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Sample records for rats chronically treated

  1. G cells and gastrin in chronic alcohol-treated rats.

    PubMed

    Todorović, Vera; Koko, Vesna; Budec, Mirela; Mićić, Mileva; Micev, Marjan; Pavlović, Mirjana; Vignjević, Sanja; Drndarević, Neda; Mitrović, Olivera

    2008-02-01

    Numerous reports have described gastric mucosal injury in rats treated with high ethanol concentrations. However, to the best of our knowledge, ultrastructural characteristics of G cells and antral gastrin levels have not been previously reported, either in rats that chronically consumed alcohol or in human alcoholics. The goal of this study was to examine the effect of ethanol consumption (8.5 g/kg) over a 4-month period, under controlled nutritional conditions, on antral and plasma levels of gastrin, ultrastructure of G cells, morphometric characteristics of G cells by stereological methods, and analysis of endocrine cells in the gastric mucosa by immunohistochemistry. The chronic alcohol consumption resulted in a nonsignificant decrease in gastrin plasma levels and unchanged antral gastrin concentrations. A slightly damaged glandular portion of the gastric mucosa and dilatation of small blood vessels detected by histological analysis, suggests that ethanol has a toxic effect on the mucosal surface. Chronic alcohol treatment significantly decreased the number of antral G cells per unit area, and increased their cellular, nuclear, and cytoplasmatic profile areas. In addition, the volume density and diameter of G-cell granules, predominantly the pale and lucent types, were increased, indicating inhibition of gastrin release. Ethanol treatment also decreased the number of gastric somatostatin-, serotonin-, and histamine-immunoreactive cells, except the somatostatin cells in the pyloric mucosa, as well as both G: D: enterochromaffin cells (EC) cell ratios in the antrum and D: ECL cell ratios in the fundus. These results indicate that the change of morphometric parameters in G cells may be related to cellular dysfunction. Our findings also suggest that regulation of G-cell secretion was not mediated by locally produced somatostatin in ethanol-consuming rats, but may involve gastric luminal content and/or neurotransmitters of gastric nerve fibers. PMID:18249268

  2. Urinary concentrating mechanism and Aquaporin-2 abundance in rats chronically treated with aluminum lactate.

    PubMed

    Mahieu, Stella; Millen, Néstor; Contini, María del Carmen; Gonzalez, Marcela; Molinas, Sara M; Elías, María Mónica

    2006-06-15

    The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis. PMID:16675087

  3. Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia?

    PubMed

    Ali, Badreldin H; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A; Ramkumar, Aishwarya; Waly, Mostafa I; Yasin, Javid; Adham, Sirin A; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine-induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  4. Does Swimming Exercise Affect Experimental Chronic Kidney Disease in Rats Treated with Gum Acacia?

    PubMed Central

    Ali, Badreldin H.; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A.; Ramkumar, Aishwarya; Waly, Mostafa I.; Yasin, Javid; Adham, Sirin A.; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  5. Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons chronically treated with donepezil.

    PubMed

    Takada-Takatori, Yuki; Kume, Toshiaki; Ohgi, Yuta; Izumi, Yasuhiko; Niidome, Tetsuhiro; Fujii, Takeshi; Sugimoto, Hachiro; Akaike, Akinori

    2008-12-01

    Previously, we showed that in rat cortical neurons, chronic donepezil treatment (10 microM, 4 days) up-regulates nicotinic receptors (nAChR) and makes neurons more sensitive to the neuroprotective effect of donepezil. Here we examined the mechanism of donepezil-induced neuroprotection in neurons chronically treated with donepezil. The mechanism of neuroprotection was examined under different conditions of exposure to glutamate, acute and moderate, that induce cell death associated with necrotic and apoptotic cell death, respectively. Concomitant treatment with antagonists of nAChRs but not muscarinic receptors inhibited donepezil pretreatment-induced neuroprotection against acute glutamate treatment-induced death. Donepezil pretreatment prevented acute glutamate- and ionomycin-induced neurotoxicity, but not S-nitrosocysteine-induced neurotoxicity, suggesting that donepezil protects neurons via nAChR at levels before nitric oxide synthase activation against acute glutamate neurotoxicity. Concomitant treatment with antagonists of nAChR or phosphatidylinositol 3-kinase (PI3K) signaling inhibitors significantly inhibited neuroprotection against moderate glutamate neurotoxicity and decreased the phosphorylation level of Akt. Neuroprotection was also inhibited by treatment with inhibitor of mitogen-activated protein kinase (MAPK) kinase. These results suggest that donepezil protects neurons against moderate glutamate neurotoxicity via nAChR-PI3K-Akt and MAPK signaling pathways. This study provides novel insight into the mechanism of donepezil-induced neuroprotection that involves nAChR up-regulation. PMID:18655200

  6. Effects of excessive dietary methionine on oxidative stress and dyslipidemia in chronic ethanol-treated rats

    PubMed Central

    Kim, Seon-Young; Kim, Hyewon

    2015-01-01

    BACKGROUND/OBJECTIVE The aim of this study was to examine the effect of high dietary methionine (Met) consumption on plasma and hepatic oxidative stress and dyslipidemia in chronic ethanol fed rats. MATERIALS/METHODS Male Wistar rats were fed control or ethanol-containing liquid diets supplemented without (E group) or with DL-Met at 0.6% (EM1 group) or 0.8% (EM2 group) for five weeks. Plasma aminothiols, lipids, malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase were measured. Hepatic folate, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS DL-Met supplementation was found to increase plasma levels of homocysteine (Hcy), triglyceride (TG), total cholesterol (TC), and MDA compared to rats fed ethanol alone and decrease plasma ALT. However, DL-Met supplementation did not significantly change plasma levels of HDL-cholesterol, cysteine, cysteinylglycine, and glutathione. In addition, DL-Met supplementation increased hepatic levels of folate, SAM, SAH, and SAM:SAH ratio. Our data showed that DL-Met supplementation can increase plasma oxidative stress and atherogenic effects by elevating plasma Hcy, TG, and TC in ethanol-fed rats. CONCLUSION The present results demonstrate that Met supplementation increases plasma oxidative stress and atherogenic effects by inducing dyslipidemia and hyperhomocysteinemia in ethanol-fed rats. PMID:25861420

  7. ATP metabolism in rat liver chronically treated with ethanol and high fat

    SciTech Connect

    Miyamoto, K.; French, S.W.

    1986-03-01

    Five pairs of Wistar male rats weighing about 350 g were continuously infused with a liquid diet in which 25-35% of total calories was derived from fat, plus ethanol or isocaloric dextrose through gastrostomy cannulas for 3 wks to 3.5 mos. Mean ethanol intake was 12.9 +/- 0.7 g/kg B.W. (55% of total calories). High blood alcohol levels (BAL, 342 +/- 151 mg/dl) were maintained. The liver showed severe steatosis (4+) in all the ethanol-fed rats (ER). Two had mild focal mononuclear cell infiltration, one had mild fibrosis and one had spotty necrosis. Mild steatosis (1+) was seen in 4 out of 5 pair-fed control rats (CR). Serum ALT was significantly higher in ER (129 +/- 44 U) compared with Cr (59 +/- 30 U) or rats fed chow ad lib (NR) (48 +/- 26 U). Biopsied liver tissue was used to measure the concentration of adenine nucleotides by HPLC (6 pairs). There was a significant decrease of ATP in ER (1.7 +/- 0.3 ..mu..mol/g liver) as compared to CR (2.5 +/- 0.5 ..mu..mol/g) or NR (2.8 +/- 0.2 ..mu..mol/g, n = 6). There was no significant change in the ADP or AMP content, however. The total adenylate pool of the liver was also significantly reduced in ER when compared to that of CR or NR (3.2 +/- 0.4, 4.0 +/- 0.5 and 4.3 +/- 0.2 ..mu..mol/g liver, respectively). Adeynlate energy charge (E.C.) of the ER livers (0.71 +/- 0.05) was significantly reduced compared to NR (0.77 +/- 0.02) but not with CR (0.75 +/- 0.06). The results indicate that ethanol decreases the level of ATP as well as the biological mechanism to compensate for the lowered level.

  8. Alterations of the renal function and oxidative stress in renal tissue from rats chronically treated with aluminium during the initial phase of hepatic regeneration.

    PubMed

    Mahieu, Stella; Millen, Néstor; González, Marcela; Contini, María del Carmen; Elías, María Mónica

    2005-09-01

    Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys. PMID:16129492

  9. Nephrotoxic effects on offspring of rats chronically treated with mercuric chloride

    SciTech Connect

    Rusk, T.L.

    1983-08-01

    Repeated subcutaneous injections of HgCl/sub 2/ at a dose of either 4.0 or 2.0 mg/kg produced toxic effects in rats when administered during the last 9 days of gestation. Females exhibited diarrhea, anorexia and weight loss of varying severity. Maternal renal function was monitored by urinalysis and was shown to be impaired during the early days of treatment but returned to normal later. Histological evaluation of adult kidneys after 2 days of treatment demonstrated the nephrotoxic effects of HgCl/sub 2/. Evidence of the regenerative process was found in tubules lined with densely packed, flattened cuboidal epithelial cells. Pup birth weight among HgCl/sub 2/-exposed litters was significantly lower than that of control litters. Nephrotoxic effects were not identifiable in pups though the presence of mercury was confirmed in fetal kidneys. 93 refs., 7 figs., 3 tabs.

  10. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    PubMed Central

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction. PMID:19166917

  11. Molsidomine, a nitric oxide donor, modulates rotational behavior and monoamine metabolism in 6-OHDA lesioned rats treated chronically with L-DOPA.

    PubMed

    Lorenc-Koci, Elżbieta; Czarnecka, Anna; Lenda, Tomasz; Kamińska, Kinga; Konieczny, Jolanta

    2013-12-01

    Some biochemical and histological studies of Parkinson's disease patients' brains and 6-OHDA-lesioned rats suggest that dopaminergic dennervation of the striatum leads to the nitrergic system hypofunction in this structure. Hence, recently the modulation of nitric oxide (NO)- soluble guanylyl cyclase-cyclic GMP signaling is considered to be a new target for the treatment of Parkinson's disease. The aim of our study was to examine the impact of chronic combined treatment with low doses of the NO donor molsidomine (2 and 4mg/kg) and L-DOPA (12.5 and 25mg/kg) on rotational behavior and monoamine metabolism in the striatum (STR) and substantia nigra (SN) of unilaterally 6-OHDA-lesioned rats. Chronic administration of molsidomine at a dose of 2mg/kg jointly with 25mg/kg of L-DOPA significantly decreased the number of contralateral rotations when compared to L-DOPA alone. Other combinations of the examined drug doses were less effective. The tissue DA levels in the ipsilateral STR and SN after the last chronic doses of molsidomine (2mg/kg) and L-DOPA (12.5 or 25mg/kg), were significantly higher than after L-DOPA alone. Chronic L-DOPA treatment alone or jointly with a lower dose of molsidomine decreased 5-HT levels and accelerated its catabolism in the examined structures. However, combination of a higher dose of molsidomine with L-DOPA (25mg/kg) did not reduce 5-HT content while its catabolism was less intensive. The obtained results show that low doses of molsidomine can modulate rotational behavior and tissue DA and 5-HT concentrations in the STR and SN of 6-OHDA-lesioned rats treated chronically with L-DOPA. PMID:24090640

  12. Periarteritis nodosa in rats treated with chronic excess sodium chloride (NaCl) after X-irradiation

    SciTech Connect

    Watanabe, H.; Nakagawa, Y.; Ito, A.; Kajihara, H.

    1987-07-01

    Five-week-old male Crj:CD (SD) rats were treated with excess sodium chloride after abdominal X-irradiation. The gastric regions of the rats were irradiated with a total dose of 20 Gy given in two equal fractions separated by 3 days. After X-irradiation, animals were fed a diet containing 10% sodium chloride. Red blood cell anemia appeared 22 weeks after the last irradiation. By gross observation, the mesenteric arteries became reddish in color, and bead- or lead pipe-like nodular thickenings were present. Microscopically, these nodularly thickened mesenteric arteries showed fibrinoid necrosis with massive inflammatory infiltration including eosinophils and neutrophils. In more advanced lesions, elastica interna and externa and medial smooth muscle cells disappeared completely and were replaced by granulation tissue. In old lesions, arterial walls were markedly thickened with fibrous or fibromuscular tissue. These findings were quite similar to those of the human periarteritis nodosa. These arterial lesions could not be found in the rats with X-irradiation only, sodium chloride only, or in nontreated animals. This study demonstrates X-ray-induced, NaCl-promoted periarteritis nodosa-like lesions in rats.

  13. Periarteritis nodosa in rats treated with chronic excess sodium chlorides (NaCl) after X-irradiation

    SciTech Connect

    Watanabe, H.; Nakagawa, Y.; Ito, A.; Kajihara, H.

    1987-07-01

    Five-week-old male Crj:CD (SD) rats were treated with excess sodium chloride after abdominal X-irradiation. The gastric regions of the rats were irradiated with a total dose of 20 Gy given in two equal fractions separated by 3 days. After X-irradiation, animals were fed a diet containing 10% sodium chloride. Red blood cell anemia appeared 22 weeks after the last irradiation. By gross observation, the mesenteric arteries became reddish in color, and bead- or lead pipe-like nodular thickenings were present. Microscopically these nodularly thickened mesenteric arteries showed fibrinoid necrosis with massive inflammatory infiltration including eosinophils and neutrophils. In more advanced lesions, elastica interna and externa and medial smooth muscle cells disappeared completely and were replaced by granulation tissue. In old lesions, arterial walls were markedly thickened with fibrous or fibromuscular tissue. These findings were quite similar to those of the human periarteritis nodosa. These arterial lesions could not be found in the rats with X-irradiation only, sodium chloride only, or in nontreated animals. This study demonstrates X-ray-induced, NaCl-promoted periarteritis nodosa-like lesions in rats.

  14. Tolerance to repeated stress in rats with lesions of the serotoninergic neurons of the Median Raphe Nucleus and chronically treated with imipramine.

    PubMed

    Silva, K; Carvalho, M C; Padovan, C M

    2016-04-01

    Repeated exposure to aversive events leads to the development of tolerance to stress, which involves the serotonergic pathway originated in the Median Raphe Nucleus (MnRN) to the Dorsal Hippocampus (DH). However, it is not clear whether these lesion-induced deficits can be attenuated by treatment with antidepressants. Therefore, the aim of this work was to investigate the effects of chronic treatment with Imipramine (IMI) in rats with lesions in the MnRN and exposed to restraint stress. Male Wistar rats with or without neurochemical lesions of the MnRN serotonergic neurons with the neurotoxin 5,7-DHT were submitted to acute (2h) or chronic restraint (2h/day/seven consecutive days) and treated with saline (1 ml/kg) or imipramine (15 mg/kg) via intraperitoneal twice a day during the same period. In acutely restrained rats, stress occurred on the last day of treatment. Test in the elevated plus maze (EPM) was performed 24h later. After EPM test, animals were sacrificed and had their brains removed. Dorsal hippocampus and striatum were dissected and the levels of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) measured by HPLC analysis. Our results showed that in control rats exposure to acute restraint stress decreased exploration of the open and enclose arms of the EPM, an effect that was attenuated by imipramine. In rats with 5,7-DHT lesions, acute restraint did not change the exploration of the EPM, independently of the treatment. On the other hand, when chronically restrained, saline treated rat with 5,7-DHT lesion showed a reduced exploration of the open arms of the EPM. This effect was attenuated by simultaneous treatment with imipramine. HPLC analysis showed significantly decreases on 5-HT and 5-HIAA levels in the hippocampus, but not in the striatum. These later results confirm that 5,7-DHT lesions of the MnRN had significant impact on the serotonergic projections to the dorsal hippocampus which seems to be essential for the development of tolerance to repeated

  15. Antidepressant effects of the extract YZ-50 from Polygala tenuifolia in chronic mild stress treated rats and its possible mechanisms.

    PubMed

    Hu, Yuan; Liu, Ping; Guo, Dai-Hong; Rahman, Khalid; Wang, Dong-Xiao; Xie, Ting-Ting

    2010-07-01

    YZ-50 is an active fraction obtained from the root of Polygala tenuifolia Willd. (Polygalaceae) extract and it has been reported previously to exert beneficial effects on mental health in depressed sufferers, however, its mechanism of action remains unresolved. This study utilized the chronic mild stress (CMS) model of depression in Sprague-Dawley rats to evaluate the effects of YZ-50 on depressive behaviors. Furthermore, we tested the hypothesis that the capacity of YZ-50 to reverse the harmful effects of CMS is relative to the hypothalamo-pituitary-adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Repeated administration of YZ-50 for 28 days at the doses of 140 and 280 mg/kg in CMS, YZ-50 reversed the CMS-induced changes in sucrose consumption, plasma corticosterone levels and open field activity. In addition, CMS significantly decreased hippocampal BDNF mRNA levels. However, YZ-50 counteracted a decrease in hippocampal BDNF mRNA caused by CMS. In conclusion, YZ-50 reversed the harmful effects of CMS on mood and behaviors in rats and it possesses an antidepressant property that is at least in part mediated by the neuroendocrine and neuropropective systems, and it is likely that the HPA system plays an important role in this process. PMID:20645779

  16. Effect of chronic treatment with angiotensin type 1 receptor antagonists on striatal dopamine levels in normal rats and in a rat model of Parkinson's disease treated with L-DOPA.

    PubMed

    Dominguez-Meijide, Antonio; Villar-Cheda, Begoña; Garrido-Gil, Pablo; Sierrra-Paredes, German; Guerra, Maria J; Labandeira-Garcia, Jose L

    2014-01-01

    Beneficial effects of angiotensin type-1 receptor (AT1) inhibition have been observed in a number of brain processes mediated by oxidative stress and neuroinflammation, including Parkinson's disease. However, important counterregulatory interactions between dopamine and angiotensin systems have recently been demonstrated in several peripheral tissues, and it is possible that a decrease in dopamine levels due to AT1 inhibition may interfere with neuroprotective strategies. The present experiments involving rats with normal dopaminergic innervation indicate that chronic treatment with the AT1 antagonist candesartan does not significantly affect striatal levels of dopamine, serotonin or metabolites, as does not significantly affect motor behavior, as evaluated by the rotarod test. Interestingly, chronic administration of candesartan to normal rats induced a marked increase in dopamine D1 and a decrease in dopamine D2 receptor expression. In a rat model of Parkinson's disease treated with L-DOPA, no differences in striatal dopamine and serotonin levels were observed between candesartan-treated rats and untreated, which suggests that chronic treatment with candesartan does not significantly affect the process of L-DOPA decarboxylation and dopamine release in Parkinson's disease patients. Candesartan did not induce any differences in the striatal expression of dopamine D1 and D2 and serotonin 5-HT1B receptors in 6ydroxydopamine-lesioned rats treated with L-DOPA. The results suggest that chronic treatment with AT1 antagonists as a neuroprotective strategy does not significantly affect striatal dopamine release or motor behavior. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. PMID:23973568

  17. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with lamotrigine.

    PubMed

    Zalewska-Kaszubska, Jadwiga; Bajer, Bartosz; Gorska, Dorota; Andrzejczak, Dariusz; Dyr, Wanda; Bieńkowski, Przemysław

    2015-02-01

    Several recent studies have indicated that lamotrigine, similarly to other antiepileptic drugs, may be useful in the therapy of alcohol dependence. The rationale for using lamotrigine in the treatment of alcohol addiction is based on its multiple mechanisms of action which include inhibition of voltage-sensitive sodium channels, modulation voltage-gated calcium currents and transient potassium outward current. However, the known mechanism of lamotrigine does not fully explain its efficacy in alcohol addiction therapy. For this reason we have decided to examine the effect of lamotrigine on the opioid system. Our previous studies showed that topiramate and levetiracetam (antiepileptic drugs) as well as the most effective drugs in alcohol addiction therapy i.e. naltrexone and acamprosate, when given repeatedly, all increased plasma beta endorphin (an endogenous opioid peptide) level, despite operating through different pharmacological mechanisms. It is known that low beta-endorphin level is often associated with alcohol addiction and also that alcohol consumption elevates the level of this peptide. This study aims to assess the effect of repeated treatment with lamotrigine on voluntary alcohol intake and beta-endorphin plasma level in alcohol preferring rats (Warsaw high preferring (WHP) rats). We observed a decrease in alcohol consumption in rats treated with lamotrigine. However we didn't observe significant changes in beta-endorphin level during withdrawal of alcohol, which may indicate that the drug does not affect the opioid system. We suppose that lamotrigine may be useful in alcohol dependence therapy and presents a potential area for further study. PMID:25449391

  18. CCK-8 injected into the nucleus accumbens attenuates the supersensitive locomotor response to apomorphine in 6-OHDA and chronic-neuroleptic treated rats.

    PubMed

    Weiss, F; Ettenberg, A; Koob, G F

    1989-01-01

    Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 micrograms) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6-hydroxydopamine (6-OHDA; 8 micrograms/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 micrograms) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced "biphasic" dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 microgram) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only short-term reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens. PMID:2574480

  19. Hydrogen peroxide-induced oxidative damage in peripheral blood lymphocytes from rats chronically treated with corticosterone: The protective effect of oxytocin treatment.

    PubMed

    Stanić, Dušanka; Plećaš-Solarović, Bosiljka; Petrović, Jelena; Bogavac-Stanojević, Nataša; Sopić, Miron; Kotur-Stevuljević, Jelena; Ignjatović, Svetlana; Pešić, Vesna

    2016-08-25

    Contemporary lifestyle is commonly associated with chronic stress, an environmental factor contributing to development of various psychological and somatic disorders. Increased levels of glucocorticoids, observed in the chronic stress, induce the production of reactive oxygen species leading to genotoxicity. The aim of this study was to investigate whether chronic administration of oxytocin (OXY) 10 IU/400 μL/day, s.c., for 14 days, a hormone presumed to exert antioxidant effect, may prevent DNA damage in the comet assay of peripheral blood lymphocytes of Wistar rats treated chronically with corticosterone (CORT) 100 mg/L ad libitum, per os, for 21 days, as well as, to influence some plasma oxidative stress parameters, i.e. levels of total lipid hydroperoxide (LOOH), and malondialdehyde (MDA), and the activity of antioxidative enzyme superoxide dismutase (SOD). Even though there was no reduction in overall number of damaged cells after oxytocin treatment only, the marked increase in total comet score (TCS) after incubation with H2O2 in CORT group compared to controls, was absent in the CORT + OXY experimental group. Furthermore, significant decrease of highly damaged cells compared to corticosterone group was noted. Chronic oxytocin administration thus protected lymphocytes from high intensity damage that leads to cellular death. In addition, treatment with OXY along with CORT, significantly decreased concentration of LOOH in plasma, and increased SOD compared to CORT treatment only. This finding corresponds well with current reports on beneficial effects of OXY in conditions of HPA axis hyperactivity, and supports the hypothesis of OXY-mediated antioxidant action. PMID:27402529

  20. Microbubble-mediated ultrasound promotes accumulation of bone marrow mesenchymal stem cell to the prostate for treating chronic bacterial prostatitis in rats

    PubMed Central

    Yi, Shanhong; Han, Guangwei; Shang, Yonggang; Liu, Chengcheng; Cui, Dong; Yu, Shuangjiang; Liao, Bin; Ao, Xiang; Li, Guangzhi; Li, Longkun

    2016-01-01

    Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared with a healthy control group. A therapeutic-ultrasound apparatus was used to treat the prostate in the presence of circulating microbubbles and BMMSCs. The BMMSC distribution was assessed with in vivo imaging, and the prostate structure with light microscopy. Real-time quantitative RT-PCR, ELISA, and immunohistochemistry were used to assess the expressions of TNF-α and IL-1β. More BMMSCs were found in the prostate in the MMUS group than in the CBP, ultrasound, and BMMSC groups. Inflammatory cell infiltration, fibrous tissue hyperplasia, and tumor-like epithelial proliferation were significantly reduced in the MMUS group, as were the mRNA and protein expressions of TNF-α and IL-1β. Microbubble-mediated ultrasound-induced accumulation of BMMSCs can inhibit inflammation and decrease TNF-α and IL-1β expressions in the prostate of CBP rats, suggesting that this method may be therapeutic for CPB. PMID:26797392

  1. Anti-inflammatory effect of glycosaminoglycan derived from Gryllus bimaculatus (a type of cricket, insect) on adjuvant-treated chronic arthritis rat model.

    PubMed

    Ahn, Mi Young; Han, Jea Woong; Hwang, Jae Sam; Yun, Eun Young; Lee, Byung Mu

    2014-01-01

    Anti-inflammatory effects of glycosaminoglycan (GAG) derived from cricket (Gryllus bimaculatus, Gb) were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritic rat model. This GAG produced a significant anti-edema effect as evidenced by inhibition of C-reactive protein (CRP) and rheumatoid factor, and interfered with atherogenesis by reducing proinflammatory cytokine levels of (1) vascular endothelial growth factor (VEGF) production in human umbilical vein endothelial cells (HUVEC), (2) interleukin-6, (3) prostaglandin E2-stimulated lipopolysaccharide in RAW 264.7 cells, and (4) tumor necrosis factor (TNF)-α production in normal splenocytes, in a dose-dependent manner. This GAG was also found to induce nitric oxide (NO) production in HUVEC cells and elevated endothelial nitric oxide synthase (eNOS) activity levels. Histological findings demonstrated the fifth lumbar vertebrae (LV) dorsal root ganglion, which was linked to the paw treated with Gb GAG, was repaired against CFA-induced cartilage destruction. Further, combined indomethacin (5 mg/kg)-Gb GAG (10 mg/kg) inhibited more effectively CFA-induced paw edema at 3 h and 2 or 3 d after treatment to levels comparable to only the anti-inflammatory drug indomethacin. Ultraviolet (UV)-irritated skin inflammation also downregulated nuclear factor κB (NFκB) activity in transfected HaCaT cells. Data suggest that the anti-inflammatory effects of GAG obtained from cricket (Gb) may be useful for treatment of inflammatory diseases including chronic arthritis. PMID:25343284

  2. Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats

    PubMed Central

    Allen, Patricia J.; DeBold, Joseph F.; Rios, Maribel; Kanarek, Robin B.

    2015-01-01

    Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine + T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine + EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy

  3. CATALYTICALLY AND NONCATALYTICALLY TREATED AUTOMOBILE EXHAUST: BIOLOGICAL EFFECTS IN RATS

    EPA Science Inventory

    Chronic exposure to catalytically treated or noncatalytically treated automobile exhaust significantly depressed the spontaneous locomotor activity (SLA) of rats. Exposure to H2SO4 alone or CO at comparable levels did not alter the SLA. Exposure to noncatalytically treated exhaus...

  4. Diagnosing and Treating Chronic Urticaria

    PubMed Central

    Epstein, Norman

    1972-01-01

    Chronic urticaria is differentiated from the acute type by its persistence and by its causative agents. It can result from histamine, and other chemical mediators, released from damaged mast cells either by an antigen-antibody reaction or some other mechanism. The cause, often elusive, may be common foods or medications. External temperature changes can be manifested by urticaria through various mechanisms. The endogenous causes include chronic foci of infections such as in teeth, sinuses or tonsils, endocrine changes, parasitic infestations. Chronic urticaria may be a symptom of underlying more serious systemic diseases such as lymphomas. PMID:20468756

  5. Epigallocatechin-3-Gallate Attenuates Impairment of Learning and Memory in Chronic Unpredictable Mild Stress-Treated Rats by Restoring Hippocampal Autophagic Flux

    PubMed Central

    Tang, Ya-Ling; Zeng, Yang; Jing, Kai-Quan; Zheng, Xi-Long; Liao, Duan-Fang

    2014-01-01

    Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS)-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.) significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1–42 (Aβ1−42) levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux. PMID:25393306

  6. The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor.

    PubMed

    Pilutin, Anna; Misiakiewicz-Has, Kamila; Kolasa, Agnieszka; Baranowska-Bosiacka, Irena; Marchlewicz, Mariola; Wiszniewska, Barbara

    2014-01-01

    The function of testis is under hormonal control and any disturbance of hormonal homeostasis can lead to morphological and physiological changes. Therefore the aim of the study was to investigate the expression of androgen and estrogen receptors (AR, ERs), vanilloid receptor (TRPV1), cytochrome P450 aromatase (P450arom), as well as apoptosis of cells in testis of adult rats chronically treated with letrozole (LT), a non-steroidal aromatase inhibitor, for 6 months. The testicular tissues were fixed in Bouin's fixative and embedded in paraffin. Immunohistochemistry with monoclonal antibodies (abs) against AR, ERa, P450arom, and polyclonalabs against ERβ, TRPV1, caspase-3 was applied. Long-lasting estradiol deficiency, as an effect of LT treatment, produced changes in the morphology of testis and altered the expression of the studied receptors in cells of the seminiferous tubules and rate of cell apoptosis. The immunostaining for AR was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle. The intensity of staining for P450arom was lower in the testis of LT-treated rats as compared to control animals. The immunofluorescence of ERα and ERβ was observed exclusively in the nuclei of Leydig cells of LT-treated rats. There were no changes in localization of TRPV1, however, the intensity of reaction was stronger in germ cells of the seminiferous epithelium after LT treatment. The apoptosis in both groups of animals was observed within the population of spermatocytes and spermatids in II and III stages of the seminiferous epithelium cycle. In testis of LT-treated rats the immunoexpression of caspase-3 was additionally found in the germ cells in I and IV stages, and Sertoli, myoid and Leydig cells. In conclusion, our results underline the important role of letrozole treatment in the proper function of male reproductive system, and additionally demonstrate that hormonal imbalance can

  7. Quantitation of pyridyloxobutyl-DNA adducts in tissues of rats treated chronically with (R)- or (S)-N'-nitrosonornicotine (NNN) in a carcinogenicity study.

    PubMed

    Zhao, Lijiao; Balbo, Silvia; Wang, Mingyao; Upadhyaya, Pramod; Khariwala, Samir S; Villalta, Peter W; Hecht, Stephen S

    2013-10-21

    We quantified DNA adducts resulting from 2'-hydroxylation of enantiomers of the tobacco-specific nitrosamine N'-nitrosonornicotine (NNN) in tissues of male F-344 rats after 10, 30, 50, and 70 weeks of treatment with 14 ppm in the drinking water. These rats were in subgroups of a carcinogenicity study in which (S)-NNN was highly tumorigenic in the oral cavity and esophagus, while (R)-NNN was relatively weakly active. DNA adducts were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry in six tissues: oral mucosa, esophageal mucosa, nasal respiratory mucosa, nasal olfactory mucosa, liver, and lung. O²-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O²-POB-dThd, 7) and 7-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxyguanosine (7-POB-dGuo, 8), the latter as 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine (7-POB-Gua, 11), were detected at each time point in each tissue. In the target tissues for carcinogenicity, oral mucosa and esophageal mucosa, levels of 7-POB-Gua (11) and O²-POB-dThd (7) were similar, or 11 predominated, while in all other tissues at all time points for both enantiomers, 7 was clearly present in greater amounts than 11. Total measured DNA adduct levels in esophageal mucosa and oral mucosa were higher in rats treated with (S)-NNN than (R)-NNN. The highest adduct levels were found in the nasal respiratory mucosa. DNA adducts generally persisted in all tissues without any sign of substantial decreases throughout the 70 week time course. The results of this study suggest that inefficient repair of 7-POB-dGuo (8) in the rat oral cavity and esophagus may be important in carcinogenesis by NNN and support the development of these DNA adducts as potential biomarkers of NNN metabolic activation in people who use tobacco products. PMID:24001146

  8. Panax ginseng extract modulates oxidative stress, DNA fragmentation and up-regulate gene expression in rats sub chronically treated with aflatoxin B1 and fumonisin B 1.

    PubMed

    Hassan, Aziza M; Abdel-Aziem, Sekena H; El-Nekeety, Aziza A; Abdel-Wahhab, Mosaad A

    2015-10-01

    Aflatoxins and fumonisins are important food-borne mycotoxins implicated in human health and have cytotoxic effects. The aims of the current study were to evaluate the protective role of Panax ginseng extract (PGE) against the synergistic effect of subchronic administration of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on DNA and gene expression in rat. Female Sprague-Dawley rats were divided into eight groups (ten rats/group) and treated for 12 weeks including the control group, the group having received AFB1 (80 µg/kg bw), the group having received FB1 (100 µg/kg bw), the group having received AFB1 plus FB1 and the groups having received PGE (20 mg/kg bw) alone or with AFB1 and/or FB1. At the end of experiment, liver and kidney were collected for the determination of DNA fragmentation, lipid peroxidation (LP), glutathione (GSH) contents and alterations in gene expression. The results indicated that these mycotoxins increased DNA fragmentation, LP and decreased GSH content in liver and kidney and down-regulated gene expression of antioxidants enzymes. The combined treatments with AFB1 and/or FB1 plus PGE suppressed DNA fragmentation only in the liver, normalized LP and increased GSH in the liver and kidney as well as up-regulated the expression of GPx, SOD1 and CAT mRNA. It could be concluded that AFB1 and FB1 have synergistic genotoxic effects. PGE induced protective effects against their oxidative stress and genotoxicity through its antioxidant properties. PMID:24748134

  9. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    PubMed

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders. PMID:26919286

  10. Rat growth during chronic centrifugation

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.; Oyama, J.

    1978-01-01

    Female weanling rats were chronically centrifuged at 4.15 G with controls at terrestrial gravity. Samples were sacrificed for body composition studies at 0, 28, 63, 105 and 308 days of centrifugation. The centrifuged group approached a significantly lower mature body mass than the controls (251 and 318g) but the rate of approach was the same in both groups. Retirement to 1G on the 60th day resulted in complete recovery. Among individual components muscle, bone, skin, CNS, heart, kidneys, body water and body fat were changed in the centrifuged group. However, an analysis of the growth of individual components relative to growth of the total fat-free compartment revealed that only skin (which increased in mass) was responding to centrifugation per se.

  11. Renal kallikrein in chronic hypoxic rats.

    PubMed

    Chen, C F; Chen, L W; Chien, C T; Wu, M S; Tsai, T J

    1996-09-01

    1. We have studied the role of kallikrein (KK) in the maintenance of renal function in chronic hypoxic rats (high altitude; HA), compared with control rats kept at sea level (SL). Hypoxia was induced by placing female Wistar rats (198-290 g) in an altitude chamber (5500 m) 15 h/day for 4 weeks. Experiments were also conducted to study the interaction of KK with renal nerve activity and endothelin (ET), two parameters previously shown to be altered in this model. 2. It was found that renal cortex tissue KK activity (TKA) was not significantly different in 10 SL and 10 HA rats. However, the urinary KK activity (UKA) was reduced nearly to half (from 35.2 +/- 4.6 to 18.5 +/- 1.7 pkat/min) in HA rats after 4 weeks of chronic hypoxia. 3. Acute renal denervated diuresis was accompanied by a significant increase in UKA (from 9 +/- 2 to 14 +/- 2 pkat/min in HA and denervated HA rats, respectively; P < 0.05) in HA rats. Intrarenal arterial pretreatment of aprotinin reduced the denervated diuresis. 4. Endothelin (600 ng/kg per h) reduced urine flow, sodium and potassium excretion in the ipsilateral kidney in another 10 SL and 10 HA rats. The extent of the drop of these parameters was significantly less in HA rats. Urinary KK activity was correlated significantly with the measured renal functional parameters (r ranging from 0.472 to 0.612) in SL rats, but was insignificant in HA rats (r ranging from 0.032 to 0.192). 5. We have demonstrated that chronic exposure to hypoxia decreases urinary KK excretion and that KK is involved in acute renal denervated diuresis generated in these animals. The present study suggests that KK plays a partial role in the maintenance of renal function in chronic hypoxic rats. PMID:8911720

  12. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    PubMed

    Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  13. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    PubMed Central

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  14. Calcium kinetics in the Solanum malacoxylon-treated rat.

    PubMed

    Cabrejas, M; Ladizesky, M; Mautalen, C A

    1975-12-01

    The chronic ingestion of the leaves of the plant Solanum malacoxylon (SM) causes an endemic disease in the cattle of some areas of Buenos Aires province. The animals affected manifest loss of appetite and weight, hypercalcemia, hyperphosphatemia, and ectopic calcifications. In order to study the mechanism of the hypercalcemia provoked by the administration of SM, a calcium kinetic study was performed in control and treated adult intact rats. The animals receiving SM showed higher levels of serum calcium throughout the study. The body excretion of 47Ca and the size of the most rapidly exchangeable calcium pool were also elevated. On the other hand, the bone accretion rate and the urinary excretion of total hydroxyproline were significantly diminished. The results indicate that during the early phase of SM administration in intact rats, bone turnover rate is depressed. PMID:1195017

  15. Chronic ethanol consumption depresses hypothalamic-pituitary-adrenal function in aged rats

    SciTech Connect

    Nolan, C.J.; Bestervelt, L.L.; Mousigian, C.A.; Maimansomsuk, P.; Yong Cai; Piper, W.N. )

    1991-01-01

    In separate experiments, nine (n=20) and fifteen (n=12) month old rats were treated with either 6% ethanol or 12% sucrose in the drinking water to examine the effect of chronic ethanol consumption on the hypothalamic-pituitary-adrenal axis of aged rats. Blood was collected and plasma concentrations of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. Adrenal glands were cleaned, quartered and used to test in vitro responsiveness to ACTH. Anterior pituitary glands from all 15 month old rats and one half of the nine month old rats were collected, frozen and extracted for measurement of tissue ACTH concentration. The remaining anterior pituitary glands from the nine month old rats were challenged with corticotropin releasing hormone (CRH) to test in vitro responsiveness. In nine month old rats, chronic ethanol consumption decreased plasma ACTH and corticosterone. Pituitary ACTH concentrations were unchanged in treated nine month old rats, but the amount of pituitary ACTH released in response to CRH was decreased in rats consuming ethanol. In vitro responsiveness of the adrenal gland to ACTH in nine month old rats consuming ethanol was unchanged. Plasma ACTH and corticosterone concentrations were also decreased in 15 month old rats chronically consuming ethanol. No differences were noted in responsiveness of the adrenal gland or in the amount of pituitary ACTH due to ethanol consumptions in 15 month old rats.

  16. Respiratory plasticity in the behaving rat following chronic intermittent hypoxia.

    PubMed

    Edge, Deirdre; Skelly, J Richard; Bradford, Aidan; O'Halloran, Ken D

    2010-01-01

    Chronic intermittent hypoxia (CIH), a feature of obstructive sleep apnoea (OSA) has been shown to have myriad effects on the respiratory control system. The effects on breathing are of great clinical significance for the sleep apnoea patient. We sought to determine the effect of CIH on normoxic ventilation. Both male and female adult Wistar rats were studied due to the evident sex difference in the prevalence of OSA. A role for oxidative stress in respiratory modifications was also explored. Adult male (n = 30) and female (n = 16) rats were exposed to alternating periods of N(2) and O(2) for 90 s each, bringing the ambient oxygen concentration to 5% at nadir (CIH) group. Sham groups were subject to cycles of air/air under identical experimental conditions. A subset of male rats (8 controls, 8 CIH) had free access to water containing 1 mM Tempol (SOD-mimetic) at all times. Treatments were carried out for 8 hours a day for 9 days. Following treatment, normoxic ventilation was assessed by whole body plethysmography in sleeping animals. Baseline normoxic ventilation was increased in both male and female treated rats but this did not achieve statistical significance. However, ventilatory drive (V(T)/Ti) was significantly increased in male rats. Chronic treatment with Tempol abolished this effect. Conversely, CIH had no significant effect on VT/Ti in female rats. Our results indicate subtle effects of intermittent hypoxia on breathing in conscious behaving rats. We speculate the increased ventilatory drive following CIH represents a form a neural plasticity - a ROS dependent phenomenon - with sexual dimorphism. PMID:20217363

  17. Treating Chronic Pain with Opioids: Comparing Effectiveness and Cost

    MedlinePlus

    Treating Chronic Pain with Opioids: Comparing Effectiveness and Cost What are opioids? Opioids are very strong prescription ... using opioids. We compared the effectiveness, safety, and cost of different opioids. We chose these as Consumer ...

