Glycogen Deposition Research Articles

MiR-1a-3p mitigates isoproterenol-induced heart failure by enhancing the expression of mitochondrial ND1 and COX1

MicroRNAs (miRNAs) have become potential targets for the treatment of heart failure (HF). It has been shown that miR-1 can reverse cardiac hypertrophy during the compensatory phase of HF development, but it is unknown whether miR-1 can still reverse cardiac dysfunction and improve cardiac remodeling after HF progresses to the decompensation stage. We established a mouse model of isoproterenol-induced HF and then injected miR-1a-3p agomir (agomir-1) into the tail vein. Echocardiography showed that the mice treated with agomir-1 had significantly increased ejection fraction and fractional shortening. These mice also showed a decrease in the N-terminal pro-B type natriuretic peptide (NT-proBNP) levels, but this remained higher than in controls. Cardiac hypertrophy, myocardial fibrosis, apoptosis, and glycogen deposition were reduced in mice treated with agomir-1. Furthermore, we found that supplementation of agomir-1 increased the expression of two mitochondrial DNA-encoded proteins, mitochondrially encoded NADH dehydrogenase 1 (ND1) and mitochondrially encoded cytochrome c oxidase I (COX1). In conclusion, our study found that miR-1a-3p alleviated the symptoms of ISO-induced HF in mice by enhancing mitochondrial ND1 and COX1. The results of this work may provide new therapeutic strategies for the treatment of HF patients.

Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor

BackgroundThe effects of phosphodiesterase-type 5 (PDE5) inhibitors on the in vivo clitoral structure of women with diabetes have never been investigated. AimTo study the in vivo structural and hemodynamic changes of the clitoris in premenopausal women with type 1 diabetes on PDE5 inhibitors. Methods38 premenopausal women with type 1 diabetes aged 36 -46 years. A randomized 1:1 study design was used: Study Group (group A) on Tadalafil 5 mg daily, and control group (group B). Blood samples were taken from each woman to measure HbA1c, testosterone, and Free Androgen Index. The women underwent microbiopsy of the clitoral body by means of semiautomatic gun during total anesthesia for surgery therapy of a benign gynecological pathology. The tissue removed was processed for electron microscopy. Translabial color Doppler ultrasound was used to measure the peak systolic velocity (PSV), the end diastolic velocity (EDV), and the pulsatility index (PI) of clitoral arteries. Main Outcome MeasuresMicro-ultrastructure observation of clitoral tissue and color Doppler sonography of clitoral blood flow. ResultsOf the 38 women, 13 (68.4%) of group A and 15 (78.9%) of group B completed the study. Group A showed a mean PSV and EDV increase, and a mean PI decrease with respect to baseline (P < .001). Group B did not show any change in both the parameters (P = NS). By a quantitative study in both groups a variable degree of ultrastructural abnormalities of smooth muscle cells (SMCs) was observed, consisting in increased glycogen and lipoic deposits, cytoplasmic vacuoles, and focal increase of electron density of SMCs. Moreover, the mean SMC thickness of group A (1.83 ± 0.68 µm) was larger than that of group B (1.3 ± 0.41 µm) (P = .02). Clinical ImplicationsPDE5 inhibitors could be used to treat diabetic women with genital arousal disorder. Strengths & LimitationsThe study shows a clear effect of PDE5 inhibitors on clitoral SMCs. However, a limit was to not have investigated the sexual function/behavior of women of both groups, this was because of the short time of the study. ConclusionThis study could help to understand in what way PDE5 inhibitors act on the ultrastructural pathophysiological clitoral cavernous tissue of women with diabetes. It could support PDE5 inhibitor usage in women with genital sexual arousal disorder due to metabolic diseases.Caruso S, Cianci A, Cianci S, et al. Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor. J Sex Med 2019;16:375–382.

Defective fasting-induced PKA activation impairs adipose tissue glycogen degradation in obese Zucker rats.

