Invited Review Articles
Peripheral Mechanism of Hyperalgesia - Sensitization of Nociceptors -
KAZUE MIZUMURA
pg(s) 69- 87
<Close> - < PDF >
The peripheral mechanism of hyperalgesia is considered to be the result of nociceptor sensitization. As possible agents causing nociceptor sensitization, bradykinin, histamine, prostaglandin (PG)s, protons and nerve growth factor are evaluated with respect to their release into the injured tissue, their sensitizing potencies. Whether blocking these agents suppresses sensitization was also evaluated. In addition, the intracellular mechanisms by which bradykinin, histamine and PGs cause sensitization are reviewed.
New Concepts and Insights on Pathogenesis and Treatment of Diabetic Complications: Polyol Pathway and its Inhibition
NIGISHI HOTTA
pg(s) 89-100
<Close> - < PDF >
The polyol pathway is one of the possible biochemical mechanisms by which hyperglycemia could impair the function and structure of the cells affected by diabetic complications. As possible hypothesis for the pathogenesis of diabetic complications, the polyol osmotic theory, alterations in myo-inositol and sodium metabolism, intermediary metabolites, abnormal changes of the redox state (NADH/NAD+ ratio) and an abnormality of kinase C dependent protein phosphorylation have been proposed. Recently, increasing evidence suggests that glycation and oxidative stress may have a cross-link with polyol pathway, contributing to the development of diabetic complications. If hyperglycemia-induced polyol pathway hyperactivity has an important role in the etiology of late-onset diabetic complications, the inhibition of aldose reductase (AR), a rate-limiting enzyme of the pathway, could become a key element in the prevention and reversal of diabetic complications. Recent evidence from both animal experiments and clinical studies has emerged to support this theory, resulting in the development of drugs available for the clinical treatment of diabetic neuropathy. From the results obtained mainly in animal models of diabetic complications, it is well recognized at present that AR inhibitors have a positive inhibitory effect on neuropathy, retinopathy, nephropathy, keratopathy, cataract-formation, possibly infection and atherosclerosis. It is now clear that AR inhibitors may offer various benefits to patients with diabetic complications. However, more extensive efforts are needed for the evaluation of their effects.
Cytokines and Local Cellular Immunity
KAORU SHIMOKATA
pg(s)101-108
<Close> - < PDF >
The characteristics and function of human lymphocytes at a morbid site were studied. Exudative-sensitized lymphocytes in tuberculous pleural fluid reacted to the specific antigen more effectively and produced higher titers of lymphokines including interferon gamma (IFN-gamma) and interleukin 2 (IL-2) than circulating lymphocytes. CD4+/CD8- T-cell subset is responsible for the antigen-specific IFN-gamma production in pleural T-lymphocytes of patients with tuberculous pleurisy. Thus, activated T-lymphocytes involve the production of lymphokines at the morbid site and they effectively exert local cellular immunity through the action of such lymphokines. Immunofluorescence study showed an increased production of inducible nitric oxide synthase (iNOS) and peroxynitrite in bacille de Calmette-Guérin (BCG)-inoculated human alveolar macrophages (AM). Reverse transcriptase-polymerase chain reaction methods also revealed the higher expression of iNOS-coding mRNA. Colony assay demonstrated that human AM effectively killed BCG in their cytoplasm. However, treatment of AM with NG-monomethyl-L-arginine monoacetate resulted in markedly reduced killing activity. These results clearly show that BCG-induced nitric oxide (NO) and its reactive product with the oxygen radical, peroxynitrite, could play an important role in BCG killing in human AM.
Original Papers
Morphological Studies on Middle Ear Barotrauma in Guinea Pigs
SHIGENORI SATO, HISASHI YOKOI, SHIGEJI FUKUTA, MAKOTO KOZUKA and NORIYUKI YANAGITA
pg(s)109-117
<Close> - < PDF >
Experimental middle ear barotrauma was studied morphologically. White guinea pigs were placed in an experimental hyperbaric chamber, and middle ear barotrauma was created by increasing the pressure in the hyperbaric chamber from 1 atmosphere absolute (ATA) to 2 ATA using pure oxygen, maintaining the pressure at 2 ATA for 10 minutes, then again reducing the pressure to 1 ATA. Selected experimental animals were decapitated immediately after, one day after, one week after, or weeks after pressure loading, and their middle ears were examined by a light microscope (LM), a scanning electron microscope (SEM) and a transmission electron microscope (TEM). Hemorrhaging in the tympanic cavity immediately after pressure exposure was apparent even macroscopically. LM also revealed evidence of submucous hemorrhage. Submucous edema was seen in the "one week after" cases. SEM showed a minor loss of cilia in some ciliated cells just after the experiment. In nonciliated cells, the terminal web was somewhat indistinct in the "one week after" cases. TEM also indicated a minor loss of cilia in some ciliated cells in "one day after" cases as well as apparent vacuoles within the cells. These findings suggest that although trauma during compression is more marked than during decompression, recovery from this damage progressed with time.