  18. Hemodynamic alterations in chronically conscious unrestrained diabetic rats

    SciTech Connect

    Carbonell, L.F.; Salmon, M.G.; Garcia-Estan, J.; Salazar, F.J.; Ubeda, M.; Quesada, T.

    1987-05-01

    Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. Plasma volume was measured by dilution of radioiodinated (/sup 125/I) human serum albumin. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dt/sub max/ and dP/dt/sub min/ of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic states, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

  19. Treating Alcoholism As a Chronic Disease

    PubMed Central

    McKay, James R.; Hiller-Sturmhöfel, Susanne

    2011-01-01

    For many patients, alcohol and other drug (AOD) use disorders are chronic, recurring conditions involving multiple cycles of treatment, abstinence, and relapse. To disrupt this cycle, treatment can include continuing care to reduce the risk of relapse. The most commonly used treatment approach is initial intensive inpatient or outpatient care based on 12-step principles, followed by continuing care involving self-help groups, 12-step group counseling, or individual therapy. Although these programs can be effective, many patients drop out of initial treatment or do not complete continuing care. Thus, researchers and clinicians have begun to develop alternative approaches to enhance treatment retention in both initial and continuing care. One focus of these efforts has been the design of extended treatment models. These approaches increasingly blur the distinction between initial and continuing care and aim to prolong treatment participation by providing a continuum of care. Other researchers have focused on developing alternative treatment strategies (e.g., telephone-based interventions) that go beyond traditional settings and adaptive treatment algorithms that may improve outcomes for clients who do not respond well to traditional approaches. PMID:23580020

  20. Effects of propranolol and sucralfate on ethanol-induced gastric mucosal damage in chronic portal hypertensive rats.

    PubMed

    Geoffroy, P; Duchateau, A; Thiéfin, G; Zeitoun, P

    1987-10-01

    In a rat model of chronic portal hypertension we studied ethanol-induced gastric mucosal damage and the effects of pretreatment by propranolol and sucralfate. Susceptibility to ethanol was increased in chronic portal hypertensive rats compared with sham-operated rats (55 +/- 8% vs. 25 +/- 4%). Both acute pretreatment (10 min) and chronic pretreatment (3 weeks) with propranolol reduced gastric mucosal injury induced by ethanol in portal hypertensive rats, compared with saline-treated rats. Acute and chronic pretreatment with propranolol had no protective effect in sham-operated rats. In portal hypertensive rats, sucralfate in two different doses (500 and 125 mg/kg) protected the gastric mucosa against ethanol-induced gastric injury compared with animals receiving saline (2 +/- 1% and 3 +/- 2% vs. 25 +/- 3%). Sucralfate at the higher dose did not reduce portal pressure in portal hypertensive rats. We conclude that: (1) chronic portal hypertension increases ethanol-induced gastric damage; (2) acute and chronic propranolol treatment reduces ethanol-induced gastric injury in portal hypertensive rats, probably by decreasing portal hypertension; (3) sucralfate has a cytoprotective effect in portal hypertensive rats without reducing portal pressure. These results suggest a potential application of sucralfate in patients otherwise treated by sclerotherapy. PMID:3693860

  1. Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

    PubMed

    Li, Peng; Yin, Ya-Ling; Zhu, Mo-Li; Pan, Guo-Pin; Zhao, Fan-Rong; Lu, Jun-Xiu; Liu, Zhan; Wang, Shuang-Xi; Hu, Chang-Ping

    2016-04-01

    Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. PMID:26818681

  2. Damage of hippocampal neurons in rats with chronic alcoholism

    PubMed Central

    Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear membrane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin. PMID:25368648

  3. Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

    PubMed

    García-Moreno, Luis M; Cimadevilla, Jose M

    2012-12-01

    Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities. PMID:22944615

  4. Neonatal capsaicin treatment in rats induces chronic hyperthermia resulting in infectious disease

    PubMed Central

    JEONG, KEUN-YEONG; KIM, HWAN MOOK

    2015-01-01

    Treatment of neonatal animals with capsaicin has previously been associated with long-lasting hyperthermia and severe cutaneous lesions. The present study analyzed the effects of capsaicin-induced hyperthermia on the occurrence of infectious disease and pruritic dermatitis in a rat model. Pregnant Sprague-Dawley (SD) rats were obtained 1 week prior to parturition. Pups from each litter were randomly assigned to the following experimental groups: Capsaicin-treated (cap-treated; n=10) or vehicle-treated (n=5). Capsaicin (50 mg/kg) or vehicle were systemically administered to the SD rat pups (age, 48 h), after which body temperature was measured using a biotelemetry system, and the effects of hyperthermia on the ability of the rat pups to resist bacterial infection were analyzed. Furthermore, pruritus-induced scratching behavior and dermatitis were assessed, and changes in interleukin (IL)-4- and IL-13-induced immunoglobulin E expression were measured. Treatment of neonatal rats with capsaicin resulted in chronic hyperthermia, which had negative effects on the host immune defense response. The expression levels of T-helper type 2 cell-associated cytokines were significantly increased (P<0.01) in the cap-treated rats following bacterial infection with Staphylococcus aureus or Streptococcus agalactiae. Furthermore, cap-treated rats exhibited pruritus-induced scratching behavior and dermatitis. The results of the present study suggested that treatment of neonatal rats with capsaicin induces chronic hyperthermia and decreases the effectiveness of the host defense system. Therefore, a cap-treated neonatal rat model may be considered useful when investigating the association between hyperthermia and infectious disease. PMID:26668650

  5. Sensitization of the Hypothalamic-Pituitary-Adrenal Axis in a Male Rat Chronic Stress Model.

    PubMed

    Franco, Alier J; Chen, Chun; Scullen, Tyler; Zsombok, Andrea; Salahudeen, Ahmed A; Di, Shi; Herman, James P; Tasker, Jeffrey G

    2016-06-01

    Stress activation of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by rapid glucocorticoid negative feedback. Chronic unpredictable stress animal models recapitulate certain aspects of major depression in humans, which have been attributed to impaired glucocorticoid negative feedback. We tested for an attenuated HPA sensitivity to fast glucocorticoid feedback inhibition in male rats exposed to a chronic variable stress (CVS) paradigm. In vitro, parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus recorded in slices from CVS rats showed an increase in basal excitatory synaptic inputs and a decrease in basal inhibitory synaptic inputs compared with neurons from control rats. There was no difference between control and CVS-treated rats in the rapid glucocorticoid suppression of excitatory synaptic inputs, a fast feedback mechanism. In vivo, CVS-treated rats showed an increase in ACTH secretion at baseline and after both iv CRH and acute stress and no impairment of the corticosterone suppression of the ACTH response, compared with controls. In an in vitro pituitary preparation, an increase in basal ACTH release, a small increase in CRH-induced ACTH release, and no decrement in the glucocorticoid suppression of ACTH release were seen in pituitaries from CVS rats. Thus, CVS does not suppress rapid glucocorticoid negative feedback at the hypothalamus or pituitary, but increases the synaptic excitability of paraventricular nucleus CRH neurons and the CRH sensitivity of the pituitary. Therefore, increased HPA activity in chronically stressed male rats is due to sensitization of the HPA axis, rather than to desensitization to rapid glucocorticoid feedback. PMID:27054552

  6. Treating chronic arsenic toxicity with high selenium lentil diets

    SciTech Connect

    Sah, Shweta; Vandenberg, Albert; Smits, Judit

    2013-10-01

    Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

  7. Chronic stress sensitizes rats to pancreatitis induced by cerulein: Role of TNF-α

    PubMed Central

    Binker, Marcelo G; Binker-Cosen, Andres A; Richards, Daniel; Gaisano, Herbert Y; de Cosen, Rodica H; Cosen-Binker, Laura I

    2010-01-01

    AIM: To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. METHODS: Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. RESULTS: In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases’ activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases’activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues’ ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. CONCLUSION: In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. PMID:21105189

  8. Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression.

    PubMed

    Matchkov, Vladimir V; Kravtsova, Violetta V; Wiborg, Ove; Aalkjaer, Christian; Bouzinova, Elena V

    2015-10-15

    Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with >30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS-susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with >20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX-2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways. PMID:26269522

  9. Denver Potable Water Reuse Demonstration Project: comprehensive chronic rat study.

    PubMed

    Condie, L W; Lauer, W C; Wolfe, G W; Czeh, E T; Burns, J M

    1994-11-01

    The health effects testing program for the Denver Water Department's Potable Water Reuse Demonstration Project was designed to evaluate the relative health effects of highly treated reclaimed water derived from secondary wastewater in comparison with Denver's present high-quality drinking water. The 1 x 10(6) gal/day treatment plant provided 500-fold concentrates of water that had been treated by multiple processes to remove microbial and chemical contaminants. Fischer 344 rats were exposed to the complex mixture solutions for up to 2 yr to evaluate chronic toxicity and oncogenicity effects. The following parameters were evaluated: clinical observations, survival rate, growth, food and water consumption, haematology, clinical chemistry, urinalysis, organ weights, gross autopsy and histopathological examination of all lesions, major tissues and organs. Clinical pathology, gross pathology, and microscopic pathology conducted at wk 26 and 65 and at the end of the study did not reveal any findings that could be considered to be treatment related. Administration of drinking water concentrates at up to 500 times the original concentration in the original water samples to F344 rats for up to 104 wk did not result in any overt toxicological or carcinogenic effects. PMID:7959456

  10. Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-16

    B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  11. Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats

    PubMed Central

    Zhang, Ning; Liang, Hanyu; Farese, Robert V.; Li, Ji

    2015-01-01

    Aims To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. Materials and Methods For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Results Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Conclusions Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo. PMID:26196892

  12. Renal Response to Chronic Centrifugation in Rats

    NASA Technical Reports Server (NTRS)

    Ortiz, Rudy M.; Wang, T. J.; Corbin, B. J.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

  13. Prostaglandins in the brain of rats given, acutely, and chronically, a hyperthermic dose of met-enkephalin.

    PubMed

    Scoto, G M; Spadaro, C; Spampinato, S; Arrigo-Reina, R; Ferri, S

    1979-01-31

    An enhanced prostaglandinlike activity is shown in homogenates of brain from rats treated intracerebroventricularly with 100 microgram of metenkephalin. The increase is significantly reduced by naloxone pretreatment. A relationship is proposed between generation of prostaglandins in the brain following met-enkephalin administration and hyperthermic effect of the opiatelike factor in the rat. Normalization of prostaglandinlike activity following chronic administration of met-enkephalin in the rat may also account for the development of tolerance to its thermic effect. PMID:106433

  14. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    PubMed

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  15. Chronic ethanol consumption impairs spatial remote memory in rats but does not affect cortical cholinergic parameters.

    PubMed

    Pereira, S R; Menezes, G A; Franco, G C; Costa, A E; Ribeiro, A M

    1998-06-01

    We have studied learning, memory and cortical cholinergic parameters after oral administration of 20% v/v ethanol solution to male Fisher rats for 6 months. A group of rats were trained to behave efficiently in an eight-arm radial maze and after that split into two subgroups submitted to ethanol or control treatment. Ethanol-treated rats had more difficulty in relearning the same task 1 year later, compared to ethanol-untreated rats (control). Differences in working memory performance were found, but only in the first 10 training sessions. Another group of rats, which had not been pretrained, was also split into two subgroups submitted to ethanol or control treatment. After that, these rats were trained in the radial maze task for the first time. No significant difference was found between the reference memory performance of the untreated subgroup and the treated one. These two subgroups did not significantly differ in their working memory performance either. Moreover, there were no significant differences between treated and control subjects in the following biochemical brain cortical parameters: in vitro acetylcholinesterase (AChE) activity, and stimulated acetylcholine (ACh) release. This work presents an experimental design that allows assessment of remote memory performance after ethanol chronic consumption and shows that the experimental subject is able to retain the behaviors learned 1 year before. It was concluded that chronic ethanol treatment may cause retrograde amnesia, which does not seem to be linked with a cortical cholinergic deficit. PMID:9632211

  16. Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

    PubMed Central

    Laferrière, André; Abaji, Rachid; Tsai, Cheng-Yu Mark; Ragavendran, J. Vaigunda; Coderre, Terence J.

    2015-01-01

    Background Growing evidence indicates that patients with complex regional pain syndrome (CRPS) exhibit tissue abnormalities caused by microvascular dysfunction in the blood vessels of skin, muscle and nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in an animal model of CRPS. We hypothesized that topical administration of either α2-adrenergic (α2A) receptor agonists or nitric oxide (NO) donors given to increase arterial blood flow, combined with either phosphatidic acid (PA) or phosphodiesterase (PDE) inhibitors to increase capillary blood flow, would effectively reduce allodynia and signs of microvascular dysfunction in the animal model of chronic pain. Methods Mechanical allodynia was induced in the hind paws of rats with chronic postischemia pain (CPIP). Allodynia was assessed before and after topical application of vehicle, single drugs or combinations of an α2A receptor agonist (apraclonidine) or an NO donor (linsidomine), with PA or PDE inhibitors (lisofylline, pentoxifylline). A topical combination of apraclonidine + lisofylline was also evaluated for its effects on a measure of microvascular function (post-occlusive reactive hyperemia) and tissue oxidative capacity (formazan production by tetrazolium reduction) in CPIP rats. Results Each of the single topical drugs produced significant dose-dependent antiallodynic effects compared to vehicle in CPIP rats (n = 30), and the antiallodynic dose-response curves of either PA or PDE inhibitors were shifted 5 to 10 fold to the left when combined with nonanalgesic doses of α2A receptor agonists or NO donors (n = 28). The potent antiallodynic effects of ipsilateral treatment with combinations of α2A receptor agonists or NO donors with PA or PDE inhibitors, were not reproduced by the same treatment of the contralateral hindpaw (n = 28). Topical combinations produced antiallodynic effects lasting up to 6 h (n = 15), and were significantly enhanced by

  17. Natural killer (NK) activity of pit cells perfused from livers of rats treated with ethanol

    SciTech Connect

    Albornoz, L.; Jones, J.M.; Crutchfield, C.; Veech, R.L. Univ. of Arkansas Medical Sciences, Little Rock )

    1991-03-11

    The liver is the major site of ethanol (ETOH) metabolism. Liver sinusoids contain lymphocytes with NK activity. The authors treated LEW rats for 2 weeks with i.p. injection of 1.25 ml 25% ETOH/kg 3 times/week and 5% ETOH in drinking water. Livers were perfused at 5-fold physiological pressure and cells obtained were banded on 1.077 density Ficoll. Their cytotoxicity was tested against {sup 51}Cr-labeled YAC-1 or U937 and compared to spleen and blood lymphocytes. In untreated rats, pit cell NK activity was 2-fold that of splenic lymphocytes and 4-fold that of blood lymphocytes. Compared to controls, ETOH-treated rats exhibited a 30 to 90% rise in pit cell NK activity detected with YAC-1 or U937 targets. The pit cell enhanced NK activity in ETOH-treated rats was further increased if polyinosinicpolycytidilic acid was injection i.p. 18 hours before the assay. Blood and spleen lymphocyte NK activity of ETOH-treated rats was also greater than in controls. There was no evidence that ETOH merely redistributed lymphocytes among the tissues. Although ETOH acutely inhibits NK activity in vitro, chronic ETOH increases in vivo.

  18. Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  19. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    SciTech Connect

    Neisewander, J.L.; Lucki, I.; McGonigle, P. )

    1991-05-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with ({sup 3}H)SCH-23390 and D2 receptors labeled with ({sup 3}H)spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia.

  20. Working Memory in Bisphenol-A Treated Middle-Aged Ovariectomized Rats

    PubMed Central

    Neese, Steven L.; Bandara, Suren B.; Schantz, Susan L.

    2014-01-01

    Over 90% of the U.S. population has detectable bisphenol-A (BPA) in their urine according to recent biomonitoring data. BPA is best known for its estrogenic properties, and most rodent research on the nervous system effects of BPA has focused on determining if chronic exposures during pre- and perinatal development have organizational effects on brain development and behavior. Estrogens also have important impacts on brain and behavior during adulthood, particularly in females during aging, but the impact of BPA on the adult brain is less studied. We have published a series of studies documenting that chronic exposure to various estrogens including 17β-estradiol, ERβ selective SERMs and soy phytoestrogens impairs performance of middle-aged female rats on an operant working memory task. The purpose of this study was to determine if chronic oral exposure to BPA would alter working memory on this same task. Ovariectomized (OVX) middle-aged Long Evans rats were tested on an operant delayed spatial alternation (DSA) task. Rats were treated for 8–10 weeks with either a 0 (vehicle control), 5 or 50 μg/kg bw/day oral bolus of BPA. A subset of the vehicle control rats were implanted with a Silastic implant containing 17β-estradiol (low physiological range) to serve as a positive control. All rats were tested for 25 sessions on the DSA task. BPA treatment did not influence performance accuracy on the DSA task, whereas 17β-estradiol significantly impaired performance, as previously reported. The results of this study suggest that chronic oral exposure to BPA does not alter working memory processes of middle-aged OVX rats assessed by this operant DSA task. PMID:23339879

  1. Hypothalamic circuit regulating colonic transit following chronic stress in rats.

    PubMed

    Yoshimoto, Sazu; Cerjak, Diana; Babygirija, Reji; Bulbul, Mehmet; Ludwig, Kirk; Takahashi, Toku

    2012-03-01

    Although acute stress accelerates colonic transit, the effect of chronic stress on colonic transit remains unclear. In this study, rats received repeated restraint stress (chronic homotypic stress) or various types of stress (chronic heterotypic stress) for 5 and 7 days, respectively. Vehicle saline, oxytocin (OXT), OXT receptor antagonist or corticotropin-releasing factor (CRF) receptor antagonists were administered by intracerebroventricular (ICV) injection prior to restraint stress for 90 min. Immediately after the stress exposure, the entire colon was removed and the geometric center (GC) of Na51CrO4 (a nonabsorbable radioactive marker; 0.5 μCi) distribution was calculated to measure the transit. Gene expression of OXT and CRF in the paraventricular nucleus (PVN) was evaluated by in situ hybridization. Accelerated colonic transit with the acute stressor was no longer observed following chronic homotypic stress. This restored colonic transit was reversed by ICV injection of an OXT antagonist. In contrast, chronic heterotypic stress significantly accelerated colonic transit, which was attenuated by ICV injection of OXT and by a CRF receptor 1 antagonist. OXT mRNA expression in the PVN was significantly increased following chronic homotypic stress, but not chronic heterotypic stress. However, CRF mRNA expression in the PVN was significantly increased following acute and chronic heterotypic stress, but not chronic homotypic stress. These results indicate that central OXT and CRF play a pivotal role in mediating the colonic dysmotility following chronic stress in rats. PMID:21936687

  2. Chronic toxicity study of neosaxitoxin in rats.

    PubMed

    Zepeda, Ramiro J; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F

    2014-09-01

    Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. PMID:25257789

  3. Chronic Toxicity Study of Neosaxitoxin in Rats

    PubMed Central

    Zepeda, Ramiro J.; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F.

    2014-01-01

    Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. PMID:25257789

  4. Preventing dyslipidemia by Chlorella pyrenoidosa in rats and hamsters after chronic high fat diet treatment.

    PubMed

    Cherng, Jong-Yuh; Shih, Mei-Fen

    2005-05-13

    The effects of Chlorella pyrenoidosa on serum lipid profiles, after concomitant long-term treatment of high-fat diet (HFD) in rats and hamsters was studied. Wistar rats and Syrian hamsters were fed with or without various concentrations of Chlorella pyrenoidosa contained high-fat diet (CHFD) for 2, 4 and 8 weeks prior to assay of serum lipids. Fasting triglycerides, total cholesterol, and LDL cholesterol as well as HDL cholesterol levels in high-fat diet treated rats and hamster were determined. Results showed that triglycerides, total cholesterol and LDL cholesterol levels in HFD treated rats and hamsters were increased from the normal rodent diet (NRD) treated controls after 2, 4, and 8-week treatments. However, the presence of Chlorella pyrenoidosa in high-fat diets significantly decreased the levels of triglycerides, total cholesterol and LDL cholesterol with comparison to HFD group in rats and hamsters. The total cholesterol/HDL ratios, an indication of occurrence of coronary heart disease, were decreased in all CHFD treated grouped rats and hamsters which suggests administration of Chlorella pyrenoidosa could lower the occurring risk of heart diseases. In conclusion, Chlorella pyrenoidosa has the ability to prevent dyslipidemia in chronic high-fat fed animals and could be potential in use to prevent intestinal absorption of redundant lipid from our daily intake and subsequently to prevent hyperlipidemia as well as atherosclerosis. PMID:15850594

  5. Salt-Induced Changes in Cardiac Phosphoproteome in a Rat Model of Chronic Renal Failure

    PubMed Central

    Su, Zhengxiu; Zhu, Hongguo; Zhang, Menghuan; Wang, Liangliang; He, Hanchang; Jiang, Shaoling; Hou, Fan Fan; Li, Aiqing

    2014-01-01

    Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed. PMID:24945867

  6. Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

    ClinicalTrials.gov

    2016-07-26

    Adult Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Chronic Myelomonocytic Leukemia-1; Chronic Myelomonocytic Leukemia-2; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts

  7. Enhanced recovery from chronic ischemic injury by bone marrow cells in a rat model of ischemic stroke.

    PubMed

    Yoo, Jongman; Seo, Jin-Ju; Eom, Jang-Hyeon; Hwang, Dong-Youn

    2015-01-01

    Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Thrombolytic drugs effectively treat the very acute stage of stroke, and several neuroprotectants that are designed to treat secondary injury following stroke are being tested in clinical trials. However, these pharmacological approaches primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In recent years, stem cell-mediated regenerative approaches have emerged as promising therapeutic strategies for treating the chronic stage of stroke. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. Our transplantation experiments using BMCs obtained from ischemic donor rats showed functional and structural recovery during the chronic stage of stroke. BMC-mediated neural proliferation was prominent in the brains of rats with chronic stroke, and most of the new cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neural proliferation coincided with a significant reduction (∼50%) in the number of activated microglia, which is consistent with previous reports of enhanced neural proliferation being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic ischemic brain were CD25(+) cells, suggesting that these cells may exert the beneficial effects associated with BMC transplantation. Based on the reported anti-inflammatory role of CD25(+) regulatory T-cells in acute experimental stroke, we propose a working model delineating the positive effects of BMC transplantation during the chronic phase of stroke; infiltrating BMCs (mostly CD25(+) cells) reduce activated microglia, which leads to enhanced neural proliferation and enhanced recovery from neuronal damage in this rat model of chronic stroke. This study provides valuable insights into the effect

  8. Metabolic Effects of Chronic Sleep Restriction in Rats

    PubMed Central

    Vetrivelan, Ramalingam; Fuller, Patrick M.; Yokota, Shigefumi; Lu, Jun; Saper, Clifford B.

    2012-01-01

    Study Objectives: Chronic partial sleep loss is associated with obesity and metabolic syndrome in humans. We used rats with lesions in the ventrolateral preoptic area (VLPO), which spontaneously sleep about 30% less than intact rats, as an animal model to study the consequences of chronic partial sleep loss on energy metabolism. Participants: Adult male Sprague-Dawley rats (300-365 g). Interventions: We ablated the VLPO in rats using orexin-B-saporin and instrumented them with electrodes for sleep recordings. We monitored their food intake and body weight for the next 60 days and assessed their sleep-wake by 24-h EEG/EMG recordings on day 20 and day 50 post-surgery. On day 60, after blood samples were collected for metabolic profiling, the animals were euthanized and the brains were harvested for histological confirmation of the lesion site. Measurements and Results: VLPO-lesioned animals slept up to 40% less than sham-lesioned rats. However, they showed slower weight gain than sham-lesioned controls, despite having normal food intake. An increase in plasma ghrelin and a decrease in leptin levels were observed, whereas plasma insulin levels remained unaffected. As expected from leaner animals, plasma levels of glucose, cholesterol, triglycerides, and C-reactive protein were reduced in VLPO-lesioned animals. Conclusions: Chronic partial sleep loss did not lead to obesity or metabolic syndrome in rats. This finding raises the question whether adverse metabolic outcomes associated with chronic partial sleep loss in humans may be due to factors other than short sleep, such as circadian disruption, inactivity, or diet during the additional waking hours. Citation: Vetrivelan R; Fuller PM; Yokota S; Lu J; Saper CB. Metabolic effects of chronic sleep restriction in rats. SLEEP 2012;35(11):1511-1520. PMID:23115400

  9. Effects of chronic ethanol administration on receptor mediated endocytosis of asialoorosomucoid (ASOR) in isolated rat hepatocytes

    SciTech Connect

    Casey, C.A.; Kragskow, S.L.; Sorrell, M.F.; Tuma, D.J.

    1986-05-01

    The authors have previously shown that acute and chronic ethanol administration decreases hepatic glycoprotein secretion and membrane biogenesis. The present study was undertaken to determine the effects of chronic ethanol feeding on receptor-mediated endocytosis using the endocytosis of ASOR as a model system. Rats were fed either rat chow ad lib or pair-fed with Lieber-DeCarli diet (ethanol or isocaloric glucose as 36% of total calories) for 5 to 7 weeks. Binding of /sup 125/I ASOR to isolated hepatocytes was studied at 0-4/sup 0/C. Internalization (cell-associated acid precipitable radioactivity) and degradation (acid soluble radioactivity) were determined at 37/sup 0/C for periods up to 240 min. Results were expressed as pmoles ASOR bound, degraded or internalized/10/sup 6/ cells. In ethanol-fed rats the number of pmoles ASOR bound/10/sup 6/ cells was decreased by 40-50% (p< 0.01) as compared to pair-fed and chow-fed animals. Rates of degradation and internalization of the ligand were also 50-70% lower (p< 0.01) in chronic ethanol-treated animals. No significant differences were observed for either binding or internalization of ASOR between chow-fed and pair-fed animals. These results indicate that chronic ethanol feeding decreases internalization and degradation of ASOR in rat hepatocytes.

  10. Chronic effects of mercuric chloride ingestion on rat adrenocortical function

    SciTech Connect

    Agrawal, R.; Chansouria, J.P.N. )

    1989-09-01

    Mercurial contamination of environment has increased. Mercury accumulates in various organs and adversely affects their functions. Some of the most prominent toxic effects of inorganic mercury compounds include neurotoxicity, hepatotoxicity and nephrotoxicity. Besides this, mercury has also been reported to affect various endocrine glands like pituitary, thyroid, gonadal and adrenal glands. There have been no reports on the toxic effects of chronic oral administration of varying doses of mercuric chloride on adrenocortical function in albino rats. The present work was undertaken to study the adrenocortical response to chronic oral administration of mercuric chloride of varying dose and duration in albino rats.

  11. Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts

    PubMed Central

    Murray, David B.; Voloshenyuk, Tetyana G.; Brower, Gregory L.; Bradley, Jessica M.; Janicki, Joseph S.

    2010-01-01

    We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload. PMID:19933421

  12. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain

    PubMed Central

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2015-01-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model. PMID:25465043

  13. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.

    PubMed

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2015-03-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model. PMID:25465043

  14. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    SciTech Connect

    Gonzales, R.A.; Crews, F.T. )

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  15. Effect of chronic d-fenfluramine administration on rat hypothalamic serotonin levels and release

    NASA Technical Reports Server (NTRS)

    Schaechter, Judith D.; Wurtman, Richard J.

    1988-01-01

    D-fenfluramine, an anorectic agent in rats and man, was administered daily at doses 1.25, 2.5, 5, or 10 mg/kg/day for 10 days, and sacrificed 6 days later. Hypothalamic serotonin (5-HT) levels were unchanged in rats receiving 1.25-5 mg/kg/day of d-fenfluramine but reduced by 22 percent (p less than 0.01) at the highest drug dose (10 mg/kg/day); hypothalamic 5-hydroxyindole acetic acid (5-HIAA) levels were reduced by 15 percent (p less than 0.05) or 28 percent (p less than 0.01) in rats receiving 5 or 10 mg/kg/day of the drug, respectively. Hypothalamic slices prepared from rats which were previously treated with any of the drug doses spontaneously released endogenous 5-HT at rates that did not differ from those of vehicle-treated rats. 5-HT released with electrical field-stimulation was unaffected by prior d-fenfluramine treatment at doses of 1.25-5 mg/kg/day, and was reduced by 20 percent (p less than 0.05) from slices prepared from rats which received 10 mg/kg/day. 5-HIAA efflux was also attenuated by the highest drug dose. These data indicate that chronic administration to rats of customary anorectic doses of d-fenfluramine (i.e. 0.06-1.25 mg/kg) fail to cause long-lasting reductions in brain 5-HT release.

  16. Effect of chronic alcohol feeding on the ultrastructure of rat peripheral blood neutrophils: a morphometric study.

    PubMed

    Todorović, V; Koko, V; Lacković, V; Milin, J; Varagić, J

    1994-03-01

    Morphometric methods were used to analyze the ultrastructural characteristics of peripheral blood polymorphonuclear neutrophils (PMN) in 10 rats chronically consuming ethanol and 20 rats fed an isoenergetic standard diet (10 ad libitum and 10 pair fed control rats). Morphometric measurements were made, after a 4-month experimental period, of the following: the profile area of the cell, nucleus and cytoplasm; nucleus to cell profile area; volume density of the nucleus, cytoplasm, mitochondria, Golgi system, endoplasmic reticulum and cytoplasmic granules; number of mitochondria per cell profile; number of cytoplasmic granules per cell profile and per micron2 of cytoplasm, as well as the azurophilic to specific granule ratio and mean diameter of granules. A significant decrease in cell profile area and cytoplasm profile area was shown in ethanol-treated rats. The volume density of mitochondria and endoplasmic reticulum nearly doubled during ethanol abuse. The results also showed that there were highly significant effects of ethanol on the total number of cytoplasmic granules per cell. In addition, changes were observed in mitochondria such as clumping, elongation, swelling and disruption of cristae, as well as changes in the topographic distribution of granules in the cytoplasm such as registration of cytoplasmic areas with numerous granules and areas with a smaller number or without any granules. Some neutrophils of ethanol-treated rats had autophagic vacuoles. The results indicate some ultrastructural abnormalities of PMN in chronic experimental alcoholism that may be related to polymorphonuclear phagocyte dysfunction. PMID:8189745

  17. Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats

    PubMed Central

    Su, Qiaoer; Cheng, Yifan; Jin, Kunlin; Cheng, Jianhua; Lin, Yuanshao; Lin, Zhenzhen; Wang, Liuqing; Shao, Bei

    2016-01-01

    The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy. PMID:27602095

  18. Emphysema model in rats treated intratracheally with elastase

    SciTech Connect

    Yokoyama, E.; Nambu, Z.; Uchiyama, I.; Kyono, H.

    1987-04-01

    Pulmonary functions, morphology, and morphometry were examined in rats at 3, 7, and 10 weeks after a single intratracheal administration of 6.5 units of porcine pancreatic elastase in order to obtain a model of pulmonary emphysema which would be suitable for studying the responses of emphysematous lungs to atmospheric pollutants. Functional residual capacity and residual volume of the elastase-treated rats increased at all the times studied, but their total lung capacity increased only at 7 and 10 weeks compared with those of the saline-treated control rats. The increase in static lung compliance and the decrease in peak flow and maximum flow at 50% of total lung capacity during forced expiration were also observed in all except the 3-week elastase animals. The elastase-treated lungs showed morphological changes characteristic of emphysematous lesions. The increase in mean linear intercept length and the decrease in total alveolar surface area were demonstrated by these elastase-treated lungs. Based on these results, they conclude that an adequate and suitable model of pulmonary emphysemia could be obtained in rats 7-10 weeks after treatment with the present dose of elastase.

  19. Microarray analysis of thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-04-01

    It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

  20. Beneficial effects of polydatin on learning and memory in rats with chronic ethanol exposure

    PubMed Central

    Zhang, Yan; Li, Shuang; Wang, Weifeng; Xu, Chunyang; Liang, Shuainan; Liu, Meng; Hao, Wei; Zhang, Ruiling

    2015-01-01

    The purpose of this paper is to examine the effects of polydatin on cognitive function in rats self-administered with chronic ethanol levels. The levels of cyclin-dependent kinase 5 (Cdk5) were also determined. In the in vivo study, adult male Sprague-Dawley rats were used to establish an ethanol-administered rat model. Cognitive function was measured using the Morris water maze and the level of Cdk5 expression was measured to evaluate the effect of polydatin treatment. Cdk5 kinase activity and cell survival rate in primary hippocampal neuron cultures treated with ethanol or ethanol and polydatin were measured in the in vitro study. Polydatin reversed the performance impairments in chronic ethanol treated rats in Morris water maze test, and decreased unregulated Cdk5 expression. Moreover, polydatin increased cell survival rate, and decreased Cdk5 activity in the ethanol-treated primary culture of hippocampal neurons. The study results suggest that polydatin exhibits neuroprotective potential for ethanol induced neurotoxicity, both in vivo and in vitro, which is most likely related to its ability to target Cdk5 in neurons. PMID:26617831

  1. EXTRACORPOREAL SHOCKWAVE TERAPY TO TREAT CHRONIC MUSCLE INJURY

    PubMed Central

    Astur, Diego Costa; Santos, Bruno; de Moraes, Eduardo Ramalho; Arliani, Gustavo Gonçalves; dos Santos, Paulo Roberto Dias; Pochini, Alberto de Castro

    2015-01-01

    ABSTRACT Objective: To evaluate the low energy extracorporeal shock waves therapy (ESWT) associated with physical therapy in the treatment of chronic muscle injuries classified as grades 2 and 3 in the lower limbs of amateur athletes. Methods: Eight athletes presenting with lower limb muscle injury for more than three weeks were treated with physiotherapy and ESWT. We evaluated the following parameters during treatment: palpable gap, muscle strength, pain, and Tegner score, as well as ultrasound image features and the ability to return to sports practice. Results: The average time of the first evaluation of the injury was 8.75 weeks. All patients presented muscle strength grade V after eight weeks. The pain score evolved from 5.75 to 0.5 points of the visual analogue scale (VAS), at the end of the treatment. The Tegner score after treatment was six points on average. Patients returned to sports practice after 8.14 weeks. Conclusion: ESWT associated with physical therapy proved to be effective to treat long-term muscle injury, with good performance and the ability to return to sport practice for all patients. Level of Evidence IV, Case Series, Prospective Study. PMID:26981031

  2. Dysregulation of Glucose Homeostasis Following Chronic Exogenous Administration of Leptin in Healthy Sprague-Dawley Rats

    PubMed Central

    Wjidan, Khalil; Ibrahim, Effendi; Caszo, Brinnell; Gnanou, Justin

    2015-01-01

    Introduction Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. Aim To examine the effects of chronic leptin administration on plasma glucose regulation in rats. Materials and Methods Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 μg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. Results Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. Conclusion Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats. PMID:26816939

  3. Estrogen provokes the depressant effect of chronic nicotine on vagally mediated reflex chronotropism in female rats.

    PubMed

    El-Mas, Mahmoud M; El-Gowelli, Hanan M; El-Gowilly, Sahar M; Fouda, Mohamed A; Helmy, Mai M

    2012-08-01

    We recently reported that acute nicotine impairs reflex tachycardic activity in estrogen-depleted, but not estrogen-repleted, female rats, suggesting a restraining influence for estrogen against the nicotine effect. In this study, we tested whether the baroreflex-protective effect of estrogen can be replicated when nicotine was administered chronically. We also report on the dose dependence and autonomic modulation of the nicotine-baroreflex interaction. The effects of nicotine (0.5, 1, or 2 mg/kg/day for 14 days) on baroreflex curves relating changes in heart rate to increases [phenylephrine (PE)] or decreases [sodium nitroprusside (SNP)] in blood pressure were evaluated in sham-operated (SO), ovariectomized (OVX), and estrogen-replaced OVX (OVXE(2)) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(SNP)). In SO rats, both reflex bradycardic and tachycardic responses were attenuated by nicotine in a dose-related fashion. In nicotine-treated rats, blockade of β-adrenergic (propranolol), but not muscarinic (atropine), receptors caused additional reductions in reflex chronotropic responses, implying that nicotine selectively impairs reflex vagal activity. OVX selectively decreased BRS(PE) but not BRS(SNP) and abolished the nicotine-induced impairment of either response. These effects of OVX were reversed after treatment with estrogen or the estrogen receptor modulator raloxifene. In atropine-treated rats, comparable BRS values were demonstrated in all rat preparations regardless of the estrogen or nicotine milieu. Collectively, the inhibition of vagal activity accounts for the depressant effect of chronic nicotine on baroreflex activity. Furthermore, contrary to nicotine's acute effects, the baroreflex-attenuating effect of chronic nicotine is exacerbated by estrogen. PMID:22619254

  4. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats

    PubMed Central

    Zheng, Jun; Babygirija, Reji; Bülbül, Mehmet; Cerjak, Diana; Ludwig, Kirk

    2010-01-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression. PMID:20689056

  5. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats.