Obesity is associated with development of insulin resistance in adipose tissue (AT). Human obesity has been associated with increased glycogen deposition in adipocytes. Adipocytes synthesise glycogen prior to the formation of lipids. The present study examined adipose glycogen content in obese Zucker rats and the effect of fasting on glycogen-metabolising enzymes. We hypothesised that obesity imposes a blunted response to fasting through impaired activation of glycogen-metabolizing enzymes, which dampens glycogen mobilization in obese Zucker rats. We investigated the effect of 24h fasting on AT glycogen metabolism in12-week old obese Zucker rats. Epididymal fat pads were collected from rats fed ad-libitum and fasted for 24h. Glycogen content, glycogen synthase and phosphorylase enzyme activity, and PKA activity were analysed as well as total and phosphorylated protein content for glycogen-metabolizing enzymes glycogen synthase and phosphorylase, glucose transporter GLUT4, and cAMP-dependent response element binding protein levels. Twelve-week old obese Zucker rats showed increased AT glycogen content (adipose glycogen content [mean ± SD], lean: 3.95 ± 2.78 to 0.75 + 0.69 µg.mg-1; p < 0.005 fed vs fasted, and obese: 5.23 ± 3.38 to 5.019 ± 1.99 µg.mg-1; p = ns fed and fasted and p < 0.005 lean vs obese), and impaired fasting-induced glycogen mobilization following a 24h fast. These defects wereassociated with dysfunctional glycogen-metabolizing enzymes, characterized by: (1) blunted phosphorylation-mediated activation and downregulated protein expression of glycogen phosphorylase, and (2) an impaired phosphorylation-mediated inactivation of glycogen synthase. Furthermore,these defects were related to impaired fasting-induced protein kinase A (PKA) activation. This study provides evidence of a defective glycogen metabolism in the adipose associated with impaired fasting-induced activation of the upstream kinase protein kinase A, which render a converging point to obesity-related primary alterations in carbohydrate and lipid metabolism in the AT.

Qi-dan-di-huang decoction alleviates diabetic nephropathy by inhibiting the NF-kappaB pathway.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus, for which no effective treatment currently exists. We tested the hypothesis that Qi-dan-di-huang (QDDH) might have therapuetic effects in an experimental rat model of DN. The levels of I kappa KinaseAlpha and Beta, p-p65, p-IκB alpha, TGF-β1 and Alpha-SMA were significantly increased in kidneys in DN. QDDH decoction only partially reversed the increased Ikappa KinaseAlpha/Beta, p-p65, p-IKappaB alpha, TGF-Beta1 and alpha-SMA in the kidneys in DN. However, treatment of diabetic rats with QDDH decoction significantly inhibited the production and release of inflammatory cytokines IL-6, IL-1 beta and TNF-alpha into the serum. QDDH decoction also significantly improved the physiologic and biochemical indicators of DN, reduced glycogen and protein deposition in DN and prevented renal fibrosis. Together, the data show that QDDH decoction exerts a protective effect on kidneys in diabetic rats and reverses the inflammatory milieu of the serum in DN.

Immunohistochemical Localization of Catalase in Geese (Anser anser) Kidney

Summary The aim of the present study was to investigate immunohistochemical localization of catalase (CAT) in geese liver as well as its histological structure. Six healthy female geese (Anser anser, aging between 10-12 months and weighing 2-3 kg), were used in this study. Tissues were fi xed in Bouin solution for histological and immunohistochemical examinations and embedded in paraffi n. Serial cross-sections were taken from paraffi n blocks and then stained whit Crossman’s triple stain (Triple stain), Hematoxylin and Eosin (HE) and Periodic Acid Schiff (PAS) for histological examinations. After incubation cross section with for 1 hr, 1:3000 diluted anti-CAT Avidin-Biotin-Peroxidase Complex (ABC) method was applied for immunohistochemical staining. It was histologically observed that hepatocytes formed hepatic cords (also called Remark cords) mostly surrounding the central vein of goose liver. Globuler glycogen deposits were observed in some of the hepatocytes. Catalase immunoreactivity was diffusely observed in hepatocyte cytoplasms. Furthermore, some of hepatocyte nuclei were positively stained for catalase immunoreactivity. In addition, primary antibody was prepared against bovine liver catalase was immunoreactived in geese liver was detected. As a result, antioxidant defense system was carried out especially by the hepatocytes in geese liver and this study was thought to contribute to studies about antioxidant in poultry.

Glucocorticoid treatment affects liver glycogen deposition and gene expression in beef cattle

Glucocorticoid treatment affects liver glycogen deposition and gene expression in beef cattle

Effects of Bauhinia forficata on glycaemia, lipid profile, hepatic glycogen content and oxidative stress in rats exposed to Bisphenol A.

