Antinociceptive effects of ONO-9902, an enkephalinase inhibitor,after visceral stress condition in rats

Purpose

The present study was designed to examine the antinociceptive effects of orally administered ONO-9902, an enkephalinase inhibitor, on both somatic and visceral pain after visceral stress conditions.

Methods

Twenty six male rats were examined. Tail-flick (TF) and colorectal distension (CD) tests were used to determine somatic and visceral antinociceptive effects, respectively. Measurements were performed in rats under immediate post-stress conditions (group ST; n = 14) and in rats nor under stress conditions (group NST; n = 12). In the stressed group, the same device, CD, for visceral antinociceptive effects was used for visceral stress and was applied with an intracolonic pressure of 60 mmHg for 20 min after drug administration. The TF latency and CD threshold were measured before and at 30, 40, 50, 60 and 90 min after administration of ONO-9902 300 mg · kg^?1 or distilled water.

Results

Orally administered ONO-9902 did not produce any changes in the % maximum possible effect (%MPE) in either TF or CD tests in the unstressed group. In the stressed group, %MPE in the CD test increased 18% and 31% at 30 and 40 min, respectively, after oral administration of ONO-9902 compared with the control group (P < 0.05). However, %MPE to TF test did not alter even after the CD-induced stress condition.

Conclusion

These results suggest that ONO-9902 may have analgesic effects on visceral pain but not on somatic pain under immediate post-stress conditions.     

Composition and function of “hornmark” in cutaneous horns

Summary In an attempt to elucidate the mechanism underlying the formation of cutaneous horns, 43 cases of cutaneous horns were examined histologically and histochemically. Three of 43 cases were also investigated by using direct immunofluorescence technique and electron microscopy. The structure identical to Hornmark was found in all of 43 cases of cutaneous horns except two which consisted only of horny masses. The substance found in the intercellular space of Hornmark was homogenous, eosinophilic and mostly diastase-resistant PAS positive, and showed strongly positive immunofluorescence for immunoglobulins, complement, and fibrinogen. Electron microscopically, it was moderately electron dense, fine granular and in part fine fibrillar, and was similar to the contents of capillary lumen. From these findings, it was suggested that the substance found in Hornmark consisted mainly of the components of plasma protein, and that coagulated plasma protein might play an important role on the increased cohesiveness of the horny cells, i.d. on the formation of cutaneous horns.

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Zusammenfassung Um den Mechanismus der Hauthornbildungen zu erklären, wurden 43 Fälle der Hauthörner mittels der Histologie und Histochemie untersucht. Drei Hauthörner wurden auch mit Hilfe von direkten Immunofluorescenzen-Techniken und Elektronenmikroskopien untersucht. Sogenanntes Hornmark wurde in allen Fällen der 43 Hauthörner, abgesehen von 2 Fällen, beobachtet, die nur aus Hornmassen bestehen. Die Substanz, die in den intercellulären Räumen des Hornmarks beobachtet wurde, war homogen, eosinophil und meistens diastase-resistent PAS positiv. Stark positive Immunofluorescenz für Immunoglobulinen, Complement und Fibrinogen wurde auch in den Substanzen beobachtet. Elektronenmikroskopische Untersuchungen zeigten, daß die Substanz ziemlich opak, granulär und zum Teil fibrillär war und dem Inhalt der Capillaren ähnelte. Aus diesen Befunden wurde geschlossen, daß die Substanz, die im Hornmark der Hauthörner beobachtet wurde, hauptsächlich aus den Bestandteilen des Blutplasma gebildet wurde, und daß coaguliertes Plasmaprotein eine wichtige Rolle für die zunehmende Kohäsion der Hornzellen, d. h. für die Hauthornbildung, spielen mag.

     

Comparison between multiple lacunar infarcted patients with and without dementia in nursing homes in shimane prefecture, Japan

We evaluated the activity of daily living (ADL) scores, the frequency of hypertension (HT) and diabetes mellitus (DM), and the frequency and distribution of white matter lesions in a vascular dementia group with multiple lacunar infarctions (VD group; 20 cases) and a nondemented group with multiple lacunar infarctions (non-D group; 32 cases), relative to a normal control group (29 cases). There were no significant differences in HT and DM among the three groups. ADL scores were significantly lower in the VD than in the non-D group, each of which was lower than in the control group. Frequency of white matter lesions (Binswanger's disease-like lesions in the frontal and parietal lobes) was significantly higher in the VD than in the non-D group, which was higher than in the control group. We believe that for dementia with multiple lacunar infarctions, diffusely affected cerebrum including white matter lesions, which results in low ADL scores for symptoms, may be a prerequisite.     

