Ethoxy mansonone G as an anticancer agent in estrogen receptor-positive and endocrine-resistant breast cancer.

OBJECTIVES: To study anticancer effects, underlying mechanism and safety of ethoxy mansonone G (EMG) which is the potent derivative of mansonone G (MG) in breast cancer cells. METHODS: Anticancer, antimigration, anti-invasion effects and anchorage-independent growth were investigated by MTT, scratch, matrigel invasion and soft agar assays. Estrogen receptor (ER)-targeted genes and endocrine-resistant genes were assessed by RT-PCR and Western blot. KEY FINDINGS: Ethoxy mansonone G is the most potent MG derivative and has anticancer effects in ER-positive, endocrine-resistant and ER-negative breast cancer cells. Our results demonstrated that EMG can significantly inhibit estrogen-induced cell proliferation and the expression of ER-targeted genes in ER-positive breast cancer cells, suggesting the anti-estrogenic property of EMG which is consisting with the virtual molecular docking that EMG could possibly bind to the ERα. Moreover, EMG has synergistic effect with tamoxifen in endocrine-resistant cells. EMG also inhibited cell proliferation, invasion and anchorage-independent growth by reducing expression of genes involved in endocrine resistance and invasive factors during the metastatic process. CONCLUSION: Ethoxy mansonone G has an anticancer effect in breast cancer cells and is possible to use as a therapeutic agent in patients with breast cancer.

A subchronic (180-day) oral toxicity study of ethyl tertiary-butyl ether, a bioethanol, in rats.

A subchronic (180-day) toxicity study was conducted to evaluate the effects of ethyl tertiary-butyl ether (ETBE), a biomass fuel, in male and female rats. ETBE was administered at dose levels of 0, 5, 25, 100 and 400 mg/kg/body weight (b.w.)/day by gavage. No treatment-related adverse effects were observed at 5, 25 or 100 mg/kg. Centrilobular hypertrophy of hepatocytes was observed in males and females and their relative liver weights were increased, suggesting enhanced metabolic activity. From these results, we concluded that the no observed adverse effect level of ETBE was 100 mg/kg b.w./day under the conditions tested.

Lack of micronucleus induction activity of ethyl tertiary-butyl ether in the bone marrow of F344 rats by sub-chronic drinking-water treatment, inhalation exposure, or acute intraperitoneal injection.

Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice. These reports raise concern about the effects of human exposure being brought about by the increased use of ETBE. The present study was conducted to evaluate the genotoxicity of ETBE using micronucleus induction of polychromatic erythrocytes in the bone marrow of male and female rats treated with ETBE in the drinking-water at concentrations of 0, 1,600, 4,000 or 10,000 ppm or exposed to ETBE vapor at 0, 500, 1,500 or 5,000 ppm for 13 weeks. There were no significant increases in micronucleus induction in either the drinking water-administered or inhalation-administered groups at any concentration of ETBE; although, in both groups red blood cells and hemoglobin concentration were slightly reduced in the peripheral blood in rats administered the highest concentration of ETBE. In addition, two consecutive daily intraperitoneal injections of ETBE at doses of 0, 250, 500 or 1,000 mg/kg did not increase the frequency of micronucleated bone marrow cells in either sex; all rats receiving intraperitoneal injections of ETBE at a dose of 2,000 mg/kg died after treatment day 1. These data suggest that ETBE is not genotoxic in vivo.

No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats.

The carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined by oral administration using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats were given drinking water containing ETBE at doses of 0, 625, 2,500 or 10,000 ppm (w/w) for 104 weeks. No significant increase in the incidence of tumors was detected in any organ of either sex. Rat-specific non-neoplastic lesions were observed in the kidney: An increase in the severity of chronic progressive nephropathy was observed in the male and female 10,000 ppm groups, and increased incidences of urothelial hyperplasia of the pelvis and mineral deposition in the renal papilla were observed in the male 2,500 and 10,000 ppm groups. Besides these lesions, no treatment-related histopathological changes were observed in any organ or tissue in either sex. Thus, the present study demonstrated that a two year administration ETBE in the drinking water did not exert any carcinogenic effects in either male or female rats.

