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Biomedical subjects

A Nyska

Publications and source records attributed to A Nyska.

At least 55 records · Page 3Linked to original sources
PubMed1998

Isobutyraldehyde administered by inhalation (whole body exposure) for up to thirteen weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344/N rats and B6C3F1 mice.

Isobutyraldehyde (a chemical structurally related to formaldehyde and used as a flavoring agent) was studied for toxicity and carcinogenicity by exposing male and female F344/N rats and B6C3F1 mice. Animals were exposed to isobutyraldehyde vapors 6 h per day, 5 days per week for up to 13 weeks or 2 years. In the 13-week studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were exposed to concentrations of 0, 500, 1000, 2000, 4000, or 8000 ppm. Chemical-related body weight depression and deaths occurred in rats and mice exposed to 4000 and 8000 ppm. Necrosis of the epithelium accompanied with acute inflammatory reaction was observed in the nasal turbinate, larynx, and trachea of rats exposed to 8000 ppm. Exposure of rats to 4000 ppm resulted in metaplasia of the nasal respiratory epithelium, inflammation, degeneration of the olfactory epithelium, and osteodystrophy of the nasal turbinate bone. In the 13-week mouse study, exposure to 8000 ppm or 4000 ppm resulted in necrosis of the epithelium lining of the nasal turbinates. Osteodystrophy of the nasal turbinate bone and squamous metaplasia of the nasal respiratory epithelium were noted in mice exposed 4000 ppm. Degeneration of the olfactory epithelium was noted in males exposed 2000 ppm and in females exposed to 4000 ppm. In the 2-year studies, groups of 50 male and 50 male F344/N rats and B6C3F1 were exposed to concentrations isobutyraldehyde vapors of 0, 500, 1000, or 2000 ppm 6 h per day, 5 days per week. There were no differences in survival rates or mean body weights between exposed groups and control rats. Survival of male mice exposed to 2000 ppm and mean body weights of female mice exposed to 1000 or 2000 ppm were lower than those of the of the controls. No increase in neoplasm incidence was observed in rats and mice in the 2-year studies that could be attributed to isobutyraldehyde exposure. Chemical-related nonneoplastic lesions were limited to the nose of rats and mice. They included squamous metaplasia of the respiratory epithelium (rats), suppurative inflammation (rats), and olfactory epithelial degeneration (rats and mice) at 1000 and 2000 ppm.

Aldehydes↗
PubMed1998

Theophylline-induced mesenteric periarteritis in F344/N rats.

The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall.

Administration, Oral↗
PubMed1998

Effect of individual versus group caging on the incidence of pituitary and Leydig cell tumors in F344 rats: proposed mechanism.

Recently, an increase in pituitary tumor (pars distalis adenoma) incidence, and decrease in testicular interstitial cell tumor incidence, has been noted in F344 rats, in 2 year National Toxicology Program dermal and inhalation studies. One of the factors that may have contributed to this correlation is the difference in housing protocols. Rats in inhalation and dermal toxicity studies are singly caged, in contrast to other types of studies in which rats are group-caged, such as dosed-feed, dosed-water, or gavage studies. We propose that stress, related to individual caging, particularly among males, directly impairs testosterone synthesis and produces Leydig cell atrophy which leads to a feedback increase in the synthesis of luteinizing hormone by the anterior pituitary. This is followed by anterior pituitary cell functional hypertrophy, hyperplasia, and eventually neoplasia. It is known that individual caging of male rats produces a stress response associated with increased serum corticosteroids. The testicular interstitial cells (Leydig cells) have specific receptors for the glucocorticoid hormones. The Leydig cell enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) inactivates gluococorticoids; however, prolonged stress depletes this enzyme, enabling the gluococorticoids to impair steroidogenesis and eventually to lead to compensatory pituitary proliferations, including neoplasms.

Adrenal Cortex Hormones↗
PubMed1998

Effect of very high single dose of cisplatinum and of radiation on the brain of the rabbit.

The importance of chemotherapy and radiotherapy for treating brain tumors, is well established. In a previous study, a rabbit's brain was treated with doses of up to 12 mg kg-1 of cisplatinum and 4000 cGy, without any morphological or pathological changes. The purpose of this study is to establish the effect of very high single doses of cisplatinum and radiation on the rabbit's brain, applied in 12, 16 and 18 mg kg-1, and 5000, 7500 and 8000 cGy, respectively. The general clinical and neurological condition of the rabbits was unaffected, but areas of alopecia and scalp ulcers appeared. Although these are very high doses of chemotherapy and radiotherapy, the histopathological and morphological examination of the rabbit's brain remained normal.

Animals↗
PubMed1998

Castration prevents calcium channel blocker-induced gingival hyperplasia in beagle dogs.

1. The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodipine-inducing gingival hyperplasia in a dog model. 2. Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone. 3. A significant positive correlation between GI, GHI and plasma testosterone was noted. Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI. 4. Since it is known that testosterone receptors are present in the gingiva, it is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels.

Animals↗
PubMed1998

Intestinal and hepatic cell kinetics and mucous changes in vitamin-A-deficient rats.

