Hypertrophy Of Mucous Cells Research Articles

Role of the melanocortin system in zebrafish skin physiology

The agouti-signaling protein (ASIP) acts as both a competitive antagonist and inverse agonist of melanocortin receptors which regulate dorsal-ventral pigmentation patterns in fish. However, the potential role of ASIP in the regulation of additional physiological pathways in the skin is unknown. The skin plays a crucial role in the immune function, acting as a physical limitation against infestation and also as a chemical barrier due to its ability to synthesize and secrete mucus and many immune effector proteins. In this study, the putative role of ASIP in regulating the immune system of skin has been explored using a transgenic zebrafish model overexpressing the asip1 gene (ASIPzf). Initially, the structural changes in skin induced by asip1 overexpression were studied, revealing that the ventral skin of ASIPzf was thinner than that of wild type (WT) animals. A moderate hypertrophy of mucous cells was also found in ASIPzf. Histochemical studies showed that transgenic animals appear to compensate for the lower number of cell layers by modifying the mucus composition and increasing lectin affinity and mucin content in order to maintain or improve protection against microorganism adhesion. ASIPzf also exhibit higher protein concentration under crowding conditions suggesting an increased mucus production under stressful conditions. Exposure to bacterial lipopolysaccharide (LPS) showed that ASIPzf exhibit a faster pro-inflammatory response and increased mucin expression yet severe skin injures and a slight increase in mortality was observed. Electrophysiological measurements show that the ASIP1 genotype exhibits reduced epithelial resistance, an indicator of reduced tissue integrity and barrier function. Overall, not only are ASIP1 animals more prone to infiltration and subsequent infections due to reduced skin epithelial integrity, but also display an increased inflammatory response that can lead to increased skin sensitivity to external infections.

Multiomics Provide Insights into the Key Molecules and Pathways Involved in the Physiological Adaptation of Atlantic Salmon (Salmo salar) to Chemotherapeutic-Induced Oxidative Stress

Although chemotherapeutics are used to treat infections in farmed fish, knowledge on how they alter host physiology is limited. Here, we elucidated the physiological consequences of repeated exposure to the potent oxidative chemotherapeutic peracetic acid (PAA) in Atlantic salmon (Salmo salar) smolts. Fish were exposed to the oxidant for 15 (short exposure) or 30 (long exposure) minutes every 15 days over 45 days. Unexposed fish served as the control. Thereafter, the ability of the remaining fish to handle a secondary stressor was investigated. Periodic chemotherapeutic exposure did not affect production performance, though survival was lower in the PAA-treated groups than in the control. Increased ventilation, erratic swimming, and a loss of balance were common behavioural manifestations during the oxidant exposure. The plasma reactive oxygen species levels increased in the PAA-treated groups, particularly after the third exposure, suggesting an alteration in the systemic oxidative stress status. Plasma indicators for internal organ health were affected to a certain degree, with the changes mainly observed after the second and third exposures. Metabolomics disclosed that the oxidant altered several circulating metabolites. Inosine and guanosine were the two metabolites significantly affected by the oxidative stressor, regardless of exposure time. A microarray analysis revealed that the gills and liver were more responsive to the oxidant than the skin, with the gills being the most sensitive. Moreover, the magnitude of the transcriptomic modifications depended on the exposure duration. A functional analysis showed that genes involved in immunity and ribosomal functions were significantly affected in the gills. In contrast, genes crucial for the oxidation-reduction process were mainly targeted in the liver. Skin mucus proteomics uncovered that the changes in the mucosal proteome were dependent on exposure duration and that the oxidant interfered with ribosome-related processes. Mucosal mapping revealed gill mucous cell hypertrophy after the second and third exposures, although the skin morphological parameters remained unaltered. Lastly, repeated oxidant exposures did not impede the ability of the fish to mount a response to a secondary stressor. This study provides insights into how a chemical oxidative stressor alters salmon physiology at both the systemic and mucosal levels. This knowledge will be pivotal in developing an evidence-driven approach to the use of oxidative therapeutics in fish, with some of the molecules and pathways identified as potential biomarkers and targets for assessing the physiological cost of these treatments.

