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Background: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel., Methods and Design: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session., Discussion: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial., Trial Registration: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018., (© 2022. The Author(s).)

Aims: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis., Background: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported., Design: A Randomized, Double-Blind, Active-Controlled Trial., Methods: The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein., Results: Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment., Conclusion: Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate., Impact: Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122., (© 2020 John Wiley & Sons Ltd.)

Background: Diclofenac and curcumin is anticipated to have synergistic action. Hence, topical route of administration can be used in minimizing the issues with oral administration of both drugs., Objective: This research aims at formulation of controlled release dosage form containing curcumin microspheres and diclofenac diethylamine and then incorporating it into gel formulation for treatment of inflammation associated with rheumatoid arthritis., Methods: Curcumin microspheres were prepared, optimized and assayed. Gel containing microspheres was formulated and evaluated for physicochemical parameters like spreadability and viscosity. In vitro and ex vivo diffusion studies were carried out followed by evaluation of efficacy. Efficacy of the developed formulation was evaluated for anti-inflammatory activity., Results: Particle size, Zeta potential, pH, spreadability and viscosity of optimized Batch F1 was found to be in range 0.5 µm - 5 µm,-27.9 mV, 6.2, 105 g cm/s and 7500 cps respectively. In vitro diffusion of developed gel of diclofenac diethylamine and curcumin was found to be 92.16 ± 0.0040 % in 3 h and 92.54 ± 0.0036 % in 12 h as compared to 79.57 ± 0.004 % diffusion in 2 h for marketed gel, thus showing controlled delivery of curcumin., Conclusion: Decreased inflammation in formulation treated group by 72.53% and 50.75% in marketed treated group was seen. Thus the formulation developed showed prolonged activity as well as better anti-inflammatory activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this paper, the author study on the effect of drug treatment on sports injury, and makes a comparative analysis of drug effects. In sports, the incidence of various types of injuries is increasing, especially in muscle injury. In the experiment, we compared the effects of three different drugs on the treatment and relief of muscle loss. After 3 weeks, the average optical density of desmin in muscle fiber positive region have decreased, as xiaotong plaster (0.4708±0.0126), votalin (0.5124±0.0264) and placebo (0.3856±0.0312). It has a certain effect to promote the repair and regeneration of desmin expression by drugs. Through the analysis of the effect of drug intervention on sports injury repair, we can effectively improve the therapeutic effect of sports injury.

Objective: To study the clinical efficacy of sacral manual therapy in the treatment of coccygodynia., Methods: From November 2013 to July 2015, 184 patients with sacrococcygeal pain were divided into treatment group and control group. There were 26 males and 65 females in the treatment group, with an average age of (39.63±11.62) years old. In the control group, there were 31 males and 62 females, with an average age of (41.47±11.56) years old. The patients in the treatment group were treated with sacrococcygeal massage therapy, 3 times a week for 2 weeks. The patients in the control group were treated with Diclofenac Diethylamine Emulgel, 2 times a day for 2 weeks. The VAS pain score, score in rating scale of sacrococcygeal pain and degree of tenderness were obtained on the first day of treatment, 2, 7, 14 days and 3 months after treatment to evaluate clinical results., Results: When comparing the VAS pain score of sacrococcygeal pain within the two groups, the differences began to reach statistical significance on the second day( P <0.001). The chagne of VAS pain scores, the change of scores in rating scale of sacrococcygeal pain and the degree of tenderness in the treatment group were all significontly larger that those in the contral group from the second day., Conclusions: The curative effect of sacral manipulation group is better than that of Diclofenac Diethylamine Emulgel group in the treatment of sacrococcygeal pain., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

The authors studied the effects of T-588 on scopolamine-induced memory impairments in the acquisition of a classical eyeblink conditioning in behaving adult mice. Mice injected with 0.3 mg/kg of scopolamine showed a marked deficit, compared with nontreated mice, in the acquisition of classical eyeblink conditioning using a trace paradigm. Coadministration of T-588 (0.05% wt/vol, in water) with scopolamine (0.3 mg/kg) significantly prevented this deficit in associative learning. To further assess the effects of T-588 on motor coordination and the cognitive deficits induced by scopolamine, the authors compared adult controls or scopolamine-treated mice in different behavioral tasks: rotarod, object recognition, passive avoidance, and prepulse inhibition. In all of these tasks, the authors found a significant impairment in the motor or cognitive abilities in scopolamine-injected mice, compared with controls. In addition, the coadministration of T-588 with scopolamine restored deficits induced by scopolamine alone. Importantly, the administration of T-588 alone did not evoke any change compared with values obtained for controls. These results suggest that T-588 could be used as a pharmacological agent to improve motor and associative learning disorders.

Objectives/hypothesis: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.R(-)-1-(benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models., Study Design: Animal study., Methods: Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold., Results: T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls., Conclusion: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.

