Mechanism of action of the phorbol ester tumor promoters: Specific receptors for lipophilic ligands

Cells and tissue preparations specifically bind the phorbol ester tumor promoters. The agreement in structure-activity relationships between binding and biological response strongly argues that these binding sites function as phorbol ester receptors. Upon subcellular fractionation, the phorbol ester binding activity is particulate. In addition, a phorbol ester apo-receptor can be detected in cytosol which requires phospholipids for reconstitution. This apo-receptor appears to correspond to protein kinase C. Diacylglycerols, the probable natural activators of protein kinase C, competitively inhibit phorbol ester binding, consistent with their being the postulated endogenous phorbol ester analogs. In certain systems, heterogeneity of phorbol ester binding is found. An outstanding issue therefore is whether protein kinase C is the phorbol ester receptor or whether it is only the most abundant class of receptor. Although this question remains unresolved, we can demonstrate heterogeneity of phorbol ester binding by reconstitution of apo-receptor into a heterogeneous lipid environment.     

Attenuation of SAH-induced cerebral vasospasm by a selective ECE inhibitor

CGS 26303, a dual inhibitor of endothelin-converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11, was previously shown to prevent and reverse vasospasm in an experimental model of subarachnoid hemorrhage (SAH). However, reversal of the vasospastic response was not very efficacious. This study was designed to examine the effects of a highly selective ECE-1 inhibitor, CGS 35066, on SAH-induced cerbrovasospasm. Experimental SAH was induced in New Zealand white rabbits by injecting autogenous blood into cisterna magna and CGS 35066 was injected i.v. twice daily, either at 1 h (prevention protocol) or 24 h (reversal protocol) after SAH. Treatment with CGS 35066 significantly attenuated basilar arterial narrowing at a dose of 1 mg/kg in both protocols. These findings provide support for the use of selective ECE-1 inhibitors for the treatment of SAH-induced vasospasm even after the process of arterial narrowing has begun.     

Free radial forearm flap with adipofascial tissue extension for reconstruction of oral cancer defect

The radial forearm flap has been one of the most popular flaps used to reconstruct defects after oral cancer ablation. However, it sometimes may not provide sufficient soft tissue to obliterate the dead space after tumor excision and lymph node dissection, which can result in deep wound infection of the neck or even orocervical fistula. The authors modified the radial forearm flap with a sheet of adipofascial tissue extension to prevent such postoperative complications. From January 1997 to December 2000, 52 patients who underwent ablative oral cancer surgery were studied. A total of 29 patients (group I) underwent reconstruction with the traditional radial forearm flap retrospectively, and 23 patients (group II) underwent reconstruction with the radial forearm flap along with a sheet of adipofascial tissue extension. The radial forearm flap was designed on the axis of the radial artery, was 8 x 4 to 12 x 10 cm in size, and was sufficient to resurface the intraoral defect. In group II, the radial forearm skin flap along with a sheet of adipofascial tissue 8 x 8 to 12 x 10 cm was used to obliterate the dead space of the oral floor and neck. The donor site of both groups was resurfaced with a split-thickness skin graft. In group II, the skin flap of the adipofascial tissue was resutured to its original site. Two flaps in group I failed because of arterial occlusion and required other skin flaps for reconstruction. Postoperative hematoma, which required surgical treatment for drainage, developed in five patients in group I. None of the patients in group II had hematoma formation. Nine patients in group I had a neck wound infection compared with only 2 patients in group II (a significant difference). The average volume of drainage and days of hospitalization were similar in both groups. The morbidity of the donor site of both groups was not significant. The advantages of this modification include 1) suitable soft tissue available for dead space obliteration to decrease the chance of postoperative hematoma; 2) the important vessels in the neck can be protected; 3) there is a decrease in neck wound infections; and 4) donor site morbidity is similar to the traditional group.     

Versatility of the free anterolateral thigh flap for reconstruction of soft-tissue defects: review of 140 cases

From August 1995 to June 1999, 140 free anterolateral thigh (ALT) flaps were transferred to reconstruct a variety of soft-tissue defects. The size of ALT flap ranged from 10 to 33 cm in length and 4 to 14 cm in width. Based on the anatomic variations of the perforators, the blood supply to the skin island came from the septocutaneous perforators only in 19 patients (13.6%), arising from the descending or transverse branch of the lateral circumflex femoral artery (LCFA), or originating directly from LCFA. The other flaps were supplied by musculocutaneous perforators that were elevated as a true perforator flap via intramuscular dissection (N = 34, 24.3%), or used a cuff of vastus lateralis muscle for added bulk (N = 87, 62.1%). The overall success rate was 92% (129 of 140). After a 2-year follow-up, all flaps have healed unevenffully and donor thigh morbidity is minimal. Anatomic variations must be considered if the ALT flap is to be used safely and reliably.     

