Effects of ATP on Phosphoinositide Hydrolysis and Prostaglandin E2 Generation in Rabbit Astrocytes

Extracellular ATP secreted from stimulated nerves plays a role in neurotransmission. This study examined the effects of extracellular ATP on phospholipase A₂ and C signalling pathways in rabbit astrocytes. ATP caused prostaglandin E₂ (PGE₂) generation and phosphoinositide hydrolysis in a time- and concentration-dependent manner. A P_2y purinoceptor-selective agonist, 2-methylthio-ATP also caused phosphoinositide hydrolysis, but not PGE₂ generation. A P_2x purinoceptor-selective agonist, α,β-methylene-ATP did not cause either phosphoinositide hydrolysis or PGE₂ generation. Although pertussis toxin had no effect on 2-methylthio-ATP-induced phosphoinositide hydrolysis, it markedly decreased ATP-induced PGE₂ generation, with significant inhibition of phosphoinositide hydrolysis. Dexamethasone and indomethacin which potently inhibited ATP-induced PGE₂ generation, caused partial inhibition of phosphoinositide hydrolysis, suggesting that pertussis toxin-sensitive component of ATP-induced phospholipase C activation is mediated by cyclo-oxygenase metabolites of arachidonic acid. These results suggest that a stimulation of P_2y receptor results in phospholipase C activation in a pertussis toxin-insensitive manner, and that a P₂ receptor other than the P_2y or P_2x subtypes is involved in ATP-induced phospholipase A₂ activation via a pertussis toxin-sensitive G protein.     

What are parents of obese children concerned about in their children?

We retrospectively examined the issues that concern parents of obese children to determine the most effective means of motivating them to seek treatment for obesity in their children. Children with an obesity index > 40%, aged six to 12 years, were screened in Kagoshima City in 1992. Parents were notified if their children needed an evaluation that included a family history and measurements of the blood pressure, total cholesterol, high density lipoprotein (HDL)-cholesterol, atherogenic index (ASI), triglycerides, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Parents were informed of the results of the evaluation and invited to attend a lecture on the treatment of obesity in children. A total of 378 obese children were evaluated. However, the parents of only 39 children attended the lecture. Children whose parents attended had higher mean total levels of cholesterol (190 ± 25 vs 175 ± 28, P < 0.01) and ASI values (3.2 ± 0.9 vs 2.7 ± 0.9, P < 0.02) than those whose parents did not attend. There were no significant differences in other factors. Only 4.2% of parents whose children showed no abnormal values, except for obesity, attended the lecture, compared with 20.3% (P< 0.01) or 16.9% (P< 0.05) of parents whose children had abnormal levels of cholesterol or abnormal ASI. Parents may be more concerned about hypercholesterolemia or arteriosclerosis than obesity per se. We should perhaps use the total cholesterol or ASI values, not just the severity of obesity, to motivate parents to enter their children into treatment programs for obesity.     

Successful laparoscopic management of chylous ascites following laparoscopic radical nephrectomy

A 44-year-old woman developed chylous ascites following laparoscopic transperitoneal left radical nephrectomy with para-aortic lymph node dissection. Because conservative managements failed to stop the lymphatic leakage, laparoscopic lymphostasis was performed. Drinking milk 6 h prior to the operation enabled visualization of chylous ascites. Although a definite fistula was hard to identify, most of the chylous leak disappeared after ligation of the para-aortic tissues at the distal and proximal ends of the previous lymph node dissection. Laparoscopic ligation of the para-aortic bundle of lymph ducts was effective in managing long-standing postoperative chylous ascites.     

Acute Changes in Left Atrial and Left Ventricular Diameters After Physiological Pacing

The present study examined alterations in left atria! diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 ± 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters ware expressed per body surface area (LADI and LVDdl; mm/m). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 ± 0.9 L/min to 3.9 ± 1.0 L/min: P < 0.001). LADI decreased from 24.9 ± 4.2 mm/m² to 21.8 ± 4.4 mm/m² (P < 0.001) in 22 patients with AV block and from 24.1 ± 3.4 mm/m² to 20.4 ± 3.8 mm/m² (P < 0.001) in 15 SSS patients. However, LVDdl did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e. LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prim- to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.     

Update on Cutting Balloon Angioplasty

Cutting balloon (CB) is a unique balloon catheter with 3 or 4 metal blades on its surface making controlled endovascular surgical incisions that show promise of causing less vessel wall injury and less intimai proliferation. Multicenter randomized trials have revealed that CB angioplasty with multiple inflations achieved better lumen enlargement than single inflation and reduced coronary dissection more than plain old balloon angioplasty (POBA). Follow-up results showed CB angioplasty had a smaller late loss and loss index, resulting in lessened restenosis and target lesion revascularization rates. The main indication of CB angioplasty is basically a noncalcified lesion with concentric plaque; however, it could be applied effectively to some lesions unsuitable for POBA including in-stent restenosis, small vessel, long diffuse lesion, or ostial lesion. Additional evaluation would be necessary to determine the role of CB angioplasty in the stent era.     

Prevention of Tumor Metastasis after Surgical Removal of Primary Tumor by Using In Vitro Activated Macrophages

In vitro activation of peritoneal macrophages by Propionibacteriumacnes and its immunotherapeutic potential for inhibiting metastasiswas investigated. C3H/HeN mouse adherent peritoneal exudatecells as a source of macrophages were treated in vitro withP. acnes. These P. acnes-activated macrophages were tested fortumoricidal activity in vitro and antimetastatic activity invivo. In vitro cytotoxicity tests revealed that they had potentcytotoxicity. Surgical resection of X5563 tumors in syngeneicC3H/HeN mice 10 days after the tumor implantation failed torescue the hosts from tumor metastasis despite successful removalof the primary tumor. When the activated macrophages were transferredintravenously into C3H/HeN mice following the surgical operation,an appreciable number of mice survived without exhibiting anysign of metastasis. Thus, these results demonstrate that macrophagescan be activated in vitro by utilizing appropriate stimulatingreagents, and that these activated macrophages have a potentantimetastatic effect.