Two cases of culture proven Mycobacterium tuberculosis presenting with a broad-complex tachycardia and non-caseating granulomas.

Tuberculosis is a leading cause of death worldwide. It affects pulmonary and extra-pulmonary sites with a multitude of differing presentations. In this report, we describe two cases in which TB causes myopericarditis and presents with a broad-complex tachycardia that did not respond typically to standard anti-arrhythmic therapy; a very rare presentation with limited description in the literature. Both patients required extensive investigation culminating in identifying lymph nodes amenable to biopsy under endobronchial ultrasound guidance. It was not until both patients received anti-tuberculous chemotherapy alongside anti-arrhythmic management that any improvement to their condition was witnessed. Therefore, we recommend that the clinician should have a high index of suspicion for TB in any patient presenting with a broad-complex tachycardia that is not responding to standard first line management, especially if the patient is from a high risk background. We recommend an active diagnostic pursuit, and lymph node biopsy under endobronchial ultrasound guidance.

Concentrations and interactions of selected essential and non-essential elements in bowhead and beluga whales of arctic Alaska.

In this study, we evaluated concentrations of twelve essential and non-essential elements (As, Cd, Co, Cu, Pb, Mg, Mn, Hg, Mo, Se, Ag, and Zn) in tissues of bowhead (Balaena mysticetus) and beluga (Delphinapterus leucas) whales from arctic Alaska (USA) and northwestern Canada. Tissue samples were collected between 1983 and 1997, mostly in 1995-97. The essential elements are reported to develop reference ranges for health status determination, and to help assess known or suspected interactions affecting toxicoses of cadmium (Cd) and mercury (Hg). In some tissues, Cd, Hg, and selenium (Se) were present at concentrations that have been associated with toxicoses in some domestic animals. Nevertheless, tissue levels of all elements were within ranges that have been reported previously in marine mammals. While mean Ag concentrations in beluga whale liver were relatively high (15.91 micrograms/g ww), Ag was not associated with hepatic Se levels or age, contrary to previous findings. Significant associations included: Cd with age, Zn, or Cu; Cu with age, Zn or Ag; and Hg with age, Se, Zn, or Cu. This study found hepatic Hg:Se molar ratios to be consistently lower than unity and different between species. Possible explanations for observed elemental correlations (i.e., interactions) and ancillary mechanisms of Cd and Hg detoxification are discussed.

Concentrations and interactions of selected essential and non-essential elements in ringed seals and polar bears of arctic Alaska.

In this study, we evaluated concentrations of twelve essential and non-essential elements (As, Cd, Co, Cu, Pb, Mg, Mn, Hg, Mo, Se, Ag, and Zn) in tissues of ringed seals (Phoca hispida) and polar bears (Ursus maritimus) of arctic Alaska (USA). All samples were collected between 1995-97 in conjunction with subsistence harvests. The essential elements are reported to help develop reference ranges for health status determination and to help assess known or suspected interactions affecting toxicoses of cadmium (Cd) and mercury (Hg). In some tissues, Cd, Hg, and selenium (Se) were present at concentrations that have been associated with toxicoses in some domestic animals. Nevertheless, tissue levels of all elements were within ranges that have been reported previously in other pinnipeds and polar bears. Significant associations included: Cd with Zn or Cu; Cu with Zn or Ag; and Hg with Se, Zn, or Cu. This study found hepatic Hg:Se molar ratios to be lower than unity and different between the two species. Based upon significant differences in mean tissue elemental concentrations for polar bear versus ringed seal, we concluded that biomagnification factors (bear/seal) were significant for: Cu in liver and muscle; Pb in kidney; Se in kidney and muscle; Zn in liver and muscle; and Hg in liver. Possible explanations for observed elemental correlations (i.e., interactions) and ancillary mechanisms of Cd and Hg detoxification are discussed.

Microcystin-LR decreases hepatic and renal perfusion, and causes circulatory shock, severe hypoglycemia, and terminal hyperkalemia in intravascularly dosed swine.

