Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full‐thickness cutaneous wound model in rats

Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic‐pituitary‐adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full‐thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6‐epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6‐EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = ?.630). Finally, the mechanical withdrawal threshold in the 5,6‐EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6‐EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.     

A surgical case of aortic regurgitation with Beh?et disease

A case of Beh?et disease associated with aortic valve regurgitation treated with aortic valve replacement is reported. The patient was treated successfully with special surgical techniques for prevention of post operative paravalvular leakage and occurrence of pseudo aneurysm because the patient was under long-term steroid therapy for Beh?et disease.     

Middle-ear pressure variations during total intravenous anesthesia with propofol, fentanyl, and ketamine

Purpose As the middle-ear cavity is one of the noncompliant gas-filled cavities, an increase in middle-ear pressure (MEP) instead of volume expansion is observed with inhalation of nitrous oxide (N₂O). Changes in MEP cause many complications, such as ear pain, temporary hearing impairment, and postoperative emesis. Therefore, we investigated changes in MEP during total intravenous anesthesia (TIVA) with propofol, fentanyl, and ketamine (PFK) and inhalation of N₂O. Methods Twelve patients were anesthetized with PFK until 60 min after the induction of anesthesia, and then N₂O (60%) inhalation was started. MEP was measured by impedance audiometry (ranging from −300 daPa to +200 daPa) at 10-min intervals during PFK, and at 2-min intervals after the inhalation of N₂O. Results MEP gradually but significantly increased from the preanesthetic value of 16±8 to 34±12 (SEM) daPa 50 min after the induction of PFK. However, MEP did not exceed the normal limit. The values of MEP in all patients were more than 200 daPa within 36 min after the start of inhalation of N₂O in oxygen. Conclusion PFK had a minimal effect on MEP, whereas addition of N₂O to PFK increased MEP dramatically. Therefore, TIVA, or at least PFK, would be a better choice for patients with middle-ear or upper-airway diseases.     

Development of a high-level expression system for deuterium-labeled human serum albumin

We have developed an expression system for recombinant human serum albumin (rHSA) using methylotrophic yeast Pichia pastoris Mut(+) transformants together with the multiple cross-over integration of the vector containing human serum albumin (HSA). After 86 h of methanol induction, the secreted rHSA reached levels of approximately 320 mg/l in 100% H(2)O medium and approximately 180 mg/l in 70% D(2)O/30% H(2)O (v/v) medium in a fed-batch fermenter. The structures of the obtained rHSA and plasma-derived HSA (pHSA) were virtually identical as viewed from various physicochemical techniques such as HPLC, SDS gel electrophoresis, and CD. NMR peaks of the partially deuterium (D)-labeled rHSA (DrHSA) were quite sharp compared to those of pHSA due to suppression of the intramolecular nuclear Overhauser effect, promising further structural studies of the whole HSA molecule in the solution state using the recent NMR techniques.     

Advance in animal experiments with the undulation pump total artificial heart: 50 and 54 day survival periods with 1/R control

The undulation pump total artificial heart (UPTAH) is a unique, implantable, total artificial heart (TAH) that uses undulation pumps. To achieve long-term survival in animals with physiologic hemodynamic conditions, a control method based on conductance and arterial pressure was applied to UPTAH. With this control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6 kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No. 0016, 1/R control was applied to the left pump, whereas in No. 0030, it was applied to the right pump. Another pump was used for left-right balance control. The control stability was better in No. 0030 than in No. 0016. The sucking effect of the left atrium was remarkable in No. 0016, possibly because of a time delay when left-right balance control was performed with the right pump. In No. 0016, the cause of death was probably a thrombus flown from a panus in the left atrium. It is possible that the left atrial suction effect influenced the thrombus and panus formation in the left atrium. In No. 0030, the cause of death was a small rupture of the membrane in the right pump. The rupture may have been caused by excessive negative pressure inside the pump. This pressure resulted from suction of the right atrium because of an unexpected control excursion, which was probably caused by a software bug. It will be necessary to redesign the undulation pump and improve the software to achieve longer survival periods for animals with physiologic hemodynamic conditions.     

XIdax, an inhibitor of the canonical Wnt pathway, is required for anterior neural structure formation in Xenopus.

