on herbal and homeopathic agents. This paper presents the results of a meta-analysis of four recent clinical trials evaluating the homeopathic preparation Vertigoheel (VH) compared with usual therapies (betahistine, Ginkgo biloba extract, dimenhydrinate) for vertigo in a total of 1388 patients. Two trials were observational studies and the other two were randomised double-blind controlled trials. The duration of treatment (6-8 weeks) and dosage were comparable in all studies. Treatments were evaluated for the variables "number of vertigo episodes", "intensity of episodes" and "duration of episodes". As the studies differed in the age of patients and in the baseline values of vertigo, the individual reductions of number, intensity and duration of episodes were adjusted on equal age and baseline values (total means). An analysis of variance (with studies as random effects) showed no relevant influence of studies on the adjusted reductions and no relevant interaction between studies and treatment effects. The meta-analysis of all four trials showed equivalent reductions with VH and with control treatment: mean reduction of the number of daily episodes 4.0 for VH and 3.9 for control (standard error 0.11 for both groups); mean reduction of the duration (on a scale 0-4) for VH 1.1 and for the control 1.0 (standard error 0.03 for both groups); mean reduction of the intensity (on a scale 0-4) for VH 1.18 and for the control 1.8 (standard error 0.03 for both groups). In the non-inferiority analysis from all trials, VH was non-inferior in all variables. The results show the applicability of meta-analyses on the data from studies with homeopathicdrugs and support the results from the individual studies indicating good efficacy and tolerability of VH in patients with vertigo.

Effect of Different Amount of Dietary n-3 PUFA on Colon Carcinogenesis in DMH-treated Rats

The objective of the study was to observe the effect of n-3 PUFA on cell proliferation and apoptosis by determining mRNA and protein of COX-2 and eicosanoid product and the mRNA and protein of Bu and Bcl-2 related to apoptosis in colon carcinogenesis of 1,2- dimethylhydrazine (DMH)-treated rats. Ninety male Sprague Dawley rats weighing about 170g were divided into 3 groups, control and n-3 PUFA supplemented groups (FO group: 6.2 mmoles n-3 PUFA; 2FO group: 12.4 mmoles n-3 PUFA) and fed experimental diet for 14 weeks. All rats were intramuscularly injected with DMH 15 mg/kg twice a week for 6 weeks to deliver total dose of 180 mg/kg body weight. Compared with the control group, 6.2 mmoles n-3 PUFA significantly reduced the levels of mRNA and protein expression of COX-2 and 2-series eicosanoids (TXB2 and PGE2 and decreased cell proliferation in colonic mucosa. However, high levels of n-3 PUFA supplementation significantly increased the levels of mRNA and protein expression of COX-2, TXB2 and PGE2. and increased cell proliferation which was similar level to that of control group. Compared with the control group, n-3 PUFA, regardless of the amount, significantly increased apoptotic index in colonic mucosa. Western blot and RT-PCR analyses showed that the levels of mRNA and protein expression of Bax were significantly increased by 6.2 mmoles n-3 PUFA, but decreased by 12.4 mmoles n-3 PUFA. The analyses also showed the levels of mRNA and protein expression of Bcl-2 were significantly reduced by 6.2 mmoles n-3 PUFA, but increased by 12.4 mmoles n-3 PUFA. The ratio of Bcl-2/Bax in mRNA and protein was significantly reduced by 6.2 mmoles n-3 PUFA but increased by 12.4 mmoles n-3 PUFA. Overall, these results indicate that n-3 PUFA could be effective in preventing colon carcinogenesis by reducing cell proliferation with lower level of COX-2 and 2-series eicosanoid, and increasing apoptosis by inducing pro-apoptotic gene, Bax and inhibiting anti-apoptotic gene, Bcl-2 in the colonic mucosa of DMH-treated rats. However, high level of n-3 PUFA supplementation could stimulate colon carcinogenesis by increasing cell proliferation and inhibiting apoptosis.

Postoperative nausea and vomiting after Faden operation.

