Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

Study of cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) in renal cell cancer

We studied subsets and cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) from renal cell cancer (RCC) patients. TIL were successfully expanded in 13 of 14 RCC cases using anti-CD3 during initial 48 hours of culture. Percentages of CD8 positive cells among rIL-2 expanded TIL at 1 tp 4 week(s) of culture were 56.2 +/- 15.1% (range 26.2 to 79.8%, N = 13) and not necessarily predominant over CD4 positive cells. NK and LAK activities of TIL at 3 to 6 weeks of culture were 31.6 +/- 15.8% (range 1.4 to 57.4%, N = 9) and 16.6 +/- 11.6% (range 3.8 to 35.6%, N = 6), respectively. Autologous and allogeneic RCC cytotoxicity of TIL at 3 to 4 weeks of culture were 17.9 +/- 19.7% (range 0 to 47.6%, N = 4) and 18.9 +/- 14.8% (range 0 to 47.3%, N = 12), respectively. Since there was no statistical difference between them, autologous specific cytotoxicity was not demonstrated. From these results of present study, it is unlikely that most of effector cells of rIL-2 expanded TIL in autologous RCC lysis are major histocompatibility complex restricted cytotoxic T cells. And we concluded that it is doubtful that TIL is significantly superior over LAK cells in immunotherapy of human RCC.     

A case of congenital antithrombin II deficiency with pulmonary infarction

A 48-year-old woman was admitted because of increased bloody sputum. Since she had had a history of repeated thrombotic episodes including venous thrombosis in the lower limbs (21 year old) and pulmonary emboli developing into pulmonary infarction (41 years old), the patient was treated with anti-coagulant therapy using Warfarin for 7 years. Warfarin was discontinued after admission and heparin was administered instead at a relatively low dose of 5,000 units daily, resulting in a considerable diminution of hemoptysis. Unfortunately however, it caused a relapse of active thrombosis associated not only with a significant increase of the product of fibrinolysis (FDP), LDH and GOT but with a concomitant decrease of the platelet count. Hematological examinations concerning coagulation and fibrinolysis remained within a normal range except for the serum concentration of antithrombin III (AT III) and its functional property with regard to the heparin cofactor, which were 8.8 mg/dl and 48%, respectively. Since the findings were consistent with congenital deficiency of AT III, some members of her family were also examined. The concentration of AT III and its activity in the patient's son and her daughter deteriorated in a similar manner, indicating that this was a definite case of congenital deficiency of AT III. The clinical manifestations of 87 cases with congenital AT III deficiency, belonging to 24 families reported in Japan were reviewed.     

Comparison of Tympanic, Esophageal and Blood Temperatures during Mild Hypothermic Cardiopulmonary Bypass: A Study using an Infrared Emission Detection Tympanic Thermometer

Objective. Tympanic temperature can be obtained instantaneously using an infrared emission detection (IRED) thermometer. Its accuracy has been documented in a variety of clinical settings, but its performance at low body temperatures is still unknown. In this study we evaluated its performance during coronary artery revascularization surgery in which mild hypothermic cardiopulmonary bypass (CPB) was used. Methods. Thirty adult patients undergoing coronary artery bypass graft surgery were enrolled in the study. Tympanic temperature obtained using IRED thermometry (Tt1) was compared with core temperatures from the esophagus (Te), and venous blood of CPB (Tv) before, during, and after CPB. We also measured tympanic temperature using a thermocouple probe (Tt2) in 16 of the 30 patients in order to study the agreement between the two methods. Values for correlation coefficients and limits of agreement were computed to assess the degree of agreement among the temperatures obtained. Results. The highest agreement with Tv during CPB was obtained from Tt1 (r = 0.94, 0.41 ± 1.73, limits of agreement) and from Te (0.91, 0.36 ± 2.46). Tt1 also showed good agreement with Tt2 during surgery. Conclusions. Infrared tympanic thermometry is a reliable, alternative method to measure tympanic temperature and may be useful to assess core temperature in both normothermic and mild hypothermic conditions.     

Light microscopy of GTP-binding protein (Go) immunoreactivity within the retina of different vertebrates

To examine species differences in the distribution pattern of guanosine triphosphate (GTP)-binding protein (Go) within the vertebrate retina, paraffin-embedded retinae from a number of vertebrate species, including the goldfish, frog, turtle, chicken, monkey, and human, were immunohistochemically stained with affinity-purified antibody against the alpha-subunit of Go. Go-immunoreactive products were found to be located in the neuropil, but not in the cell bodies of neurons, in the retina of all these species. However, some species differences were observed. In the frog, monkey and human, the inner plexiform layer (IPL) was homogeneously stained with this antibody, but in the goldfish, turtle and chicken, the IPL was heterogeneously stained. In the frog, chicken, turtle and human, the outer plexiform layer (OPL) was densely stained with this antibody, but in the goldfish and monkey, the OPL was rather faintly immunoreactive to the antibody. In the goldfish, monkey and human, the outer nuclear layer (ONL) was not immunoreactive to the Go-antibody, whereas in the frog, turtle and chicken, the ONL was immunoreactive to it. The implications of these species differences in Go localization in the vertebrate retina are discussed.     

Development of a new wound dressing with antimicrobial delivery capability

A bilaminar wound dressing composed of an outer membrane and an inner three-dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial-impregnated polyurethane membrane. In this study, a gentamycin sulfate-impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full-thickness and split-thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open-label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.     

Post operative upper gastrointestinal bleeding in the aged]

A 10-year experience with 2,441 patients over 65 years of age undergoing operations for non-upper gastrointestinal tracts was reviewed to evaluate both the incidence of postoperative upper gastrointestinal bleeding and the clinical risk factors associated with the complication. A total of 18 (0.7%, 7 males and 11 females) patients had overt postoperative upper gastrointestinal bleeding of non-variceal origin documented by endoscopic findings or blood transfusions. Of these, the complication developed in 10 (1.5%) of 646 patients after an operation for biliary or pancreatic disease, 1 (1.5%) of 64 for aneurysmal or obstructive arterial disease, 5 (1.1%) of 43 for colorectal cancer and 2 (0.3%) of 916 for hernia. The incidences of bleeding after an operation for obstructive jaundice (3.8%), for biliary or pancreatic malignancy (4.5%), and of unavoidable diversion colostomy for colorectal anastomosis (3.1%) were significantly higher than for non-jaundice (0.6%), for non-malignancy (1.1%) and of postoperative upper gastrointestinal bleeding in the present study. The origins of bleeding were gastric ulcer in 11, acute gastric mucosal lesion in 4, duodenal ulcer in 1 and other in 2. All cases of bleeding were treated and met success in hemostasis using H2-blockers. Of these, however, 5 patients died of multiple organ failure despite discontinued hemorrhage, prophylactic use of H2-blockers showed a decrease in occurrence of postoperative upper gastrointestinal bleeding in the present study.