Dynamic morphometrics of mucous cells reveal the minimal impact of therapeutic doses of peracetic acid on Atlantic salmon gill health

Mucous cells, the microscopic structural hallmark of mucosal surfaces, are highly responsive to environmental changes. Here we report how the gills of Atlantic salmon (Salmo salar) smolts responded to peracetic acid (PAA), a potent oxidative disinfectant and a candidate chemotherapeutant in aquaculture, through the Mucosal Mapping showing mucous cell size, volumetric density and defence activity, coupled with two-way histopathological scoring strategies. Two hundred and forty smolts were exposed to therapeutic doses of PAA on two occasions. The initial exposure included a 5-min bathing at concentrations of 0, 0.6, 1.2, and 2.4 ppm PAA. After a two-week recovery, the treatment groups were re-exposed to the same PAA concentrations for 30 min. Gill samples were collected at 2 h, 2 days, and 2 weeks after each exposure. The dynamic changes (i.e., size, volumetric density and defence activity) of the mucous cells were analysed on the distinct mucous cell populations in the gill filament and the lamella, as well as the lamellar thickness. Lamellar mucous cells were always significantly smaller (<70 μm2) and less dense (<2% volume) than those in the filament (70–100 μm2 and 8–11% volume) giving defence activities (combination of mean mucous cell area and volumetric density in a given tissue) of 0.1–0.4 for lamellae and about 0.6–1.4 for filaments, consistent with the functions of these branchial areas. A transient sub-acute mucous cell hypertrophy was a striking response in the gill lamella to PAA during the initial and re-exposure, particularly demonstrated by the groups exposed to 0.6 and 1.2 ppm where this size change was significant. Nonetheless, the recovery was quick, suggesting more an effect of general stress than dose of PAA. Similarly, a transient reduction in hyperplasia was noted as mucous cell density decreased on the filament, but generally significant hyperplasia was not detected, and volumetric density remained unaltered regardless of treatment doses and duration of exposure. The defence activity of the lamella and the filament demonstrated a transient tendency to decrease after the initial exposure but was minimally affected by re-exposure. Lamellar thickness was not markedly affected by the highest PAA dose and overall was positively correlated with mucous cell size. The results from two independent histopathological scorings revealed that at least 93% of the evaluated gill filaments per fish were categorised as healthy. Taken together, mucous cells in the gills of salmon smolts responded with transient hypertrophy of mucous cells to therapeutic doses of PAA however the impact was minimal, and the mucosal morphometrics were in agreement with the marginal alterations in tissue structure and integrity. The data suggest that the PAA doses used in the study are safe for salmon and do not pose substantial impact on gill mucosal health.

Histopathological effects of the antibiotic erythromycin on the freshwater fish species Oncorhynchus mykiss

Pharmaceuticals are found in the aquatic compartment due to their continuous release in wastewater effluents or direct dispersal in aquaculture practices raising serious threats to human and environmental health. Erythromycin (ERY) is a macrolide antibiotic widely prescribed in human and veterinary medicine to threat a number of bacterial infections, being consequently found in the aquatic environment. The present work intends to evaluate the sub-lethal effects of ERY on juveniles of rainbow trout (Oncorhynchus mykiss) in terms of tissue damage using histochemical staining procedures. Individuals were exposed for 96 h (acute exposure: 0.001–10 mg/L) and 28 days (chronic exposure: 0.05–0.8 μg/L) to environmentally realistic concentrations of ERY. Qualitative and quantitative approaches were used to assess O. mykiss gills and liver tissue alterations after exposure to ERY. For both exposures the most common gill changes recorded were progressive (e.g. hypertrophy of mucous cells and hyperplasia of the epithelial cells). However, circulatory (e.g. aneurysms and oedemas) and regressive (e.g. epithelial lifting of lamellae and lamellar fusion) changes were also observed in the acute assay. Gill morphometric analysis revealed to be a good indicator of subtle alterations in gill architecture in agreement with the qualitative scoring system. In liver, regressive (e.g. cytoplasmic vacuolization, pyknotic nucleus and hepatocellular degeneration) and circulatory disturbances (e.g. hemorrhage and increase of sinusoidal space) were the most frequently observed alterations, but only for the acute assay. Furthermore, all histological changes observed contributed to a significant increase in the pathological index for both organs. The current data demonstrate the existence of a direct dose-effect relationship between the exposure to this specific macrolide antibiotic and the histological disorders recorded in different tissues of the exposed fish. The histopathological findings observed in this study may have been the result of several physio-metabolic dysfunctions. However, the observed tissue lesions were of minimal or moderate pathological importance, non-specific and reversible. Further investigation into the cellular mechanism of action of ERY is needed.

