Capsaicin combined with ice stimulation improves swallowing function in patients with dysphagia after stroke: A randomised controlled trial.

BACKGROUND: Dysphagia is a common condition after stroke, and it is associated with many complications. Early and effective treatments are essential to the prognosis of patients with dysphagia. We aimed to evaluate the effects and safety of capsaicin combined with ice stimulation in patients with dysphagia after stroke. METHODS: Patients with dysphagia admitted to our hospital from December 2017 to December 2019 were included. The control group received the ice stimulation, and the experimental group received the combined capsaicin and ice stimulation. The grade of water swallowing test (WST), standard swallowing assessment (SSA) scores and the serum substance P level was compared between control (ice only) and experimental group (capsaicin plus ice). RESULTS: No differences before treatment and significance following treatment in each group (before and after) and between groups (capsaicin plus ice vs ice only) were found (all P > .05); the SSA scores were significantly reduced after intervention for both groups (all P < .001), and after intervention, SSA score in experimental group was significantly less than that of control group (P < .001). After intervention, the number of patients graded as WST level I-II in experimental group was significantly more than that of control group (P < .001); the serum substance P level was significantly increased after intervention for both groups (all P < .05), and after intervention, the serum substance P level in experimental group was significantly higher than that of control group (P = .007). CONCLUSIONS: The combined use of capsaicin with ice stimulation is beneficial to the recovery of swallowing function of patients with dysphagia, which should be included into the clinical practice.

Synthesis and biological activity of novel 5'-arylamino-nucleosides by microwave-assisted one-pot tandem Staudinger/aza-Wittig/reduction.

Novel pseudonucleosides with benzylamino group on 5'-position (4) were synthesized by using the microwave-assisted one-pot tandem Staudinger/aza-Wittig/reduction reaction in good yields of 55.2-71.7%. The deacetylation of 4 afforded compounds 5. HIV-1 reverse transcriptase (RT) inhibitory and antitumor activities were preliminarily evaluated with 5. The results showed that the new pseudonucleosides (5) could effectively inhibit HIV-1 RT activity, but no antitumor activity.

Microwave-assisted synthesis of dinucleoside analogues containing a thiazolidin-4-one linkage via one-pot tandem Staudinger/aza-Wittig/cyclization.

Dinucleosides containing a thiazolidin-4-one linkage were prepared by one-pot tandem Staudinger/aza-Wittig/intermolecular cyclization under microwave irradiation and their structures were confirmed. Preliminary examination of HIV-RT inhibition showed that the dinucleosides containing (R)-thiazolidin-4-one linkage are significantly more active than those containing (S)-thiazolidin-4-one linkage.

Design, microwave-assisted synthesis and HIV-RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(4,6-dimethyl-5-(un)substituted-pyrimidin-2-yl)thiazolidin-4-ones.

A series of novel thiazolidin-4-ones bearing a hydrophobic substituent at 5-position on the 4,6-dimethyl-pyrimidine ring at N-3 (5c-i and 6c-i) were designed on the prediction of QSAR studies, synthesized in good yields of 60.1-85.3% by microwave-assisted one-pot protocol with the combination of using dicyclohexylcarbonimide (DCC) as the promotor, and evaluated as HIV-1 reverse transcriptases inhibitors. The results of in vitro HIV-1 RT kit assay showed that some of the new compounds, such as 5c, 6c, 5d, 6d, 5g, 5h and 6i, could effectively inhibit RT activity. Among them, compounds 5c and 6c where ethyl group existed at 5-position on N-3 pyrimidine ring were the best ones with the IC(50) value of 0.26 microM and 0.23 microM, respectively. Structure-activity relationship analysis of these analogues suggested that the overall hydrophobicity and steric factor were important to the anti-HIV RT activity. The mechanism of the intramolecular cycloamidation promoted by DCC was also investigated with the key uncyclized intermediate 13.

Synthesis and biological activities of novel isoxazoline-linked pseudodisaccharide derivatives.

A series of novel isoxazoline linked pseudodisaccharide derivatives were regiospecifically synthesized by 1,3-dipolar cycloaddition of α-allyl-C-glycopyranosides and sugar-derived nitrile oxides with good yields. The structures of the compounds were characterized by NMR spectroscopy and MS spectrometry and confirmed by the X-ray crystallographic analysis of compound ((5S)-3-(2,3-O-isopropylidene-5-deoxy-d-lyxofuranose-4-yl)isoxazoline-5-yl) methyl α- C-D-galactopyranoside. Their biological activities against glycosidases (α-amylase, α-glucosidase, and ß-glucosidase) and HIV-RT, and antitumor activity were preliminarily evaluated. Some of them exhibited potent inhibitory activity to HIV-RT.

A convenient synthesis of novel thiazolidin-4-one-linked pseudodisaccharides by tandem Staudinger/aza-Wittig/cyclization and their biological evaluation.

Novel thiazolidin-4-one-linked pseudodisaccharides 3-6 were synthesized by the one-pot tandem Staudinger/aza-Wittig/cyclization reaction at room temperature. The deacetylation of 3-6 afforded compounds 7-10, respectively. The structures of the new compounds were determined using single crystal X-ray crystallography, (1)H, (13)C, and 2D NMR spectroscopy, and HR mass spectrometry. The preliminary biological evaluation of compounds 7-10 showed that compounds 7aa, 8aa, 7ab, 8ab, 7bb and 8bb were found to have significant immunopotentiating activity. Yet none of these tested compounds have obvious inhibition against glycosidases or HIV reverse transcriptase, or show cancer cell growth inhibition.

Synthesis of C-Pseudonucleosides Bearing Thiazolidin-4-one as a Novel Potential Immunostimulating Agent.

Several novel C-pseudonucleosides bearing thiazolidin-4-one were synthesized by one-pot three-component condensation using unprotected sugar aldehyde at room temperature, and their effects on T cells, B cells, the cytokine secretion of IL-2, IL-4, and IFN-γ, T cell-associated molecules (CD3, CD4, CD8), and B cell-associated molecules (CD19) were first evaluated. The experimental data demonstrated that such thiazolidin-4-one C-pseudonucleosides hold potential as immunostimulating agents.