Toxicology and carcinogenesis studies of bis(2-chloroethoxy)methane (CAS No. 111-91-1) in F344/N rats and B6C3F1 mice (dermal studies).

UNLABELLED: Bis(2-chloroethoxy)methane is used as a solvent and the starting agent in the production of fungicides and polysulfide polymers. Bis(2-chloroethoxy)methane was nominated for study by the National Institute of Environmental Health Sciences because of its widespread use as a starting material to produce polysulfide elastomers, and because there were no 2-year carcinogenicity studies reported in the literature. Male and female F344/N rats and B6C3F1 mice received dermal applications of bis(2-chloroethoxy)-methane in ethanol (greater than 98% pure) for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli, rat bone marrow cells, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were dermally administered 0, 12.5, 25, 50, 100, or 200 mg bis(2-chloroethoxy)methane/kg body weight in ethanol, 5 days per week for 16 days. All rats survived to the end of the study. Mean body weights of dosed rats were similar to those of the vehicle control groups. There were no histopathologic lesions related to bis(2-chloroethoxy)methane administration. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were dermally administered 0, 12.5, 25, 50, 100, or 200 mg bis(2-chloroethoxy)methane/kg body weight in ethanol, 5 days per week for 17 days. All mice survived to the end of the study. Mean body weights of dosed mice were similar to those of the vehicle control groups. There were no histopathologic lesions related to bis(2-chloroethoxy)methane administration. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were dermally administered 0, 50, 100, 200, 400, or 600 mg bis(2-chloroethoxy)methane/kg body weight in ethanol, 5 days per week for 14 weeks. Additional clinical pathology groups of 10 male and 10 female rats were administered the same doses for 23 days. All core study 600 mg/kg males and females and two 400 mg/kg females died before the end of the study. The cause of death was considered to be related to the cardiotoxic effect of bis(2-chloroethoxy)methane. There were no significant differences between final mean body weights of dosed rats and those of the vehicle control groups; the mean body weight gain of 400 mg/kg males was significantly less than that of the vehicle controls. Clinical findings included prostration and ataxia in 600 mg/kg rats during the first week of the study and nasal/eye discharge, lethargy, ataxia, and abnormal breathing in 400 and 600 mg/kg females beginning week 5. An enlarged heart was noted in one 100 mg/kg female rat. Relative kidney weights of 100, 200, and 400 mg/kg males were significantly greater than that of the vehicle control group. Increased incidences and severities of myofiber cytoplasmic vacuolization and interstitial mononuclear cell infiltration in the heart occurred in 400 and 600 mg/kg male and female rats and in 200 mg/kg females. Increased incidences and severities of myofiber necrosis occurred in 600 mg/kg males and females; one female each in the 200 and 400 mg/kg groups also had this lesion. Three 600 mg/kg males had atrial thrombosis. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were dermally administered 0, 50, 100, 200, 400, or 600 mg bis(2-chloroethoxy)methane/kg body weight in ethanol, 5 days per week for 14 weeks. Except for three 600 mg/kg females, all mice survived to the end of the study. Mean body weights of dosed and vehicle control mice were similar. One 600 mg/kg female that died early exhibited lethargy, abnormal breathing, and tremors, and one animal had clonic seizures. One 600 mg/kg female that died early had focal erosion of the glandular stomach and a focus in the duodenum found to consist of acute suppurative inflammation and thrombosis. Absolute and relative kidney weights of 400 and 600 mg/kg males and 600 mg/kg females were significantly greater than those of the vehicle control groups. Absolute liver weights of 400 and 600 mg/kg females were also significantly increased. Significantly increased incidences of myofiber cytoplasmic vacuolization occurred in 400 and 600 mg/kg females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were dermally administered 0, 75, 150, or 300 mg bis(2-chloroethoxy)methane/kg body weight in ethanol, 5 days per week for 105 weeks. Survival of all dosed groups of rats was generally similar to that of the vehicle controls. Mean body weights of dosed rats were similar to those of the vehicle controls throughout the study. Clinical findings in 300 mg/kg females that died during the first year of the study included abnormal breathing, lethargy, thinness, nasal discharge, and ataxia. Significantly increased incidences of degeneration of the olfactory epithelium in the nose occurred in all dosed groups of males and in 150 and 300 mg/kg females. The incidences of inflammation of the forestomach were significantly increased in 150 and 300 mg/kg males, and the incidence of ulcers was significantly increased in 300 mg/kg males. Increased incidences of cystic degeneration of the liver occurred in 150 and 300 mg/kg male rats; the incidence was significantly increased in the 300 mg/kg group. 2-YEAR STUDY IN MICE: Groups of 50 male mice were dermally administered 0, 150, 300, or 600 mg bis(2-chloroethoxy)methane/kg body weight in ethanol, 5 days per week for 105 weeks. Groups of 50 female mice were dermally administered 0, 100, 200, or 400 mg/kg in ethanol, 5 days per week for 104 weeks. Survival of 600 mg/kg male mice was significantly less than that of the vehicle control group. Mean body weights of dosed mice were generally similar to those of the vehicle controls throughout the study. Clinical findings observed in 600 mg/kg male mice that died during the first year of the study included lethargy and thinness. Myocardial heart changes were recorded according to the characteristic lesions of cardiomyopathy syndrome (necrosis, mononuclear cell infiltration, myocardial cell vacuolization, and interstitial fibrosis) separately, and in addition, where appropriate, they were also categorized as cardiomyopathy. Increased incidences of cardiomyopathy and mononuclear cell infiltration occurred in 600 mg/kg males and 400 mg/kg females; the incidences were significantly increased in 600 mg/kg males compared to the vehicle controls. Significantly increased incidences of cardiomyocyte vacuolization and interstitial fibrosis occurred in 600 mg/kg males. A few early deaths in the 600 mg/kg males were considered to be due, at least in part and probably exclusively, to bis(2-chloroethoxy)methane-induced cardiotoxicity. The incidence of ulceration of the forestomach was significantly increased in 600 mg/kg males. Significantly increased incidences of dermal inflammation and fibrosis and epidermal hyperplasia at the site of application occurred in 600 mg/kg male mice. GENETIC TOXICOLOGY: Bis(2-chloroethoxy)methane was mutagenic in S. typhimurium strains TA100 and TA1535 in the presence of exogenous metabolic activation enzymes (S9) in one study; results from a second bacterial mutagenicity test were judged to be equivocal based on responses observed in TA100 and in E. coli strain WP2 uvrA/pKM101 in the presence of S9. No mutagenicity was observed in other tester strains or in the absence of S9. Bis(2-chloroethoxy)methane did not increase the frequency of micronucleated reticulocytes in bone marrow of male F344/N rats following three daily treatments by gavage or micronucleated erythrocytes in peripheral blood of male or female mice after 3 months of dermal exposure. CONCLUSIONS: Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenic activity of bis(2-chloroethoxy)methane in male or female F344/N rats administered 75, 150, or 300 mg/kg. There was no evidence of carcinogenic activity of bis(2-chloroethoxy)methane in male B6C3F1 mice administered 150, 300, or 600 mg/kg or in female B6C3F1 mice administered 100, 200, or 400 mg/kg. The administration of bis(2-chloroethoxy)methane for 2 years resulted in increased incidences of nonneoplastic lesions in the nose of male and female rats, the forestomach of male rats, the heart of male and female mice, and the forestomach and skin of male mice.