Cross-bred, anesthetized female swine were given intravascularly a lethal (72 microg/kg; n = 6) or toxic-sublethal (25 microg/kg; n = 6) dose of microcystin-LR (MCLR), from Microcystis aeruginosa, or the vehicle (n = 4). At the high dose, from 12 to 18 min after administration, central venous pressure and hepatic perfusion were significantly lower, and shortly thereafter, portal venous pressure was significantly higher and aortic mean pressure was significantly lower than controls. By 45 min postdosing, serum bile acids, lactate, potassium, and total bilirubin, as well as blood pO2, were significantly higher, while hematocrit, platelet count, and blood bicarbonate, pCO2, and base excess were significantly lower than controls. By 90 min, serum arginase, urea nitrogen, inorganic phosphorus, and creatinine were significantly higher, while glucose and blood pH were significantly lower than in controls. By 150 min, serum alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase, and creatinine phosphokinase activities were significantly higher than controls. At the low dose, significant differences from controls occurred in hemodynamic, organ perfusion, and serum chemistry parameters, but such changes generally took longer to occur and were of a lesser magnitude than at the high dose. Livers of the high-dose swine were swollen and dark red-purple, and exuded excessive blood on the cut surface. Based on increases in liver weight and liver hemoglobin, 38% of the total blood volume was lost into the liver. Terminally, all high-dose swine experienced hyperkalemia, and most had severe hypoglycemia. Death due to acute MCLR toxicosis in intravascularly dosed swine appears to result from severe intrahepatic hemorrhage, partial obstruction of blood flow through the liver, circulatory shock, severe hypoglycemia, and/or terminal hyperkalemia.

Organochlorine pesticide and polychlorinated biphenyl residues in Canada geese (Branta canadensis) from Chicago, Illinois.

Breast muscle samples, with or without overlying adipose tissue and skin, were obtained from Canada geese collected in northeastern illinois while undergoing feather molt. Specimens were evaluated for contaminant concentrations to determine if they would be acceptable as human food provided through government-subsidized programs. Samples were baked, allowing fat to drip free, and assayed for persistent organochlorine pesticides and polychlorinated biphenyls. Residues of heptachlor epoxide, dieldrin, DDE and PCBs (as Arochlor 1248) were detected. The specimens contained relatively low concentrations of contaminants, such that US Department of Agriculture residue limits for meat were exceeded in only 1 sample. Baking of breast muscle without the overlying skin and adipose tissue resulted in reductions in concentrations of detectable compounds. Fewer samples baked with the skin attached had detectable concentrations of heptachlor epoxide, dieldrin and PCB then samples cooked without skin; however, the converse was true for DDE. Periodic monitoring for environmental contaminants such as PCBs, exclusion of geese from localities where samples have contaminants such as PCBs, exclusion of geese from localities where samples have contaminants at concentrations that exceed recommended dietary limits, the use of processing and/or cooking methods which remove large amounts of lipid, and advisories that provide information on known health risks are recommended if wild resident Canada geese from the Chicago area are provided as food for underprivileged humans.

Development of fumonisin-induced hepatotoxicity and pulmonary edema in orally dosed swine: morphological and biochemical alterations.

The fumonisin (FB) mycotoxins induce liver injury in all species but induce fatal pulmonary edema (PE) only in pigs. They inhibit ceramide synthase in the sphingolipid biosynthetic pathway. To study the pathogenesis of PE, we examined the early events in the development of FB-induced PE and hepatotoxicity in pigs. Pigs were fed FB-contaminated culture material at 20 mg fumonsin B1 (FB1)/kg body weight/day. Groups of 4 pigs were to be euthanatized on 0, 1, 2, 3, 4, or 5 days after initial exposure to FB or when PE developed. Pigs developed PE beginning on day 3; none survived beyond day 4. Progressive elevations in hepatic parameters, including serum enzymes, bile acids, total bilirubin, and histologic changes, began on day 2. Early histologic changes in the lung (day 2) consisted of perivascular edema followed by interlobular and peribronchial edema. Ultrastructurally, alveolar endothelial cells contained unique accumulations of membranous material in the cytocavitary network beginning on day 2. Marked elevations in sphinganine, sphingosine, and their ratio began on day 1 for all tissues whether affected morphologically (lung, liver) or not (kidney, pancreas). The membranous material in endothelial cells may be accumulations of sphingoid bases with damage to the cytocavitary network. Thus, FB induces early elevations in sphingolipids and hepatic injury, followed by alveolar endothelial damage, which may be the critical event in the pathogenesis of PE in pigs.