    PubMed

    Zheng, Jun; Babygirija, Reji; Bülbül, Mehmet; Cerjak, Diana; Ludwig, Kirk; Takahashi, Toku

    2010-10-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression. PMID:20689056

  6. Chronic Stress Induces Neurotrophin-3 in Rat Submandibular Gland

    PubMed Central

    Saruta, Juri; Iida, Michitaro; Kondo, Yusuke; To, Masahiro; Hayashi, Takashi; Hori, Mayumi; Sato, Sadao

    2012-01-01

    Purpose Plasma neurotrophin-3 (NT-3) levels are associated with several neural disorders. We previously reported that neurotrophins were released from salivary glands following acute immobilization stress. While the salivary glands were the source of plasma neurotrophins in that situation, the association between the expression of neurotrophins and the salivary gland under chronic stress conditions is not well understood. In the present study, we investigated whether NT-3 levels in the salivary gland and plasma were influenced by chronic stress. Materials and Methods Expressions of NT-3 mRNA and protein were characterized, using real-time polymerase chain reactions, enzyme-linked immunosorbent assay, and immunohistochemistry, in the submandibular glands of male rats exposed to chronic stress (12 h daily for 22 days). Results Plasma NT-3 levels were significantly increased by chronic stress (p<0.05), and remained elevated in bilaterally sialoadenectomized rats under the same condition. Since chronic stress increases plasma NT-3 levels in the sialoadenectomized rat model, plasma NT-3 levels were not exclusively dependent on salivary glands. Conclusion While the salivary gland was identified in our previous study as the source of plasma neurotrophins during acute stress, the exposure to long-term stress likely affects a variety of organs capable of releasing NT-3 into the bloodstream. In addition, the elevation of plasma NT-3 levels may play important roles in homeostasis under stress conditions. PMID:23074106

  7. Effects of milnacipran on cognitive flexibility following chronic stress in rats.

    PubMed

    Naegeli, Kale J; O'Connor, Joann A; Banerjee, Pradeep; Morilak, David A

    2013-03-01

    Cognitive dysfunction is a component of affective disorders, including depression. Chronic stress is a risk factor for depression, and we have shown that exposing rats to chronic unpredictable stress (CUS) induces a deficit of cognitive flexibility, the ability to modify behavior based on feedback from a changing environment. Deficits of cognitive flexibility, measured by extra-dimensional set-shifting on the Attentional Set-shifting Test (AST), are consistent with dysregulation of prefrontal cortical function, also characteristic of depression. We have shown that increasing norepinephrine in the medial prefrontal cortex facilitated set-shifting, and chronic treatment with the selective norepinephrine reuptake blocker, desipramine, restored cognitive flexibility in rats that had been compromised by CUS. Serotonin reuptake blockade also prevented CUS-induced deficits in cognitive flexibility, suggesting a role for both monoamines in this process. Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) with moderate preference for blocking norepinephrine reuptake. In this study, we tested the effects of chronic milnacipran treatment on cognitive set-shifting after CUS. Male Sprague-Dawley rats were treated chronically by minipump with milnacipran (30 mg/kg/day), the positive control drug, desipramine (5mg/kg/day), or vehicle, and exposed to CUS or unstressed control conditions. For CUS, a different acute stressor was presented daily for 14 days. On Day 17, rats were tested on the AST. Consistent with previous results, CUS impaired cognitive set-shifting. Further, chronic treatment with either milnacipran or desipramine preserved cognitive flexibility after CUS, suggesting that milnacipran may have efficacy in the management of cognitive dysfunction as a component of stress-related illnesses, including fibromyalgia and depression. PMID:23422875

  8. Chronic treatment with epigallocatechin gallate reduces motor hyperactivity and affects in vitro tested intestinal motility of spontaneously hypertensive rats

    PubMed Central

    Potenza, Maria Assunta; Montagnani, Monica; Nacci, Carmela; De Salvia, Maria Antonietta

    2016-01-01

    Background Green tea catechins seem to contribute toward reducing body weight and fat. Objective We aimed to investigate whether chronic administration of (–)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. Design Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 µM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. Results Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle-treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05–5 µM) and increased inhibitory response to electrical field stimulation (EFS, 1–10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG

  9. Toxic effect on the rat small intestine of chronic administration of asbestos in drinking water.

    PubMed

    Delahunty, T J; Hollander, D

    1987-12-01

    Sprague-Dawley rats were given a 0.5 g/l Chrysotile asbestos solution in their drinking water (approximately 7 mg/day ingested) for 1.5 years and compared to control rats of the same age. During this time there were no differences in weight or appearance of the asbestos-treated rats in comparison to controls maintained under the same conditions. However, when in vivo intestinal permeability studies were performed using a gavage/urinary collection technique, some significant changes were noted. The recovery of lactulose in the urine of asbestos-treated rats was 0.66 +/- 0.07%, significantly less than that of the controls (1.01 +/- 0.08, P less than 0.005). The recovery of mannitol was similarly decreased (2.2 +/- 0.28 vs. 3.0 +/- 0.17, P less than 0.02), but that of rhamnose was unchanged. Creatinine clearance studies indicated that there was no impairment of kidney function in the asbestos-treated group and polarized light microscopy did not reveal any asbestos fibers in sections of the small bowel. The results suggest that the chronic exposure of rats to asbestos fibers in the drinking water results in a decreased ability of the intestine to absorb some non-metabolizable sugars. PMID:3120357

  10. Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats

    PubMed Central

    Ko, Ya-Hui; Tsai, Ming-Shian; Chang, Ru-Wen; Chang, Chun-Yi; Wang, Chih-Hsien; Wu, Ming-Shiou; Liang, Jin-Tung; Chang, Kuo-Chu

    2015-01-01

    It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal

  11. Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate

    PubMed Central

    Sarobo, Carolina; Lacorte, Lívia M; Martins, Marcela; Rinaldi, Jaqueline C; Moroz, Andrei; Scarano, Wellerson R; Delella, Flavia K; Felisbino, Sérgio L

    2012-01-01

    Coffee intake has been associated with a low risk of developing cancer, including prostate cancer, which is one of the most commonly diagnosed cancer in men. However, few studies have evaluated the chronic effects of caffeine, which is the most abundant methylxanthine in coffee, on prostate morphology and physiology. In the present study, we investigated the effects of chronic, low-dose caffeine intake on rat prostate morphology from puberty to adulthood. Five-week-old male Wistar rats were randomized into two experimental groups: caffeine-treated (20 ppm in drinking water, n = 12) and control (n = 12). The ventral and dorsolateral prostates were dissected, weighted and submitted to morphological, morphometrical and immunohistochemical analysis of cellular proliferation, apoptosis and androgen receptor (AR) tissue expression. The testosterone (T) and dihydrotestosterone (DHT) concentrations were measured in the plasma. Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe. All the ventral prostates from the caffeine-treated animals presented various degrees of epithelial and stromal hyperplasia. Our results suggest that chronic caffeine intake from puberty increases androgenic signalling and cell proliferation in the rat prostate gland and can be related to the development of benign prostatic hyperplasia. PMID:23136995

  12. Low blood alcohol levels in rats despite chronic alcohol consumption

    SciTech Connect

    Sankaran, H.; Deveney, C.W.; Lin, J.C.; Larkin, E.C.; Rao, G.A. )

    1989-02-09

    Rats fed liquid diets containing 36% or 26% of calories from ethanol consume similar amounts of alcohol each day. After 3 weeks on ethanol diet, the blood alcohol levels (BAL) are high in rats fed the 36% alcohol diet, but low or insignificant in those fed the 26% alcohol diet. Rats in either alcohol diet group consume most of their diet in the night. Hence, the low BAL in 26% ethanol diet-fed rats may not be due to a more rapid diet consumption after feeding and clearance of the bulk of ingested alcohol as compared to the rats fed the 36% alcohol diet. BAL at various times during the day (7 AM, 10 AM, 1 PM, 4 PM, 7 PM and 10 PM) are high in rats fed the 36% ethanol diet. However, BAL in those fed the 26% ethanol diet are low during the corresponding times. It appears that the low BAL produced by the enhanced hepatic metabolism of ethanol is related to the improved nutritional status in rats fed the 26% ethanol diet, compared to those fed 36% ethanol diet, because rats fed the 36% ethanol diet ingest reduced amounts of calories and other nutrients. Extrahepatic effects of chronic alcohol consumption caused by high BAL may be abated by an enhanced daily intake of nutrients by the animal.

  13. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  14. The effect of chronic administration of safranal on systolic blood pressure in rats.

    PubMed

    Imenshahidi, Mohsen; Razavi, Bibi Marjan; Faal, Ayyoob; Gholampoor, Ali; Mousavi, Seyed Mehran; Hosseinzadeh, Hossein

    2015-01-01

    Safranal, the main component of Crocus sativus essential oil, exhibits different pharmacological activities. In this study, the effects of safranal, on blood pressure of normotensive and desoxycorticosterone acetate (DOCA) - salt induced hypertensive rats in chronic administration were investigated. Three doses of safranal (1, 2 and 4 mg/Kg/day) and spironolactone (50 mg/Kg/day) were administrated to the different groups of normotensive and hypertensive rats (at the end of 4 weeks treatment by DOCA-salt) for Five weeks. Then the effects of safranal on mean systolic blood pressure (MSBP) and heart rate (HR) were evaluated using tail cuff method. The duration of effect of safranal on SBP, was also evaluated. Our results indicated that chronic administration of safranal could reduce the MSBP in DOCA salt treated rats in a dose dependent manner. Safranal did not decrease the MSBP in normotensive rats. The data also showed that antihypertensive effects of safranal did not persist. In summary, our results showed that safranal exhibits antihypertensive and normalizing effect on BP in chronic administration. PMID:25901167

  15. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  16. Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders

    ClinicalTrials.gov

    2016-07-20

    Accelerated Phase of Disease; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase of Disease; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Recurrent Disease

  17. Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

    PubMed

    da Silva, Marcel Gianni C; Amorim, Raimundo Neilson L; Câmara, Carlos C; Fontenele Neto, José Domingues; Soto-Blanco, Benito

    2014-09-01

    The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats. PMID:24892475

  18. Chronic ethanol treatment potientials ethanol-induced increases in interstitial nucleus accumbens endocannabinoid levels in rats

    PubMed Central

    Alvarez-Jaimes, Lily; Stouffer, David G.; Parsons, Loren H.

    2013-01-01

    We employed in vivo microdialysis to characterize the effect of an ethanol challenge injection on endocannabinoid levels in the nucleus accumbens of ethanol-naïve and chronic ethanol-treated rats. Ethanol (0.75 and 2 g/kg, i.p.) dose-dependently increased dialysate 2-arachidonoylglycerol (to a maximum 157 ± 20% of baseline) and decreased anandamide (to a minimum 52 ± 9% of baseline) in ethanol-naïve rats. The endocannabinoid clearance inhibitor N-(4-hydrophenyl) arachidonoylamide (AM404; 3 mg/kg) potentiated ethanol effects on 2-arachidonoylglycerol levels but did not alter ethanol-induced decreases in anandamide. AM404 alone did not alter dialysate levels of either endocannabinoid. Then, we characterized the effect of ethanol challenge on nucleus accumbens endocannabinoid levels in rats previously maintained on an ethanol-containing liquid diet. Ethanol challenge produced a greater and more prolonged increase in 2-arach-idonoylglycerol (to a maximum 394 ± 135% of baseline) in ethanol-experienced than in ethanol-naïve rats. The profile in ethanol-experienced rats was similar to that produced by AM404 pre-treatment in ethanol-naïve rats. AM404 in ethanol-experienced rats led to a further enhancement in the 2-arachidonoylglycerol response to ethanol challenge (to a maximum 704 ± 174% of baseline). Our findings demonstrate that ethanol-induced increases in nucleus accumbens 2-arachidonoylglycerol are potentiated in animals with a history of ethanol consumption. PMID:19650871

  19. Metabolomic analysis of rat plasma following chronic low-dose exposure to dichlorvos.

    PubMed

    Yang, J; Wang, H; Xu, W; Hao, D; Du, L; Zhao, X; Sun, C

    2013-02-01

    This study aims to assess the metabolomic profile and related histopathological outcomes of rat plasma after chronic low-dose exposure to dichlorvos (DDVP). A total of 120 male Wistar rats were treated with 0, 2.4, 7.2, and 21.6 mg/kg of body weight/day DDVP continuously for 24 weeks by drinking water. Rat plasma samples were collected at different time-points to measure the metabolomic profiles by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Liver tissue analysis was performed to correlate histopathological outcome status to plasma metabolomics. Significant changes in some of the metabolites were found in all the treated groups compared with the control group. LysoPC (15:0/0:0), LysoPC (16:0/0:0), LysoPC (17:0/0:0), LysoPC (0:0/18:0), sphingosine, sphinganine, C16 sphinganine, C17 sphinganine, and arachidonic acid were decreased in the treated groups. LysoPE (16:0/0:0) was increased after dosing with DDVP. Histopathological test outcomes coincided with the plasma metabolomic-profile analysis results obtained by UPLC-MS. The livers were damaged following chronic exposure to DDVP. Abnormal changes in some lipids in the plasma, such as LysoPC (0:0/18:0), were closely related to liver dysfunction. Therefore, metabolomic analysis provides the unique advantages of unveiling the mechanisms of DDVP. PMID:23060408

  20. [Clinical study on niaodujing in treating chronic renal failure].

    PubMed

    Wang, Y J; Xu, L; Cheng, X X

    1996-11-01

    One hundred and five chronic renal failure patients were divided randomly into two groups, 75 cases of Niaodujing (NDJ) treatment group and 30 cases of control group treated with aldehyde coated oxystarch. The effects were compared between two groups and within the same group before and after the entry. Results indicated that the total effective rate and markely effecive rate of NDJ group (74.1% and 44.0%) were better than those of the control group (56.6% and 23.3%) respectively (P < 0.05). The serum creatinine, blood urea nitrogen and middle molecular substance were decreased and creatinine clearance rate was increased significantly after NDJ treatment as compared with before treatment (P < 0.05-0.01). In comparison of two groups, the decrement of creatinine clearance rate and middle molecular substance and the increment of creatinine in NDJ group were higher than that in control group (P < 0.05-0.01). NDJ was especially effective in patients with azotemia or early renal failure. PMID:9772612

  1. [Tumoral proliferations in chronic plantar ulcers: how to treat?].

    PubMed

    Grauwin, M Y; Mane, I; Cartel, J L

    1996-01-01

    Between 1983 and 1994, 66 Senegalese leprosy patients were seen for cauliflower growths developed in chronic plantar ulcer (CPU), (2 patients had each 2 tumors). 68 biopsies for pathological examination were taken: the diagnosis of squamous cell carcinoma was effectively made in 39 cases (38 patients) and that of pseudo-epitheliomatous hyperplasia in the remaining 29 cases (28 patients). The mean annual frequency of cauliflower growths was 0.45 per 100 CPU. Among these tumors, the percentage of carcinoma was 57%. Of the 38 patients with a carcinoma, 5 refused amputation and all of them died. The 33 others were amputated and of these 8 died as a direct result of their carcinoma (24%). In the case of the 28 patients with hyperplasia, amputation was carried out on 18 patients and local excision on 10. In the months following the operation 8 recurrences were observed in 10 of the patients on whom excision had been carried out. These recurrences were treated by amputation. This gives a total of 93% of amputations in the cases of hyperplasia. These facts lead as to conclude that at least in countries where pathological examination is not available below knee amputation is the most reasonable action to take in the proliferative tumors developed on a CPU. PMID:9054196

  2. Psychological characteristics of patients treated by chronic maintenance hemodialysis.

    PubMed

    Pop-Jordanova, Nada D; Polenakovic, Momir H

    2013-02-01

    Studies related to psychological aspects of dialysis patients show that depression and anxiety are the most common characteristics. The aim of our study was to analyze the personality profile in patients on chronic maintenance dialysis and to evaluate more specifically the level of depression. The total number of patients was 68 (30 females and 38 males), with mean age 62.3 and 56.5 for females and males respectively. Mean duration of dialysis was 6.73 years for females and 6.68 years for men (the period varied from 0.5 to 18 years). For the evaluation of psychological characteristics, we used two psychometric instruments: Minnesota Multiphase Personality Inventory (MMPI- 201) and Beck Depression Inventory. The obtained results confirmed the presence of depression in patients treated with hemodialysis. The level of depression is variable (minimal is present in 21.43%; mild in 35.71%; moderate in 17.85% and severe in 14.28% of patients). The depression is significantly positively correlated with age (p<0.05) as well as with educational level, and negatively with the duration of dialysis. Specific characteristics of personality obtained with MMPI are hypersensitivity, depressive mood, and withdrawal from friends and relatives. More specific emotional traits are the accentuated anxiety, low level of hostility, but very high passive aggression which destroys their social communications. Some response measures for depression such as relaxation training, psychological support, music therapy, or peripheral biofeedback are recommended. PMID:23335381

  3. Effects of Mild Chronic Intermittent Cold Exposure on Rat Organs

    PubMed Central

    Wang, Xiaohui; Che, Honglei; Zhang, Wenbin; Wang, Jiye; Ke, Tao; Cao, Rui; Meng, Shanshan; Li, Dan; Weiming, Ouyang; Chen, Jingyuan; Luo, Wenjing

    2015-01-01

    Cold adaptation is a body's protective response to cold stress. Mild chronic intermittent cold (CIC) exposure has been used to generate animal models for cold adaptation studies. However, the effects of mild CIC exposure on vital organs are not completely characterized. In the present study, we exposed rats to mild CIC for two weeks, and then measured the body weights, the weights of brown adipose tissue (BAT), the levels of ATP and reactive oxygen species (ROS) in the brains, livers, hearts, muscles and BATs. Rats formed cold adaptation after exposure to CIC for two weeks. Compared to rats of the control group that were hosted under ambient temperature, rats exposed to mild CIC showed a lower average body weight, but a higher weight of brown adipose tissue (BAT). Rats exposed to CIC for two weeks also exhibited higher levels of ATP and ROS in all examined organs as compared to those of the control group. In addition, we determined the expression levels of cold-inducible RNA binding protein (Cirbp) and thioredoxin (TRX) in rat tissues after 2 weeks of CIC exposure. Both Cirbp and TRX were increased, suggesting a role of these two proteins for establishment of cold adaptation. Together, this study reveals the effects of mild CIC exposure on vital organs of rats during CIC exposure. PMID:26327811

  4. Chronic Normobaric Hypoxia Induces Pulmonary Hypertension in Rats: Role of NF-κB.

    PubMed

    Fan, Junming; Fan, Xiaofang; Li, Yang; Ding, Lu; Zheng, Qingqing; Guo, Jinbin; Xia, Dongmei; Xue, Feng; Wang, Yongyu; Liu, Shufang; Gong, Yongsheng

    2016-03-01

    Junming Fan, Xiaofang Fan, Yang Li, Lu Ding, Qingqing Zheng, Jinbin Guo, Dongmei Xia, Feng Xue, Yongyu Wang, Shufang Liu, and Yongsheng Gong. Chronic normobaric hypoxia induces pulmonary hypertension in rats: role of NF-κB. High Alt Med Biol 17:43-49, 2016.-To investigate whether nuclear factor-kappa B (NF-κB) activation is involved in chronic normobaric hypoxia-induced pulmonary hypertension (PH), rats were treated with saline or an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC, 150 mg/kg, sc, twice daily), and exposed to normoxia or chronic normobaric hypoxia with a fraction of inspired oxygen of ∼0.1 for 14 days. Lung tissue levels of NF-κB activity, and interleukin (IL)-1β, IL-6, and cyclooxygenase-2 mRNAs, were determined, and mean pulmonary arterial pressure, right ventricular hypertrophy, and right heart function were evaluated. Compared to the normoxia exposure group, rats exposed to chronic normobaric hypoxia showed an increased NF-κB activity, measured by increased nuclear translocation of p50 and p65 proteins, an increased inflammatory gene expression in the lungs, elevated mean pulmonary arterial blood pressure and mean right ventricular pressure, right ventricular hypertrophy, as assessed by right ventricle-to-left ventricle plus septum weight ratio, and right heart dysfunction. Treatment of hypoxia-exposed rats with PDTC inhibited NF-κB activity, decreased pulmonary arterial blood pressure and right ventricular pressure, and ameliorated right ventricular hypertrophy and right heart dysfunction. Hypoxia exposure increased protein kinase C activity and promoted pulmonary artery smooth muscle cell proliferation in vitro. Our data suggest that NF-κB activation may contribute to chronic normobaric hypoxia-induced PH. PMID:26788753

  5. Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats.

    PubMed

    Schneider, Miriam; Koch, Michael

    2003-10-01

    There is evidence from studies in humans and animals that a vulnerable period for chronic cannabinoid administration exists during certain phases of development. The present study tested the hypothesis that long-lasting interference of cannabinoids with the developing endogenous cannabinoid system during puberty causes persistent behavioral alterations in adult rats. Chronic treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN) (1.2 mg/kg) or vehicle was extended over 25 days either throughout the rats' puberty or for a similar time period in adult rats. The rats received 20 injections intraperitoneally (i.p.), which were not delivered regularly. Adult rats were tested for object recognition memory, performance in a progressive ratio (PR) operant behavior task, locomotor activity, and prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI was significantly disrupted only by chronic peripubertal cannabinoid treatment. This long-lasting PPI deficit was reversed by the acute administration of the dopamine antagonist haloperidol. Furthermore, we found deficits in recognition memory of pubertal-treated rats and these animals showed lower break points in a PR schedule, whereas food preference and locomotion were not affected. Adult chronic cannabinoid treatment had no effect on the behaviors tested. Therefore, we conclude that puberty in rats is a vulnerable period with respect to the adverse effects of cannabinoid treatment. Since PPI deficits, object recognition memory impairments, and anhedonia/avolition are among the endophenotypes of schizophrenia, we propose chronic cannabinoid administration during pubertal development as an animal model for some aspects of the etiology of schizophrenia. PMID:12888772

  6. Chronic Alcohol Treatment in Rats Alters Sleep by Fragmenting Periods of Vigilance Cycling in the Light Period with Extended Wakenings

    PubMed Central

    Mukherjee, Sanjib; Simasko, Steven M.

    2009-01-01

    Studies have shown that disturbed sleep produced by chronic alcohol abuse in humans can predict relapse drinking after periods of abstinence. How alcohol produces disturbed sleep remains unknown. In this study we used a novel analysis of sleep to examine the effects of alcohol on sleep patterns in rats. This analysis separates waking into multiple components and defines a period labeled vigilance cycling (VC) in which the rat rapidly cycles through various vigilance states. These VC episodes are separated by long duration wake periods (LDW). We find that 6 weeks of alcohol (6% in a liquid diet) caused fragmentation of extended VC episodes that normally occur in the light period. However, total daily amounts of slow-wave sleep (SWS) and rapid-eye movement sleep (REMS) remained constant. The daily amount of wake, SWS, and REMS remained constant because the alcohol treated rats increased the amount of VC in the dark period, and the sleep nature of VC in the dark period became more intense. In addition, we observed more wake and less REMS early in the light period in alcohol treated rats. All effects completely reversed by day 16 of alcohol withdrawal. Comparison of the effects of chronic alcohol to acute alcohol exposure demonstrated the effects of chronic alcohol are due to adaptation and not the acute presence of alcohol. The effects of chronic alcohol treatment in rats mimic the effects reported in humans (REMS suppression, difficulty falling asleep, and difficulty remaining asleep). PMID:19014977

  7. Chronic ethanol treatment changes the number of beta-receptors in rat brain microvessels

    SciTech Connect

    Lucchi, L.; Cazzaniga, A.; Picotti, G.B.; Covelli, V.; Magnoni, M.S.; Borriero, L.; Spano, P.F.; Trabucchi, M.

    1984-01-01

    The effect of chronic ethanol consumption on the binding (125I)-iodohydroxybenzylpindolol to beta-adrenergic receptors in rat brain microvessels has been studied. The results show that chronic ethanol treatment increases the number of beta-receptors present in brain microvessels without changing the binding affinity of the binding site for the beta-adrenoceptor ligand. This effect is apparently not associated with changes in peripheral adrenergic tone, since no differences in platelet epinephrine or norepinephrine concentrations were found between ethanol-treated and control animals. An increase in beta-receptor density in brain microvessels might contribute to the alterations of cerebral blood flow and oxygen consumption reported during chronic ethanol intoxication.

  8. [Growth and metabolism of calcium in rats chronically poisoned with aluminium hydroxide].

    PubMed

    Mahieu, S; Calvo, M L; Millen, N; Gonzalez, M; Contini, M C

    1998-01-01

    The effects of aluminum on growth have been studied in rats chronically poisoned with aluminum hydroxide (80 mg/kg b.w.-i.p.-three times a week, during 6 months) and in control rats, between 3 and 26 weeks of age. The growth data was evaluated according to Parks 'theory of feeding an growth. At the end of the poisoning period, the calcium metabolism was studied through a balance of calcium and the determination of bone Ca++ accretion and resorption rates with the aid of 45Ca++. The parathyroid glands function was studied using an indirect method. Treated rats showed a significant decrease in asymptotic weights and in the initial efficiency of food conversion into biomass regarding controls. No differences were observed in food intake between both group. Aluminum affected neither the peak growth rate nor the time necessary to attain maturity. The calcium balance in treated rats was significantly less than in the control group. This was accompanied by a significant increase in the calcium excreted by faces, caused perhaps by a less intestinal absorption. An important amount of aluminum on the surface of the trabecular bone and a reduction in the skeletal Ca++ mass, was observed in all treated rats. Nevertheless there are no differences in the latter when expressed for 100 g of body weight. The rate of skeletal Ca++ accretion was found to be significantly decreased in treated group with respect to controls, without any changes in the bone Ca resorption rate. The reduction in bone turnover revealed by the decrease of Vo+/Vo- was accompanied by less recovery velocity of calcemia in the aluminum treated group, being indirectly related to the parathyroid gland response to calcium depletion. In the model that we studied the decreased bone turnover could have been caused by deposits of aluminum in bone; however there could exist associated factors such as dysfunction in the secretion of PTH, or less affinity between its receptors at the bone level. PMID:9504191

  9. Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia

    PubMed Central

    Byrd, J.C.; Brown, J.R.; O’Brien, S.; Barrientos, J.C.; Kay, N.E.; Reddy, N.M.; Coutre, S.; Tam, C.S.; Mulligan, S.P.; Jaeger, U.; Devereux, S.; Barr, P.M.; Furman, R.R.; Kipps, T.J.; Cymbalista, F.; Pocock, C.; Thornton, P.; Caligaris-Cappio, F.; Robak, T.; Delgado, J.; Schuster, S.J.; Montillo, M.; Schuh, A.; de Vos, S.; Gill, D.; Bloor, A.; Dearden, C.; Moreno, C.; Jones, J.J.; Chu, A.D.; Fardis, M.; McGreivy, J.; Clow, F.; James, D.F.; Hillmen, P.

    2014-01-01

    Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL

  10. The impact of chronic stress on the rat brain lipidome.

    PubMed

    Oliveira, T G; Chan, R B; Bravo, F V; Miranda, A; Silva, R R; Zhou, B; Marques, F; Pinto, V; Cerqueira, J J; Di Paolo, G; Sousa, N

    2016-01-01

    Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits. PMID:25754084

  11. Chronic hepatitis C: treat everyone now or stratify by disease?

    PubMed

    Reiberger, T

    2015-03-01

    Given the advent of highly effective interferon (IFN)-free direct-acting antivirals (DAAs), this review aims to provide evidence to help determine whether doctors should prefer the "watch and wait" or "treatment for all" approach for chronic hepatitis C virus (HCV) infection. The novel treatment regimens usually consist of a 12 week course of both a NS5A inhibitor and a NS5B polymerase inhibitor, and result in excellent sustained virological response (SVR) rates of >90%. NS5A/NS5B inhibitor combinations are also highly effective for previously "difficult-to-treat" and/or "difficult-to-cure" HCV subgroups including patients with cirrhosis, HIV/HCV co-infection, or recurrent HCV infection after liver transplantation. An individualized treatment plan based on careful evaluation of the severity of the disease (need) versus the expected outcome (efficacy) while considering potentially severe side effects (safety) and the socioeconomic situation (costs) seems to be the most reasonable approach. Achieving SVR in patients with advanced cirrhosis represents a virological "cure" but does not universally prevent decompensation or completely abolish the risk of hepatocellular carcinoma (HCC) development. Thus, patients with advanced cirrhosis still need to be monitored after SVR for hepatic decompensation and must undergo regular HCC screening. Economic barriers likely represents a major hurdle for the universal use of the novel IFN-free DAA regimens. Local policies differ amongst health-care systems and reimbursement for DAA-based (ideally IFN-free) treatment regimens is often limited to certain HCV patient groups depending on individual need, expected efficacy, and available safety/efficacy data of the respective treatment regimen. PMID:25356568

  12. The anticonvulsant and behavioral effects of phencyclidine and ketamine following chronic treatment in rats.

    PubMed

    Leccese, A P; Marquis, K L; Mattia, A; Moreton, J E

    1986-12-01

    The effects of chronic phencyclidine (PCP) or ketamine (KET) on their respective acute behavioral and anticonvulsant actions were investigated. Female rats were treated for 15 days with twice daily i.p. injections of saline, 20 mg/kg PCP or 40 mg/kg KET. Subjects treated chronically with PCP were challenged with either 10 mg/kg or 20 mg/kg i.p. PCP, while subjects treated chronically with KET were challenged with 40 mg/kg i.p. KET only. Neither chronic drug treatment induced tolerance to the acute anticonvulsant effect, nor to hyperlocomotion and stereotypy as measured by automated activity monitors. However, evidence of tolerance to the stereotypy induced by acute KET was obtained when an observer-based rating scale was employed. In addition, tolerance occurred to the ataxia induced by KET and the 10 mg/kg, but not 20 mg/kg, dose of PCP. Thus, tolerance occurs to some of the acute behavioral effects of PCP and KET while the anticonvulsant action of these compounds remains unaffected. PMID:3790247

  13. Chronic Nicotine Exposure Stimulates Biliary Growth and Fibrosis in Normal Rats

    PubMed Central

    Jensen, Kendal; Afroze, Syeda; Ueno, Yoshiyuki; Rahal, Kinan; Frenzel, Amber; Sterling, Melanie; Guerrier, Micheleine; Nizamutdinov, Damir; Dostal, David E.; Meng, Fanyin; Glaser, Shannon S.

    2013-01-01

    Background: Epidemiological studies have indicated smoking to be a risk factor for the progression of liver diseases. Nicotine is the chief addictive substance in cigarette smoke and has powerful biological properties throughout the body. Nicotine has been implicated in a number of disease processes, including increased cell proliferation and fibrosis in several organ systems. Aims: The aim of this study was to evaluate the effects of chronic administration of nicotine on biliary proliferation and fibrosis in normal rats. Methods: In vivo, rats were treated with nicotine by osmotic minipumps for two weeks. Proliferation, α7-nicotinic receptor (α7-nAChR) and profibrotic expression were evaluated in liver tissue, cholangiocytes and a polarized cholangiocyte cell line (NRIC). Nicotine-dependent activation of the Ca2+/IP3/ERK 1/2 intracellular signaling pathway was also evaluated in NRIC. Results: Cholangiocytes express α7-nAChR. Chronic administration of nicotine to normal rats stimulated biliary proliferation and profibrotic gene and protein expression such as alpha-smooth muscle actin (α-SMA) and fibronectin 1 (FN-1). Activation of α7-nAChR stimulated Ca2+/ERK1/2-dependent cholangiocyte proliferation. Conclusion: Chronic exposure to nicotine contributes to biliary fibrosis by activation of cholangiocyte proliferation and expression of profibrotic genes. Modulation of α7-nAChR signaling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies. PMID:23587498

  14. Regulation of body mass in rats exposed to chronic acceleration

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.; Bull, L. S.; Oyama, J.

    1975-01-01

    Female rats approximately 6 mo old were chronically centrifuged for up to 30 days at 2.76 G or 3.18 G and sacrificed at intervals for body-composition study. Both fat and the fat-free body mass (FFBM) were reduced during the 1st wk of centrifugation, with the fat showing considerably more variation both within and between groups. The FFBM was reduced below control level to the same extent in rats fed commercial chow, a high-fat diet, or a high-protein diet or in rats prefasted to produce a body-mass deficit at the start of centrifugation. There were no centrifugation-associated changes in body water content. It was concluded that body fat showed no evidence of regulation, FFBM is regulated at any constant level of acceleration between 1 and 4.15 G, and the change in FFBM induced by a change in acceleration is probably not regulated.

  15. Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats.

    PubMed

    Naud, Judith; Harding, Jessica; Lamarche, Caroline; Beauchemin, Stephanie; Leblond, Francois A; Pichette, Vincent

    2016-08-01

    Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (≥40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response. PMID:27271372

  16. Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes.

    PubMed

    Ríos-Silva, Mónica; Trujillo, Xóchitl; Trujillo-Hernández, Benjamín; Sánchez-Pastor, Enrique; Urzúa, Zorayda; Mancilla, Evelyn; Huerta, Miguel

    2014-01-01

    Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant. PMID:24688307

  17. Effect of Chronic Administration of Forskolin on Glycemia and Oxidative Stress in Rats with and without Experimental Diabetes

    PubMed Central

    Ríos-Silva, Mónica; Trujillo, Xóchitl; Trujillo-Hernández, Benjamín; Sánchez-Pastor, Enrique; Urzúa, Zorayda; Mancilla, Evelyn; Huerta, Miguel

    2014-01-01

    Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant. PMID:24688307

  18. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption

    PubMed Central

    Xie, Guoxiang; Zhong, Wei; Li, Houkai; Li, Qiong; Qiu, Yunping; Zheng, Xiaojiao; Chen, Huiyuan; Zhao, Xueqing; Zhang, Shucha; Zhou, Zhanxiang; Zeisel, Steven H.; Jia, Wei

    2013-01-01

    Our understanding of the bile acid metabolism is limited by the fact that previous analyses have primarily focused on a selected few circulating bile acids; the bile acid profiles of the liver and gastrointestinal tract pools are rarely investigated. Here, we determined how chronic ethanol consumption altered the bile acids in multiple body compartments (liver, gastrointestinal tract, and serum) of rats. Rats were fed a modified Lieber-DeCarli liquid diet with 38% of calories as ethanol (the amount equivalent of 4–5 drinks in humans). While conjugated bile acids predominated in the liver (98.3%), duodenum (97.8%), and ileum (89.7%), unconjugated bile acids comprised the largest proportion of measured bile acids in serum (81.2%), the cecum (97.7%), and the rectum (97.5%). In particular, taurine-conjugated bile acids were significantly decreased in the liver and gastrointestinal tract of ethanol-treated rats, while unconjugated and glycine-conjugated species increased. Ethanol consumption caused increased expression of genes involved in bile acid biosynthesis, efflux transport, and reduced expression of genes regulating bile acid influx transport in the liver. These results provide an improved understanding of the systemic modulations of bile acid metabolism in mammals through the gut-liver axis.—Xie, G., Zhong, W., Li, H., Li, Q., Qiu, Y., Zheng, X., Chen, H., Zhao, X., Zhang, S., Zhou, Z., Zeisel, S. H., Jia, W. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. PMID:23709616

  19. Protective effects of triptolide on retinal ganglion cells in a rat model of chronic glaucoma

    PubMed Central

    Yang, Fan; Wang, Dongmei; Wu, Lingling; Li, Ying

    2015-01-01

    Purpose To study the effects of triptolide, a Chinese herb extract, on retinal ganglion cells (RGCs) in a rat model of chronic glaucoma. Methods Eighty Wistar rats were randomly divided into triptolide group (n=40) and normal saline (NS) group (n=40). Angle photocoagulation was used to establish the model of glaucoma, with right eye as laser treated eye and left eye as control eye. Triptolide group received triptolide intraperitoneally daily, while NS group received NS. Intraocular pressure (IOP), anti-CD11b immunofluorescent stain in retina and optic nerve, RGCs count with Nissel stain and microglia count with anti-CD11b immunofluorescence stain in retina flat mounts, retinal tumor necrosis factor (TNF)-α mRNA detection by reverse transcription–polymerase chain reaction, and double immunofluorescent labeling with anti-TNF-α and anti-CD11b in retinal frozen section were performed. Results Mean IOP of the laser treated eyes significantly increased 3 weeks after photocoagulation (P<0.05), with no statistical difference between the two groups (P>0.05). RGCs survival in the laser treated eyes was significantly improved in the triptolide group than the NS group (P<0.05). Microglia count in superficial retina of the laser treated eyes was significantly less in the triptolide group (30.40±4.90) than the NS group (35.06±7.59) (P<0.05). TNF-α mRNA expression in the retina of the laser treated eyes in the triptolide group decreased by 60% compared with that in the NS group (P<0.01). The double immunofluorescent labeling showed that TNF-α was mainly distributed around the microglia. Conclusion Triptolide improved RGCs survival in this rat model of chronic glaucoma, which did not depend on IOP decrease but might be exerted by inhibiting microglia activities and reducing TNF-α secretion. PMID:26604697

  20. Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

    PubMed Central

    Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; de Cabo, Rafael; Ingram, Donald K.; Mattison, Julie A.

    2009-01-01

    Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound. PMID:20026095

  1. Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

    SciTech Connect

    Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; Cabo, Rafael de; Ingram, Donald K.; Mattison, Julie A.

    2010-03-15

    Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

  2. No evidence of drug-induced pancreatitis in rats treated with exenatide for 13 weeks

    PubMed Central

    Tatarkiewicz, K; Belanger, P; Gu, G; Parkes, D; Roy, D

    2013-01-01

    Aims The potential association of glucagon-like peptide receptor agonists (GLP-1RAs) with the development of pancreatitis or pancreatic malignancies in patients with diabetes has been suggested. This study evaluated the long-term effects of the GLP-1RA exenatide on pancreatic exocrine structure and function in the Zucker diabetic fatty (ZDF) rat model of type 2 diabetes. Methods Rats received subcutaneous twice-daily injections of 0 (control), 6, 40 and 250 µg/kg/day exenatide for 3 months. Clinical signs, body and pancreas weight, food consumption, HbA1c, fasting serum amylase, lipase, glucose and insulin concentrations were evaluated during treatment and after a 28-day off-drug period to assess the reversibility of any observed effects. Morphometric analysis of pancreatic ductal cell proliferation and apoptosis were performed. Results Plasma exenatide concentrations were several-fold higher than therapeutic levels observed in humans. No exenatide-related effects were observed on clinical signs, lipase concentration, pancreatic weight, pancreatic histology, ductal cell proliferation or apoptosis. Exenatide improved animal survival, physical condition, glucose concentrations and HbA1c, decreased food intake, and increased serum insulin concentration. Total amylase concentrations, although within normal ranges, were slightly higher in exenatide-treated rats; following the off-drug period, total amylase concentrations were comparable in treated and untreated rats. Exenatide-related minimal-to-moderate islet hypertrophy was observed at doses ≥6 µg/kg/day, with dose-related increases in incidence and degree. These changes were still present after the off-drug period. Conclusions Chronic administration of exenatide in ZDF rats resulted in the expected metabolic benefits and improved animal survival, with no adverse effects noted on pancreatic exocrine structure and function. PMID:23163898

  3. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  4. Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats.

    PubMed

    Raval, Ami P; Sick, Justin T; Gonzalez, Gabriel J; Defazio, R Anthony; Dong, Chuanhui; Sick, Thomas J

    2012-05-23

    Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E₂) and inhibits E₂-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E₂-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-D-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16 days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30 min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80 ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E₂ in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E₂-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation. PMID:22521583

  5. Femoral development in chronically centrifuged rats

    NASA Technical Reports Server (NTRS)

    Smith, S. D.

    1977-01-01

    Groups of 30-d-old male and female rats were centrifuged at 2.00 G (RE, Rotation Experimental), 1.05 G (RC, Rotation Control) or exposed to the noise and wind of the centrifuge at 1.00 G (EC, Earth Control) for periods of 1, 2, 4, 8, and 16 weeks. Measurements of their femurs indicated that exposure to centrifugation a) decreased femoral length in RE animals, b) increased femoral length in RC animals, c) reduced femoral diameter in RE and RC animals, d) increased L/D ratios in RC animals, e) decreased L/D ratios in RE animals, f) increased femur length/body weight in RE animals, g) decreased cortical thickness (CT) in RE animals, h) increased relative CT in RE animals, and decreased it in RC animals, i) accelerated ossification in RC femoral heads, j) thinned and distorted RE epiphyseal plates, and k) thickened condylar cartilage in RE females. The effects tended to be strongly sexually dimorphic, with females more severely affected by the stress than males.

  6. Gene expression analysis in the hippocampal formation of tree shrews chronically treated with cortisol.

    PubMed

    Alfonso, Julieta; Agüero, Fernán; Sanchez, Daniel O; Flugge, Gabriele; Fuchs, Eberhard; Frasch, Alberto C C; Pollevick, Guido D

    2004-12-01

    Adrenal corticosteroids influence the function of the hippocampus, the brain structure in which the highest expression of glucocorticoid receptors is found. Chronic high levels of cortisol elicited by stress or through exogenous administration can cause irreversible damage and cognitive deficits. In this study, we searched for genes expressed in the hippocampal formation after chronic cortisol treatment in male tree shrews. Animals were treated orally with cortisol for 28 days. At the end of the experiments, we generated two subtractive hippocampal hybridization libraries from which we sequenced 2,246 expressed sequenced tags (ESTs) potentially regulated by cortisol. To validate this approach further, we selected some of the candidate clones to measure mRNA expression levels in hippocampus using real-time PCR. We found that 66% of the sequences tested (10 of 15) were differentially represented between cortisol-treated and control animals. The complete set of clones was subjected to a bioinformatic analysis, which allowed classification of the ESTs into four different main categories: 1) known proteins or genes (approximately 28%), 2) ESTs previously published in the database (approximately 16%), 3) novel ESTs matching only the reference human or mouse genome (approximately 5%), and 4) sequences that do not match any public database (50%). Interestingly, the last category was the most abundant. Hybridization assays revealed that several of these clones are indeed expressed in hippocampal tissue from tree shrew, human, and/or rat. Therefore, we discovered an extensive inventory of new molecular targets in the hippocampus that serves as a reference for hippocampal transcriptional responses under various conditions. Finally, a detailed analysis of the genomic localization in human and mouse genomes revealed a survey of putative novel splicing variants for several genes of the nervous system. PMID:15505804

  7. Changes in the adrenals in lead treated rats

    SciTech Connect

    Chowdhury, A.R.; Gautam, A.K.; Rao, R.V.; Sathwara, N.G.; Parikh, D.J.; Chatterjee, B.B.

