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BDNF and its expressing neurons in the brain critically control feeding and energy expenditure (EE) in both rodents and humans. However, whether BDNF neurons would function in thermoregulation during temperature challenges is unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMH

The source data of four individual randomised, double-blind, reference- and/or placebo-controlled clinical trials with virtually identical study design were pooled for the present meta-analysis. The main objective was to further evaluate the efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in comparison to various other antivertigo treatments in patients suffering from central and/or peripheral vestibular vertigo.Adult male and female outpatients were subjected to a 4-week treatment with the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg, cinnarizine (20 mg, 50 mg), dimenhydrinate (40 mg, 100 mg), betahistine dimesylate (12 mg), betahistine dihydrochloride (16 mg) and placebo, respectively. The primary efficacy endpoint was the reduction of a validated mean vertigo score (MVS), a composite score of 12 individual vertigo symptoms, the intensities of which were each evaluated by the patients on a 5-point visual analogue scale. For analysis of primary and further secondary efficacy endpoints, baseline-adjusted analysis of covariance (ANCOVA) was used to calculate adjusted least squares means (LSM) with associated two-sided 95% confidence intervals (CIs) for the difference in MVS reductions between treatment groups. Moreover, various sensitivity analyses, responder and subgroup analyses as well as descriptive analyses with respect to safety/tolerability of the treatments were conducted.Of 795 randomised patients, 779 belonged to the intent-to treat (ITT) and 723 to the per-protocol (PP) population. The main efficacy analysis was based on the ITT population (mean age 52.1 years, 61% female). The mean decrease of the MVS from baseline to Week 4 in the cinnarizine/dimenhydrinate group (-1.10) proved to be significantly larger than in any of the comparator groups. LSM differences for comparators versus the fixed combination ranged between 0.16 (95% confidence interval (CI) 0.03; 0.30, p = 0.017) for cinnarizine 20 mg and 0.60 (95% CI 0.42; 0.78; p0.001) for betahistine dimesylate 12 mg in favour of the fixed combination. Furthermore, after 4 weeks of treatment, 74 patients (24.7%) in the cinnarizine/dimenhydrinate group were completely symptom free (MVS = 0), a significantly greater proportion than in any of the comparator groups. Sensitivity analyses showed that baseline characteristics such as age, sex, duration of vertigo and antivertigo pretreatment had only a very minor and clinically non-relevant impact on the efficacy results regarding the primary efficacy outcome. Subgroup analyses with respect to age groups (65 years/≥ 65 years) and sex showed no significant differences in efficacy within any of the treatment groups. All treatments were well tolerated. A total of 55 patients (6.9%) reported 75 non-serious adverse events (AEs), and 19 patients (2.4%) discontinued the study prematurely because of AEs. Nearly 95% of the patients (cinnarizine/dimenhydrinate group: 97.9%) rated the tolerability of the study medications as either "good" or "very good".The findings of the present meta-analysis indicate that the fixed combination of cinnarizine and dimenhydrinate is a safe and potentially superior treatment option for patients suffering from central and/or peripheral vestibular vertigo, as compared to current standard treatments such as cinnarizine, dimenhydrinate or betahistine given alone in monotherapy.

Dorsomedial hypothalamus (DMH) is a part of the feeding center involved in food intake and regulation of the metabolism. DMH neurons express many receptors for different metabolic cues which can modulate its network and influence animals' behaviour. One of the metabolic peptides deliveredto this structure is ghrelin, the only well-known hunger signal, produced mainly in the stomach. Diet-induced obesity is a physiological model of obesity widely used in research. Here we investigated how time-of-day and high-fat diet (HFD) affect neuronal networks and the sensitivity to the metabolic information received by the DMH. Our results indicate that even a short period of HFD (2-3 weeks) consumption can cause dysregulation of the DMH neuronal network, manifested as a disruption of the day/night pattern of basal activity and altered sensitivity to incoming information. We showed for the first time a day/night pattern of sensitivity to ghrelin in the DMH, with a higher level during the behaviorally active phase of animals. This day/night rhythm of sensitivity to ghrelin was reversed in HFD group, causing a stronger effect during the non-active phase. After prolongation of the HFD consumption to 7-8 weeks we observed an increase in the responsiveness to ghrelin, than during the short-term diet.

Background: Bowl or colorectal cancer (CRC) is the third most common type of cancer with about two million new cases every year. CRC is the second leading cause of cancer related mortalities. Objective: The study aims to evaluate the anticancer activity of ethanolic Ginger Extract (GE) in HCT-116 colon cells and colorectal tumors induced by dimethylhydrazine (DMH). Methods: The antiproliferative activity was measured by MTT assay and the gene expression was assessed by q-RTPCR. For the antitumor study, rats were divided into five groups in random; control, group two was orally treated with 300 mg/kg of GE for 21 weeks, group three was s.c. injected with DMH (20 mg/kg) for 9 weeks, and groups four and five were treated with DMH and then treated with cisplatin (2.5 mg/kg, i.p) or GE, respectively, for 21 weeks. Results: GE had a significant antiproliferative activity with IC50~ 12.5 μg/ml. GE induced both extrinsic and intrinsic apoptotic pathways. GE induced the expression of FasL, TRAIL, p53, and caspase-8 and downregulated Bcl-2 and survivin genes. Treatment of rats with DMH resulted in 100% tumor incidence and 2.3 tumors/rat. DMH significantly elevated the serum ALT, urea, and creatinine and significantly decreased the body weight gain. DMH also caused significant reductions in the hepatic GSH level, and the activities of catalase, SOD, GST, and GR in the liver as well as the renal GSH content and γ-GT activity. The colon from rats insulted with DMH showed adenomatous polyps with polymorphism and mitosis. The mucosa and submucosa were infested with inflammatory cells while serosa and muscularis were devoid from these cells. However, the muscularis was infiltrated with cystic formation, anaplastic changes, and hemorrhage. GE was able to alleviate all the previous deleterious effects of DMH and it was superior to cisplatin in its ameliorative effects. It did so without eliciting hepatotoxicity or nephrotoxicity which were shown in the group treated with DMH and cisplatin. Conclusion: This study proved that the antitumor activity of GE against the DMH induced-CRC is superior to cisplatin. GE was also safer than cisplatin and did not elicit hepatotoxicity or nephrotoxicity. GE induced apoptosis and has carcinostatic activity.

Made available in DSpace on 2022-04-28T19:46:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Indole-3 carbinol (I3C) has shown dual effects on the promotion and progression stages of colon carcinogenesis while synbiotics (Syn) have exerted anti-carcinogenic activities in most rodent studies. This study aimed to investigate the effects of I3C given alone or together with a Syn intervention on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. All animals were given four subcutaneous DMH injections (4×40 mg/kg bodyweight, twice a week for two weeks) and then received either basal diet (G1), basal diet containing I3C (1g/kg chow) (G2) or basal diet containing I3C+Syn (I3C + inulin 50g/kg chow + Bifidobacterium lactis BB-12®), 2.5×1010 cfu/g of basal diet), (G3) for 21 weeks. Dietary I3C (G2) significantly increased tumour volume and cell proliferation when compared to the DMH control group (G1). Syn intervention (G3) significantly reduced tumour volume and cell proliferation when compared to I3C (G2). The colon tumours found were classified into well-differentiated tubular adenomas or adenocarcinomas. Dietary I3C or I3C+Syn did not significantly affect the incidence and the multiplicity of tumours in comparison with the DMH control group. Furthermore, Syn intervention (G3) increased Gstm1 and reduced Mapk9 gene expression in colonic tumours. The findings of the present study show that the dietary I3C shows a weak promoting activity, while the combination with Syn ameliorates I3C effects. Department of Structural and Functional Biology Institute of Biosciences Sao Paulo State University (UNESP), Prof. Dr. Antônio Celso Wagner Zanin 250 Distrito de Rubião Junior SP Molecular Oncology Research Center Barretos Cancer Hospital, SP Barretos School of Health Sciences Dr. Paulo Prata - FACISB, SP Department of Pathology School of Medicine Sao Paulo State University (UNESP), SP Department of Structural and Functional Biology Institute of Biosciences Sao Paulo State University (UNESP), Prof. Dr. Antônio Celso Wagner Zanin 250 Distrito de Rubião Junior SP Department of Pathology School of Medicine Sao Paulo State University (UNESP), SP

Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy.To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children.The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 December 2021.Randomised controlled trials (RCTs) in susceptible adults and children in whom motion sickness was induced under natural conditions such as air, sea and land transportation. We also included studies in which motion sickness was induced under experimental conditions (analysed separately). Antihistamines were included regardless of class, route or dosage and compared to no treatment, placebo or any other pharmacological or non-pharmacological interventions.We used standard Cochrane methods. Our primary outcomes were 1) the proportion of susceptible participants who did not experience any motion sickness symptoms; 2) the proportion of susceptible participants who experienced a reduction or resolution of existing symptoms. Secondary outcomes were 1) physiological measures (heart rate, core temperature and gastric tachyarrhythmia (electrogastrography)) and 2) adverse effects (sedation, impaired cognition, blurred vision). We used GRADE to assess the certainty of the evidence for each outcome.We included nine RCTs (658 participants). Studies were conducted across seven countries, with an overall age range of 16 to 55 years. Motion sickness was induced naturally in six studies and experimentally in four studies (rotating chair). All the naturally induced studies only evaluated first-generation antihistamines (cinnarizine and dimenhydrinate). Risk of bias across the studies varied, with mostly low risk for random sequence generation and allocation concealment, and mostly high risk for selective reporting. Only the experimentally induced studies measured physiological parameters and only the naturally induced studies evaluated adverse effects. There were no studies that clearly assessed the paediatric population. Antihistamines versus placebo or no treatment Antihistamines are probably more effective than placebo at preventing motion sickness symptoms under natural conditions (symptoms prevented: 25% placebo; 40% antihistamines) (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.23 to 2.66; 3 studies; 240 participants) (moderate-certainty). The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under experimental conditions (standardised mean difference (SMD) 0.32, 95% CI -0.18 to 0.83; 2 studies; 62 participants) (very low-certainty). No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia under experimental conditions (mean difference (MD) -2.2, 95% CI -11.71 to 7.31; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. When compared to placebo, antihistamines may be more likely to cause sedation (sedation: 44% placebo; 66% antihistamines) (RR 1.51, 95% CI 1.12 to 2.02; 2 studies; 190 participants) (low-certainty); they may result in little or no difference in blurred vision (blurred vision: 12.5% placebo; 14% antihistamines) (RR 1.14, 95% CI 0.53 to 2.48; 2 studies; 190 participants) (low-certainty); and they may result in little or no difference in terms of impaired cognition (impaired cognition: 33% placebo; 29% antihistamines) (RR 0.89, 95% CI 0.58 to 1.38; 2 studies; 190 participants) (low-certainty). Antihistamines versus scopolamine The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under natural conditions when compared to scopolamine (symptoms prevented: 81% scopolamine; 71% antihistamines) (RR 0.89, 95% CI 0.68 to 1.16; 2 studies; 71 participants) (very low-certainty). No studies were performed under experimental conditions. No studies reported results on the resolution of existing motion sickness symptoms. The evidence is very uncertain about the effect of antihistamines on heart rate under natural conditions (narrative report, 1 study; 20 participants; "No difference in pulse frequency"; very low-certainty). No studies reported results for any other physiological measures. When compared to scopolamine, the evidence is very uncertain about the effect of antihistamines on sedation (sedation: 21% scopolamine; 30% antihistamines) (RR 0.82, 95% CI 0.07 to 9.25; 2 studies; 90 participants) (very low-certainty) and on blurred vision (narrative report: not a significant difference; 1 study; 51 participants; very low-certainty). No studies evaluated impaired cognition. Antihistamines versus antiemetics Antihistamines may result in little or no difference in the prevention of motion sickness under experimental conditions (MD -0.20, 95% CI -10.91 to 10.51; 1 study; 42 participants) (low-certainty). The evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. No studies assessed the effects of antihistamines versus antiemetics under natural conditions. No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. No studies evaluated sedation, impaired cognition or blurred vision. One study reported physiological data for this outcome, evaluating gastric tachyarrhythmia specifically. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants; low-certainty evidence). This evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. Antihistamines versus acupuncture The evidence is very uncertain about the effects of antihistamines on the prevention of motion sickness under experimental conditions when compared to acupuncture (RR 1.32, 95% CI 1.12 to 1.57; 1 study; 100 participants) (very low-certainty). This study did not assess the prevention of motion sickness under natural conditions, nor the resolution of existing motion sickness symptoms. There was no study performed under natural conditions. Physiological measures and adverse effects were not reported.There is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines.

Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis.Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified.Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma.This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.

Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of Ficus dubia latex extract (FDLE) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis and its mechanisms. The experiment included an initiation model in which rats were orally administered with FDLE daily for 1 week before DMH injection until the end of the experiment, while only after DMH injection until the end in the post-initiation model. The results firstly indicated that FDLE treatment could reduce the level of methylazoxymethanol (MAM) in rat colonic lumen by inhibition of the activities of both phase I xenobiotic metabolizing enzymes in the liver and β-glucuronidase in the colon, leading to reduced DNA methylation in colonic mucosal cells, related to the number of ACF in the initiation stage. Besides, FDLE modulated the inflammation which could suppress the growth and induce apoptosis of aberrant colonic mucosal cells, leading to retardation of ACF multiplicity. Therefore, FDLE showed the ability to suppress the DMH-induced rat ACF formation and inflammation promoted growth of ACF. In conclusion, FDLE had the potential to prevent carcinogens-induced rat colorectal carcinogenesis in the initiation stage.

Studies have previously demonstrated a relationship between social status and anxiety disorders such as panic disorder. Repeated episodes of panic attacks do not occur in combination with an actual fear stimulus or stressor. However, social ranking modulates the perception of the social signals of a threat or stressor. The hypothalamic nuclei are well‑known for their role in the elaboration of fear‑induced reactions. The dorsomedial hypothalamus (DMH) and the ventromedial hypothalamic (VMH) nuclei are hypothalamic subnuclei involved in the processing of threatening stimuli‑evoked aversive response and innate fear development. These structures are also located in the medial amygdala‑hypothalamus‑brainstem circuit that modulates innate fear‑induced defensive behaviors. This work aimed to investigate the relationship between social hierarchy and innate fear‑induced panic‑like responses in male rats. In our study, the dominance tube test was used to determine the social hierarchy. Then, DMH/VMH nuclei were unilaterally implanted with a guide cannula. After intra‑DMH/VMH injection of bicuculline (GABAA receptor antagonist), both innate fear induction and differences in dominant/subordinate rats were evaluated by the open field test. Intra‑DMH/VMH bicuculline increased the frequency of defensive immobility, forward escape movements, and crossing behaviors, as well as the duration of defensive immobility and forward escape movements in dominant rats. Subordinate rats showed a higher frequency of defensive attention, defensive immobility, and crossing than dominant rats. Additionally, dominant rats demonstrated a lower duration of defensive attention and defensive immobility than subordinate rats. Dominant rats seemed to adopt a form of innate‑fear characterized by increased proactivity with the environment. In contrast, subordinate rats exhibited a reactive form of innate‑fear characterized by passivity and freezing.

Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50 mg/kg (i.p.) for 24 weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group. Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50 mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.

We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) in the ventromedial hypothalamus (VMH) enhances feeding during the dark cycle and after fasting, and inhibits feeding during the light cycle. On the other hand, galanin is highly expressed in the hypothalamus and has been reported to be involved in feeding regulation. In this study, we investigated the involvement of the VMH-PACAP to the dorsomedial hypothalamus (DMH)-galanin signaling in the regulation of feeding. Galanin expression in the hypothalamus was significantly increased with fasting, but this increment was canceled in PACAP-knockout (KO) mice. Furthermore, overexpression of PACAP in the VMH increased the expression of galanin, while knockdown (KD) of PACAP in the VMH decreased the expression of galanin, indicating that the expression of galanin in the hypothalamus might be regulated by PACAP in the VMH. Therefore, we expressed the synaptophysin-EGFP fusion protein (SypEGFP) in PACAP neurons in the VMH and visualized the neural projection to the hypothalamic region where galanin was highly expressed. A strong synaptophysin-EGFP signal was observed in the DMH, indicating that PACAP-expressing cells of the VMH projected to the DMH. Furthermore, galanin immunostaining in the DMH showed that galanin expression was weak in PACAP-KO mice. When galanin in the DMH was knocked down, food intake during the dark cycle and after fasting was decreased, and food intake during the light cycle was increased, as in PACAP-KO mice. These results indicated that galanin in the DMH may regulate the feeding downstream of PACAP in the VMH.