Occult cardiotoxicity: subtoxic dosage of Bis(2-chloroethoxy)methane impairs cardiac response to simulated ischemic injury.

The effect of Bis(2-chloroethoxy)methane (CEM) on myocardial response to ischemia was tested in rats. CEM was dermally applied for 3 days to F344/N male rats, at 0, 100, 400, or 600 mg/kg/d. Subsequently, left ventricular sections were prepared from each rat heart. Part of the sections from each heart were exposed to 90 minutes of simulated ischemia, followed by 90 minutes of reoxygenation. The rest of the sections were continuously oxygenated. Mitochondrial activity was assessed in the sections by the MTT colorimetric assay, reflecting dehydrogenases redox activity. Myocardial toxicity occurred in response to 400 and 600 mg/kg, characterized by myofiber vacuoles, necrosis, and mononuclear infiltrates. The latter dose was lethal. In sections from rats treated with 400 mg/kg CEM, redox activity was decreased by 21% (p<0.01) in oxygenated conditions and by 45% (p<0.01) in ischemia-reoxygenation, compared to controls. Hearts of rats treated with 100 mg/kg/d CEM showed normal histology. Their mitochondrial activity did not differ from that of untreated rat hearts in oxygenated conditions. However, in ischemia-reoxygenation, their redox activity was significantly lower (by 46%, p<0.01) than that of untreated rat hearts. These results demonstrate that subtoxic dosage of a cardiotoxic agent may cause occult cardiotoxicity, reflected by impaired response to ischemia.

