PubMed HealthSearch

Biomedical subjects

B Tandler

Publications and source records attributed to B Tandler.

At least 19 recordsLinked to original sources

The malonyl-CoA-sensitive form of carnitine palmitoyltransferase is not localized exclusively in the outer membrane of rat liver mitochondria.

The data used to support the idea that malonyl-coenzyme A (CoA)-sensitive carnitine palmitoyltransferase (CPT-I) is localized on the outer mitochondrial membrane are based on harsh techniques that disrupt mitochondrial physiology. We have turned to the use of the French press, which produces a shearing force that denudes mitochondria of their outer membrane without the physiologically disruptive effects characteristic of phosphate swelling. Our results indicate that the mitoplasts contain just 15-19% of the outer membrane marker enzyme activity while retaining 85% of the total CPT activity and 50% of both CPT-I, as well as long-chain acyl-CoA synthase activity, the latter two supposed outer membrane enzymes. These mitoplasts were shown by electron microscopy to have the configuration of mitochondria that merely have been divested of their outer membranes. Carnitine-dependent fatty acid oxidation was retained in the mitoplasts, showing that they were physiologically intact. Moreover, protein immunoblotting analysis showed that CPT-I, as well as the inner CPT-II, was localized in the mitoplast fraction. The outer membrane fraction, which consisted of membrane "ghosts," contained most (50-60%) of marker enzyme activity, monoamine oxidase-B and porin proteins, but only about 27-29% CPT-I activity. Because CPT-I and long-chain acyl-CoA synthetase appear to be associated with both inner and outer membranes, we postulate that these enzymes reside in contact sites, which represent a melding of both limiting membranes.

2,4-Dinitrophenol

Ultrastructure of the binary parotid glands in the free-tailed bat, Tadarida thersites. I. Principal parotid gland.

BACKGROUND: Many species of bats have two sets of submandibular glands, principal and accessory. The accessory gland may resemble the principal one but more often shows wide morphological divergence. The free-tailed bat, Tadarida thersites, is very unusual in that it has two sets of parotid glands rather than binary submandibular glands. We studied the ultrastructure of the principal parotid gland to establish a baseline for comparison with the accessory parotid. METHODS: Two specimens of adult free-tailed bats, one male and one female, were live-trapped in western Kenya. Parotid glands were fixed for electron microscopy using a protocol expressly designed for field fixation and then embedded by conventional means. RESULTS: Histologically, the principal parotid is a typical serous gland. The secretory granules of the endpiece cells have an unusual substructure in that they contain variable numbers of lucent halos and one or several spherules. Intercalated duct cells contain a significant number of dense, serous-like granules. Striated ducts have the usual basal configuration of mitochondria and folded plasma membranes, but the supranuclear cytoplasm contains many small, dense granules, so that these ducts resemble the granular convoluted tubules found in the submandibular glands of many families of rodents. The apices of the duct cells have a peculiar contour--the luminal surfaces obliquely invaginate into the apical cytoplasm, so that in thin section the luminal membranes appear to be underlaid by a layer of vacuoles. CONCLUSION: Although the principal parotid gland of the free-tailed bat shows some distinctive, species-specific ultrastructural features, it basically is similar to the parotid gland in two other molossid bats, Tadarida brasiliensis and Molossus molossus. The distinctive features in the principal parotid gland of T. thersites might relate to its feeding on hard-bodied insects and perhaps to the production of lysozyme.

Animals

Ultrastructure of the binary parotid glands in the free-tailed bat, Tadarida thersites. II. Accessory parotid gland.