Background: Cinnarizine is used to treat nausea and vomiting accompanied by motion sickness. Dimenhydrinate is used in the treatment of nausea and vomiting and dizziness. The coformulation of the two drugs showed the lowest rate of adverse effects compared to single dimenhydrinate. Objective: A fully validated ultra-performance liquid chromatographic method has been conducted for the simultaneous estimation of cinnarizine (CIN) and dimenhydrinate (DIM). Materials and Methods: The UPLC method used Acquity Column as stationary phase and mobile phase methanol: buffer (pH = 3.5 ± 0.05) and acetonitrile in the ratio of 50: 25: 25 at a flow rate of 0.2 mL/min. Detection was performed by DAD at 260 nm. Results and Discussion: Retention time was 0.71 and 1.12 min for DIM and CIN, respectively. The linearity was found to be 1-40 μg/mL and 2-80 μg/mL for CIN and DIM; respectively. Conclusion: The method was appropriately used for the quantitation of both drugs in pure form, synthetic mixtures and tablet preparation.

Dimenhydrinate is a therapeutic agent used for the treatment of nausea and vomiting. A conventional dose of dimenhydrinate is 50 mg per 8 h. Once-daily controlled release tablets of dimenhydrinate were formulated intended to treat emesis. The tablets were formulated using hydrophilic polymers Methocel® and hydrophobic polymers Ethocel® and subsequently analyzed for pre-compression and post-compression characteristics, % moisture uptake, dissolution profiles and release behavior of the drug. Identification of active ingredient and compatibility of blends were analyzed through FT-IR. Drug release kinetics of dimenhydrinate was assessed at pH 1.2, 4.5 and 6.8. The results of release profiles were evaluated for different kinetic models including model dependent and model independent. The optimized formulation K100M 30% showed ideal pre-compression properties and in vitro characteristics. Tablets exhibited a controlled drug release pattern due to the formation of a viscous gel layer followed by erosion. Furthermore, zero-order best described the release pattern with the value of r2 ˃ 0.99. Once-daily tablets released 98–100% drug in 24 h. Significantly more concentration and higher viscosity grade of hydrophilic polymer ensured the required pattern of drug release.

Graphical abstract, Cuscuta reflexa has been traditionally used as an antiemetic. Additionally, it has been used in various herbal formulations for the treatment of emesis. So far, there is no scientific evidence of the plant extract as antiemetic. Therefore, this study was intended to assess the antiemetic activity of Juice (JCR), aqueous (CRAE) and methanolic extract (CRME) of C. reflexa in pigeons. Emesis was induced through GIT irritants like ampicillin (300 mg/kg, IM), copper sulphate (100 mg/kg, PO), conc. sodium chloride solution (1600 mg/kg, PO) and cisplatin (5-HT3 receptor stimulator) (6 mg/kg, IM). Dimenhydrinate acted as a positive control (2 mg/kg; IM). JCR [(1 ml/kg (1 %) and 1 ml/kg (2 %)], CRAE, and CRME were administered intramuscularly at different doses (50, 100 and 200 mg/kg) to each pigeon (n = 6). In each group, calculation of total number of jerks & vomiting episodes, and vomiting-weight was carried out to evaluate its antiemetic activity. The JCR exhibited a significant (p < 0.05) antiemetic impact on both the frequency and onset of emesis at 1 ml/kg (2 %) against various emesis mediator, except sodium chloride. Similarly, CRAE and CRME elicited marked dose dependent inhibition both on onset and frequency of emesis with highly significant (p < 0.001) effect at 200 mg/kg. The study reflects that juice, aqueous and methanolic extract of C. reflexa have significant antiemetic potential and possess pharmacological active constituent(s) that interfered with the emetic mediators by acting through GIT irritation and 5-HT3 receptor stimulations. Results of this study provide a scientific background to its traditional antiemetic uses.

Bavachinin is a flavanone obtained from the Chinese herb, Fructus Psoraleae. Flavonoids and flavanones are recognized as cancer preventive agents. We investigated the anticancer properties of bavachinin using a model of dimethylhydrazine (DMH and dextran sodium sulfate (DSS) induced rat colon cancer. We investigated aberrant crypt foci (ACF), hyperplastic lesions, catalase (CAT), superoxide dismutase (SOD) and glutathione (GST) levels in Wistar rats. Expression of cancer biomarkers including IL-6, p53, Bcl2 and BAX was investigated. We found that bavachinin administered to rats re-established the colonic crypts that were damaged by DMH and prevented progression of the cancer.

The paper describes the current state of development of seasickness as one of movement disease variants. The given type of pathology occurs when combining different types of ship’s motion (rolling and pitching). Circular, vertical and slow movements induce more pronounced and frequent signs of seasickness than linear, horizontal and quick ones. In the view of majority of researchers, the most likely is an intersensory conflict theory i.e. violation of coherent functioning of afferent body systems performing spatial orientation, statokinetic equilibrium and keeping balance. The leading role is played by the functional dysfunction of the vestibular analyzer. The classification of means of preventing and stopping of motion sickness is given, the mechanisms of their action, specific activity and side effects are described. It has been shown that currently the most effective drugs are M-cholinergic antagonists (scopolamine hydrobromide) and H1-histamine antagonists of the 1st generation (dimenhydrinate, diphenhydramine, cyclizine, meclizine, promethazine, etc.). Of the antipsychotics and blockers of D2receptors, prochlorperazine and metoclopramide are recommended. It is also worth to use prokinetics (domperidone, cisapride, renzapride, etc.), tranquilizers (barbiturates, benzodiazepines), sleeping pills and local anesthetics. Particular attention is paid to combination drugs, consisting of antiemetic and psychostimulating drugs, designed to maintain working capacity under the influence of seasickness factors on the body. Non-pharmacological means of preventing seasickness and alleviating its symptoms are described. The main directions of improving the system of measures aimed at maintaining efficiency in the presence of symptoms of seasickness are determined.

KEY POINTSAt 4:00 am, a 71-year-old man turned over in bed onto his left side and experienced a sudden onset of dizziness, described as if the bed was moving. Although lasting only 10–15 seconds, he became sweaty afterwards without nausea or vomiting. He came to the emergency department an hour

Intraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures.Sprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI).Administration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8-40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4-16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015).DORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

The anticancer activity and pharmacokinetic properties of encapsulated polyherbal nanoparticles (gallic acid (GA) and quercetin nanocomposite) and polyherbal extract (amla and pomegranate fruit peels) in normal and DMH-induced colorectal cancer in rats were examined in this work. In normal and DMH-induced rats, a pharmacokinetic study demonstrated that polyherbal nanoparticles had a typical sustained release profile with a fourfold increase in bioavailability when compared to polyherbal extract. Based on serum-concentration profiles of polyherbal nanoparticles and polyherbal extract following oral administration, the pharmacokinetic parameters for polyherbal nanoparticles and polyherbal extract were established using a single compartmental approach. This research suggests that encapsulating GA and quercetin in polymeric nanoparticles improves their oral bioavailability and anti-colon cancer efficacy. Polymeric nanoparticles could be a novel therapeutic possibility for carcinogenesis prevention.

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. Resumo Chrozophora tinctoria (L.) A.Juss. é uma planta anual herbácea, monoica, usada tradicionalmente para curar distúrbios gastrointestinais. O presente estudo foi realizado para encontrar os compostos bioativos por Cromatografia Gasosa-Espectrometria de Massa (GC-MS), a toxicidade aguda do potencial inibitório da acetilcolinesterase e a atividade emética presente na fração acetato de etila de Chrozophora tinctoria (EAFCT) e fração diclorometano de Chrozophora tinctoria (DCMFCT). Os compostos detectados em ambas as frações foram principalmente ácidos graxos, com cerca de sete compostos em EAFCT e 10 em DCMFCT. Estes incluíam compostos farmacologicamente ativos, como a imipramina, usada para tratar a depressão, ou éster metílico do ácido hexadecanoico, um antioxidante, nematicida, pesticida, hipocolesterolêmico, ácido 9,12,15-octadecatrienoico, éster etílico, (Z,Z,Z)- é usado como preventivo do câncer, antiartrítico, anti-histamínico, hepatoprotetor, inseticida, nematicida, ácido pentadecanoico, 14-metil-, éster metílico tem atividades antifúngicas, antimicrobianas e antioxidantes, ácido 10-octadecanoico, éster metílico tem a propriedade de diminuir o colesterol no sangue, antioxidante e antimicrobiano, o 1-Eicosanol é usado como antibacteriano, o 1-Hexadeceno possui atividades antibacteriana, antioxidante e antifúngica. Ambas as frações DCMFCT e EAFCT inibiram a atividade da acetilcolinesterase (AChE) com valores de IC50 de 10µg e 130µg, respectivamente. Ambas as frações foram consideradas tóxicas de maneira dose-dependente, induzindo vômitos a partir de 0,5g e letargia e mortalidade de 3g a 5g para cima. Ambas as frações combinadas com água destilada apresentaram atividade altamente emética. O aumento significativo no número de vômitos foi demonstrado pelo EAFCT mais água destilada, que são 7,50±1,29, 7,25±3,10 e 11,75±2,22 número de vômitos nas concentrações de 1g, 2g e 3g/kg, respectivamente, enquanto DCMFCT mais água destilada mostrou 5,25±2,22, 7,50±2,52 e 10,25±2,22 número de vômitos em 1g, 2g e 3g/kg, respectivamente. A droga padrão antiemética metoclopramida tem um impacto maior contra a emese induzida por ambas as frações do que o dimenidrinato. A metoclopramida diminui o número de vômitos causados por EAFCT para 1,00±0,00, 2,00±0,00, 4,00±1,00 a 1g, 2g e 3g/kg, sequencialmente, enquanto o dimenidrinato diminui o número de vômitos para 1,33±0,58, 2,33±1,15, 4,33± 0,58 a 1g, 2g e 3g, respectivamente. Da mesma forma, a metocloprimida diminui o número de vômitos causados por DcmCt de 5,25±2,22, 7,50±2,52, 10,25±2,22 para 1,33±0,58, 2,33±1,1, 4,33±0,58 nas concentrações de 1g, 2g e 3g/kg. O presente estudo é o primeiro relato documentado que valida cientificamente o uso folclórico de Chrozophora tinctoria como agente emético.

