Six months studies

The traditional second long-term carcinogenicity study can be replaced by a shorter-term alternative model. In practical terms, this guideline is beginning to result in sponsors conducting a two-year study in the rat and a six-month study in an alternative mouse model, such as the P53 or the TG.AC genetically manipulated mouse strains. 

Meurer, M., Folster-Holst, R., Wozel, G. et al. Pimecrolimus cream in the long-term management of atopic dermatitis in adults a six-month study. Dermatology 2002 205 271-7. 

Six months studies may be acceptable for indications of chronic conditions associated with short-term, intermittent drug exposure, such as bacterial infections, migraine, erectile dysfunction, and herpes. 

Six month studies may be acceptable for drugs intended for treatment of life-threatening diseases for which substantial long-term human clinical data are available, such as cancer chemotherapy in advanced disease or in adjuvant use. 

S. Backman, B. Gunilla, J. Unn-Britt, L. Michael, M. Agneta, S. Ulla, E. Ragnhild Aune, F. Claes, K. Sigbritt, Material wear of polymeric tracheostomy mbes a six-month study. The Laryngoscope 119, 657-664 (2009)... 

The time taken to complete a base line study and EIA should not be underestimated. The baseline study describes and inventorises the natural initial flora, fauna, the aquatic life, land and seabed conditions prior to any activity. In seasonal climates, the baseline study may need to cover the whole year. The duration of an EIA depends upon the size and type of area under study, and the previous work done in the area, but may typically take six months. The EIA is often an essential step in project development and should not be omitted from the planning schedule. 

Human and animal studies indicate that inorganic manganese compounds have a very low acute toxicity by any route of exposure. The toxicity values for a given Mn compound are shown in Table 20 to depend on the species of test animal as well as the route of exposure. Manganese concentrations as high as 2000 ppm were found to be tolerated by test animals over a six-month period without any ill effects (208). 

Aniracetam (6), launched in 1993 in both Japan and Italy for the treatment of cognition disorders, is in Phase II trials in the United States as of this writing. In clinical studies it has been shown to cause some improvement in elderly patients with mild to moderate mental deterioration (63), and in geriatric patients with cerebral insufficiency (64). In a multicenter double-blind placebo-controUed trial involving 109 patients with probable AD, positive effects were observed in 36% of patients after six months of treatment (65), a result repeated in a separate study of 115 patients (66). A review of the biological and pharmacokinetic properties, and clinical results of aniracetam treatment in cognitively impaired individuals is available (49). 

A comprehensive study of the tolerance of laboratory animals to vapors of 2-nitropropane was reported in 1952 (100). In a study pubHshed in 1979, rabbits and rats survived exposure to nitromethane for six months at 750 and 100 ppm, respectively, with no unexpected findings (101). Similarly, no compound-related effects were found for rabbits exposed to 2-nitropropane at 200 ppm or for rabbits or rats exposed at 27 ppm. Liver damage was extensive in male rats exposed at 207 ppm for six months, and hepatocellular carcinomas were observed. Subsequendy, the International Agency for Research on Cancer (lARC) found that there is "sufficient evidence" to conclude that 2-nitropropane causes cancer in rats but that epidemiologic data are inadequate to reinforce the conclusion in humans (102). The National Toxicology Program also concluded that it "may reasonably be anticipated to be a carcinogen" (103). 

A number of studies have shown that vitamins moderate the induction of chromosomal aberrations by radiation. Vitamins C and E given orally to mice either 2 h before, immediately after, or 2 h after 1 Gy (100 rad) of y-ray TBI significantly reduce the frequencies of micronuclei and chromosomal aberrations in BM cells. Vitamin E is the more effective (95). Administration of vitamins C and E within 5 min of irradiation is as effective as pretreatment. Protection by vitamin C has also been shown in humans. Whereas chronic treatment of rats using vitamin C (100 or 300 mg/(kg/d)) for six months prior to TBI protects against chromosomal aberrations, vitamin E is not radioprotective in this setting (96). 

Internal antistats are considered permanent antistats. This permanence is based on the concept that most plastic products are disposable, so that the antistat is not required to last long. The antistatic effectiveness of an internal antistat can decrease over time. One study showed large increases in surface resistivity on antistatic bags stored at 71 °C for six months. Antistatic bags stored at room temperature showed only a small increase in surface resistivity (137). Loss of antistatic effectiveness is attributed to the volatility of the antistatic agent. The antistat does not easily wear off the plastic, but it can be removed with solvents and/or repeated wear. 

In 1907, she went to Berlin to study under Max Planck, promising her devoted parents that she would return to Vienna in six months at the most. She stayed in Berlin for thirty-one years. In Berlin, Meitner met Otto Flahn, a professor of chemistiy, and took an unpaid position assisting Flahn with his research on the chemistry of radioactive substances. At that time women were not allowed to v ork in the Chemical Institute, and she had to set up her laboratory in a carpenter s workshop outside the Institute. 

The hardness of such coatings may reach a maximum of about 400 Hy as compared with approximately 50 Hy for a soft gold deposit. A series of corrosion studies in industrial and marine atmospheres by Baker" has indicated that the protective value of hard gold coatings is comparable with that of the pure metal, and that a thickness of only 0-002 5 mm gives good protection to copper base alloys during exposure for six months. 

They also seeded autologous vSMC and ECs obtained from ovine carotid arteries to study autologous tissue-engineering blood vessels in the descending aorta of juvenile sheep. They found that after three months implantation, grafts were fully patent, without dilatation, occlusion, or intimal thickening. A continuous luminal EC layer was formed. However, after six months ... 

The mean dietary intake of soy isoflavones in Asian populations consuming soy-based diets ranges from 20-40 mg isoflavones/day, with upper percentile consumer intakes of 70 mg/day (corresponding to around 1 mg/kg body weight). In the six month intervention studies in Western postmenopausal women, the effective dose for improved BMD was around 80-90 mg/day, while in the one year, randomized, double-blind, placebo controlled clinical trial, the effective dose was 54 mg/day. Overall, the dietary recommendation is to consume 50 mg isoflavones/day in combination with standard nutritional requirements for calcium and vitamin D. 

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