    1986-07-01

    That the endocrine functions of tests, ovary, thyroid, and adrenals were affected by lead are known from observations on either man or laboratory animals. In one study adrenal steroid excretion was first found to increase and then to decrease considerably during advanced stages of lead intoxication in exposed workers. No comprehensive studies on this aspect of lead poisoning seem to have been carried out. The present investigation was undertaken to contribute to a better understanding of the adrenal functions in rats treated with different dosages of lead.

  8. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    PubMed Central

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  9. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  10. Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment.

    PubMed

    Kim, Helena K; Isaacs-Trepanier, Cameron; Elmi, Nika; Rapoport, Stanley I; Andreazza, Ana C

    2016-05-01

    Chronic N-methyl-d-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA-induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithium treatment prevented changes in 8-isoprostane and 4-hydroxynonenal, which may contribute to lithium's reported neuroprotective effect and efficacy in bipolar disorder. PMID:26894301

  11. Nephroprotection of plantamajoside in rats treated with cadmium.

    PubMed

    Jung, Ha-Young; Seo, Dong-Won; Hong, Chung-Oui; Kim, Ji-Yeon; Yang, Sung-Yong; Lee, Kwang-Won

    2015-01-01

    Cadmium (Cd), an environmental and industrial pollutant, generates free radicals responsible for oxidative stress. Cd can also lead to various renal toxic damage such as the proximal tubules and glomerulus dysfunction. Plantamajoside (PMS), a major compound of Plantago asiatica (PA), was reported to have the antioxidant effects. In this study, we investigated the protective effects of PMS on Cd-induced renal damage in the NRK-52E cell and rat kidney tissue. Cd exposure increased the ROS generation, lipid peroxidation, serum biochemical values of renal damage, and mRNA and protein expressions of KIM-1 in vitro and in vivo. The significant reduction in glutathione (GSH)/glutathione disulfide (GSSG) ratio and activities of antioxidant enzymes were also observed in the rats treated with Cd. PMS significantly decreased the ROS generation and lipid peroxidation, thus enhancing GSH/GSSG ratio, antioxidant enzyme activities in the cells and rats, and improved histochemical appearances, indicating that PMS has protective activities against Cd-induced renal injury. PMID:25499790

  12. MRI-based measurements of aerosol deposition in the lung of healthy and elastase-treated rats.

    PubMed

    Oakes, Jessica M; Breen, Ellen C; Scadeng, Miriam; Tchantchou, Ghislain S; Darquenne, Chantal

    2014-06-15

    Aerosolized drugs are increasingly being used to treat chronic lung diseases or to deliver therapeutics systemically through the lung. The influence of disease, such as emphysema, on particle deposition is not fully understood. With the use of magnetic resonance imaging (MRI), the deposition pattern of iron oxide particles with a mass median aerodynamic diameter of 1.2 μm was assessed in the lungs of healthy and elastase-treated rats. Tracheostomized rats were ventilated with particles, at a tidal volume of 2.2 ml, and a breathing frequency of 80 breaths/min. Maximum airway pressure was significantly lower in the elastase-treated (Paw = 7.71 ± 1.68 cmH2O) than in the healthy rats (Paw = 10.43 ± 1.02 cmH2O; P < 0.01). This is consistent with an increase in compliance characteristic of an emphysema-like lung structure. Following exposure, lungs were perfusion fixed and imaged in a 3T MR scanner. Particle concentration in the different lobes was determined based on a relationship with the MR signal decay rate, R2 (*). Whole lung particle deposition was significantly higher in the elastase-treated rats (CE,part = 3.03 ± 0.61 μm/ml) compared with the healthy rats (CH,part = 1.84 ± 0.35 μm/ml; P < 0.01). However, when particle deposition in each lobe was normalized by total deposition in the lung, there was no difference between the experimental groups. However, the relative dispersion [RD = standard deviation/mean] of R2 (*) was significantly higher in the elastase-treated rats (RDE = 0.32 ± 0.02) compared with the healthy rats (RDH = 0.25 ± 0.02; P < 0.01). These data show that particle deposition is higher and more heterogeneously distributed in emphysematous lungs compared with healthy lungs. PMID:24790020

  13. Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

    PubMed

    Wach, R; Emery, C J; Bee, D; Barer, G R

    1987-02-01

    The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection

  14. Sodium Hydrosulfide Relieves Neuropathic Pain in Chronic Constriction Injured Rats

    PubMed Central

    Lin, Jian-qing; Luo, Hui-qin; Lin, Cai-zhu; Chen, Jin-zhuan; Lin, Xian-zhong

    2014-01-01

    Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats. PMID:25506383

  15. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  16. Treating Chronic Pain with SSRIs: What Do We Know?

    PubMed Central

    Patetsos, Elias

    2016-01-01

    Serotonin is a monoamine neurotransmitter that plays a major role in both nociception and mood regulation. Alterations in the 5-hydroxytryptophan (5HT) system have been reported in chronic pain patients. In recent years, Selective Serotonin Reuptake Inhibitors (SSRIs) have been suggested as an alternative treatment for chronic pain due to the fact that they are better tolerated presenting less secondary effects than other antidepressants such as tricyclic antidepressants. Although several clinical trials have been published, the effectiveness of SSRI as treatment for pain conditions is inconclusive. This review aims to summarise what is known, regarding the effectiveness of SSRI as a treatment for chronic pain conditions in adults. A total of 36 studies involving a total of 1898 participants were included in this review. Of the 36 trials included in the review, 2 used zimelidine as treatment, 3 used escitalopram, 4 used fluvoxamine, 4 used sertraline, 6 used citalopram, 8 used paroxetine, 9 used fluoxetine, and one used both citalopram and paroxetine. Because the trials included in this review are quite heterogeneous, only qualitative analyses were performed. SSRI seems to have an effect on most of chronic pain conditions; however, further clinical trials with good methodology leading to low risk of bias are needed in order to conclude once and for all the effect of this drug class as treatment for chronic pain conditions.

  17. Treating Chronic Pain with SSRIs: What Do We Know?

    PubMed

    Patetsos, Elias; Horjales-Araujo, Emilia

    2016-01-01

    Serotonin is a monoamine neurotransmitter that plays a major role in both nociception and mood regulation. Alterations in the 5-hydroxytryptophan (5HT) system have been reported in chronic pain patients. In recent years, Selective Serotonin Reuptake Inhibitors (SSRIs) have been suggested as an alternative treatment for chronic pain due to the fact that they are better tolerated presenting less secondary effects than other antidepressants such as tricyclic antidepressants. Although several clinical trials have been published, the effectiveness of SSRI as treatment for pain conditions is inconclusive. This review aims to summarise what is known, regarding the effectiveness of SSRI as a treatment for chronic pain conditions in adults. A total of 36 studies involving a total of 1898 participants were included in this review. Of the 36 trials included in the review, 2 used zimelidine as treatment, 3 used escitalopram, 4 used fluvoxamine, 4 used sertraline, 6 used citalopram, 8 used paroxetine, 9 used fluoxetine, and one used both citalopram and paroxetine. Because the trials included in this review are quite heterogeneous, only qualitative analyses were performed. SSRI seems to have an effect on most of chronic pain conditions; however, further clinical trials with good methodology leading to low risk of bias are needed in order to conclude once and for all the effect of this drug class as treatment for chronic pain conditions. PMID:27445601

  18. How we treat chronic graft-versus-host disease

    PubMed Central

    Martin, Paul J.

    2015-01-01

    Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GVHD requiring systemic treatment is ∼30% to 40% by National Institutes of Health criteria. The risk of chronic GVHD is higher and the duration of treatment is longer after HCT with mobilized blood cells than with marrow cells. Clinical manifestations can impair activities of daily living and often linger for years. Hematology and oncology specialists who refer patients to centers for HCT are often subsequently involved in the management of chronic GVHD when patients return to their care after HCT. Treatment of these patients can be optimized under shared care arrangements that enable referring physicians to manage long-term administration of immunosuppressive medications and supportive care with guidance from transplant center experts. Keys to successful collaborative management include early recognition in making the diagnosis of chronic GVHD, comprehensive evaluation at the onset and periodically during the course of the disease, prompt institution of systemic and topical treatment, appropriate monitoring of the response, calibration of treatment intensity over time in order to avoid overtreatment or undertreatment, and the use of supportive care to prevent complications and disability. PMID:25398933

  19. Endogenous prostaglandin E2 mediates inhibition of rat thick ascending limb Cl reabsorption in chronic hypercalcemia.

    PubMed Central

    Peterson, L N; McKay, A J; Borzecki, J S

    1993-01-01

    The hypothesis that endogenous PGE2 mediates defective thick ascending limb (TAL) Cl reabsorption (percent delivered load: FRCl%) in rats with vitamin D-induced chronic hypercalcemia (HC) was tested by measuring FRCl% in loop segments microperfused in vivo in HC and control rats treated acutely with indomethacin (Indo) or its vehicle, and obtaining the corresponding outer medullary [PGE2]. Microperfusion conditions were developed in which FRCl% was exclusively furosemide sensitive. To determine the cellular mechanism, tubules were perfused acutely with forskolin (FSK), cAMP, or the protein kinase C inhibitor staurosporine (SSP). Outer medullary [PGE2] in HC rats was 9 to 10 times greater than control and could be normalized by Indo. FRCl% was 20% lower in HC rats infused with vehicle, and Indo, FSK, and cAMP returned FRCl% to normal despite sustained HC. Indo or FSK had no effect on FRCl% in control rats and Indo did not prevent inhibition of FRCl% by luminal PGE2 (1 microM). Luminal SSP (10(-7), 10(-8) M) in HC did not return FRCl% to control values. We conclude that impaired TAL FRCl% in HC occurs at a pre-cAMP site and is due to endogenous PGE2 and not to HC. Images PMID:8390479

  20. Effect of acute and chronic ethanol pre-treatment on the disposition of phencyclidine (PCP) in the rat.

    PubMed

    Vadlamani, N L; Pontani, R B; Misra, A L

    1982-05-01

    Disposition of [H] Phencyclidine in brain, plasma and adipose tissue of rats acutely and chronically-treated with ethanol was studied using a method possessing high sensitivity and specificity for PCP. In rats acutely-treated with ethanol (5 g/kg PO dose) and PCP (10 mg/kg IP dose), dispositional factors did not play a role in the intensifies pharmacological and behavioral effects of PCP. However in rats chronically-treated with 2.5 g/kg PO dose of ethanol twice a day for 19 days, the disposition of PCP (5 mg/kg IP dose) was significantly altered and the values of PCP in brain, plasma and adipose tissue were significantly higher than those in the control group. Although inhibition of PCP metabolism and a comparatively slower rate of its elimination appear to account for the potentiation of drug effects in animals chronically-treated with ethanol, interaction of drugs at the level of the central nervous system cannot be ruled out. PMID:7089042

  1. Increased extracellular levels of glutamate in the hippocampus of chronically epileptic rats.

    PubMed

    Soukupova, M; Binaschi, A; Falcicchia, C; Palma, E; Roncon, P; Zucchini, S; Simonato, M

    2015-08-20

    An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state. PMID:26073699

  2. Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles.

    PubMed

    Grissa, Intissar; Elghoul, Jaber; Ezzi, Lobna; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; El Mir, Lassaad; Mehdi, Meriem; Ben Cheikh, Hassen; Haouas, Zohra

    2015-12-01

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity. We investigated the hematological effects and genotoxicity of anatase TiO2 NPs following sub-chronic oral gavage treatment. TiO2-NPs were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Wistar rats were treated with anatase TiO2 NPs by intragastric administration for 60 days. Hematological analysis showed a significant decrease in RBC and HCT and a significant increase in MCV, PLT, MPV and WBC at higher doses. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, and hyper-segmented neutrophil nuclei were observed with TiO2 NPs treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow at 100 and 200mg/kg bw; the comet assay showed significant DNA damage at the same doses. PMID:26653980

  3. Chronic cola drinking induces metabolic and cardiac alterations in rats

    PubMed Central

    Milei, José; Losada, Matilde Otero; Llambí, Hernán Gómez; Grana, Daniel R; Suárez, Daniel; Azzato, Francisco; Ambrosio, Giuseppe

    2011-01-01

    AIM: To investigate the effects of chronic drinking of cola beverages on metabolic and echocardiographic parameters in rats. METHODS: Forty-eight male Wistar rats were divided in 3 groups and allowed to drink regular cola (C), diet cola (L), or tap water (W) ad libitum during 6 mo. After this period, 50% of the animals in each group were euthanized. The remaining rats drank tap water ad libitum for an additional 6 mo and were then sacrificed. Rat weight, food, and beverage consumption were measured regularly. Biochemical, echocardiographic and systolic blood pressure data were obtained at baseline, and at 6 mo (treatment) and 12 mo (washout). A complete histopathology study was performed after sacrifice. RESULTS: After 6 mo, C rats had increased body weight (+7%, P < 0.01), increased liquid consumption (+69%, P < 0.001), and decreased food intake (-31%, P < 0.001). C rats showed mild hyperglycemia and hypertriglyceridemia. Normoglycemia (+69%, P < 0.01) and sustained hypertriglyceridemia (+69%, P < 0.01) were observed in C after washout. Both cola beverages induced an increase in left ventricular diastolic diameter (C: +9%, L: +7%, P < 0.05 vs W) and volumes (diastolic C: +26%, L: +22%, P < 0.01 vs W; systolic C: +24%, L: +24%, P < 0.05 vs W) and reduction of relative posterior wall thickness (C: -8%, L: -10%, P < 0.05 vs W). Cardiac output tended to increase (C: +25%, P < 0.05 vs W; L: +17%, not significant vs W). Heart rate was not affected. Pathology findings were scarce, related to aging rather than treatment. CONCLUSION: This experimental model may prove useful to investigate the consequences of high consumption of soft drinks. PMID:21526048

  4. Persistent increases in rat hypothalamic POMC gene expression following chronic withdrawal from chronic “binge” pattern escalating-dose, but not steady-dose, cocaine

    PubMed Central

    Zhou, Yan; Kreek, Mary Jeanne

    2016-01-01

    Recent research suggests an involvement of pro-opiomelanocortin (POMC) gene products (e.g., beta-endorphin) in modulating cocaine-induced reward and addiction-like behaviors in rodents. In this study, we investigated whether chronic “binge” cocaine and its withdrawal altered POMC gene expression in the brain of rats. Male Fischer rats were treated with two different chronic (14-day) “binge” pattern cocaine administration regimens (3 injections at 1-h intervals, i.p.): steady-dose (45 mg/kg/day) and escalating-dose (90 mg/kg on the last day). Although there was no POMC mRNA alteration after chronic steady-dose cocaine, a significant decrease in POMC mRNA levels in the hypothalamus was found after chronic escalating-dose cocaine. In contrast, after acute (1-day) withdrawal from chronic “binge” escalating-dose regimen, but not steady-dose regimen, there were increased hypothalamic POMC mRNA levels that persisted into 14 days of protracted withdrawal. To study the role of the endogenous opioid systems in the cocaine withdrawal effects, we administered a single naloxone injection (1 mg/kg) that caused an elevated POMC mRNA levels observed 24 h later in cocaine naïve rats, but it did not lead to further increases in cocaine-withdrawn rats. Our results suggest that during withdrawal from chronic “binge” escalating-dose cocaine: (1) there was a persistent increase in hypothalamic POMC gene expression; and (2) hyposensitivity of the POMC gene expression to naloxone indicates altered opioidergic tone at or above the hypothalamic level. PMID:25595971

  5. Corpus Callosum Anatomy in Chronically Treated and Stimulant Naive ADHD

    ERIC Educational Resources Information Center

    Schnoebelen, Sarah; Semrud-Clikeman, Margaret; Pliszka, Steven R.

    2010-01-01

    Objective: To determine the effect of chronic stimulant treatment on corpus callosum (CC) size in children with ADHD using volumetric and area measurements. Previously published research indicated possible medication effects on specific areas of the CC. Method: Measurements of the CC from anatomical MRIs were obtained from children aged 9-16 in…

  6. Chronic PTSD Treated with Metacognitive Therapy: An Open Trial

    ERIC Educational Resources Information Center

    Wells, Adrian; Welford, Mary; Fraser, Janelle; King, Paul; Mendel, Elizabeth; Wisely, Julie; Knight, Alice; Rees, David

    2008-01-01

    This paper reports on an open trial of metacognitive therapy (MCT) for chronic PTSD. MCT does not require imaginal reliving, prolonged exposure, or challenging of thoughts about trauma. It is based on an information-processing model of factors that impede normal and in-built recovery processes. It is targeted at modifying maladaptive styles of…

  7. Neuroprotective effect of escitalopram oxalate in rats with chronic hypoperfusion.

    PubMed

    Ma, Li; Lu, Zu-Neng; Hu, Pei; Yao, Chang-Jiang

    2015-08-01

    The neuroprotective effects of escitalopram oxalate in rats with chronic hypoperfusion and the possible mechanism were explored. Chronic hypoperfusion (2-VO) model was prepared and given escitalopram oxalate (experimental group) or PBS (control group) after 6 weeks. Eight weeks after the operation, Morris water maze test was carried out to evaluate the learning and memory ability of the rats. The cell proliferation, three-dimensional vascular distribution, cell morphological changes in ischemic area and the plasma vascular endothelial growth factor (VEGF) were detected to explore the possible mechanisms. (1) Morris water maze test showed that the escape latency in the experimental group was significantly shorter than in the control group, while the first quadrant swimming time in the experimental group was significantly longer than the control group (both P<0.01). (2) Cerebrovascular confocal detection results showed that the inside diameter of capillaries was significantly less in the experimental group than in the control group; the vascular density was significantly increased in the experimental group and the total area of capillaries was also significantly increased in the experimental group as compared with the control group. (3) There was statistically significant difference in BrdU-positive cells in the ischemic brain tissue between the experimental group and the control group (P=0.003<0.01). (4) VEGF concentrations in the plasma and the ischemic area were higher in the experimental group than in the control group (P<0.05). It was concluded that escitalopram oxalate could significantly improve the learning and memory ability of the rats with chronic cerebral ischemia probably by the VEGF-mediated angiogenesis. PMID:26223919

  8. Chronic Kidney Disease Impairs Bone Defect Healing in Rats

    PubMed Central

    Liu, Weiqing; Kang, Ning; Seriwatanachai, Dutmanee; Dong, Yuliang; Zhou, Liyan; Lin, Yunfeng; Ye, Ling; Liang, Xing; Yuan, Quan

    2016-01-01

    Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson’s Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects. PMID:26955758

  9. Effect of chronic centrifugation on body composition in the rat.

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.; Bull, L. S.; Oyama, J.

    1972-01-01

    Two groups of adult female rats were chronically centrifuged for 60 days (2.76 G, 4.15 G, controls at 1.00 G). Live weights of centrifugal rats decreased about 20 g (6%) per Delta 1 G above control. This weight loss comprised reductions in both body fat and fat-free body weight (FFBW) as determined by body-composition studies on eight rats per group killed at the end of centrifugation. Of nine components constituting the FFBW, only skeletal muscle, liver, and heart changed significantly in weight. Chemical composition showed reductions (compared with controls) in the fat fraction of most components and increases in the water fraction of liver and gut. Identical measurements were made on the remaining eight rats per group killed 43 days after return to 1 G. Neither centrifuged group had reached the control body-weight level at this time. No statistically significant effect of previous G level was found in any of the body-composition parameters. The possible involvment of physiological regulation was considered.

  10. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    PubMed Central

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. PMID:25029646

  11. Chronic Psychosocial Stress Impairs Bone Homeostasis: A Study in the Social Isolation Reared Rat

    PubMed Central

    Schiavone, Stefania; Morgese, Maria G.; Mhillaj, Emanuela; Bove, Maria; De Giorgi, Angelo; Cantatore, Francesco P.; Camerino, Claudia; Tucci, Paolo; Maffulli, Nicola; Cuomo, Vincenzo; Trabace, Luigia

    2016-01-01

    Chronic psychosocial stress is a key player in the onset and aggravation of mental diseases, including psychosis. Although a strong association between this psychiatric condition and other medical co-morbidities has been recently demonstrated, few data on the link between psychosis and bone homeostasis are actually available. The aim of this study was to investigate whether chronic psychosocial stress induced by 4 or 7 weeks of social isolation in drug-naïve male Wistar rats could alter bone homeostasis in terms of bone thickness, mineral density and content, as well as markers of bone formation and resorption (sclerostin, cathepsin K, and CTX-I). We found that bone mineral density was increased in rats exposed to 7 weeks of social isolation, while no differences were detected in bone mineral content and area. Moreover, 7 weeks of social isolation lead to increase of femur thickness with respect to controls, suggesting the development of a hyperostosis condition. Isolated rats showed no changes in sclerostin levels, a marker of bone formation, compared to grouped animals. Conversely, bone resorption markers were significantly altered after 7 weeks of social isolation in terms of decrease in cathepsin K and increase of CTX-I. No alterations were found after 4 weeks of isolation rearing. Our observations suggest that chronic psychosocial stress might affect bone homeostasis, more likely independently from drug treatment. Thus, the social isolation model might help to identify possible new therapeutic targets to treat the burden of chronic psychosocial stress and to attempt alternative therapy choices. PMID:27375486

  12. Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver.

    PubMed

    Reza, Hasan Mahmud; Tabassum, Nabila; Sagor, Md Abu Taher; Chowdhury, Mohammed Riaz Hasan; Rahman, Mahbubur; Jain, Preeti; Alam, Md Ashraful

    2016-01-01

    Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control + ramipril; Group-III, CCl4; and Group-IV, CCl4 + ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl4) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl4 administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl4-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl4-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl4-administered rats. PMID:26862777

  13. Chronic sodium depletion increases myocardial calcium content in normotensive rats.

    PubMed

    Rossi, G; Bond, M; Fouad-Tarazi, F M

    1989-03-01

    Increased myocardial contractility was found in the perfused heart isolated from sodium depleted Sprague-Dawley rats. Previously, it was reported that in vitro exposure of different cardiac preparations to low Na+ buffers was associated with both an increased contractility and an increased Ca2+ content in the cells. Therefore, this study was designed to examine increases in ventricular Ca2+ content in the hearts of chronically sodium depleted rats. Two groups of 12-week-old Sprague-Dawley rats were studied. One group (n = 5) received furosemide (5 mg/kg/day IP for 4 days), a low Na+ diet and distilled drinking water for 6 weeks (low sodium plus diuretics group = LSD). The other group (n = 5) received the same low Na+ diet, but 0.5% NaCl was supplemented in drinking water (regular sodium group = RS). Body weight and blood pressure were measured weekly during the dietary period in all rats. At the end of the 6 weeks, heart weight as well as water and electrolyte contents of the heart were measured in all animals. Results showed that both body weight and heart weight were significantly lower in LSD than in RS. Moreover, ventricular Na+ content was reduced while ventricular Ca2+ content was doubled in LSD compared to RS (8.2 +/- 0.2 units vs. 9.2 +/- 0.3 units, p less than .05 and 0.45 +/- 0.13 units vs. 0.23 +/- 0.01 units, p less than .01, respectively). We conclude that in vivo sodium depletion induces an increase in ventricular calcium content; this increased myocardial calcium may be related to the increased in vitro cardiac contractility observed after chronic in vivo sodium depletion, but its distribution between intracellular and extracellular compartments needs to be determined. PMID:2923136

  14. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  15. Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

    PubMed Central

    2012-01-01

    Background This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells Methods Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with heterologous bone marrow cells suspension; Group 4, experimental model of femoral pseudarthrosis treated with cultures of heterologous mesenchymal stromal cells from bone marrow. When pseudarthrosis was confirmed by simple radiological studies, digital radiography and histopathology after a 120-day postoperative period, Groups 2, 3 and 4 were treated as above. At 30, 60 and 90 days after the treatment, all animals were evaluated by simple radiological studies, and at the end of the experiment, the animals were assessed by computed axial tomography and anatomopathological and histomorphometric examinations. Results Injected cells were detected in the areas affected by pseudarthrosis using scintigraphy within the first 24 hours after their administration. After 60 days, the animals of Group 3 showed callus formation while the animals of Group 4 presented periosteal reaction and had some consolidated areas. In contrast, Group 2 showed a predominance of fibro-osteoid tissue. After 90 days, bone consolidation and remodeling was observed in all animals from Group 3 whereas animals from Group 4 exhibited partial consolidation and those ones from Group 2 persisted with pseudarthrosis. Conclusion The treatment with heterologous bone marrow cells suspension proved to be effective in the treatment of pseudarthrosis whereas cultures of heterologous bone marrow mesenchymal stromal cells did not show the same potential to aid bone healing. PMID:22429995

  16. Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue

    PubMed Central

    Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo

    2015-01-01

    Objective: This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Methods: Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral “Pishu” once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Results: Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes and correct CD4+/CD8+ ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Conclusions: Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively. PMID:26770528

  17. Cromolyn ameliorates acute and chronic injury in a rat lung transplant model

    PubMed Central

    Chang, Jui-Chih; Leung, Jason; Tang, Tao; Holzknecht, Zoie E.; Hartwig, Matthew G.; Davis, R. Duane; Parker, William; Abraham, Soman N.; Lin, Shu S.

    2015-01-01

    BACKGROUND Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown. METHODS In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control. RESULTS The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected. CONCLUSIONS These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation. PMID:24768366

  18. The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

    NASA Technical Reports Server (NTRS)

    Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

    2002-01-01

    BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no

  19. How I treat newly diagnosed chronic myeloid leukemia in 2015.

    PubMed

    Gambacorti-Passerini, Carlo; Piazza, Rocco

    2015-02-01

    The initial treatment for chronic myeloid leukemia in chronic phase (CP-CML) represents a complex process, which includes a prompt and precise diagnosis, the choice among three available tyrosine kinase inhibitors (TKIs), and the initial management of care for these patients, which will protract over a very long period of time. This manuscript summarizes different data on activity, side effects, and supportive measures available for each TKI, the need for particular care in the logistical organization of CML management, the scenario which will be opened by the future availability of generic imatinib. The opinion of the authors is that imatinib remains the first-line treatment for CP-CML; this strategy, accompanied by intensive monitoring and possible dose modification/drug switch after the initial 3-12 months of treatment presently assures a normal life expectancy to the population of newly diagnosed patients with CP-CML. PMID:25370814

  20. Differences in pulmonary responses of rats, other animals, and humans to chronic inhalation of silica and other particles

    SciTech Connect

    Mauderly, J.L.

    1993-12-31

    The pulmonary carcinogenicity of quartz in rats supports the plausibility of silica-induced lung cancer in humans. However, pulmonary responses of rats to dusts differ from those of other rodents, and may differ from those of humans. Dust-exposed rats have a greater propensity than mice or hamsters for epithelial hyperplasia, metaplasia, and fibrosis. Lung tumors occur in rats, but not mice or hamsters, treated with quartz, or exposed chronically to several other dusts. There are few opportunities for directly comparing the susceptibilities of rats and humans to dust-induced lung tumors. Because of the uncertain human responses to silica and many other particles, the negative human lung cancer response to coal dust may provide the best opportunity to calibrate responses of rats against those of humans. Historical dust lung burdens in coal miners were in the range of those associated with carcinogenicity in rats exposed to several dusts, but the carcinogenicity of coal dust in rats is unknown. The usefulness of tumor data from rats for predicting human lung cancer risk from inhaled silica and other dusts remains uncertain.

  1. Increased Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

    PubMed Central

    Parent, Alexandre J.; Beaudet, Nicolas; Beaudry, Hélène; Bergeron, Jenny; Bérubé, Patrick; Drolet, Guy; Sarret, Philippe; Gendron, Louis

    2013-01-01

    For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund’s adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: 1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), 2) a decrease in number of central squares visited in the open field (OF), and 3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance travelled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3 mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1 mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety. PMID:22245257

  2. Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats

    PubMed Central

    Lauterborn, Julie C.; Palmer, Linda C.; Jia, Yousheng; Pham, Danielle T.; Hou, Bowen; Wang, Weisheng; Trieu, Brian H.; Cox, Conor D.; Kantorovich, Svetlana

    2016-01-01

    Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. SIGNIFICANCE STATEMENT Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be

  3. NEUROMODULATORY EFFECTS OF THYMOQUINONE IN EXTENUATING OXIDATIVE STRESS IN CHLORPROMAZINE TREATED RATS.

    PubMed

    Safhi, Mohammed Mohsin

    2016-01-01

    The present study was undertaken to evaluate the possible protective effect of thymoquinone on chlorpromazine induced catalepsy, locomotor activity and cerebral oxidative stress in rats. The rats were divided into four groups, each group containing eight animals. The animals were evaluated after repeated administration of chlorpromazine (CPZ) 30 min before the administration of thymoquinone (TQ) for 21 days. Catalepsy was assessed using block method whereas the locomotor activity was assessed using acceleratory rotarod and actophotometer. Markers of oxidative stress parameters (LPO, GSH, GPx, GR, GST and CAT) were evaluated in the brain of rats. The cataleptic scores were significantly increased in CPZ treated rats when compared with normal control rats. Oral administration of TQ (5 and 10 mg/kg) significantly decreased cataleptic scores when compared with chlorpromazine (CPZ) treated rats. The muscle coordination and spontaneous locomotor activity was significantly decreased in CPZ treated rats when compared with normal control rats. Treatment with TQ significantly improved the muscle coordination and spontaneous locomotor activity when compared with CPZ treated rats. TQ treated rats significantly reduced the elevated levels of lipid peroxidation (LPO), increased levels of antioxidant enzymes i.e., reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and catalase (CAT) when compared with CPZ treated rats. The results clearly suggest that supplementation with TQ can be used to preclude CPZ induced extrapyramidal side effects and may find a role in reducing the oxidative stress. PMID:27180446

  4. Changes in Nitrergic and Tachykininergic Pathways in Rat Proximal Colon In Response to Chronic Treatment With Otilonium Bromide

    PubMed Central

    Cipriani, Gianluca; Gibbons, Simon J.; Arumugam, Saravanaperumal Siva; Malysz, John; Sha, Lei; Szurszewski, Joseph H.; Linden, David R.; Evangelista, Stefano; Faussone-Pellegrini, Maria Simonetta; Vannucchi, Maria Giuliana; Farrugia, Gianrico

    2015-01-01

    Background Otilonium bromide (OB) is used as a spasmolytic in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well-characterized, little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function. Methods Adult Sprague-Dawley rats were treated with OB in drinking water at a dose of 2 mg/kg for 30 days. The colons of OB-treated and age-matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology. Results Using immunohistochemistry, chronic OB administration did not change total neuron number, assessed by anti-Hu IR, but resulted in a significant increase in NK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase (nNOS) expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic OB administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic ICC, detected by Kit IR, were not altered nor were slow waves or smooth muscle membrane potential. Conclusions and Inferences Chronic treatment with OB caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon. PMID:25930994

  5. Copper and zinc in CCl/sub 4/ treated rats

    SciTech Connect

    Loyke, H.F.

    1984-04-01

    The role of two trace metals, copper and zinc, are important in maintaining blood pressure and the effect of carbon tetrachloride (CCl/sub 4/) has been found to be a depressor. Experimental renal hypertension has been reduced to normotension after multiple subcutaneous injections of CCl/sub 4/. By dose adjustment, the degree of liver damage has been reduced to a level of mild to moderate degree of fatty metamorphosis of the liver. It is possible that the depressor effect could be mediated by imbalance of copper and/or zinc. In the present study, copper and zinc levels were determined following CCl/sub 4/ treatment. The present work used normotensive rats treated for periods, which, in hypertensive animals, caused the blood pressure to fall.

  6. Bone metabolism of male rats chronically exposed to cadmium

    SciTech Connect

    Brzoska, Malgorzata M. . E-mail: mmbr@poczta.onet.pl; Moniuszko-Jakoniuk, Janina

    2005-09-15

    Recently, based on a female rat model of human exposure, we have reported that low-level chronic exposure to cadmium (Cd) has an injurious effect on the skeleton. The purpose of the current study was to investigate whether the exposure may also affect bone metabolism in a male rat model and to estimate the gender-related differences in the bone effect of Cd. Young male Wistar rats received drinking water containing 0, 1, 5, or 50 mg Cd/l for 12 months. The bone effect of Cd was evaluated using bone densitometry and biochemical markers of bone turnover. Renal handling of calcium (Ca) and phosphate, and serum concentrations of vitamin D metabolites, calcitonin, and parathormone were estimated as well. At treatment with 1 mg Cd/l, corresponding to the low environmental exposure in non-Cd-polluted areas, the bone mineral content (BMC) and density (BMD) at the femur and lumbar spine (L1-L5) and the total skeleton BMD did not differ compared to control. However, from the 6th month of the exposure, the Z score BMD indicated osteopenia in some animals and after 12 months the bone resorption very clearly tended to an increase. The rats' exposure corresponding to human moderate (5 mg Cd/l) and especially relatively high (50 mg Cd/l) exposure dose- and duration-dependently disturbed the processes of bone turnover and bone mass accumulation leading to formation of less dense than normal bone tissue. The effects were accompanied by changes in the serum concentration of calciotropic hormones and disorders in Ca and phosphate metabolism. It can be concluded that low environmental exposure to Cd may be only a subtle risk factor for skeletal demineralization in men. The results together with our previous findings based on an analogous model using female rats give clear evidence that males are less vulnerable to the bone effects of Cd compared to females.

  7. Effect of clofibrate on cholesterol metabolism in rats treated with polychlorinated biphenyls

    SciTech Connect

    Nakagawa, M.; Shimokawa, T.; Noguchi, A.; Ishihara, N.; Kojima, S.

    1986-02-01

    Serum and hepatic cholesterol content in rats treated with polychlorinated biphenyls (PCBs, KC-400) were increased compared to those of control rats. This increase of cholesterol content was reduced to control level by simultaneous administration of ethyl p-chlorophenoxyisobutyrate (CPIB). Also, when lecithin-cholesterol acyltransferase (LCAT) activity was expressed as the net cholesterol esterification, the acyltransferase activity in rats treated with PCBs was elevated, while the elevated acyltransferase activity was brought to control level by simultaneous administration of CPIB. On the other hand, the amount of bile of rats treated with CPIB, PCBs and PCBs-CPIB was increased, but free and total cholesterol content in bile of these treated rats was decreased to 40-60% of those of control rats. Moreover, cytochrome P-450 content in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB was increased. At the same time, cholesterol-metabolizing activity in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB also was elevated. Similar results were obtained for drug metabolizing (aniline hydroxylation and aminopyrine N-demethylation) activity. In addition, the amount of bile acids excreted from rats treated with CPIB, PCBs and PCBs-CPIB was increased compared to that of control rats. These results suggest that hypercholesterolemia induced by oral ingestion of PCBs is recovered by CPIB treatment and that this hypocholesterolemic effect of CPIB may be related partly to the elevation of hepatic mixed function oxidase activity for cholesterol catabolism.

  8. Age related changes in functions and physicochemical properties of rat jejunal brush border membrane after chronic ethanol administration.

    PubMed

    Lindi, C; Marciani, P; Omodeo-Sale, F

    1993-02-01

    1. We investigated the chronic effects of a 4 week treatment with ethanol on functions and physicochemical properties of BBM of young and adult rats (2 and 7 months old respectively). 2. In the ethanol treated groups the cholesterol/phospholipid and the protein/lipid ratios as well as the D-glucose uptake and lactase specific activity and Vmax were increased. In spite of a minor alcohol consumption the adult group was the more affected. 3. Membranes from the ethanol fed rats were less fluid and more tolerant to the in vitro addition of ethanol. PMID:8098680

  9. Chronic ethanol consumption alters effects of ethanol in vitro on brain membrane structure of high alcohol sensitivity and low alcohol sensitivity rats.

    PubMed

    Avdulov, N A; Chochina, S V; Draski, L J; Deitrich, R A; Wood, W G

    1995-08-01

    In this study, we examined if differences in initial membrane sensitivity to ethanol were associated with development of membrane tolerance to ethanol. High Alcohol Sensitivity (HAS) and Low Alcohol Sensitivity (LAS) rats were administered a 15% ethanol solution in water as the sole source of fluid for 30 days. The amount of ethanol consumed per day did not significantly differ between the HAS and LAS rats. Development of membrane tolerance to in vitro effects of ethanol has been previously reported for bulk membrane fluidity and protein-lipid interaction. Our data expands the understanding of "membrane tolerance" phenomenon to protein distribution and bilayer interdigitation. We also introduce genotype-dependent and genotype-independent properties of the membrane tolerance to ethanol. ethanol treatment produced genotype-dependent and genotype-independent membrane tolerance to ethanol. The in vitro effects of ethanol on synaptic plasma membrane (SPM) protein distribution and lipid bilayer interdigitation were abolished or decreased in the SPM of chronic ethanol-treated HAS rats, as compared with the SPM of HAS control rats (genotype-dependent tolerance). Protein distribution and bilayer interdigitation were not affected by ethanol in vitro in either chronic ethanol-treated or control LAS rats. Genotype-independent tolerance to ethanol in vitro was observed for SPM annular and bulk bilayer fluidity in chronic ethanol-treated HAS and LAS rats. It is concluded that initial sensitivity to ethanol contributes to the development of membrane tolerance to ethanol in HAS and LAS rats. PMID:7485835

  10. Effect of antisecretory agents and vagotomy on healing of chronic cysteamine-induced duodenal ulcers in rats

    SciTech Connect

    Poulsen, S.S.; Raaberg, L.; Therkelsen, K.; Skov Olsen, P.; Kirkegaard, P.

    1986-07-01

    Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphology of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.

  11. Wound healing and treating wounds: Chronic wound care and management.

    PubMed

    Powers, Jennifer G; Higham, Catherine; Broussard, Karen; Phillips, Tania J

    2016-04-01

    In the United States, chronic ulcers--including decubitus, vascular, inflammatory, and rheumatologic subtypes--affect >6 million people, with increasing numbers anticipated in our growing elderly and diabetic populations. These wounds cause significant morbidity and mortality and lead to significant medical costs. Preventative and treatment measures include disease-specific approaches and the use of moisture retentive dressings and adjunctive topical therapies to promote healing. In this article, we discuss recent advances in wound care technology and current management guidelines for the treatment of wounds and ulcers. PMID:26979353

  12. Chronic thromboembolic pulmonary hypertension: treat the patient not the haemodynamics.

    PubMed

    Dunne, Ben; van den Broek, Annika; Williams, Vaughan; Smith, Gregory; Revesz, Tamas; Edwards, Mark; Gabbay, Eli

    2012-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a disabling condition that is being increasingly recognised. It is unique as a cause of pulmonary hypertension in that it is surgically curable. We wish to highlight the importance of recognition and early referral of any patient who may have CTEPH even in the absence of resting pulmonary hypertension as excellent results can be achieved by restoring pulmonary vascular anatomy, reducing exercise-induced pulmonary hypertension, and reducing dead-space ventilation. We present a case that illustrates these points and discuss our experience as a referral centre for CTEPH. PMID:23133777

  13. Chronic Thromboembolic Pulmonary Hypertension: Treat the Patient Not the Haemodynamics

    PubMed Central

    Dunne, Ben; van den Broek, Annika; Williams, Vaughan; Smith, Gregory; Revesz, Tamas; Edwards, Mark; Gabbay, Eli

    2012-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a disabling condition that is being increasingly recognised. It is unique as a cause of pulmonary hypertension in that it is surgically curable. We wish to highlight the importance of recognition and early referral of any patient who may have CTEPH even in the absence of resting pulmonary hypertension as excellent results can be achieved by restoring pulmonary vascular anatomy, reducing exercise-induced pulmonary hypertension, and reducing dead-space ventilation. We present a case that illustrates these points and discuss our experience as a referral centre for CTEPH. PMID:23133777

  14. Plasma cortisol activity in rats under conditions of chronic stress supplemented with resveratrol

    PubMed Central

    Hurtado Salazar, Alejandro; Uribe-Velásquez, Luis F

    2012-01-01

    Objective: To determine the activity of cortisol in rats treated with exogenous adrenocorticotropic hormone (ACTH) and a resveratrol supplement. Methods: Forty-eight adult female rats and 16 male rats of the strain (Rattus norvegicus) that were three months old and with body weights ranging from 200 to 250 g for females and 300 to 350 g for males were used and kept in controlled environmental conditions: temperature of 20±2° C and light-dark cycles of 14 and 10 hours. They were fed a balanced diet and had free access to water. The rats were randomly divided into four groups: group 1 - was treated with 5 µg/kg of ACTH i.p. every twelve hours; group 2 - received the same treatment with ACTH plus a grape extract supplement (resveratrol) of 40 mg/kg; group 3 - only received grape extract (resveratrol); and group 4 - received a saline solution (0.9%) i.p. and oral, and served as controls. The experimental design was a 2×2 factorial with two levels ACTH and two polyphenol levels (grape extract). Results: No significant differences were found in blood cortisol concentrations, by day and gender, or by treatment effects (0.75 µg/dL ± 0.11; p <0.001). Conclusion: Results suggest that chronic stress and consumption of resveratrol did not directly alter levels of plasmatic cortisol in either stressed or unstressed rats. It was concluded that the given dosage levels of ACTH possibly did not produce sufficient stimulation of the adrenal gland for these animals. PMID:24893196

  15. [Influence of chronic melipramine administration abolition on locomotion and defensive conditioned reflexes in passive and active avoidance in rats].