Cancer is one of the leading causes of death worldwide, and natural agents have shown some promise in fighting it. Thus, the present study tried to evaluate the healing potential of an equal combination of olive and sesame extract (MOS) against the colorectal cancerous lesions that were induced by dimethylhydrazine (DMH) in male rats and also compare the anticarcinogenic potential of the MOS and vitamin E with each other. Therefore, the mixture of equal olive and sesame extract (MOS) was used as the main treatment, alongside vitamin E as a parallel treatment. This study examined the red blood cell (RBC) and white blood cell (WBC) levels, biochemical indices, lactate dehydrogenase (LDH), C-reactive protein (CRP), total protein (TP), creatine kinase (CPK), albumin, and the colon tissue pathology, as well as the level of protein expression of the adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet-derived growth factor (PDGF). Also, the tissue stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were analyzed. Overall, the results represented a significant reduction in the congestion, mitotic index, inflammation, and cell destruction in the MOS group compared to the DMH group. In terms of the oxidative stress level, a significant increase was observed in the DMH group in comparison with the DMH-MOS group ( P < 0.05 ), and the MOS significantly increased TAC level ( P < 0.05 ). Furthermore, the DMH+MOS-exposed group exhibited a significantly lower expression of the PCNA, CEA, and PDGF proteins than those of the DMH group. Overall, the MOS showed that it can effectively prevent DMH-induced colon lesions. This mixture, as a strong antioxidant agent, can be clinically applied for preventing and treating colorectal cancer, the effectiveness of which is higher than that of vitamin E.

Colorectal cancer was inducted in Wister rats using titanium dioxide nanoparticles (TiO

Covered stent placement (CSP) is gaining popularity for the management of delayed massive hemorrhage (DMH) after pancreatic or biliary surgery. However, early studies have produced conflicting results regarding the potential advantages of the procedure. We aimed to compare the short- and medium-term outcomes of arterial embolization (AE) and CSP for DMH.We analyzed data for patients who underwent AE or CSP as an endovascular treatment (EVT) for DMH from the common hepatic artery (CHA) and its distal arteries between January 2009 and December 2019. We evaluated the major hepatic complications, in-hospital mortality, and 1-year mortality associated with the procedures, according to age, sex, reintervention, arterial variant, interval between surgery and EVT, and portal vein stenosis.All hemorrhages were treated using AE (n = 50) or CSP (n = 20). CSP was associated with no in-hospital mortality (32% vs. 0%, p = 0.003), and lower incidences of major hepatic complications (44% vs. 10%, p = 0.011) and 1-year mortality (54% vs. 25%, p = 0.035) compared with AE, respectively. There was no significant difference in technical success and reintervention rates. Compared with AE, the risk-adjusted odds ratios for CSP (95% confidence intervals) for major hepatic complications and 1-year mortality were 0.06 (0.01-0.39) and 0.19 (0.05-0.71), respectively.CSP is superior to AE regarding major hepatic complications and in-hospital- and 1-year mortality in patients with DMH from hepatic arteries.

The dorsomedial nucleus of the hypothalamus (DMH) is part of the brain circuits that modulate organism responses to the circadian cycle, energy balance, and psychological stress. A large group of thyrotropin-releasing hormone (Trh) neurons is localized in the DMH; they comprise about one third of the DMH neurons that project to the lateral hypothalamus area (LH). We tested their response to various paradigms. In male Wistar rats, food restriction during adulthood, or chronic variable stress (CVS) during adolescence down-regulated adult DMH Trh mRNA levels compared to those in sedentary animals fed ad libitum; two weeks of voluntary wheel running during adulthood enhanced DMH Trh mRNA levels compared to pair-fed rats. Except for their magnitude, female responses to exercise were like those in male rats; in contrast, in female rats CVS did not change DMH Trh mRNA levels. A very strong negative correlation between DMH Trh mRNA levels and serum corticosterone concentration in rats of either sex was lost in CVS rats. CVS canceled the response to food restriction, but not that to exercise in either sex. TRH receptor 1 (Trhr) cells were numerous along the rostro-caudal extent of the medial LH. In either sex, fasting during adulthood reduced DMH Trh mRNA levels, and increased LH Trhr mRNA levels, suggesting fasting may inhibit the activity of TRH

An appropriate balance between explorative and defensive behavior is essential for the survival and reproduction of prey animals in risky environments. However, the neural circuit and mechanism that allow for such a balance remains poorly understood. Here, we use a semi-naturalistic predator threat test (PTT) to observe and quantify the defense-exploration balance, especially risk exploration behavior in mice. During the PTT, the activity of the putative dorsal CA3 glutamatergic neurons (dCA3

Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular projections from the preoptic area of the hypothalamus (POA) to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory role for the DMH in the control of torpor. This work adds to the evidence that the POA and the DMH form part of a circuit within the mouse hypothalamus that controls entry into daily torpor.SignificanceDaily heterotherms such as mice employ torpor to cope with environments in which the supply of metabolic fuel is not sufficient for the maintenance of normothermia. Daily torpor involves reductions in body temperature, as well as active suppression of heart rate and metabolism. How the central nervous system controls this profound deviation from normal homeostasis is not known, but a projection from the preoptic area to the dorsomedial hypothalamus has recently been implicated. We demonstrate that the dorsomedial hypothalamus contains neurons that are active during torpor. Activity in these neurons promotes torpor entry and maintenance, but their activation alone does not appear to be sufficient for torpor entry.

Background and Objective Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert®) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo. Methods In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient’s and investigator’s judgment of global efficacy, the patient’s rating of impairment of daily activities, and safety/tolerability of the treatments. Results Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: − 0.093, 95% CI − 0.180; − 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient’s ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients. Conclusion The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders. Study Registration EudraCT No. 2011-004025-27.

The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of dimenhydrinate. Final composition of SEDDS was established based on drug solubility and stability studies. Dimenhydrinate was loaded into the SEDDS pre-concentrates to 7.5% (m/v). The droplet size of the final SEDDS formulations was in a range between 60 and 220 nm. Permeability, as well as tissue toxicity, of the formulations was investigated using bovine nasal mucosa. Enhancement in permeation up to 2.8-fold compared to pure dimenhydrinate was confirmed. Furthermore, toxicity studies did not reveal any serious tissue damages related to the SEDDS. Additionally, irritation potential of SEDDS was evaluated in ciliary beat frequency measurements. Incorporation of dimenhydrinate into SEDDS might therefore be considered as a promising approach within the field of nasal delivery of antiemetics by utilizing permeation enhancement strategy. Electronic supplementary material The online version of this article (10.1007/s13346-019-00634-1) contains supplementary material, which is available to authorized users.

