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The paper reports experimental radioisotopic animal studies of the inclusion of lysine 1C14, P32, and Ca45 in the mineral fraction of molars and bones of rats after semilateral application of fluoride lacquer
The author reviews the prevalence of onychomycoses and the factors influencing it. Among the precipitating factors, age and various predisposing diseases play a role in the development of the disease play a role in the development of the disease. The problem affects the toenails more frequently than the fingernails. Distal subungual onychomycosis caused by dermatophytons is most often seen among the various types of the disease. Yeasts and moulds mainly act as contaminants. New diagnostic methods facilitate more precise diagnosis but they cannot replace basic mycological investigations. Orally administered antifungal agents have appeared in the foreground of treatment. Among them fluconazole, itraconazole and terbinafin derivatives can safely be applied in combination with certain cauterants. Each of the three agents are effective in approximately 70-80% of cases, especially when applied on fingernails. Combined therapy, such as the application of oral antimycotics and antifungal lacquerers or oral treatment accompanied by the surgical, laser or chemical removal of the affected nail regions, can improve the results. Surviving fungal residues in the substance of the nail may restart the disease. Relapse may also be attributed to neglecting the desinfection of shoes. When choosing the drugs, drug interaction should also be considered. The above three oral antimycotics have few (1-20%) side effects, gastrointestinal ones being the most common among them. A transitory elevation in hepatic enzyme levels may sometimes occur but the changes go back to normal after treatment is over.
Despite the appearance of the new systemic drugs there is still an incompressible failure rate in treating patients affected by onychomycosis. Moreover some patients are unable or unwilling to take oral drugs. They perceive the infection to be too trivial to deserve systemic therapy. In addition the use of the new potent systemic drugs may sometimes be limited by adverse effects and drug-drug interactions. A rationale for a stepped therapeutic approach to the treatment of onychomycosis is suggested using the transungual antifungal delivery systems, the systemic antifungal drugs and surgical or chemical debridement. Long-term management with the nail lacquers applied twice a month should still improve the cure rate and its economic implication.
The clinical management of severe onychomycosis is known to be a long and difficult task. When deciding which treatment to prescribe to our patients we may be tempted to use the efficacy rate as the only objective measurement or on the other hand to assess treatment costs only by looking at the drug acquisition cost. The role of pharmacoeconomics is to provide a method that evaluates outcomes and costs at the same time; it is an aid to better decision making. Cost effectiveness studies take into account the efficacy of each treatment regimen balanced against the global cost of treatment. So we can assess the number of patients cured for a given health care budget. Two recent studies presenting the results of a combination therapy of an antifungal therapy and antifungal lacquer give us the opportunity to illustrate some pharmacoeconomic principals.
BACKGROUND: Propylene glycol mono-t-butyl ether is used as a solvent in all-purpose cleaners, inks, and nail polish lacquers. We studied the effects of propylene glycol mono-t-butyl ether on male and female rats to identify potential toxic or cancer-related hazards to humans. METHODS: We exposed groups of male and female rats and mice to air containing vapors of propylene glycol mono-t-butyl ether at concentrations of 75, 300, or 1,200 parts per million (ppm) for 6 hours per day, 5 days a week for 2 years. Untreated control animals were housed in similar exposure chambers but without chemical exposure for comparison. Tissues from more than 40 sites were examined for every animal. RESULTS: Rats receiving 1,200 ppm propylene glycol mono-t-butyl ether weighed less on average than the control animals. Tumors were seen in the liver and kidney of a few male rats exposed to propylene glycol mono-t-butyl ether. No increases in the numbers of tumors were seen in female rats. In male and female mice there were large increases in the numbers of liver tumors compared with the control animals. CONCLUSIONS: We conclude that propylene glycol mono-t-butyl ether caused cancer in the liver of male and female mice. Propylene glycol mono-t-butyl ether did not cause cancer in female rats, and its effect on the liver and kidney of male rats was considered uncertain.