    PubMed

    Orlova, N V; Folomkina, A A; Koshtoiants, O Kh; Bazian, A S

    2005-01-01

    The chronic (21 days duration) administration of tricyclic antidepressant melipramine of Wistar rats strain (15 mg/kg daily, intraperitoneally) evoked weight loss of animals. The 7 days after melipramine abolition its sedative effect was observed in the "open field" test by decrease of locomotion and the number of boles. The 7 and 14 days after melipramine abolition the difference between control and melipramine treated animals in passive and active avoidance learning and memory not found. The experimental results comparison with the literature data show, that chronic melipramine administration of intact animals evokes a sedative state. This conclusion does not contradict to idea of punishment function of brain serotoninergic system. PMID:15828425

  16. Biochemical, Metabolic, and Behavioral Characteristics of Immature Chronic Hyperphenylalanemic Rats.

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2016-02-01

    Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16 h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25-27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least 3 weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired. PMID:26224289

  17. [How I treat... chronic insomnia by cognitive and behavioral therapy].

    PubMed

    Dethier, M; Blairy, S; Poirrier, R

    2016-04-01

    Today, insomnia is predominantly treated by pharmacotherapy. Yet, cognitive-behavioral therapy has better long-term outcomes. In this paper, we describe the basic principles of this short-term psychotherapeutic treatment. It combines methods of sleep restriction and stimulus control, the learning of relaxation techniques, advices on sleep hygiene and cognitive therapy techniques applied to cognitions that overwhelm insomniac moments. PMID:27295894

  18. Sexual dimorphic effects of chronic phencyclidine in rats.

    PubMed

    Wessinger, W D

    1995-04-13

    The behavioral effects of phencyclidine (PCP) were studied in male and female Sprague-Dawley rats to determine if chronic infusions would result in sexually dimorphic effects. Rats were trained to make operant responses for food during 30-min response periods that occurred 4 times each day. After attaining stable baseline behaviors, 10 mg of PCP/kg/day was infused s.c. for 10 days. Females were more profoundly affected than males. In the females, response rates were suppressed to 30-71% of control rates during the first 7 days of infusion. In contrast, response rate in male rats never fell below 77% of control during the infusion period. By the eighth infusion day both sexes had become tolerant to these behavioral effects. After stopping infusions there was clear evidence that behavioral dependence had developed; however, the abstinence effects in males and females were similar. Saturation studies of [3H]dizocilpine (MK-801; (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) binding to brain membranes were conducted to determine if there were sex-dependent receptor differences. There were no significant differences in Kd +/- S.D. (7.6 +/- 1.5 and 7.1 +/- 0.9 nM for males and females, respectively) or Bmax +/- S.D. (4.1 +/- 0.2 and 4.0 +/- 0.5 pmol/mg protein for males and females, respectively). PMID:7635165

  19. Whiplash-associated chronic headache treated with home cervical traction.

    PubMed

    Olson, V L

    1997-04-01

    The subject of this case report was a 56-year-old woman who sustained a whiplash-associated disorder as a result of a motor vehicle accident. Within a few hours after the accident, she developed a headache, which became chronic, creating disability and hindering the quality of her life. In the following year, a variety of diagnostic tests, medications, and physical therapy were unsuccessful in determining the cause of her complaints or in relieving them. After this year, she expressed anger, frustration, and a reluctance to undergo additional physical therapy. By listening to her explain how she coped with her problem and observing that she lacked the ability to reduce her cervical lordosis, the therapist developed and implemented a home program of supine cervical traction and exercise. After 30 days of treatment, she was able to reduce and control her headache. This treatment and the approach used to develop the treatment may benefit other patients who have whiplash-associated chronic headache. PMID:9105344

  20. A model for chronic, intrahypothalamic thyroid hormone administration in rats.

    PubMed

    Zhang, Z; Bisschop, P H; Foppen, E; van Beeren, H C; Kalsbeek, A; Boelen, A; Fliers, E

    2016-04-01

    In addition to the direct effects of thyroid hormone (TH) on peripheral organs, recent work showed metabolic effects of TH on the liver and brown adipose tissue via neural pathways originating in the hypothalamic paraventricular and ventromedial nucleus (PVN and VMH). So far, these experiments focused on short-term administration of TH. The aim of this study is to develop a technique for chronic and nucleus-specific intrahypothalamic administration of the biologically active TH tri-iodothyronine (T3). We used beeswax pellets loaded with an amount of T3 based on in vitro experiments showing stable T3 release (∼5 nmol l(-1)) for 32 days. Upon stereotactic bilateral implantation, T3 concentrations were increased 90-fold in the PVN region and 50-fold in the VMH region after placing T3-containing pellets in the rat PVN or VMH for 28 days respectively. Increased local T3 concentrations were reflected by selectively increased mRNA expression of the T3-responsive genes Dio3 and Hr in the PVN or in the VMH. After placement of T3-containing pellets in the PVN, Tshb mRNA was significantly decreased in the pituitary, without altered Trh mRNA in the PVN region. Plasma T3 and T4 concentrations decreased without altered plasma TSH. We observed no changes in pituitary Tshb mRNA, plasma TSH, or plasma TH in rats after placement of T3-containing pellets in the VMH. We developed a method to selectively and chronically deliver T3 to specific hypothalamic nuclei. This will enable future studies on the chronic effects of intrahypothalamic T3 on energy metabolism via the PVN or VMH. PMID:26865639

  1. Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs.

    PubMed

    Razali, Norhafiza; Agarwal, Renu; Agarwal, Puneet; Kapitonova, Marina Y; Kannan Kutty, Methil; Smirnov, Alexey; Salmah Bakar, Nor; Ismail, Nafeeza M

    2015-02-15

    Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects. PMID:25481859

  2. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain. PMID:25939577

  3. Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats

    PubMed Central

    Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A.; Hernández-Reyes, Ana Gabriela

    2015-01-01

    Abstract One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity. PMID:25599112

  4. Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

    PubMed

    Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

    2015-08-01

    One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity. PMID:25599112

  5. Chronic Treatment with Ivabradine Does Not Affect Cardiovascular Autonomic Control in Rats.

    PubMed

    Silva, Fernanda C; Paiva, Franciny A; Müller-Ribeiro, Flávia C; Caldeira, Henrique M A; Fontes, Marco A P; de Menezes, Rodrigo C A; Casali, Karina R; Fortes, Gláucia H; Tobaldini, Eleonora; Solbiati, Monica; Montano, Nicola; Dias Da Silva, Valdo J; Chianca, Deoclécio A

    2016-01-01

    A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mmHg, p

  6. Chronic Treatment with Ivabradine Does Not Affect Cardiovascular Autonomic Control in Rats

    PubMed Central

    Silva, Fernanda C.; Paiva, Franciny A.; Müller-Ribeiro, Flávia C.; Caldeira, Henrique M. A.; Fontes, Marco A. P.; de Menezes, Rodrigo C. A.; Casali, Karina R.; Fortes, Gláucia H.; Tobaldini, Eleonora; Solbiati, Monica; Montano, Nicola; Dias Da Silva, Valdo J.; Chianca, Deoclécio A.

    2016-01-01

    A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine—a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mm

  7. Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem Bark Extract in Rats

    PubMed Central

    Okonkwo, T. J. N.; Okorie, O.; Okonta, J. M.; Okonkwo, C. J.

    2010-01-01

    The extracts of Anacardium occidentale have been used in the management of different cardiovascular disorders in Nigeria. These have necessitated the assessment of the toxicity of this plant extract in sub-chronic administration. The inner stem bark of Anacardium occidentale was extracted with 80 % methanol and quantitatively analysed for antinutrients and some heavy metals. The phytochemical compositions and acute toxicity of the extract were determined also. Toxicity profiles of the extract on some liver function parameters were evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87 g/kg. The phytochemical screening of extract revealed the presence of high amount of tannins, moderate saponins and trace of free reducing sugars. The antinutrient levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 % (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had LD50of 2.154g/kg p.o. in mice. Sub-chronic administration of the extract significantly increased the serum levels of alanine aminotransaminase and aspartate aminotransaminase, which are indicative of liver damage. The serum levels of alkaline phosphatase and total protein of the treated animals were not significantly increased. The effects of sub-chronically administered extract on hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and total protein levels in treated animals were not significant (p< 0.05). Thus, sub-chronic administrations of Anacardium occidentale inner stem bark extract did not significantly (p< 0.05) depress the function of hepatocytes in Wistar rats. PMID:21188045

  8. Chronic Oral Administration of the Arginase Inhibitor 2(S)-amino-6-boronohexanoic Acid (ABH) Improves Erectile Function in Aged Rats

    PubMed Central

    Segal, Robert; Hannan, Johanna L.; Liu, Xiaopu; Kutlu, Omer; Burnett, Arthur L.; Champion, Hunter C.; Kim, Jae Hyung; Steppan, Jochen; Berkowitz, Dan E.; Bivalacqua, Trinity J.

    2014-01-01

    Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/ mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function. PMID:22492840

  9. Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats.

    PubMed

    Segal, Robert; Hannan, Johanna L; Liu, Xiaopu; Kutlu, Omer; Burnett, Arthur L; Champion, Hunter C; Kim, Jae Hyung; Steppan, Jochen; Berkowitz, Dan E; Bivalacqua, Trinity J

    2012-01-01

    Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function. PMID:22492840

  10. Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats

    PubMed Central

    McIlwrath, Sabrina L; Westlund, Karin N

    2015-01-01

    AIM: To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. METHODS: Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, μ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). RESULTS: Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher

  11. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    PubMed

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID:26677163

  12. Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats.

    PubMed

    Jameson, Heather; Bateman, Ryan; Byrne, Peter; Dyavanapalli, Jhansi; Wang, Xin; Jain, Vivek; Mendelowitz, David

    2016-06-01

    Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H. To assess OXT release from PVN fibers, Chinese hamster ovarian (CHO) cells were engineered to be highly sensitive to OXT by stable expression of the human recombinant OXT receptor and the calcium indicator R-GECO1. PVN fibers in the DMNX were selectively photoactivated in vitro by expression of channelrhodopsin. The release of OXT onto CHO cells in the DMNX was blunted in rats exposed to 21 days of CIH/H. Chronic activation of PVN OXT neurons in vivo, using designer receptors exclusively activated by designer drugs, restored the release of OXT onto CHO cells in the DMNX. Chronic PVN OXT neuron activation in vivo also prevented the hypertension that occurred in conscious unrestrained telemetry-equipped sham rats exposed to 3 wk of CIH/H. These results demonstrate that chronic activation of OXT neurons restores the release of OXT from PVN fibers in the DMNX and prevents the hypertension that occurs with 3 wk of CIH/H exposure. PMID:27016581

  13. How I treat newly diagnosed chronic phase CML

    PubMed Central

    Kantarjian, Hagop

    2012-01-01

    The progress made in the understanding of chronic myeloid leukemia (CML) since the recognition of a common chromosomal abnormality to the introduction of ever more effective tyrosine kinase inhibitors is unprecedented in cancer. The expected survival for patients diagnosed with CML today, if properly managed, is probably similar to that of the general population. When managing patients with CML the goal is to achieve the best long-term outcome and we should base the treatment decisions on the data available. The results from cytogenetic and molecular analyses have to be interpreted judiciously and all available treatment options integrated into the treatment plan properly. The availability of several treatment options in CML is an asset, but the temptation of rapid succession of treatment changes because of perceived suboptimal response or for adverse events that could be managed needs to be avoided. Any decision to change therapy needs to weigh the expected long-term outcome with the current option versus the true expectations with any new option, particularly as it relates to irre-versible outcomes, such as transformation to blast phase and death. In this manuscript, we discuss the treatment approach that has helped us manage successfully a large CML population. PMID:22613793

  14. Treating the systemic effects of chronic obstructive pulmonary disease.

    PubMed

    Vogelmeier, Claus F; Wouters, Emiel F M

    2011-08-01

    Many patients with chronic obstructive pulmonary disease (COPD) also suffer from other disorders that are considered to be comorbidities and that may have a major impact on morbidity and mortality. So far, it is not clear if these diseases in the context of COPD need specific drugs or if patients diagnosed with COPD should receive certain medications to prevent the development of systemic effects of COPD. Cachexia may be caused by many contributing factors and thus may prove to be very difficult to reverse. For the treatment of osteoporosis in patients with COPD, treatment recommendations have been published. COPD is associated with reduced systemic levels of vitamin D, which has not only calcemic, but also extracalcemic effects that may play a role in the development of COPD and its consequences. Available evidence suggests that statins have a high potential, although definitive studies have not been published yet. Physical inactivity may be a major cause for systemic inflammation. In turn, exercise training may be an effective form of therapy. Although smoking cessation is very effective, it is not successful in the majority of cases. PMID:21816995

  15. Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

    PubMed

    Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

    2015-11-01

    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. PMID:26241170

  16. Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic pulsatile L-Dopa treatment induced cognitive and emotional alterations.

    PubMed

    Hernández, Vito S; Luquín, Sonia; Jáuregui-Huerta, Fernando; Corona-Morales, Aleph A; Medina, Mauricio P; Ruíz-Velasco, Silvia; Zhang, Limei

    2014-07-01

    L-Dopa is the major symptomatic therapy for Parkinson's disease, which commonly occurs in elderly patients. However, the effects of chronic use on mood and cognition in old subjects remain elusive. In order to compare the effects of a chronic pulsatile L-Dopa treatment on emotional and cognitive functions in young (3 months) and old (18 months) intact rats, an L-Dopa/carbidopa treatment was administered every 12 h over 4 weeks. Rats were assessed for behavioural despair (repeated forced swimming test, RFST), anhedonia (sucrose preference test, SPT) and spatial learning (Morris water maze, MWM) in the late phase of treatment (T). Neuronal expression of Fos in the hippocampus at the early and late phases of T, as well as after MWM was studied. The density and ratio of dopamine D5r, D3r and D2r receptors were also evaluated in the hippocampus using immunohistochemistry and confocal microscopy. Young rats showed similar patterns during behavioural tests, whereas aged treated rats showed increased immobility counts in RFST, diminished sucrose liquid intake in SPT, and spatial learning impairment during MWM. Fos expression was significantly blunted in the aged treated group after MWM. The density of D5r, D3r and D2r was increased in both aged groups. The treatment reduced the ratio of D5r/D3r and D5r/D2r in both groups. Moreover, aged treated subjects had significant lower values of D5r/D3r and higher values of D5r/D2r when compared with young treated subjects. These results indicate that chronic L-Dopa treatment in itself could trigger emotional and cognitive dysfunctions in elderly subjects through dopamine receptor dysregulation. PMID:24291463

  17. Anti-inflammatory Effect of Isaria sinclairii Glycosaminoglycan in an Adjuvant-treated Arthritis Rat Model

    PubMed Central

    Jee, Sang Duck; Hwang, Jae Sam; Yun, Eun Young; Ahn, Kwang Seok; Kim, Yeong Shik

    2013-01-01

    The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund’s adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin® as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-κB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-α production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin® (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future. PMID:24386520

  18. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats.

    PubMed

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The chronic toxicity and potential carcinogenicity of sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder

  19. Ciproxifan differentially modifies cognitive impairment evoked by chronic stress and chronic corticosterone administration in rats.

    PubMed

    Trofimiuk, Emil; Braszko, Jan J

    2015-04-15

    Despite the development of neuroscience and spectacular discoveries, the clear functions and the role of histamine are still not fully understood, especially in the context of the negative impact of prolonged stress exposure on the cognition. The purpose of this study was to evaluate the participation of hypercortisolemia in the detrimental effect of stress on cognitive function and their preclusion by affecting the histaminergic system with ciproxifan. Specifically, we attempted to characterize the preventive action of a single dose of ciproxifan (3mg/kg, i.p.) against an impairment caused by chronic restraint stress as well as parallel exogenous corticosterone (equivalent to that seen in chronically stressed rats), and show differences in the interaction on reference and working memories tested in both aversive (Morris water maze - MWM) and appetitive (Barnes maze-BM) incentives. We found that administration of ciproxifan potently prevented equally deleterious effects of chronic restraint stress (p<0.01) as well as prolonged administration of corticosterone (p<0.01), especially in the tests, which themselves generate high levels of stress. As it turns out, test provided in the less stressful conditions (BM) showed that administration of the H3 receptor antagonist to naïve rats resulted in even memory impairment (p<0.01, in some aspects of reference memory). These data support the idea that modulation of H3 receptors represents a novel and viable therapeutic strategy in the treatment but rather not for prevention of stress-evoked cognitive impairments. Even a single dose abolishes the effect of prolonged exposure to stress or steroids. PMID:25639546

  20. Effect of chronic nicotine pre-treatment on phencyclidine (PCP) disposition in the rat.

    PubMed

    Vadlamani, N L; Pontani, R B; Misra, A L

    1983-09-01

    Disposition of [3H] phencyclidine (5 mg kg-1 i.p.) in brain, liver and plasma of rats treated chronically with 0.9% saline or nicotine (1 mg kg-1 s.c. twice a day for 11 days) was studied using a method possessing high sensitivity and specificity for PCP. No significant differences were observed in the values of PCP in plasma and tissues and in brain or liver to plasma PCP concentration ratios in the 2 groups 0.5, 1, 2 hr after [3H] PCP injection. With the exception of the value of PCP metabolites in plasma at 0.5 hr, the PCP metabolites concentrations were also not significantly different in the 2 groups. Data suggested that chronic nicotine pretreatment of rats did not affect the disposition of PCP and the potentiation of PCP-induced locomotor stimulant effects by nicotine possibly involves the additive pharmacodynamic interaction of 2 compounds at the level of the central nervous system. PMID:6651404

  1. Transurethral electrolaser complex therapy to treat chronic prostatitis

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.

    2000-05-01

    According to the world statistics, from 30 to 60 percent of elderly male population suffer from chronic prostatitis in different countries. This disease has a number of consequences such as urino-genital inflammation, dysuria, perineal pain, reduction in the physiological activity of smooth muscles, blockage of the anus passages with micro-organism vital activity products, appearance of stagnant zones and low blood circulation complicated by disorders of the sexual function. Most of these features make it difficult to use standard drug therapies with antibiotics or immunocorrectors. For that reason, the objective of this study is to develop and to investigate a novel combined electrolaser therapy which improves drug delivery in the prostate gland and simultaneously provides an independent physiotherapeutic effect. The main feature of this therapy is the utilization of two diode lasers emitting in the red (0.67 micrometer, 10 mW) and in the infrared (0.85 micrometer, 1 W) spectrum ranges in combination with transurethral electrostimulation. An electrolaser catheter containing both hollow cylindrical electrodes and an axial optical fiber to deliver laser radiation was brought along the urethra to the seminal vesicles. The red laser in combination with a photosensitizer ('Photosens,' Russia) was used to realize the antibacterial treatment of the urethra. The infrared laser was employed to heat the prostate gland and to stimulate the blood perfusion without thermal damage of tissues. The laser heating of the prostate at a local tissue temperature of 41 degrees Celsius in combination with the electrostimulation provided approximately a 4.5-fold increase in the blood flow. The realization of an additional mode of photovacuum therapy inside the urethra together with the electrostimulation made it possible to 'clean' the anus passages and to improve the DNA diagnosis reliability in respect of the urogenital infectious remainder. The clinical data obtained in 980 patients

  2. Mechanical properties and reactivity of vessels in isolated perfused lungs of chronically hypoxic rats.

    PubMed

    Emery, C J; Bee, D; Barer, G R

    1981-11-01

    1. Chronically hypoxic rats kept in 10% (v/v) O2 for 3--6 weeks, were compared with littermate control rats. Pulmonary vascular resistance, measured from the slope of the pressure-flow relationship in isolated lungs perfused with blood of normal packed cell volume was higher in chronically hypoxic than control rats even during normoxia. 2. Chronically hypoxic rats weighed less than control rats but their pulmonary vascular volume, measured with labelled albumin was similar to control rats. This, together with evidence that the number of precapillary vessels is not reduced, does not suggest a large reduction in the vascular bed in chronic hypoxia. 3. A greater vasodilator action of isoprenaline and adenosine in chronically hypoxic than control lungs suggested a higher normoxic vascular tone. This higher tone was not the sole cause of increased resistance in chronically hypoxic lungs, since maximal vasodilatation did not reduce resistance to control levels. The chief cause was probably encroachment of new muscle on the vascular lumen of small vessels. 4. Pulmonary arterial compliance was reduced in chronically hypoxic lungs. 5. Reactivity of vessels to ventilation hypoxia, over a wide range of oxygen tension, to angiotensin II (ANG II) and to adenosine 5'-triphosphate (ATP) was significantly greater in chronically hypoxic than control lungs, but thresholds to these stimuli were not reduced. PMID:7285503

  3. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    PubMed

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  4. Chronic toxicity, oncogenic potential, and reproductive toxicity of p-nitroaniline in rats.

    PubMed

    Nair, R S; Auletta, C S; Schroeder, R E; Johannsen, F R

    1990-10-01

    Dose levels for these studies were selected mainly on the basis of subchronic studies, although consideration was also given to workplace exposure levels and proposed mechanism of tumor formation with structurally similar compounds. For the chronic study, groups of 60 male and 60 female Sprague-Dawley CD (Registered Trademark of Charles River Breeding Laboratories, Portage, MI) rats were given 0, 0.25, 1.5, or 9.0 mg/kg/day paranitroaniline (PNA) by gavage in corn oil for a period of 2 years. Parameters monitored included clinical observations, ophthalmoscopic exams, body weights, food consumption, hematology, clinical chemistry, and urinalysis at regular intervals throughout the study. All gross lesions and over 40 tissues were examined histologically for all control and high-dosage-level animals. Gross lesions, spleens, and livers of low- and mid-dosage groups were also examined histologically. For the reproduction study, groups of 15 male and 30 female rats, designated as F0 generation, were given PNA at the same levels as the chronic study for 14 weeks prior to mating and during mating, gestation, and lactation. Selected groups of 15 male and 30 female rats of the F1 generation received the same dose of PNA for 18 weeks prior to mating and during mating, gestation, and lactation. F2 pups were observed through weaning at which time they were euthanized. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. In the chronic study, except for a slight decrease in survival of high-dose male rats late in the study, survival in all treated groups was comparable to controls. Blood methemoglobin levels were elevated in the mid- and high-dosage groups, while slight anemia was observed in the high-dosage group also. Spleen weights were significantly increased in the high-dosage groups. An accumulation of brown pigment was observed in the cytoplasm of

  5. Some histological effects of chronic administration of chloroquine on the medial geniculate body of adult wistar rat.

    PubMed

    Adjene, J O; Caxton-Martins, A E

    2006-06-01

    Some histological effects of chronic administration of chloroquine commonly used for prophylaxis or treatment of malaria. rheumatoid arthritis and lupus erythematosus on the medial geniculate body (MGB) of adult wistar rats was carefully studied. The rats of both sexes (n= 18), average weight of 184g were randomly assigned into treatment (n= 10) and control (n=7) groups. The rats in the treatment group received 2mg/kg body weight of chloroquine base dissolved in distilled water daily for fourteen days through the orogastric tube administration while the control rats received equal volume of distilled water daily through the same route. The rats were fed with rat pellets purchased from Topfeed Ltd. Sapele. Delta State. Nigeria and given water liberally and were then sacrificed on day fifteen of the experiment. The MGB were carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H & E and thionin methods. The histological findings after H & E methods indicated that the treated sections of the MGB showed faintly reduced nuclei size, with the presence of many autophagic vacuoles and degenerative neurons when compared to the control sections. On the other hand. the thionin method indicated that the treated sections showed sparsely distributed neurons, which stain less intensely when compared with the control. The nissl substance in some of the neurons appeared degenerative while some hypertrophied with some vacuolations. These findings indicated that chronic administration of chloroquine has a deleterious effect on the neurons and nissl substance of the MGB. Chloroquine may probably have adverse effects on auditory sensibilities by its deleterious effects on the nerve cells and nissl substances of the MGB of the adult wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out. PMID:17209307

  6. Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats

    PubMed Central

    LI, YAN; XUAN, YAN-HUA; LIU, SHUANG-SHUANG; DONG, JING; LUO, JIA-YING; SUN, ZHI-JUN

    2015-01-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  7. Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver.

    PubMed

    Aydin, O; Akyuz, F; Tekin, N; Ustuner, Mc; Degirmenci, I; Burukoglu, D; Ozden, H

    2016-07-01

    Transglutaminase 2 (TG2) has been implicated in wound healing, cellular differentiation, apoptosis and cell survival. TG2 activity increases following acute and chronic liver injury; however, the role of TG2 in tumors, is controversial. TG2 is a retinoid-inducible enzyme. We investigated the effects of retinyl acetate (RA) on the activity and levels of TG2 during the initiation and promotion stages of liver cancer. p-Dimethylaminoazobenzene (p-DAB) was used as initiator and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was used as promoter in our model of carcinogenesis. Rats were divided into four groups of 24: control, corn oil control, p-DAB + TCDD, and p-DAB + TCDD + RA. Six rats from each group were sacrificed at days 30, 60, 90 and 120. TG2 activity decreased in the p-DAB + TCDD treated group, but TG2 immunostaining scores did not change by days 90 and 120. Neither TG2 enzyme activity nor the immunostaining score of TG2 protein changed in the tissues of the p-DAB + TCDD + RA group by days 90 and 120. TG2 activity was not be ameliorated by RA during the initiation or promotion stages of carcinogen induced liver cancer. PMID:27089473

  8. Absence of organ specific toxicity in rats treated with Tonica, an aqueous herbal haematinic preparation.

    PubMed

    Martey, Orleans Nii-Korley; Armah, George; Okine, Laud K N-A

    2010-01-01

    The sub-chronic toxicity of Tonica, an aqueous herbal haematinic prepared from the stem barks of Khaya senegalensis, Mitragyna stipulosa and Kigelia africana, was investigated in male Sprague-Dawley rats at 28, 280 and 560 mg kg(-1) day(-1), representing the normal human dose, 10x and 20x that dose, respectively for 6 weeks. The growth rate of animals over the period of treatment and certain serum biochemical and haematological indices as well as urinalysis and weight of selected organs at termination, were determined. Results show that the extract did not affect the weight gain of the animals with time or the mean wet weights of selected organs. Although there were slight but insignificant (p>0.05) elevations in WBC (16-27%) and PLT (8-11%) counts in Tonica-treated animals compared to controls at 10x and 20x the normal dose, most serum biochemical, haematological and urinalysis data indicated no significant differences (p>0.05) between tests and control rats. There were also no changes in the morphology of liver, kidney, lung and heart tissues as a result of Tonica treatment. These findings suggest that Tonica is safe at the dosage regimens administered to the animals in this study, and there appears to be no overt organ specific toxicity associated with it. PMID:21461151

  9. Chronic prostatitis/chronic pelvic pain syndrome and pelvic floor spasm: can we diagnose and treat?

    PubMed

    Westesson, Karin E; Shoskes, Daniel A

    2010-07-01

    National Institutes of Health category III prostatitis, also known as chronic prostatitis/chronic pelvic pain syndrome, is a common condition with significant impact on quality of life. This clinically defined syndrome has a multifactorial etiology and seems to respond best to multimodal therapy. At least half of these patients have pelvic floor spasm. There are several approaches to therapy including biofeedback, acupuncture, and myofascial release physical therapy. However, the only multicenter study of pelvic floor physical therapy for pelvic floor spasm in men failed to show an advantage over conventional Western massage. We have proposed a clinical phenotyping system called UPOINT to classify patients with urologic chronic pelvic pain and subsequently direct appropriate therapy. Here, we review the current approach to category III prostatitis and describe how clinical phenotyping with UPOINT may improve therapy outcomes. PMID:20490725

  10. Temsirolimus and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-11

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia

  11. Rat models of asthma and chronic obstructive lung disease.

    PubMed

    Martin, James G; Tamaoka, Meiyo

    2006-01-01

    The rat has been extensively used to model asthma and somewhat less extensively to model chronic obstructive pulmonary disease (COPD). The features of asthma that have been successfully modeled include allergen-induced airway constriction, eosinophilic inflammation and allergen-induced airway hyperresponsiveness. T-cell involvement has been directly demonstrated using adoptive transfer techniques. Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13). Repeated allergen exposure causes airway remodeling. Dry gas hyperpnea challenge also evokes increases in lung resistance, allowing exercise-induced asthma to be modeled. COPD is modeled using elastase-induced parenchymal injury to mimic emphysema. Cigarette smoke-induced airspace enlargement occurs but requires months of cigarette exposure. Inflammation and fibrosis of peripheral airways is an important aspect of COPD that is less well modeled. Novel approaches to the treatment of COPD have been reported including treatments aimed at parenchymal regeneration. PMID:16337418

  12. Totally implantable robot to treat chronic atrial fibrillation.

    PubMed

    Tozzi, Piergiorgio; Hayoz, Daniel; Thévenaz, Pierrick; Roulet, Jean-Yves; Salchli, Francois; von Segesser, Ludwig K

    2008-09-01

    Chronic atrial fibrillation affects millions of people worldwide. Its surgical treatment often fails to restore the transport function of the atrium. This study first introduces the concept of an atrial assist device (AAD) to restore the pump function of the atrium. The AAD is developed to be totally implantable in the human body with a transcutaneous energy transfer system to recharge the implanted battery. The ADD consists of a motorless pump based on artificial muscle technology, positioned on the external surface of the atrium to compress it and restore its muscular activity. A bench model reproduces the function of a fibrillating atrium to assess the circulatory support that this pump can provide. Atripump (Nanopowers SA, Switzerland) is a dome-shaped silicone-coated nitinol actuator 5 mm high, sutured on the external surface of the atrium. A pacemaker-like control unit drives the actuator that compresses the atrium, providing the mechanical support to the blood circulation. Electrical characteristics: the system is composed of one actuator that needs a minimal tension of 15 V and has a maximum current of 1.5 A with a 50% duty cycle. The implantable rechargeable battery is made of a cell having the following specifications: nominal tension of a cell: 4.1 V, tension after 90% of discharge: 3.5 V, nominal capacity of a cell: 163 mA h. The bench model consists of an open circuit made of latex bladder 60 mm in diameter filled with water. The bladder is connected to a vertically positioned tube that is filled to different levels, reproducing changes in cardiac preload. The Atripump is placed on the outer surface of the bladder. Pressure, volume and temperature changes were recorded. The contraction rate was 1 Hz with a power supply of 12 V, 400 mA for 200 ms. Preload ranged from 15 to 21 cm H(2)O. Maximal silicone membrane temperature was 55 degrees C and maximal temperature of the liquid environment was 35 degrees C. The pump produced a maximal work of 16 x 10

  13. Epigenetically modified nucleotides in chronic heroin and cocaine treated mice.

    PubMed

    Chao, Mu-Rong; Fragou, Domniki; Zanos, Panos; Hu, Chiung-Wen; Bailey, Alexis; Kouidou, Sofia; Kovatsi, Leda

    2014-09-17

    Epigenetic changes include the addition of a methyl group to the 5' carbon of the cytosine ring, known as DNA methylation, which results in the generation of the fifth DNA base, namely 5-methylcytosine. During active or passive demethylation, an intermediate modified base is formed, 5-hydroxymethylcytosine. We have currently quantified 5-methylcytosine and 5-hydroxymethylcytosine in the liver and brain of mice treated with cocaine or heroin, using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Our results show that global 5-methylcytosine levels are not affected by heroin or cocaine administration, neither in the liver nor in the brain. However, 5-hydroxymethylcytosine levels are reduced in the liver following cocaine administration, while they are not affected by cocaine in the brain or by heroin administration in the liver and the brain. Elucidation of the epigenetic phenomena that takes place with respect to drug abuse and addiction, via quantitative analysis of different modified bases, may enable a better understanding of the underlying mechanisms and may lead to more personalized and effective treatment options. PMID:25064621

  14. Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung.

    PubMed Central

    Zhao, L.; al-Tubuly, R.; Sebkhi, A.; Owji, A. A.; Nunez, D. J.; Wilkins, M. R.

    1996-01-01

    1. Angiotensin II (AII) binding density and the effect of chronic AII receptor blockade were examined in the rat model of hypoxia-induced pulmonary hypertension. 2. [125I]-[Sar1,Ile2]AII binding capacity was increased in lung membranes from rats exposed to hypoxia (10% fractional inspired O2) for 7 days compared to normal rats (Bmax 108 +/- 12 vs 77 +/- 3 fmol mg-1 protein; P < 0.05), with no significant change in dissociation constant. Competition with specific AII receptor subtype antagonists demonstrated that AT1 is the predominant subtype in both normal and hypoxic lung. 3. Rats treated intravenously with the AT1 antagonist, GR138950C, 1 mg kg-1 day-1 rather than saline alone during 7 days of exposure to hypoxia developed less pulmonary hypertension (pulmonary arterial pressure: 21.3 +/- 1.7 vs 28.3 +/- 1.1 mmHg; P < 0.05), right ventricular hypertrophy (right/left ventricle weight ratio: 0.35 +/- 0.01 vs 0.45 +/- 0.01; P < 0.05) and pulmonary artery remodelling (abundance of thick-walled pulmonary vessels: 9.6 +/- 1.4% vs 20.1 +/- 0.9%; P < 0.05). 4. The reduction in cardiac hypertrophy and pulmonary remodelling with the AT1 antagonist was greater than that achieved by a dose of sodium nitroprusside (SNP) that produced a comparable attenuation of the rise in pulmonary arterial pressure during hypoxia. 5. The data suggest that AII, via the AT1 receptor, has a role in the early pathogenesis of hypoxia-induced pulmonary hypertension in the rat. PMID:8937726

  15. Acute and chronic tramadol administration impair spatial memory in rat

    PubMed Central

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  16. Paeoniflorin improves menopause depression in ovariectomized rats under chronic unpredictable mild stress

    PubMed Central

    Huang, Hongli; Zhao, Juan; Jiang, Lin; Xie, Yuan; Xia, Yanqiu; Lv, Rong; Dong, Li

    2015-01-01

    Paeoniflorin has been shown to effectively relieve neurologic impairments and lessen depression. It remains poorly understood whether it can be used to treat menopause depression; therefore, in the present study, animal model of menopause depression were established by resecting the ovaries in combined with long-term chronic unpredictable stress. Animal model of menopause depression was established by ovariectomy. Sprague-Dawley rats were given 10 mg/kg of paeoniflorin by gastrogavage for 2 weeks. Fluoxetine (2.5 mg/kg) served as a positive control. Sucrose solution consumption test, open-field test, real-time PCR and western blot results demonstrated that paeoniflorin increased sucrose solution consumption, voluntary behaviors and 5-HT1AR mRNA and protein expression. Paeoniflorin decreased the levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol (CORT) and 5-HT2AR mRNA and protein expression in rats with menopause depression. These results indicate that paeoniflorin unregulated 5-HT1AR expression, but downregulated 5-HT2AR expression in brains of rats with menopause depression, and thus exert antidepressant effects. PMID:26131083

  17. A chronic toxicity study of the ground root bark of Capparis erythrocarpus (Cappareceae) in male Sprague-Dawley rats.

    PubMed

    Martey, O N K; Armah, G E; Sittie, A A; Okine, L K N

    2013-12-01

    The safety evaluation of Capparis erythrocarpus (CE) on chronic administration at 18 and 180 mg kg(-1) body weight for 6 months was investigated in male Sprague-Dawley rats. The effects of CE on certain serum biochemical, haematological, urine and histopathological determinations were used as indices of organ specific toxicity. Also the effects of CE on rat blood clotting time and pentobarbital-induced sleeping time were determined. Results indicate that CE had no effect on urine, haematological and serum biochemical indices at termination of treatment with the exception of serum ALT level which was significantly (p < 0.05) attenuated in a dose-dependent fashion (21-35%). There were also no differences in blood clotting time and pentobarbital-induced sleeping time between CE-treated and control animals. Histopathological studies showed that CE did not adversely affect the morphology of the liver, kidney and heart tissues. However, lungs of CE-treated animals showed slight but insignificant inflammatory response in alveolar areas and Clara cell hyperplasia without the thickening of alveolar septa and bronchiolar epithelial wall. Organ weights were not adversely affected by CE treatment. There were significant (p < 0.05) changes in weight of CE-treated animals with duration of treatment compared to control. These results suggest that there is no organ specific toxicity associated with chronic administration of CE in rats and its ability to reduce body weight may be useful for slimming in obese persons. PMID:24506037

  18. Ghrelin ameliorates catabolic conditions and respiratory dysfunction in a chronic obstructive pulmonary disease model of chronic cigarette smoke-exposed rats.

    PubMed

    Kamiide, Yoshiyuki; Inomata, Norio; Furuya, Mayumi; Yada, Toshihiko

    2015-05-15

    Cigarette smoking, which is a well-known major risk factor for chronic obstructive pulmonary disease (COPD), causes both pulmonary and extrapulmonary abnormalities. Ghrelin is a gastric peptide that regulates energy homeostasis. In the present study, we investigated the effects of ghrelin on the catabolic changes, respiratory function and emphysema in an animal model of COPD induced by chronic exposure to cigarette smoke. Rats were exposed to cigarette smoke, and they were administered human ghrelin (0.1 or 1 mg/kg, subcutaneous, twice daily) for 12 weeks. Compared with air-exposed rats, body weight gain, food intake, food efficiency, tidal volume, peak expiratory flow rate, and forced expiratory volume at 100 ms were significantly lower, while functional residual capacity, lung capacity, and neutrophils in bronchoalveolar lavage fluid were significantly higher in cigarette smoke-exposed rats. These indicated that the systemic abnormalities associated with COPD developed after the exposure to cigarette smoke. Ghrelin significantly and dose-dependently increased the body weight gain and food efficiency in cigarette smoke-exposed rats. In ghrelin-treated rats, skeletal muscle strength, which tended to be lowered by cigarette smoke exposure, was improved. Ghrelin ameliorated respiratory function and emphysema in a dose-dependent manner, but did not inhibit the increase in neutrophils in the bronchoalveolar lavage fluid. The respiratory functional parameters and lung capacity were significantly correlated with body weight gain. These results suggest that ghrelin inhibited the development of the catabolic changes, respiratory dysfunction, and emphysema that were induced by cigarette smoke exposure in rats, at least in part, through the amelioration of nutritional status. PMID:25771457

  19. Chronic effects of lead on renin and renal sodium excretion. [Rats

    SciTech Connect

    Fleischer, N.; Mouw, D.R.; Vander, A.J.