BACKGROUND: Many bat species have an extra set of major salivary glands. In some species, the accessory glands are quite similar to the principal one, but in others they may be radically different. Accessory glands usually are associated with the submandibular gland, but the free-tailed bat, Tadarida thersites, also has an accessory parotid gland. In the present study, we compared the accessory parotid gland with its principal counterpart. METHODS: Salivary glands were removed from two specimens of free-tailed bats, one of each sex, that had been live-trapped in western Kenya and immersion-fixed in a specially formulated mixture designed for field fixation. Once back in the laboratory, the tissue was further prepared for electron microscopy by conventional means. RESULTS: The secretory endpieces consist of serous tubules composed of typical serous cells that contain numerous dense granules. In contrast, the intralobular duct system shows a radical departure from normal. These ducts are enormous in caliber, their lumina measuring greater than 100 microm in diameter. They appear to arise by amalgamation of the homologues of intercalated and striated ducts into macroducts. The walls of the macroducts consist of intermingled patches of simple cuboidal and simple columnar epithelia that occasionally include a tuft cell and are underlaid by an almost continuous layer of myoepithelium. A few cells have some modified basal striations, but most cells display a cytological organization that differs radically from either of their two putative ancestral cell types. Both tall and short epithelial macroduct cells have a paranuclear collection of ovate mitochondria and aggregates of what presumably are peroxisomes. Macroduct cells in both the female and male are pervaded by a system of tubular smooth endoplasmic reticulum (SER). In the female, the SER gives rise to membranous whorls that consist of numerous plies. As the macroducts approach their termini, a single row of small dense secretory granules appears just beneath their luminal surface. At the lobular periphery, the ducts taper down to become excretory ducts of normal dimensions. CONCLUSIONS: An accessory parotid gland occurs in T. thersites, but apparently is absent in the related species, T. brasiliensis. The ultrastructural data are consistent with a possible steroidogenic function, although other features of the gland might relate to the elaboration of a secretory product associated with feeding on chitinous beetles. The macroducts conceivably function as reservoirs of preformed saliva.

Animals

Intercellular material in the basal and lateral folds of parotid serous cells in four species of bats.

BACKGROUND: Basal folds are slender plications at the basal surface of acinar cells in the salivary glands of many mammalian species. These largely organelle-free folds increase the surface area of the basal plasmalemma manyfold and are unquestionably involved in the translocation of organic and inorganic molecules and water into the acinar cells. METHODS: Specimens of salivary glands were obtained from over 230 species of live-trapped bats from major areas of the globe. Tissues for electron microscopy were fixed and processed by conventional means. RESULTS: A number of the bat species examined had dense material in the intercellular spaces between basal and lateral folds of serous cells in the parotid gland. This intercellular material was particularly prominent in three species of New World bats, viz., Pteronotus parnellii, P quadridens, and Phyllostomus latifolius, and in one species of Old World bats, Chalinolobus argentatus. This dense material, which has a farinaceous texture, appears not to pass through tight junctions, so it is excluded from the lumina of intercellular canaliculi and acini. The dense material originates in the acinar cells--it is carried to the membranes of the folds via coated vesicles, which empty their dense content by exocytosis into the intercellular space. Similar dense material is present in the intercellular spaces of the basal labyrinth of striated ducts in the two species of Pteronotus. The manner in which this material accumulates in the striated duct is unclear. CONCLUSIONS: Although the function of the intracellular dense material is undetermined, it appears to be placed strategically to influence molecular traffic into acinar cells or to modulate the paracellular pathway. From a comparative evolutionary perspective, we hypothesize that, in bats, the combination of basal folds and extracellular densities is associated with insectivory. Similar morphologies appear to be lacking in frugivorous or nectarivorous species.

Animals

An unusual parotid gland in the tent-building bat, Uroderma bilobatum: possible correlation of interspecific ultrastructural differences with differences in salivary pH and buffering capacity.

