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.     

ENDOSCOPIC NASOBILIARY DRAINAGE: CURRENT INDICATIONS AND EVALUATION OF THE PRODUCTS

Endoscopic nasobiliary drainage (ENBD) is a well established mode of biliary decompression. Although ENBD is certainly an uncomfortable procedure with the potential risk of spontaneous dislocation or removal of the drainage catheter by disoriented patients, it has several advantages over endoscopic biliary drainage (EBD) using an indwelling stent. The current indications for ENBD are: (i) temporary drainage to treat obstructive jaundice and cholangitis caused by malignant or benign biliary stricture; (ii) urgent drainage to treat suppurative cholangitis primarily caused by common bile duct stones; (iii) temporary drainage after stone removal in patients with suspected incomplete clearance and/or with cholangitis; and (iv) biliary leaks that occur primarily after surgery, as well as other indications. Different types of nasobiliary catheters are currently available that have been designed with various diameters, shapes, and materials. However, the current catheters are not considered by most endoscopists to be sufficient. Further improvements are needed to achieve better drainage and better maneuverability.     

Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases

Among 355 autopsy cases of hepatocellular carcinoma (HCC), 14 cases exhibited sarcomatous appearance (incidence, 3.9%). A clinicopathologic study was performed in these 14 cases, and the immunohistochemical localization of keratin (KRT), vimentin (VMT), albumin (ALB), fibrinogen (FBG) and alpha-fetoprotein (AFP) was also examined using the avidin-biotin complex method. Clinically, the HCCs with sarcomatous appearance were characterized by negative or low serum AFP levels and high incidence of extrahepatic metastasis. Grossly they were of infiltrative, mixed expansive and infiltrative, and pedunculated types. Histologically, the tumor consisted mainly of spindle-shaped cells and partly of multinucleated cells, and showed a sinusoidal growth pattern at the tumor-nontumor boundary. Immunohistochemically, tumor cells in the regions showing sarcomatous appearance were frequently found to be positive to KRT and VMT, whereas the percentage of positivity to ALB, FBG, and AFP were not significantly different from those in ordinary HCC. These results strongly suggest that the lesion showing sarcomatous appearance represents the sarcomatous change of HCC rather than being regarded as the complication of HCC and sarcoma.     

Reduction of Nitric Oxide with L–/Vc–Monomethyl Arginine in lnterleukin–2 and Anti–CD3 Monoclonal Antibody Combination Therapy

We evaluated nitric oxide induction in antitumor therapy consisting of anti–CD3 monoclonal antibody (anti–CD3) and interleukin–2 (IL–2), then determined the effect of nitric oxide reduction with L–N^G–monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK–resistant murine fibrosarcoma cell line), and 145–2C11 (hamster anti–murine–CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO₂^–+ NO₁ was observed at 19 hours after anti–CD3 (10 μ, IV) and additional IL–2 administrations (40times10¹ U, twice, If) induced a further increase. The NO₂, + NO_3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti–CD3 + IL–2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h.     

A Rare Case of Biliobiliary Fistula

Abstract: Biliobiliary fistula is a rare clinical entity. The case of a 72 year old female, who presented with epigastric pain and jaundice, is detailed herein. Endoscopic retrograde cholangiopancreatography (ERCP) revealed two stones, one each in the common bile duct and the gallbladder. Continuous endoscopic nasobiliary drainage (ENBD) was performed to relieve obstructive jaundice. Further study with contrast medium administered via the ENBD tube revealed a fistula between the neck of the gallbladder and the common bile duct. The cystic duct was intact. A stone was considered to have migrated into the common bile duct through the fistula. A diagnosis of biliobiliary fistula, Corlette type I was made. However, in this particular case, a biliobiliary fistula was noted at a site below the junction of the cystic duct and common bile duct. Removal of the gallbladder stones was followed by cholecystectomy. The common bile duct was then repaired by utilizing a T-tube. No evidence of malignancy was recognized in the resected gallbladder specimen. In the one year to date since surgery, the patient has been asymptomatic and without signs of biliary disease.     

Effect of magnetic field on pineal gland volume and pinealocyte size in the rat

Abstract: Light microscopic observations on the superficial pineal gland of Wistar-King rats were made to examine whether or not pineal volume and pinealocyte size, expressed as nuclear density, at daytime or nighttime are affected by long-term exposure to 50 Hz rotating magnetic field (MF) at 5.0 μT. Determinations of pineal volume and pinealocyte size were repeated twice (April and October) during the year. Size of pinealocytes in MF-exposed and sham-exposed rats exhibited, in addition to the difference between peripheral and central regions, regional differences in a proximodistal direction; pinealocytes in the distal and middle-peripheral regions were usually larger than those in the proximal and middle-central regions at daytime or nighttime. In October, distal and proximal pinealocytes showed significant day-night changes in size in sham-exposed rats, but not in MF-exposed animals. The situations in the two groups were almost reversed in April. Significant day-night differences were scarcely found in pinealocyte size in the middle region in the two groups. Throughout the study, pineal volume and pinealocyte size in each region were generally the same between MF-exposed and sham-exposed rats at daytime or nighttime. The results suggest that pinealocytes in the distal and proximal regions, but not those in the middle region, are affected by MF-exposure; day-night differences in sizes of distal and proximal pinealocytes appear in April and disappear in October under the influence of MF. MF may exert an effect on mechanisms controlling day-night rhythms of pinealocyte size in the rat.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.