    1980-05-01

    Rats were chronically give 0.5 mg/ml Pb in drinking water. This produced blood and renal lead concentratoins of approximately 30 )g/dl and 20)g/gm, respectively, significant kidney swelling, but no change in body weight or hematocrit. After 6 weeks of Pb treatment and during ingestion of a sodium-free diet, plasma, renin activity (PRA) was elevated (controls: same diet, no lead), but there was no change in plasma resin substrate (PRS). After 5 months the PRA was significantly higher in the lead-treated group even on a 1% NaCl diet, but the difference between groups disappeared on an Na-free diet; that is, the renin response to sodium deprivation was blunted. As early as 6 weeks after beginning lead treatment, the treated group manifested reduced ability to decrease Na excretion following removal of NaCl from the diet; steady-state sodium excretion was normal on either the 1% NaCl or Na-free diet. We conclude that changes in the renin angiotensin system and renal sodium handling may be important toxic effects of low doses of lead on the kidneys of rats.

  20. Subarachnoid midazolam: histologic study in rats and report of its effect on chronic pain in humans.

    PubMed

    Schoeffler, P; Auroy, P; Bazin, J E; Taxi, J; Woda, A

    1991-01-01

    Subarachnoid administration via a catheter of a water-soluble benzodiazepine, midazolam, was tested in the control of cancer pain. First, the lack of its toxicity during constant subarachnoid administration (50 micrograms per day) was assessed in the rat. After 15 days of treatment, a histologic examination of the spinal cord revealed the same amount of fibrosis, infiltration, and deformation in the control group (n = 14), which had received only saline, as in the test group (n = 18), treated with subarachnoid midazolam. Therefore, the histologic changes observed in the spinal cord probably are related to the presence of the catheter. After these results, a mixture of 2 mg midazolam and a variable dose of subarachnoid morphine was injected in two patients presenting chronic neoplastic pain resistant to high doses of morphine. In these two cases, the addition of midazolam appeared to be effective in controlling intractable neoplastic pain. PMID:1772817

  1. [Effects of Kaixin San formulas on behavioristics and central monoamine neurotransmitters of chronic stress rats].

    PubMed

    Liu, Wan-wan; Xu, Lu; Dong, Xian-zhe; Tan, Xiao; Wang, Shi; Zhu, Wei-yu; Liu, Ping

    2015-06-01

    The efficacy of Chinese herbal formula in treating depression has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on central monoamine neurotransmitters of chronic stress rats and against depression based on their different components in plasma, in order to discuss the efficacy-comparability relationship and the possible efficacy mechanism. The classic isolation method and the chronic unpredictable mild stress (CUMS) depression model were combined to investigate the changes in contents in hippocampus and monoamine neurotransmitters (NE, DA, 5-HT) and the components of some formulas in plasma with HPLC and UPLC-Q-TOF-MSE methods. As a result, Dingzhi Xiaowan recorded in Essential Recipes for Emergent Use Worth A Thousand significantly increased the behavioral scores, NE and 5-HT contents in hippocampus and NE, DA and 5-HT contents in cortex, with the best anti-depressant effect. Dingzhi Xiaowan recorded in Complete Records of Ancient and Modern Medical Works showed a notable increase in sucrose preference and open field score in model rats, NE content in hippocampus and NE, DA and 5-HT contents in cortex, with a certain anti anti-depressant effect. Kaixin San recorded in Ishinpo showed remarkable rise in weight of model rats. NE content in hippocampus and DA content in cortex. Puxin Decoction recorded in A Supplement to Recipes Worth A Thousand Gold showed 5-HT content in hippocampus and DA content in cortex. Kaixin San recorded in Yimenfang only showed DA content in cortex. Kaixin Wan recorded in Essential Recipes for Emergent Use Worth A Thousand did not mention the antidepressant effect. According to the results, the formulas' different anti-depressant effects may be related to the different plasma components. PMID:26552177

  2. Alteration of Behavioral Changes and Hippocampus Galanin Expression in Chronic Unpredictable Mild Stress-Induced Depression Rats and Effect of Electroacupuncture Treatment

    PubMed Central

    Mo, Yuping; Yao, Haijiang; Song, Hongtao; Wang, Xin; Chen, Wanshun; Abulizi, Jiawula; Xu, Anping; Tang, Yinshan; Han, Xiangbo; Li, Zhigang

    2014-01-01

    To explore new noninvasive treatment options for depression, this study investigated the effects of electric acupuncture (EA) for depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighteen male Sprague-Dawley rats were randomly assigned into three groups: control, model, and EA groups. Rats were treated by EA once daily for 21 days. The results showed that body weight and sucrose consumption were significantly increased in EA group than in the model group. The crossing numbers and rearing numbers in the open field test significantly decreased in the model group but not in the EA group. And EA treatments upregulated levels of hippocampus galanin (Gal) in UCMS rats back to relative normal levels. The present study suggested that EA had antidepressant effects on UCMS model rats. The potential antidepressant effect may be related to upregulating Gal expression in hippocampus. PMID:25530777

  3. Transcriptional responses in thyroid tissues from rats treated with a tumorigenic and a non-tumorigenic triazole conazole fungicide

    SciTech Connect

    Hester, Susan D. Nesnow, Stephen

    2008-03-15

    Conazoles are azole-containing fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay. The goal of this study was to identify pathways and networks of genes that were associated with thyroid tumorigenesis through transcriptional analyses. To this end, we compared transcriptional profiles from tissues of rats treated with a tumorigenic and a non-tumorigenic conazole. Triadimefon, a rat thyroid tumorigen, and myclobutanil, which was not tumorigenic in rats after a 2-year bioassay, were administered in the feed to male Wistar/Han rats for 30 or 90 days similar to the treatment conditions previously used in their chronic bioassays. Thyroid gene expression was determined using high density Affymetrix GeneChips (Rat 230{sub 2}). Gene expression was analyzed by the Gene Set Expression Analyses method which clearly separated the tumorigenic treatments (tumorigenic response group (TRG)) from the non-tumorigenic treatments (non-tumorigenic response group (NRG)). Core genes from these gene sets were mapped to canonical, metabolic, and GeneGo processes and these processes compared across group and treatment time. Extensive analyses were performed on the 30-day gene sets as they represented the major perturbations. Gene sets in the 30-day TRG group had over representation of fatty acid metabolism, oxidation, and degradation processes (including PPAR{gamma} and CYP involvement), and of cell proliferation responses. Core genes from these gene sets were combined into networks and found to possess signaling interactions. In addition, the core genes in each gene set were compared with genes known to be associated with human thyroid cancer. Among the genes that appeared in both rat and human data sets were: Acaca, Asns, Cebpg, Crem, Ddit3, Gja1, Grn, Jun, Junb, and Vegf. These genes were major contributors in the previously developed network from triadimefon-treated rat thyroids. It is

  4. Effect of Pueraria tuberosa tuber extract on chronic foot shock stress in Wistar rats.

    PubMed

    Pramanik, S S; Sur, T K; Debnath, P K; Bhattacharyya, D

    2010-12-01

    The present study was undertaken to explore the protective effects of tuberous root extract of Pueraria tuberosa on chronic foot shock stress (CS) induced physiological, neurobehavioral and neuropathological alterations. Male Wistar rats (120-150 g) were divided into seven groups, consisting of ten animals in each. Group I served as normal, group II as positive control, while group III-VII as test drug treated. P tuberosa tuber extract (PTE) was given to rats of groups III-VI at the doses of 50, 100, 200 and 400 mg/kg respectively, while group VII treated with Withania somnifera rhizome extract (WSE) (100 mg/kg) as reference drug. Group II (stress control) received only equivalent volume of distilled water (0.5 ml/100 g) orally. All the drugs were given orally once/day for 14 consecutive days. The last dose was given 1 h before study. Simultaneously, all the animals (except group I) were subjected to 1 h of foot-shock (2 mA) through a grid floor for those 14 days in a standard conditioning chamber with the escape route closed [Chronic stress (CS)]. Thereafter, the rats were placed on open-field and plus maze apparatus for studying the behavioral patterns of them, and the anxiolytic effects of the putative drug. Sexual activities of the animals were also studied. Finally, the animals were sacrificed and their ulcer formation in gastric mucosa was noted. Weights of adrenals and spleen were also taken. Further, plasma corticosterone levels were estimated spectroflurometrically. Results indicated that, CS significantly altered the behavioral patterns, decreased the sexual urge and activities, damaged the gastric mucosal layers, enhanced plasma corticosterone levels and increased adrenal glands and spleen weights. PTE and WSE showed significant anxiolytic activity, protected the gastric mucosa, lowered plasma corticosterone level (indicating HPA axis inhibition) and negated the hypertrophy of adrenals and spleen. PTE also enhanced the sexual urge and activities in

  5. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain.

    PubMed

    Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A; Wang, Jun Ming

    2015-07-01

    Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex, and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus, or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase-3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage and

  6. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain

    PubMed Central

    Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A.; Wang, Jun Ming

    2015-01-01

    Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase (MAO) A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase 3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage

  7. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

    PubMed Central

    Jiang, Pei; Zhang, Li-Hong; Cai, Hua-Lin; Li, Huan-De; Liu, Yi-Ping; Tang, Mi-Mi; Dang, Rui-Li; Zhu, Wen-Ye; Xue, Ying; He, Xin

    2014-01-01

    Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function. PMID:25533012

  8. Salivary Alterations in Rats with Experimental Chronic Kidney Disease

    PubMed Central

    Romero, Ana Carolina; Bergamaschi, Cassia Toledo; de Souza, Douglas Nesadal; Nogueira, Fernando Neves

    2016-01-01

    Objective This study aimed to analyze changes in saliva composition and salivary secretion process of rats with chronic kidney disease induced by 5/6 nephrectomy to set the foundation for salivary studies related to CKD. Methods CKD was induced in Wistar rats via 5/6 nephrectomy. Blood and saliva samples were collected from Control, Sham and CKD groups at 8 and 12 weeks after the surgery. Salivation was stimulated via intraperitoneal injections of pilocarpine (1.0 mg/Kg body weight) or isoproterenol (5.0 mg/Kg body weight). Saliva was collected and immediately stored at -80°C until analysis. The salivary flow rate, total protein, amylase and peroxidase activities, and urea concentrations were measured. The blood urea nitrogen (BUN) and serum creatinine concentrations were also evaluated. Results Increases in BUN and serum creatinine concentrations were observed in the CKD groups. Amylase activity was significantly reduced in response to both stimuli in the CKD groups at 8 weeks and increased in the CKD groups at 12 weeks in response to isoproterenol stimulus. The peroxidase activities of the CKD groups were significantly reduced in response to isoproterenol stimulation and were increased at 12 weeks in response to pilocarpine stimulation. Salivary urea was significantly increased in the CKD groups at 8 weeks in response to the isoproterenol stimuli and at 12 weeks in response to both salivary agonists. Conclusions The pattern of alterations observed in this experimental model is similar to those observed in patients and clearly demonstrates the viability of 5/6 nephrectomy as an experimental model in future studies to understand the alterations in salivary compositions and in salivary glands that are elicited by CKD. PMID:26859883

  9. Effect of chronic poisoning with aluminum on the renal handling of phosphate in the rat.

    PubMed

    Mahieu, S; Calvo, M L

    1998-01-16

    The effects of aluminum on renal function and phosphate handling were studied using clearance techniques in chronically-intoxicated rats. Rats were given aluminum hydroxide (80 mg/kg b.w., i.p.), three times per week during 6 months. The phosphate tubular transport capacity was evaluated by determining the maximum tubular transport (TmRPi) and the fractional excretion of phosphate (FE% Pi) during the infusion of phosphate solutions with increasing concentrations (0, 9, 18, 33 mM). Parathyroid gland function was studied using indirect methods: calcemia recovery after EDTA administration and the nephrogenic excretion of cAMP as indicative of renal PTH actions, by RIA. The systemic acid base status was determined and food intake and rat growth were controlled in both groups. No changes were observed in the renal function. Pi reabsorption values per ml glomerular filtration rate (TRPi/GFR microg/ml) for different Pi plasmatic concentrations were distributed following a saturation curve compatible with a saturation kinetics. Aluminum increased TmRPi/GFR in treated animals (T) 76+/-4 as compared with control animals (C) 57+/-7 microg/ml, without a statistical modification in the apparent affinity. The FE% Pi and FE% Na were significantly lower in treated animals than in control animals. There were neither systemic variations in the acid-base balance nor in the Ca and Pi concentrations in plasma. The calcemia recovery following a hypocalcemic stimulus and the nephrogenic excretion of cAMP (T: 44+/-4; C: 91+/-7 pmol/min) were diminished. Considering all these facts, it can be postulated that the aluminum renal effect is associated from a decrease in PTH phosphaturic capacity. Nevertheless, other associated factors like minor phosphate intestinal absorption rate may not be disregarded, even though there were no significant intake variations. PMID:9544698

  10. CHRONIC METHYLPHENIDATE TREATMENT DURING EARLY LIFE IS ASSOCIATED WITH GREATER ETHANOL INTAKE IN SOCIALLY ISOLATED RATS

    PubMed Central

    Gill, Kathryn E; Chappell, Ann; Beveridge, Thomas J R; Porrino, Linda J; Weiner, Jeffrey L

    2014-01-01

    Background Methylphenidate is a stimulant prescribed to treat Attention Deficit Hyperactivity Disorder. Its primary mechanism of action is in the dopamine system, alterations of which are associated with vulnerability to alcohol abuse. There are concerns that juvenile MPH treatment may influence adult drinking behavior. This study examined the interaction of MPH treatment and environmental rearing conditions, which are known to independently influence ethanol (EtOH) drinking behavior, on anxiety-like behavior and vulnerability to alcohol abuse in a juvenile rodent model. Methods Male Sprague Dawley rats were housed in enriched, standard, or isolated conditions for four weeks, starting at postnatal day 21. Rats were concurrently treated with 8 mg/kg/day MPH or saline, delivered via osmotic minipump. Anxiety-like behavior was determined at the end of the treatment session, and 5 weeks later. After MPH treatment, rats were exposed to a two-bottle choice EtOH drinking procedure that lasted three weeks. Results Early life chronic MPH treatment was associated with greater EtOH intake and greater EtOH preference, but only in socially isolated animals. Isolated animals had greater levels of anxiety-like behavior than standard-housed or enriched animals after 4 weeks of exposure to the housing conditions, a difference that persisted even after all animals had been individually housed for an additional 5 weeks and exposed to EtOH. Conclusions These results suggest that early life MPH treatment may increase vulnerability to EtOH drinking in adulthood in a subset of the population. Additionally, this study highlights the importance of early rearing condition for establishing long-lasting behavioral phenotypes. Environmental histories should be considered when prescribing MPH treatment to young children. PMID:25156616

  11. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

    PubMed

    Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

    2016-05-01

    Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease. PMID:26789275

  12. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

    PubMed Central

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-01-01

    Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolomic analysis. Results: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Conclusion: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines. PMID:24632844

  13. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    PubMed Central

    Liu, Ru-Peng; Fang, Ji-Liang; Rong, Pei-Jing; Zhao, Yufeng; Meng, Hong; Ben, Hui; Li, Liang; Huang, Zhan-Xia; Li, Xia; Ma, Ying-Ge; Zhu, Bing

    2013-01-01

    To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA) at the auricular concha region (ACR) of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS), and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. PMID:23431349

  14. Effects of Omega-3 Fatty Acids on Erectile Dysfunction in a Rat Model of Atherosclerosis-induced Chronic Pelvic Ischemia

    PubMed Central

    Kim, Dae Hee; Bae, Jae Hyun

    2016-01-01

    The aim of this study was to investigate whether the omega-3 fatty acids help to improve erectile function in an atherosclerosis-induced erectile dysfunction rat model. A total of 20 male Sprague-Dawley rats at age 8 weeks were divided into three groups: Control group (n = 6, untreated sham operated rats), Pathologic group (n = 7, untreated rats with chronic pelvic ischemia [CPI]), and Treatment group (n = 7, CPI rats treated with omega-3 fatty acids). For the in vivo study, electrical stimulation of the cavernosal nerve was performed and erectile function was measured in all groups. Immunohistochemical antibody staining was performed for transforming growth factor beta-1 (TGF-β1), endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor 1-alpha (HIF-1α). In vivo measurement of erectile function in the Pathologic group showed significantly lower values than those in the Control group, whereas the Treatment group showed significantly improved values in comparison with those in the Pathologic group. The results of western blot analysis revealed that systemically administered omega-3 fatty acids ameliorated the cavernosal molecular environment. Our study suggests that omega-3 fatty acids improve intracavernosal pressure and have a beneficial role against pathophysiological consequences such as fibrosis or hypoxic damage on a CPI rat model, which represents a structural erectile dysfunction model. PMID:27051243

  15. Effects of chronic administration of (+)-amphetamine on maze performance of the rat

    PubMed Central

    Breda, J. B.; Carlini, E. A.; Sader, N. F. A.

    1969-01-01

    1. The influence of (+)-amphetamine, given 1 min after each training session, on the performance of 124 rats in a Lashley III maze was measured every 48 hr. 2. The first three injections of the drug significantly improved the learning ability of naive rats. 3. With prolonged treatment, (+)-amphetamine strongly impaired the maze performance of these rats. 4. The chronic administration of (+)-amphetamine to previously trained rats produced the same adverse effect. 5. Amylobarbitone sodium given to previously trained rats 30 min before the training sessions completely blocked the adverse effect of (+)-amphetamine. 6. (+)-Amphetamine did not produce impairment of performance when given chronically 30 min before training sessions, to previously trained rats. PMID:5343359

  16. The upregulation of acetylcholine release at endplates of alpha-bungarotoxin-treated rats: its dependency on calcium.

    PubMed Central

    Plomp, J J; van Kempen, G T; Molenaar, P C

    1994-01-01

    1. The presynaptic component of an adaptive feedback mechanism leading to increased acetylcholine (ACh) release was studied in endplates of diaphragms from rats treated chronically with alpha-bungarotoxin (alpha BTX). 2. Quantal contents were calculated 'directly' from the amplitude of miniature endplate potentials (MEPPs) and endplate potentials (EPPs) which were recorded after mu-conotoxin treatment to prevent muscle action potentials. 3. In vitro application of the Ca2+ channel blockers nifedipine (10 microM) or omega-conotoxin (40 nM) had no significant effect on the increased quantal content of endplates from alpha BTX-treated rats. 4. At control endplates, in vitro block of presynaptic K+ channels by 5 microM 3,4-diaminopyridine did increase the quantal content to a level which was similar to that found in endplates of alpha BTX-treated rats but also induced a broadening of EPPs, which was not found at endplates after alpha BTX treatment. 5. The difference between quantal contents of alpha BTX-treated and control rats was highly dependent on the [Ca2+]o/[Mg2+]o ratio when [Mg2+]o was fixed at 1 mM. At low [Ca2+]o, the quantal content of endplates from alpha BTX-treated rats was lower than that of controls while at [Ca2+]o in the normal and high range this was reversed. However, changing the [Ca2+]o/[Mg2+]o ratio by means of [Mg2+]o, at a fixed [Ca2+]o of 2 mM, did not influence the relative increase of quantal contents at endplates from alpha BTX-treated rats. Double logarithmic plots of the 'toxin-induced' myasthenia gravis (TIMG) and control quantal content versus [Ca2+]o had an approximately linear part between 0.2 and 1.5 mM [Ca2+]o. The slopes of the TIMG and control lines were 1.81 and 0.96, indicating that the ACh release in TIMG muscles was more sensitive to changes of [Ca2+]o than controls. 6. At normal [Ca2+]o and [Mg2+]o, the depression of EPP amplitude during stimulation of the phrenic nerve at 30-50 Hz was somewhat larger at endplates from alpha

  17. Effect of different chronic intermittent stressors and acetyl-l-carnitine on hypothalamic beta-endorphin and GnRH and on plasma testosterone levels in male rats.

    PubMed

    Bidzinska, B; Petraglia, F; Angioni, S; Genazzani, A D; Criscuolo, M; Ficarra, G; Gallinelli, A; Trentini, G P; Genazzani, A R

    1993-06-01

    Chronic stress affects the reproductive function by modifying the neuroendocrine homeostasis. The aim of the present study was to clarify the neuroendocrine and the gonadal changes following chronic intermittent stress in male rats and the action of a neuroactive drug, acetyl-l-carnitine (ALC). The effect of two different stressors, cold water swimming or ether, on central beta-endorphin (beta-EP) and GnRH contents, and on plasma testosterone levels was investigated. In addition, the response to an acute stress in chronically stressed rats, treated or untreated with ALC (10 mg/day/rat p.o.), was evaluated. The stressors were applied twice a day for 10 days, and rats were killed before, during and after the last stress session. Mediobasal hypothalamus (MBH) beta-EP and GnRH contents, and plasma testosterone levels were evaluated by radioimmunoassay. The following results were obtained: (1) both chronic swimming and ether stress caused a decrease in hypothalamic beta-EP contents; (2) MBH GnRH contents increased after chronic swimming stress but not after ether stress; (3) chronic swimming stress induced a twofold decrease in plasma testosterone levels, while no changes were observed after ether stress; (4) the treatment with ALC prevented the decrease in plasma testosterone levels after chronic swimming stress, and (5) acute stress in chronically stressed animals caused an increase in MBH-beta-EP. The present data showed that chronic swimming stress reduces the reproductive capacity and impairs the capacity to respond to the acute stress and that ALC modulates the hormonal changes to physical stress and prevents the antireproductive effect of chronic cold swimming. PMID:8232773

  18. CHRONIC EXPOSURE OF RATS TO 100-MHZ (CW) RADIOFREQUENCY RADIATION: ASSESSMENT OF BIOLOGICAL EFFECTS

    EPA Science Inventory

    A multidisciplinary approach was employed to assess the possible biological effects of chronic exposure of rats to 100-MHz continuous wave (CW) radiofrequency (RF) radiation. A group of 20 time-bred rats were exposed in a transverse electronmagnetic mode (TEM) transmission line t...

  19. Osteoprotective Effect of Alfacalcidol in Female Rats with Systemic Chronic Inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have shown that alfacalcidol (a hydroxylated form of vitamin D) mitigates glucocorticoid-induced bone loss. This study was undertaken to explore the mechanism and bone microarchitecture of alfacalcidol in rats with systemic chronic inflammation. Thirty female rats (3-month-old) assigned to ...

  20. Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Our previous study demonstrated that green tea polyphenols (GTP) benefit bone health in female rats with chronic inflammation, because of GTP’s antioxidant capacity. The current study further evaluates whether GTP can restore bone microstructure along with related mechanism in rats wit...

  1. Sympathoadrenal responses to acute and chronic hypoxia in the rat.

    PubMed Central

    Johnson, T S; Young, J B; Landsberg, L

    1983-01-01

    The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla

  2. Changes in rat frontal cortex gene expression following chronic cocaine.

    PubMed

    Freeman, Willard M; Brebner, Karen; Lynch, Wendy J; Patel, Kruti M; Robertson, Daniel J; Roberts, David C S; Vrana, Kent E

    2002-07-15

    Alterations in gene expression caused by repeated cocaine administration have been implicated in the long-term behavioral aspects of cocaine abuse. The frontal cortex mediates reinforcement, sensory, associative, and executive functions and plays an important role in the mesocortical dopamine reinforcement system. Repeated cocaine administration causes changes in frontal cortex gene expression that may lead to changes in the behaviors subserved by this brain region. Rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days were screened for changes in relative mRNA abundance in the frontal cortex by cDNA hybridization arrays. To confirm changes, immunoreactive protein was measured (via protein-specific immunoblots) in a second group of identically-treated animals. Protein levels of protein tyrosine kinase 2 (PYK2), activity-regulated cytoskeletal protein (ARC), as well as an antigen related to nerve growth factor I-B (NGFI-B-RA) were shown to be significantly induced after cocaine administration. Levels of NGFI-B mRNA were confirmed by real-time RT-PCR to be increased with cocaine administration. These observations are similar to previously reported cocaine-responsive changes in gene expression but novel to the frontal cortex. This study also validates the use of hybridization arrays for screening of neuronal gene expression changes and the utility of relative protein quantification as a post-hoc confirmation tool. PMID:12117546

  3. Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats.

    PubMed

    Liu, Y-J; Song, G-H; Liu, G T

    2016-08-01

    According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect. PMID:26840892

  4. Chronic Valproate Treatment Blocks D2-like Receptor-Mediated Brain Signaling via Arachidonic Acid in Rats

    PubMed Central

    Ramadan, Epolia; Basselin, Mireille; Taha, Ameer Y.; Cheon, Yewon; Chang, Lisa; Chen, Mei; Rapoport, Stanley I.

    2011-01-01

    Background and Objective Hyperdopaminergic signaling and an upregulated brain arachidonic acid (AA) cascade may contribute to bipolar disorder (BD). Lithium and carbamazepine, FDA-approved for the treatment of BD, attenuate brain dopaminergic D2-like (D2, D3, and D4) receptor signaling involving AA when given chronically to awake rats. We hypothesized that valproate (VPA), with mood-stabilizing properties, would also reduce the D2-like-mediated signaling via AA. Methods An acute dose of quinpirole (1 mg/kg) or saline was administered to unanesthetized rats that had been treated for 30 days with a therapeutically relevant dose of VPA (200 mg/kg/day) or vehicle. Regional brain AA incorporation coefficients, k*, and incorporation rates, Jin, markers of AA signaling and metabolism, were measured by quantitative autoradiography after intravenous [1-14C]AA infusion. Whole brain concentrations of prostaglandin (PG)E2 and thromboxane (TX)B2 also were measured. Results Quinpirole compared to saline significantly increased k* in 40 of 83 brain regions, and increased brain concentrations of PGE2 in chronic vehicle-treated rats. VPA treatment by itself reduced concentrations of plasma unesterified AA and whole brain PGE2 and TXB2, and blocked the quinpirole-induced increments in k* and PGE2. Conclusion These results further support our hypothesis that similar to lithium and carbamazepine, VPA downregulates brain dopaminergic D2-like receptor-signaling involving AA. PMID:21839100

  5. Green tea polyphenols avert chronic inflammation-induced myocardial fibrosis of female rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. Treatments: Fo...

  6. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure

    PubMed Central

    2010-01-01

    Background Accumulating evidence suggests glucagon-like peptide-1 (GLP-1) exerts cardioprotective effects in animal models of myocardial infarction (MI). We hypothesized that chronic treatment with GLP-1 or the exenatide analog AC3174 would improve cardiac function, cardiac remodeling, insulin sensitivity, and exercise capacity (EC) in rats with MI-induced chronic heart failure (CHF) caused by coronary artery ligation. Methods Two weeks post-MI, male Sprague-Dawley rats were treated with GLP-1 (2.5 or 25 pmol/kg/min), AC3174 (1.7 or 5 pmol/kg/min) or vehicle via subcutaneous infusion for 11 weeks. Cardiac function and morphology were assessed by echocardiography during treatment. Metabolic, hemodynamic, exercise-capacity, and body composition measurements were made at study end. Results Compared with vehicle-treated rats with CHF, GLP-1 or AC3174 significantly improved cardiac function, including left ventricular (LV) ejection fraction, and end diastolic pressure. Cardiac dimensions also improved as evidenced by reduced LV end diastolic and systolic volumes and reduced left atrial volume. Vehicle-treated CHF rats exhibited fasting hyperglycemia and hyperinsulinemia. In contrast, GLP-1 or AC3174 normalized fasting plasma insulin and glucose levels. GLP-1 or AC3174 also significantly reduced body fat and fluid mass and improved exercise capacity and respiratory efficiency. Four of 16 vehicle control CHF rats died during the study compared with 1 of 44 rats treated with GLP-1 or AC3174. The cellular mechanism by which GLP-1 or AC3174 exert cardioprotective effects appears unrelated to changes in GLUT1 or GLUT4 translocation or expression. Conclusions Chronic treatment with either GLP-1 or AC3174 showed promising cardioprotective effects in a rat model of CHF. Hence, GLP-1 receptor agonists may represent a novel approach for the treatment of patients with CHF or cardiovascular disease associated with type 2 diabetes. PMID:21080957

  7. Effects of chronic cocaine in rat C6 astroglial cells.

    PubMed

    Badisa, Ramesh B; Goodman, Carl B

    2012-09-01

    Investigations with astroglial cells carry equal importance as those with neurons in drug abuse studies. The present study was aimed to investigate the effect of chronic cocaine administration on cell viability, nitric oxide (NO) production, general respiratory status of mitochondria and total protein levels in rat astroglioma cells after 24 h of treatment. In addition, the effect of cocaine was assessed for 24 h on brine shrimp larvae in order to study their sensitivity to the drug. It was observed that cocaine caused a significant dose-dependent decrease in astroglial cell viability with an LC(50) of 4.717 mM. It was found that cocaine did not induce or inhibit NO production in the cells. Evaluation of mitochondrial dehydrogenase activity in terms of formazan production in astroglial cells indicated that cocaine significantly interfered with the general respiratory status of mitochondria with an ED(50) of 6.153 mM. Furthermore, cocaine was shown to deplete the total protein levels in the cells with an ED(50) of 5.435 mM. In vivo study with brine shrimp larvae showed that these larvae were highly sensitive to cocaine with an ED(50) of 2.41 mM. In summary, our findings suggest that cocaine-induced cytotoxicity in the cells was non-specific. The cumulative effect arising from the significant loss of respiration and total cellular proteins is the cause of astroglial cell death. PMID:22735768

  8. Behavioral and neurochemical effects of chronic L-DOPA treatment on non-motor sequelae in the hemiparkinsonian rat

    PubMed Central

    Eskow Jaunarajs, Karen L.; Dupre, Kristin B.; Ostock, Corinne Y.; Button, Thomas; Deak, Terrence; Bishop, Christopher

    2010-01-01

    Depression and anxiety are prevalent non-motor symptoms that worsen quality of life for Parkinson’s disease (PD) patients. While dopamine (DA) cell loss is a commonly proposed mechanism, the reported efficacy of DA replacement therapy with L-DOPA on affective symptoms is inconsistent. In order to delineate the effects of DA denervation and chronic L-DOPA treatment on affective behaviors, male Sprague-Dawley rats received unilateral 6-OHDA or sham lesions and were treated daily with L-DOPA (12 mg/kg + benserazide, 15 mg/kg, sc) or vehicle (0.9% NaCl, 0.1% ascorbic acid) for 28 days before commencing investigations into anxiety (locomotor chambers, social interaction) and depression-like behaviors (forced swim test) during the OFF phase of L-DOPA. One h after final treatments, rats were killed and striatum, prefrontal cortex, hippocampus, and amygdala were analyzed via high performance liquid chromatography for monoamine levels. In locomotor chambers and social interaction, DA lesions exerted mild anxiogenic effects. Surprisingly, chronic L-DOPA treatment did not improve these effects. While DA lesion reduced climbing behaviors on day 2 of exposure to the forced swim test, chronic L-DOPA treatment did not reverse these effects. Neurochemically, L-DOPA treatment in hemiparkinsonian rats reduced NE levels in the prefrontal cortex, striatum, and hippocampus. Collectively, the present data suggest that chronic L-DOPA therapy in severely DA-lesioned rats does not improve non-motor symptoms and may impair non-dopaminergic processes, indicating that long-term L-DOPA therapy does not exert necessary cause neuroplastic changes for improving affect. PMID:20838211

  9. Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

    PubMed Central

    Mendley, Susan R.; Spyropoulos, Fotios; Counts, Debra R.

    2015-01-01

    We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty. PMID:26101681

  10. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons

    PubMed Central

    2010-01-01

    Background Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P < 0.05), compared to controls (120.3 ± 4 a.u.). Calcium imaging showed significantly enhanced capsaicin (TRPV1 agonist), responses after acute 20 μg/ml oxaliplatin treatment where the second of paired capsaicin responses increased from 80.7 ± 0.6% without oxaliplatin, to 171.26 ± 29% with oxaliplatin, (n = 6 paired t test, P < 0.05); this was reduced to 81.42 ± 8.1% (P < 0.05), by pretretreatment with the cannabinoid CB2 receptor agonist GW 833972. Chronic oxaliplatin treatment also resulted in dose related increases in capsaicin responses. Similarly, second responses to icilin (TRPA1/TRPM8 agonist), were enhanced after acute (143.85 ± 7%, P = 0.004, unpaired t test, n = 3), and chronic (119.7 ± 11.8%, P < 0.05, n = 3) oxaliplatin treatment, compared to control (85.3 ± 1.7%). Responses to the selective TRPM8 agonist WS-12 were not affected. Conclusions Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin. PMID:21106058

  11. Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

    PubMed

    Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

    2016-04-01

    There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats. PMID:25990367

  12. An experimental study on drugs for improving blood circulation and removing blood stasis in treating mild chronic hepatic damage.

    PubMed

    Xie, F; Li, X; Sun, K; Chu, Y; Cao, H; Chen, N; Wang, W; Liu, M; Liu, W; Mao, D

    2001-09-01

    Large and small doses of drugs for improving blood circulation and removing blood stasis were used in model rats to treat mild chronic hepatic damage induced by carbon tetrachloride (CCl4). The results show that large dose of Dang Gui ([symbol: see text] Radix Angelicae Sinensis) and Dan Shen ([symbol: see text] Radix Salviae Miltiorrhizae) (drugs for regulating blood flow) and small dose of Yu Jin ([symbol: see text] Radix Curcumae) and Niu Xi ([symbol: see text] Radix Achyranthis Bidentatae) (drugs for activating blood flow) can significantly elevate the activity of SOD (P < 0.05) and/or lower the T/K ratio, markedly reduce the MDA content (P < 0.05 or P < 0.01) and significantly decrease the activities of ALT and AST (P < 0.05 or P < 0.01), demonstrating that these drugs are effective in combating oxygen free radicals (OFR) in chronic liver damage. On the contrary, large dose of Tu Bie Chong ([symbol: see text] Eupolyphaga seu Steleophaga) and E Zhu ([symbol: see text] Rhizoma Curcumae) (drugs for removing blood stasis) tend to increase the ALT and AST (P < 0.05) activities. The results suggest that the synergism of elevation of the SOD activity and reduction of T/K ratio contributes to the action of drugs for improving blood circulation and removing blood stasis in combating the liver damage induced by CCl4. PMID:11789334

  13. Preventive effect of oral goshajinkigan on chronic oxaliplatin-induced hypoesthesia in rats

    PubMed Central

    Kono, Toru; Suzuki, Yasuyuki; Mizuno, Keita; Miyagi, Chika; Omiya, Yuji; Sekine, Hitomi; Mizuhara, Yasuharu; Miyano, Kanako; Kase, Yoshio; Uezono, Yasuhito

    2015-01-01

    Oxaliplatin, a widely used chemotherapeutic agent, induces peripheral neuropathy that manifests itself as two distinct phases: acute cold hyperesthesia and chronic peripheral hypoesthesia/dysesthesia. The latter is a serious dose-limiting side effect that can often lead to withdrawal of treatment. We have developed a rat model expressing both phases and used the model to investigate the action of goshajinkigan (GJG), a traditional Japanese herbal medicine, which was reported to ameliorate oxaliplatin-induced neuropathy in a placebo-controlled double-blind randomized phase II study. In this study, neuropathy was induced by injection of oxaliplatin twice weekly for 8 wks. The maximum level of cold hyperesthesia was observed at 4 wks with heat hypoesthesia developing later. Microscopy studies revealed atrophy of axons of myelinated sciatic nerve fibers in oxaliplatin-treated rats at 8 wks. Co-administration of GJG ameliorated both abnormal sensations as well as histological damage to the sciatic nerve. A pharmacokinetic study revealed numerous neuroprotective components of GJG that are rapidly absorbed into the blood. GJG and some of its components attenuated the generation of oxaliplatin-induced reactive oxygen species, which is a possible mechanism of oxaliplatin-induced neurotoxicity. The present study provides a useful animal model for oxaliplatin-induced neurotoxicity as well as a promising prophylactic agent. PMID:26542342

  14. Treadmill exercise alleviates chronic mild stress-induced depression in rats

    PubMed Central

    Lee, Taeck-Hyun; Kim, Kijeong; Shin, Mal-Soon; Kim, Chang-Ju; Lim, Baek-Vin

    2015-01-01

    Depression is a major cause of disability and one of the most common public health problems. In the present study, antidepressive effect of treadmill exercise on chronic mild stress (CMS)-induced depression in rats was investigated. For this, sucrose intake test, immunohistochemistry for 5-bromo-2′-deoxyuridine, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Western blot analysis for brain-derived neurotrophic factor, cyclic adenosine monophosphate response element binding protein, and endothelial nitric oxide synthase were conducted. Following adaptation to the animal vivarium and two baseline fluid intake tests, the animals were divided into four groups: the control group, the CMS-induced depression group, the CMS-induced depression and exercise group, and the CMS-induced depression and fluoxetine-treated group. The animals in the CMS groups were exposed to the CMS conditions for 8 weeks and those in the control group were exposed to the control conditions for 8 weeks. After 4 weeks of CMS, the rats in the CMS-induced depression and exercise group were made to run on a motorized treadmill for 30 min once a day for 4 weeks. In the present results, treadmill exercise alleviated CMS-induced depressive symptoms. Treadmill exercise restored sucrose consumption, increased cell proliferation, and decreased apoptotic cell death. The present results suggest the possibility that exercise may improve symptoms of depression. PMID:26730380

  15. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

    PubMed Central

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2015-01-01

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy. PMID:26712750

  16. Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats.

