The acne-therapeutic effects of Oriental herb extracts were investigated in terms of antichemotactic effect on polymorphonuclear leucocytes, antilipogenic actions, antibacterial activity against Propionibacterium acnes and resistance induction potency in the bacteria. The ethanol extract (0.01%) of Angelica dahurica markedly suppressed neutrophil chemotaxis, comparable to the effect of erythromycin (0.01%), whereas a strong antilipogenic effect was obtained with rhizoma coptidis (Coptis chinensis) extract (0.01%), leading to a higher efficacy than that of retinoic acid (0.01%). Interestingly, only Glycyrrhiza glabra showed a remarkable antibacterial activity against P. acnes, resulting in negligible induction of resistance, in comparison with a marked development of resistance in the bacteria treated with erythromycin. We suggest that an appropriate formulation containing A. dahurica, rhizoma coptidis and G. glabra could be helpful for the prevention and treatment of acne lesions.

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

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Two experiments were conducted in litter floor pens with broiler-type chicks to determine the effect of amprolium-ethopabate, lasalocid, monensin, and lincomycin on growth, feed efficiency, and feathering responses to graded levels of methionine. In Experiment 1, a pea-corn diet was supplemented with 5 levels of methionine (0 to .3%) in combination with amprolium-ethopabate (125 to 140 ppm), lasalocid (125 ppm), or monensin (121 ppm). In the second experiment, two different types of diets (corn-soy and pea-corn) were used which differed primarily in the source of protein. These two diets were supplemented with methionine (.1%), lincomycin (2 ppm), or a combination of lincomycin and methionine. Either lasalocid (100 ppm) or monensin (100 ppm) was used as a coccidiostat.At a suboptimum level of sulfur-containing amino acids (SAA), lasalocid in Experiments 1 and 2 and lincomycin in Experiment 2 were found to have growth and feed efficiency stimulating effects. The SAA requirement for growth was reduced by as much as .1% in the presence of lasalocid. The SAA requirement was not affected by the use of monensin up to 49 days, but it was considerably increased after 49 days due to a faster rate of gain brought on by the withdrawal of monensin from the diet. The different coccidiostats and methionine had significant effects on the score for feathers in the litter and on feather weight. Overall floor-feather score and feather weight were better on the diet containing lasalocid than on diets containing the other two coccidiostats.Growth response to a lincomycin supplement was much more pronounced on the corn-soy or pea-corn diet containing lasalocid and no supplemental methionine than on other combinations. In contrast, growth response to the lincomycin supplement was very small in the presence of added methionine. Lincomycin gave a considerable and a significant growth response in the presence of monensin on the corn-soy and pea-corn diets, respectively. Lincomycin had no effect on growth on the pea-corn diet containing monensin and no added methionine. Even though the monensin fed birds outgained the lasalocid fed birds during the 5-day withdrawal period, their body weight was lower than that of the lasalocid or amprolium fed birds. The growth depressing effect of monensin was also seen at the level of 100 ppm, and this was not counteracted by adding the high level of methionine beyond the NRC (1977) requirement. (

Abstract. ØC31 integrase can integrate targeted plasmid DNA into preferred locations in mammalian genomes, resulting in robust, long-term expression of the integrated transgene. This system represents an effective tool that opens up promising possibilities for gene therapy. The classical treatment for hypoparathyroidism was calcium and vitamin D replacement. Recently, parathyroid hormone (PTH) replacement was reported to be a more potentially physiologic treatment option. However, PTH synthesis is technically difficult and costly. These issues may be minimized by using PTH gene therapy. We attempted to achieve site-specific genomic integration of the PTH gene into a human cell line and mice using this system. We cotransfected 293 HEK cells with PTH-attB plasmid with or without ØC31 integrase plasmid. Expression and secretion of PTH into culture supernatants and site-specific genomic integration of PTH cDNA were assessed by immunoradiometric assays and pseudo-site analysis, respectively. In in vivo experiments, we injected the PTH-attB plasmid with or without ØC31 integrase plasmid into a mouse tail vein using the hydrodynamic method. Plasma PTH concentrations were serially measured, and site-specific integration of PTH cDNA into the mouse genome was confirmed by examining hepatic genomic DNA. PTH was expressed and secreted from 293 HEK cells and mouse hepatocytes, and pseudo-site analysis confirmed the site-specific integration of PTH cDNA into the host genomes. The site-specificity and efficiency of this system are advantageous in many areas, including, potentially, gene therapy. PTH gene therapy is one candidate; however, for clinical applications, we need to regulate PTH expression and secretion in the future. A safe and effective gene delivery system is a prerequisite for clinical gene therapy. Gene therapy has been successfully used in several genetic diseases [1,2], nevertheless, it is far from being popular. A major reason why it has not been established as a general treatment is the lack of a safe and effective gene delivery system. These systems are largely divided into 2 categories: viral and non-viral delivery systems. The former can effectively and efficiently deliver a relatively large gene into the genome; however, the intrinsic biological hazard raises medical concerns about infections and mutations. The non-viral gene delivery

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

ABSTRACT. It is known that Helicobacter hepaticus or Helicobacter bilis infection causes chronic inflammation of the colon and liver. Chronic active hepatitis was found in radiation exposure experiments using male C3H/HeNrs mice at our institute. Histopathologically, 103 cases among 978 mice (64-91 weeks of age at autopsy) had hepatic lesions regardless of irradiation exposure. Mild lesions showed only focal necrosis and focal inflammation in the liver. Severe cases were accompanied by hepatocytomegaly, bile duct hyperplasia, hypertrophy and activation of Kupffer cells, cholangitis, pleomorphic hepatocytes and/or tumor. Helical-shaped bacteria were detected between hepatocytes by Warthin-Starry silver stain and immunohistochemistry (IHC) with an antibody against Helicobacter pylori. It was suggested that these cases of chronic hepatitis were caused by Helicobacter spp. Although chronic hepatitis occurred frequently in mice exposed high-dose irradiation compared with nonirradiated mice in one lot, it was not concluded that radiation might influence the incidence or degree of hepatitis. Our report suggested that natural Helicobacter spp. infection in mice can occur in an experimental animal facility. Therefore, it is suggested that monitoring of Helicobacter infection is very important for quality control of animal experiments.

The Draize test has long been used as a method to evaluate skin irritancy. However, alternative methods have since been developed, in response to pressure from the ever-increasing movement of animal protectionists. Cell culture represents the most promising alternative method, and many trials of various kinds are under way, for example the monolayer culture, skin explant culture and three-dimensional skin equivalent culture. It is quite likely that better-qualified three-dimensional culture systems constitute the final goal in the search for alternative methods to evaluate skin irritancy. However, its effective validation will require not only further large-scale studies, but also the development of superior artificial skin models, with properties more closely resembling those of normal skin. In this review, we focus mainly on the skin equivalent culture method for measuring skin irritancy. Its superiority to other models as well as its problems and limitations are discussed.