Neutral red assay modification to prevent cytotoxicity and improve reproducibility using E-63 rat skeletal muscle cells.

Cellular uptake of neutral red dye (NR) is currently used as an indirect measure of viable cells in cultures. We used E-63 rat skeletal muscle cells to identify causes of NR assay variability and to develop modifications that substantially reduce it. Three methods of NR preparation and/or addition to cells were used. When NR medium was prepared, incubated overnight, and filtered to remove precipitates, the amount of dye precipitated varied greatly. Coefficients of variation (CVs) in NR uptake were greater than 25% between assays. Higher NR concentrations, longer incubation times, increased pH, and decreased temperature promoted NR precipitation in media. NR media prepared and filtered just prior to use or direct addition of prefiltered NR stock solution to cell cultures resulted in much smaller CVs between assays. NR was cytotoxic to E-63 rat muscle and primary quail myoblasts in a time- and concentration-dependent manner. NR exposure to E-63 cells for greater than 1.25 and 2 hr at 157 or 127 microg/ml, respectively, was associated with swelling and rupture of lysosomes. By contrast, there was no evidence of cytotoxicity when E-63 cells were exposed to NR for 1 hr at either 127 or 157 microg/ml. Primary quail myoblasts developed lysosomal swelling and ruptured more rapidly than E-63 cells when exposed to NR at either 127 or 157 microg/ml. For confluent 10-day cultures of E-63 cells exposed to NR at 127 microg/ml for 1 hr, the CVs within assay and between assays were 3.3-3.9% and 5.1%, respectively. For similarly exposed, actively replicating 3-day cultures of E-63 cells, the CVs within and between assays were 6.2-9.6% and 2.4%, respectively. NR uptake by the E-63 cells was linear with respect to viable cell number.

Forms and prevalence of intersexuality and effects of environmental contaminants on sexuality in cricket frogs (Acris crepitans).

Cricket frogs (Acris crepitans) from several different sites in Illinois were collected to assess the effects of environmental contamination on the prevalence of intersex gonads. Of 341 frogs collected in 1993, 1994, and 1995, 2.7% were intersex individuals. There was no statistically significant relationship between the chemical compounds detected and cricket frog intersexuality. However, there was an association approaching significance (p = 0.07) between the detection of atrazine and intersex individuals. A comparison of reference sites with sites that had point polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF) contamination revealed a significant relationship between sex-ratio reversal and contamination with PCBs and PCDFs. The sex ratio of juvenile frogs studied from three sites with PCB and PCDF point contamination favored males over females, which was the opposite of the sex ratio in control ponds (p = 0.0007). The statistically significant correlation between organochlorine contamination and sex-ratio reversal suggests PCBs and PCDFs can influence cricket frog sexual differentiation. The current study suggests that in cricket frogs, sex ratios and the prevalence of intersex gonads are altered by environmental contamination.

Rhamnus cathartica (buckthorn) hepatocellular toxicity in mice.