Histological alterations in gills and liver of rainbow trout (Oncorhynchus mykiss) after exposure to the antibiotic oxytetracycline

The aim of this study was to investigate the histopathological effects of oxytetracycline (OTC) on the gill and liver tissues of rainbow trouts (Oncorhynchus mykiss) following acute (96h: 0.005–50mg/L) and chronic (28days: 0.3125–5μg/L) exposures. Results suggest the existence of a cause-and-effect relationship between the exposure to OTC and tissue damage. Most predominant disorders observed in gills were progressive (e.g. hypertrophy of mucous cells and hyperplasia of epithelial cells) in acute exposure and regressive (e.g. lamellar fusion, epithelial lifting of lamellae and some changes in tissue architecture) in chronic exposure. However, only the acute exposure was responsible for a significant increase of the total gill pathological index. PAGE index, reflecting the extent of gill tissue available for gas exchanges in fish, remained unchanged for both exposures. In liver, circulatory (e.g. hemorrhage and increase of sinusoidal space), regressive (e.g. pyknotic nucleus, vacuolization and hepatocellular degenerations) and progressive (e.g. hypertrophy of hepatocytes) changes were observed, but just after acute exposure. After chronic exposure, only inflammatory changes (e.g. leucocytes infiltration) were observed. Following both exposures, a significant increase of the total liver pathological index was recorded. Despite the increase of the histological damage in individuals exposed to OTC, lesions observed were of minimal or moderate pathological importance, non-specific and reversible. The data gathered following acute and chronic exposures also suggest the onset of adaptive mechanisms of fish, namely for longer exposure periods. Furthermore the observed histological alterations appear to be result of several physio-metabolic disorders consequence of the biochemical and molecular modes of action of OTC.

Is the use of turmeric in the diet safe for fish?

With this study, we aimed to assess the safety of using Curcuma longa in fish feed. Juvenile Astyanax aff. bimaculatus (0.83 ± 0.04 g) were kept in 24 80-L aquaria, at a density of 0.5 fish L−1 for 60 days. Six diets supplemented with 0.0, 20.0, 40.0, 60.0, 80.0 and 100.0 g kg−1 were evaluated. Histopathological analysis of the gills showed that there was an increasing linear effect of turmeric on the frequency of lamellar aneurysm, hypertrophy of mucous cells, oedema and necrosis. There was a quadratic effect of turmeric supplementation on the frequency of fusion and disruption of secondary lamellae, vacuolation and hypertrophy of the epithelial cells, and the estimated values to minimize these variables were 4.63, 25.93 and 24.46 g kg−1 respectively. There was a quadratic effect of turmeric on the gills index (IBRA), and the estimated value to minimize this index was 30.23 g kg−1. No effect of turmeric on the frequency of histopathological changes and organ index in fish liver was observed. Thus, we conclude that turmeric is not hepatotoxic for A. aff. bimaculatus; however, its use is safe at concentrations up to 30.23 g kg−1 diet as a function of its gill toxic effect at higher doses.

Lead- and cadmium-induced histopathological changes in gill, kidney and liver tissue of freshwater climbing perch Anabas testudineus (Bloch, 1792)

The objective of this study was to examine the toxicological effect of two major heavy metal pollutants, lead chloride (PbCl2) and cadmium chloride (CdCl2), in the freshwater climbing perch, Anabas testudineus. Fish were exposed to 1.0 and 2.0 mg/L both metals and histopathological changes in gill, kidney and liver tissues were studied. Major changes observed in gill tissue were epithelial lifting, proliferation of epithelial cells, fusion of secondary lamellae, hyperplasia and hypertrophy of mucous cells, and necrosis of epithelial cells. Cell necrosis, degenerated kidney tubules, congestion, lymphocytic infiltration and vacuolation were the major abnormalities observed in kidney tissue. The most conspicuous changes in liver were darker nucleoli, irregularly shaped hepatocytes with dilated blood capillaries, and focal as well as single necrosis. Fish specimens exposed to PbCl2 exhibited pronounced changes in all tissues examined compared with those exposed to CdCl2. It is evident from this study that heavy metals can cause significant histopathological changes in fish tissue.