Based on the concept that tumor suppressor genes are involved in the pathogenesis of urinary bladder carcinogenesis, we analysed the mRNA expression of the retinoblastoma (Rb) and p16 (CDKN2, INK4A, MTS1) genes as well as of the proto-oncogene cyclin D-dependent kinase 4 (CDK4) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and with reference to certain lifestyle and occupational risk factors. Using real-time quantitative reverse transcription-polymerase chain reaction, high-stage muscle invasive TCC expressed the Rb, p16 and CDK4 mRNA at lower levels than low-stage superficial cancers, indicating down-regulation to be linked with tumor progression. The drop of the expression in the group of grade 2 TCC when invading the muscle layer compared to grade 2 carcinomas with a superficial pattern of growth is considered to represent a key event in promoting urothelial carcinogenesis in this subset of carcinomas. The protein expression of the Rb gene evaluated by immunohistochemistry proved to be closely related to the tumor grades and stages as well as to the mRNA expression, high-grade and high-stage TCC disclosing a lower rate of positive immunoreactivity than low-grade and low-stage carcinomas. The p16 protein product was expressed at a lower level in grade 3 than in grade 1 TCC, but there was no correlation with the tumor stages or the mRNA expression. TCC with loss of heterozygosity (LOH) at the INK4A region showed a decreased expression of p16 mRNA compared to those without an allelic loss. Tobacco smoke was not identified to substantially modulate the Rb/p16/CDK4 pathways, except for a ten-fold elevated mRNA expression of the p16 gene in TCC of light compared to heavy smokers. Heavy coffee consumption was associated with a reduced expression of CDK4 mRNA. Among occupational exposures, TCC of patients in contact with stone dust, paints and lacquer, plastics, wood and wood preservers and chemical solvents and adhesives displayed altered partly elevated, partly reduced levels of Rb, p16 and CDK4 mRNA compared to non-exposed subjects. Although the underlying molecular-genetic pathways are not yet fully understood, the current results suggest functional reduction of the tumor suppressor genes Rb and p16 to be associated with progression of bladder cancer to a more malignant and aggressive behaviour.
Treatment of onychomycosis is associated with substantial disease reappearance rates. Identification of factors associated with therapeutic failure may help develop strategies to prevent recurrence of onychomycosis. Aspects of a patient's health and lifestyle, local factors involving the nail, therapeutic options, and environmental conditions are associated with poor therapeutic response. Strategies to reduce recurrence of disease involve the reduction of both relapse (delayed failure) and reinfection. The topical antifungal agent ciclopirox nail lacquer, may be a consideration for prophylaxis of this chronic disease.
Transitional cell carcinomas (TCC) of the urinary bladder develop by a multistep process characterized by various stages of transformation differing in their grade of malignancy and biological behaviour. Since the prospective clinical outcome cannot be reliably predicted on histopathological grounds, we analysed the mRNA expression of the MDM2-p73-P14ARF tumour surveillance pathway in an attempt to detect alterations of gene activity, allowing a better understanding of the mechanisms responsible for conversion of low to high malignant TCC. Expression of the mRNA was determined in 71 TCC of various grades and stages using the real-time quantitative reverse transcription-polymerase chain reaction. The MDM2-p73-P14ARF pathway was dominated by the MDM2 gene, the mRNA expression of which proved to be significantly (5-fold) lower in advanced high-grade, high-stage than in superficial low-grade, low-stage TCC. Conversely, the expression of p73 mRNA increased with increasing tumour grades and stages, while the activity of the P14ARF gene was not substantially altered during early and late phases of urothelial carcinogenesis. Analysing the expression of spliced variants of MDM2 mRNA, we found a heterogeneous pattern including a novel splicing transcript coding for an abnormal protein. Promoter hypermethylation of P14ARF occurred in 10% of the TCC with an under-expression of mRNA. An analysis of the effects of lifestyle and occupational bladder cancer risk factors revealed that TCC of smokers showed a 2-fold elevated expression of MDM2 mRNA and an approximately 2-fold lower expression of P14ARF mRNA, whereas the activity of the p73 gene was unchanged. Heavy coffee consumption was associated with a 2-fold decreased expression level of P14ARF mRNA. Exposure to certain occupational hazards (plastic products, paints and lacquer, polycyclic hydrocarbons, chemical solvents) was observed to modulate the activity of the genes analysed. Our findings suggest that an alteration in the MDM2-p73-P14ARF pathway is involved in the progression of bladder cancer to a more malignant and aggressive form.