Efficacy of 1% 4-ethoxybenzaldehyde in reducing facial erythema.

BACKGROUND: Facial erythema is a common postsurgical and dermatologic problem. It is commonly the result of dermal inflammation arising from either a facial surgical procedure, such as laser resurfacing, dermabrasion, or a face peel, or from an underlying dermatologic condition, such as rosacea. Facial erythema is difficult for the dermatologist to treat in both settings because topical corticosteroids cannot be used long term on the thin facial skin and anti-inflammatory oral or topical antibiotics have associated side effects. OBJECTIVE: The goal of this pilot study was to evaluate the anti-inflammatory effect of 1% 4-ethoxybenzaldehyde in a rosacea model of facial erythema. METHODS: Thirty subjects with mild to moderate stable rosacea were enrolled in this 4-week, double-blind, vehicle-controlled study. Photographs, investigator assessment, and subject assessment were the efficacy criteria. RESULTS: There was a statistically significant reduction in facial erythema (p<.01) in those subjects who used the active for 4 weeks, as well as a statistically significant improvement in uneven skin tone (p<.01) and the overall severity of the disease (p<.01). There was no statistically significant difference in any of these three indices in the vehicle-treated group. CONCLUSION: The results suggest that benzaldehyde-derived anti-inflammatory agents may be useful in reducing facial erythema in a rosacea model.

Short-term oral toxicity of pentyl ether, 1,4-diethoxybutane, and 1,6-dimethoxyhexane in male rats.

Pentyl ether (PE) and two newly synthesized polyoxy ethers, 1,4-diethoxybutane (DEB) and 1,6-dimethoxyhexane (DMH), have been proposed as candidate diesel fuel additives. To characterize and compare their toxicity and to provide information for risk assessment, a 4-week oral study was conducted on these compounds. Male Sprague-Dawley rats (288 +/- 20 g) were divided into groups of seven animals each, and were administered by gavage low (2 mg/kg body weight), medium (20 mg/kg body weight), or high (200 mg/kg body weight) doses of PE, DEB, or DMH, respectively, 5 days/week for 4 weeks. Animals in the control group received the vehicle (corn oil, 1 ml/100 g body weight) only. At the end of the exposure period, relative testis and thymus weights were reduced by 30 and 46%, respectively, in animals treated with the high dose of DMH. Significant reductions in serum lactate dehydrogenase (LDH), serum uric acid, and blood platelet counts were also observed in the high dose of DMH. Serum corticosterone was significantly depressed in the high doses of PE and DEB and in the low dose of DMH. Serum thiobarbituric acid-reactive substances (TBARS) were decreased (p < 0.05) in all DMH treatment groups and in the medium and high dose PE and DEB groups, while liver TBARS were unaffected by treatment. In the liver, increased glutathione (GSH) level and glutathione-S-transferases activity were detected in the high dose DMH group. Urinary ascorbic acid levels were markedly increased in animals receiving the high doses of PE, DEB, and DMH. Urinary formic acid was increased by 13 times in the high dose PE and DEB groups. Testes of all animals receiving the high dose of DMH showed a moderate to marked degree of degeneration of the seminiferous tubules, including a mild degree of vacuolation. At the same time, the epididymis of these animals had substantially reduced sperm density with prominent presence of spermatid giant cells. Mild histological changes were seen in the liver at all dose levels for all three chemicals. Thyroid effects were also observed in the high dose PE and DEB groups and in the medium and high dose DMH groups. It was concluded that DMH is the most toxic of the three ethers tested, with testicular, epidiymal, and thymic effects being the most prominent at 200 mg/kg. Other significant changes included depressed platelet counts and serum biochemical changes. Increased production of formic acid, an ocular toxin, from PE and DEB treatments may also be of toxicological concern.

