Weak effects of local and systemic administration of the GABA uptake inhibitor,SK&F 89976, on extracellular GABA in the rat striatum

Summary The effects of local and systemic administration of the potent GABA uptake inhibitor, SK&F 89976, on GABA overflow from the striatum of conscious rats were investigated in brain dialysis experiments. Administration of the compound via the dialysis probe at concentrations of 25 or 100 gmol/l significantly increased basal GABA overflow about 2-fold. Overflow evoked by 104 mmol/l K⁺ remained unaltered at the lower and was almost doubled at the higher concentration; this increase did, however, not reach statistical significance.Given systemically at 50 mg/kg i.p., a dose which is severalfold higher than those which exhibit anticonvulsant effects, SK&F 89976 caused a significant enhancement of K⁺-stimulated GABA overflow by about a factor of 2; the lower dose of 20 mg/kg i.p. was not effective. Basal GABA overflow was not significantly increased by either dose. These results suggest that the marked effects of nipecotic acid on basal GABA overflow reported by several authors seem to be related to GABA displacement rather than uptake inhibition, and that uptake inhibition does not improve the interpretability of measurements of GABA release by brain dialysis. They neither support the idea that the relative insensitivity of extracellular GABA to low Ca²⁺ and tetrodotoxin is indirectly due to very efficient removal of GABA by neuronal and/or glial uptake, leaving only residual amounts to be measured. Send offprint requests to P. Waldmeier at the above address     

Toxicodynamics of tumour promoters of mouse skin

Summary In binding competition assays using a protein kinase C preparation from mouse brain (particulate fraction)³H-labelled 12-O-tetradecanoylphorbol-13-acetate (TPA), for a series of new diterpene esters (DTE) the relative binding affinity [rba=K _i ^a (TPA)/K _i ^a (DTE)] in relation to TPA was determined. A wide range of values was noticed, some of the DTE binding more strongly than TPA (rba >1), others binding less strongly than TPA (rba <1) In comparative terms, competition for specific binding sites appears to correlate better with irritant than with promoting acitvity of the DTE. Using mouse peritoneal neutrophils, binding of [³H]-TPA was determined by a modification of the cold-acetone filter assay; saturation of high-affinity sites (K _d ^a =0.2 nM) was obtained at concentrations 1 nM, but there was also evidence for specific binding at low-affinity sites (K _d ^a =26 nM). Induction of chemoluminescence in the presence of luminol in mouse peritoneal neutrophils with a set of DTE usually elecited two peaks; at concentrations 10 nM DTE a short-lived, spike-like response lasting only from 0 to about 5 min (phase A) ist followed by a plateau response from about 5–120 min (phase B). This latter phase of chemoluminescence stimulation with luminol correlated well with theirritant potential of the DTE used. The sequence of the two phases can be inverted partially by using first TPA at 2,5 nM followed by a quick concentration increase to 100 nM; this indicates two different concentration-dependent events. As regards the intensity of the chemoluminescent response, quantitative but not qualitative differences between DTE were observed, which show some correlation with strong and weak tumour-promoting activity. Inhibition studies suggest the involvement of the myeloperoxidase/H₂O₂/Cl^– system in the luminogenic response; it is suggested that the release of hypochlorite or a closely related oxidant may be instrumental in tumour promotion.Abbreviations DMSO dimethylsulphoxide - DTE diterpene ester - K10 Gnidia factor K10 (Kraussianin) - K _i ^a ,K _d ^a apparent inhibition and dissociation constants - muPMN mouse peritoneal neutrophils - P2 Pimelea factor P2 - PDD phorbol-12,13-didecanoate - RPA 12-O-retinoylphorbol-13-acetate - rba relative binding affinity - TPA 12-O-tetradecanoylphorbol-13-acetate - 3-TI 3-O-tetradecanoylingenol See loc. cit. Kloz et al. 1989 for I. Comm. of this series     

阿莫西林对格列美脲血浆蛋白结合率的影响

目的 研究阿莫西林对格列美脲蛋白结合率的影响。方法 采用平衡透析法结合高效液相色谱法，比较未加和加入阿莫西林后格列美脲的血浆蛋白结合率。结果 4种浓度下，单用格列美脲时的血浆蛋白结合率分别为94.2％、92.8％、91．4％、91．0％；与阿莫西林合用时，格列美脲的血浆蛋白结合率依次变为90．9％、89．0％、89．6％、90．0％。结论 与阿莫西林合用后，格列美脲的血浆蛋白结合率下降。     

子宫下段剖宫产不缝合腹膜168例临床分析

目的：探讨子宫下段剖宫产术不缝合腹膜对手术后效果影响。方法：对2000年7月～2001年7月在我院行改良式腹壁横切口子宫下段剖宫产168例，分成缝合腹膜组与不缝合腹膜组，在手术时间、术后镇痛药使用、肛门排气时间、术后发热、术后切口愈合方面进行观察和总结。结果：不缝合腹膜组在手术后发热，腹壁切口延期愈合方面与缝合腹膜组差异无显著性，在手术时间、术后肛门排气时间、术后镇痛药使用上比缝合腹膜组少。结论：施行子宫下段剖宫产，不缝合腹膜具有手术时间短、术后排气早、疼痛轻等优点，不会增加腹腔脏器粘连。     

Intravenous glycerol therapy should not be used in patients with unrecognized fructose-1,6-bisphosphatase deficiency

