Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that nitric oxide (NO) plays an important role in mediating the anti-adrenergic effect of adenosine on atrioventricular (AV) nodal conduction. In guinea-pig hearts instrumented for measurement of AV nodal conduction time (atrium-to-His bundle, A-H, interval), the NO synthase (NOS) inhibitor, l-NMMA (100 microm), reversibly inhibited 80% (P=0.009, n=6) of adenosine's anti-adrenergic action on the positive dromotropic effect of isoproterenol (0.01 microm). In parallel studies carried out in rabbit AV nodal myocytes, intracellular mechanisms whereby NO mediates the inhibitory effect of adenosine on isoproterenol-induced A-H interval shortening were studied. Adenosine (3 microm) inhibited isoproterenol-stimulated (0.1 microm) I(Ca,L)(beta -I(Ca,L)) by 46+/-6% (P<0.001, n=17). Consistent with isolated heart data, the NOS inhibitors, l -NMMA (100 microm) and L-NNA (500 microm) attenuated the effect of adenosine on beta -I(Ca,L)by 69+/-8% (P<0.001, n=16) and 69+/-7% (P<0.001, n=10), respectively. An inhibitor of NO-stimulated guanylyl cyclase LY83538 (40 microm) reduced the inhibitory effect of adenosine on beta -I(Ca,L)by 97+/-6% (P=0.004, n=15). Similarly, the non-specific inhibitor of cAMP-phosphodiesterases IBMX (50 microm) decreased the anti-adrenergic effect of adenosine by 60% (P=0.02, n=6), whereas the extracellular application of the non-hydrolyzeable cAMP analog 8-Br-cAMP (500 microm) prevented this action of adenosine. Activation of cGMP-dependent protein kinase (PKG) by CPT-cGMP (300 microm) diminished beta -I(Ca,L), but to a significantly smaller degree (16+/-4%, P=0.025, n=12) than that caused by adenosine. NO mediates the anti-adrenergic effect of adenosine on AV nodal conduction by a mechanism predominately involving activation of cGMP-dependent cAMP-phosphodiesterase and to a lesser extent activation of PKG.
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PMID:Antagonism of the positive dromotropic effect of isoproterenol by adenosine: role of nitric oxide, cGMP-dependent cAMP-phosphodiesterase and protein kinase G. 1096 24

Lack of a standardized experimental counterpart of peripheral lymphedema (LE) in a small animal has hampered research into treatment of this debilitating condition. We recently refined a rodent model consisting of radical unilateral lymphatic/nodal groin excision in conjunction with a circumferential integumental gap, followed by regional irradiation of the groin to reproduce stable unilateral hindlimb LE (1). In the current study, Wistar-Fuzzy rats with established right hindlimb LE, were subdivided into five groups and subjected to one of the following daily physical regimens over a 5-day period: pneumatic compression pumping at 30 torr (PCP); low-stretch multi-layered compressive bandaging using Coban (CB); manual lymphedema drainage (MLD) or a light massage consisting of stationary circular motions using the fingertips; combined physiotherapy (CPT consisting of MLD + CB); and a no treatment or control group (CTRL). Hindlimb and LE volumes were serially measured before and after treatment. Whereas CTRL showed progressive worsening of hindlimb swelling, PCP, CB, CPT and MLD each produced similar and substantial edema reduction over the 5 day interval, PCP, CB and CPT induced vacillating edema reduction which, however, exceeded rebound swelling on a daily basis. MLD, on the other hand, showed a steady gradual daily decline in LE volume.
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PMID:Limb volume reduction after physical treatment by compression and/or massage in a rodent model of peripheral lymphedema. 1193 69

A 78-year-old woman was admitted to our hospital complaining of persistent abdominal pain and diarrhea. Computed tomography (CT) and colonoscopy (CF)revealed a huge ascending colon tumor, invading the descending part of the duodenum. The patient was treated preoperatively with a combination of S-1 plus CPT-11 (S-1 80 mg/body day 1-29, CPT- 11 100 mg/body day 1, 8, 15 and 22). No serious side effect was observed except low-grade fever and grade 2 appetite loss and diarrhea. Tumor reduction was significant on the preoperative CT and CF, with the invasion to the duodenum obscured. Right hemicolectomy with wedge resection of the duodenum was performed. Resected specimen revealed residual tumor in a small area of the submucosal to proper muscular layer of the contracted ascending colon, without pathological invasion to the duodenum. No nodal metastasis was observed. The patient was administered UFT (300 mg daily)postoperatively for two years and is still alive and free of disease after three years and ten months since the operation.
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PMID:[Huge ascending colon carcinoma, treated successfully with S-1 plus CPT-11, followed by significant tumor reduction and curative resection--a case report]. 1992 Mar 99