Biotransformation of MTBE, ETBE, and TAME after inhalation or ingestion in rats and humans.

The biotransformation of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) was studied in humans and in rats after inhalation of 4 and 40 ppm of MTBE, ETBE, and TAME, respectively, for 4 hours, and the biotransformation of MTBE and TAME was studied after ingestion exposure in humans to 5 and 15 mg in water. tert-Butyl alcohol (TBA), a TBA conjugate, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate were found to be metabolites of MTBE and ETBE. tert-Amyl alcohol (TAA), free and glucuronidated 2-methyl-2,3-butanediol (a glucuronide of TAA), 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3-methyl butyrate were found to be metabolites of TAME. After inhalation, MTBE, ETBE, and TAME were rapidly taken up by both rats and humans; after termination of exposure, clearance from blood of the ethers by exhalation and biotransformation to urinary metabolites occurred with half-times of less than 7 hours in rats and humans. Biotransformation of MTBE and ETBE was similar in humans and rats after inhalation exposure. 2-Hydroxyisobutyrate was recovered as a major product in urine. All metabolites of MTBE and ETBE excreted with urine were eliminated with half-times of less than 20 hours. Biotransformation of TAME was qualitatively similar in rats and humans, but the metabolic pathways were different. In humans, 2-methyl-2,3-butanediol, 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3methyl butyrate were recovered as major urinary products. In rats, however, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine. After ingestion of MTBE and TAME, both compounds were rapidly absorbed from the gastrointestinal tract. Hepatic first-pass metabolism of these ethers was not observed, and a significant part of the administered dose was transferred into blood and cleared by exhalation. Metabolic pathways for MTBE and TAME and kinetics of excretion were identical after ingestion and inhalation exposures. Results of studies presented here suggest (1) that excretion of MTBE, ETBE, and TAME in rats and humans is rapid, (2) that biotransformation and excretion of MTBE and ETBE are identical in rats, and (3) that biotransformation and excretion of TAME is quantitatively different in rats and humans.

Efeito de cálculos biliares humanos na cavidade peritoneal de ratos / Effects of human gallstones on the peritoneal cavity of rats

Este estudo tem por objetivo analisar experimentalmente as características macroscópicas e microscópicas de cálculos biliares humanos na cavidade peritoneal de ratos. Foram utilizados 32 ratos Wistar, machos, pesando entre 205 e 268 g. Estes animais foram distribuídos em dois grupos e o procedimento cirúrgico foi realizado em cada grupo: no grupo A (n=16), os animais foram submetidos a manipulaçao intestinal; no grupo B (n=16), cálculos biliares humanos foram colocados na cavidade peritoneal. Os ratos foram avaliados no 21º e 42º dias do período pós-operatório. Os resultados mostraram que a simples manipulaçao causou aderências no animais (n=10). As aderências foram notadas em 11 cálculos no grupo B. Histologicamente nao houve fibrose intensa em torno do cálculo, principalmente no 42º dia do período pós-operatório. Nao foram observados macro ou micro abscessos e nao houve evidências de fluído livre intra-peritoneal. Este estudo demonstra que apesar da baixa incidência de complicaçoes, todas as tentativas devem ser feitas para recuperar cálculos perdidos durante colecistectomia.

Alteraçöes histopatológicas em ratos anestesiados com éter sulfúrico / Hystopathological alterations in rats anesthetized with sulfuric ether

O rato é o animal preferencialmente utilizado, tanto no âmbito anestésico como no cirúrgico experimental. Neste animal várias drogas e técnicas anestésicas têm sido utilizadas, dentre elas o éter por via inalatória, com uso de câmaras de induçäo e de vaporizadores de fluxo contínuo. Desta forma, o objetivo deste trabalho foi estudar a estrutura histológica de órgäos de ratos anestesiados com éter sulfúrico por via inalatória. Foram utilizados 24 Rattus norvegicus albinus, machos, adultos, pesando 285 (+/-20) gramas, com 120 a 150 dias de vida, distribuídos em dois grupos: Grupo A (n=12), no qual foi utilizado éter sulfúrico como agente anestésico inalatório, e Grupo C, grupo controle (n=12), em cujos animais näo foi realizado nenhum anestésico, sendo submetidos à eutanásia com injeçäo de 5 ml de cloreto de potássio a 10 por cento por via intra-peritonial. O grupo A foi dividido em 3 subgrupos: A1 (n=4), A7 (n=4) e A15 (n=4), cujos animais receberam anestesia por 30 minutos diários durante, um, sete e quinze dias consecutivos. Completado o ciclo anestésico de cada subgrupo, os animais foram submetidos à eutanásia com dose inalatória letal de éter sulfúrico, sendo retiradas vísceras (cérebro, fígado, pulmäo, rim e traquéia), para análise macroscópica e estudo histopatológico. Dentre os resultados observados, fígado e encéfalo mostraram-se normais em ambos os grupos...