Neoangiogenesis is assumed to play an important role in the progression, metastasis and prognosis of a wide variety of tumors. To get insights into the molecular-genetic pathways and the biological role of angiogenesis in urothelial carcinogenesis, we analyzed comparatively the expression of the mRNA of the vascular endothelial growth factor (VEGF) and of the angiopoietins-1 and -2 (Ang-1 and Ang-2) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and referring to epidemiological risk factors. Using real-time quantitative reverse transcription-polymerase chain reaction, low-stage superficial TCC expressed VEGF and Ang-2 mRNA at a significantly higher level than high-stage muscle invasive carcinomas, and low-grade TCC at an insignificantly higher level than high-grade tumors. The activity of both angiogenic factors was found to be significantly correlated. Conversely, Ang-1 mRNA was expressed at a 3-fold significantly lower level in low-grade, low-stage compared to high-grade, high-stage TCC. A significantly 3- and 2-fold respectively, drop of the VEGF and Ang-2 mRNA expression in conjunction with a 2-fold significantly higher expression of Ang-1 mRNA in the group of grade 2 TCC when infiltrating the muscle layer may represent a crucial event during urothelial carcinogenesis, and possibly indicates an important step in promoting the conversion of bladder cancer from a low to a high malignancy in this subset of carcinomas. By immunhistochemistry, high-grade, high-stage carcinomas less frequently displayed areas with a strong reactivity for the VEGF protein ('hot spots") than low-grade, low-stage TCC, paralleling the expression of the mRNA. The expression patterns observed are compatible with a reduced vascular destabilization and decreased formation of new blood vessels in advanced TCC, suggesting a balance between vessel regression and vascular growth, with a less pronounced vascular remodeling during late phases of urothelial carcinogenesis. Analyzing the effect of life-style bladder cancer risk factors, habitual smoking and coffee consumption was not observed to substantially alter the expression of the angiogenic mediators, except for weakly elevated levels of VEGF and Ang-2 mRNA in TCC of strong smokers and a borderline significantly decreased VEGF mRNA expression associated with heavy coffee consumption. Certain hazardous occupational exposures (polycyclic hydrocarbons, paints and lacquer, stone dust) may play a role in modulating tumor angiogenesis. The current data indicate that the signaling molecular-genetic pathways underlying vascular remodeling are involved in the progression of urinary bladder cancer to a more malignant and aggressive behaviour.
The authors review the literature on the contact allergy to acrylate plastics used in many branches of industry, construction, dental prosthetics, conservative dentistry, orthopedics and also in the production of glue, binding materials, and lacquers, especially printer's ink. The most frequent sources of non-occupational allergy are presented. In addition, the authors draw attention to new allergy-producing chemical compounds, difficulties in the interpretation of skin test results, mostly because of polyvalence of allergy to acrylates, and to characteristic clinical picture of skin changes.