Acute responses of juvenile cobiaRachycentron canadum(Linnaeus 1766) to acid stress

Fish are potentially submitted to water acidification when reared in recirculating aquaculture systems. This study evaluated the responses of juvenile cobia Rachycentron canadum after acute exposure to acid water. Juvenile cobia (12.6 ± 0.5 g; 14.2 ± 0.2 cm) were acutely exposed to four pH levels (7.9 (control), 6.5, 6.0, and 5.5). After 24 h of exposure to different pH values, fish were sampled for physiological and histopathological evaluation. Acid water affected physiological parameters and induced morphological histopathologies on gill and skin of juvenile cobia, and these effects were more conspicuous with decreasing pH values. Acid stress induced blood acidosis in juvenile cobia, coupled to a decrease in bicarbonate (HCO3−) and saturated O2 (sO2) in fish blood. On the other hand, haematocrit, haemoglobin and glucose concentration increased their values (P < 0.01) comparing to control level. Hyperplasia with completely fusion of secondary lamella was observed in all pH treatments (6.5. 6.0 and 5.5), while telangiectasia and proliferation of chloride cells were present for fish exposed to pH 6.0 and 5.5. In skin hyperplasia and hypertrophy of mucous cells, necrosis of these cells for fish exposed to pH 6.0 and 5.5 was observed. The results of this study demonstrate that acute acid water exposition affected physiology and histopathology in juvenile cobia, especially at pH values below 6.5. Accordingly, particular attention must be given to pH during cobia reared in recirculating aquaculture.

Histopathological effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in the gills, intestine and liver of turbot (Psetta maxima)

Polybrominated diphenyl ethers (PBDEs) have become ubiquitous environmental pollutants because of their widespread use as flame retardants in various consumer products (plastics, textiles, electronic appliances and building materials) and their long half-life. BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether) is the major PBDE congener detected in the environment and in animal tissues. In the present study, the histopathological effects are examined of BDE-47 on the gills, intestine and liver tissues of juvenile turbot (Psetta maxima).The specimens were exposed to two concentrations of BDE-47 (0.03 and 0.3µg/L) for a period of 15 days. The histological changes were detected microscopically and evaluated with quantitative or semi-quantitative analyses. At the doses of BDE-47 assayed, the most common gill injuries were lamellar fusion, blood congestion and hyperplasia and hypertrophy of the epithelial and mucous cells. In the intestine of fish exposed to BDE-47, the alterations detected were hyperplasia and hypertrophy of mucous cells. Hepatic lesions in the liver of fish exposed to BDE-47 were characterized by circulatory disturbances, irregular morphology of hepatocytes, cellular and nuclear hypertrophy, and nuclear vacuolation and pyknosis. As BDE-47 is present in food and other material related to aquaculture systems, our results indicate that exposure to this pollutant could have serious consequences on health in turbot and other cultured fish.

Acute tolerance and histopathological effects of ammonia on juvenile maroon clownfishPremnas biaculeatus(Block 1790)

This study evaluated the median lethal concentration values (LC50) and the histopathological effects of un-ionized ammonia (NH3 - -N) on juvenile maroon clownfish Premnas biaculeatus. After 96 h of exposure to different concentrations of ammonia, juveniles were sampled for histopathological evaluation. The 24 and 96 h LC50 values of NH3 -N determined were 1.68 and 0.89 mg L 1 respectively. Maroon clownfish exposed to different ammonia concentrations displayed histopathological alterations in the gills, kidney, liver and brain. Gill tissue damage included lamellar hyperplasia, lamellar shorting and hyperplasia and hypertrophy of mucous cells. The kidney showed hyperanaemia, enlarged sinusoids within an apparently decreased amount of haematopoietic tissue, oedema on tubular cells and tubular necrosis, and an enlarged Bowman’s capsule. The liver presented dilatation of hepatic sinusoids, fatty deposition in hepatocytes and Mallory bodies. Examination of the brain revealed a proliferation of glial cells, and the Virchow-Robin space indicated a severe perivascular oedema and signs of neuronal suffering with satellitosis. The results of this study indicate that juvenile maroon clownfish are relatively sensitive to ammonia and particular attention must be given to this toxic compound in culture systems.

IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient mice

Huntingtin interacting protein 1 related (Hip1r) is an F-actin- and clathrin-binding protein involved in vesicular trafficking that is crucial for parietal cell function and epithelial cell homeostasis in the stomach. Gastric parietal cells in Hip1r-deficient mice are lost by apoptotic cell death, which leads to a progressive epithelial cell derangement, including glandular hypertrophy, zymogenic cell loss and expansion of a metaplastic mucous cell lineage known as spasmolytic polypeptide-expressing metaplasia (SPEM). The epithelial cell changes are associated with infiltration of inflammatory cells. As inflammatory mediators, such as IFNγ, have been shown to contribute to the development of the gastric epithelial cell metaplasia after Helicobacter infection, we tested whether IFNγ played a role in the spontaneous progressive epithelial metaplasia observed in Hip1r-deficient mice. Hip1r-deficient mice were crossed with IFNγ-deficient mice and single- and double-mutant mice were analyzed at 3 and 12 months of age. Histopathology scoring showed that loss of IFNγ tempered the spontaneous development of metaplastic lesions in Hip1r-deficient mice. Loss of IFNγ was observed to abrogate the glandular hypertrophy evident in Hip1r mutant stomach, although increased epithelial cell proliferation and elevated gastrin levels were not affected by the presence or absence of this pro-inflammatory cytokine. An analysis of cell lineage markers in the double-mutant mice demonstrated that IFNγ specifically affected the development of metaplastic mucous cells in the neck region, whereas the parietal cell, surface mucous cell and zymogenic cell alterations remained similar to the histopathology in the Hip1r mutant. Morphometric analysis showed that IFNγ was required for the mucous cell hypertrophy and hyperplasia observed in Hip1r-deficient mice. Together, these findings demonstrate that IFNγ is critical for the development of the gastric epithelial cell metaplasia that results from parietal cell atrophy in the Hip1r-deficient mice.

The impact of an oil spill on organs of bream Abramis brama in the Po River

An oil spill into the River Lambro occurred on 23 February 2010 and reached the Po River the following day. Breams captured here on 1 March 2010, along with a sample from a control site, were examined by light and electron microscopy. The main affected organs were skin and gill with slight or no damage to liver, kidney, and intestine. The gills exhibited lamellar aneurisms, fusion of secondary lamellae, edema with epithelial lifting, mucous cell hypertrophy, and mucus hypersecretion. Significantly higher mucous cell density was observed in the skin of exposed fish. Histochemical staining revealed that acid glycoconjugates were prevalent in epidermal mucous cells in the exposed Abramis brama, whereas neutral and mixed glycoconjugates were dominant in the control fish. Rodlet cells were significantly more abundant in the kidney of exposed fish and showed ultrastructural differences compared to controls. These histopathologic effects were indicators of chemical stress due to exposure to oil. The present study is one of the first which explores the acute effects of this incident and makes part of a few reports focused on freshwater oil spill.

Monitoring pollution in River Mureş, Romania, part II: Metal accumulation and histopathology in fish

As a part of an exposure and effect monitoring conducted along the river Mureş, Western Romania in 2004, the health status of two indigenous fish species, sneep (Chondrostoma nasus) and European chub (Leuciscus cephalus) was investigated upstream and downstream the city of Arad. In fish, histopathology was assessed in liver and gills, and heavy metals (cadmium, copper, lead and zinc) were analyzed in liver samples. In both fish species, histopathological reactions in the gills (epithelial lifting, focal proliferation of epithelial cells of primary and secondary lamellae and resulting fusion of secondary lamellae, hyperplasia and hypertrophy of mucous cells, focal inflammation and necrosis of epithelial cells) were most severe at the two sampling sites upstream Arad city, which were shown to be polluted by copper, cadmium, faecal coliforms and streptococci in a parallel study. At these two sites, also histopathology in the liver of L. cephalus was more prominent than at the two downstream sites. In C. nasus, symptoms in the liver (focal inflammation with lymphocytic infiltrations, macrophage aggregates and single cell necrosis) were also highly pronounced at the sampling site located directly downstream the municipal sewage treatment plant of Arad. With the exception of copper accumulation in L. cephalus caught at the most upstream sampling site, in both fish species cadmium and copper accumulation were exceptionally high and did not differ significantly between the four sampling sites.