The tent-building bat, Uroderma bilobatum, is a small, frugivorous phyllostomid bat with a broad neotropical distribution. Generally found in humid forest, this bat lives in small groups that create daytime "roosts" from large leaves of a variety of tropical plants. Fruit eating engenders a variety of ecological and physiological challenges for bats, some of which could require adaptive features in their salivary glands. The parotid salivary glands of Uroderma bilobatum were prepared for transmission electron microscopy by using methods that have become standard for field work. The parotid gland is extremely unusual in structure. Although the secretory endpieces still produce serous granules with a complex substructure, they are modified into quasi striated ducts. Their basal folds, which are extensive, occasionally harbor some vertically oriented mitochondria, imparting a resemblance to striated ducts. Other evidence for the endpiece origin of these parenchymal components is a well-developed system of intercellular canaliculi, structures that never occur in bona fide striated ducts. The long but sparse intercalated ducts consist of two types of cells, each of which elaborates a modest number of secretory granules of differing substructure. Striated ducts are of conventional morphology, except that a few dark cells shaped like wine glasses are present in their walls. The striated duct cells produce no secretory granules, but their apical cytoplasm may contain some small, empty vesicles. Capillaries lie in longitudinal grooves in the base of the duct cells, an arrangement that might enhance electrolyte exchange. Excretory ducts consist of simple cuboidal epithelium composed of cytologically unspecialized cells that sometimes includes a dark cell. It was concluded that salivary glands could have a major role in adapting species to acquire nutrients from marginal sources, such as tropical fruits, which have a low protein and sodium content. The unusual parotid acinar cells in Uroderma bilobatum are discussed in the context of salivary pH and buffering capacity. Comparisons are made with four other bat species, including an insectivorous species with a salivary pH > 8.0 and a very high buffering capacity, an intermediate species, and a fruit bat with acidic-stimulated saliva and very low buffering capability. Such interspecific comparisons provide a foundation for hypothesizing that ultrastructural features of the acinar cell basolateral membranes and intercellular canaliculi correlate with differences involving Na/H+ exchangers and release of HCO3- and, thus, are associated with the species differences that are important to diet and nutrient acquisition.

Animals

Cytomegalovirus infection in the submandibular and parotid salivary glands of an African grass mouse (Arvicanthus dembeensis).

The submandibular and parotid glands of one of five specimens of African grass mice (Arvicanthus dembeensis) were found to be infected with cytomegaloviruses, producing a profound cytomegaly in certain cells at the juncture of secretory endpieces and intercalated ducts. These cytomegalic cells tended to have multiple nuclei, many of which contained a characteristic reticular inclusion. The viruses appeared to arise in association with the intranuclear inclusions, then passed through the nuclear envelope to the cytoplasm where they budded into Golgi saccules or into small vacuoles, presumably of Golgi origin. Fusion of small virus-carrying vacuoles led to the formation of large vacuoles containing a plethora of viruses. Viruses were liberated into gland lumina via fusion of the vacuoles with the luminal plasmalemma. Fusion of vacuoles with dehiscent ones resulted in a form of chain exocytosis. The development of cytomegaloviruses in salivary glands may differ in details in a species-specific manner.

Animals

Plasticity and patterns of evolution in mammalian salivary glands: comparative immunohistochemistry of lysozyme in bats.

Salivary gland plasticity was a significant adaptive feature in the mammalian radiation. This plasticity is reflected in remarkable and well-documented interspecific phenotypic variation in gland ultrastructure and in the chemical components of saliva. However, comparative data are still too sparse for determination of evolutionary trends that combine phenotypic patterns with evolutionary history and the actual secretory products. Although our theoretical approach assumes that natural selection has taken advantage of salivary gland plasticity in gene regulation, gland development, and secretory cell organelles and processes, it still is difficult to delineate the biological roles of secretory products in the context of ecological adaptation. In the present investigation we used immunohistochemical techniques and a polyclonal antiserum against lysozyme to compare the parotid and principal submandibular glands in a set of 12 species of microchiropteran bats. With this data set we used comparative methods and phylogenetic trees to develop the foundations for testable hypotheses about the molecular genetics and adaptive significance of lysozyme production in bats. By comparing immunohistochemical results with ultrastructure, lysozyme-like immunoreactivity was associated with serous secretory granules in parotid gland acinar calls, parotid gland intercalated duct cells, and submandibular gland demilune cells. Lysozyme production in submandibular gland demilune cells marks a point of evolutionary divergence between three families of insectivorous bats and four families composed of species with diverse diets (ranging from carnivory to nectarivory). In terms of diet, lysozyme-like immunoreactivity corresponded most strongly with feeding on hard-bodied insects, leading to the hypothesis that lysozyme serves as an important chitinase in bat saliva.