BACKGROUND: In Asian countries, glycerol solution that contains fructose (5%) is often used for management of brain edema. However, glycerol and fructose may cause severe hypoglycemia and metabolic acidosis in patients with fructose-1,6-bisphosphatase (FBPase) deficiency, even under stable conditions. The aim of the present study was to determine whether glycerol solution was used for brain edema during acute metabolic decompensation of hypoglycemia and metabolic acidosis in patients with unrecognized FBPase deficiency in Japan and to examine a long-term prognosis of the patients who had this kind of severe metabolic decompensation with or without glycerol therapy. METHODS: A retrospective study of 20 children with FBPase deficiency was conducted, based on their medical records. RESULTS: Six of the 20 children were given glycerol solution for the presence or possibility of brain edema during acute metabolic decompensation of hypoglycemia and metabolic acidosis; two of the six patients administered with glycerol were given dialysis. In four patients treated with glycerol alone without dialysis, two had no brain edema before glycerol administration but it developed later after the administration. These four patients treated with glycerol alone died or developed severe neurological complications. Fourteen patients who were not treated with glycerol solution had no brain edema and showed good prognosis. CONCLUSIONS: Glycerol solution, which contains fructose in Asian countries including Japan, should not be used as an osmotic agent for treatment of brain edema in patients who have hypoglycemia and retention-type metabolic acidosis, until FBPase deficiency is ruled out by measuring blood concentration of lactate.     

Hemodialysis in elderly patients

International Urology and Nephrology -     

Natural changes in peritoneal equilibration test results in continuous ambulatory peritoneal dialysis patients: a retrospective, seven year cohort survey

We conducted a retrospective, 7 year cohort survey to examine the natural changes in peritoneal equilibration test (PET) results in patients with long-term uneventful continuous ambulatory peritoneal dialysis (CAPD). Thirty-two (17 males, 15 females) patients on CAPD with two or more standard PETs performed more than 6 months apart, in the absence of peritoneal insult, were included. Changes and pattern of PET results were evaluated by the dialysate to plasma ratio of creatinine (D:P-cre), the fourth h dialysate to instilled glucose ratio (D4:Do) and ultrafiltration volume (UF, ml). The subgroups included high (H), high-average (HA), low-average (LA), or low (L) transporters with the dividing ratios (D:P-cre) of >0.81, >0. 65 to 0.81, >0.5 to 0.65, and <0.5, respectively. The median D:P-cre significantly decreased (p = 0.04), but neither the D4:Do nor the final median UF significantly decreased. The change in D:P-cre was strongly and inversely correlated with the initial D:P-cre value (r = -0.68; p < 0.05). A similar relationship was found between the change in the final D4:Do and the initial D4:Do (r = -0.752; p < 0. 01) and between the change in the final UF and the initial UF (r = -0.875; p < 0.01). No correlation was found between the change in D:P-cre and the age of the patient, the time interval between PETs, monthly dialysate glucose exposure, or underlying diabetes/non-diabetes. The final peritoneal transport pattern was altered with 5 (15.6%) patients remaining in the extreme subgroups (H or L) and, by contrast, 84.4% (27/32) of the patients now in the averaged (HA or LA) groups (p < 0.01, chi2 test). We demonstrated a natural "centralization" migration of PET results after long-term uneventful CAPD, which may help to explain why patients with extreme PET characteristics, that is, H or L, continued to do well on CAPD.     

腹腔灌注联合射频透热治疗28例晚期卵巢癌

[目的]探讨晚期卵巢癌腹腔转移的治疗方法。[方法]以顺铂 卡铂 依托泊甙为主的联合方案行腹腔持续热灌注化疗并腹腔射频透热治疗28例晚期卵巢上皮癌，观察其疗效及毒副反应。[结果]完全缓解(CR)5例，部分缓解(PR)16例，稳定（NC）5例，进展（PD）2例，总有效率75.0%。主要毒副反应为骨髓抑制。[结论]双铂联合依托泊甙腹腔热灌注并射频透热治疗对中晚期卵巢癌疗效较好，毒副反应少。     

Prognostic factors for patients with advanced stage serous borderline tumours of the ovary.

BACKGROUND: The aim of this study was to determine the prognostic factors for patients with advanced stage, low malignant potential ovarian tumour (LMPOT). PATIENTS AND METHODS: A retrospective review of 80 patients with serous LMPOT and peritoneal implants treated at or referred to our institution was carried out. RESULTS: Sixty-five patients had non-invasive implants. Fifteen patients had invasive implants. Twenty-nine patients had stage II and 51 patients had stage III disease. Three patients died of evolutive invasive disease and four of complications of treatment. The only prognostic factor of progression to 'evolutive invasive disease' is the pathologic subtype of peritoneal implants. The 5-year rates of evolutive invasive disease in patients with non-invasive implants and invasive implants were 2% and 31%, respectively (P <0.002). CONCLUSIONS: In this series, the only prognostic factor for patients with advanced stage borderline tumour is the type of peritoneal implant. More patients died of the treatment's complications than of the disease itself. The patients' prognosis with non-invasive implants seems to be excellent, and conservative management could be discussed in younger patients.     

腹腔巨噬细胞产生一氧化氮对腹膜透析失超滤的作用

目的 研究腹腔巨噬细胞产生的一氧化氮（ＮＯ）对腹膜淋巴孔的作用,探讨腹膜淋巴孔的淋巴重吸收对长期腹膜透析失超滤的影响。方法 应用腹透液建立腹宁的小鼠模型,用全自动酶标仪动态测定怛,用扫描电镜观察不同时间点腹膜间皮超微病理变化,使用计算机与扫描电镜联机的图象处理系统,测定不同腹膜透析时间点腹膜淋巴孔的变化。结果 腹腹膜管析时程延长,透析组有大量巨噬细胞从腹膜淋巴孔游出,在腹膜表面形成许多乳斑。巨噬细