UNLABELLED: Stoddard solvent (white spirit/mineral spirit) is the most widely used solvent in the paint industry. It is used as a dry cleaning agent; as an extraction, cleaning, and degreasing solvent; and as a solvent in aerosols, paints, wood preservatives, asphalt products, lacquers, and varnishes. Stoddard solvent IIC was nominated by the International Union, United Auto Workers, for carcinogenicity testing because of the large volume used in industrial and other settings. Male and female F344/N rats and B6C3F1 mice were exposed to Stoddard solvent IIC (greater than 99% pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 16 days. All rats survived to the end of the study, and mean body weights of all exposed groups were similar to those of the chamber controls. Liver weights of males exposed to 550 mg/m3 or greater and of females exposed to 275 mg/m3 or greater were increased. Minimal diffuse cytoplasmic vacuolization of hepatocytes of the liver occurred in all females exposed to 2,200 mg/m3. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 17 days. All mice survived to the end of the study, and mean body weights of all exposed groups were similar to those of the chamber controls. Liver weights of males and females exposed to 275 mg/m3 or greater were significantly increased. Cytomegaly of the liver occurred in all males and females exposed to 2,200 mg/m3. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 14 weeks. All rats survived to the end of the study, and the final mean body weight of females exposed to 275 mg/m3 was greater than that of the chamber controls. The relative kidney, liver, and testis weights of all exposed groups of males and the absolute kidney weights of males exposed to 550 mg/m3 or greater were increased. The sperm motility of 550 mg/m3 or greater males was significantly decreased. The incidences of renal tubule granular casts were significantly increased in males exposed to 550 mg/m3 or greater, and the severities of renal tubule hyaline droplet accumulation, granular casts, and regeneration increased with increasing exposure concentration in males. The incidences of goblet cell hypertrophy of the nasal respiratory epithelium in males and females exposed to 2,200 mg/m3 were significantly increased. Sperm motility was decreased in males exposed to 550 mg/m3 or greater. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 14 weeks. Mean body weights of exposed groups were similar to those of the chamber controls, but liver weights of males exposed to 2,200 mg/m3 were significantly increased. The sperm motility of 2,200 mg/m3 males was significantly decreased. This reduction in sperm motility, while statistically significant, is probably of modest importance as studies in mice have found that fertility is unaffected by motility decreases of less than 40%. The incidences of hematopoietic cell proliferation of the spleen in all exposed groups of females were greater than that in the chamber controls. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138 (males), 550, 1,100, or 2,200 (females) mg/m3, 6 hours per day, 5 days per week for 104 to 105 weeks. Additional groups of 10 males and 10 females were exposed to the same concentrations for 3 months for renal toxicity analyses. Survival in the top exposure concentration groups of males and females was significantly less than that of the chamber controls. Mean body weights of exposed males and females were similar to those of the chamber controls. Cell proliferation analyses were performed in the left kidney of males and females after 3 months of exposure. The mean numbers of labeled cells and the labeling indices in males exposed to 550 and 1,100 mg/m3 were significantly increased. The amount of alpha2u-globulin in the right kidney of males increased with increasing exposure concentration. Also, the incidences of granular casts and cortical tubule degeneration and regeneration were generally increased in exposed males, as was the severity of hyaline droplets. These effects did not occur in females. At 2 years, the incidences of benign and benign or malignant pheochromocytoma (combined) of the adrenal medulla occurred with positive trends in males, and the incidences in the 550 and 1,100 mg/m3 groups were significantly increased. Due to increased incidences of renal tubule hyperplasia in males at 2 years, extended kidney evaluations were conducted; a slightly increased incidence of renal tubule adenoma occurred in the 1,100 mg/m3 group. Nonneoplastic lesions related to Stoddard solvent IIC exposure occurred in the kidney of males. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 105 weeks. Survival of exposed mice was similar to that of the chamber controls. Mean body weights of exposed females were greater than those of the chamber controls. The incidences of hepatocellular adenoma occurred with a positive trend in females, and the incidence of multiple hepatocellular adenoma in females exposed to 2,200 mg/m3 was significantly increased. However, the incidences of hepatocellular adenoma or carcinoma (combined) and hepatocellular carcinoma alone in exposed males and females were not significantly increased. GENETIC TOXICOLOGY: Stoddard solvent IIC was tested for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535, with and without S9 metabolic activation enzymes; all results were negative. In vivo, the frequency of micronucleated erythrocytes was assessed in peripheral blood samples from male and female B6C3F1 mice after 3 months of inhalation exposure to Stoddard solvent IIC, and results were negative. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of Stoddard solvent IIC in male F344/N rats based on increased incidences of adrenal medulla neoplasms; the slightly increased incidences of renal tubule adenoma may have been related to Stoddard solvent IIC exposure. There was no evidence of carcinogenic activity of Stoddard solvent IIC in female F344/N rats exposed to 550, 1,100, or 2,200 mg/m3. There was no evidence of carcinogenic activity of Stoddard solvent IIC in male B6C3F1 mice exposed to 550, 1,100, or 2,200 mg/m3. There was equivocal evidence of carcinogenic activity of Stoddard solvent IIC in female B6C3F1 mice based on increased incidences of hepatocellular adenoma; this slight increase was associated with increased body weight in exposed females. Exposure of male rats to Stoddard solvent IIC resulted in nonneoplastic lesions of the kidney characteristic of alpha2u-globulin accumulation.