Bisphenol A (BPA) is an abundant raw material applied in the production of daily necessities, such as food cans, baby bottles, electronic and medical equipment. Phytotherapeutic use of plant preparations has long been known for multiple target medicinal uses. The species Bauhinia forficata is widely used as hypoglycemic, anti-inflammatory, antioxidant, diuretic and hypocholesterolemic agent. The aim of this study was to verify the effects of B. forficata extract in association with BPA exposure on serological parameters, hepatic antioxidant status and glycogen store capacity in Wistar rats. B. forficata was able to reduce BPA-induced glucose levels; it also prevented the early glucose elevation in control and BPA-exposed animals after the glucose provocative test. This effect was related to the hepatic glycogen content; while BPA reduced the hepatic glycogen deposits B. forficata treatment contributed to minimize it. BPA and B. forficata singly caused elevation in triacylglycerol and VLDL levels and reduction in cholesterol and LDL concentrations. BPA increased hepatic malondialdehyde levels and reduced catalase activity, thus inducing liver oxidative stress. Conversely, B. forficata treatment reduced malondialdehyde concentration without interfering with catalase activity; this antioxidant capacity is attributed to the flavonoids content (e.g., kaempferol and myricetin). Based on these results, we demonstrated that B. forficata commercial extract has hypoglycemic and antioxidant properties capable of minimizing the effects of BPA. However, it should be considered that the consumption of herbal commercial extract must be judicious to avoid deleterious health effects.

Novel metabolic disorders in skeletal muscle of Lipodystrophic Bscl2/Seipin deficient mice

Bscl2−/− mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatosteatosis, muscular hypertrophy, and insulin resistance. Metabolic defects in Bscl2−/− mice with regard to glucose and lipid metabolism in skeletal muscle have never been investigated. Here, we identified Bscl2−/− mice displayed reduced intramyocellular triglyceride (IMTG) content but increased glycogen storage predominantly in oxidative type I soleus muscle (SM). These changes were associated with increased incomplete fatty acid oxidation and glycogen synthesis. Interestingly, SM in Bscl2−/− mice demonstrated a fasting duration induced insulin sensitivity which was further confirmed by hyperinsulinemic-euglycemic clamp in SM of overnight fasted Bscl2−/− mice but reversed by raising circulating NEFA levels through intralipid infusion. Furthermore, mice with skeletal muscle-specific inactivation of BSCL2 manifested no changes in muscle deposition of lipids and glycogen, suggesting BSCL2 does not play a cell-autonomous role in muscle lipid and glucose homeostasis. Our study uncovers a novel link between muscle metabolic defects and insulin resistance, and underscores an important role of circulating NEFA in regulating oxidative muscle insulin signaling in BSCL2 lipodystrophy.

Epidermal growth factor-like domain multiple 7 (EGFL7): Expression and possible effect on biliary epithelium growth in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with limited treatment options and low survival rates. The intrahepatic subtype comprises two forms: mucin-iCCA and mixed-iCCA. Epidermal growth factor-like domain multiple (EGFL7) is overexpressed in less differentiated liver tumors. The aim of this study was to assess the presence of EGFL7 due to its possible role in the growth of CCA. Hematoxylin & Eosin and periodic acid- Schiff staining were used to evaluate the morphological aspects and glycogen deposition. Immunohistochemistry and immunofluorescence were performed to identify the presence of EGFL7 both in tumor sections ex vivo and in appropriate cell lines in culture. We found that EGFL7 is expressed in malignant cholangiocytes of mixed-iCCA and absent in mucin-iCCA. In conclusion the expression of EGFL7 might be useful in the classification of CCA subtypes.

English

English

Excessive treadmill training enhances the insulin signaling pathway and glycogen deposition in mice hearts.

