Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022575 (keratoconjunctivitis sicca)
 772 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autotransplantation of the submandibular gland is effective for severe keratoconjunctivitis sicca. However, most transplants show decreased secretion shortly after the operation, which leads to obstruction of Wharton's duct. The hypothesis that decreased catecholamine release due to denervation contributes to hypofunction in the early phase was tested in transplanted glands in rabbits. We found that salivary flow, expression of beta(1)- and beta(2)-adrenoceptor, and the maximum binding capacity were markedly decreased in the transplanted glands. Isoproterenol significantly reversed the decreased secretion, enhanced the expressions of beta(1)- and beta(2)-adrenoceptor, and ameliorated the atrophy of acinar cells. The contents of cAMP and phospho-ERK 1/2 were increased after isoproterenol treatment. These results indicate that lack of beta-adrenoceptor stimulation is involved in early dysfunction of the transplanted gland. Isoproterenol treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through up-regulating beta(1)- and beta(2)-adrenoceptor expression and post-receptor signal transduction.
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PMID:Isoproterenol improves secretion of transplanted submandibular glands. 1949 94

Infusion of high-KCl cardioplegic solution (High-KCS) is the most common method used to induce asystole before cardiac surgery. However, our previous study showed the High-KCS can cause the apoptosis of cardiomyocytes in patients who were administered High-KCS prior to undergoing coronary artery bypass graft (CABG) to treat coronary artery disease (CAD). Therefore, it is urgent today to find a complementary medicine to reduce this damage. Dilong (earthworm) has been used as a traditional medicine in China for several thousand years, and extract from the dilong has been empirically used in Asia for the treatment of vascular disorders. In this study, we applied dilong extract to reduce myocardial cell damage from High-KCS infusion and further investigated the mechanisms. H9c2 cardiomyoblast cells were cultured in serum-free medium for 4 h and then treated with dilong at 31.25, 62.5, 125, and 250 mg/mL for 24 h, which was then followed by High-KCS treatment for 3 h to detect the protective mechanisms of dilong behind cardiomyocyte apoptosis and cardiac fibrosis. Cells were harvested for MTT assay, TUNEL assay, and western blot analysis. We found that High-KCS-induced cardiomyocyte apoptosis, enhanced the protein level of pro-apoptotic Bad, released cytochrome c, and activated caspase-3 in H9c2 cells. The IGF-I/IGF-IR/ERK pathway involved in non-cardiomyocyte proliferation, and the expression/activation of uPA, Sp-1 and CTGF, which are implicated in the development of cardiac fibrosis were up-regulated, but the Akt for cardiomyocyte survival was greatly deactivated in postcardioplegic H9c2 cardiomyoblast cells. However, dilong was highly protective and totally reversed the apoptosis and cardiac fibrosis effects induced by High-KCS. Chemical inhibitors P38 (SB203580), JNK (SP600125), MEK (U0126), IGF-1 (AG1024), and PI3K (LY294002) were applied to investigate which is the mediator for dilong attenuated High-KCS stimulated caspase 3 activation. MEK (U0126) inhibitor completely blocked dilong inhibited caspase 3 activation in High-KCS treated H9c2 cells. The MEK siRNA was further applied to knockdown MEK to confirm our finding. We found dilong worked through MEK to inhibit caspase 3 activity induced by High-KCS in H9c2 cells. Furthermore, we used the pure component of dilong, Lumbrokinase, to block the High-KCS effect. Using the microscope to observe the cell viability, we found Lumbrokinase could reverse the High-KCS effect. Lumbrokinase could also reduce the protein levels of caspase 8, caspase 9, and caspase 3, and enhance the survival related proteins PI3K/Akt and Bcl2. These results demonstrate that dilong could be used as a potential agent to block the side effects caused by High-KCS in CABG surgery patients.
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PMID:Dilong prevents the high-KCl cardioplegic solution administration-induced apoptosis in H9c2 cardiomyoblast cells mediated by MEK. 2548 76