    PubMed Central

    Carmignani, M; Boscolo, P; Artese, L; Del Rosso, G; Porcelli, G; Felaco, M; Volpe, A R; Giuliano, G

    1992-01-01

    Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics. Images PMID:1571292

  17. Sini tang prevents depression-like behavior in rats exposed to chronic unpredictable stress.

    PubMed

    Guo, Jian-You; Huo, Hai-Ru; Li, Lan-Fang; Guo, Shu-Ying; Jiang, Ting-Liang

    2009-01-01

    Sini Tang, a Chinese traditional prescription containing three herbs, has been widely used for Yang-deficiency. Recent clinical studies have shown that Sini Tang could treat and improve depression symptoms, but the mechanisms underlying the antidepressant effect of Sini Tang remains unknown. In rats with chronic unpredictable stress (CUS), we examined the effects of Sini Tang on sucrose preference and open field exploratory behavior. The levels of corticosterone level in plasma and corticotropin-releasing hormone (CRH) mRNA expression in hypothalamus were also measured by enzyme-linked immunosorbent assays (ELISA) and real-time reverse transcription PCR (RT-PCR), respectively. Rats subjected to CUS exhibited decreases in sucrose preference and ambulation in the open field test. These were all attenuated by Sini Tang in a dose-dependent manner. Biochemically, Sini Tang also reversed CUS-induced increases in corticosterone in plasma and CRH mRNA in the hypothalamus. The behavioral effects of the Sini Tang were correlated to the biochemical actions. These results suggest that Sini Tang produces an antidepressant-like effect, which appears to involve CRH in the brain. PMID:19507271

  18. Chronic administration of aqueous extract of Stevia rebaudiana (Bert.) Bertoni in rats: endocrine effects.

    PubMed

    Oliveira-Filho, R M; Uehara, O A; Minetti, C A; Valle, L B

    1989-01-01

    1. The effects of the active principles of S. rebaudiana (SR) on endocrine parameters of male rats were studied upon chronic administrations (60 days) of a concentrated, crude extract of its leaves, starting at prepubertal age (25-30 days old). 2. The following determinations were made: glycemia; serum levels of T3 and T4; available binding sites in thyroid hormone-binding proteins (T3R index); binding of [3H]R 1881 to prostate cytosol; zinc content in prostate, testis, submandibular salivary gland (SMG) and pancreas; water content in testis and prostate. The body weight gain and the final weight of testis, prostate, seminal vesicle, SMG and adrenal were also studied. 3. Results showed that the SR-treated group did not significantly differ from the control group, with exception to the seminal vesicle weight, which fell by about 60%. 4. It is concluded that if the SR extract does have some potential to decrease rat fertility at all, this effect is almost certainly not exerted on the male. PMID:2785472

  19. Treadmill exercise alleviates chronic mild stress-induced depression in rats.

    PubMed

    Lee, Taeck-Hyun; Kim, Kijeong; Shin, Mal-Soon; Kim, Chang-Ju; Lim, Baek-Vin

    2015-12-01

    Depression is a major cause of disability and one of the most common public health problems. In the present study, antidepressive effect of treadmill exercise on chronic mild stress (CMS)-induced depression in rats was investigated. For this, sucrose intake test, immunohistochemistry for 5-bromo-2'-deoxyuridine, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Western blot analysis for brain-derived neurotrophic factor, cyclic adenosine monophosphate response element binding protein, and endothelial nitric oxide synthase were conducted. Following adaptation to the animal vivarium and two baseline fluid intake tests, the animals were divided into four groups: the control group, the CMS-induced depression group, the CMS-induced depression and exercise group, and the CMS-induced depression and fluoxetine-treated group. The animals in the CMS groups were exposed to the CMS conditions for 8 weeks and those in the control group were exposed to the control conditions for 8 weeks. After 4 weeks of CMS, the rats in the CMS-induced depression and exercise group were made to run on a motorized treadmill for 30 min once a day for 4 weeks. In the present results, treadmill exercise alleviated CMS-induced depressive symptoms. Treadmill exercise restored sucrose consumption, increased cell proliferation, and decreased apoptotic cell death. The present results suggest the possibility that exercise may improve symptoms of depression. PMID:26730380

  20. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

    PubMed

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2016-01-01

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy. PMID:26712750

  1. Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory.

    PubMed

    Ribeiro, Leandro Rodrigo; Della-Pace, Iuri Domingues; de Oliveira Ferreira, Ana Paula; Funck, Vinícius Rafael; Pinton, Simone; Bobinski, Franciane; de Oliveira, Clarissa Vasconcelos; da Silva Fiorin, Fernando; Duarte, Marta Maria Medeiros Frescura; Furian, Ana Flávia; Oliveira, Mauro Schneider; Nogueira, Cristina Wayne; Dos Santos, Adair Roberto Soares; Royes, Luiz Fernando Freire; Fighera, Michele Rechia

    2013-09-01

    The methylmalonic acidemia is an inborn error of metabolism (IEM) characterized by methylmalonic acid (MMA) accumulation in body fluids and tissues, causing neurological dysfunction, mitochondrial failure and oxidative stress. Although neurological evidence demonstrate that infection and/or inflammation mediators facilitate metabolic crises in patients, the involvement of neuroinflammatory processes in the neuropathology of this organic acidemia is not yet established. In this experimental study, we used newborn Wistar rats to induce a model of chronic acidemia via subcutaneous injections of methylmalonate (MMA, from 5th to 28th day of life, twice a day, ranged from 0.72 to 1.67 μmol/g as a function of animal age). In the following days (29th-31st) animal behavior was assessed in the object exploration test and elevated plus maze. It was performed differential cell and the number of neutrophils counting and interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the blood, as well as levels of IL-1β, TNF-α, inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in the cerebral cortex were measured. Behavioral tests showed that animals injected chronically with MMA have a reduction in the recognition index (R.I.) when the objects were arranged in a new configuration space, but do not exhibit anxiety-like behaviors. The blood of MMA-treated animals showed a decrease in the number of polymorphonuclear and neutrophils, and an increase in mononuclear and other cell types, as well as an increase of IL-1β and TNF-α levels. Concomitantly, MMA increased levels of IL-1β, TNF-α, and expression of iNOS and 3-NT in the cerebral cortex of rats. The overall results indicate that chronic administration of MMA increased pro-inflammatory markers in the cerebral cortex, reduced immune system defenses in blood, and coincide with the behavioral changes found in young rats. This leads to speculate that, through mechanisms not yet elucidated, the

  2. The effects of chronic L-name and L-arginine administration on beta-adrenergic responsiveness of STZ-diabetic rat atria.

    PubMed

    Dincer, U D; Ozcelikay, A T; Yilmaz, E D

    2000-05-01

    Recent studies have shown that NO acts as a negative inotrope and chronotrop in cardiac muscle. In the present study, we investigated the effects of the chronic administration of L-NAME and L -arginine on 14-week streptozotocin (STZ)-diabetic rat atria. To study these effects, we compared the alterations of inotropic and chronotropic responses to isoprenaline (ISO) on electrically-driven left atria and spontaneously beating right atria. In addition, we compared the blood pressures of rats in all groups. The chronic administration of L-arginine resulted in a significant reduction in blood pressure of the diabetic rats. On the other hand, the chronic nitric oxide synthase inhibition resulted in a significant increase in blood pressure of diabetic animals. To our findings, maximum positive inotropic responses of ISO diminished in STZ-diabetic, L-arginine and L-NAME treated diabetic groups relative to controls but neither the basal contractility of the left atria nor the pD(2)values were altered significantly in all groups. The basal atrial rate and maximum positive chronotropic responses to ISO were found to be significantly lower in treated and untreated diabetic groups, no significant changes were observed in pD(2)values. Our results demonstrate that the changes in inotropic and chronotropic responses in diabetic rat atria were not influenced by the chronic administration of L-arginine and L-NAME treatments. PMID:10753556

  3. Gadolinium chloride, a Kupffer cell inhibitor, attenuates hepatic injury in a rat model of chronic cholestasis.

    PubMed

    Zandieh, Ali; Payabvash, Seyedmehedi; Pasalar, Parvin; Morteza, Afsaneh; Zandieh, Basira; Tavangar, Seyed Mohammad; Dehpour, Ahmad Reza

    2011-11-01

    The aim of the current study was to elucidate the effect of Kupffer cells inhibition on hepatic injury induced by chronic cholestasis. Sprague-Dawley rats underwent bile duct ligation (BDL) or sham operation and were treated with either saline solution or gadolinium chloride (GdCl(3), a specific Kupffer cell inhibitor, 20 mg/kg i.p. daily). Serum and liver samples were collected after 28 days. Direct and total bilirubin concentrations and serum enzyme activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT) increased following BDL (p < 0.01). On the contrary to bilirubin concentrations and AST activity, GdCl(3) partially prevented the elevation in ALP, ALT and GGT enzyme activities (p < 0.05). GdCl(3) alleviated lipid peroxidation (reflected by malondialdehyde [MDA] concentration) and increased the activities of antioxidant enzymes (i.e. catalase and glutathione peroxidase) in liver samples after BDL (p < 0.05). Fibrosis, ductular proliferation and portal inflammation were also scored in liver samples. Among morphological changes appeared following BDL (i.e. marked fibrosis, portal inflammation and ductular proliferation); only ductular proliferation was not alleviated by GdCl(3). Therefore, Kupffer cells inhibition has beneficial effects against the development of hepatic injury induced by chronic cholestasis. PMID:21339256

  4. Treatment of chronic ulcer in diabetic rats with self assembling nanofiber gel encapsulated-polydeoxyribonucleotide

    PubMed Central

    Chen, Xi; Zhou, Wu; Zha, Kun; Liu, Guohui; Yang, Shuhua; Ye, Shunan; Liu, Yi; Xiong, Yuan; Wu, Yongchao; Cao, Faqi

    2016-01-01

    Objective: This study aims to explore the treatment effects of chronic ulcer in diabetic rats with self assembling nanofiber gel encapsulated-polydeoxyribonucleotide. Methods: Diabetic skin ulcer mouse model was established in this study. They were divided into control group, common wound group and infectious wound group. Human embryonic fibroblast cells and vascular endothelial cells were treated with short poly-N-acetyl glucosamine nanofibers and polydeoxyribonucleotide. Their effects on cell proliferation, revascularization and inhibiting infection were detected by RT-PCR, western-blotting, HE staining and immunohistochemical methods respectively. Results: The expression levels of cytokines and angiogenic factors increased in the treatment groups especially in sNAG encapsulated-PDRN group. HE staining results indicated that PDRN, sNAG and sNAG encapsulated-PDRN could improve the wound healing, immunohistochemical results showed that PDRN, sNAG and sNAG encapsulated-PDRN promoted cell proliferation and new vessel formation especially sNAG encapsulated-PDRN. Conclusions: sNAG encapsulated-PDRN may have a potential application in the treatment of diabetic ulcers and chronic wound healing. PMID:27508027

  5. Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model

    PubMed Central

    Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M.

    2016-01-01

    Objectives Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Methods Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. Results A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Conclusion Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring. PMID:26976028

  6. Chronic resveratrol reverses a mild angiotensin II-induced pressor effect in a rat model.

    PubMed

    Gordish, Kevin L; Beierwaltes, William H

    2016-01-01

    Resveratrol is reported to reduce blood pressure in animal models of hypertension, but the mechanisms are unknown. We have shown that resveratrol infusion increases sodium excretion. We hypothesized that chronic ingestion of resveratrol would reduce angiotensin II (Ang II)-induced increases in blood pressure by decreasing oxidative stress and by also decreasing sodium reabsorption through a nitric oxide-dependent mechanism. We infused rats with vehicle or 80 μg Ang II/d over 4 weeks. Vehicle or Ang II-infused rats were individually housed, pair fed, and placed on a diet of normal chow or normal chow plus 146 mg resveratrol/d. Groups included 1) control, 2) resveratrol-fed, 3) Ang II-treated, and 4) Ang II plus resveratrol. Systolic blood pressure was measured by tail cuff. During the 4th week, rats were placed in metabolic caging for urine collection. NO2/NO3 and 8-isoprostane excretion were measured. Ang II increased systolic blood pressure in the 1st week by +14±5 mmHg (P<0.05) in Group 3 and +10±3 mmHg (P<0.05) in Group 4, respectively. Blood pressure was unchanged in Groups 1 and 2. After 4 weeks, blood pressure remained elevated in Group 3 rats with Ang II (+9±3 mmHg, P<0.05), but in Group 4, blood pressure was no longer elevated (+2±2 mmHg). We found no significant differences between the groups in sodium excretion or cumulative sodium balance (18.49±0.12, 17.75±0.16, 17.97±0.17, 18.46±0.18 μEq Na+/7 d in Groups 1-4, respectively). Urinary excretion of NO2/NO3 in the four groups was 1) 1631±207 μmol/24 h, 2) 1045±236 μmol/24 h, 3) 1490±161 μmol/24 h, and 4) 609±17 μmol/24 h. 8-Isoprostane excretion was 1) 63.85±19.39 nmol/24 h, 2) 73.57±22.02 nmol/24 h, 3) 100.69±37.62 nmol/24 h, and 4) 103.00±38.88 nmol/24 h. We conclude that chronic resveratrol supplementation does not blunt Ang II-increased blood pressure, and while resveratrol has mild depressor effects, these do not seem to be due to natriuresis or enhanced renal nitric oxide

  7. Chronic resveratrol reverses a mild angiotensin II-induced pressor effect in a rat model

    PubMed Central

    Gordish, Kevin L; Beierwaltes, William H

    2016-01-01

    Resveratrol is reported to reduce blood pressure in animal models of hypertension, but the mechanisms are unknown. We have shown that resveratrol infusion increases sodium excretion. We hypothesized that chronic ingestion of resveratrol would reduce angiotensin II (Ang II)-induced increases in blood pressure by decreasing oxidative stress and by also decreasing sodium reabsorption through a nitric oxide-dependent mechanism. We infused rats with vehicle or 80 μg Ang II/d over 4 weeks. Vehicle or Ang II-infused rats were individually housed, pair fed, and placed on a diet of normal chow or normal chow plus 146 mg resveratrol/d. Groups included 1) control, 2) resveratrol-fed, 3) Ang II-treated, and 4) Ang II plus resveratrol. Systolic blood pressure was measured by tail cuff. During the 4th week, rats were placed in metabolic caging for urine collection. NO2/NO3 and 8-isoprostane excretion were measured. Ang II increased systolic blood pressure in the 1st week by +14±5 mmHg (P<0.05) in Group 3 and +10±3 mmHg (P<0.05) in Group 4, respectively. Blood pressure was unchanged in Groups 1 and 2. After 4 weeks, blood pressure remained elevated in Group 3 rats with Ang II (+9±3 mmHg, P<0.05), but in Group 4, blood pressure was no longer elevated (+2±2 mmHg). We found no significant differences between the groups in sodium excretion or cumulative sodium balance (18.49±0.12, 17.75±0.16, 17.97±0.17, 18.46±0.18 μEq Na+/7 d in Groups 1–4, respectively). Urinary excretion of NO2/NO3 in the four groups was 1) 1631±207 μmol/24 h, 2) 1045±236 μmol/24 h, 3) 1490±161 μmol/24 h, and 4) 609±17 μmol/24 h. 8-Isoprostane excretion was 1) 63.85±19.39 nmol/24 h, 2) 73.57±22.02 nmol/24 h, 3) 100.69±37.62 nmol/24 h, and 4) 103.00±38.88 nmol/24 h. We conclude that chronic resveratrol supplementation does not blunt Ang II-increased blood pressure, and while resveratrol has mild depressor effects, these do not seem to be due to natriuresis or enhanced renal nitric oxide

  8. Glycemia-dependent Nuclear Factor κB Activation Contributes to Mechanical Allodynia in Rats with Chronic Postischemia Pain

    PubMed Central

    Ross-Huot, Marie-Christine; Laferrière, André; Khorashadi, Mina; Coderre, Terence J.

    2015-01-01

    Background Ischemia-reperfusion injury causes chronic postischemia pain (CPIP), and rats with higher glycemia during ischemia-reperfusion injury exhibit increased allodynia. Glycemia-induced elevation of nuclear factor kappa-B (NFκB) may contribute to increased allodynia. Methods Glycemia during a 3 h ischemia-reperfusion injury was manipulated by: normal feeding; or normal feeding with administration of insulin; dextrose; or insulin/dextrose. In these groups, NFκB was measured in ipsilateral hind paw muscle and spinal dorsal horn by ELISA, and SN50, an NFκB inhibitor, was administered to determine its differential anti-allodynic effects depending on glycemia. Results CPIP fed/insulin rats (12.03 ± 4.9, N = 6) had less allodynia than fed, fed/insulin/dextrose and fed/dextrose rats (6.29 ± 3.37 N = 7, 4.57 ± 3.03 g, N = 6, 2.95 ± 1.10, N = 9), respectively. Compared to fed rats (0.209 ± 0.022, N = 7), NFκB in ipsilateral plantar muscles was significantly lower for fed/insulin rats and significantly higher for fed/dextrose rats (0.152 ± 0.053, N = 6; 0.240 ± 0.057, N = 7, respectively). Furthermore, NFκB in the dorsal horn of fed, fed/insulin/dextrose and fed/dextrose rats (0.293 ± 0.049, N = 6) was significantly higher than in fed/insulin animals (0.267 ± 0.037, N = 6). The anti-allodynic SN50 dose-response curves of CPIP rats in the fed/insulin/dextrose, fed/dextrose and fed conditions exhibited a rightward shift compared to the fed/insulin group. The threshold SN50 dose of CPIP fed/dextrose, fed/insulin/dextrose and fed rats (328.94 ± 92.4, 77.80 ± 44.50 and 24.89 ± 17.20, respectively) was higher than that for fed/insulin rats (4.06 ± 7.04). Conclusions NFκB was activated in a glycemia-dependent manner in CPIP rats. Hypoglycemic rats were more sensitive to SN50 than rats with higher glycemia. The finding that SN50 reduces mechanical allodynia suggests that NFκB inhibitors might be useful for treating postischemia pain. PMID:23695173

  9. Spatial cognition and sexually dimorphic synaptic plasticity balance impairment in rats with chronic prenatal ethanol exposure.

    PubMed

    An, Lei; Zhang, Tao

    2013-11-01

    Prenatal ethanol exposure can lead to long-lasting impairments in the ability of rats to process spatial information, as well as produce long-lasting deficits in long-term potentiation (LTP), a biological model of learning and memory processing. The present study aimed to examine the sexually dimorphic effects of chronic prenatal ethanol exposure (CPEE) on behavior cognition and synaptic plasticity balance (SPB), and tried to understand a possible mechanism by evaluating the alternation of SPB. The animal model was produced by ethanol exposure throughout gestational period with 4 g/kg bodyweight. Offspring of both male and female were selected and studied on postnatal days 36. Subsequently, the data showed that chronic ethanol exposure resulted in birth weight reduction, losing bodyweight gain, microcephaly and hippocampus weight retardation. In Morris water maze (MWM) test, escape latencies were significantly higher in CPEE-treated rats than that in control ones. They also spent much less time in the target quadrant compared to that of control animals in the probe phase. In addition, it was found that there was a more severe impairment in females than that in males after CPEE treatment. Electrophysiological studies showed that CPEE considerably inhibited hippocampal LTP and facilitated depotentiation in males, while significantly enhanced LTP and suppressed depotentiation in females. A novel index, developed by us, showed that the action of CPEE on SPB was more sensitive in females than that in males, suggesting that it might be an effective index to distinguish the difference of SPB impairment between males and females. PMID:24050890

  10. Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

    NASA Astrophysics Data System (ADS)

    Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta

    2015-03-01

    In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (p<0.05). The comparison of the induced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (p<0.001). The largest bone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

  11. A Brain Signature to Differentiate Acute and Chronic Pain in Rats

    PubMed Central

    Guo, Yifei; Wang, Yuzheng; Sun, Yabin; Wang, Jin-Yan

    2016-01-01

    The transition from acute pain to chronic pain entails considerable changes of patients at multiple levels of the nervous system and in psychological states. An accurate differentiation between acute and chronic pain is essential in pain management as it may help optimize analgesic treatments according to the pain state of patients. Given that acute and chronic pain could modulate brain states in different ways and that brain states could greatly shape the neural processing of external inputs, we hypothesized that acute and chronic pain would show differential effects on cortical responses to non-nociceptive sensory information. Here by analyzing auditory-evoked potentials (AEPs) to pure tones in rats with acute or chronic pain, we found opposite influences of acute and chronic pain on cortical responses to auditory inputs. In particular, compared to no-pain controls, the N100 wave of rat AEPs was significantly enhanced in rats with acute pain but significantly reduced in rats with chronic pain, indicating that acute pain facilitated cortical processing of auditory information while chronic pain exerted an inhibitory effect. These findings could be justified by the fact that individuals suffering from acute or chronic pain would have different vigilance states, i.e., the vigilance level to external sensory stimuli would be increased with acute pain, but decreased with chronic pain. Therefore, this auditory response holds promise of being a brain signature to differentiate acute and chronic pain. Instead of investigating the pain system per se, the study of pain-induced influences on cortical processing of non-nocicpetive sensory information might represent a potential strategy to monitor the progress of pain chronification in clinical applications. PMID:27199727

  12. The Effect of Chronic Mild Stress and Imipramine on the Markers of Oxidative Stress and Antioxidant System in Rat Liver.

    PubMed

    Duda, Weronika; Curzytek, Katarzyna; Kubera, Marta; Iciek, Małgorzata; Kowalczyk-Pachel, Danuta; Bilska-Wilkosz, Anna; Lorenc-Koci, Elżbieta; Leśkiewicz, Monika; Basta-Kaim, Agnieszka; Budziszewska, Bogusława; Regulska, Magdalena; Ślusarczyk, Joanna; Gruca, Piotr; Papp, Mariusz; Maes, Michael; Lasoń, Władysław; Antkiewicz-Michaluk, Lucyna

    2016-08-01

    Liver abnormalities have been reported to occur in up to 20 % of patients on a long-term therapy with the tricyclic antidepressant drug imipramine (IMI). The mechanism involved in this IMI-induced process is unknown but a contribution of oxidative stress is highly likely. Chronic mild stress (CMS) is widely used for modeling depressive-like behavior in rats. In the present study, we examined the effects of CMS and chronic IMI treatment, applied alone or in combination, on the levels of oxidative stress markers, such as reactive oxygen species (ROS), malondialdehyde (MDA), non-protein sulfhydryl groups, and sulfane sulfur as well as on activities of key antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase in the rat liver. Administration of IMI for 5 weeks to rats subjected to CMS resulted in a gradual significant reduction of anhedonia measured by sucrose intake, in a majority of animals (CMS IMI-reactive, CMS IMI-R), although about 20 % of rats did not respond to the IMI treatment (CMS IMI non-reactive, CMS IMI-NR). CMS-induced hepatic oxidative stress, estimated by increased ROS and MDA concentrations, was not prevented by the IMI administration, moreover, in CMS IMI-NR animals, the level of the marker of lipid peroxidation, i.e., MDA was increased in comparison to CMS-subjected rats and activity of antioxidant enzymes (GPx and CAT) was decreased compared to IMI-treated rats. The clinical significance of this observation remains to be established. PMID:26961706

  13. Treating Interstitial Cystitis/Bladder Pain Syndrome as a Chronic Disease

    PubMed Central

    Bosch, Philip C; Bosch, David C

    2014-01-01

    The management of interstitial cystitis/bladder pain syndrome (IC/BPS) is both frustrating and difficult. The etiology is uncertain and there is no definitive treatment. Consequently, both patients and doctors tend to be unhappy and unsatisfied with the quality of care. The American Urological Association (AUA) provides a guideline for the diagnosis and treatment of IC/BPS. Recommended first-line treatments include patient education, self-care practices, behavior modifications, and stress management. Management of IC/BPS may be also improved if both patients and doctors treat this condition as a chronic disease. This article reviews the AUA first-line treatments for IC/BPS and considers the benefits of treating this condition as a chronic disease. PMID:25009448

  14. The use of generics to treat chronic hepatitis C: not quite ready for the big stage.

    PubMed

    Sarpel, Dost; Dieterich, Douglas

    2016-07-01

    Recently developed direct acting antivirals have been highly effective in treating patients with chronic hepatitis C infection. Due to their expense, there has been development of generic formulations of these medications in many countries. However, there has been controversy regarding the bioequivalence of generics when compared to brand name medications. Inactive ingredients, which may differ in generic medications, can alter the bioequivalence of the active ingredient as well as provoke intolerance or confusion among patients. There is also concern regarding the quality control and assessment of the manufacturing process of generics. When taken together these issues have the potential to lead to treatment failure. The use of generics to treat chronic hepatitis C will remain controversial, until these issues are adequately addressed. PMID:27306304

  15. Chronic omega-3 supplementation in seizure-prone versus seizure-resistant rat strains: a cautionary tale.

    PubMed

    Gilby, K L; Jans, J; McIntyre, D C

    2009-10-20

    Several studies have shown fatty acid supplementation to be efficacious in the treatment of attention deficit hyperactivity disorder/autism spectrum disorder (ADHD/ASD) and epilepsy. Interestingly, rats bred to be seizure-prone (Fast), unlike those bred for seizure-resistance (Slow), naturally exhibit behaviors and physiology reminiscent of ADHD/ASD in humans, suggesting a fundamental link between seizure disposition and these developmental disorders. To determine whether chronic omega-3 supplementation might ameliorate ADHD-like behaviors in the seizure-prone rat strain and/or alter natural predispositions for or against seizure in either strain, Fast and Slow weanlings were maintained on a control or omega-3-supplemented diet. As adults, rats were tested in paradigms known to elicit ADHD-like behaviors from Fast rats and then kindled from the amygdala to assess relative seizure disposition. While omega-3 supplementation did not significantly alter the relative hyperactivity, learning deficits or heightened seizure sensitivity naturally exhibited by Fast rats, it dramatically reduced their impulsivity to Slow-like levels. In contrast, typical behavioral patterns in Slow rats were largely unaffected by omega-3 supplementation yet their proclivity for seizure was greatly increased. This heightened vulnerability to seizure in Slow rats was paralleled by a drop in circulating plasma non-esterified fatty acids (NEFA) to match levels normally observed in Fast rats. These findings suggest a delicate balance between seizure predisposition and ADHD-like behaviors that can be influenced by omega-3 treatment. Further, a relationship between circulating NEFA levels and seizure susceptibility has surfaced that advocates caution when treating different genetic backgrounds with omega-3 fatty acids. PMID:19596053

  16. Chronic variable stress prevents amphetamine-elicited 50-kHz calls in rats with low positive affectivity.

    PubMed

    Kõiv, Kadri; Metelitsa, Mait; Vares, Marten; Tiitsaar, Kai; Raudkivi, Karita; Jaako, Külli; Vulla, Kaspar; Shimmo, Ruth; Harro, Jaanus

    2016-04-01

    The relationship between stress response and positive affective states is thought to be bidirectional: whilst stress can lead to a blunted hedonic response, positive affect reduces the negative effects of stress. We have previously shown that persistently high positive affectivity as measured by 50-kHz ultrasonic vocalizations (USVs) is protective against chronic variable stress (CVS). The present study examined the effect of CVS on 50-kHz USVs elicited by amphetamine administration, simultaneously considering the stable inter-individual differences in positive affectivity. Forty juvenile male Wistar rats were categorised as of high (HC) or low (LC) positive affectivity based on their 50-kHz USV response to imitation of rough-and-tumble play ('tickling'). As adults, the rats were subjected to four weeks of CVS, after which D-amphetamine was administered in five daily doses followed by a challenge dose (all 1mg/kg IP) nine days later. CVS reduced sucrose preference in LC-rats only. After CVS, amphetamine-elicited 50-kHz USVs were significantly reduced in LC-rats, the effect of stress in HC-rats being smaller and less consistent. In previously stressed and amphetamine-treated LC-rats, locomotor response to amphetamine was attenuated. In stressed LC-rats, DOPAC levels and dopamine turnover were increased in striatum after amphetamine treatment, and dopamine D1 receptor levels were upregulated in nucleus accumbens. LC-rats had lower isoleucine levels in frontal cortex. These results show that stress-related changes in response to amphetamine are dependent on inter-individual differences in positive affectivity both at neurochemical and behavioural levels, and further support the notion of higher vulnerability of animals with low positive affect. PMID:26951611

  17. Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in rats: In vivo and ex vivo studies

    PubMed Central

    2010-01-01

    Background The present study was designed to examine the effect of chronic treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2 diabetes mellitus for its insulin sensitizing effects - on the Leydig cell steroidogenic capacity and expression of the steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc) in normal adult rats. Methods Twelve adult male Wistar rats were treated with rosiglitazone (5 mg/kg) administered by gavage for 15 days. Twelve control animals were treated with the vehicle. The ability of rosiglitazone to directly affect the production of testosterone by Leydig cells ex vivo was evaluated using isolated Leydig cells from rosiglitazone-treated rats. Testosterone production was induced either by activators of the cAMP/PKA pathway (hCG and dbcAMP) or substrates of steroidogenesis [22(R)-hydroxy-cholesterol (22(R)-OH-C), which is a substrate for the P450scc enzyme, and pregnenolone, which is the product of the P450scc-catalyzed step]. Testosterone in plasma and in incubation medium was measured by radioimmunoassay. The StAR and P450scc expression was detected by immunocytochemistry. Results The levels of total circulating testosterone were not altered by rosiglitazone treatment. A decrease in basal or induced testosterone production occurred in the Leydig cells of rosiglitazone-treated rats. The ultrastructural and immunocytochemical analysis of Leydig cells from rosiglitazone-treated rats revealed cells with characteristics of increased activity as well as increased StAR and P450scc expression, which are key proteins in androgen biosynthesis. However, a number of rosiglitazone-treated cells exhibited significant mitochondrial damage. Conclusion The results revealed that the Leydig cells from rosiglitazone-treated rats showed significant reduction in testosterone production under basal, hCG/dbcAMP- or 22 (R)-OH-C/pregnenolone-induced conditions, although increased labeling of St

  18. The effect of acute and chronic hypoxia on thoracic gas volume in anaesthetized rats.

    PubMed Central

    Barer, G R; Herget, J; Sloan, P J; Suggett, A J

    1978-01-01

    1. Thoracic gas volume at end expiration (functional residual capacity, FRC) was measured in chronically and acutely hypoxic anaesthetized rats by a plethysmograph method. 2. FRC, measured during air breathing, was 34-62% larger in rats which had been kept in an environmental chamber in 8, 10 or 12% O2 for 3 weeks than in littermate controls. FRC returned to normal after the rats had returned to air for 9 days. There was no constant difference in the pattern of breathing between control and chronically hypoxic rats. 3. Pressure-volume curves measured post mortem showed no difference in the volume of the lung at 25 cm H2O pressure or in the compliance of the lung between chronically hypoxic and control rats. Thus there was no gross mechanical change in the lung to account for the increase in FRC. 4. Acute hypoxia caused by breathing 12% O2 increased FRC in control but not in chronically hypoxic rats. The increase in FRC in control rats was abolished by combined blockade of the vagus nerves and carotid bodies (with procaine) but not by vagal blockade alone. 5. The combined vagal and carotid body blockade reduced FRC significantly in rats which had been in 10% O2 for 3 days but not in those which had been in 10% O2 for 21 days. 6. Lung area measured from radiographs was not reduced by a muscle relaxant in chronically hypoxic rats. Electromyograms from anterior intercostal muscles and the diaphragm showed no electrical activity in expiration in chronically hypoxic rats which might indicate an active muscular basis for their increased FRC. However when FRC was raised by acute hypoxia in control animals there was also no increase in electrical activity in expiration which could have explained their increase in lung volume. 7. We concluded that the increase in FRC during acute hypoxia in control rats was probably due to a reflex from the carotid body. The increase in FRC in chronically hypoxic rats, which was present while they breathed air, may have had an active

  19. Clinical Impact and Evidence Base for Physiotherapy in Treating Childhood Chronic Pain

    PubMed Central

    Amaria, Khush; Campbell, Fiona; McGrath, Patricia A.

    2011-01-01

    ABSTRACT Purpose: As part of the special series on pain, our objectives are to describe the key features of chronic pain in children, present the rationale for interdisciplinary treatment, report a case study based on our biopsychosocial approach, and highlight the integral role of physiotherapy in reducing children's pain and improving function. We also evaluate the evidence base supporting physiotherapy for treating chronic neuropathic pain in children. Summary of Key Points: Chronic pain affects many children and adolescents. Certain challenging pain conditions begin primarily during adolescence and disproportionately affect girls and women. Children with these conditions require an interdisciplinary treatment programme that includes physiotherapy as well as medication and/or psychological intervention. Converging lines of evidence from cohort follow-up studies, retrospective chart reviews, and one randomized controlled trial support the effectiveness of physiotherapy within an interdisciplinary programme for treating children with chronic pain. Conclusions: Evidence-based practice dictates that health care providers adopt clear guidelines for determining when treatments are effective and for identifying children for whom such treatments are most effective. Thus, additional well-designed trials are required to better identify the specific physiotherapy modalities that are most important in improving children's pain and function. PMID:22210976

  20. Treating histologically mild chronic hepatitis C: monotherapy, combination therapy, or tincture of time?

    PubMed

    Levine, R A

    1998-08-15

    The recent National Institutes of Health Consensus Conference on hepatitis C solidified the justification for a selective approach to treatment. Nevertheless, the high profile of chronic hepatitis C has led to a sense of urgency about treating "all-comers" and thus has caused the variable natural history of this disease to be overlooked. The debate about whom to treat has failed to focus attention on the alternative approach of waiting for better emerging therapies for the subset of patients with histologically mild chronic hepatitis C. Practitioners should be more confident about postponing treatment in less symptomatic patients if liver biopsy specimens show no more than grade 1 necroinflammatory activity or stage 1 fibrosis. Patients with these lesions, in the absence of clinical signs of advancing disease, are much less likely than patients with higher grades or stages to progress to cirrhosis. A "cure" for chronic hepatitis C remains elusive. End points of treatment depend on the achievement of sustained clearance of serum hepatitis C virus RNA, which is influenced, in turn, by the patient's viral replication and immune balance. Treatment of histologically mild chronic hepatitis C may ultimately mimic that of HIV infection. PMID:9729187

  1. Nurse case management program of chronic pain patients treated with methadone.

    PubMed

    Lamb, Louise; Pereira, John Xavier; Shir, Yoram

    2007-09-01

    Methadone treatment in chronic pain patients is still limited owing to misconceptions about addiction, safety, and its unique pharmacokinetic and pharmacodynamic properties. Nevertheless, patients with chronic noncancer pain are frequently treated with methadone at our Pain Centre either as the first opioid of choice, for specific pain conditions, or as a second-line opioid in patients developing tolerance or intractable side effects with other opioids. The aim of this study was to examine whether a nurse case management program of chronic pain patients treated with methadone is feasible and safe in trying to improve patients' care in an ambulatory setting. This program consisted of three phases: initial primary education session, telephone follow-up during methadone titration, and a subsequent maintenance period. The nurse case manager functioned autonomously and when required reported to and consulted the physician. The study included 75 subjects and was done over a nine-month period by completing follow-up questionnaires for every call. Of a total of 194 recorded calls, 41% were unscheduled. Forty-four percent of phone calls resulted in a methadone increase and 11% led to a decrease or cessation of methadone. No patients developed serious morbidity or mortality. Fifty-seven percent of patients were either satisfied or very satisfied with their treatment. A nurse-led case management program of methadone in chronic pain patients can improve patient care in an ambulatory setting. PMID:17723930

  2. Beneficial effects of desipramine on cognitive function of chronically stressed rats are mediated by alpha1-adrenergic receptors in medial prefrontal cortex

    PubMed Central

    Bondi, Corina O.; Jett, Julianne D.; Morilak, David A.

    2010-01-01

    Chronic stress is a risk factor for many psychopathological conditions, including depression and anxiety disorders. Cognitive impairments associated with prefrontal cortical dysfunction are a major component of such illnesses. Using an attentional set shifting test (AST), we have previously shown that elevating noradrenergic activity in rat medial prefrontal cortex (mPFC) can facilitate cognitive set-shifting, and that chronic unpredictable stress (CUS) caused set-shifting deficits. It is not known, however, if noradrenergic modulatory function is compromised by chronic stress, perhaps contributing to the stress-induced cognitive deficit. Thus, the first study investigated whether acutely elevating noradrenergic activity in mPFC still enhances cognitive function after chronic stress. As previously demonstrated, CUS impaired cognitive set-shifting on the AST. This deficit was abolished by acute systemic administration of the α2-adrenergic autoreceptor antagonist, atipamezole. Microdialysis revealed no differences in extracellular norepinephrine (NE) levels in mPFC of CUS-exposed and unstressed control rats at baseline or during behavioral testing, and comparable increases after atipamezole. In the second experiment, rats were treated chronically with the selective NE reuptake blocker, desipramine, during the CUS treatment through behavioral testing. Again, CUS impaired cognitive set-shifting in vehicle-treated rats, and chronic desipramine treatment prevented such deficits. Acute blockade of post-synaptic α1-adrenergic receptors in mPFC prior to testing blocked the beneficial effect of desipramine on cognitive set-shifting. These results suggest that desipramine restores cognitive set-shifting capability that has been compromised by chronic stress by activating α1-adrenergic receptors in the mPFC. Thus, noradrenergic modulatory capability in mPFC remains intact after CUS, and this represents one possible substrate by which antidepressants may exert their

  3. Effects of Chronic Electroacupuncture on Depression- and Anxiety-Like Behaviors in Rats with Chronic Neuropathic Pain

    PubMed Central

    Li, Qian; Yue, Na; Liu, Shen-Bin; Wang, Zhi-Fu; Mi, Wen-Li; Jiang, Jian-Wei; Wu, Gen-Cheng; Yu, Jin; Wang, Yan-Qing

    2014-01-01

    Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints “Bai-Hui” (GV20) and unilateral “Yang-Ling-Quan” (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus. PMID:24795763

  4. Middle cerebral artery alterations in a rat chronic hypoperfusion model

    PubMed Central

    Márquez-Martín, Ana; Jiménez-Altayó, Francesc; Dantas, Ana P.; Caracuel, Laura; Planas, Anna M.

    2012-01-01

    Chronic cerebral hypoperfusion (CHP) induces microvascular changes that could contribute to the progression of vascular cognitive impairment and dementia in the aging brain. This study aimed to analyze the effects of CHP on structural, mechanical, and myogenic properties of the middle cerebral artery (MCA) after bilateral common carotid artery occlusion (BCCAO) in adult male Wistar rats. Sham animals underwent a similar surgical procedure without carotid artery (CA) ligation. After 15 days of occlusion, MCA and CA were dissected and MCA structural, mechanical, and myogenic properties were assessed by pressure myography. Collagen I/III expression was determined by immunofluorescence in MCA and CA and by Western blot in CA. mRNA levels for 1A1, 1A2, and 3A1 collagen subunits were quantified by quantitative real-time PCR in CA. Matrix metalloproteinase (MMP-1, MMP-2, MMP-9, and MMP-13) and hypoxia-inducible factor-1α (HIF-1α) protein expression were determined in CA by Western blot. BCCAO diminished cross-sectional area, wall thickness, and wall-to-lumen ratio. Nevertheless, whereas wall stress was increased, stiffness was not modified and myogenic response was diminished. Hypoperfusion triggered HIF-1α expression. Collagen I/III protein expression diminished in MCA and CA after BCCAO, despite increased mRNA levels for 1A1 and 3A1 collagen subunits. Therefore, the reduced collagen expression might be due to proteolytic degradation, since the expression of MMP-1 and MMP-9 increased in the CA. These data suggest that BCCAO induces hypotrophic remodeling by a mechanism that involves a reduction of collagen I/III in association with increased MMP-1 and MMP-9 and that decreases myogenic tone in major arteries supplying the brain. PMID:22096118

  5. Chronic lead poisoning magnifies bone detrimental effects in an ovariectomized rat model of postmenopausal osteoporosis.

    PubMed

    Lee, Ching Ming; Terrizzi, Antonela Romina; Bozzini, Clarisa; Piñeiro, Adriana Emilce; Conti, María Inés; Martínez, María Pilar

    2016-01-01

    Lead (Pb) is a persistent environmental contaminant that is mainly stored in bones being an important source of endogenous lead exposure during periods of increased bone resorption as occurs in menopause. As no evidence exists of which bone biomechanical properties are impaired in those elderly women who had been exposed to Pb during their lifetime, the aim of the present study is to discern whether chronic lead poisoning magnifies the deterioration of bone biology that occurs in later stages of life. We investigated the effect of Pb in the femora of ovariectomized (OVX) female Wistar rats who had been intoxicated with 1000 ppm of Pb acetate in drinking water for 8 months. Structural properties were determined using a three-point bending mechanical test, and geometrical and material properties were evaluated after obtaining the load/deformation curve. Areal Bone Mineral Density (BMD) was estimated using a bone densitometer. Femoral histomorphometry was carried out on slices dyed with H&E (Hematoxylin and Eosin). Pb and OVX decreased all structural properties with a higher effect when both treatments were applied together. Medullar and cortical area of femurs under OVX increased, allowing the bone to accommodate its architecture, which was not observed under Pb intoxication. Pb and OVX significantly decreased BMD, showing lead treated ovariectomized rats (PbOVX) animals the lowest BMD levels. Trabecular bone volume per total volume (BV/TV%) was decreased in OVX and PbOVX animals in 54% compared to the control animals (p<0.001). Pb femurs also showed 28% less trabeculae than the control (p<0.05). We demonstrated that Pb intoxication magnifies the impairment in bone biomechanics of OVX rats with a consequent enhancement of the risk of fracture. These results enable the discussion of the detrimental effects of lead intoxication in bone biology in elderly women. PMID:26422677

  6. Growth is compromised in rats fed ozone-treated casein

    SciTech Connect

    Kasai, T.; Iwashita, A.; Kiriyama, S. )

    1993-05-01

    Modified casein containing few phenylalanine residues and no other aromatic amino acid residues was obtained by ozonolysis of casein. Although 68% of phenylalanine was decomposed by ozonolysis of casein, ozonolysis caused alterations beyond the destruction of aromatic amino acid residues. Nearly the same degree of decomposition of amino acid residues was observed in casein ozonated after predigestion by pepsin. Rats were fed diets containing 8% casein supplemented with methionine and aspartic acid (8C-AA), 8% ozonated casein supplemented with methionine and free amino acids lost by ozonolysis (8OC-AA), 8% casein ozonated after predigestion by pepsin supplemented with methionine and free amino acids lost during preparation (8POC-AA) or 7.6% amino acid mixture. The growth of rats fed the 8OC-AA diet was significantly lower than that of those fed 8C-AA or 7.6AA diets. The growth of rats fed the 8POC-AA diet was comparable to growth of those fed 8OC-AA. The biological values of the 8OC-AA and 8POC-AA were comparable to that of 8C-AA, but true digestibility of 8OC-AA was significantly lower than that of 8C-AA. True digestibility 8POC-AA was significantly improved relative to 8OC-AA, but the growth of rats fed 8POC-AA was not improved relative to that of those fed 8OC-AA. Kidney and cecum weights of rats fed 8OC-AA and 8POC-AA were significantly heavier than those of the 8C-AA-fed group, although histopathological examination of kidneys showed no deterioration compared to that of the 8C-AA-fed group.