Acetylcholinesterase inhibitors have beneficial effects to improve the cognitive impairment in patients with mild to moderate Alzheimer's disease (AD). In addition, a channel blocker of N-methyl-D-aspartate receptor, memantine hydrochloride, was approved as a therapeutic agent for patients with moderate to severe AD in both EU countries in 2002 and USA in 2003, while the clinical development is still ongoing in Japan. In contrast, the pharmacotherapy for a prime cure against AD is not available in the market, although there has been a worldwide search for novel compounds. The most plausible mechanism for the treatment of AD is the reduction of the amyloid beta-peptide (Abeta) plaques, one of the pathological markers of AD, in the brain. For this purpose, the inhibitors of beta-secretase and gamma-secretase, which cleave amyloid precursor protein (APP) to release Abeta, has been developed to interfere with APP processing. The beta-sheet breaker and metal chelators for the breakdown of aggregated Abeta have also been synthesized as well as the immunotherapeutic approach using Abeta vaccine. On the other hand, some nonsteroidal anti-inflammatory drugs, such as ibuprofen and sulindac, noncompetitively inhibited Abeta production but not Notch cleavage. The development of Abeta-lowering drugs is highly expected for the treatment of AD.

Purpose: To investigate the effects of repeated treatments with a neuroprotective compound, R(-)-1-(benzo [b] thiophen-5-yl)-2-[2-(N, N-diethylamino) ethoxy] ethanol hydrochloride (T-588), on retinal ganglion cell (RGC) survival in rat eyes with elevated intraocular pressure (IOP) or after optic nerve crush., Methods: An increase in IOP was induced by a single laser treatment to the trabecular meshwork in one eye of adult Wistar rats. Crush injury was unilaterally produced by clipping the optic nerve 2 mm behind the globe. RGC density was estimated by counting fluorescent dye-labeled cells in the flatmount of the retina. The optic nerve damage in the crush model was also evaluated histologically., Results: In the elevated IOP model, RGC survival decreased to 72.9% +/- 3.8% (mean +/- SEM) of that of the contralateral control eye on the eighth day after laser irradiation. Repeated treatments with T-588 at 30 mg/kg twice daily significantly enhanced RGC survival (86.0% +/- 2.2%, P = 0.0242) without the reduction of IOP. In the optic nerve crush model, RGC survival diminished to 37.2% +/- 8.4% of that of the contralateral control eye after 4 weeks. Repeated applications with T-588 at 10 mg/kg twice daily significantly enhanced RGC survival (77.8% +/- 2.1%, P = 0.0038). Histologically, the rat optic nerve in the group treated with T-588 at 10 mg/kg retained a near-normal morphology., Conclusions: T-588 has a neuroprotective effect against RGC death caused by elevated IOP and optic nerve crush in the rat.

The title compound (T-588) has been evaluated for its ameliorating effect on memory impairment generated by cerebral embolization and by a basal forebrain (BF) lesion in male Wistar rats. The memory and learning deficits induced by injection of carbon-microspheres into the internal carotid artery were significantly improved by T-588 at oral dose of 3-10 mg/kg, as determined by an active avoidance response assay, whereas the reference drugs (tacrine, idebenone and indeloxazine) proved almost inactive in the same assay procedure. As far as the embolization was concerned, a significant decrease in cerebral acetylcholine and monoamines was observed. The effect on the memory impairment caused by an electrolytic lesion of the BF was assessed by a passive avoidance task. T-588 exhibited a bell-shaped dose-response curve and was most active at 1 mg/kg (oral dose), while tacrine showed equal activity at 10 mg/kg.

Effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2- (N,N-diethylamino)ethoxy]ethanol hydrochloride (T-588) on normobaric hypoxia, histotoxic anoxia by KCN and complete ischemia by decapitation were investigated in mice. T-588 (30-100 mg/kg, p.o.) showed a significant and dose-dependent prolongation of the survival time in all of the models studied. Bifemelane (100-300 mg/kg, p.o.) was also protective against all the models. Tacrine was protective against hypoxia but had no effect on anoxia and ischemia. Imipramine was protective against anoxia, but shortened the survival time of hypoxic mice. It had no effect on ischemia. The anti-hypoxic effect of T-588 was completely inhibited by pretreatment with scopolamine (1 mg/kg, i.p.), while the anti-anoxic effect was partially inhibited. Its effect on the ischemia was not affected by scopolamine. Hypoxia decreased the cerebral contents of ATP, phosphocreatine and glucose and increased the contents of lactate in mice. T-588 had no effect on these changes. Bifemelane prolonged pentobarbital-induced sleeping time in mice with the doses inducing anti-anoxic action, but T-588 did not. These results suggest that the activation of the CNS cholinergic system is involved as one of the mechanisms for the anti-anoxic action of T-588.

