Hormetic and anti-radiation effects of tropolone-related compounds

We have previously investigated a total of 173 azulene-, tropolone- and azulenequinone-related compounds for their tumor-specificity and anti-inflammatory activity. In this study, we selected six compounds that showed tumor-specific cytotoxicity (referred to as group I compounds) and five compounds that inhibited nitric oxide production by activated macrophages (referred to as group II compounds) to investigate their possible hormetic and anti-radiation effects. We have established three oral normal cell type, human gingival fibroblast HGF-1, pulp cell HPC-1 and periodontal ligament fibroblast HPLF-1, from extracted teeth and periodontal tissue. These normal cells expressed p53 protein, regardless of the growth stage (either at growing or near confluent phase), more than oral squamous cell carcinoma cell line (HSC-2). Group I compounds slightly stimulated the growth of HPL-1 cells only at restricted durations and concentrations, but did not affect that of HGF-1 and HPC-1 cells, suggesting the minor hormetic effects displayed by these compounds. We established a new evaluation system for UV-induced cellular damage using an intact HSC-2 cell system in which sodium ascorbate (vitamin C) and gallic acid, but not N-acetyl-l-cysteine nor catalase, exerted protective effects. Three group I compounds and two group II compounds significantly protected the cells from UV-induced injury, suggesting their possible anti-UV effect.     

Differences between muscular receptors and neural receptors for cholecystokinin-octapeptide in the guinea-pig gallbladder

To investigate the differences between muscular and neural receptors for cholecystokinin-octapeptide (CCK-OP) in the guinea-pig gallbladder, we studied the effects of dibutyryl cyclic GMP (dbc GMP) on CCK-OP-evoked contraction and [3H]acetylcholine (ACh) release. 10(-3) M dbc GMP significantly reduced CCK-OP (10(-8) M)-evoked contractions without affecting the peptide-induced [3H]ACh release. It is suggested that there are two types of CCK-OP receptors in the guinea-pig gallbladder (dbc GMP-sensitive muscular receptors and dbc GMP-insensitive neural receptors).     

Dual action of cholecystokinin-octapeptide on the guinea pig antrum

We examined the mechanism of action of cholecystokinin-octapeptide (CCK-OP) on longitudinal strips of the lesser and greater curvatures of the guinea pig antrum. In the strips of the lesser curvature, CCK-OP produced a concentration-dependent tonic contraction, which was significantly reduced by atropine, but not by tetrodotoxin. In contrast, CCK-OP caused a relaxation of the preparation of the greater curvature in a concentration-dependent manner. The relaxation induced by the peptide was enhanced by atropine, whereas it was blocked by tetrodotoxin. Propranolol, phentolamine, desensitization to adenosine-5'-triphosphate, and desensitization to vasoactive intestinal polypeptide had no effect on CCK-OP-induced relaxation. Cholecystokinin-octapeptide evoked the release of acetylcholine from strips of both sides, and it was not blocked by tetrodotoxin. These findings indicate that the mechanism of action of CCK-OP on the lesser curvature differs from that on the greater curvature. The peptide seems to act directly on smooth muscle cells and to stimulate cholinergic neural activity by sodium channel-independent mechanisms. Additionally, nonadrenergic inhibitory neurons appear to be activated by CCK-OP in the greater curvature.     

Clinical features of acute obstructive suppurative cholangitis (AOSC) in the old age]

Nineteen cases (male 6, female 13) of acute obstructive suppurative cholangitis (AOSC) were divided into 2 groups and were studied, Group A; over 70 yrs old (12), Group B; under 70 yrs old (7). The most frequent etiology of AOSC was choledocholithiasis (Group A 75%, Group B 43%). Urgent biliary drainage was performed in 18 cases, and which were clinically improved. The decreasing rate of bilirubin were fair in both groups and only 2 cases in Group A were dead. Concerning with the laboratory findings on admission, Group A had a higher level of BUN than Group B, and there were no other significant differences. Complications were frequently occurred in Group A (Shock 83%, DIC 83%, Renal failure 42%). The diameter of choledochus at biliary drainage was below 9 mm in 45% of cases in Group A, which implied the rapid progression to AOSC from the onset of biliary obstruction. Early diagnosis and urgent biliary drainage were essential for the management of AOSC in the old age.     

Study on the screening of thyroidal dysfunction in adult

For the purpose of screening of thyroidal dysfunction in adult, we have collected blood of 15,905 (male 11,559, female 4,346) adult normal workers and school students on filter papers at the time of the annual health examination. Both TSH and total T4 were measured by radioimmunoassay. Either TSH or total T4 or both showed abnormal values in 148 cases. For these subjects, serum TSH, total T4 and T3, free T4, TBG, antimicrosomal and antithyroglobulin antibody were estimated. From these results, diagnosis was made as follows: 6 hyperthyroidism, 12 primary hypothyroidism (including 3 subclinical hypothyroidism who showed elevated TSH and normal free T4 values) and 29 TBG abnormality (increase: 8, decrease or deficiency: 21). The incidence by this study was: hyperthyroidism 0.038% (1/2650), primary hypothyroidism 0.075% (1/1330), TBG increase or deficiency 0.132% (1/760). Sex ratio of thyroidal dysfunction were higher in female than male. In hyperthyroidism, ratio of male to female was 1:2.66, and in hypothyroidism, it was 1:133. Most of these patients were not diagnosed before this screening. The fact that the incidence of hypothyroidism was higher than hyperthyroidism in this population was apparent in this study. TBG abnormality was noted more in male than female. This report is important to show the incidence of thyroidal abnormalities and the necessity of the screening test of thyroid in adult.     