Exhaustive and chronic physical exercise leads to peripheral inflammation, which is one of the molecular mechanisms responsible for the impairment of the insulin signaling pathway in the heart. Recently, 3 different running overtraining models performed downhill (OTR/down), uphill (OTR/up), and without inclination (OTR) increased the serum levels of proinflammatory cytokines. This proinflammatory status induced insulin signaling impairment in the skeletal muscle; however, the response of this signaling pathway in the cardiac muscle of overtrained mice was still unknown. Thus, we investigated the effects of OTR/down, OTR/up, and OTR protocols on the protein levels of phosphorylation of insulin receptor β (pIRβ) (Tyr), phosphorylation of protein kinase B (pAkt) (Ser473), plasma membrane glucose transporter-1 (GLUT1) and GLUT4, phosphorylation of insulin receptor substrate-1 (pIRS-1) (Ser307), phosphorylation of IκB kinase α/β) (pIKKα/β (Ser180/181), phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) (Thr180/Tyr182), phosphorylation of stress-activated protein kinases-Jun amino-terminal kinases (pSAPK-JNK) (Thr183/Tyr185), and glycogen content in mice hearts. The rodents were divided into naïve (N, sedentary mice), control (CT, sedentary mice submitted to performance evaluations), trained (TR, performed the training protocol), OTR/down, OTR/up, and OTR groups. After the grip force test, the cardiac muscles (ie, left ventricle) were removed and used for immunoblotting and histology. Although the OTR/up and OTR groups exhibited higher cardiac levels of pIRβ (Tyr), only the OTR group exhibited higher cardiac levels of pAkt (Ser473) and plasma membrane GLUT4. On the contrary, the OTR/down group exhibited higher cardiac levels of pIRS-1 (Ser307). The OTR model enhanced the cardiac insulin signaling pathway. All overtraining models increased the left ventricle glycogen content, with this probably acting as a compensatory organ in response to skeletal muscle insulin signaling impairment.

Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion.

Increased use of high‐risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell–based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate‐clearing (LC) and non‐lactate‐clearing (non‐LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non‐LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow >150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non‐LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non‐LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high‐risk livers.

Psychosocial Stress, Cortisol Levels, and Maintenance of Vaginal Health.

Stress stimuli are ubiquitous and women do not enjoy any exemptions. The physiologic “fight-or-flight” response may be deleterious to the female lower genital tract microbiome if the stress stimuli persist for longer than necessary. Persistent exposure to psychosocial stress and stimulation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes, and associated hormones are risk factors for several infections including genitourinary tract infections. Though this could be due to a dysregulated immune response, a cortisol-induced inhibition of vaginal glycogen deposition may be involved especially in the instance of vaginal infection. The estrogen-related increased vaginal glycogen and epithelial maturation are required for the maintenance of a healthy vaginal ecosystem (eubiosis). The ability of cortisol to disrupt this process as indicated in animal models is important in the pathogenesis of vaginal dysbiosis and the subsequent development of infection and inflammation. This phenomenon may be more crucial in pregnancy where a healthy Lactobacillus-dominated vaginal microbiota is sacrosanct, and there is local production of more corticotropin-releasing hormone (CRH) from the decidua, fetal membranes and placenta. To highlight the relationship between the stress hormone cortisol and the vaginal microbiomial architecture and function, the potential role of cortisol in the maintenance of vaginal health is examined.

Glycogenic acanthosis on mouth clinically present as white plaque

ABSTRACT Glycogenic acanthosis is a benign condition, commonly observed during endoscopic procedures in older patients, which present as slightly elevated whitish plaques often on the lower third of the oesophagus. Microscopically, glycogenic acanthosis is composed of hyperplastic squamous epithelium with intracytoplasmic glycogen deposits. The extraoesophageal glycogenic acanthosis is extremely rare, with only three case reports in the English-language literature. We report a white lesion showing glycogenic acanthosis-like features located on the left posterolateral border of the tongue, affecting a 56-year-old male patient. The medical history was non-contributory and the patient did not show any lesions during endoscopic examination of the oesophagus, stomach, and upper duodenum. Glycogenic acanthosis is a benign condition, which should be included in the differential diagnosis when assessing oral white lesions. It is important also to recognize this benign condition early and rule out the possibility of other more severe diseases, but further studies were necessary for better define their potential for persistence or recurrence, as observed in the current case.

Dietary Iron Modulates Glucose and Lipid Homeostasis in Diabetic Mice.