OBJECTIVE: The purpose of this study was to evaluate the antiemetic effect of prophylactic dimenhydrinate application prior to Faden operation and to compare the incidence of PONV between bimedial Faden operation (BMF) and horizontal recess-resect procedure (R&R). METHODS: Ninety-nine children (4-10 years) scheduled for BMF were included in this prospective double-blind study. Midazolam (0.5 mg/kg body weight, BW) was administered orally for premedication 30 min before induction of anesthesia. Additionally, children weighing >/=23 kg received either dimenhydrinate suppositories or placebo. The placebo group was compared with 148 children who underwent R&R surgery without antiemetic prophylaxis during the same period. Anesthesia was induced with thiopentone (5-10 mg/kg BW) and vecuronium (0.1 mg/kg BW) bromide and maintained with halothane (1-2 vol%) in N(2)O/O(2) (65/35 vol%). Age, height, weight, and incidence of oculocardiac reflex were documented. PONV was classified into "no vomiting", "vomiting without therapy", and "vomiting requiring rescue medication". In the latter case dimenhydrinate was given again. The chi-square test was used for statistical analysis. RESULTS: Forty-eight patients received placebo, while 51 received dimenhydrinate. No differences between any groups were observed concerning age, height, weight, and incidence of oculocardiac reflex. Compared to R&R surgery, PONV requiring rescue medication occurred significantly more frequently after BMF (45% vs 23% after R&R). PONV after BMF was significantly less severe in the dimenhydrinate group than in the placebo group. The total incidence of PONV after BMF, however, was not significantly reduced. CONCLUSION: The high incidence of PONV after BMF can be explained by the greater invasiveness of BMF than R&R surgery. PONV requiring antiemetic rescue medication can be reduced by preoperative administration of dimenhydrinate suppositories.

Experimental research on antimotion sickness effects of Chinese medicine "pingandan" pills in cats.

Pingandan was a secret prescription for treatment of stomach upset, nausea and vomiting for emperors in the Qing Dynasty of China. This study was to compare the effects of Pingandan with those of scopolamine and dramamine on motion sickness (MS) and nystagmus. Fourteen cats were tested in a parallel swing (0.22 Hz, 3.9 m/S2) for 20 min, and then in a rotating chair (10 degrees/S2, 20 rpm) for 1-2 min. The effects of scopolamine 1 mg, dramamine 25 mg and three doses of Pingandan 50x, 30x, 10x of 0.45 g/kg were observed and compared to placebos. These drugs or placebos were administered to each cat 30-60 min prior to the tests. The post-rotary nystagmus and MS symptoms were recorded. The Suri's scale for MS severity, Latin square and double blind techniques were used. The interval between any two tests was 2-5 days. It was found that Pingandan 50x and scopolamine 1 mg were more effective than placebos in reducing MS symptoms (P less than 0.01) and suppressing slow phase velocity of nystagmus (P less than 0.05), while Pingandan 30x significantly reduced MS symptoms only (P less than 0.01). Pingandan 10x and dramamine 25 mg had no anti-MS effect. Chinese medicine Pingandan is an effective anti-MS drug.

The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate.

A controlled, double-blind study was carried out to determine whether nystagmus response to optokinetic or vestibular stimuli might be altered by some agent contained in powdered ginger root (Zingiber officinale). For comparative purposes, the test subjects were examined after medication with ginger root, placebo and with dimenhydrinate. Eye movements were recorded using standard ENG equipment and evaluation was performed by automatic nystagmus analysis. It could be demonstrated that the effect of ginger root did not differ from that found at baseline, or with placebo, i.e. it had no influence on the experimentally induced nystagmus. Dimenhydrinate, on the other hand, was found to cause a reduction in the nystagmus response to caloric, rotatory and optokinetic stimuli. From the present study it can be concluded that neither the vestibular nor the oculomotor system, both of which are of decisive importance in the occurrence of motion sickness, are influenced by ginger. A CNS mechanism, which is characteristic of the conventional anti-motion sickness drugs, can thus be excluded as regards ginger root. It is more likely that any reduction of motion-sickness symptoms derives from the influence of the ginger root agents on the gastric system.

Comparison of efficacy of ginger with various antimotion sickness drugs.

UNLABELLED: Ginger and several other medications were compared with scopolamine and d-amphetamine for effectiveness in prevention of motion sickness. METHODS: Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached. Standardized N.A.S.A. techniques were used for speed of rotation and end-point of motion sickness. RESULTS: The three doses of ginger were all at the placebo level of efficacy. Amitriptyline, ethopropazine and trihexyphenidyl increased the tolerated head movements but the increase was not statistically significant. Significant levels of protection were produced by dimenhydrinate, promethazine, scopolamine and d-amphetamine. Protection was further increased by combination of these latter drugs with d-amphetamine. Efficacy was greatest as the dose was increased. CONCLUSIONS: The medication of choice in this study was scopolamine 0.6 mg with d-amphetamine 10 mg. This combination provided good protection with acceptable side effects.