Differential expression of gamma-aminobutyric acid type B receptor-1a and -1b mRNA variants in GABA and non-GABAergic neurons of the rat brain

To understand the heterogeneity of gamma-aminobutyric acid type B receptor (GABABR)-mediated events, we investigated expression of GABABR1a and 1b mRNA variants in GABA and non-GABAergic neurons of the rat central nervous system (CNS), by using nonradioactive in situ hybridization histochemistry and, in combination with GABA immunocytochemistry, double labeling. In situ hybridization with a pan probe, which recognizes a common sequence of both GABABR1a and GABABR1b mRNA variants, demonstrated widespread expression of GABABR1 mRNA at various levels in the CNS. Both GABABR1a and GABABR1b were expressed in the neocortex, hippocampus, dorsal thalamus, habenula, and septum, but only GABABR1a was detected in cerebellar granule cells, in caudate putamen, and most hindbrain structures. A majority of GABA neurons in cerebral cortex showed hybridization signals for both GABABR1a and GABABR1b, whereas those in most subcortical structures expressed either or neither of the two. GABA neurons in thalamic reticular nucleus and caudate putamen hybridized primarily for GABABR1a. Purkinje cells in the cerebellar cortex expressed predominantly GABABR1b. GABA neurons in dorsal lateral geniculate nucleus did not display significant levels of either GABABR1a or GABABR1b mRNAs. These data suggested widespread availability of GABABR-mediated inhibition in the CNS. The differential but overlapping expression of GABABR1 mRNA variants in different neurons and brain structures may contribute to the heterogeneity of GABABR-mediated inhibition. Some GABA neurons possessed, but others might lack the molecular machinery for GABABR-mediated disinhibition, autoinhibition, or both.     

Influence of parity on second-trimester uterine artery Doppler waveforms in twin pregnancy.

We performed uterine artery Doppler velocimetry in 16 nulliparous and 16 parous women with non-preeclamptic singleton gestations and 16 nulliparous and 16 parous women with dichorionic twin gestations at 17-18 and 26-27 weeks of gestation. In both singleton and twin pregnancies, the average pulsatility index (PI) in nulliparous women was significantly higher than that in parous women at 17-18 weeks of gestation. At 26-27 weeks of gestation, however, there were no significant differences in PI between nulliparous and parous women with either singleton or twin pregnancies. During the early second-trimester of non-preeclamptic singleton and twin pregnancies, parity has a significant effect on uterine artery blood flow.     

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor

We report a case of adenosquamous carcinoma of the stomach that produced granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of infection. After leukemia and metastatic leukemoid reaction were excluded by bone marrow examination, a G-CSF-producing cancer was suspected as the cause of the abnormally elevated serum G-CSF level. The resected stomach tumor was histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF by tumor cells was shown with immunohistochemical detection, which confirmed the preoperative diagnosis. Recurrent disease in the liver and lymph nodes, accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3 months after the curative gastrectomy and adjuvant chemotherapy. All of the recurrent disease was resected, restoring normal levels of serum G-CSF. The patient survived for almost 2 years after the initial surgery with extensive chemotherapy, including weekly treatment with paclitaxel, before finally succumbing to liver failure secondary to extensive liver metastasis.     

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.     

Occurrence of saxitoxins as a major toxin in the ovary of a marine puffer Arothron firmamentum.

Eleven male and 14 female specimens of a marine puffer Arothron firmamentum were collected from Oita and Iwate Prefectures, Japan. The toxicity assay using mouse showed that only ovary and skin of the female specimens were toxic, the toxicity scores being 5-740 as paralytic shellfish poison and <5-30 MU/g as tetrodotoxin (TTX), respectively. The toxin extracts from the both tissues were then treated with cartridge columns, and subjected to high performance liquid chromatography and liquid chromatography-mass spectral analyses. In the analyses, saxitoxin (STX) and decarbamoylSTX (dcSTX) were identified as the major toxins in the ovary, while the skin contained only TTX.