Subchronic Toxicity and Toxicogenomic Evaluation of Tamoxifen Citrate + Bexarotene in Female Rats

Tamoxifen (TAM) is a nonsteroidal antiestrogen that prevents estrogen receptor-positive breast cancer in rodents and humans. Bexarotene (BEX), a selective agonist for retinoid X receptors, inhibits mammary carcinogenesis in rodents. The present study was conducted to support the preclinical development of TAM (tamoxifen citrate) + BEX for use in breast cancer chemoprevention, and to investigate the influence of these agents on hepatic gene expression. Female CD rats (20 per group) received daily oral (gavage) exposure to TAM (0 or 60 microg/kg/day) and/or BEX (0, 5, 15, or 45 mg/kg/day) for a minimum of 90 days. BEX induced mild, dose-related anemia and dose-related increases in serum alkaline phosphatase, cholesterol, triglycerides, and calcium levels, and increased platelet counts. TAM had no biologically significant effect on any clinical pathology parameter and did not alter the effects of BEX on these endpoints. Microscopic alterations induced by BEX included epidermal hyperplasia, hyperkeratosis (stomach), and cytoplasmic clearing (liver). Microscopic changes in TAM-treated rats were limited to mucous cell hypertrophy in the cervix and vagina. The toxicity of administration of the combination of TAM + BEX can generally be predicted on the basis of the toxicity of each drug as a single agent. BEX induced dose-related alterations in the expression of several genes involved in steroid, drug, and/or fatty acid metabolism; TAM did not alter these effects of BEX. Differential expression of genes involved in drug and lipid metabolism may underlie the observed effects of BEX on cholesterol and triglyceride levels and its effects on liver histology.

Reversible and irreversible airway inflammation and fibrosis in mice exposed to inhaled ovalbumin

We examined the reversibility of several changes in the lungs and airways of mice immediately after exposure to ovalbumin aerosol and after a period of recovery breathing clean air. Mice were exposed for 1, 2, 4, 6, 8, or 10 weeks, with recovery in clean air for 1-3 weeks. Airway collagen content, exhaled NO, airway mucous cell hyperplasia, and lung lavage inflammatory cell content increased upon exposure to ovalbumin aerosol. All parameters except airway fibrosis decreased partially or completely to control values with recovery in clean air. Airway mucous cell hypertrophy and hyperplasia appear to be completely reversible after recovery in clean air, while exhaled NO and airway inflammation appear to be mostly reversible, except for persistence of lymphocytes in the lung lavage fluid. Airway fibrosis appears to be reversible when mice are exposed to ovalbumin aerosol for periods of up to 4 weeks of exposure, but becomes irreversible after 6 or more weeks of exposure.

Airway fibrosis in a mouse model of airway inflammation

BALB/c mice were sensitized to ovalbumin by systemic injection and then exposed for up to 8 weeks to ovalbumin aerosols in whole body chambers. A pattern of airway inflammation, mucous cell hypertrophy and hyperplasia, and airway remodeling with submucosal fibrosis was observed as lesions evolved over time. Larger conducting airways were removed from the lungs by microdissection. Airway fibrosis was quantified by direct assay for collagen content, which was significantly increased after 4 and 8 weeks of exposure to ovalbumin aerosol. Based upon PCR analysis of mRNA levels in the airways, most of the newly synthesized collagen was Type I. Relaxin, administered by continuous infusion over the second half of a 4-week exposure to ovalbumin, was able to inhibit the accumulation of collagen in the airways of exposed mice. Thus, stimulation of collagen degradation by an activator of collagen breakdown by matrix metalloproteinases appears to be an effective therapeutic strategy in prevention of airway fibrosis in this animal model. Whole body plethysmography of unrestrained mice indicated functional changes in airway reactivity in the lungs of exposed animals occurring in conjunction with the reported structural changes. This result indicates that the ovalbumin-exposed mouse may be a suitable model for examining structure–function relationships in the lungs of animals with a predictable time course of airway inflammation, remodeling, and fibrosis and for testing potential new drugs for treatment of asthma or chronic bronchitis at a mechanistic level.

