Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.

OBJECTIVE: NKH477 was recently identified as a water-soluble forskolin derivative and was reported to prolong survival of murine cardiac allografts. However, the mechanism of the efficacy is not clear in vivo. The aim of this study was to investigate the immunosuppressive effects of NKH477 on acute lung allograft rejection in the rat model and its mechanism of action in vivo. METHODS: Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. Grafts were excised on Day 3 or Day 5 to determine histopathological rejection and expressions of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma by enzyme-linked immunosorbent assay. The cytokine expression at Day 3 or Day 5 was also evaluated in recipient spleens by immunohistochemistry. Furthermore, mesenteric lymph node cells from recipients at Day 5 were cultured alone or stimulated with donor antigens for 72 hours to determine cell proliferation by means of thymidine incorporation. RESULTS: NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Expression of IL-2 and IL-10 also increased in the spleen of untreated allorecipients. NKH477 suppressed expression of both cytokines in the spleen. In addition, lymphocyte proliferation was inhibited in NKH477-treated recipients as compared with untreated recipients. CONCLUSION: These results suggest that NKH477 exerts an antiproliferative effect on lymphocytes in vivo with an altered cytokine profile in rat recipients of lung allografts.     

Surgical treatment of pseudoaneurysm of the sinus of valsalva after aortic valve replacement for active infective endocarditis.

Pseudoaneurysm is an uncommon and serious complication of infective endocarditis (IE). It is often fatal because of its rapid progress, high rates of rupture and recurrence, and worsening effects on the systemic condition. We report the rare case of a patient who developed a pseudoaneurysm of the sinus of Valsalva two months after emergency aortic valve replacement for active IE. At the previous operation, we had directly closed a small fistulous hole in the non-coronary sinus of Valsalva using two mattress sutures with autologous pericardial pledgets, because the tissue surrounding the hole did not appear to be infected on visual inspection. A pseudoaneurysm developed from this portion due to detachment of sutures. If the fistula had been completely resected during the first surgery instead of performing a simple closure, the pseudoaneurysm of the sinus of Valsalva would not have formed. However, the primary aim of the first emergency surgery was to spare the life of a critically ill patient. In the second surgery, the pseudoaneurysm was completely resected with the aortic wall--including the non-coronary sinus of Valsalva and the communicating hole. Then, patch plasty of the non-Valsalva sinus was successfully performed.     

DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.

We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism.     

Oxygen Hyperbaric Pressure Therapy (OHPT) for Decubitus Ulcers

Aim:  This study aims to establish a pressure ulcers model that visualizes the microcirculation, and to examine the participation of ischemia‐reperfusion injury in the pathophysiology of pressure ulcers.
Methods:  An original system composed of a new skinfold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia‐reperfusion injury, animals were divided into two groups: the compression‐release group in which the animals received four cycles of compression‐release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day1 (35 hours) after the first evaluation.
Results and Conclusions:  The cyclic compression‐release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia‐reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. The finding supports the significant contribution of ischemia‐reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Multiple osteonecrosis associated with allergic dermatitis

Summary A case of multiple osteonecrosis including both shoulders, hips, and knee joints and the right fourth metatarsophalangeal joint is reported.     

Increased accumulation of iodine-123-IMP in the pulmonary inflammatory lesion surrounding a lung cancer

In a patient with primary lung cancer, increased accumulation of I-123-IMP was observed in a pulmonary inflammatory lesion surrounding a lung cancer which was delineated as a photon deficient area. Ga-67-citrate uptake was observed in both the inflammatory and cancerous areas. These findings suggest that I-123-IMP may have the potential to accumulate differently in a variety of pathological conditions of the lung and thus may be a clinically useful lung imaging agent.     

Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system

Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct (type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the duodenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma.     

High Cell-Density Culture System of Hepatocytes Entrapped in a Three-Dimensional Hollow Fiber Module with Collagen Gel

Abstract: A compact three-dimensional (3D) module is needed for hepatocyte culture in order to develop an effective hybrid artificial liver system that can retain hepa-tocellular structure and differentiated functions. We treated the 3D module with collagen gel to entrap rat hepatocytes. This method yielded a high hepatocellular density (2 times 10⁷ cells/ml) over a period of 14 days and maintained the secretion of albumin and ureogenesis at the same level as the control monolayer method. The ammonia removal remained at 43% of the Day 0 value over 8 days of perfusion. Our data show that this approach may be useful for liver support therapy in an ex-tracorporeal circuit.     

Epidemiologic study on factors related to physical locomotion ability among the aged]

The present study was conducted in order to examine epidemiologic factors related to physical locomotion ability among the aged in an area with long life expectancy, a village in Okinawa Prefecture. Medical examinations and interviews were performed for 756 inhabitants aged 65 years and older, who were classified into 2 groups of physical locomotion ability, a high group and a low group. According to the results after multiple logistic regression analysis, the following factors showed positive relation to physical locomotion ability: age, working status, food intake frequencies (fish, eggs and green vegetables), skinfold thickness, grip strength and serum albumin. However, no statistical associations were observed between physical locomotion ability and other factors such as sex, smoking status, alcohol intake, hypertension, Quetelet's index, serum total cholesterol or and hemoglobin.     

Abnormalities in visceral evoked potentials from the anal canal in children with chronic constipation

The integrity of the sensory nervous system in the anal canals of chronically constipated children was investigated using evoked potential techniques examining cerebral and spinal evoked potentials from the lower extremities and anal canal. Stimulation of the posterior tibial nerve produced no significant difference in the parameters of spinal and cerebral evoked potentials between 18 controls and 12 chronically constipated chidren. However, stimulation of the anal canal resulted in evoked potentials related to the age and/or consciousness level of the control children. Reproducible cerebral responses were obtained only from nine of these control children, all aged over 4 years, who were examined while awake without sedatives. A typical response was characterized by a polyphasic wave occurring with an onset latency of 79.4± 27.7ms (mean ±SD). In the 12 chronically constipated children, the 5 sedated patients examined while asleep did not show any reproducible potential, as in the controls. However, in the remaining 7 children examined while awake, the occurrence of the anal canal evoked potential was significantly reduced, and only two exhibited a cerebral response. These findings suggest that rectal mucosal perception of the intraluminal stimuli might be disturbed in some children with chronic constipation.