The toxicity of the plant Rhamnus cathartica was assessed in mice after the plant was identified as a potential cause of an idiopathic neurologic disease in horses. Another member of the Rhamnaceae family, Karwinskia humboldtiana, is neurotoxic to mammals and birds and can induce hepatic degeneration and necrosis. To investigate the toxicity of R. cathartica, a 34-day feeding trial in mice was conducted using a complete rodent diet with 0, 5, or 25% added R. cathartica. No clinical signs or gross lesions were seen, and all major tissues were histologically normal except the liver. The livers of mice fed R. cathartica had marked hepatocellular swelling. Results from periodic acid-Schiff reaction staining and from electron microscopy confirmed that the swelling was due to deposits of monoparticulate glycogen (beta particles) in the cytoplasm. Glycogen deposition is an uncommon toxic change in cells. Apparently, compound(s) in R. cathartica directly or indirectly interfered with glycogen metabolism (either glycogenesis or glycogenolysis). Mechanistic and chronicity studies with R. cathartica are needed to investigate the pathophysiology of the glycogen disturbance and to determine if hepatic injury progresses and if other organs will be injured.

Distribution of tritiated dihydromicrocystin in swine.

The distribution of tritiated dihydromicrocystin [3H]2H-MCLR was studied in anesthetized specific-pathogen-free pigs. Two doses were administered i.m. and one dose was given via an isolated ileal loop. At 4 hr after i.v. administration of the toxin at 25 micrograms/kg, 64.6% of the total dose (%TD) was located in the liver, with smaller amounts distributed to the kidneys (1.2% TD), lungs (1.75% TD), heart (0.22% TD), ileum (0.13% TD) and spleen (0.04% TD). A similar distribution was found at 4 hr postdosing in pigs given 75 micrograms/kg, although the liver contained a lower fraction of the total dose, at 46.99% TD, and the kidneys had somewhat more, at 2.19% TD, than the low dose. At the high dose, the fractions of the amount given accounted for by the lungs (0.55% TD), heart (0.23% TD), ileum (0.20% TD) and spleen (0.07% TD) were similar to those at the low dose. The livers of the pigs given 75 micrograms/kg via the ileal loop, at 5 hr postdosing, contained 49.5% TD and the ileum had 33.94% TD. Smaller amounts were distributed to kidneys (1.04% TD), lungs (0.65% TD), heart (0.81% TD) and spleen (0.16% TD). The livers of both groups dosed at 75 micrograms/kg contained higher concentrations of toxin, but lower percentages of the total dose, than the livers of pigs dosed at 25 micrograms/kg. Larger increases in serum arginase in the two 75 micrograms/kg groups were associated with histological evidence of more severe liver damage than at the 25 micrograms/kg dose. Analysis of radiolabeled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [3H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [3H]2H-MCLR is rapidly concentrated in the liver of swine, whether given i.v. or via an isolated ileal loop, that at extremely toxic doses uptake is slowed, and that it is as toxicologically active as the parent compound.

Toxicokinetics of tritiated dihydromicrocystin-LR in swine.

The toxicokinetics of tritiated dihydromicrocystin-LR ([3H]2H-MCLR) were studied in anesthetized, specific-pathogen-free pigs. Pigs were dosed with radiolabeled plus non-labeled 2H-MCLR at 25 or 75 micrograms/kg i.v., or via an isolated ileal loop at 75 micrograms/kg. The i.v. doses were rapidly removed from the blood. At either i.v. dose, more than half the radiolabel from [3H]2H-MCLR present in the blood at 1 min postdosing was cleared by 6 min. The blood clearance at the 75 micrograms/kg dose was slower than at the 25 micrograms/kg dose. Accordingly, at the high dose, the concentrations of the toxin in blood were disproportionately higher from 10 min after dosing until the study ended 4 hr later. The decreased clearance is presumably due to decreased elimination from the blood as a consequence of the hepatic injury that was observed histologically. Following administration of [3H]2H-MCLR at 75 micrograms/kg via the ileum, the maximal toxin concentration in blood was achieved at 90 min after dosing. At that time the [3H]2H-MCLR concentration in portal venous blood was 3.6 times higher than in peripheral venous blood. Although bile production varied, following i.v. dosing radioactivity was detected in bile as early as 12 min postdosing in one animal. This study demonstrated that [3H]2H-MCLR is rapidly removed from the blood of anesthetized swine and that excretion of the radiolabel into bile may begin within 30 min of dosing.

