Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development

The roles of IgE and mast cells on expulsion of adult Hymenolepis nana from the intestine were examined in mice. IgE-dependency was determined by comparing congenitally IgE-deficient SJA/9 and IgE-producing SJL/J mice infected with 50 H. nana eggs. Anti-H. nana IgE antibody was detected at three weeks post infection (p.i.) in SJL but not in SJA mice. The number of adult worms in the intestines of SJA and of SJL mice were similar at two weeks, but significantly more were found in SJA mice at three weeks p.i. Treatment of mice with anti-ɛ antibody also resulted in an increased worm burden at three weeks, suggesting participation of IgE in expulsion of H. nana. Intestinal mastocytosis was induced by infection regardless of the IgE status of the mice. Mast cell-dependency was tested in mast cell-deficient W/W^u and in normal littermate +/+ mice infected with 100 H. nana eggs. Anti-H. nana antibody was detected in both groups of mice at three weeks p.i. Worm expulsion seemed to be mast cell dependent because expulsion was less complete in W/W^u mice at three weeks p.i. Peripheral blood eosinophilia was comparable at three weeks p.i. in both IgE and mast cell sufficient and deficient mice. These results suggest that IgE and mast cells participate in the expulsion of H. nana adults from intestine in mice.     

Prostaglandin E1‐effective,transient‐type ischemic colitis developed after surgical resection of sigmoid colon cancer. A case report

A 55‐year‐old‐man had a laparoscopic resection of the sigmoid colon due to colon cancer with submucosal invasion. After the surgery he suffered ileus and had a laparotomy. Six months later he complained of frequent defecation. Colonoscopy confirmed a circular ulcer extending from the anal side of the anastomosis in the sigmoid colon to the mid rectum. Endoscopic ultrasound demonstrated thickening of all layers of the diseased colon and rectum. We diagnosed ischemic colitis. After intravenous drip infusion of prostaglandin, symptoms and colonic stricture gradually improved. Although abdominal angiography revealed a narrowing of the peripheral sigmoid branch of the inferior mesenteric artery, blood flow was unrestricted. Colonoscopy performed 84 days after discharge revealed an ulcer scar.     

Colonoscopic classification of internal hemorrhoids: Usefulness in endoscopic band ligation

Background:  Bleeding is one of the main symptoms of internal hemorrhoids. However, the conventional Goligher's classification of internal hemorrhoids does not consider the severity of bleeding. We intended to establish a useful method for evaluating internal hemorrhoids using a colonoscope that reflected the severity of the symptoms.
Methods:  Using a colonoscope in the retroflexed and forward viewing position, 104 patients with symptomatic internal hemorrhoids were evaluated based on the criteria of range, form and red color signs (RCS). Range was determined by the circumferential distribution of internal hemorrhoids and scaled from 0 to 4. Form was determined by size and scaled from 0 to 2. The presence of RCS was also evaluated. Symptoms were determined by interview and scaled from 0 to 3. Patients were treated by endoscopic band ligation (EBL) and were examined endoscopically before and 4 weeks after the treatment.
Results:  Before the treatment, range, form and RCS were significantly correlated to bleeding ( P <  0.01), and form was significantly correlated to prolapse ( P <  0.05). The endoscopic classification scores at 4 weeks after EBL improved significantly (range from 3.25 ± 0.05–0.56 ± 0.08 [ P <  0.01] and form from 2.81 ± 0.04–0.56 ± 0.07 P <  0.01).
Conclusion:  The new endoscopic classification of internal hemorrhoids proved to be closely correlated to symptoms, particularly bleeding, and thus highly useful in evaluating the effectiveness of the treatment.     

Relationship between cellular ATP content and cellular functions of primary cultured rat hepatocytes in hypoxia

The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo , perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long-term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 × 10⁴ and 5 × 10⁴ cells/0.18 mL per cm² for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long-term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis.     

