Changes in glutathione-redox balance induced by hexachlorocyclohexane and lindane in CHO-K1 cells

1. The basal cytotoxic effect of the organochlorine pesticides hexachlorocyclohexane and lindane on CHO-K1 cultures was assessed at fractions of their lethal doses as determined by the neutral red incorporation (NRI) assay (NRI(6.25), NRI(12.5) and NRI(25)). The sulphur-redox cycle enzymes glutathione peroxidase, glutathione reductase and glutathione S-transferase, and total and oxidized glutathione were evaluated at several points during the standard growth curve of the cultures. 2. After incubation with each compound for 24 h, both glutathione peroxidase and reductase showed a substantial increase at the lowest exposure doses (NRI(6.25))--more significantly for lindane than for 1,2,3,4,5,6-hexachlorocyclohexane (HCH)--and dropped at higher doses of both compounds. The reduced and oxidized glutathione content was greatly diminished at the lower exposures, whereas the total glutathione content was higher at NRI(12.5) values. 3. Changes in cell membrane integrity were assessed for a wide range of pesticide concentrations with the lactate dehydrogenase release assay and lipid peroxidation. Membrane leakage and peroxide production were significantly enhanced at concentrations of HCH 50 microg ml(-1), although this effect was not significant at lindane concentrations < 200 microg ml(-1). 4. Lipid peroxidation increased with exposure to HCH at concentrations as low as NRI(6.25), whereas in the case of lindane, this increase was only significant at doses of NRI(25) and above.     

Phenylpropanolamine-induced intraventricular hemorrhage

Intracranial hemorrhage is an uncommon complication of phenylpropanolamine. There is an increasing awareness of this complication in the West. However, to the best of our knowledge there have been no cases reported from India. Here we report a patient who developed Intraventricular hemorrhage following ingestion of Phenylpropanolamine, from which he made an uneventul recovery over the next two weeks.     

Use of 201Tl SPECT Imaging to Assess the Response to Therapy in Patients with High Grade Gliomas

Purpose. To assess the potential role of ²⁰¹Tl single photon emission tomography (201-Thallium SPECT) when compared to other imaging modalities in the evaluation of the response to therapy in high grade gliomas. Materials and methods. Twenty patients with histologically proved high grade glioma have been included: 15 with glioblastoma (GBM), 3 with anaplastic astrocytoma (AA) and 2 with anaplastic oligoastrocytoma (AOA). Patients were assessed by ²⁰¹Tl SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) at (a) either at the moment of maximum response to first line chemotherapy, or after the completion of radiotherapy and chemotherapy if post-surgical residual disease was present, and (b) after the completion of second line chemotherapy if disease persisted, or either a relapse or disease progression was confirmed. Final response was evaluated according to the McDonald criteria, and by comparing SPECT, CT and MRI results. Results. According to the McDonald criteria, clinical response after first line chemotherapy was 5 partial response, 7 stable disease and 8 progressive disease. Evaluation by ²⁰¹Tl SPECT was in agreement with such criteria in nearly all patients (90%). MRI findings closely agreed with the clinical follow-up. CT findings clearly differed from those observed by SPECT and MRI. After second line therapy, 10 patients progressed, 3 had stable disease and 7 had partial response. ²⁰¹Tl SPECT agreed with the clinical status in 89% cases, whereas MRI and, specially CT, fared significantly lower. Conclusion. Compared to conventional neuroimaging, ²⁰¹Tl SPECT added valuable information in the assessment of the response to therapy in our patient population; whenever findings were not conclusive and in the case of disagreement between CT and MRI findings.     

在治疗克罗恩病相关性黏膜溃疡中应用英夫利昔单抗定期维持治疗优于间断治疗

背景：ACCENT Ⅰ（一项有关评估一种新的长期应用英夫利昔单抗治疗克罗恩病的临床试验）之后的内镜下研究。试验评估了英大利昔单抗对黏膜炎症与黏膜愈合的疗效及其对预后的影响。设计与机构：ACCENT Ⅰ是一项在北美、欧洲和爱尔兰进行的多中心、随机、双盲对照试验。主要检测指标：在开始及第10周和第54周进行回肠结肠镜检查。黏膜完全愈合定义为所有黏膜溃疡消失。主要观察终点是有改善的患在第10周的黏膜愈合率。同时计算第54周发现黏膜愈合率和在第10周和第54周都愈合的比率。在此次试验中，还要计算所有患从开始到第10周和第54周的内镜下克罗恩病严重指数的改变值（CDEIS）。结果：第10周黏膜痊愈比第2周明显增多，即服用3倍剂量的与单倍剂量的患比较（31％ vs 0；P=0．010）。2周好转合并计划性维持治疗组在第54周的治愈率明显高于间断治疗组（50％vs 7％；P=0．007）。     

MR spectrum in spinal dysraphism

Spinal dysraphism is a general term which encompasses a wide variety of anomalies of the spine, all of which result from imperfect midline fusion of the embryonic neural tube. This term refers to large defects that involve the spine and not to small vertical clefts commonly seen within the spinal process of L5 or S1. We present a spectrum of MR imaging findings selected from a retrospective review of 100 patients of spinal dysraphism evaluated at our institution. Received: 18 May 2000 Revised: 13 July 2000 Accepted: 13 July 2000     

Isolation of exfoliated colonic epithelial cells, a novel, non-invasive approach to the study of cellular markers.