Changes in tissue histopathology, cell morphology and kinetics and the number of mucus secreting cells were evaluated in the duodenum and colon of normal and vitamin-A-deficient rats. A lower number of goblet cells was detected both in the colon and in the duodenum of vitamin-A-deficient rats in comparison with control rats (p<0.05). vitamin-A deficiency was found to increase the proliferate rate of mucous cells in the duodenum significantly. No significant difference was noted in the proliferate index in the colon specimens in either control group of experimental rats. We suggest that the higher number of proliferating cells in the duodenal crypt and villi in the vitamin-A-deficient animals indicates that vitamin-A deficiency affects the cell proliferation and therefore could be of some importance in understanding the potency of retinoids in differentiation and their association with formation of epithelial metaplasia.

Animals↗
PubMed1998

Skin surface proteolytic activity. Partial characterization and identification.

Skin surface proteolytic activity in the living animal was determined by a sensitive, non-invasive methodology developed in our laboratory. A non-leaky well was constructed on the shaved back of an anesthetized guinea pig. The well contained the reaction mixture including the substrate 125I-S-carboxymethylated insulin B-chain (ICMI). The proteolytic activity was shown to be time-dependent. The activity was strongly inhibited by pepstatin A, indicating the involvement of aspartic proteinase(s) such as cathepsin D and/or E. Pretreatment of the skin with propylene glycol blocked the proteolytic activity. The present study demonstrates the presence of proteolytic activity located on skin surface using a unique, non-invasive method for in situ proteinase determination in the living animal.

Animals↗
PubMed1998

Acral lick dermatitis in a jackal (Canis aureus).

Acral lick dermatitis was diagnosed in a 6-mo-old female jackal (Canis aureus) that was born and housed in a zoological garden in Hafez-Haim, Israel. Other dermatologic diseases were ruled out. Although the lesions were presumed to be psychogenic in origin, they resolved with topical therapy using an ointment containing benzocaine, neomycin sulfate, and hydrocortisone acetate. No recurrence has been observed.

Animals↗
PubMed1997

Sudden death due to Paragonimus kellicotti infection in a dog.

A sudden death due to Paragonimus kellicotti infection in a dog that had had no previous clinical signs of illness until the day of admission to the veterinary hospital is documented. The clinical, haematological and biochemical abnormalities, as well as postmortem findings, are presented. This report represents the first case of canine paragonimiasis in Israel, and discusses the possibility of this fluke becoming established in the Middle East.

Animals↗
PubMed1997

Protective effect of povidone-iodine ointment against skin lesions induced by sulphur and nitrogen mustards and by non-mustard vesicants.

Mustard gas (sulphur mustard, SM) is a powerful vesicant employed as a chemical weapon. The present study demonstrates the effect of povidone iodine (PI) ointment against skin toxicity caused by SM. Gross and histopathological examinations showed that application of PI up to 20 min following exposure to the vesicant resulted in marked skin protection. The shorter the interval between exposure and treatment the better was the protection achieved. PI was also effective against other mustards such as carboxybutyl chloroethyl sulphide (CBCS) and mechlorethamine. The fact that PI protected the skin against agents which cannot be oxidized such as iodoacetic acid, divinylsulphone and cantharidine showed that the antidotal effect of PI was unrelated to oxidation of the nitrogen and sulphur atoms of the mustards. PI ointment is proposed as an efficient protective agent against skin toxicity caused by mustards and other alkylators.

Animals↗
PubMed1997

Noninvasive procedure for in situ determination of skin surface aspartic proteinase activity in animals; implications for human skin.

The present study demonstrated a noninvasive procedure for in situ determination of stratum corneum aspartic proteinase in the living animal. A non-leaky well, containing [125I]S-carboxymethylated insulin B-chain (ICMI) as a substrate, was constructed on the shaved back of anesthetized guinea pigs and rats. The enzymatic activity was determined by measuring the radiolabeled trichloroacetic acid soluble material. We demonstrated pepstatin-sensitive proteinase activity bound to the skin surface indicating the involvement of aspartic proteinase(s) such as cathepsin D and/or E. Aged rats had about six fold lower activity than young animals. The proteinase activity was inhibited by the alkylating agent mechlorethamine and by the cosmetic propylene glycol. A similar procedure was carried out with intact human skin pieces obtained during plastic surgery. The activity was inhibited by antihuman cathepsin D antibodies. Cathepsin D was immunohistochemically localized in the corneal and granular layers of the epidermis. Skin surface aspartic proteinase/cathepsin D activity may serve as a marker for skin aging or for certain skin disorders leading to a new approach to their medical treatments.

Aging↗
PubMed1997

Delayed effect of progesterone on endometrial morphology in dairy cows.