Intense infections with a variant of Myxobolus procerus (Myxosporea) in muscle of trout-perch (Percopsis omiscomaycus) in Duluth Harbor, Lake Superior.

Intense infections of a variant of Myxobolus procerus (Kudo, 1934) are described from trout-perch (Percopsis omiscomaycus (Walbaum)) collected in Duluth Harbor, Lake Superior, USA. This particular population of parasites has spores that are identical in shape (narrow pyriform) to those described for M. procerus except that they are significantly smaller (13-14.5 microm long versus 15-17 microm long). In contrast to what was originally described for M. procerus, the plasmodia develop primarily within red and white striated muscle fibres and only rarely among the subdermal connective tissue. Most plasmodia were at or near the same stage of development. Typical development involves growth within the fibre. The parasite eventually replaces the entire content of the host cell and appears to halt development before rupturing the outer cell membrane. The only obvious host response was an occasional cyst being invaded by a localized cellular infiltrate. Infected fish appeared of normal health and no grossly evident myoliquefaction was seen. The infections involved several hundred plasmodia per fish and the question of why such unusually high levels of infection would develop in hosts inhabiting a polluted habitat is raised. It is suggested that proliferation of a pollution tolerant oligochaete (the suspected alternate host) in the harbour and/or a compromised host immune system may have increased the probability of successful transmission and development in trout-perch living in the harbour.

Sequential ultrastructural and biochemical changes induced by microcystin-LR in isolated perfused rat livers.

The cyanobacterial hepatotoxin, microcystin-LR (MCLR), is a potent protein phosphatase inhibitor that disrupts actin microfilament, cytokeratin intermediate filament, and microtubule networks in hepatocytes. To determine ultrastructural and biochemical changes that develop concurrently with microcystin-induced cytoskeletal disorganization, isolated rat livers were perfused with MCLR at 0.1 to 5.0 micrograms/ml for 5 to 40 min. Lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase changed over time, but trends for toxin-treated and control livers did not differ. The earliest toxin-induced ultrastructural changes, observed in livers perfused at 0.1 microgram/ml for 15-20 min or at 0.3 microgram/ml for 5-10 min, were loss of hepatocyte microvilli in the space of Disse, widening of sinusoidal fenestrae, disruption of sinusoidal endothelium, dilation of bile canaliculi with loss of microvilli, and widening of hepatocyte intercellular spaces. Lesions progressed with increasing toxin concentrations and exposure times. In livers perfused with MCLR at 0.5 microgram/ml for 10-20 min, hepatocytes had plasma membrane blebs and concentric whorls of rough endoplasmic reticulum, and there was marked disassociation of hepatocytes resulting in disrupted hepatic cords. At toxin concentrations of 2.0 or 5.0 micrograms/ml for 10-20 min, there was mild dilation of mitochondrial cristae, cytoplasmic vacuolization or invagination of plasma membranes, redistribution of organelles, and sometimes nuclear degenerative change. Some hepatocytes exhibited clusters of plasma membrane blebs radiating from round cytoplasmic structures, which may be composed primarily of condensed microfilaments.

Microcystin-LR and kinetics of cytoskeletal reorganization in hepatocytes, kidney cells, and fibroblasts.

