ResearchPad - oral-administration Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Oral administration with a traditional fermented multi-fruit beverage modulates non-specific and antigen-specific immune responses in BALB/c mice]]> Fruits have been widely considered as the default “health foods” because they contain numerous vitamins and minerals needed to sustain human health. Fermentation strategies have been utilized to enhance the nutritive and flavor features of healthy and readily consumable fruit products while extending their shelf lives. A traditional fermented multi-fruit beverage was made from five fruits including kiwi, guava, papaya, pineapple, and grape fermented by Saccharomyces cerevisiae along with lactic acid bacteria and acetic acid bacteria. The immunomodulatory properties of the fermented multi-fruit beverage, in vivo nonspecific and ovalbumin (OVA)-specific immune response experiments using female BALB/c mice were performed. Administration of the fermented multi-fruit beverage reduced the calorie intake, thus resulting in a less weight gain in mice compared to the water (placebo)-fed mice. In the nonspecific immune study model, the fermented multi-fruit beverage enhanced phagocytosis and T cell proliferation but did not affect B cell proliferation and immunoglobulin G (IgG) production. Analysis of cytokine secretion profile also revealed that the fermented multi-fruit beverage enhanced proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and T helper (Th)1-related cytokine interferon (IFN)-γ production, thus creating an immunostimulatory effect. Nonetheless, in the specific immune study model, the results showed that the fermented multi-fruit beverage decreased the production of proinflammatory cytokines IL-6 and TNF-α production in OVA-immunized mice. Moreover, it also caused a decrease in the production of anti-OVA IgG1, which was accompanied by a decrease in Th2-related cytokines IL-4 and IL-5 production and an increase in Th1-related cytokine IFN-γ production, indicating that it may have the potential to shift the immune system from the allergen‐specific Th2 responses toward Th1-type responses. The results indicate that fermented multi-fruit beverage has the potential to modulate immune responses both in a nonspecific and specific manners.

<![CDATA[Ultra-performance hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma: Application to pharmacokinetic study in rats]]>

A fixed dose combination of lesinurad and allopurinol has been recently approved by USFDA and EMA for treatment of gout-associated hyperuricemia in patients who have not achieved target serum uric acid levels with allopurinol alone. In this study, an ultra-performance hydrophilic interaction liquid chromatography (UPHILIC) coupled with tandem mass spectrometry method was developed and validated for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma. Liquid liquid extraction using ethyl acetate as extracting agent was used for samples extraction procedure. Acquity UPLC HILIC column (100 mm x 2.1, 1.7μm) was used for separation of allopurinol, oxypurinol, lesinurad and internal standard (5-Florouracil). The mobile phase consisting of acetonitrile, water and formic acid (95:5:0.1, v/v/v), were eluted at 0.3 mL/min flow rate having total chromatographic run time of 3 min per sample. The analytes were detected on Acquity triple quadrupole mass spectrometer equipped with a Z-Spray electrospray ionization (ESI). The ESI source was operated in negative mode and multiple reaction monitoring was used for ion transition for all compounds. The precursor to product ion transition of m/z 134.94 > 64.07 for allopurinol, 150.89 > 41.91 for oxypurinol, 401.90 > 176.79 for lesinurad and 128.85 >41.92 for internal standard were used for identification and quantification. The calibration curves for all analytes were found to be linear with weighing factor of 1/x2 using regression analysis. The developed assay was successfully applied in an oral pharmacokinetic study of allopurinol, oxypurinol and lesinurad in rats.

<![CDATA[Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation]]>


The optimal sedative regime that provides the greatest comfort and the lowest risk for procedural sedation in young children remains to be determined. The aim of this randomized, blinded, controlled, parallel-design trial was to evaluate the efficacy of intranasal ketamine and midazolam as the main component of the behavioral guidance approach for preschoolers during dental treatment.

Materials and methods

Children under seven years of age, with caries and non-cooperative behavior, were randomized into three groups: (KMIN) intranasal ketamine and midazolam; (KMO) oral ketamine and midazolam; or (MO) oral midazolam. The dental sedation appointments were videotaped, and the videos were analyzed using the Ohio State University Behavioral Rating Scale (OSUBRS) to determine the success of the sedation in each group. Intra- and postoperative adverse events were recorded. Data analysis involved descriptive statistics and non-parametric tests (P < 0.05, IBM SPSS).


Participants were 84 children (28 per group; 43 boys), with a mean age of 3.1 years (SD 1.2). Children’s baseline and the dental sedation session characteristics were balanced among groups. The success of the treatment as assessed by the dichotomous variable ‘quiet behavior for at least 60% of the session length’ was: KMIN 50.0% (n = 14; OR 2.10, 95% CI 0.71 to 6.30), KMO 46.4% (n = 13; OR 1.80, 95% CI 0.62 to 5.40), MO 32.1% (n = 9) (P = 0.360). Adverse events were minor, occurred in 37 of 84 children (44.0%), and did not differ among groups (P = 0.462).


All three regimens provided moderate dental sedation with minor adverse events, with marked variability in the behavior of children during dental treatment. The potential benefit of the ketamine–midazolam combination should be further investigated in studies with larger samples.

Trial registration, identifier: NCT02447289. Registered on 11 May 2015, named “Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO).”

<![CDATA[TAK-071, a muscarinic M1 receptor positive allosteric modulator, attenuates scopolamine-induced quantitative electroencephalogram power spectral changes in cynomolgus monkeys]]>

Activation of the muscarinic M1 receptor is a promising approach to improve cognitive deficits associated with cholinergic dysfunction in Alzheimer’s disease, dementia with Lewy bodies, and schizophrenia. TAK-071 is an M1-selective positive allosteric modulator that improves cognitive deficits induced by scopolamine, a non-selective muscarinic receptor antagonist, with reduced side effects on gastrointestinal function in rats. In this study, we explored changes in quantitative electroencephalography (qEEG) power bands, with or without scopolamine challenge, as a non-invasive translational biomarker for the effect of TAK-071 in cynomolgus monkeys. Scopolamine has been reported to increase theta and delta power bands and decrease alpha power band in healthy volunteers. In line with the clinical observations, scopolamine (25–100 μg/kg, subcutaneous administration [s.c.]) increased theta and delta power bands in cynomolgus monkeys in a dose-dependent manner, whereas it had the opposite effect on alpha power band. The effects of TAK-071 on scopolamine (25 μg/kg, s.c.)-induced qEEG spectral changes were examined using an acetylcholinesterase inhibitor donepezil and a muscarinic M1/M4 receptor agonist xanomeline as comparative cholinomimetics. TAK-071 (0.3–3 mg/kg, oral administration [p.o.]), donepezil (3 mg/kg, p.o.), and xanomeline (1 mg/kg, s.c.) suppressed the scopolamine-induced increases in alpha, theta, and delta power bands. These results suggest that changes in specific qEEG power bands, in particular theta and delta power bands in the context of scopolamine challenge, could be used as translational biomarkers for the evaluation of TAK-071 in clinical studies.