Adaptation, Physiological

Ultrastructure of major intraglandular ducts in the parotid gland of the African mole-rat.

The parotid gland of a female African mole-rat, Tachyoryctes splendens, was examined by light and electron microscopy. A pure seromucous gland of conventional histology, its striated and excretory ducts contain prominent cytoplasmic inclusions that are lightly stained with toluidine blue. At the ultrastructural level, the inclusions are seen to consist of a light to moderately dense structureless matrix in which are suspended scattered, randomly oriented filaments that either are 4-7 nm or approx 14 nm thick. A few multivesicular bodies or putative lipid droplets are sparsely distributed in the inclusions. Even though the inclusions lack an encompassing membrane, all other formed cytoplasmic structures are excluded. These inclusions are not present in the ducts of the submandibular gland of the mole-rat. The inclusions may confer special properties on the parotid gland of this fossorial animal that permit it to cope with the exigencies of a subterranean existence.

Africa

The developmental role of type III and type IV cells in the rat submandibular gland.

In addition to seromucous cells and a few mucous cells (Type II cells), submandibular glands of 2-8 month old rats contain two additional cell types: type III and type IV. Type III cells contain serous-type secretory granules that sometimes have a complex substructure; type IV cells appear to be seromucous, but their granules clearly are different from those in conventional endpiece seromucous cells. Both type III and IV cells are involved in histogenesis of new endpieces in a process that differs markedly from that occurring in perinatal glands. In this process, intercalated ducts bud and give rise to immature endpieces that consist entirely of type III cells. These differentiate into type IV cells, which in turn differentiate into standard seromucous cells. Concurrently, the intercalated ducts become shorter as their most distal cells differentiate into granular duct cells. This type of developmental process begins approximately 2 months postnatally, when histogenesis of endpieces by means of terminal tubules has ended, and continues until 6 months, when its frequency sharply declines.

Animals

Megamitochondria in the serous acinar cells of the submandibular gland of the neotropical fruit bat, Artibeus obscurus.

BACKGROUND: As part of a continuing investigation of the comparative ultrastructure of chiropteran salivary glands, we examined the submandibular glands of eight species of neotropical fruit bats in the genus Artibeus. We previously described secretory granules of unusual substructure in the seromucous demilunar cells of this organ in some species in this genus. In the present study, we turned our attention to the serous acinar cells in the same glands. METHODS: Specimens of eight species of Artibeus were collected in neotropical localities. Salivary glands were extirpated in the field and thin slices were fixed by immersion in triple aldehyde-DMSO or in modified half-strength Karnovsky's fixative. Tissues were further processed for electron microscopy by conventional means. RESULTS: In contrast to seromucous cells, which exhibit species-specific diversification in bats of this genus, the secretory apparatus and secretory granules in the serous acinar cells are highly conserved across all seven species. The single exception involves the mitochondria in one species. In this instance, some of the serous cell mitochondria in Artibeus obscurus are modified into megamitochondria. Such organelles usually have short, peripheral cristae; a laminar inclusion is present in the matrix compartment of every outsized organelle. Inclusions of this nature never are present in normal-size mitochondria in the serous cells. None of the megamitochondria were observed in the process of degeneration. CONCLUSIONS: The giant mitochondria in A. obscurus have a matrical structure that is radically different from that of the only other megamitochondria reported to occur in bat salivary glands. The factors that lead to variation in megamitochondrial substructure in different species, as well as the functional capacities of such giant organelles, are unknown.

Animals

Ultrastructure of the unusual accessory submandibular gland in the fringe-lipped bat, Trachops cirrhosus.