Microcystin-LR (MCLR) is a cyanobacterial hepatotoxin that inhibits protein phosphatases 1 and 2A. To characterize cytoskeletal changes over time, hepatocytes were incubated with the toxin at 13.3 microM for 0, 2, 4, 6, 8, 16, 32, or 64 minutes. Changes in the hepatocytes were compared to those in cultured kidney cells and skin fibroblasts incubated with the toxin at 133 microM for 0, 2, 4, 8, 12, 16, or 24 hours. Cells were fixed and incubated with rhodamine-conjugated phalloidin, or primary antibodies against beta-tubulin and either vimentin or cytokeratin intermediate filaments (IFs), followed by fluorescein-conjugated secondary antibodies. The number of affected cells per 400 counted (NAC) with alterations in a specific cytoskeletal element were determined at each time point. In fibroblasts as well as kidney cells, changes occurred first in IFs, followed by microtubules (MTs), and later microfilaments (MFs). In some hepatocytes, IFs were affected first, but after 16 minutes, the NAC with altered MTs exceeded the NAC with alterations in other cytoskeletal elements. In both hepatocytes and non-hepatocytes, IFs and MTs condensed and collapsed around the nucleus. MFs similarly collapsed, but some of the actin radiated outward, producing a star-like appearance. The similarity of the cytoskeletal changes induced by MCLR in hepatocytes and non-hepatocytes suggests a common mechanism of action. Differences among cell types in sequential cytoskeletal alterations may be due to differences in phosphorylation of intracellular proteins.

Alterations in microtubules, intermediate filaments, and microfilaments induced by microcystin-LR in cultured cells.

Microcystin-LR (MCLR) is a cyanobacterial hepatotoxin that inhibits intracellular serine/threonine protein phosphatases causing disruption of actin microfilaments (MFs) and intermediate filaments (IFs) in hepatocytes. This study compared the effects of MCLR on the organization of MFs, IFs, and microtubules (MTs) in hepatocytes and nonhepatocyte cell lines and determined the sequence of toxin-induced changes in these cytoskeletal components. Rat renal epithelial cells and fibroblasts were incubated with MCLR at 100 or 200 microM for 6-18 hr. Rat hepatocytes in primary culture were exposed to the toxin at 1 or 10 microM for 2-64 min. Cells were fixed and incubated with primary antibodies against beta-tubulin, actin, and vimentin or cytokeratin IFs, followed by gold-labeled secondary antibodies with silver enhancement of the gold probe. The fraction of fibroblasts and hepatocytes with altered cytoskeletal morphology was evaluated as a function of MCLR dose and exposure time to assess the sequence of changes in cytoskeletal components. Changes in fibroblasts and some hepatocytes were characterized initially by disorganization of IFs, followed rapidly by disorganization of MTs, with the progressive collapse of both cytoskeletal components around cell nuclei. Many hepatocytes exhibited MT changes prior to effects on IF structure. Alterations in MFs occurred later and included initial aggregation of actin under the plasma membrane, followed by condensation into rosette-like structures and eventual complete collapse into a dense perinuclear bundle. The similarity of effects among different cell types suggests a common mechanism of action, but the independent kinetics of IF and MT disruption in hepatocytes suggests that there may be at least 2 sites of phosphorylation that lead to cytoskeletal alterations.

Comparative pathology of microcystin-LR in cultured hepatocytes, fibroblasts, and renal epithelial cells.

The cyanobacterial toxin microcystin-LR (MCLR) is a potent inhibitor of protein phosphatases 1 and 2A, and is selectively toxic to the liver in vivo and to isolated hepatocytes in vitro. This selectivity is believed to be due to toxin uptake via bile acid carriers. We investigated at the light and ultrastructural levels the effects of high concentrations of MCLR and long incubation times to determine in vitro whether fibroblasts and kidney cells (non-target cells) respond in the same manner as do hepatocytes (target cells) at low concentrations and short incubation times. Cultured rat skin fibroblasts (ATCC 1213) and rat kidney epithelial cells (ATCC 1571) were incubated with with MCLR at 133 microM for 1-24 hr. Lesions in these cells were compared with those in cultured hepatocytes incubated MCLR at 13.3 microM from 1 to 32 min. Lesions in hepatocytes, kidney cells, and fibroblasts were noted at 4 min, 1 hr, and 8 hr, respectively, after initial exposure to MCLR. Lesions in all three cell types progressed and included plasma membrane blebbing, loss of cell-to-cell contact, clumping and rounding of cells, cytoplasmic vacuolization, and redistribution of cytoplasmic organelles. Loss of microvilli, whorling of rough endoplasmic reticulum, dense staining and dilated cristae in mitochondria, and pinching off of membrane blebs were noted only in hepatocytes. Nuclear changes typical of apoptosis were observed only in fibroblasts and kidney cells. Similarities in responses of different cell types to MCLR exposure probably reflect a common biochemical mechanism of action, i.e., inhibition of protein phosphatases 1 and 2A as described by others.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of microcystin-LR on actin and the actin-associated proteins alpha-actinin and talin in hepatocytes.