[Biologic activity and tolerance of a preparation of polyunsaturated fatty acids, obtained by a microbiological route ["biopolyene"]]. / Biologicheskaia aktivnost' i perenosimost' preparata polinenasyshchennykh zhirnykh kislot, poluchaemykh mikrobiologicheskim putem ["biopoliena"].

Biopolyene is a mixture of ethyl ethers of polyunsaturated fatty acids isolated from biomass of Entomophthora virulenta, a mycelial fungus. Its acute and chronic toxicity was studied on rats and guinea pigs. After oral administration of the preparation in single doses exceeding 50 g/kg there were no disorders in the general state of the rats. In chronic experiments with oral biopolyene in doses of 100 and 500 mg/kg and its local application to the intact skin of the animals in a dose of 1 g/kg there were no significant changes in the functional state of the liver and kidneys as well as the peripheral blood count. Insignificant changes in the serum levels of liver enzymes and coagulation were transient. The preparation showed no allergenic or immunomodulating effects. It had neither embryotoxic, teratogenic nor mutagenic action.

[Inhalation anesthetic therapy of status asthmaticus].

Status asthmatics is characterized pathologically by bronchial smooth muscle spasm, and mucous plugging of the small airways. Clinically, it is characterized by the disturbance of gas exchange. In severe cases, unresponsive to standard therapy (including oxygen, epinephrine, aminophylline and steroids, artificial ventilation, tracheobronchial lavage and inhalation), anesthetic therapy should be started without delay. Inhalation anesthetics, halothane or ether, have potent bronchodilating properties which facilitate the removal of mucous plugging. We reported nine cases with status asthmatics treated by inhalation anesthetic therapy. Halothane (0.5-3.0%) was used in all cases, ether (1.5-3.0 ml/kg) was used in five cases. The duration of anesthesia was 0.5 to 13.5 hours. In three halothane anesthesia cases, blood pressure was reduced before there was improvement in wheezing, so we were forced to change halothane to ether. In all cases, the symptoms of status asthmatics were improved, but two patients died due to other complications. We recommended the following method, viz that halothane be administered at first, and be changed to ether in order to maintain circulatory movement.

[Effects of thermal burns of the esophagus on carcinogenesis induced by ethyl ethers of N-nitrososarcosine in rats]. / Vliianie termicheskogo ozhoga pishchevoda na kantserogenez, vyzyvaemyi étilovym éfirom N-nitrozosarkozina u krys.

The study was concerned with the effect of electro-thermocoagulation burn of the rat gullet on carcinogenesis induced by esophagotropic carcinogen--ethyl ester of N-nitrososarcosine (50 mg/kg, five times a week, four months). Treatment was started on day 15 postburn, and at 8 months tumors of the esophagus occurred in 71.8% including tumors in the burn area (46.8%). Forestomach neoplasms were observed in 15.6%. Animals treated with the carcinogen alone showed a significant decrease in both overall frequency of esophageal tumors (42.4%) and that for the burn area (18.1%) while frequency of forestomach neoplasia remained nearly the same (21.2%). Most tumors were benign papillomas. It was concluded that burn--induced cicatricial changes in the esophageal mucosa predispose to development and growth of tumors of this site.

Use of ether in life-threatening acute severe asthma.

Two patients with acute severe asthma who had failed to improve with conventional treatment, mechanical ventilation, and halothane showed prompt bronchodilator response following administration of diethyl ether by inhalation. Airway pressures fell, and there was a dramatic improvement in blood gas analysis and clinical condition.