BACKGROUND: The phyllostomid fringe-lipped bat, Trachops cirrhosus, is sui generis (in a family of ca. 138 species) in that it subsists in part on tropical frogs. These amphibians frequently possess highly toxic integument. We examined the salivary glands of this bat to determine if these glands could be the source of protective factors that permit consumption of seemingly unsavory prey. The parotid and principal salivary glands of this bat are similar to homologous glands in other phyllostomids, but the accessory submandibular gland is unique. METHODS: The accessory submandibular glands of live-trapped T. cirrhosus were fixed and processed for transmission electron microscopy by conventional means. RESULTS: The accessory submandibular gland consists of follicles and ducts. The principal cells of the follicular walls have an abundance of rough endoplasmic reticulum (RER), free ribosomes, and extensive Golgi apparatuses. Typically, these cells have relatively few serous secretory granules. The ells contain collections of peculiar lipid droplets, and some of their mitochondria have dense crystalloids within expanded cristae. A layer of irregular, moderately dense bodies lies immediately subjacent to the luminal plasmalemma; it is not clear if these structures are endocytotic or exocytotic. Clusters of mucous cells, some of which have a single, hugely distended RER cisterna, are ensconced in the follicular walls; mucus from these cells reaches the lumen via intercellular canaliculi. Ducts progress from simple cuboidal to simple columnar epithelium. They lack basal striations, and their constituent cells contain relatively few mitochondria. Follicles and ducts have numerous myoepithelial cells at their periphery, and both are heavily innervated by hypolemmal nerve terminals. CONCLUSIONS: The unusual accessory submandibular gland in T. cirrhosus documents the extreme modifications in gland histology and in cell ultrastructure that have occurred in mammalian families. The cells composing the follicle walls and ducts bear little similarity to typical acinar or duct cells. Duplication of the submandibular gland in some bat lineages might be the key innovation underlying such plasticity. The heavy innervation of both follicles and ducts also implies that these structures are sensitive to and capable of responding to various inputs, perhaps including dietary factors.

Animals

Ultrastructure of the parotid salivary glands in seven species of fruit bats in the genus Artibeus.

BACKGROUND: In previous studies, we determined that the submandibular glands of five species of Neotropical fruit bats in the genus Artibeus had seromucous granules in their demilune cells with substructures that varied interspecifically in accordance with systematic relationships. Moreover, the striated ducts in these frugivores exhibited structural modifications that apparently are related to the consumption of a diet rich in potassium, but deficient in sodium. We now turn our attention to the parotid gland in a large number of species in this genus to determine if it follows the same structural pattern as does the submandibular gland. METHODS: Members of seven different species of Artibeus were live-trapped in various Neotropical locations. The parotid glands were extirpated from euthanized bats, fixed in the field, and prepared for electron microscopic examination by conventional means. The parotid glands in all seven species were virtually identical in morphology. The acinar cells (determined to be seromucous on the basis of ultrastructural criteria) contain large numbers of what appear to be vacuoles, but which are a type of secretory granule. These granules have an electron-lucent matrix and may contain one or several circular membranous profiles arranged either concentrically or in a random array. These granules appear to form by progressive dilatation of the termini of Golgi saccules, with the nascent granules finally severing their connection with the Golgi apparatus. Many of the internal membranous profiles are formed simply by invaginations of the limiting membrane of the granule; others may result from indentation of the limiting membrane by protrusions from adjacent granules; the source of multiple internal membranes in certain granules is unclear. The exocytosis of these granules results in the acinar and intercalated duct lumina being filled with an abundance of membranous material. Such extruded membranes are present in some striated ducts, but not in others, suggesting that they are degraded during passage through the duct system. The striated ducts are of conventional appearance, lacking the frondose processes that are prominent in the submandibular glands of Artibeus. CONCLUSIONS: The parotid gland in Artibeus shows none of the interspecific ultrastructural variability that characterizes the submandibular gland in bats of this genus. The seromucous acinar cells secrete granules that release phospholipids as well as glycoconjugates into the saliva. Based on the lack of frondose processes with their sodium-transporting portasomes, the striated ducts of the parotid gland are less concerned with electrolyte homeostasis than are those in the submandibular gland.