Wnt signaling pathways are involved during various stages in the development of many species. In Xenopus, the accumulation of beta-catenin on the dorsal side of embryo is required for induction of the organizer, while the head structure formation requires inhibition of Wnt signaling. Here, we report a role for xIdax, a negative regulator of Wnt signaling. XIdax is expressed in neural tissues at the neurula stage, and in the restricted region of the tadpole brain. Ectopic expression of xIdax inhibits the target gene expression, suggesting that xIdax can inhibit canonical Wnt signaling. To examine the function of xIdax, a morpholino oligo for xIdax (xIdaxMO) was designed. An injection into an animal pole cell caused a loss of forebrain. The anterior neural marker expression is decreased in xIdaxMO-injected embryo, suggesting that xIdax is required for anterior neural development. Moreover, a negative regulator that acts downstream of xIdax rescued this defect. We propose that Idax functions are dependent on the canonical Wnt pathway and are crucial for the anterior neural development.     

The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome

Tenosynovial thickening within the confined space of the carpal tunnel is thought to be the cause of the carpal tunnel syndrome (CTS). However, little is known about the pathological mechanism of tenosynovial thickening. In this study, the role of prostaglandin E(2) (PGE(2)) and vascular endothelial growth factor (VEGF) (two representative molecules that can induce oedema by increasing vascular permeability) was analysed in CTS by using immunohistochemistry and enzyme-linked immunosorptive assay (ELISA). Expression of these molecules was compared with the patients' clinical histories and a temporary increase in production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome when the histology of the tenosynovium changes from oedematous to fibrotic. Statistical analysis clearly demonstrated that there is a close correlation between the expression of PGE(2) and VEGF. Furthermore, immunohistochemical analysis with anti-proliferating cell nuclear antigen (PCNA) revealed that the area with distinct VEGF expression closely matched the area where endothelial cells, vascular smooth muscle cells, and synovial lining cells proliferate. In contrast, despite marked alteration in the extracellular matrix (ECM) component of the tenosynovium, the fibroblasts responsible for most ECM framework production do not proliferate during any phase of CTS. Histological analysis demonstrated that angiogenesis takes place only during the intermediate phase. Since clusters of capillaries and arterioles are often surrounded by type III collagen-rich, disorganized, degenerate connective tissue, which contains fewer fibroblasts than normal, angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. These findings strongly indicate that both PGE(2) and VEGF are expressed in the tenosynovium in CTS during the intermediate phase and induce the histological changes seen in the tenosynovium.     

M pathway and areas 44 and 45 are involved in stereoscopic recognition based on binocular disparity

We characterized the visual pathways involved in the stereoscopic recognition of the random dot stereogram based on the binocular disparity employing a functional magnetic resonance imaging (fMRI). The V2, V3, V4, V5, intraparietal sulcus (IPS) and the superior temporal sulcus (STS) were significantly activated during the binocular stereopsis, but the inferotemporal gyrus (ITG) was not activated. Thus a human M pathway may be part of a network involved in the stereoscopic processing based on the binocular disparity. It is intriguing that areas 44 (Broca's area) and 45 in the left hemisphere were also active during the binocular stereopsis. However, it was reported that these regions were inactive during the monocular stereopsis. To separate the specific responses directly caused by the stereoscopic recognition process from the nonspecific ones caused by the memory load or the intention, we designed a novel frequency labeled tasks (FLT) sequence. The functional MRI using the FLT indicated that the activation of areas 44 and 45 is correlated with the stereoscopic recognition based on the binocular disparity but not with the intention artifacts, suggesting that areas 44 and 45 play an essential role in the binocular disparity.     

Postoperative mediastinitis after the coronary artery bypass grafting using internal thoracic artery graft

It has been pointed out in general that the resistance against infection is decreased in the diabetic patients. This problem is very important in patients undergoing major surgery. In cardiovascular surgery, the median wound infection may result in life threatening sequelae. We have used the internal thoracic artery as the appropriate graft for its excellent long-term patency. In this series of the diabetic patients who underwent coronary artery bypass grafting with bilateral internal thoracic artery grafts, the incidence of postoperative mediastinitis was significantly higher than other cases. Therefore the use of bilateral internal thoracic artery grafts should be avoided, if possible in the diabetic patients.