Human stool is a heterogeneous mixture of non-digestible food residues, bacteria, cells exfoliated from the gastrointestinal mucosa and other secretory products. We have demonstrated that fresh human stools dispersed in a buffered saline solution can be fractionated over Percoll/BSA gradients to yield 9 discrete bands of cells in the density range of rho 1.033 to 1.139 and which could be further purified over Histopaque 1077. Enzyme-linked immunoassays (ELISA) for colon-specific antigen (CSA) and cytokeratins (CK) were positive. Western blot analysis showed the presence of 3 cytokeratin bands in the 40-kDa to 60-kDa range suggestive of cytokeratins 8, 18, and 19. Fluorescence flow-cytometric analysis of these cells using antibodies against CSA, CK, the blood-group antigens, carcinoembryonic antigen (CEA), non-mucus-secreting columnar-epithelium-specific MAb PR1A3, and to mucus-secreting colonic-epithelium-specific MAb PR5D5 showed varying degrees of reactivity. Expression of the blood-group phenotype suggests that cells from the proximal half of the colon had survived the transit, since in the adult expression of this marker is limited to cells from the proximal region of the colon. In this report we demonstrate the feasibility of studying, non-invasively, cell-specific markers on exfoliated cells isolated from stools. The evidence strongly suggests that almost all the cells are of colonic origin.     

Isolation and partial characterization of a phospholipase A2 from the venom of Crotalus scutulatus salvini

A phospholipase A₂ (EC 3.1.1.4) has been isolated and purified from the venom of Crotalus scutulatus salvini in 33% yield. The enzyme was homogeneous on polyacrylamide gel electrophoresis. The molecular weight of the enzyme was in the same range (30,000) whether determined by gel filtration or ultracentrifugation. On polyacrylamide gel electrophoresis, in the presence of sodium dodecyl sulphate and β-mercaptoethanol, the enzyme migrated into a single protein band with a mobility corresponding to about 14,000 molecular weight, indicating that the native enzyme was a dimer. Amino acid composition of the enzyme is reported. Two NH₂-amino acid terminals were found which indicates that the dissociable monomers of the native enzyme were non-identical. Antiserum against the purified enzyme completely inhibited the phospholipase A₂ activity and immunodiffusion of the antiserum against both purified phospholipase A₂ and crude venom of Crotalus scutulatus salvini gave single precipitin lines indicating a lack of contaminating antigens.     

Modification of gamma radiation induced response of peritoneal macrophages and splenocytes by Hippophae rhamnoides (RH-3) in mice

Alcoholic extract of Hippophae rhamnoides, RH-3, reported to render >80% survival against lethal whole body Co-60-gamma irradiation (10 Gy) in mice, was investigated for its immunostimulatory effects. In comparison with un-irradiated control, whole body irradiation did not reduce peritoneal macrophage counts at 24 h post-irradiation. RH-3 treatment (30 mg kg(-1) body weight) alone or 30 min before whole-body irradiation enhanced viable counts of macrophages significantly (P< or =0.05) compared with both un-irradiated control and irradiated groups. Whole-body irradiation reduced the number of viable splenocytes significantly (P<0.05) compared with un-irradiated control at 24 h post-irradiation. RH-3 treatment alone or before whole-body irradiation appreciably countered radiation-induced decrease in splenocyte count. 3H-thymidine uptake method revealed that whole-body irradiation reduced splenocyte proliferation significantly (159 +/- 45 counts min(-1)/10(6) cells; P< or =0.05) in comparison with control (607 +/- 142 counts min(-1)) at 24 h after irradiation but RH3 treatment before irradiation reduced the steep decrease and maintained it as 444+/-153 counts min(-1). After whole-body irradiation, the ratio of spleen weight/mouse weight decreased to 1.5 +/- 04 compared with 2.9 +/- 0.32 in un-irradiated control at 24 h post-irradiation. Similarly, total protein content in splenocytes also decreased to 48 +/- 6 microg/10(6) cells in comparison with 368 +/- 16 microg/10(6) cells of un-irradiated control. RH-3 treatment before irradiation countered radiation-induced decrease in both spleen weight/mouse weight ratio (4.0 +/- 0.35) and total protein content (360 +/- 13 mug/10(6) splenocytes). In the supernatant of peritoneal macrophage cultures exposed to 2 Gy Co-60-gamma radiation ex-vivo, the total nitrite content was enhanced significantly (P<0.05) to 5.72 +/- 0.09 microM in comparison with un-irradiated control (1.64 +/- 0.09 microM). RH-3 treatment (30 microg mL(-1)) before irradiation reduced total nitrite significantly (0.93 +/- 0.3; P< or =0.05) in comparison with irradiated control group. At 24 h after whole body irradiation, the CD4+/CD8+ ratio reduced to 1.5 in comparison with un-irradiated control (1.9) but RH-3 treatment before irradiation restored the ratio to 2.1. These findings explicitly reveal the immunostimulatory activity of RH-3, which may play an important role in the manifestation of its radioprotective efficacy.