Histologic peripheral nerve changes in rats induced by deltamethrin.

Synthetic pyrethroid insecticides have been used in the last two decades largely because of their high activity as an insecticide and low mammalian toxicity. Some studies have demonstrated that these products, especially compounds with an alpha-cyano group, are toxic to the mammalian central nervous system (CNS) in acute intoxications. However, morphological studies are scarce. In the present work the histopathologic changes of the sciatic and tibial nerves of rats submitted to acute intoxication with the cyanopyrethroid deltamethrin were studied. For 3 consecutive days male Wistar rats received by oral gavage deltamethrin at a dose of 45 mg/kg body wt. On the 4th day fragments of sciatic and tibial nerves were studied by transmission electron microscopy (TEM) and teasing of individual nerve fibers. In addition, another group of rats were allowed to recover until the 10th day. Teasing of nerves of animals sacrificed on the 4th day revealed myelin ovoids, which are indicative of axonal damage. TEM demonstrated rare degenerated axons completely filled with organelles, in particular mitochondria, and with electron-dense lamellar bodies that resemble myelin figures. In addition, great cytoplasmic vacuolization caused by proliferation and dilation of the rough and smooth endoplasmic reticulum and Golgi apparatus was observed in some Schwann cells. No lesion was found 7 days after discontinuation of the treatment (group2). Since these histologic changes are transitory and scarce, the question arises: Are they related to the changes in NA(+), K(+)-ATPase activity or Na(+) channels caused by pyrethroid compounds?

Mitochondrial metabolism impairment in muscle fibres of rats chronically intoxicated with Senna occidentalis seeds.

The chronic administration of S. occidentalis seeds was found to induce a mitochondrial myopathy in hens. This study was undertaken to determine if the chronic treatment with S. occidentalis seeds of rats (as a mammalian model) would induce a mitochondrial myopathy similar to those described in humans and to determine if the histological changes could be correlated with the amount of ingested seeds. Twenty-one days old rats were fed S. occidentalis seeds at different diet concentrations (1, 2, 3%). Rats fed 1% S. occidentalis seeds had only a few COX-negative muscle fibers in the pectoralis major muscle. Rats fed 3% Senna occidentalis seeds had a greater number of COX-negative fibers. Rats fed 2% had an intermediate number of COX-negative fibers. Activity of SDH and NADH-tr were decreased in rats of groups 2% and 3%. Our data indicate that a progressive mitochondrial metabolism impairment can be produced in rats fed S. occidentalis seeds and that this impairment can be correlated with the amount of ingested seeds.

Toxicity testing of Senna occidentalis seed in rabbits.

The effect was investigated of administering ground Senna occidentalis seeds to rabbits in different concentrations (1%, 2%, 3% and 4%) in the ration. The experiment lasted 30 days and the toxic effects of the plant were evaluated on the basis of weight gain, histopathological, biochemical and morphometric parameters, as well as histochemistry and electron microscopy. Animals that received the ration containing 4% ground S. occidentalis seeds gained less weight (p < 0.05) and died in the third week. Histopathology revealed that the heart and liver were the main organs affected, with myocardial necrosis and centrolobular degeneration. There was a reduction in cytochrome oxidase activity in the glycogenolytic fibres, together with muscle atrophy, confirmed by the morphometric studies. Electron microscopy of the liver cells revealed dilated mitochondria, with destruction of the internal cristae.

The lysosomal enzymes acid phosphatase and cathepsin D in rats intoxicated with Senna occidentalis seeds.

Chronic administration of Senna occidentalis seeds induces an experimental toxic myopathy characterized by skeletal muscle fibers atrophy, decrease in histochemical activity of cytochrome oxidase, and increase of the acid phosphatase activity in muscle fibres at the light microscopic level. The mechanisms that lead to the increase of this lysosomal enzyme activity are not known and could be related to other biochemical disturbs than the mitochondrial function impairment. The main aim of the present study is to localize the acid phosphatase activity using a cytochemical method at transmission electron microscopy level and to quantify cathepsin D in muscle of rats chronically intoxicated with Senna occidentalis seeds by immunoblotting. Acid phosphatase was observed in lysosomes and over profiles of some organelles apparently not involved by lysosomal membrane. In addition immunoblotting demonstrated a decrease in the content of the precursor and of the mature form of cathepsin D in samples of muscles and liver of intoxicated animals. We concluded that there is a selective increase in acid phosphatase activity in muscle--and maybe in other tissues--of animals intoxicated with Senna occidentalis, that can be related to the skeletal muscle atrophy and the intense decrease in weight gain of these animals. Further studies should be performed to establish the mechanisms of selectivity in increase of lysosomal enzymes in different situations and pathological states.

Early expression of ubiquitin in myofibers of rats in organophosphate intoxication.