Embryonic stem cells: potential source for ocular repair

Many ocular diseases, such as retinitis pigmentosa and age-related macular degeneration, reflect damage to specific cells that are not normally repaired or replaced. Preliminary results of animal studies suggest that these degenerative diseases may be treatable by transplantation of healthy fetal cells. However, obtaining a sufficient number of suitable donor cells remains a problem. The isolation of human embryonic stem (ES) cells has drawn much attention because of their potential clinical application for patients with these degenerative diseases. Because ES cells have the potential to generate all adult cell types, ocular diseases resulting from the failure of specific cell types would be potentially treatable through the transplantation of differentiated cells derived from ES cells. In addition, because ES cells can proliferate indefinitely in their undifferentiated state, they are expected to alleviate the problem of the shortage of donor cells for cell-replacement therapy. Recently, reproducible and efficient differentiation methods for the generation of lens cells, retinal neurons, and retinal pigment epithelial (RPE) cells from ES cells have been developed. This review focuses especially on these ocular cells differentiated from ES cells. We will also discuss the potential therapeutic uses of ES cells for the treatment of ocular diseases.     

Cholecystokinin octapeptide-evoked [3H]acetylcholine release from guinea pig gallbladder

Cholecystokinin-octapeptide (CCK-OP) produced a contractile response in isolated guinea pig gallbladder; the response consisted of scopolamine-sensitive and scopolamine-insensitive components, neither of which were affected by tetrodotoxin or hexamethonium. In the presence of tetrodotoxin, CCK-OP evoked [3H]acetylcholine (ACh) release from strips of gallbladder in a concentration-dependent manner. These results suggest that CCK-OP acts at two sites in the guinea pig gallbladder, viz. the smooth muscle cell and the postganglionic cholinergic nerve terminal.     

Impaired Contractile Motility of the Gallbladder after Gastrectomy

Contractile motility of the gallbladder was compared using a real-time ultrasonography in 13 patients with gastric ulcer and 31 patients with gastric cancer who had undergone either subtotal or total gastrectomy within 1 month previously. Contractile motility of the gallbladder after oral administration of dried egg yolk (Daiyan, Maruishi, Osaka), which was slightly but not significantly reduced in patients with gastric ulcer, was remarkedly impaired in patients with gastric cancer who had either subtotal or total gastrectomy including radical lymph node dissection. Especially, maximum contractile rate after Daiyan in Billroth II patients was significantly reduced than that of Billroth I patients. Intramuscular injection of naloxone (0.4 mg), which had no effects on contractions after Daiyan in healthy subjects, significantly improved the hypomotility in response to Daiyan in these gastric cancer patients. It was suggested, therefore, that the possible roles of various anatomical and mechanical changes resulting from gastrectomy including vagotomy and sympathectomy, and in particular exclusion of duodenum from digestive circuits and relative or absolute excess of endogenous opioids, were involved in the control of the gallbladder motility within 1 month after gastrectomy including lymphadenectomy.     

Choledochal cyst. Its possible autonomic involvement in the bile duct

The properties of the choledochal cyst were compared with those of the normal common bile duct. Cholecystokinin-octapeptide and a high concentration of acetylcholine produced smaller contractions in the strips of the narrow portion of the cyst than in the strips of the dilated portion and the normal common bile duct. Nicotine did not cause contractions in the strip of the narrow portion of the cyst. gamma-Aminobutyric acid (GABA) induced atropine-sensitive, tetrodotoxin-sensitive contractions in the bile ducts through bicuculline-sensitive, furosemide-sensitive GABAA receptors located on the postganglionic cholinergic neuron. The GABA did not induce contractions in the narrow portion of the cyst. The number of ganglion cells was decreased markedly in the same portion. These findings suggest that the choledochal cyst has postganglionic neural dysfunction. This character may be one of the causes of cyst formation.     

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis

3 cases of allergic contact dermatitis from industrial rubber products were investigated using a combination of patch testing in patients and chemical analysis of causative rubber products by gas chromatography (GC), GC-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Our studies revealed N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), a typical rubber allergen, as a causative chemical in a case from a brand of heavy-duty rubber gloves and a case from a black rubber ring for car manufacture, and zinc ethylphenyldithiocarbamate (ZEPC), a dithiocarbamate (DTC)-type accelerator, as a causative chemical in a case from a brand of rubber work gloves: both IPPD and ZEPC, which showed positive patch test reactions, were confirmed in the extracts of the causative rubber products by GC, GC-MS and/or HPLC.