Animals

Ultrastructure of the salivary glands in the midtongue of the common vampire bat, Desmodus rotundus.

BACKGROUND: All examined mammals have at least two sets of lingual salivary glands: von Ebner's glands and Weber's glands. A third set, the glands of Blandin and Nuhn, is present in the tongues of some but not all mammals. Vampire bats, Desmodus rotundus, are unusual in that they possess another set of lingual glands, these being in the midtongue region. METHODS: The anterior half of the tongue was extirpated from several adult vampire bats, dissected, and tissue blocks derived from the midregions of the body of the tongue prepared for transmission electron microscopy by conventional means. RESULTS: The midlingual glands are in the form of long, tubular secretory endpieces that are succeeded by ducts of simple morphology. In general, the secretory portions consist of two cell types, which may be intermingled in the same tubule or may form tubules that consist wholly of one cell type or the other. Seromucous cells usually have one or several rough endoplasmic reticulum cisternae that are hugely distended by a homogeneously dense material. Their granules have a bizonal substructure: one or several dense bands are embedded in a lighter matrix. Mucous cells are rather typical in structure, but their secretory product is different from run-of-the-mill mucous droplets. These droplets vary in density from cell to cell. In some cells, these droplets have a relatively light matrix; in other cells, the droplet is unusually dense, consisting mainly of a dark, structureless matrix with marginal lenticular lacunae of low density in which some short, irregular filaments are scattered. A rare finding is the presence of ciliated cells intermingled with secretory endpiece cells. The cilia are of conventional morphology. Secretory tubules are succeeded by ducts that resemble intercalated ducts; the epithelium of these ducts gradually increases in height to form a kind of excretory duct, without the intervention of striated ducts. As the ducts approach the lingual surface, the epithelium changes to stratified squamous. CONCLUSIONS: Saliva produced by the midlingual glands may be an aid in the reciprocal grooming behavior of vampire bats. Based on their morphology, the excurrent ducts may not modify the initial saliva elaborated by these glands and might act simply as pipelines by which the saliva reaches the mouth.

Animals

A unique parotid gland in Hart's little fruit bat, Enchisthenes hartii.

BACKGROUND: Hart's little fruit bat, Enchisthenes hartii, is uncommon and, although it has been the subject of recent molecular genetic studies, is little known biologically. Because chiropteran salivary glands vary interspecifically in ways that reflect evolutionary history and ecology, we examined the parotid gland in E. hartii to ascertain the extent to which it resembles homologous glands in species to which this bat presumably is related. METHODS: The parotid glands were prepared for electron microscopic examination by conventional means. RESULTS: The parotid gland of E. hartii is structurally unique among all previously studied species of bats (> 230 species examined) and other mammals. In contrast to the same gland in other mammals, the parotid gland in E. hartii lacks secretory endpieces. In their place, there is a type of striated duct. Thus, in this species single secretory elements consist of (proceeding in the direction of salivary flow): striated duct--intercalated duct--and a conventionally located striated duct. The proximal ducts possess microvillus-lined intercellular canaliculi, whereas the walls of the distal ducts include occasional dark cells. Some small serous-like granules may be present in the intercalated duct cells. CONCLUSIONS: The function(s) and biological role of the unique parotid gland in E. hartii are unknown. Nevertheless, the presence of two sets of striated ducts provides two separate glandular components seemingly capable of electrolyte transport. This might be of adaptive significance in enabling this species to make use of tropical nutrient resources that otherwise would be unavailable. The uniqueness of its parotid glands lends support to the current hypothesis that E. hartii should be classified as a monotypic genus rather than as a species of Artibeus, whose members it resembles morphometrically.

Animals

Ultrastructure of Weber's salivary glands of the root of the tongue in the rat.