Electroacupuncture at Hoku elicits dual effect on autonomic nervous system in anesthetized rats

To address the effect of electroacupuncture (Ea) on the autonomic nerve activity, responses of arteriole blood pressure (BP), intragastric pressure (IGP) and parasympathetic vagal nerve activity (VNA) to Ea were investigated in alpha-chloralose anesthetized rats. The acupoint: Hoku (Li-4) was tested with two different stimulation frequencies (2 and 20 Hz). Decrease in VNA and basal IGP associated with elevation of BP were elicited during Ea at Hoku with stimulation intensity of 20 times of motor threshold. The pattern of response induced by the low frequency Ea (LFEa) was different from that by the high frequency Ea (HFEa), i.e. a tonic effect was elicited by the LFEa, while a phasic one was induced by the HFEa. All the results in this study implicated that: (1) Ea at Hoku may activate the sympathetic and simultaneously inhibit the gastric parasympathetic nerve; (2) Ea at Hoku with different stimulation frequencies may elicit distinct mechanism to induce therapeutic effect; (3) Ea at Hoku may ameliorate the hyperactive stomach in clinical therapy.     

Vascular complications in percutaneous transhepatic management of complicated hepatolithiasis with difficult intrahepatic biliary strictures: are they avoidable?

Little has been reported about hemobilia in the management of complicated residual or recurrent hepatolithiasis with intrahepatic biliary strictures by percutaneous stricture dilation and percutaneous transhepatic cholangioscopic lithotomy. To analyze retrospectively the incidence, possible factors, and management of hemobilia in such patients, a consecutive series of 177 patients was studied from 1983 to 2001: 90 patients in the early, 7.5-year period and 87 patients in the later period, in which some procedures were modified. Minor hemobilia occurred during percutaneous puncture in 6 patients: 4 (4.4%) in the early period and 2 (2.3%) in the later period. Massive hemobilia developed in 14 patients (15.5%) in only the early period, during stricture dilation, lithotripsy, or lithotomy. Immediate arteriography revealed arterial bleeding (7), extravasation (3), pseudoaneurysm (3), or an undetermined source (1). Transcatheter arterial intervention enabled successful hemostasis. Massive hemobilia is a potential serious complication of percutaneous stricture dilation and percutaneous transhepatic cholangioscopic lithotomy but is avoidable.     

Resection of peritoneal implantation from hepatocellular carcinoma

Background Peritoneal implantation is a rare presentation of hepatocellular carcinoma (HCC). This article presents the clinical features and surgical outcomes of 16 patients with HCC in whom isolated peritoneal implantation from HCC was found and who underwent surgical resection. Methods From 1988 to 2000, 16 patients with HCC after hepatic resection who underwent resection of peritoneal implantation of HCC were retrospectively reviewed. Results Four hundred sixty-five of 749 patients (62.1%) had recurrence of HCC after heptic resection. Sixteen (3.4%) developed isolated peritoneal implantation and underwent resection. During the detection of the peritoneal implantation, the alfa fetoprotein level was increased in 13 of these 16 patients. Five of 15 patients had a peritoneal mass discovered by ultrasonography, and 14 of 15 patients had a mass discovered by computed tomography. The follow-up period ranged from 2.1 to 81.6 months (median, 16 months). The median disease-free and overall survivals of the 16 patients were 7.89 and 15.98 months, respectively. Conclusions Peritoneal implantation occurs infrequently in posthepatectomy patients. Increased alfa fetoprotein values after hepatic resection should suggest recurrence of HCC. Computed tomography is superior to ultrasonography in detection of peritoneal implantation from HCC. Surgical resection of peritoneal implantation from HCC might prolong survival in selected patients.     

Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species

Hydroxychavicol (HC; 10 - 50 microM), a betel leaf component, was found to suppress the 2% H(2)O(2)-induced lucigenin chemiluminescence for 53 - 75%. HC (0.02 - 2 microM) was also able to trap superoxide radicals generated by a xanthine/xanthine oxidase system with 38 - 94% of inhibition. Hydroxyl radicals-induced PUC18 plasmid DNA breaks was prevented by HC (1.6 - 16 microM). A 24-h exposure of KB cells to HC (0.5, 1 mM) resulted in 54 - 74% cell death as analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. HC (10, 50 microM) further suppressed the growth of KB cells (15 and 76%, respectively). Long-term colony formation of KB cells was inhibited by 51% with 10 microM HC. Pretreatment of KB cells with 100 microM HC inhibited the attachment of KB cells to type I collagen and fibronectin by 59 and 29%, respectively. Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5 mM led to apoptosis as revealed by detection of sub-G(0)/G(1) peaks with a concomitant decrease in the number of cells residing in late S and G(2)/M phase. Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in reduced form of GSH (>0.2 mM) and the increasing of reactive oxygen species production (>0.1 mM) as analysed by CMF- and DCF-single cell fluorescence flow cytometry. These results indicate that HC exerts antioxidant property at low concentration. HC also inhibits the growth, adhesion and cell cycle progression of KB cells, whereas its induction of KB cell apoptosis (HC>0.1 mM) was accompanied by cellular redox changes.