The degenerative process of the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos, a compound that inhibits esterases, was studied at different intervals of intoxication. Early disorganization of the intermyofibrillar network and of the myofilaments, as well as dilatation of organelles, were observed by use of transmission electron microscopy. These changes precede macrophage invasion of the muscle fibers. Early expression of ubiquitin was observed in segments of muscle fibers by immunohistochemistry. Bands of polyubiquitin complexes in muscle homogenates were observed by immunoblotting. These bands disappeared in later stages of intoxication. A 42.5-kDa band corresponds to actin, as observed by immunoblotting using antisarcometric actin. This indicates relatively large amounts of polyubiquitin complex associated with sarcomeric actin in muscle fibers in early stages of intoxication. Based on these results it seems that actin is an important target in organophosphate-induced myofiber degradation and that the degradation of this protein-by the polyubiquitin pathway-may play an important role in the early disorganization of the sarcomere, as observed by electron microscopy. A possible role of the ubiquitin proteolytic pathway is that of trying to eliminate proteins modified in the early phases of muscle fiber degeneration, which is a necessary step for regeneration of the posterior segmental muscle.

Sarcoplasmic lipase and non-specific esterase inhibition in myofibers of rats intoxicated with the organophosphate isofenphos.

The expression of sarcoplasmic esterases, lipases as well as the lipid content in the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos was studied. Lipid accumulation was documented at light, electron microsopic and by morphometric studies. The distribution of these lipid droplets was irregular and abundant in myofibers with numerous mitochondria (predominantly oxidative fibers). Histochemical inhibition of sarcoplasmic esterases and lipases was observed in the intoxicated animals. This sarcoplasmic inhibition of esterases occurs roughly in parallel to the inhibition of plasma cholinesterase activity. The inhibition of sarcoplasmic lipases may explain, at least partially, the accumulation of lipids. This inhibition probably makes difficult the use of lipids as fuel, especially in the oxidative fibers. In contrast to the small amount of muscle necrosis, (1.30+/-0.745), metabolic muscle impairment was intense and extensive, i.e., decreased activities of esterases and lipases in the sarcoplasm, that should contribute to muscle weakness. Therefore, because segmental necrosis was most prominent in oxidative fibers (and these fibers use lipids as the principal fuel and contain the greater amount of lipases in the sarcoplasm), it is possible that inhibition of activity of lipases is responsible for the segmental necrosis. Although the exact role of these metabolic changes is not known, it is possible that they contribute not only to the induction and evolution of muscle cell necrosis but also to the muscle weakness and clinical impairment of animals and humans in the acute intoxication by these compounds.

Muscle atrophy induced in broiler chicks by parts of Senna occidentalis seeds.

Senna occidentalis (formerly Cassia occidentalis) is a common contaminant of agricultural commodities. It is toxic to cattle and poultry, reportedly being responsible for skeletal myodegeneration in these animals. All parts of the plant present toxicity, but the seeds are the most toxic. The toxin(s) responsible for the myodegeneration have not been definitively identified, nor is it known which part of the seeds is most toxic. Intoxication by this plant leads to weight loss with considerable economic repercussions. The effects of the whole seed and of parts of S. occidentalis seeds (1% in commercial feed) were compared on the pectoralis major muscle of broiler chicks intoxicated from birth until 22 days of life. There were severe clinical signals and reduced body weight in birds that received the external tegment of the seed, whereas no adverse effects were observed in birds that received the whole seed or other parts of the seed. Histological and morphometric studies showed an intense muscle fibre atrophy (both type 1 and type 2 fibres were affected) in the group that received 1% external tegment. This study may be the first step to identifying the substance(s) involved in this pathological process.

Protective effect of pralidoxime on muscle fiber necrosis induced by organophosphate compounds.

OBJECTIVE: To determine the protective effect of pralidoxime on muscle fiber necrosis induced by organophosphate acute intoxication in rats. DESIGN: Adult male Wistar rats were given oral organophosphate compounds dissolved in glycerol formal: dichlorvos, isofenphos, metamidophos, and diazinon. Half of the animals also received pralidoxime mesylate (20 mg/kg, intraperitoneal). Control animals received only the solvent. Twenty-four hours after treatment, the diaphragm muscle was collected for histological counts of necrotic muscle fibers in transverse sections. RESULTS: Metamidophos- and isofenphos-treated animals showed the highest percentage of necrotic muscle fibers: 1.66 +/- 1.112 and 1.34 +/- 0.320, respectively. Diazinon-treated animals had a lower percentage of necrotic fibers: 0.40 +/- 0.032 (p < 0.05) compared to the first 2 products, and dichlorvos-treated animals showed the smallest: 0.05 +/- 0.021 (p < 0.05) when compared to the other 3 products. Pralidoxime reduced necrotic fibers about 20 times in metamidophos-treated animals, 10 times in isofenphos-treated animals and 6 times in diazinon-treated animals. Pralidoxime administration did not increase plasma cholinesterase activity in any group, although symptoms were reduced. CONCLUSIONS: Oxime reduced diaphragmatic muscle necrosis in experimental organophosphate intoxication, despite little effect on plasma cholinesterase. Since respiratory insufficiency is an important cause of mortality and morbidity in organophosphate intoxications, early oxime administration may be particularly beneficial.

Nerve biopsy in patients with AIDS.