Imbalance of iron homeostasis has been involved in clinical courses of metabolic diseases such as type 2 diabetes mellitus, obesity, and nonalcoholic fatty liver, through mechanisms not yet fully elucidated. Herein, we evaluated the effect of dietary iron on the development of diabetic syndromes in genetically obese db/db mice. Mice (aged 7weeks) were fed with high-iron (HI) diets (1000mg/kg chow) or low-iron (LI) diets (12mg/kg) for 9weeks. HI diets increased hepatic iron threefold and led to fourfold higher mRNA levels of hepcidin. HI also induced a 60% increase in fasting glucose due to insulin resistance, as confirmed by decreased hepatic glycogen deposition eightfold and a 21% decrease of serum adiponectin level. HI-fed mice had lower visceral adipose tissue mass estimated by epididymal and inguinal fat pad, associated with iron accumulation and smaller size of adipocytes. Gene expression analysis of liver showed that HI diet upregulated gluconeogenesis and downregulated lipogenesis. These results suggested that excess dietary iron leads to reduced mass, increased fasting glucose, decreased adiponectin level, and enhancement of insulin resistance, which indicated a multifactorial role of excess iron in the development of diabetes in the setting of obesity.

Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman’s space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Mulberry and dandelion water extracts prevent alcohol-induced steatosis with alleviating gut microbiome dysbiosis.

Chronic alcohol intake causes hepatic steatosis and changes the body composition and glucose metabolism. We examined whether water extracts of mulberry (WMB) and white flower dandelion ( Taraxacum coreanum Nakai, WTC) can prevent and/or delay the symptoms of chronic ethanol-induced hepatic steatosis in male Sprague Dawley rats, and explored the mechanisms. Ethanol degradation was examined by orally administering 3 g ethanol/kg bw after giving them 0.3 g/kg bw WMB or WTC. All rats were continuously provided about 7 g ethanol/kg bw/day for four weeks and were given either of 0.1% dextrin (control), WMB, WTC, or water extracts of Hovenia dulcis Thunb fruit (positive-control) in high-fat diets. Area under the curve of serum ethanol levels was lowered in descending order of control, WTC and positive-control, and WMB in acute ethanol challenge. WMB and WTC prevented alcohol intake-related decrease in bone mineral density and lean body mass compared to the control. After glucose challenge, serum glucose levels increased more in the control group than other groups in the first part and the rate of decrease after 40 min was similar among all groups. These changes were associated with decreasing serum insulin levels. WMB had the greatest efficacy for decreasing triglyceride and increasing glycogen deposits. WMB and WTC prevented the disruption of the hepatic cells and nuclei while reducing malondialdehyde contents in rats fed alcohol, but the prevention was not as much as the normal-control. The ratio of Firmicutes to Bacteroidetes in the gut was much higher in the control than the normal-control, but WTC and WMB decreased the ratio compared to the control. WMB and WTC separated the gut microbiota community from the control. In conclusion, WMB and WTC protected against alcoholic liver steatosis by accelerating ethanol degradation and also improved body composition and glucose metabolism while alleviating the dysbiosis of gut microbiome by chronic alcohol intake. Impact statement Excessive alcohol consumption is associated with serious pathologies and is common in much of the world. Pathologies include liver damage, glucose intolerance, and loss of lean body mass and bone mass. These pathologies are mediated by changes in metabolism as well as toxic metabolic byproducts, and possibly by gut dysbiosis. In this study, we demonstrate that aqueous extracts of mulberry and dandelion protected rats against ethanol-induced losses in lean body and bone masses, improved glucose tolerance and partially normalized gut bacterial populations, with mulberry extract being generally more effective. This research suggests that mulberry and dandelion extracts may have the potential to improve some of the pathologies associated with excess alcohol consumption, and that further clinical research is warranted.