Exposure to high levels of metals/metalloids may impair semen quality. Computer-aided sperm analysis (CASA) can be used for kinematic analysis of spermatozoa, which provides additional insights into sperm motion characteristics.To explore the associations of urinary and seminal plasma metal/metalloid concentrations with CASA motion parameters and assess the degree of correspondence between the two sample types.Eighteen metals/metalloids in seminal plasma and repeated urine samples were determined among 746 men recruited from a reproductive center. We assessed their associations with 6 CASA motion parameters [i.e., straight-line velocity (VSL), curvilinear velocity (VCL), average path velocity (VAP), linearity (LIN), straightness (STR) and amplitude head displacement (ALH)] using multivariable linear regression models.We found significantly inverse dose-dependent relationships between seminal plasma arsenic (As) and VSL, VCL and VAP, between seminal plasma selenium (Se) and VSL and VAP, between seminal plasma zinc (Zn) and STR and LIN, and between seminal plasma manganese (Mn) and LIN in single-metal models [all false discovery rate (FDR) adjusted P for trend 0.05]. These dose-response relationships remained statistically significant based on multiple-metal models and restricted cubic spline functions. Metal/metalloid concentrations in urine poorly predicted the same-day seminal plasma concentrations [coefficient of determination (RExposure to high levels of As, Se, Mn and Zn may impair sperm motion capacity. Concentrations of metals/metalloids in spot urine samples cannot accurately predict same-day seminal plasma exposure levels.

Background: Over the past 20 years or so, the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as ingested for recreational purposes. OTC drugs such as antihistamines, cough/cold medications, and decongestants are reportedly the most popular in being diverted and misused.Objective: While the current related knowledge is limited, the aim here was to examine the published clinical data on OTC misuse, focusing on antihistamines (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate), dextromethorphan (DXM)- and codeine-based cough medicines, and the nasal decongestant pseudoephedrine.Methods: A systematic literature review was carried out with the help of Scopus, Web of Science databases, and the related gray literature. For data gathering purposes, both the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and PROSPERO guidelines were followed (PROSPERO identification code CRD42020209261).Results: After completion of the selection, eligibility, and screening phases, some 92 articles were here taken into consideration; case reports, surveys, and retrospective case series analyses were included. Findings were organized according to the specific OTC recorded. Most articles focused here on DXM (n = 54) and diphenhydramine (n = 12). When specified, dosages, route(s) of administration, toxicity symptoms (including both physical and psychiatric ones), and outcomes were here reported.Conclusion: Results from the systematic review showed that the OTC misusing issues are both widespread worldwide and popular; vulnerable categories include adolescents and young adults, although real prevalence figures remain unknown, due to a lack of appropriate monitoring systems. Considering the potential, and at times serious, adverse effects associated with OTC misusing issues, healthcare professionals should be vigilant, and ad hoc preventative actions should be designed and implemented.

Introduction: The Mean Vertigo Score (MVS) is a composite score for defining the burden of disease of patients suffering from vestibular disorders. It has been used in clinical research for about 30 years. This study investigates discriminant validity of the MVS and describes structural relationships of the 12 single criteria used for construction of the MVS.Materials and Methods: The statistical analyses are based on the raw data of an earlier conducted randomized, doubleblind, placebo-controlled clinical trial, which compared the following four randomized treatment groups: a fixed combination of cinnarizine and dimenhydrinate (Arlevert), two groups with only one of the two study drugs, and a group with placebo. The method used for the statistical calculations is the Wei-Lachin procedure, a multivariate generalization of the Mann-Whitney test, which takes into account correlations among the 12 single symptoms of the composite score.Results: All 12 single symptoms of the composite endpoint proved to be useful for detecting differences (Mann-Whitney effect size measures: 0.58–0.73) and thus for discriminating between treatment groups. Their Pearson product-moment correlations are all positive (range 0.07–0.71) and point to the same direction, which indicates one-dimensionality and good internal consistency of the composite index MVS. Furthermore, our statistical calculations revealed that successively increasing the number of single items of the MVS to up to twelve enhances its reliability (R12 = 0.923), which leads to a substantially higher test power and reduction of the number of patients needed (sample size) in a clinical trial.Conclusion: The use of the multivariate Wei-Lachin procedure provides further evidence of the validity of the 12-item composite score MVS, based on the efficacy data of its 12 single vertigo symptoms. The present findings demonstrate that the MVS is a powerful tool, which can be used to adequately describe the patients' self-perceived vertigo complaints, both qualitatively and quantitatively. It may therefore be regarded as a clinically meaningful alternative to other questionnaires that are presently used in vestibular research.

Fundação de Amparo a Pesquisa do Estado de Minas Gerais In this work, the potentiality of batch injection analysis with multiple pulse amperometric (BIA-MPA) detection using boron doped diamond (BDD) electrode was investigated for simultaneous determination of 8-chlorotheophylline (CTF) and diphenhydramine (DIP), and these simultaneously with pyridoxine (RIP) or caffeine (CAF) in pharmaceutical formulations. The simultaneous determination of (CTF) and (DIF) was performed with the application of three sequential pulses in function of time to the BDD electrode using NaAc/HAc 0.05 mol L-1(pH = 4.7) as supporting electrolyte. At 1.35 V/50 ms, CTF was detected (oxidation) without interference of DIF. At 1.80 V/50 ms, both compounds (CTF + DIF) were oxidized. The current of DIF can then be obtained by subtraction of the currents detected during application of both potential pulses using a correction factor. The potential pulse of 0.7 V/200 ms was applied to avoid contamination/passivation of the BDD electrode surface. The proposed method presented stability (RSD = 2.4 e 2.5% for CTF e DIF, respectively; n=20), high analytical frequency (70 injections h-1), linear concentration range between and LOD and DOQ of 2.2 and 7.3 μmol L-1 for CTF and 0.5 e 1.7 μmol L-1 for DIF, respectively. The proposed method was used for simultaneous determination of CTF and DIF in pharmaceutical formulations and the obtained results were similar to those obtained by HPLC (confidence interval = 95%). The same system (BIA-MPA) has also been adapted for simultaneous determination of PIR, CTF e DIF. In this method, the following potential pulses were applied sequentially to the BDD working electrode using H2SO4 0.1 mol L-1 as supporting electrolyte: (a) + 1.25 V/50 ms: oxidation of CTF without interference of the other compounds; b) + 1.60 V/50 ms: oxidation of CTF e PIR without interference of DIF; c) + 1.80 V/50 ms: oxidation of CTF, PIR and, DIF; d) + 1.0 V (150 ms): applied to avoid contamination/passivation of the BDD electrode surface. Simple mathematical expressions and correction factors were used to access the oxidation current of each analyte. The proposed method presented the following results: stability (RSD= 0.9, 1.5 e 1.5% for CTF, PIR and DIF, respectively; n=20), high analytical frequency (~60 injections h-1), linear concentration range between and 20.0 and 60.0 μmol L-1 for CTF and DIF and between 10.0 and 30.0 μmol L-1 for PIR and the LD and LQ of 0.19 and 0.62 μmol L-1 for CTF, 0.54 and 1.81 μmol L-1 for PIR and 0.18 e 0.60 μmol L-1 for DIF. The proposed method was applied for simultaneous determination of CTF, PIR and DIF in pharmaceutical samples and the obtained results were similar to those obtained by HPLC (confidence interval = 95%). A third method (similar to the second) was proposed for simultaneous determination of CAF, CTF e DIF. The applied potential pulses were + 1.10 V (CTF oxidation), +1.40 V (oxidation of CTF and CAF) and, + 1.70 V (oxidation of CTF, CAF and, DIF) using NaAc/HAc 0.05 mol L-1(pH = 4.7) as supporting electrolyte. The proposed BIA-MPA system presented high analytical frequency (120 injections h-1), precision (RSDs < 1.0%, n = 20) and low LD and LQ values (0.31 e 1.03 μmol L-1 for CTF, 0.49 and 1.63 μmol L-1 for CAF and 0.76 and 4.09 μmol L-1 for DIF, respectively. The proposed method was applied for determination of CTF, CAF and, DIF in pharmaceutical sample and the obtained results were similar to those obtained by HPLC (confidence interval = 95%). No presente trabalho investigou-se a potencialidade do sistema de Análise por Injeção em Batelada com detecção por Amperometria de Múltiplos Pulsos (BIA-MPA) usando diamante dopado com boro (BDD) na determinação simultânea de 8-cloroteofilina (CTF) e difenidramina (DIF), e destes simultaneamente com piridoxina (PIR) ou cafeína (CAF), em formulações farmacêuticas. A determinação simultânea de CTF e DIF por BIA-MPA foi realizada através da aplicação de três pulsos de potenciais em função do tempo ao eletrodo de BDD usando NaAc/HAc 0,05 mol L-1(pH = 4,7) como eletrólito suporte. Em +1,35 V/50ms, CTF foi detectada (oxidação) sem a interferência de DIF. Em +1,80 V/50ms, ambos os compostos (CTF + DIF) foram oxidados. A corrente de oxidação da DIF foi obtida pela subtração entre as correntes detectadas em ambos os pulsos de potenciais mediante uso de um fator de correção. O pulso de 0,7 V/200 ms foi aplicado para evitar a contaminação/passivação da superfície do eletrodo de trabalho (BDD). O método proposto apresentou estabilidade (RSD = 2,4 e 2,5% para CTF e DIF, respectivamente; n=20), alta frequência analítica (70 injeções h-1), faixa linear de resposta entre 10 e 60 μmol L-1 (r > 0,998) e os LD e LQ de 2,2 e 7,3 μmol L-1 para CTF e em 0,5 e 1,7 μmol L-1 para DIF, respectivamente. O método proposto foi aplicado na determinação simultânea de CTF e DIF em formulações farmacêuticas e os resultados obtidos foram similares ao obtidos por HPLC, a um nível de confiança de 95%. O mesmo sistema (BIA-MPA) também foi adaptado para a determinação simultânea de PIR, CTF e DIF. Neste método, os seguintes pulsos de potenciais foram aplicados sequencialmente ao eletrodo de BDD usando H2SO4 0,1 mol L-1 como eletrólito suporte: a) + 1,25 V/50 ms: oxidação da CTF sem interferência dos demais compostos; b) + 1,60 V/50 ms: oxidação de CTF e PIR sem a interferência de DIF; c) + 1,80 V/50 ms: oxidação de CTF, PIR e DIF; d) + 1,0 V (150 ms): aplicado para evitar a contaminação do eletrodo de trabalho de BDD. Expressões matemáticas simples e fatores de correção foram utilizados para obtenção das correntes de oxidação de cada analito. Este método proposto apresentou os seguintes resultados: estabilidade (RSD= 0,9, 1,5 e 1,5% para CTF, PIR e DIF, respectivamente; n=20), alta frequência analítica (~60 injeções h-1), faixa linear de resposta entre 20,0 e 60,0 μmol L-1 para CTF e DIF e entre 10,0 e 30,0 μmol L-1 para PIR e os LD e LQ de 0,19 e 0,62 μmol L-1 para CTF, 0,54 e 1,81 μmol L-1 para PIR e 0,18 e 0,60 μmol L-1 para DIF. O método proposto foi aplicado na determinação simultânea de CTF, PIR e DIF em amostras farmacêuticas comerciais e os resultados obtidos foram similares ao obtidos por HPLC a um nível de confiança de 95%. Um terceiro método (similar ao segundo) foi proposto para a determinação simultânea de CAF, CTF e DIF. Os pulsos de potencial aplicados foram + 1,10 V (oxidação da CTF), +1,40 V (oxidação de CTF e CAF) e + 1,70 V (oxidação de CTF, CAF e DIF) usando NaAc/HAc 0,05 mol L-1(pH = 4,7) como eletrólito suporte. O sistema BIA-MPA proposto apresentou alta frequência analítica (120 injeções h-1), elevada precisão (DPRs < 1,0%, n = 20) e baixos valores de LD e LQ, (0,31 e 1,03 μmol L-1 para CTF; 0,49 e 1,63 μmol L-1 para CAF e 0,76 e 4,09 μmol L-1 para DIF, respectivamente). O método proposto foi aplicado na determinação de CTF, CAF e DIF em uma amostra farmacêutica manipulada e os resultados obtidos foram similares ao obtidos por HPLC, a um nível de confiança de 95%. Mestre em Química