Patients with AIDS can present clinical involvement of the peripheral nervous system due to different causes. In the present work, it was studied the histopathological changes in sural nerve biopsy of fifteen patients with AIDS with this clinical involvement. It was observed the presence of a polyarteritis nodosa-like vasculitis of small arteries with fibrinoid necrosis in the sural nerve of 3 patients, one of them associated to polyradiculitis due to cytomegalovirus infection (CMV). Six patients presented mild axonal loss by light microscopy. Three other patients had a more important axonal neuropathy with myelin ovoids by teasing. By the electron microscopy in these patients were observed some fibers with axonal damage. The other three patients had normal sural nerves. We concluded that sural nerve biopsy may be important in peripheral neuropathies or myelo-radiculo-polyneuropathies in AIDS especially to search for nerve vasculitis, because it can change the therapeutic approach.

Toxic peripheral neuropathy of chicks fed Senna occidentalis seeds.

Plants of the genus Senna (formerly Cassia) are poisonous to livestock and other laboratory animals, leading to a syndrome of a widespread muscle degeneration, incoordination, recumbence, and death. The main histologic lesion is necrosis of skeletal muscle fibers. Recently, a mitochondrial myopathy with ragged-red and cytochrome oxidase (COX)-negative muscle fibers was recognized in hens chronically intoxicated with parts of seeds of S. occidentalis. The purpose of the present work was to investigate if there was peripheral nerve involvement in the acute intoxication of chicks with S. occidentalis seeds. Teasing of individual fibers revealed signs of extensive axonal damage with myelin ovoids. Ultrathin sections confirmed the axonal damage. Axons were filled with membranes, some residual disorganized filaments, and enlarged mitochondria. In some instances the axon disappeared and there was secondary degeneration of the myelin sheath. The present work is the first description of the neurotoxic effect of S. occidentalis intoxication. Future work should attempt to determine the mechanisms involved in this neuropathy.

Mitochondrial myopathy in Senna occidentalis-seed-fed chicken.

Plants of the genus Senna (formerly Cassia) have been recognized as the cause of a natural and experimental syndrome of muscle degeneration frequently leading to death in animals. Histologically, it demonstrated skeletal and cardiac muscle necrosis, with floccular degeneration and proliferation of sarcolemmal nuclei. Recently, it was described as an experimental model of mitochondrial myopathy in hens chronically treated with Senna occidentalis. Currently, skeletal muscles of chicks intoxicated with seeds of the poisonous plant S. occidentalis were studied by histochemistry and electron microscopy. Since birth, the birds were fed ground dried seeds of this plant with a regular chicken ration at a dose of 4% for 11 days. Microscopic examination revealed, besides muscle-fiber atrophy, lipid storage in most fibers and a moderate amount of cytochrome oxidase-negative fibers. By electron microscopy, enlarged mitochondria with disrupted or excessively branched cristae were seen. This picture was characteristic of mitochondrial myopathy. These findings have hitherto remained unnoticed in skeletal muscle of young birds treated with S. occidentalis.

[Energy metabolism and experimental malignant tumor development]. / Metabolismo energético e desenvolvimento de tumor malígno experimental.

Weight loss in cancer can be attributed to anorexia and/or increased energy expenditure. In order to understand the contribution of these variables, 36 Wistar rats fed regular diet were randomly distributed in 3 groups: T (12) bearing Walker 256 carcinosarcoma; PF (12) pair fed with T group and C (12) as control group; another group--D (12)--in which rats were fed with low protein (1%) diet. Caloric intake, body and tumor weight were measured daily. Indirect calorimetry was done sequentially each 4 days. After 2 weeks of tumor growth there was significant reduction of caloric intake and carcass weight in T group compared to those of C group. There was no difference in carcass weight between T and PF group. After 3 weeks it was significantly reduced in T group (55.7 Kcal/m2/h against 75.0 of N and 65.1 of PF group). Walker 256 carcinosarcoma is an hypometabolic tumor and the host weight loss associated to its development is due to anorexia.

Biology and physiology of development of aging.

The presentation of a new language of biology and physiology to undergraduate and graduate students in gerontology is a challenge met with varied approaches in content and form. Major issues in content are presented with reference to encyclopedic and more readable texts and journals. Use of audiovisual, discussion, and written materials are identified. The importance of ongoing evaluation, knowledge and implementation of the most current information, and goals of undergraduate and graduate courses are addressed.

The backbone of academic gerontology: introduction.

The "new age" of gerontology in institutions of higher learning has raised the important question, "What is the academic informational and experiential backbone upon which a variety of generalized tracks and gerontology programs may proceed to create unique gerontological specializations?"

The image and reality of "old": time for a change.

The development of ageism in America is rich with the fears and beliefs of the ancients from prehistory, through biblical millennia into early European and American history. Myths and stereotypes of the invalid, sexless, senile, useless elder die slowly as the relatively well, competent, "graying," population becomes the reality. Studies provide the data that support the changing view of aging, not as disease, but another stage of life with its own challenges and satisfactions. Aging older persons can best be understood within a multidisciplinary perspective which examines the interaction with time of physical, social and psychological aspects of the total personal Societal barriers to continued participation of older Americans in the mainstream of life are beginning to weaken-there is reason for hope.