Biopharmaceutics: Effect of Ointment Bases on Topical and Transdermal Delivery of Salicylic Acid in Rats: Evaluation by Skin Microdialysis

Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 μmol salicylic acid were applied for 2 h to the surface of rat skin (1 cm²) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase. white petrolatum, poloid, hydrophilic poloid. absorptive ointment. The ratio of AUC_skin (topical delivery) to the AUC of salicylic acid in plasma (AUC_plasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUC_skin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUC_skin/AUC_plasma for the different ointments was comparable, although the magnitudes of AUC_skin and AUC_plasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the retention of salicylic acid in the stratum corneum; and the stratum corneum functions strongly as a penetration barrier for solbase, moderately for poloid and hydrophilic poloid, and less for absorptive ointment and white petrolatum.     

Specific immunotherapy with tumour-draining lymph node cells cultured with both anti-CD3 and anti-CD28 monoclonal antibodies

For providing costimulatory signals, we utilized anti-CD28 monoclonal antibody (mAb) for the in vitro culture of tumour-draining lymph node (LN) cells. The proliferation of B16 melanoma-draining LN cells in the culture with anti-CD3 mAb was remarkably enhanced by the addition of anti-CD28 mAb. In culture with both anti-CD3 and anti-CD28 mAb, the B16-draining LN cells produced a higher level of interferon-γ, but not interleukin-4, than with anti-CD3 mAb alone. The B16-draining LN cells efficiently expanded in the culture with both anti-CD3 and anti-CD28 mAb and subsequently with a low dose of IL-2 (anti-CD3 plus anti-CD28/IL-2). The expanded cells consisted predominantly of CD8⁺ T cells and showed a specific cytolytic activity, in a major histocompatibility complex (MHC) class I-restricted manner, even without in vitro restimulation. In addition, the adoptive transfer of the B16-draining LN cells, expanded in the culture protocol of anti-CD3 plus anti-CD28/IL-2, showed a significant anti-tumour effect against metastatic B16 melanoma in combination with IL-2. The cured mice thus acquired a specific protective immunity. Moreover, this protocol was also moderately effective against poorly immunogenic 3LL carcinoma. Overall, our results suggest the potential for another immunotherapeutic strategy based on ‘the costimulatory theory’ other than vaccination with B7-transfected tumour cells.     

Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient’s condition.     

Differences in the Mode of Lethality Produced through Intravenous and Oral Administration of Organophosphorus Insecticides in Rats

Differences in the Mode of Lethality Produced through Intravenousand Oral Administration of Organophosphorus Insecticides inRats. TAKAHASHI, H., KOJIMA, T., IKEDA, T., TSUDA, S. and SHIRASU,Y. (1991). Fundam. Appl. Toxicol. 16, 459–468. This studywas undertaken to investigate the possibility that mechanismsother than cholinesterase (ChE) inhibition account for the acutetoxicity of organophosphorus insecticide. Both the PO type insecticide(direct ChE inhibitors: chlorfenvinphos and dichlorvos) andthe PS type insecticide (indirect ChE inhibitors: diazinon andfenthion) were employed. Rats treated with lethal doses of intravenousand oral PO type insecticides and oral PS type insecticidesexhibited typical signs of anti-ChE poisoning along with markedinhibition of brain and erythrocyte ChE activity. In contrast,rats given lethal doses of intravenous PS type insecticidesexhibited tonic convulsions and opisthotonos, with only slightinhibition of ChE activities. When PO type insecticides wereintravenously administered to anesthetized and conscious rats,animals exhibited typical anti-ChE poisoning signs in cardiorespiration:hypertension and apnea which were antagonized by atropine. Afteradministration of lethal doses of PO type insecticides, breathingdisappeared before the cessation of heart beats. Rats receivinglethal doses of intravenous PS type insecticides did not showhypertension, but exhibited transient cessation of breathingand heart beats. Breathing was observed after the disappearanceof heart beats. The electroencephalogram (EEG) was characterizedby spike and wave complexes. The EEG and cardiorespiratory changeswere not antagonized by atropine. It was concluded that lethalityfollowing intravenous PS type insecticides may be independentof ChE inhibition.     

The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis

The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosinophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.