Decalin is used as an industrial solvent for naphthalene, fats, resins, oils, and waxes. It is also used as a substitute for turpentine in lacquers, paints, and varnishes; as a solvent and stabilizer for shoe polishes and floor waxes; and as a constituent of motor fuels and lubricants. Other applications include use as a paint thinner and remover, a patent fuel in stoves, a high-density fuel in submarine-launched cruise missile systems, and in stain removal and cleaning machinery. Decalin was nominated for study by the National Cancer Institute because of its chemical structure, its potential for consumer exposure, and a lack of adequate testing of the chemical. Male and female F344/N rats and B6C3F(1) mice were exposed to decalin (greater than 99% pure) by inhalation for 2 weeks, 3 months, or 2 years. Groups of male NBR rats were exposed to decalin for 2 weeks. Male NBR rats do not produce alpha2u-globulin; the NBR rats were included to study the relationship of alpha2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. 2-WEEK STUDIES IN RATS: Groups of five male and five female F344/N rats and five male NBR rats were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 16 days. All rats survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber controls. Renal toxicity studies were performed in male F344/N and NBR rats. The numbers of labeled cells and the labeling indices in the left kidney of 200 and 400 ppm F344/N male rats were significantly greater than those in the chamber controls. The alpha2u-globulin/soluble protein ratios were significantly increased in all exposed groups of F344/N rats. Liver weights of male F344/N and NBR rats exposed to 100 ppm or greater were significantly increased, as were those of all exposed groups of females. Kidney weights of male F344/N rats exposed to 50 ppm or greater were significantly increased. Exposure-related hyaline droplet accumulation, degeneration and regeneration of renal cortical tubules, and granular casts occurred in the kidney of exposed F344/N male rats. 2-WEEK STUDIES IN MICE: Groups of five male and five female B6C3F(1) mice were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 17 days. All mice survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber control groups. Liver weights of 200 and 400 ppm males and females and 100 ppm females were significantly increased. 3-MONTH STUDY IN RATS: Groups of 25 male and 20 female F344/N rats were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 2 (five male renal toxicity rats), 6 (10 male and 10 female clinical pathology rats), or 14 (10 core study rats) weeks. All rats survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber control groups. Urinalysis results indicated that decalin exposure caused increases in urine glucose and protein concentrations and enzyme activities that were consistent with the renal lesions observed microscopically. Renal toxicity studies were performed on rats sacrificed at 2 and 6 weeks and at the end of the study. In kidney tissue examined for cell proliferation, the numbers of PCNA-labeled cells and labeling indices were generally significantly greater than those of the chamber controls in exposed groups of rats at all three time points. Concentrations of alpha2u-globulin in the kidney as well as the alpha2u-globulin/soluble protein ratios were significantly increased at week 2 in all exposed groups and in the 200 and 400 ppm groups at week 6 and at the end of the study. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm or greater were increased. Incidences of renal tubule regeneration and granular casts in the medulla of the kidney in exposed male rats were increased, and the severities of hyaline droplets generally increased with increasing exposure concentration. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female B6C3F(1) mice were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 14 weeks. All mice survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber control groups. Liver weights of 200 and 400 ppm males and females were significantly increased. There was a significant exposure concentration-related decrease in the absolute spermatid head count and a significant decrease in absolute head count of the 400 ppm group compared to the chamber controls. Incidences of centrilobular cytomegaly of the liver were increased in exposed male mice. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to 0, 25, 50 (male rats only), 100, or 400 ppm (female rats only) decalin vapor 6 hours per day, 5 days per week for 105 weeks. A group of 20 male rats was exposed to 400 ppm. Survival of exposed groups was similar to that of the chamber control groups. Mean body weights of 400 ppm males were slightly less than those of the chamber controls during the second year of the study. Incidences of renal tubule adenoma and adenoma or carcinoma (combined) and of benign or malignant pheochromocytoma (combined) of the adrenal medulla in 100 and 400 ppm males were significantly increased. There was a significant association between nephropathy severity and adrenal pheochromocytoma incidence. Nonneoplastic lesions related to decalin exposure occurred in the kidney of male rats. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F(1) mice were exposed to 0, 25, 100, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 105 weeks. Survival of exposed mice was similar to that of the chamber controls. Mean body weights of exposed groups were generally similar to those of the chamber control groups throughout the study. Increased incidences of hepatocellular neoplasms occurred in 25 and 400 ppm female mice, and the incidences of centrilobular hypertrophy, necrosis, syncytial alteration, and erythrophagocytosis of the liver in 400 ppm males were significantly increased. The incidences of uterine stromal polyp and stromal polyp or stromal sarcoma (combined) occurred with positive trends in female mice. PHARMACOKINETIC MODEL: The rate of metabolism of decalin was the same for males and females in rats and mice. Also in rats and mice, decalin metabolism was saturated at less than 400 ppm. Increased labeling indices in male rats were likely due to changes related to alpha2u-globulin. GENETIC TOXICOLOGY: Decalin was not mutagenic in S. typhimurium strains TA97, TA98, TA100, or TA1535, with or without induced hamster or rat liver S9 enzymes. A small but significant increase in the frequency of micronucleated normochromatic erythrocytes was noted in male mice exposed to decalin for 3 months; however, no induction of micronuclei was observed in female mice. CONCLUSIONS: Under the conditions of these studies, there was clear evidence of carcinogenic activity of decalin in male F344/N rats based on increased incidences of renal tubule neoplasms. The increased incidences of benign or malignant pheochromocytoma (combined) of the adrenal medulla in male rats were also considered to be exposure related. There was no evidence of carcinogenic activity of decalin in female F344/N rats exposed to 25, 100, or 400 ppm. There was no evidence of carcinogenic activity of decalin in male B6C3F(1) mice exposed to 25, 100, or 400 ppm. There was equivocal evidence of carcinogenic activity of decalin in female B6C3F(1) mice based on marginally increased incidences of hepatocellular and uterine neoplasms. Exposure of male rats to decalin resulted in nonneoplastic lesions of the kidney characteristic of alpha2u-globulin accumulation. Nonneoplastic lesions of the liver were observed in male mice exposed to decalin.
OBJECTIVE: To investigate the mechanism of retinal apoptosis in chick experimental myopia and the therapy of Caspase 3 inhibitor Ac-DEVD-CHO. METHODS: Chick myopia was induced by lid-suture. After Ac-DEVD-CHO had been injected into vitreous, myopia was confirmed by optometry. Subsequently, chick eyeballs removed were measured its extro-dimensions, and the change of fundus were observed. Retinal apoptotic cells were determined by electron microscopy, TUNEL technique and flow cytometry. Retinal Caspase 3 proteins and its activities were measured by immunohistochemistry, flow cytometry and a colorimetric method using Ac-DEVD-pNA as a substrate. RESULTS: Ocular diopters and extro-diameters in all sutured eyes remarkly increased in comparison with its control eyes at 12 weeks after lid-suture. Lacquer crack lesions were found in 41 of 90 sutured eyes (45.56%). Apoptotic cells were observed in retinal outer and inner nuclear layer of the sutured eyes, and its apoptotic rate was significantly more than in control eyes (P < 0.05). Moreover, the expression of retinal Caspase 3 proteins and its activities were increased. After Ac-DEVD-CHO was injected into vitreous, the decrease of retinal apoptotic rate, Caspase 3 proteins and its activities was found. The treated effect of Ac-DEVD-CHO was in a dose dependent manner. CONCLUSIONS: Caspase 3 plays an important role in retinal apoptosis of chick myopia. Ac-DEVD-CHO can effectively ameliorate retinal apoptosis by blocked the effect of Caspase 3.