The effectiveness of repeated pharamacotherapy in acute poisonings with fluostigmine was studied in rats. It was demonstrated, that the second i.p. administration of obidoxime (40 mg/kg) was without effect. Repeated i.p. administration of atropine (10 mg/kg) shown marked efficacy only in animals treated previously with atropine (10 mg/kg) and diazepam (2.5 mg/kg). This procedure was without effect in animals treated just after intoxication with atropine (10 mg/kg) or atropine (10 mg/kg) and obidoxime (40 mg/kg). Subsequent administration of diazepam (2.5 mg/kg) or caramiphen (10 mg/kg) was without effect.

The topical bioavailability of a potential anti-acne agent ([14C]-SC-23110) was determined in the rhesus monkey, an animal model relevant to man. By the method of cumulative excretion in urine and feces the percutaneous absorption of 21 microgram/cm2 of the free base form was determined to be 0.58 +/- 0.16 (SD) percent of the applied dose. The mean areas under the plasma concentration time curves (AUC) following topical and intravenous administration were also determined. The ratior of the AUC's following topical and iv administration gave a bioavailability of 0.49% of the applied dose, a value in good agreement with the 0.58% obtained by cumulative excretion. Plasma AUC curves can be used to determined the percutaneous absorption (bioavailability) of compounds. Percutaneous absorption of [14C]-SC-23110 (80 microgram/cm2) when topically applied as the salt or free base form was compared. Twice the amount of compound was absorbed as the free base (0.34%) than as the salt (0.17%).

A new cholinesteras reactivator--chlorohydrate of S-diethylaminoethyl ether p-bromo benzoylthiohydroxime acid (diethixime), containing a tertiary nitrogen atom in the molecule, was shown to produce a central effect in a dose of 20 mg/kg--1/50 LD50--in contrast to diproxime in a dose of 3 mg/kg, containing a quarternary nitrogen atom, under intoxication of albino rats and rabbits with dimethyl-dichlorynylphosphate. This effect was confirmed by the restortion of the cholinesterase activity in different parts of the rabbit brain, by the normalization of the EEGand of the functional stateof motor neurons of the rat spinal cord.

67 patients who are suffering from a non-acute perceptive hearing loss were treted by several vasoactive medicaments. Besides pharmacological aspects of derivatives of di-ethyl-amino-ethyl-alcohol and of xanthine were discussed. The therapeutical results were subjected to comparing views.

The atrioventricular block was produced in dogs 24 hours after the occlusion of the left descending coronary artery by formalin injection into the atrioventricular node or the bundle of His. The intensity and duration of the ectopic foci inhibition produced by ethmozine and by its diethylamine analogue (ethmozine DAA) were compared. It was shown that intravenous infusion of 3 mg/kg ethmozine reduced the frequency of the ectopic ventricular excitations by 28% (n = 6), 0.5 mg/kg ethmozine DAA - by 46% (n = 7), and 1 mg/kg ethmozine DAA - by 78% (n = 8). In 50% of the animals 1 mg/kg ethmozine DAA completely suppressed the ectopic activity. Duration of the drugs action was determined by the time necessary for the attainment of 50% of the maximal effect in the inhibition of ectopic exitation frequency (for 3 mg/kg ethmozine it was 32.7 +/- 2.5 min, for 0.5 mg/kg ethmozine DAA - 5.1 +/- 7.2 min, and for 1 mg/kg ethomozine DAA - 55.0 +/- 9.8 min). The results obtained suggest that the ethmozine DAA action is more intensive and of longer duration than ethmozine, and effective at the late stage of experimental myocardial infarction.

Clove oil injection in the anterior chamber of the rabbit eye produces an uveitis and a disruption of the blood-ocular barrier which can be evaluated by the leakage of 125I-radiolabelled rabbit serum albumin (RSA) administered intravenously. In the normal rabbit eye the amount of RSA in the aqueous humor is quite small. The disruption of the blood-ocular barrier by clove oil injection increases the RSA level in the anterior chamber of the eye. Topically applied chromocarb diethylamine reduces significantly the disruption of the blood-ocular barrier in the inflamed eye. Despite of its lack of anti-inflammatory activity, this compound, as a 10% eye-drop formulation, was shown nearly as effective as prednisolone 0.1%, in the corneal edema and the disruption of the blood-ocular barrier.

The effect of a new cholinolytic drug ethpenal, that is applied clinically as an antiparkinsonian and antiulcer agent, on the course of experimental myocardial infarction has been studied. The experiments have shown that in the test animals (white rats and rabbits) with myocardial infarction, ethpenal increases by 9.3% the contractile function of myofibrils, makes tissue respiration return to normal, and approximates the P/O magnitude to the control level. Administration of ethpenal to the animals with experimental myocardial infarction induces a considerable increase in the content of polyglycerophosphatides, which, in its turn, leads to stabilization of the cellular membranes. The drug improves permeability of the bilayer lecithin membranes by calcium ions. A conclusion is made that the myocardial infarction, ethpenal exerts a beneficial effect on the processes occurring at a level of the cellular membranes.