Microcystin-LR (MCLR) is a commonly encountered blue-green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments, microtubules, and actin microfilaments (MFs) in affected cells. In this study, the effect of MCLR on the sequence of alterations in MFs and actin-associated proteins (AAPs) of isolated hepatocytes was examined in an effort to determine whether morphologic changes induced in MFs by microcystins are a result of prior dislocation of AAPs. We studied the effects of MCLR exposure on alpha-actinin and talin, two AAPs that play a role in the orientation of the MFs. Primary hepatocytes were incubated with 10 microns MCLR for 0-64 min. The distribution of actin, alpha-actinin, and talin were examined using fluorescence microscopy. MCLR induced similar changes in the distribution of actin and the AAPs. Actin filament redistribution was first observed after 12 min of MCLR exposure, and was characterized by detachment of MFs from the cell periphery, followed by condensation at distinct focal points and progressive collapse into the interior of affected cells. Changes in alpha-actinin and talin distribution were first observed after 20 min of toxin exposure. The AAPs appeared to detach from focal contacts on the cytoplasmic surface of the plasma membrane, condense into cytoplasmic aggregates, and ultimately collapse into a juxtanuclear bundle. The results of this study indicate that, in hepatocytes exposed to MCLR, the collapse of actin MFs occurs prior to the dislocation of alpha-actinin and talin. Changes in these actin associated proteins are not likely to account for the initial changes in actin MFs.

Effects of intravenous fumonisin B1 in rabbits: nephrotoxicity and sphingolipid alterations.

Fumonisin B1 is hepatotoxic in all species, but nephrotoxicity has only been reported in rats. It is a specific inhibitor of sphinganine N-acyltransferase. Our objective was to determine the target organs for fumonisin toxicosis in the rabbit. We administered fumonisin B1 ( > 95% pure) intravenously to adult rabbits and examined selected clinical, biochemical, and histological parameters for up to 5 days. In a pilot study, rabbits were given fumonisin B1 at 1, 0.5, 0.3, 0.15, or 0 mg/kg daily for 4 or 5 days and then euthanized. Additional rabbits were given a single dose of fumonisin B1 at 1 mg/kg and euthanized on day 2 or 4. In the formal time-course study, rabbits were given a single dose of fumonisin B1 at 0 or 1.25 mg/kg and euthanized on days 1, 3, or 5. Rabbits given multiple doses of fumonisin B1 were lethargic and anorectic, and had decreased urine production. Liver- and renal-associated clinical chemistry parameters were elevated. Renal lesions consisted of severe proximal tubular necrosis. Liver lesions were variable and consisted of mild necrosis, hepatocyte vacuolation, and bile stasis. The sphinganine-to-sphingosine ratio, in both target and nontarget tissues, was markedly elevated in treated rabbits. A single dose of fumonisin B1 induced renal but not hepatic injury. Therefore, the target organs for fumonisin B1 toxicity in rabbits are kidney and liver, with the kidney being more sensitive.

A report of Dactylogyrus amphibothrium (Monogenea) on the gills of European ruffe in western Lake Superior.

The Eurasian monogenean Dactylogyrus amphibothrium Wagener, 1857 is reported from the gills of ruffe (Gymnocephalus cernuus) in western Lake Superior. The parasite must have arrived with fish discharged with ship ballast in the mid 1980s. It is the 12th species of monogenean known to have been introduced and established with its host in North America.