Vertigo is not itself a disease, but rather a symptom of various syndromes and disorders that jeopardize balance function, which is essential for daily activities. It is an abnormal sensation of motion that usually occurs in the absence of motion, or when a motion is sensed inaccurately. Due to the complexity of the etiopathogenesis of vertigo, many pharmacological treatments have been tested for efficacy on vertigo. Among these drugs, cinnarizine, usually given together with dimenhydrinate, appears to be the first-line pharmacotherapy for the management of vertigo and inner ear disorders. Based on these considerations, the present non-interventional study aimed to investigate the clinical efficacy and tolerability of a fixed combination of cinnarizine (20 mg) and dimenhydrinate (40 mg) in patients suffering from vertigo-related symptoms. To this end, we enrolled 120 adults—70 males, and 50 females—with an average age of 64 years. Before beginning pharmacological treatment, all patients were screened for the intensity of vertigo, dizziness, and concomitant symptoms through the Visual Scale of Dizziness Disorders and Dizziness Handicap Inventory scales. At the end of the anamnestic evaluation, patients received the fixed-dose combination of cinnarizine (20 mg) plus dimenhydrinate (40 mg) 3 times daily, for 60 days. The results of this study provide further insight regarding the efficacy of the fixed combination when used to reduce symptoms of vestibular vertigo of central and/or peripheral origin, after both the 15- and 60-day therapies. Independent of the type of vertigo, the fixed combination was able to reduce dizziness- and vertigo-associated symptoms in more than 75% of all patients treated, starting from 15 days of therapy, and improving 60 days after starting the therapy. Interestingly, we also found differences between male and female patients in the framework of the pharmacological effects of therapy. This study provides further details concerning the therapeutic efficacy of the fixed combination of cinnarizine and dimenhydrinate, and also focuses attention on the possibility that these drugs could act in a gender-specific manner, paving the way for further research.

Obesity is associated with chronic inflammation, intestinal dysbiosis, and colorectal cancer risk. The anti-cancer effects of kefir are highlighted. Here, lactating Wistar rats were divided into: Normal litter (NL); Kefir normal litter (KNL); Small litter (SL); Kefir small litter (KSL). The NL and SL groups received 1 mL of water/day; KNL and KSL received kefir milk daily (108 CFU/mL) during lactation. After weaning, the pups continued to receive the same treatments until 60 days. At 67 days old, colorectal carcinogenesis was induced through intraperitoneal injection of 1,2-dimethylhydrazine. At 240 days, visceral adipose tissue was higher in SL compared to NL, KNL, and KSL. Kefir intake was found to suppress the number of tumors in both KNL and KSL groups (-100% and −71.43%; p

Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m).We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms.A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended.We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.

Microcrystalline cellulose was isolated from rami (Boehmeria Nivea L. Gaud), and applied as disintegrant in tablets of dimenhydrinate, made by direct compression and wet granulation. The aim of this study is to produce dimenhydrinate tablets with Microcrystalline Cellulose Rami (MCC Rami) isolated from Rami (Boehmeria Nivea L. Gaud), as a disintegrant and assess the effect of MCC Rami and Granulation technique on physical properties of drug such as, disintegration time, drug release and dissolution. Formulations of dimenhydrinate 100mg tablets were prepared with a combination of mannitol and lactose as a filler and MCC Rami as disintegrant in a concentration of 10-20%. The formulas were directly compressed or were compressed into tablets after wet granulation. The mechanical properties, drug release, physical properties and effects of process parameters, methods of applying disintegrant in tablet formulas were examined. A significant difference in disintegration time of tablets that were produced by direct compression and wet granulation was seen, that can be attributed to the porous structure of granules that enhanced fast disintegration, which had eventually improved dissolution and drug release. F1 and F2 with MCC Rami and physical mixture of MCC Rami with crosspovidone as a disintegrant that were directly compressed disintegrated in 79 and 72 seconds respectively thats not a significant difference, however when MCC was applied in an intragranular way its disintegration time is 67 seconds. The results showed that the method of disintegrant application and press of tableting has a significant effect on drug release and dissolution.Keywords : Microcrystalline Cellulose, wet granulation, disintegrant, Boehmeria Nivea L. Gaud.

Recently, experimental design has beaten the traditional optimization approach (one variable at a time) by providing better quality for chromatographic separation using minimal effort and resources. Benzophenone (BZP) and [1-(diphenylmethyl)piperazine] (DPP) were reported to be the most toxic impurities for dimenhydrinate (DMH) and cinnarizine (CIN), respectively. Additionally, there is no reported HPLC method for the simultaneous determination of DMH, CIN and their toxic impurities. A custom experimental design was adopted to estimate the optimum conditions that achieved the most acceptable resolution with adequate peak symmetry within the shortest run time. Desirability function was used to define the optimum chromatographic conditions and the optimum separation was achieved using XBridge® HPLC RP-C18 (4.6 × 250 mm, 5 μm), acetonitrile: 0.1% sodium lauryl sulphate (SLS) in water (90 : 10, v/v) as a mobile phase at flow rate 2 mL min−1 and UV detection at 215 nm. Method validation was carried out according to ICH guidelines and linearity was achieved in the ranges of 2–25, 1–25, 1–12.5, and 1–12.5 μg mL−1 for DMH, CIN, BZP and DPP, respectively. By application of the proposed method to the market dosage form, no interference from excipients was observed. Moreover, the greenness of the method was evaluated using the National Environmental Method Index (NEMI), Analytical Eco-Scale and Green Analytical Procedure Index (GAPI) metrics and the results revealed the green environmental impact of the developed method.