Induction of ductal and stromal hyperplasia by basic fibroblast growth factor produced by human pancreatic carcinoma.

A histopathology study of 22 pancreatic adenocarcinoma cases revealed that 13 of the patients presented with hyperplastic lesions (atypical and non-atypical hyperplasia, mucous cell hypertrophy, focal epithelial hyperplasia, and ductal papillary hyperplasia), and 9 exhibited fibrosis adjacent to the carcinoma. All lesions expressed high levels of epidermal growth factor receptor (EGF-R) (p<0.0001 and p=0.0008, respectively) as compared with normal ductal epithelium. Non-atypical and atypical hyperplastic lesions also had a higher proliferating cell nuclear antigen (PCNA) labeling index (p<0.001 and p=0.0008, respectively) than normal ductal epithelium. A gradient in PCNA+ nuclei was found in acinar cells adjacent to the tumors. In 16 cases with marked fibrosis, we observed a significant increase of PCNA+ nuclei in stromal fibroblasts (p=0.0041) and significant upregulation of basic fibroblast growth factor (bFGF) mRNA expression in adjacent tumor cells (p=0.0213). These data suggest that the production of bFGF by pancreatic cancer cells induces ductal and stromal hyperplasia of the pancreas.

Nature and Time Course of Acclimation to Aluminum in Juvenile Brook Trout (Salvelinus fontinalis). II. Gill Histology

Gill samples from juvenile brook trout (Salvelinus fontinalis) acclimated to low-level aluminum at pH 5.2 showed severe damage by day 4, with necrosis and fusion of secondary lamellae and hyperplasia and hypertrophy of mucous cells. Over the following 20 d, there was a continual process of repair with proliferation and hypertrophy of mucous cells. Qualitative analysis of gill samples plus physiology and mortality data collected in a companion study indicated progressive development (by day 10 onward) of increasing acclimation to Al. Quantitative analysis of gill samples on day 13 showed that mucous cell volume density had tripled and mucous cell area had doubled in Al-exposed fish compared with control fish. A lamellar fusion index showed evidence of fusion in Al-exposed fish by day 4 with recovery to nearly control levels by day 13. Physiological disturbances appear to be directly related to the histological changes observed in the gill epithelium. At the cellular level, changes in either mucous cell production and secretion or changes in mucus chemistry contribute, in part, to acclimation to Al.

Epidermal Response to pH, Aluminum, and Calcium Exposure in Brook Trout (Salvelinus fontinalis) Fry

Eyed brook trout eggs were exposed to various combinations of pH (4.3–6.3), aluminum (0–1000 μg/L), and calcium (0.5 to 8.0 mg/L) for 40 d through hatching until the swim-up life stage. High resolution light microscopy, image analysis, and stereological techniques were used to quantitatively determine morphological changes in the epidermis of fry surviving this exposure. Exposure to increased acidity resulted in both mucous cell hypertrophy (increase in size) and hyperplasia (increase in number); exposure to low calcium resulted in mucous cell hyperplasia. Aluminum did not significantly affect mucous cell size or number. Epidermal thickness was not consistently affected by exposure to pH, aluminum, or calcium. The changes observed in epidermal mucous cells may be a compensatory mechanism used by brook trout fry to counter ionoregulatory stress resulting from extended exposure to acidic conditions.

Effects of crude oil on the air-breathing organs of the striped gourami, Colisa fasciatus: A SEM study

Pathological effects of crude oil on the air-breathing organs of the striped gourami, Colisa fasciatus, were studied using SEM. Buccal epithelium appeared to be more sensitive to crude oil than epithelia of the suprabranchial chamber and the labyrinthine organ. Lower doses of crude oil caused mucous cell hyperplasia, shrinkage of respiratory epithelium, and telangiectasis of blood capillaries in the air-breathing organs. Manifestations of lethal pathological effects including mucous cell hypertrophy, lesions, and sloughing of air-breathing epithelium increased with increasing crude oil concentration and exposure period.