INTRODUCTION: Mushroom-shaped choroidal melanoma is known to be associated with breaks in Bruch's membrane and is more likely to develop when Bruch's membrane is diseased. The study's goal is to determine if diseases causing breaks in Bruch's membrane predispose a choroidal melanoma to develop into a mushroom-shaped melanoma. MATERIALS AND METHODS: A retrospective review of cases of choroidal melanoma seen at our institution was carried out to determine if mushroom-shaped melanomas are more common than dome-shaped tumours in patients with macular abnormalities involving a loss of Bruch's membrane integrity. Forty-nine eyes of 48 patients were included in this retrospective study. A dome-shaped or mushroom-shaped configuration was assigned to each tumour. Macular degeneration, macular drusen, retinal pigment epithelial (RPE) stippling, macular oedema, choroidal neovascularisation (CNV), angioid streaks, disciform scars, lacquer cracks, and myopia greater than -3.00 D, were considered to constitute evidence of potential Bruch's membrane breaks and were determined in both eyes. A chi-square evaluation was used to compare the proportion of eyes with macular abnormalities in the 2 tumour configuration groups. RESULTS: The tumour was dome-shaped in 40 eyes (82%) and mushroom-shaped in 9 eyes (18%). Macular abnormalities, indicative of loss of Bruch's membrane integrity, were seen in 21 (53%) of 40 eyes with dome-shaped melanomas and 5 (56%) of 9 eyes with mushroom-shaped melanomas. The proportion of eyes with macular abnormalities was not statistically different between the dome-shaped and mushroom-shaped tumours, as assessed by chi-square analysis (P = 0.87). CONCLUSIONS: Bruch's membrane disease does not influence the differentiation of choroidal melanoma into mushroom-shaped or dome-shaped tumour growth patterns.
OBJECTIVE: To study the apoptosis of retina and the expression of c-myc protein in form-deprivation myopia. METHODS: Two-day-old chickens were sutured with right eyelid for 4, 8 and 12 weeks. After measurement of refracation, the eyeballs were observed by light microscope and taken photos. Retinal apoptotic cells were measured by TUNEL staining and flow cytometry. C-myc protein were examined by immunohistochemistry and flow cytometry. RESULTS: Lacquer crack lesions were found in sutured eyes at 12 weeks. Apoptotic cells were observed in retinal outer and inner nuclear layer of the sutured eyes at 12 weeks and obvious peak of apoptosis was observed in sutured eyes at 12 weeks. The expression of c-myc protein was significantly more than control eyes at 8 and 12 weeks. CONCLUSION: The apoptosis of retinal was present in form-deprivation myopia with the degeneration of retina. C-myc protein plays an important role in retinal apoptosis of myopia.
Endogenic auto-rosetting in peripheral blood was studied in workers exposed to paint-and-lacquer materials. Findings are increased numbers of general auto-rosettes and of auto-rosettes with extracellular RBC lysis (p < 0.001). That was associated with decrease of RBC and hemoglobin (p < 0.01).
Because of its availability, the skin has been used over the years for self-experimentation. Many examples can be cited, including the heroic self-experiments of Carrión of Peru with verruga peruana and those of Goldberger with pellagra and Pediculoides ventricosus. My personal self-experimentation began with sensitization to Japanese lacquer. From that starting point I experimented with chemical warfare agents, cortisone versus hydrocortisone, bites of various arthropods, and finally, experiments with lasers. Some dermatologists will continue to do self-experimentation when they acquire infections from their patients. I believe that sometimes, for their patients' benefit, they should go first.
The most frequent cause of porphyria attacks in this time period were drugs used in symptomatic treatment (in 69 out of 195 cases). In 42 women attacks were induced by sex hormone disturbances, in 21 cases by contact with paints and lacquer in 7 by alcohol and in 3 by calorie deficiencies. The main cause of porphyria attacks in carriers of this metabolic error is lack of porphyria considering in the differential diagnosis of abdominal pains, polyneuropathy and vague mental disorders, which leads to erroneous treatment worsening the course and prognosis of the disease.