Effects of sodium hyaluronate on the nociceptive response of rats with experimentally induced arthritis]

Antinociceptive effects of sodium hyaluronate (Na-HA) were studied on the basis of improvement in the graded abnormal gait elicited by arthritis induced by intra-articular administration of monosodium urate crystal (MSU) to rats. One hour before MSU injection, intra-articular administration of a 1.0% solution of Na-HA with different molecular weights, ranging from 4.70 x 10(5) to 2.02 x 10(6) (HA-200), improved the score of abnormal gait in a molecular weight-dependent manner in the experimental arthritis model. Similarly, administrations of HA-200 at concentrations ranging from 0.1 to 1.0% prior to MSU treatment resulted in improvement of the score in abnormal gait in a dose-dependent manner. To elucidate the antinociceptive mechanisms of Na-HA, effects of pretreatment with Na-HA (1.0%) of different molecular weights on prostaglandin E2 (PGE2) and bradykinin (BK) releases in synovial fluid 3 hr after MSU injection were studied. Increases in PGE2 and BK concentration in the synovial fluid were depressed in a molecular weight-dependent manner by Na-HA (1.0%) pretreatment. These results indicate that Na-HA attenuates the nociceptive responses inflicted by the MSU-induced arthritis. Such an antinociceptive effect may be due to the inhibition of PGE2 and BK synthesis in the synovial joint of rats.     

Specific [125I]brain natriuretic peptide-26 binding sites in rat and pig kidneys

Specific binding sites for porcine brain natriuretic peptide-26 (BNP-26), a member of the atrial natriuretic peptide family (ANPs), were investigated in the kidney by using receptor autoradiographic and membrane binding techniques with [125I]BNP-26. The binding sites were discretely localized in rat and porcine kidney areas corresponding anatomically to the glomeruli and inner medulla. There were no differences between the localization of [125I]BNP-26 and [125I]alpha-rat ANP binding sites in the kidney. [125I]BNP-26 binding to solubilized membranes from isolated glomeruli of the rat kidney was saturable, and a single class of high-affinity sites was labeled with a KD of 372 pM. The radioligand bound to two sites in solubilized inner medullary membranes of the rat, a low-affinity site with a KD of 30 nM, and a high-affinity site with a KD of 33 pM. The rank order of potency to inhibit binding was BNP-26 = alpha-rat ANP-(1-28) greater than atriopeptin III (ANP-(103-126)) much greater than atriopeptin I (ANP-(103-123)) greater than des-Cys105,Cys121- ANP-(104-126). Thus, [125I]BNP-26 presumably recognizes ANP receptors in the kidney. The possibility that BNP-26 regulates, as a circulating hormone, kidney functions by binding to ANP receptors would have to be considered.     

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 ± 0.38, 2.12 ± 0.37, and 1.38 ± 0.24 (μg/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. Received: 12 August 1996 Accepted: 17 December 1996     

Papillo-Choledochectomy in the Operative Management of Mucosal Neoplasms of the Periampullary Region

Two patients with mucosal cancer of the periampullary region were treated with papillocholedochectomy, which entails removal of the papilla of Vater and the whole length of the common bile duct. The neoplasm is dissected out through the plane between the duodenal circular and longitudinal muscles, deep to the sphincter of Oddi and the fibromuscular layer of the bile duct. Pathological examination showed that cancer was confined to the mucosal layer without stromal invasion, and that the operation achieved radical cure. For mucosal cancer, papillo-choledochectomy is an alternative to pancreatoduodenectomy, provided that repeated frozen-section studies confirm the completeness of excision.     

A case of retroperitoneal Hodgkin's disease with dysuria

A case of retroperitoneal Hodgkin's disease with dysuria is reported. A 56-year-old man visited our hospital with the complaints of dysuria and lower abdominal mass. On physical examination, an unmovable hard smooth mass of fist size was palpable in the lower abdomen and prostate was slightly swelling by rectal digital examination. Excretory urography demonstrated medial deviation of left lower ureter and bladder deformity. Retrograde urethrocystography showed deviation and compression of prostatic urethra. On CT, tumors were composed of several round masses, which surrounded the left common iliac artery on angiography. Surgical extirpation was carried out and histological examination revealed Hodgkin's disease. As postoperative treatment, chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone was performed, and 30 months after the operation the patient was asymptomatic.     

Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer.

Frequent loss of heterozygosity at chromosomal loci in a specific tumor type may indicate the presence of a tumor suppressor gene. We have examined loss of heterozygosity on chromosome 8p in paired tumor and constitutional DNA from 346 patients representing seven different types of human cancer. Frequent allelic losses were observed in hepatocellular carcinoma (22 of 46 cases, 47.8%), in colorectal cancer (12 of 26, 46.2%), and in non-small cell lung cancer (14 of 35, 40.0%), in contrast to low frequencies detected in breast cancer (5 of 56, 8.9%) and renal cell carcinoma (2 of 27, 7.4%). Ovarian cancer and gastric cancer showed intermediate frequencies of 33.3% and 22.2%. Subsequent analysis of 120 hepatocellular carcinomas and 94 colorectal cancers with five polymorphic markers along the short arm of chromosome 8 defined commonly deleted regions within the same chromosomal interval, 8p23. 1-8p21.3, suggesting that one or more tumor suppressor genes for both cancers may be present in that region.     

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991.     

Morphologic analysis of rat retinocollicular neuron terminals containing monoamine oxidase

The retino-collicular neuron terminals containing type A monoamine oxidase (MAO-A) in the stratum griseum superficiale of the rat superior colliculus were analyzed to provide a morphologic basis for the physiologic role of these neurons in the visual pathway. A computer-assisted, three-dimensional re-construction of the terminal complex associated with the MAO-A-positive terminals was performed. MAO-A-positive terminals originated in the retina and terminated in the stratum griseum superficiale. This was confirmed by tract tracing and enucleation experiments. The terminals were densely grouped in clusters of irregularly shaped swellings. Electron microscopy revealed that the MAO-A-positive terminals were located in a glomerulus-like structure. In this terminal complex, a significant proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which represent intermediate elements between the retinal terminals and conventional dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A-positive terminal swellings were not located in the central part of the terminal complex. The terminals had an irregular shape and were located in the complex. The terminal complex was partially ensheathed by glial processes. Furthermore, the membrane surfaces exhibiting synaptic specializations were very small compared with the total surface of the terminal swellings. The membrane length of the synaptic specialization was 5.38% of the total perimeter of the MAO-A-positive terminals.