Background:Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disorder characterized by autoimmune activation, microvascular endothelium damage, and excessive collagen proliferation. The most affected hand presents claw hand deformity and microvascular disease. Deformed hands can cause functional disability and decrease the quality of life. A daily home program can improve mobility of scleroderma patients.Objective:We sought to determine the effect of a daily home exercise program on hand mobility among scleroderma patients.Materials and Methods:This was a randomized control trial. Twenty-eight participants were divided into two groups, both of which received the same daily home treatment: Group 1 with gloves (n = 14) and Group 2 without gloves (n = 14). The 2-week daily home program combined traditional Thai massage (TTM) with stretching exercises and heat. Hand mobility was assessed using hand mobility in scleroderma (HAMIS). The study was conducted in patients who were already on vasodilator drugs.Results:Both groups showed a significant improvement in hand mobility after 2 weeks of daily home exercise program (P < 0.05). Wearing the glove, however, resulted in better thumb mobility.Conclusions:A daily home exercise program improved hand mobility among patients with scleroderma and wearing gloves may improve thumb mobility.

Oxazepam (CAS 604-75-1) 4a served as building block in the synthesis of substituted 3-amino-1,4-benzodiazepines, which were subsequently tested in various CNS animal models. The hydroxy group of oxazepam was either activated as a chloride (Method A) or as a phosphor-oxy derivative (Method B) giving the desired 3-amino-1,4-benzodiapines 6a-6r in high yields with primary and secondary amines in a typical nucleophilic substitution reaction. Eighteen 3-substituted 1,4-benzodiazepines were prepared and served as new chemical entities and for lead structure discovery. The mixed cholecystokinin (CCK) antagonist 6e showed anxiolytic and antidepressant effects from 10 microg/kg in mice in the elevated x-maze test and the forced swimming test. The CCK1 antagonist 6 g has shown antidepressant effects from the same dose, but lacked anxiolytic properties. Both compounds potentiated at a dose of 0.5 mg/kg morphine antinociception with a maximum possible effect (MPE) about 35%. By assessing initially the MPE of antinocipection for the 18 newly synthesised benzodiazepines in the tail-flick test, 4 other benzodiazepines were found active. In further in vive evaluation the cyclohexyl derivative 6 i displayed anxiolytic, antidepressant and antinociceptive properties as single agent at a dose of 5 mg/kg without toxicity. The benzodiazepines 6i and 6p, which initially showed a higher MPE in terms of morphine potentiation (43/44%) showed analgesic effects as single agents, without having anxiolytic or antidepressant properties. The amino-piperidinyl derivative 6p displayed a similar dose-response relationship to morphine, but was 3 times more potent.

4-Amino-2(5H)-furanones were synthesized in high yields over two synthetic steps from readily available mucochloric acid. These 5-alkyloxy-4-amino-2(5H)-furanones were screened in a ([125]) I-CCK-8 radioligand receptor binding assay for CCK2 affinity and novel active ligands in the nanomolar range were identified. SAR was optimized leading to the cyclohexyl derivative 25 with an IC50 of 27 nM. Furanone 18 was obtained as a stable crystalline material with an IC50 of 85 nM, but had a higher CCK2 selectivity. It was subsequently tested in the isolated guinea pig ileum assay with sulfated CCK8 , and the CCK antagonizing properties of the ligand were confirmed. The CCK2 selective antagonist 18 was found to potentiate analgesia in the tail flick assay in mice, for the strong opiate morphine, the partial opiate agonist tramadol and the tricyclic antidepressant desimipramine.

The structure-activity relationship optimization of the pyrazoline template 3a resulted in novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides 4a-4e. These non-peptidal CCK ligands have been shown to act as potent CCK1 ligands in a [125]I-CCK-8 receptor binding assay. The best amides (4c and 4d) of this series displayed an IC50 of 20/25 nM for the CCK1 receptor. In a subsequent in-vivo evaluation using various behaviour pharmacological assays, an anxiolytic effect of these novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides was found at high doses in the elevated plus-maze. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.33/0.41 mg kg(-1) was determined for amide 4c/4d and the antidepressant effect had a magnitude comparable to desimipramine.

Modified-active release therapy (mART) was developed to treat patients experiencing upper quarter pain. The objective of the study was to determine the effectiveness of the mART in treating pain, promoting function, and measuring emotions in patients with scapulocostal syndrome (SCS) and masticatory myofascial pain (MMP). A stratified-randomized controlled trial was employed in 38 participants separated into two groups. All participants underwent the same series visual analog scale (VAS), pressure pain threshold (PPT), mouth opening (MO), maximum mouth opening (MMO), craniovertebral angle (CV-angle), and pain catastrophizing scale Thai version (PCS-Thai-version) at the baseline. The mART group underwent the mART program three times a week for 4 weeks with a hot pack and an educational briefing while the control group received only a hot pack and the educational briefing. After treatment, both groups showed significant improvement (p < 0.05) in all parameters except MO, MMO, and CV-angle. When comparing outcomes between the groups, the mART group showed a statistically significant greater number of improvements than did the control group. In conclusion, the mART program can improve pain experienced by patients with SCS and MMP and it can be used as an adjuvant technique with conservative treatment.