Two experiments were conducted to investigate the effect of vaginal progesterone (P4) administered during the luteal phase, on endometrial morphology during the subsequent oestrous cycle. In experiment 1, lactating Holstein cows were allotted to three groups: (1) Control group in which cows remained untreated; (2) The CIDR group in which cows were treated with two P4-containing controlled intravaginal-drug releasing devices (CIDR) during days (d) 6-12 of the cycle; and (3) The PG + CIDR group of cows that received two prostaglandin F2 alpha (PGF2 alpha) injections on d 6 and 7 of the oestrous cycle, to regress the corpus luteum (CL), and were treated with CIDRs on d 6-12, like the CIDR group. All cows were slaughtered on d 3 of the subsequent oestrous cycle. In experiment 2, cows were allotted to three groups: (1) Control cows that remained untreated; (2) CIDR cows that were treated with two CIDRs from d 6 to 15; and (3) Early PG cows that received three i.m. injections of PGF2 alpha on d 3 and 4 of the oestrous cycle to reduce plasma P4. All cows were slaughtered on d 15 of the subsequent cycle. In both experiments, blood was collected during the treated and subsequent cycles to determine P4 and oestradiol (E2) concentrations, and tissue samples from the uterine horn ipsilateral to the CL were collected on the day of slaughter to evaluate endometrial morphology. In both experiments, plasma P4 differed between treatments during the treated cycle but no differences in P4 and E2 concentrations were recorded during the subsequent cycle. In experiment 1, the endometrial morphology of the cows from CIDR and PG + CIDR groups differed from that found in the control group: The surface epithelium was medium to high and the glands were round and tortuous, as compared with low epithelium and oblong glands in the control. In addition, the density of blood vessels and the level of edema was higher in the CIDR-treated cows than in the control cows. In experiment 2, the endometrial morphology of the CIDR-treated group differed from that of the control and early PG groups: Low surface epithelium and oblong glands in the former compared with high epithelium and tortuous glands in the latter. In summary, P4 supplementation during the luteal phase had delayed effect on endometrial morphology at different stages of the subsequent oestrous cycle.

Administration, Intravaginal↗
PubMed1997

A new transmissible AIDS-like disease in mice induced by alloimmune stimuli.

The search for a suitable and reliable animal model for human AIDS that is easy to use on a large scale continues. Here we describe a new condition in mice that closely resembles human AIDS, namely, chronic lymphoproliferation with dramatic depletion of CD4-positive cells, progressive impairment of the immune responses, and Kaposi's sarcoma-like tumors or terminal B-lymphomas. The AIDS-like disease was primarily induced by mating BALB/c female mice to C57BL/6 males during a 1-year period (7-10 allogeneic pregnancies) followed by immunization with paternal lymphocytes. The disease is sexually and vertically transmissible, transferrable by cell-free plasma and is associated with autoimmune reactions to major histocompatibility complex antigens and CD4 cells. We hope that this becomes a model for studying the mechanisms of AIDS immunopathogenesis and immune-based treatment approaches.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Effect of high simple dose of cisplatinum and of radiation on the brain of rabbit.

In former studies of intracarotid and intravenous administration of cisplatinum, separate and combined with brain irradiation, we found no cerebral damage. In this study, gradually increasing high doses (above the therapeutic ones) of cisplatinum were administered intravenously to one series of rabbits and increasing high amounts of irradiation (above the therapeutic amounts) were given to another series. Although the rabbits that received highest doses of irradiation developed areas of alopecia and skin ulcers on the head, the general clinical and histopathologic examination of the rabbits' brains in both series was normal. The purpose of this study was to establish the effects of high doses of intravenous cisplatinum and irradiation on the rabbits brains.

Alopecia↗
PubMed1997

Functional intestinal hypomotility in association with neuronal damage in a dog.

A young, crossbred dog with a 13-month history of progressively worsening, recurrent episodes of vomiting, anorexia, depression and dehydration was diagnosed as having a functional hypomotility disorder of the small intestines. During hospitalisation, the dog's condition improved only when total parenteral nutrition was administered. When fed orally, the dog developed severe gastric dilatation. Intestinal motility was minimal, but was induced by neostigmine. Post mortem findings included dilatation of the duodenum and progressive narrowing of the small bowel up to the ileum. Histopathology revealed various grades of neuronal degeneration and necrosis of the myenteric plexuses throughout the small intestine. Microscopic changes resembled those reported in dysautonomia, but were limited to small intestinal myenteric plexuses. A localised congenital neuronal defect causing a lack of parasympathetic tone is suspected.

Animals↗
PubMed1997

Lead toxicosis in a captive bottlenose dolphin (Tursiops truncatus) consequent to ingestion of air gun pellets.

A captive bottlenose dolphin (Tursiops truncatus) in a dolphinarium in Tel Aviv, Israel, had signs of anorexia, weight loss and a reluctance to train over a 4-week period in June 1995 and died shortly thereafter. On necropsy, it had an enlarged, yellow discolored liver, and about 55 air gun pellets in the second stomach. The pellets were composed of 40% lead. Samples of liver and kidney cortex contained 3.6 and 4.2 micrograms/g lead, respectively. There was hemosiderosis in the liver and kidneys, status spongiosus in the brain, and vacuolization in the optic nerve; acid-fast intranuclear inclusion bodies were seen in the kidneys. We propose that chronic lead toxicosis had been induced after the gradual dissolution of the lead-based pellets in the acid environment of the stomach.

Animals↗