BACKGROUND: The mammalian tongue encompasses several sizeable agglomerations of minor salivary glands. The ultrastructure of the various glands in the body of that organ has already been determined. In contrast, almost nothing is known of the structure of Weber's glands, a collection of salivary glands in the root of the tongue. METHODS: The entire tongue was extirpated from anesthetized adult male rats that had been perfused with fixative and specimens of tissue that included Weber's glands were dissected from the lingual root. These were prepared for electron microscopic examination by conventional means. RESULTS: Weber's glands in the rat are mixed glands, consisting of long mucous tubules that often are capped by serous demilunes. There appear to be no ducts per se, the mucous tubules increasing in caliber and approaching the crypts of the dorsal lingual surface while still retaining their mucous secretory character. As these ducts near the surface, their lining changes to stratified squamous epithelium. The mucous cells are cytologically similar to those in the sublingual glands of the same animal. Mucous droplets undergo vertical fusion to form centrally situated intracellular channels through which mucus is exocytosed, much in the same manner as goblet cells. The serous cells, which have all of the hallmarks of protein-secreting cells, probably empty their secretory granules via cellular extensions that directly reach the tubule lumen since there are no intercellular canaliculi between adjacent mucous cells. CONCLUSIONS: The mucus elaborated by Weber's glands undoubtedly aids in swallowing dry food. We postulate that the serous cells in these glands, as in the more anterior von Ebner's glands, might play a role in the mechanism of taste, especially where posteriorly situated, nonlingual taste buds are concerned.

Animals

Iron overload in the rat pancreas following portacaval shunting and dietary iron supplementation.

Reproduction of pancreatic iron overload in an animal model has been difficult to achieve primarily because of the first-pass extraction of iron by the liver. We hypothesized that portacaval shunting would avoid this hepatic phenomenon and increase pancreatic iron deposition. An end-to-side portacaval shunt was surgically created in male Sprague-Dawley rats, and they were subsequently fed a carbonyl iron-supplemented diet for 17 weeks. This resulted in marked iron accumulation in the pancreas (1621 +/- 188 micrograms/g) compared to minimal deposition in sham-operated rats fed the same diet (138 +/- 53 micrograms/g). Iron deposition in the acinar and centroacinar cells was confirmed histologically by Gomori staining, as well as by ultrastructural examination. Iron overloading was associated with enhanced oxidative stress evidenced by a twofold increase in the levels of glutathione disulfide and thiobarbituric acid-reactive substances. Also, adducts of proteins with malondialdehyde and 4-hydroxynonenal were demonstrated in acinar and ductal cells. Other apparent consequences of iron overload were a 50% reduction in pancreatic amylase content and a decrease in pancreatic protein concentration. These hypotrophic changes were associated with a reduced mass of zymogen granules in the acinar cells noted histologically. Our results show that a combination of portacaval shunting and carbonyl iron feeding achieve pancreatic iron overload and support the role of oxidative stress in the pathogenesis of iron-induced damage in the pancreas.

Aldehydes

Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria.

The effect of myocardial ischemia on mitochondrial oxidative phosphorylation was investigated using isolated, buffer-perfused rabbit hearts. After 45 min of global ischemia, oxidative phosphorylation was decreased only in the subsarcolemmal population of mitochondria with all substrates tested. The oxidation of N,N,N',N' tetramethyl p-phenylenediamine-ascorbate, an electron donor to cytochrome oxidase via cytochrome c, was decreased in subsarcolemmal mitochondria [ischemia (n = 6): 76 +/- 3 vs. control (n = 5): 105 +/- 6 nanoatoms O.min-1.mg-1, P < 0.01] but not in interfibrillar mitochondria. Only minor morphological changes were observed by electron microscopy in the isolated mitochondria after ischemia. Neither cytochrome oxidase activity measured under conditions for maximal activity nor the apparent Michaelis constant and maximum velocity values of the two cytochrome c binding sites were different in subsarcolemmal mitochondria isolated from ischemic and control hearts. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in intact subsarcolemmal mitochondria. Ischemic damage to the terminal segment of the electron transport chain involves a decrease in the content of cytochrome c, whereas the expressible catalytic activity of cytochrome oxidase remains unchanged.

Adenosine Diphosphate