Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD). The subjects were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic studies showed that VH(-) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt-table testing was greater in VH(+) than VH(-). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.     

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.     

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.     

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.     

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.     

Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver.

Organic anion transporter 2 (Oat2 [SLC22A7]) is a multispecific organic anion transporter. Although several substrates of human Oat2 (hOat2) have been elucidated, a possible involvement of hOat2 in drug interaction is less defined. The purpose of this study was to investigate the interaction of theophylline with erythromycin mediated by hOat2 using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, hOat2 mediated the transport of theophylline and erythromycin. The finding indicates that the two compounds are novel substrates for hOat2. The apparent K(m) values for the uptake of hOat2 that mediated the transport of theophylline and erythromycin were 12.6 muM and 18.5 muM, respectively. The hOat2-mediated uptake of [(14)C]theophylline and [(14)C]erythromycin was cis-inhibited by adding erythromycin and theophylline, respectively. Our present findings suggest that hOat2 may, at least in part, be involved in the theophylline-erythromycin interaction in the human liver.