Clinicopathological Evaluation of Clear Cell Hidradenoma (Acrospiroma) Within Multiple Tumor Complex in a Dog

Background: Clear cell hidradenoma (acrospiroma) is adnexal tumors that arise from the distal excretory duct of eccrine sweat glands. It is generally defined in humanbeings. It presents solitary structure in firmness nodule. Most frequently are encountered in head, face, and upper extremities in humans. Hidradenomas are called generally by definition benign. Their malignant transformations and metastasis are seen very rarely. In veterinary literature database, the malignant form of tumor has been defined as an unique report in four dogs. They are extremely rare tumors in dogs. It is not documented within multiple tumor complex up to now.Case: In the case, three tumors were detected in a 9-year-old neutered female German shepherd dog. After clinical examination, a complete surgical resection of all masses was performed and masses were sent to Pathology for diagnosis. A mass on the right last rib was a 8x6 cm in diameters with severe ulceration. The mass had a hard texture, immobility and irregular borders. Other masses were localized on the back and left caudo-abdominal mammary lobe. Tumors on the back and the mammary lobe did not invade muscle layer, but the tumor on the last rib aggressively invaded surrounding tissue and were very difficult to remove surgically After macroscopy, all the masses were stained with hematoxylin-eosin (H&amp;E), Mayer’s mucicarmine and Periodic Acid Shiff (PAS) stainings. In the first mass, there were multilobular epithelial islands between prominent fibrous septa from the upper to deep of dermis. The neoplastic cells were generally round or polyhedral in shape. Some of cytoplasms were eosinophilic at different degree. But cytoplasms were generally finely granular and vesicular or clear in appearance. Some cells had possible glycogen deposits. Nucleus was oval to round and had fine reticular chromatin and a distinct nucleolus. The tumor was diagnosed as clear cell hidradenoma. Others were was belonged to hemangioma on the back and malignant mixed tumor in the mammary gland.Discussion: In our case, two cell types having benign characteristics were also noted. Some clear cells contained PAS (+) material showing glycogen deposits. Additionally, there were some fibrous septa separating those cell islands. Thus, it is thought that the histopathology shows parallelism to many reports described in human beigns. Clear cell hidradenoma described in this case is first documentation as benign counterpart on the basis of veterinary literatures even though a previous report including clear cell hidradenocarcinoma in four dogs. And also, it has been reported to be very rarely seen tumor in human beings. However, any hormonies in terms of its predilection site can not be found among the cases with clear cell hidradenoma in human counterparts, because the tumor is encountered at skin of last right rib. This situation has shown us the tumor does not select any predilection site as described in this case. It has been understood on the basis of literatures that this is the first case report of describing benign tumor of ecrine sweat duct in dogs. Also, there has been no any documentation regarding in this multiple tumor complex

Study of melatonin-mediated effects on various hepatic inflammatory responses stimulated by IL-6 in a new HepG2-on-a-chip platform.

Hepatocytes exhibit diverse reactions upon stimulation with the interleukin IL-6, mainly in the context of inflammation and energy metabolism. Melatonin has been shown to exert pleiotropic protective actions, such as anti-inflammation and anti-oxidative stress on many cell- and organ-types. The key role of the liver to maintain homeostasis and metabolic regulation prompted us to evaluate the direct modification of IL-6-induced alterations in HepG2 cells in a chip by melatonin. IL-6 administration was followed by the reduced expression and activity of MRP2, a loss of CYP1A activity, and the decline of PXR expression. Other effects were the induction of acute phase responses (reduced albumin production as well as increased CRP and hepcidin expression) and lowered expression of CREB3L3. IL-6 affected also the mitochondrial membrane potential together with elevated mitochondrial superoxide generation, and glycogen deposition was reduced. Melatonin counteracted all observed IL-6-induced alterations except the rise in CRP release and CYP1A activity. Altogether, this new in vitro model can be applied to investigate hepatic inflammatory responses stimulated by IL-6, and these results indicate that hepatocellular inflammatory responses to IL-6 are mitigated by melatonin.

A description of liver and blood changes in matrinxã (Brycon amazonicus) during induced spawning

We investigated the effects of induced spawning on liver and blood cell changes in matrinxã breeders, a commercially valuable South American fish that requires hormonal manipulation and stripping to spawn, a trait shared by other important aquaculture species. Little attention has been given to this topic despite the mortality rates commonly reported by fish farmers following this practice. In this study, we show that the overall handling required in induced spawning severely impaired the liver (hypertrophy of the hepatocytes, enlargement of the cell nuclei and reductions of glycogen deposits) which was mainly attributed to hormonal therapy. Additionally, the induced spawning procedure increased the number of red blood cells and decreased the white blood cell and thrombocyte count. These results corroborate the stressful conditions and immunosuppression, which together with the liver damage may explain the reported mortality rates. Finally, our findings outline important approaches for improving induced spawning technique.