Background: Medication use during pregnancy is a common practice that has been increasing in recent years. The aim of this study is to describe medication use among pregnant women from the 2015 Pelotas (Brazil) Birth Cohort Study. Methods: This paper relies on a population-based cohort study including 4270 women. Participants completed a questionnaire about the antenatal period, including information about medication use. We performed descriptive analyses of the sample and the medications used and adjusted analyses for the use of medications and self-medication. Results: The prevalence of medication use was 92.5% (95% CI 91.7&ndash, 93.3), excluding iron salts, folic acid, vitamins, and other minerals. The prevalence of self-medication was 27.7% (95% CI 26.3&ndash, 29.1). In the adjusted analysis, women who had three or more health problems during pregnancy demonstrated higher use of medicines. Self-medication was higher in lower income groups and among smokers and multiparous women (three pregnancies or more). Acetaminophen, scopolamine, and dimenhydrinate were the medications most commonly used. Conclusions: This study describes the pattern of drug use among pregnant women in a population-based cohort study, with a high prevalence of self-medication. Greater awareness of the risks of self-medication during pregnancy is required, focusing on groups more prone to this practice, as well as ensuring qualified multidisciplinary prenatal care.

Background This study aimed to compare the therapeutic efficacy of dimenhydrinate and metoclopramide in patients with nausea and vertigo. Methods A prospective, double-blind, randomized clinical trial was performed on patients who presented to the emergency department (ED) with nausea and vertigo in the six month period between Nov 1st 2012 and May 1st 2013. Adult patients who were 18 to 65 years old presenting to the ED with nausea and vertigo or motion sickness were included in the study. A total of 200 patients were divided into 2 groups who were admitted to ED with complaints of vertigo accompanied by nausea. In the first group, 50 mg dimenhydrinate and 10 mg metoclopramide infusions were given intravenously for 15 min. The efficacy of treatment was measured by using a 10 mm Visual Analog Scale (VAS) performed at 0, 15 and the 30th minute. The primary outcome variable was a reduction in vertigo intensity documented on the VAS at the 30th minute after medication administration. Results A total of 200 patients were included in the randomization (n=100 in both groups). The baseline vertigo VAS scores were 7.57±1.42 in the dimenhydrinate (DMT) group and 7.27±1.40 in the metoclopramide (MTP) group (p=0.09). In the 30th minute of treatment, the average vertigo VAS score was 2.46 ± 2.39 in the DMT group and 2.31±1.96 in the MTP group; no significant differences were detected between groups. The baseline nausea VAS scores were 7.62±1.48 in the DMT group and 7.45±1.27 in the MTP group (p=0.36). In the 30th minute of treatment the average vertigo VAS score decreased to 2.27±2.24 in the DMT group and 2.70±2.48 in the MTP group, no significant differences were detected between groups. No significant differences were detected between nausea VAS changes and vertigo VAS changes at 30th minutes of the treatment (p=0.06, p=0.85 respectively). Rescue medication need was similar in both treatment groups (p=0.94). No significant differences were detected about the side effects which are sedation (p=0.56) and hypotension (p=0.57). Conclusions In conclusion, this prospective, double-blind, randomized study showed that both DMT and MTP have similar efficacy in reducing nausea and vertigo symptoms in the ED.

Benign paroksismal pozisyonel vertigo (BPPV) iç kulakta bulunan otokonilerin yerlerinden çıkıp yarım daire kanallarında serbestçe dolaşması veya kupulaya tutunarak kupulayı yer çekimine karşı yapılan baş hareketlerine karşı hassaslaştırması sonucu ortaya çıkan baş dönmesiyle kendini gösteren vestibüler bir hastalıktır. Çalışmanın amacı akut BPPV hastalarına hekim tarafından başlanan farmakolojik tedavi ile fizyoterapistler tarafından uygulanan vestibüler rehabilitasyon egzersizlerinin etkinliklerini karşılaştırmaktır. Çalışmaya Özel Bağcılar Safa Hastanesi'ne başvuran 18-50 yaş aralığındaki 30 hasta alındı. Hastaların 15' i farmakolojik tedavi, 15' i de vestibüler rehabilitasyon olmak üzere iki gruba ayrıldı. Farmakolojik tedavi grubundaki 8 hastaya hekim tarafından betahistin içeren ilaç, 7 hastaya da betahistine ek dimenhidrinat içeren ilaç verildi. Rehabilitasyon grubundaki hastalara ise baş ve göz hareketlerini içeren egzersizler uygulandı, egzersiz sonrasında tutulan kanalın yönüne göre manevra uygulaması yapıldı ve hastalara ev egzersiz programı verildi. Tedavi 4 hafta boyunca devam etti. Hastalara tedavi öncesi ve sonrası Vizüel Analog Skala (VAS), dinamik görme keskinliği testi, kronometre ile romberg, semitandem, tandem duruş testleri, sert ve yumuşak zeminde gözler açık ve kapalı tek ayak üzerinde durma testi ve unterberger testleri uygulandı. Sonuç olarak her iki grupta da iyileşme görülmesine karşın, vestibüler rehabilitasyon uygulanan grupta sonuçlar istatistiksel olarak daha anlamlı bulunmuştur. Betahistin ile kombine uygulanan dimenhidrinatın, yalnızca betahistine göre bir üstünlüğü bulunmamıştır. Benign paroxysmal positional vertigo (BPPV) is a vestibular disorder that manifests itself as a result of dizziness caused by the otoconia in the inner ear coming out of their places and circulating freely in the semicircular canals or by attaching to the cupula and sensitizing the cupula to head movements against gravity. The aim of the study is to compare the effectiveness of pharmacological treatment initiated by the physician and vestibular rehabilitation initiated by physiotherapist in patients with acute benign paroxysmal positional vertigo (BPPV). Thirty patients, aged 18-50 years, who applied to the Bağcılar Safa Hospital, were included in the study. The patients were divided into two groups, 15 pharmacological control group and 15 vestibular rehabilitation group. 8 patients in the pharmacological control group were given the drug containing betahistine by the physician, and 7 patients received the drug containing additional dimenhydrinate to the betahistine. In the rehabilitation group, exercises including head and eye movements and maneuvering were performed according to the direction of the canal after the exercise, and the patients were given a home exercise program. Treatment continued for 4 weeks. Visual Analogue Scale (VAS), dynamic visual acuity test, romberg, semitandem, tandem posture tests with a stopwatch, standing test on one leg with eyes open and closed, and unterberger tests were applied to patients before and after treatment. As a result, although improvement was observed in both groups, the results were found statistically more significant in the group that underwent vestibular rehabilitation. Dimenhydrinate administered in combination with betahistine was not superior to the betahistine-only.

Vestibular migraine (VM) is one of the most debilitating chronic diseases that is currently underdiagnosed and undertreated. The treatment of VM is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualized treatments for this condition. In this review, we discussed the progress of evidence-based treatment of VM, including pharmacotherapy and nonmedical methods. A search of the literature was conducted up to September 2019. In order to control or cure VM, patients should follow three steps. First, patients should comply with diet and behavioral medication; Second, during the attack of VM, patients should take medicine to control the symptoms. These acute attack treatment of VM consists of antiemetic medications (e.g., dimenhydrinate and benzodiazepines), anti-vertigo medicine, and analgesics (e.g. triptans). Third, prophylactic medicine (e.g., propranolol, topiramate, valproic aid, lamotrigine, and flunarizine) can be used to reduce the frequency and severity of VM attack. Also, vestibular rehabilitation (VR) treatment should be considered for all VM. Meanwhile, we also propose to establish a culture of prevention which is essential for reducing the personal, social and economic burden of VM.