The Advantage of Gastrectomized Patients in Management of their Chronic Hepatitis C
HISAO HAYASHI, TOSHIKUNI TAKIKAWA, NORIKO ARAI and MOTOYOSHI YANO
pg(s)119-127
<Close> - < PDF >
Because the majority of patients with chronic hepatitis C do not respond to interferon, alternative treatments need to be established. Several lines of evidence suggest that iron depletion is beneficial for such patients. Thus, gastrectomized patients with a reduced capacity for iron absorption might have an advantage in treatment of their liver damage over patients with intact gastrointestinal tracts. Four male gastrectomized patients had post-transfusion chronic hepatitis C. The iron load in three patients was adjusted below 10 ng/ml of serum ferritin level by phlebotomy. Subsequent interferon treatment for the four patients without iron load cleared circulating hepatitis C virus RNA in one patient only. However, serum ferritin concentrations were stabilized at low levels without maintenance phlebotomy, and sustained normalization of serum liver enzyme activities was obtained in all four patients. Similar treatments were done for 10 male patients with intact gastrointestinal tracts. The amount of removed iron from these patients was more than that from gastrectomized patients. Interferon also failed to clear circulating hepatitis C virus RNA except in one case. Low ferritin levels and sustained normalization of liver enzymes were seen in three patients. A transient elevation of ferritin levels with low enzyme activities was seen in two patients. Relapsing hepatitis was seen in five of the seven patients who needed maintenance phlebotomy due to a rebound in serum ferritin levels, probably because of active iron absorption from the intestine. Our data suggest that depletion of cytotoxic iron is a key to managing patients with chronic hepatitis C.
Structure and Function of the Hemolymph Node in Rats
KEN-ICHI SAKITA, MASAHIKO FUJINO, TAKASHI KOSHIKAWA, NAOKI OHMIYA, MASAHARU OHBAYASHI and JUNPEI ASAI
pg(s)129-137
<Close> - < PDF >
Hemolymph nodes (HLs) are unique lymph nodes, in that their lymphatic sinuses contain numerous erythrocytes. In this study, we compared the internal structure and immunologic function of HLs with those of ordinary lymph nodes (OLs) and the spleen. Electron microscopy revealed erythrocytes passing through the walls of blood vessels in the intermediate sinus area (IMSA) of a HL between expanded endothelial cell junctions. However, no direct communication was found between lymphatic sinuses and blood vessels. Numerous carbon particles appeared in the IMSA of HLs on 5 days after intravenous carbon particle injection, while OLs lacked particle deposition. Immunohistochemical studies showed that lipopolysaccharide (LPS) reached the IMSA of HLs and extravasated into medullary cords 4 hours after intravenous LPS injection, resulting in the appearance of more IgM-stained lymphocytes in the IMSA of HLs than in that of OLs on day 5. The ability of organs to produce antibodies was determined by counting the number of plaque forming colonies after intravenous injection of sheep red blood cells (SRBC). The HLs antibody-producing ability was between that of OLs and the spleen. These results suggest that HLs possess functionally open blood vessels in the IMSA and their immunologic capability is between that of OLs and the spleen. These findings suggests that HLs are lymphoid organs that have characteristics between those of the OLs and the spleen, both ultrastructurally and functionally.
Case Report
Conservative Handling of the Uterus in a 10-Week Cervical Pregnancy Case
SEIYA YOSHIDA, MADOKA FURUHASHI, ATSUO ITAKURA, YOSHIHITO FURUHASHI and NOBUHIKO SUGANUMA
pg(s)139-143
<Close> - < PDF >
A patient with a living 10-week old cervical pregnancy who desired to preserve fertility was successfully treated with methotrexate, intraamniotic KCI injection and endocervical curettage. In the case of living cervical pregnancy even after 10 weeks, conservative treatment remains an option, although intensive management and care should be given.
Abstracts
Annual Research Meetingfor Graduate Students: Nagoya, December 1996
pg(s)145-167
< PDF >