Introduction: Vertigo appears as a result of a sudden neural activity imbalance of the vestibular system. The vertigo prevalence is higher in patients over 60 years of age compared to patients under 40 years of age. Objectives: The purpose of this study was to analyze the effect of craniosacral osteopathy on dizziness and balance in individuals who have peripheral vestibular pathology. Methods: A total of 30 individuals, aged 24–50 years, participated in this study. Twenty-four of the participants were female (80%) and 6 were male (20%). The participants were separated into 2 groups, with 15 patients included in the cranial osteopathy treatment group (study group) and 15 patients included in the group that used dimenhydrinate (control group). The individuals were evaluated in terms of dizziness and balance. A visual analog scale was used to evaluate dizziness. Balance was evaluated using the Berg balance scale and the Activities-Specific Balance Confidence scale. The craniosacral treatment program was applied once per week for 6 sessions. All of the individuals included in this study were evaluated 3 times, i.e., prior to treatment, on the third week of treatment, and on the sixth week of treatment. Results: Significant improvement was noted within each group in terms of dizziness and balance (p < 0.05). When the groups were compared with each other, it was observed that craniosacral osteopathy was more effective than dimenhydrinate treatment for dizziness and balance (p < 0.05). Conclusion: Craniosacral osteopathy is an effective treatment choice in individuals who have chronic peripheral vestibular pathology. In individuals who have resistant and chronic vestibular pathology, craniosacral osteopathy should be evaluated among the treatment choices.

The main objective of this study was to formulate orodispersible tablets of Dimenhydrinate for quick relief of emesis. Orodispersible tablets were prepared by direct compression method using co-processed super-disintegrants. Co-processed super-disintegrants are the mixture of crospovidone and guar gum in different ratios. The powder mixtures and tablets were subjected to various pre-compression and post-compression evaluations. IR spectroscopy showed no interaction between drug and other excipients. Angle of repose and Carr’s index was found in the range of 23.89°-28.27° and 23.29-15.48 respectively. These results indicated that powder mixtures showed good to acceptable flow properties. All formulations containing co-processed super-disintegrant showed short disintegration time (38.23-17.67 s) and maximum water absorption ratio 73.39%-91.35% compared to control formulation (3.54 min wetting time). Among all formulation F7 containing crospovidone: guar gum in 1:3 ratio showed highest percentage of drug release (98.89%) in 30 min, which is due to high degree of swelling caused by guar gum along with rapid hydration of tablets by crospovidone. Formulation F7 was subjected for 3 months of stability studies; results reviled that the tablet formulation was stable throughout the study period. In conclusion the obtained results suggested that orodispersible tablets of Dimenhydrinate with rapid disintegration and fast drug release can be successfully formulated by employing co-processed super-disintegrants. Kathmandu University Journal of Science, Engineering and TechnologyVol. 12, No. I, June, 2016 Page: 23-33

Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation.

Objetivo: Analisar os riscos potenciais às Gestantes e Fetos, causados pela automedicação de anti-inflamatórios não esteroides. Métodos: A proposta de metodologia para esta pesquisa segue uma estratégia de revisão de literatura, pesquisa exploratória e descritiva, cuja coleta fora realizada em diferentes bases de dados, tais como Scientific Electronic Library Online (SCIELO), registros tanto da Biblioteca Virtual em Saúde (BVS), quanto registros da Medical Literature Analysis and Retrievel System Online (MEDLINE/PUBMED). A busca se deu através do uso dos descritores “AUTOMEDICAÇÃO”; “GESTANTES”, “AINES” e “RISCOS”. Resultados: Percebeu-se que a utilização de medicamentos durante a gravidez pela prática da automedicação com Ibuprofeno 9 (27%), Dipirona 6 (18%), Bromoprida 2 (6%), Paracetamol 13 (40%), Dimenidrinato 3 (9%), sendo 31 (94%) em forma de comprimidos foi relatada por 27 (33,75%) gestantes, e 3 (11,1%) que apresentaram queixas de uso como cefaleia, êmese e náuseas e a indicação foi relatada por 2 (6%) gestantes pela a mãe e as demais por conta própria. Conclusão: Após a análise de diversos artigos científicos, o que fica bem explicito é que, o uso de anti-inflamatórios não esteroidais no início da gravidez não demonstrou ser um fator de risco, porém, após o primeiro trimestre pode ser fatal, tanto para a ocorrência de malformações congênitas estruturais no feto, quanto para problemas renais. Em se tratando da Mãe percebe-se que os AINEs podem prolongar seu tempo de parto, causar hemorragias e enfraquecer seus óvulos para uma futura reprodução.

Antiemetic drugs are used to control excessive vomiting and nausea and generally absorbed through gastrointestinal tract. In present study, the in-vitro binding interactions two of the antiemetic drugs (dimen-hydrinate and ondansetron) between Trypsin (Tsn) secreted from pancreas to small intestine for protein digestion were investigated by fluorescence emission spectroscopy (FES), UV-VIS spectroscopy, synchronous fluorescence spectroscopy (SFS), FT-IR spectroscopy and molecular modeling methods. Also, the effect of these drugs on the catalytic activity of Tsn was determined. The fluorescence quenching experiments indicated that each drugs quenched the intrinsic fluorescence of Tsn with their increased concentrations. The results of SFS and UV-VIS spectra proved the interaction of dimenhydrinate and ondansetron with Tsn. FT-IR spectra showed that the secondary structure of enzyme was altered in the presence of the drugs. All these spectroscopy results were validated and explained by molecular docking studies. Both drugs have inhibition effect on the catalytic activity of Tsn and the IC50 values were determined as 2.6 x 10(-4) M and 6.4 x 10(-4) M for dimenhydrinate and ondansetron, respectively. Docking results revealed that the hydrogen bond interaction of dimenhydrinate with active-site residue Ser195 and ondansetron with active-site residues His57 and Ser195 hydrogen bonds might be cause the inhibition of enzyme activity. The results of this study can provide valuable information in the field of pharmacokinetics and pharmacodynamics. (C) 2021 Elsevier B.V. All rights reserved.

Dimenhydrinate is an over-the-counter medication that is used to relieve nausea, vomiting, and vertigo caused by motion sickness. It has a short elimination half-life, possibly due to its first-pass metabolism. The current study aimed to prepare and evaluate new transdermal formulations of dimenhydrinate to prolong the drug’s release and improve its cutaneous permeation. First, the patches were fabricated and evaluated to determine their properties. The results were statistically investigated and considered significant at the p &lt, 0.05 level. Additionally, the quantitative analysis of the drug-release data and kinetic modeling was performed by using the DDSolver software to decide the candidate formula dependably. The effect of the penetration enhancers on the permeability of dimenhydrinate from the selected patch was then studied ex vivo compared to the control sample, and the patch’s safety was evaluated in rabbits, using the skin-irritation test.

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.

Objective It has long been suggested that antivertiginous medications exert their symptomatic effect through inhibition of the vestibulo-ocular reflex (VOR). We tested this hypothesis by directly measuring the VOR after administration of three agents from different substance classes: an antihistamine, a benzodiazepine and a calcium channel antagonist. Methods The gain and the variability of the high velocity VOR was assessed using video head impulses (vHIT) under the following conditions: baseline, after dimenhydrinate, after diazepam and after cinnarizine. Results We found that all three medications did not change any VOR gain or variability parameter: At 60 ms, the gain was 0.95 at baseline, 0.99 under dimenhydrinate, 0.99 under diazepam and 0.96 under cinnarizine. The gain variability across repetitive head impulses remained also uninfluenced. Conclusions The human high frequency VOR remains robust to pharmacological perturbations at common clinical doses and the assumption that symptomatic vertigo relief is achieved merely through impairment of the VOR requires re-examination. Significance Alternative mechanisms of pharmacological action might be operant, such as the modulation of vestibulo-cortical pathways, a differential effect on the low frequency VOR and an altered sensitivity to drugs in acute unilateral vestibulopathy.

Two chromatographic methods have been established and validated for simultaneous determination of mixture of Dimenhydrinate (DMH) and Cinnarizine (CIN) in their pharmaceutical formulation and in presence of Cinnarizine impurity (1-(Diphenylmethyl) piperazine); CIN impurity. The first method was TLC-densitometric one, depends on separation and quantitation of DMH, CIN and CIN impurity on TLC silica gel 60 F 254 plates, using chloroform:methanol:glacial acetic acid:ammonia solution (9.5:0.5:0.1:0.1, by volume) as a developing system followed by densitometric measurement at 235 nm. Linear relationships were obtained in the range of 0.2–2, 0.4–1.6 and 0.1–1 μg/band for DMH, CIN and CIN impurity, respectively. The studied components were well resolved from each other with significantly different R f values of 0.35, 0.52 and 0.04 for DMH, CIN and CIN impurity, respectively. The second method was RP-HPLC, separation on C8 column using 0.05 M KH 2 PO 4 (pH = 3):methanol (35:65, v/v) as the mobile phase at a flow rate of 1 mL/min and DAD detection at 240 nm. Linear relationships were obtained in the ranges of 3–30, 2–20 and 1–10 μg/mL, with significantly different R t values of 3.27, 6.95 and 2.87 min for DMH, CIN and CIN impurity, respectively. The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared with those obtained by reported HPLC method and no significant difference was obtained.