  7. Molecular basis of bilirubin UDP-glucuronosyltransferase induction in spontaneously diabetic rats, acetone-treated rats and starved rats.

    PubMed Central

    Braun, L; Coffey, M J; Puskás, F; Kardon, T; Nagy, G; Conley, A A; Burchell, B; Mandl, J

    1998-01-01

    The co-ordinated induction of several hepatic drug-metabolizing enzymes is a common feature in the regulation of drug biotransformation under normal and pathological conditions. In the present study the activity and expression of bilirubin UDP-glucuronosyltransferase (UGT1A1) were investigated in livers of BioBreeding/Worcester diabetic, fasted and acetone-treated rats. Bilirubin glucuronidation was stimulated by all three treatments; this was correlated with an increase in the UGT1A1 protein concentration in hepatic microsomes. Transcriptional induction of UGT1A1 was also observed in diabetes and starvation but not with acetone treatment, which apparently caused translational stabilization of the enzyme protein. The hormonal/metabolic alterations in diabetes and starvation might be a model for postnatal development. The sudden interruption of maternal glucose supply signals the enhanced expression of UGT1A1, giving a novel explanation for the physiological induction of bilirubin glucuronidation in newborn infants. PMID:9841869

  8. 5-HT2A-receptors in the orbitofrontal cortex facilitate reversal learning and contribute to the beneficial cognitive effects of chronic citalopram treatment in rats

    PubMed Central

    Furr, Ashley; Lapiz-Bluhm, M. Danet; Morilak, David A.

    2012-01-01

    Chronic stress is a risk factor for depression, and chronic stress can induce cognitive impairments associated with prefrontal cortical dysfunction, which are also major components of depression. We have previously shown that 5-weeks of chronic intermittent cold (CIC) stress induced a reversal learning deficit in rats, associated with reduced serotonergic transmission in the orbitofrontal cortex (OFC), that was restored by chronic treatment with a selective serotonin reuptake inhibitor (SSRI). However, the mechanisms underlying the beneficial cognitive effects of chronic SSRI treatment are currently unknown. Thus, the purpose of the present study was to investigate the potential modulatory influence specifically of 5-HT2A-receptors in the OFC on reversal learning, and their potential contribution to the beneficial cognitive effects of chronic SSRI treatment. Bilateral microinjections of the selective 5-HT2A-receptor antagonist, MDL 100,907 into OFC (0.02–2.0 nmoles) had a dose-dependent detrimental effect on a reversal learning task, suggesting a facilitatory influence of 5-HT2A-receptors in the OFC. In the next experiment, rats were exposed to 5-weeks of CIC stress, which compromised reversal learning, and treated chronically with the SSRI, citalopram (20 mg/kg/day) during the final 3 weeks of chronic stress. Chronic CIT treatment improved reversal learning in the CIC-stressed rats, and bilateral microinjection of MDL 100,907 (0.20 nmoles, the optimal dose from the preceding experiment) into OFC once again had a detrimental effect on reversal learning, opposing the beneficial effect of citalopram. We conclude that 5-HT2A-receptors in the OFC facilitate reversal learning, and potentially contribute to the beneficial cognitive effects of chronic SSRI treatment. PMID:22008191

  9. A Chronic Oral Toxicity Study of Marine Collagen Peptides Preparation from Chum Salmon (Oncorhynchus keta) Skin Using Sprague-Dawley Rat

    PubMed Central

    Liang, Jiang; Pei, Xin-Rong; Zhang, Zhao-Feng; Wang, Nan; Wang, Jun-Bo; Li, Yong

    2011-01-01

    Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet. PMID:22363218

  10. Chronic exposure to mercuric chloride during gestation affects sensorimotor development and later behaviour in rats.

    PubMed

    Chehimi, Latifa; Roy, Vincent; Jeljeli, Mustapha; Sakly, Mohsen

    2012-09-01

    The current study was performed to assess the effects of inorganic mercury (mercuric chloride - HgCl(2)) on the development of offsprings from intoxicated-mother during pregnancy. In this respect, pregnant rats were chronically treated with HgCl(2) at 50 ppm (Hg50) and 100 ppm (Hg100) in drinking water. After parturition, maternal behaviour was recorded during 30 min at 1st to 6th postnatal day (Pnd). The development of their offspring was studied during the first 17 days after birth. Sensorimotor development of pups was measured by different tests: rooting reflex, vibrissae placing response, righting reflex, negative geotaxis, suspension test and rotating grid. Two month after birth, the anxiety of offspring was tested using the elevated plus maze test. Our results indicate that mercury treatment significantly reduced the nursing and increased the time out the nest or drinking and eating. We also showed that prenatal exposure to HgCl(2) decreased weight gain. Importantly, the rooting reflex, the development of the vibrissae placing response, the righting reflex, the grip strength and the negative geotaxis behaviour were delayed in the offspring of dams treated with Hg50, the delay being more severe with Hg100. We also found a decrease in anxiety in adulthood. Cross-fostering test support the direct toxic effects of mercury. PMID:22705860

  11. Effects of glutamate and {alpha}2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats

    SciTech Connect

    Alam, Mesbah Danysz, Wojciech; Schmidt, Werner Juergen; Dekundy, Andrzej

    2009-10-15

    Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD). The aim of this study was to elucidate whether neramexane (NMDA, nicotinic {alpha}9/{alpha}10 and 5-HT{sub 3} receptor antagonist), idazoxan ({alpha}{sub 2}-adrenoceptor antagonist) or 2-methyl-6-(phenyl-ethyl)-pyrimidine (MPEP, metabotropic glutamate receptor 5 antagonist) prevents rotenone-induced parkinsonian-like behaviours and neurochemical changes in rats. Rotenone (2.5 mg/kg i.p. daily) was administered over 60 days together with saline, neramexane (5 mg/kg i.p., b.i.d.), idazoxan (2.5 mg/kg i.p., b.i.d.) or MPEP (2.5 mg/kg i.p., b.i.d.). The same doses of neramexane, idazoxan and MPEP were administered to rats treated with vehicle instead of rotenone. Treatment-related effects on parkinsonian-like behaviours, such as hypokinesia/rigidity and locomotor activity, were evaluated. Moreover, concentrations of dopamine, serotonin and their metabolites were measured in rats from each experimental group. Over the 60-day treatment period, the rotenone + saline treated animals developed hypokinesia, expressed as an increase in the bar and grid descent latencies in the catalepsy test, and a decrease in locomotor activity. Neramexane and idazoxan partially prevented the development of catalepsy in rotenone-treated rats. Co-administration of MPEP with rotenone resulted only in a decrease in descent latency in the grid test on day 60. Chronic rotenone treatment reduced concentrations of dopamine and serotonin in the anterior striatum, which was blocked by co-treatment with neramexane or idazoxan but not with MPEP. Only neramexane treatment blocked the rotenone-induced decrease in dopamine levels in the substantia nigra pars compacta. In conclusion, neramexane and idazoxan counteracted to some extent the development of parkinsonian symptoms and neurochemical alterations in the rotenone model of Parkinson's disease.

  12. The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior.

    PubMed

    Ferraz, Marcia M D; Quintella, Suelen L; Parcial, André L N; Ferraz, Marcos R

    2016-01-01

    Ferraz MMD, Quintella SL, Parcial ALN, Ferraz MR. The effects of sildenafil citrate and L-NAME on male rat sexual behaviour. PHARMACOL BIOCHEM BEHAV. Erectile dysfunction (ED) affects up to 50% of men between 40 and 70years of age. Significant advances in the pharmacological treatment of ED occurred in recent years, most notably the introduction of the first oral selective phosphodiesterase type-5 inhibitor, sildenafil. This study investigated the effectiveness of chronic oral treatment with L-NAME in rats as an experimental model of erectile dysfunction to evaluate new pharmacological agents that affect the sexual response. The effects of chronic oral L-NAME treatment, separately or in combination with sildenafil, on the sexual behaviour of male rats were evaluated. Filtered water was used as a control. Acute administration of L-NAME did not alter the sexual response compared with control, but sildenafil administration facilitated sexual behaviour after acute and chronic administration. Chronic L-NAME treatment inhibited motivational and consummatory measures of male rat sexual behaviour. Sildenafil prevented the inhibitory effects of L-NAME. The present results confirm that chronic oral treatment with a nitric oxide synthase inhibitor may be a relevant peripheral ED model to evaluate the effects of drugs on erectile function of male rats. PMID:27132237

  13. Baclofen reversed thermal place preference in rats with chronic constriction injury.

    PubMed

    Salte, K; Lea, G; Franek, M; Vaculin, S

    2016-06-20

    Chronic constriction injury to the sciatic nerve was used as an animal model of neuropathic pain. Instead of frequently used reflex-based tests we used an operant thermal place preference test to evaluate signs of neuropathic pain and the effect of baclofen administration in rats with neuropathy. Chronic constriction injury was induced by four loose ligations of the sciatic nerve. Thermal place preference (45 °C vs. 22 °C and 45 °C vs. 11 °C) was measured after the ligation and after the administration of baclofen in sham and experimental rats. Rats with the chronic constriction injury spent significantly less time on the colder plate compared to sham operated animals at the combination 45 °C vs. 11 °C. After administration of baclofen (10 mg/kg s.c.), the aversion to the colder plate in rats with chronic constriction injury disappeared. At the combination 45 °C vs. 22 °C, no difference in time spent on colder and/or warmer plate was found between sham and experimental animals. These findings show the importance of cold allodynia evaluation in rats with chronic constriction injury and the effectiveness of baclofen in this neuropathic pain model. PMID:26447518

  14. Effects of acute and chronic uremia on active cation transport in rat myocardium

    SciTech Connect

    Druml, W.; Kelly, R.A.; England, B.K.; O'Hara, D.S.; Mitch, W.E. )

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  15. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    SciTech Connect

    Sorrell, M.F.; Nauss, J.M.; Donohue, T.M. Jr.; Tuma, D.J.

    1983-03-01

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate (/sup 14/C)glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring (/sup 14/C)leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, (/sup 14/C)fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration.

  16. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat.

    PubMed

    Sorrell, M F; Nauss, J M; Donohue, T M; Tuma, D J

    1983-03-01

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [14C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [14C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [14C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration. PMID:6822326

  17. Modulation of phase-II enzyme activities in benzene treated ovariectomized rats.

    PubMed

    Verma, Yeshvandra; Rana, S V S

    2011-05-01

    The aim of the study was to determine the influence of ovariectomy on phase II enzymes viz. glutathione-S-transferase (GST), glutathione peroxidase (GPX) and catalase (CAT) in liver and kidney of female rats treated with benzene. The results showed the significant decrease of the GST and GPX activity in benzene treated rats after ovariectomy. However progesterone supplementation stimulated the activity of GST and GPX in liver and kidney of benzene treated non ovariectomized and ovariectomized rats. Progesterone supplementation to benzene treated ovariectomized rats helps to gain in CAT activity. Our results on DNA damage using single cell gel electrophoresis also confirmed our findings on antioxidant enzymes. The results showed that lack of protective progesterone against benzene toxicity is reflected in alterations in antioxidant enzyme activities. However progesterone therapy to benzene treated ovariectomized rats results in activating the antioxidant defence system. Since female workers are engaged in industrial sector, these results are important from occupational health point of view. Benzene exposure affects their reproductive health. Nevertheless, it could be modulated by suitable hormonal therapy. PMID:21787707

  18. Chronic Bilateral Tibial Stress Fractures with Valgus Treated with Bilateral Intramedullary Nailing: A Case Report

    PubMed Central

    Dailey, Steven K; Archdeacon, Michael T.

    2014-01-01

    Introduction: Stress fractures are overuse injuries most commonly seen in athletes, military recruits, and individuals with endocrine abnormalities. It has been demonstrated that chronic cases of anterior tibial stress fractures refractory to conservative management respond well to intramedullary nailing. To our knowledge, only one report has been published concerning patients with bilateral tibial stress fractures treated with bilateral intramedullary nailing. All patients in the series were high-level athletes. We present the case of a non-athletic patient with chronic bilateral tibial stress fractures and associated deformity successfully treated with bilateral intramedullary nails. Case Report: A 23-year-old Caucasian female full-time student presented with chronic bilateral shin pain for approximately five years. She had failed an extensive regimen of conservative management. She was diagnosed with chronic bilateral tibial stress fractures based on history, physical examination, and radiologic findings. She subsequently underwent sequential intramedullary nailing of her tibiae. Both tibiae were in valgus alignment; however, this did not preclude nail placement. The nails deformed upon insertion into the sclerotic canals to conform to the deformation. Post operatively the tibiae united and patient was relieved of her symptoms. Conclusion: Bilateral intramedullary nailing of chronic bilateral tibial stress fractures should be considered as a treatment option for all patients, not just high-level athletes, who fail a trial of conservative management. Additionally, mild to moderate tibial malalignment does not necessarily preclude tibial nailing as the smaller nails placed in sclerotic canals will likely deform on insertion and conform to the canal. PMID:27298944

  19. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    SciTech Connect

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  20. Metabolic and neurochemical profiles in insulin-treated diabetic rats.

    PubMed

    Bellush, L L; Reid, S G

    1994-01-01

    Plasma glucose concentration was measured at 3-h intervals in streptozotocin-induced diabetic rats placed on various insulin replacement regimens using three different kinds of insulin. High insulin dosages produced at least periodic hypoglycemia, even though there were no overt signs of insulin overdose. Low- and single-dose regimens produced periods of hyperglycemia. Both high and low doses of protamine zinc insulin normalized diabetes-induced reductions in 5-hydroxyindole-3-acetic acid [5-HIAA; the principal metabolite of 5-hydroxytryptamine (5-HT)] and 5-HT turnover (5-HIAA/5-HT), despite the failure of the low-dose regimen to normalize plasma glucose. Diabetic rats evidenced continued hyperphagia and hyperdipsia during insulin treatment, and insulin treatment also induced hyperphagia and excessive weight gain in nondiabetic rats. Insulin treatment only partially normalized diabetes-induced adrenal hypertrophy. Adrenal hypertrophy is an indication of a continued stresslike physiological state in diabetes even during insulin therapy. This state may be involved in the enhanced risk in diabetic humans for development of anxiety disorders and clinical depression. PMID:7508209

  1. Heart Rate Changes in Electroacupuncture Treated Polycystic Ovary in Rats

    PubMed Central

    Ramadoss, Mukilan; Subbiah, Angelie Jessica; Natrajan, Chidambaranathan

    2016-01-01

    Introduction Polycystic Ovary Syndrome (PCOS) is a common metabolic disorder, it affects both humans and animals. It may induce coronary heart disease, obesity and hyperandrogenism. Previous studies show that Low frequency Electroacupuncture (EA) have an effect on PCOS, however the exact pathway is unclear. Aim To find the effect of EA on autonomic activity of the heart in Estradiol Valerate (EV) induced PCOS rats. Materials and Methods Heart rate variability (HRV) was assessed in 3 groups: 1) Control; 2) PCOS rats; and 3) PCOS rats after EA treatment (n=8 in each group). From the time domain analysis and frequency domain analysis (linear measures) HRV analysis was done. EA stimulation was given at low frequency of 2Hz for 15 min on alternate days for 4-5 weeks. Collected data were statistically analysed using One-Way Analysis of Variance with the application of multiple comparisons of Tukey test. Results EA treatment group shows significant reduction in Heart Rate (HR) and low frequency, high frequency ratio (LF/HF); and increase in RR interval, Total Power (TP) when compared to PCOS group. Conclusion The study concludes that EA treatment has a significant effect on reducing sympathetic tone and decreasing HR in PCOS. PMID:27134868

  2. Antioxidant Effects of Cranberry Powder in Lipopolysaccharide Treated Hypercholesterolemic Rats

    PubMed Central

    Kim, Mi Joung; Kim, Jung Hee; Kwak, Ho-Kyung

    2014-01-01

    This study was conducted to investigate the effects of cranberry power on antioxidant defense system in rats fed an atherogenic diet and injected with lipopolysaccharide (LPS). Sprague-Dawley rats were divided into the following 5 groups: normal diet+saline (NS), atherogenic diet+saline (AS), atherogenic diet+LPS (AL), atherogenic diet with 5% cranberry powder+LPS (AL-C5), and atherogenic diet with 10% cranberry powder+LPS (AL-C10). Total antioxidant status measured by ferric reducing ability of plasma (FRAP) was significantly reduced by LPS injection (24%) and was restored by the cranberry powder treatment (P<0.05). In addition, the mean level of plasma total phenolics was significantly decreased by LPS injection (P<0.05) and tended to be increased when cranberry powder was incorporated in to the diet. Activity of serum superoxide dismutase (SOD) tended to be lowered by LPS injection and declined further in cranberry powder fortified groups. Overall results indicate that dietary cranberry powder may provide appropriate antioxidants to counter the diminished antioxidant status induced by exposing hypercholesterolemic rats to LPS. PMID:25054105

  3. Chronic stress and excessive glucocorticoid exposure both lead to altered Neuregulin-1/ErbB signaling in rat myocardium.

    PubMed

    Dang, Ruili; Guo, Yujin; Zhang, Ling; Chen, Lei; Yang, Ranyao; Jiang, Pei

    2016-08-01

    Exposure to chronic stress or excess glucocorticoids is associated with the development of depression and heart disease, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in cardiac function, much is still unknown concerning the biological link between NRG1/ErbB pathway and the stress-induced comorbidity of depression and cardiac dysfunction. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the myocardium of rats following chronic unpredictable mild stress (CUMS) or rats treated with two different doses (0.2 and 2mg/kg/day, respectively) of dexamethasone (Dex). The stressed rats showed elevated expression of NRG1 and phosphorylated ErbB4 (pErbB4) in the myocardium, whereas ErbB2 and pErbB2 were inhibited. The lower dose of Dex enhanced myocardial NRG1/ErbB signaling, but as the dose is increased, while ErbB4 remained activated, the expression of ErbB2 and pErbB2 became compromised. Both CUMS and 2mg/kg of Dex suppressed the downstream Akt and ERK phosphorylation. Although the lower dose of Dex increased myocardial antiapoptotic Bcl-xl expression, a significant decrease of Bcl-xl expression was found in rats treated with the higher dose. Meanwhile, both CUMS and two different doses of Dex induced proapoptotic Bax level. Combined, our data firstly showed (mal)adaptive responses of NRG1/ErbB system in the stressed heart, indicating the potential involvement of NRG1/ErbB pathway in the stress-induced cardiac dysfunction. PMID:27133902

  4. The effects of chronic lead treatment and hypertension on the severity of cardiac arrhythmias induced by coronary artery occlusion or by noradrenaline in anaesthetised rats.

    PubMed

    Evis, M J; Dhaliwal, K; Kane, K A; Moore, M R; Parratt, J R

    1987-02-01

    The aim of this study was to investigate whether chronic (3 months) lead (250 or 1000 ppm), administered as lead acetate in the drinking water, commencing either after weaning (in normotensive or spontaneously hypertensive male rats) or from conception (normotensive rats only) altered the susceptibility of the heart to arrhythmias induced either by coronary artery occlusion or by noradrenaline. Treatment with lead alone had no marked effect on the arrhythmias elicited by either method. Spontaneously hypertensive rats treated with either dose of lead exhibited more ectopic beats following coronary artery occlusion than normotensive rats but not more than those observed in control spontaneously hypertensive rats. An enhanced arrhythmogenic effect of noradrenaline was observed only in hypertensive rats administered 250 ppm lead. Both doses of lead accelerated the development of high blood pressure and in normotensive rats the higher dose also resulted in an elevated pressure. Following administration of lead, blood lead concentrations were elevated to 0.96 and 2.11 mumol l-1 after 250 and 1000 ppm, respectively. Accumulation of lead in heart and bone was also observed. We conclude that chronic exposure to these concentrations of lead, when combined with high blood pressure, slightly enhances the susceptibility of the heart to arrhythmias induced by myocardial ischaemia. PMID:3579598

  5. Chronic ethanol intake leads to structural and molecular alterations in the rat endometrium.

    PubMed

    Martinez, Marcelo; Milton, Flora A; Pinheiro, Patricia Fernanda F; Almeida-Francia, Camila C D; Cagnon-Quitete, Valeria H A; Tirapelli, Luiz F; Padovani, Carlos Roberto; Chuffa, Luiz Gustavo A; Martinez, Francisco Eduardo

    2016-05-01

    We described the effects of low- and high-dose ethanol intake on the structure and apoptosis signaling of the uterine endometrium of UChA and UChB rats (animals with voluntary ethanol consumption). Thirty adult female rats, 90 days old, were divided into three groups (n = 10/group): UChA rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking < 1.9 g/kg/day; UChB rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking from 2 to 5 g/kg/day; control rats without ethanol (only water). After 120 days of treatment, rats displaying estrus were euthanized. Uterine epithelial cells of the UCh rats showed dilated cisterns of the rough endoplasmic reticulum, presence of lipid droplets, altered nuclear chromatin, and disrupted mitochondria. The UCh rats exhibited intense atrophied epithelial cells with smaller areas and perimeters of cytoplasm and nuclei. The endometrium of UChA rats showed higher levels of caspase-3 while Xiap and Bcl2 varied from moderate to weak. Both UChA and UChB rats exhibited a stronger immunoreaction to Ki-67 and IGFR-1 on epithelial and stromal cells. Chronic ethanol intake leads to structural and molecular alterations in the uterine endometrium of UCh rats, regardless of low- or high-dose consumption, promoting reproductive disorders. PMID:27139238

  6. Exacerbation of myocardial dysfunction and autonomic imbalance contribute to the estrogen-dependent chronic hypotensive effect of ethanol in female rats

    PubMed Central

    El-Mas, Mahmoud M.; Abdel-Rahman, Abdel A.

    2012-01-01

    Our previous studies showed that the hypotensive effect of chronic ethanol in female rats is reduced by ovariectomy (OVX) rats and was restored after estrogen replacement (OVXE2). Further, in randomly cycling rats, chronic ethanol increased cardiac parasympathetic dominance and subsequently reduced myocardial contractility and blood pressure (BP). In this study, we tested the hypothesis that alterations in myocardial contractility and sympathovagal control account for the E2 exacerbation of the hemodynamic effects of ethanol. BP, myocardial contractility (+dP/dtmax), and spectral cardiovascular autonomic profiles were evaluated in radiotelemetered OVX, and OVXE2 rats receiving liquid diet with or without ethanol (5%, w/v) for 13 weeks. In OVX rats, ethanol caused modest hypotension along with significant increases in +dP/dtmax during weeks 2–5. The high-frequency (IBIHF, 0.75–3 Hz) and low-frequency (IBILF, 0.25–0.75 Hz) bands of interbeat intervals were briefly increased and decreased, respectively, by ethanol. Compared with its effects in OVX rats, chronic treatment of OVXE2 rats with ethanol elicited significantly greater and more sustained reductions in systolic (SBP) and diastolic (DBP) blood pressures and +dP/dtmax. Altered sympathovagal balance and parasympathetic overactivity were more evident in ethanol-treated OVXE2 rats as suggested by the sustained: (i) increases in high-frequency bands of interbeat intervals (IBIHF, 0.75–3 Hz), and (ii) decreases in low-frequency IBI bands (IBILF, 0.25–0.75 Hz), IBILF/HF ratio and +dP/dtmax. The plasma ethanol concentration was not affected by changes in the hormonal milieu. These findings suggest that estrogen exacerbates the ethanol-evoked reductions in myocardial contractility and BP and the associated parasympathetic overactivity in female rats. PMID:22305881

  7. Somatic and Neuroendocrine Changes in Response to Chronic Corticosterone Exposure During Adolescence in Male and Female Rats.

    PubMed

    Kaplowitz, E T; Savenkova, M; Karatsoreos, I N; Romeo, R D

    2016-02-01

    Prolonged stress and repeated activation of the hypothalamic-pituitary-adrenal axis can result in many sex-dependent behavioural and metabolic changes in rats, including alterations in feeding behaviour and reduced body weight. In adults, these effects of stress can be mimicked by corticosterone, a major output of the hypothalamic-pituitary-adrenal axis, and recapitulate the stress-induced sex difference, such that corticosterone-treated males show greater weight loss than females. Similar to adults, chronic stress during adolescence leads to reduced weight gain, particularly in males. However, it is currently unknown whether corticosterone mediates this somatic change and whether additional measures of neuroendocrine function are affected by chronic corticosterone exposure during adolescence in a sex-dependent manner. Therefore, we examined the effects of non-invasively administered corticosterone (150 or 300 μg/ml) in the drinking water of male and female rats throughout adolescent development (30-58 days of age). We found that adolescent animals exposed to chronic corticosterone gain significantly less weight than controls, which may be partly mediated by the effects of corticosterone on food consumption, fluid intake and gonadal hormone function. Our data further show that, despite similar circulating corticosterone levels, males demonstrate a greater sensitivity to these changes than females. We also found that Npy1 and Npy5 receptor mRNA expression, genes implicated in appetite regulation, was significantly reduced in the ventral medial hypothalamus of corticosterone-treated males and females compared to controls. Finally, parameters of gonadal function, such as plasma sex steroid concentrations and weight of reproductive tissues, were reduced by adolescent corticosterone treatment, although only in males. The data obtained in the present study indicate that chronic corticosterone exposure throughout adolescent development results in significant and sex

  8. Epoetin beta pegol prevents endothelial dysfunction as evaluated by flow-mediated dilation in chronic kidney disease rats.

    PubMed

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Hirata, Michinori; Endo, Koichi

    2015-11-15

    Chronic kidney disease (CKD) patients have a poor prognosis due to cardiovascular disease. Anemia and endothelial dysfunction are important risk factors for cardiovascular events in CKD patients, and treatment with erythropoiesis-stimulating agent (ESA) has been reported to improve the quality of life in CKD patients. In this study, we evaluated the effect of anemia correcting dose of epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.) on endothelial function in 5/6 nephrectomized rats (Nx rats). C.E.R.A. was subcutaneously administered once a fortnight, 5 times in total, from 1 week after nephrectomy. Twenty-four hours after last administration, endothelial function was evaluated by measuring flow-mediated dilation (FMD) in the femoral arteries of anesthetized Nx rats by ultrasound system. Femoral arteries were harvested for western blot analysis. C.E.R.A. significantly increased FMD of Nx rats. Endothelium-independent vasodilation induced by nitroglycerin injection was not influenced by C.E.R.A treatment. Nox4 expression and nitrotyrosine accumulation were significantly decreased, and phosphorylation of eNOS was significantly enhanced in the femoral arteries of C.E.R.A.-treated rats. C.E.R.A. normalized hemoglobin levels but did not affect body weight, systolic blood pressure, heart rate, urinary protein excretion and plasma creatinine. These results indicate that C.E.R.A. prevented endothelial dysfunction in Nx rats, possibly through reduction of local oxidative stress and enhancement of eNOS phosphorylation in the arteries. This study provides the first evidence that C.E.R.A. prevented endothelial dysfunction in CKD model rats under conditions of amelioration of anemia. PMID:26432688

  9. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    PubMed

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats. PMID:25539049

  10. Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide.

    PubMed

    Jung, Jin Woo; Lee, Mi Suk; Choi, Hyo-Jung; Jung, Sunhee; Lee, Yu-Jung; Hwang, Geum-Sook; Kwon, Tae-Hwan

    2016-06-01

    In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using matrix-assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the change of metabolites in the COR, OM, and IM of the rat kidney after furosemide treatment compared with vehicle-treated controls. Osmotic minipumps were implanted in male Sprague-Dawley rats to deliver 12 mg·day(-1)·rat(-1) of furosemide. Vehicle-treated (n = 14) and furosemide-treated (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g·220 g body wt(-1)·day(-1) for each rat) with free access to water intake for 6 days. At day 6, higher urine output (32 ± 4 vs. 9 ± 1 ml/day) and lower urine osmolality (546 ± 44 vs. 1,677 ± 104 mosmol/kgH2O) were observed in furosemide rats. Extracts of COR, OM, and IM were analyzed by ultraperformance liquid chromatography coupled with quadrupole time-of-flight (TOF) mass spectrometry, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetylcarnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed. The changes of metabolites were further identified by MALDI-TOF/TOF and IMS. Their spatial distribution and relative quantitation in the kidneys were analyzed by IMS. Carnitine compounds were increased in COR and IM, whereas carnitine and acetylcarnitine were decreased in OM. Choline compounds were increased in COR and OM but decreased in IM from furosemide rats. Betaine and GPC were decreased in OM and IM. Taken together, MALDI-TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney. PMID:26962105

  11. Rats with Chronic, Stable Pulmonary Hypertension Tolerate Low Dose Sevoflurane Inhalation as Well as Normal Rats Do

    PubMed Central

    Qin, Gang; Luo, Hui; Liu, Xiao; Zhang, Fan; Ye, Zhi; Zhang, Junjie; Wang, E.

    2016-01-01

    Background The effects of low concentration of sevoflurane on right ventricular (RV) function and intracellular calcium in the setting of pulmonary arterial hypertension (PAH) have not been investigated clearly. We aim to study these effects and associated signaling pathways in rats with PAH. Methods Hemodynamics were assessed with or without sevoflurane inhalation in established PAH rats. We analysis the classic RV function parameters and RV-PA coupling efficiency using steady-state PV loop recordings. The protein levels of SERCA2, PLB and p-PLB expression was analyzed by western blot to assess their relevance in PAH. Results Rats with PAH presented with RV hypertrophy and increased pulmonary arterial pressure. The values of Ea, R/L ratio, ESP, SW, PRSW, +dP/dtmax and the slope of the dP/dtmax-EDV relationship increased significantly in PAH rats (P<0.05). Sevoflurane induced a concentration-dependent decrease of systemic and pulmonary blood pressure, HR, RV contractility, and increased the R/L ratio in both groups. Sevoflurane reduced the expression of SERCA2 and increased the expression of PLB in both groups. Interestingly, sevoflurane only reduced the p-PLB/PLB ratio in PAH rats, not in normal rats. Conclusions Rats with chronic, stable pulmonary hypertension tolerate low concentrations of sevoflurane inhalation as well as normal rats do. It may be related to the modulation of the SERCA2-PLB signaling pathway. PMID:27144451

  12. Outcome assessment in patients with chronic obstructive rhinitis CO2 laser treated

    PubMed Central

    Testa, D; Motta, G; Galli, V; Iovine, R; Guerra, G; Marenzi, G; Testa, B

    2006-01-01

    Summary Surgical lasers have been used to restore nasal flow in chronic obstructive rhinitis, with a significant improvement in symptoms having been reported in almost all cases. However, evidence supporting the efficacy at long-term, and studies on the assessment of quality of life remain limited. In the present study, efficacy at long term and improvement in the quality of life were assessed in patients with chronic obstructive rhinitis, treated with CO2 laser. A total of 308 patients with chronic obstructive rhinitis were enrolled. The primary outcome measure assessed was the change in score regarding specific and general symptoms, between baseline to 2-4.5 and 7.8 mean years follow-up. Laser turbinotomy restored nasal flow and induced a change in total score which was statistically significant, for specific and general symptoms at the first, second and third follow-up, p < 0.01. CO2 laser turbinate surgery improved symptoms and quality of life in patients with chronic obstructive rhinitis as observed at 2-4.5 and 7.8 mean years follow-up. PMID:18383755

  13. Maggot debridement therapy as primary tool to treat chronic wound of animals

    PubMed Central

    Choudhary, Vijayata; Choudhary, Mukesh; Pandey, Sunanda; Chauhan, Vandip D.; Hasnani, J. J.

    2016-01-01

    Maggot debridement therapy (MDT) is a safe, effective, and controlled method ofhealing of chronic wounds by debridement and disinfection. In this therapy live, sterile maggots of green bottle fly, Lucilia (Phaenicia) sericata are used, as they prefernecrotic tissues over healthy for feeding. Since centuries, MDT is used in humanbeings to treat chronic wounds. Lately, MDT came out as a potent medical aid in animals. In animals, although, this therapy is still limited and clinical studies are few. However, with the increasing antibiotic resistance and chronic wound infections in veterinary medicine, maggot therapy may even become the first line of treatment for some infections. This paper will present a brief discussion of MDT and its role in veterinary medicine that may add one more treatment method to utilize in non-healing wounds of animals and overcome the use of amputation and euthanasia. The objective of this review paper is to assemble relevant literature on maggot therapy to form a theoretical foundation from which further steps toward clinical use of maggot therapy in animals for chronic wounds can be taken. PMID:27182137

  14. Maggot debridement therapy as primary tool to treat chronic wound of animals.

    PubMed

    Choudhary, Vijayata; Choudhary, Mukesh; Pandey, Sunanda; Chauhan, Vandip D; Hasnani, J J

    2016-04-01

    Maggot debridement therapy (MDT) is a safe, effective, and controlled method ofhealing of chronic wounds by debridement and disinfection. In this therapy live, sterile maggots of green bottle fly, Lucilia (Phaenicia) sericata are used, as they prefernecrotic tissues over healthy for feeding. Since centuries, MDT is used in humanbeings to treat chronic wounds. Lately, MDT came out as a potent medical aid in animals. In animals, although, this therapy is still limited and clinical studies are few. However, with the increasing antibiotic resistance and chronic wound infections in veterinary medicine, maggot therapy may even become the first line of treatment for some infections. This paper will present a brief discussion of MDT and its role in veterinary medicine that may add one more treatment method to utilize in non-healing wounds of animals and overcome the use of amputation and euthanasia. The objective of this review paper is to assemble relevant literature on maggot therapy to form a theoretical foundation from which further steps toward clinical use of maggot therapy in animals for chronic wounds can be taken. PMID:27182137

  15. Chronic oedema/lymphoedema: under-recognised and under-treated.

    PubMed

    Keast, David H; Despatis, Marc; Allen, Jill O; Brassard, Alain

    2015-06-01

    Even though it is estimated that at least 300 000 people in Canada may be affected by chronic oedema/lymphoedema, recognition of the seriousness of this chronic disease in health care is scarce. Lymphoedema affects up to 70% of breast and prostate cancer patients, substantially increasing their postoperative medical costs. Adding to this problem are the escalating rates of morbid obesity across North America and the fact that 80% of these individuals are thought to suffer with an element of lymphoedema. The costs related to these patient populations and their consumption of health care resources are alarming. Untreated chronic oedema/lymphoedema is progressive and leads to infection, disfigurement, disability and in some cases even death. Thus, prognosis for the patient is far worse and treatment is more costly when the disease is not identified and treated in the earlier stages. Although the number of individuals coping with chronic oedema/lymphoedema continues to increase, the disparity between diagnosis, treatment and funding across Canada endures. The reasons for this include a lack of public awareness of the condition, insufficient education and knowledge among health care providers regarding aetiology and management and limited financial coverage to support appropriate methods and materials. PMID:24618210

  16. Histopathology and histomorphometry of the urogenital tract in 15-month old male and female rats treated neonatally with SERMs and estrogens.

    PubMed

    Karlsson, Stefan

    2006-08-01

    In this study, two selective estrogen receptor modulators (SERMs), tamoxifen (TAM) and toremifene (TOR) or two estrogens, ethinylestradiol (EE) and diethylstilbestrol (DES) were administered to newborn male and female Sprague-Dawley rats (days 1-5) to investigate the occurrence of developmental abnormalities in the adulthood. The compounds were dosed (s.c.) at an equimolar dose of 24.9 micromol/kg. During the follow-up period, mortality occurred mainly in DES-treated male rats (3/4), associated with obstructive urinary calculi and suppurative renal inflammation in 2/3 rats. Similar lesions were not evident in other groups. At the age of 15 months, the animals were necropsied and organs were collected for histopathology and histomorphometry. Treatment-related abnormalities were restricted to the reproductive organs. Chronic prostatitis and epithelial abnormalities in the vas deferens were observed in all treatment groups. The columnar epithelium of vas deferens showed hyperplasia and development of subepithelial glandular structures resembling epididymal cysts reported in humans exposed in utero to DES. Testicular atrophy was observed especially in estrogen-treated rats. Mainly in SERM-treated female rats, the uterus showed luminal dilation or obstruction, loss of endometrial glands and myometrium disorganization including foci of muscular disruption. TOR-treated female rats showed polyp-like nodules (incidence 4/15) and a high incidence (9/15) of a simple cuboidal epithelium in cervical regions normally occupied by multilayered epithelia. In conclusion, the vas deferens is a main target organ following neonatal administration of SERMs and estrogens. In addition, female rats were significantly more susceptible to SERM treatment than to treatment with estrogens. PMID:16709447

  17. The effectiveness of Echinacea extract or composite glucosamine, chondroitin and methyl sulfonyl methane supplements on acute and chronic rheumatoid arthritis rat model.

    PubMed

    Arafa, Nadia Ms; Hamuda, Hayam M; Melek, Samuel T; Darwish, Sahar K

    2013-03-01

    The study aimed to investigate the effect of the oral administration for 15 days of either Echinacea (E) or genuphil (a composite of chondroitin sulphate, glucosamine and methyl sulfonyl methane [GCM]) nutraceutical supplements on female rat model of acute or chronic arthritis induced by bacterial outer membrane protein (OMP) from faecal flora of healthy and rheumatic humans. Anti-cyclic citrullinated peptide (anti-CCP2), C-reactive protein (CRP) and rheumatoid factor (RF) values increased (p < 0.05) in both arthritic groups as compared to normal values. The rheumatic markers anti-CCP2, CRP and RF values decreased significantly in E- and GCM-treated groups compared to arthritic none-treated acute or chronic groups. The results of RF values of GCM-treated groups in acute and chronic models decreased exhibiting no statistical difference compared with the normal value. Histological examinations of the hind paw sections revealed moderate inflammation, oedema and mild proliferation of synovial cells in acute arthritic rats and more damage to cartilage and bone with severe inflammation in chronic ones. Echinacea acute treated group showed edema with proliferated synovial membrane and partial damage in cartilage and bone. While in the E-chronic treated group, rough edge with destructed cartilage and bone existed. However, the acute GCM group revealed mild cartilage damage. But the chronic GCM group showed mild synovial cells proliferation and revealed no inflammation with mild cartilage damage edge. Results demonstrated the OMP arthropathic property and through promising light on arthritis treatment using E- or GCM, with the advantage of GMC results over that of E-. The composite GCM is needed for further studies over the dose and duration to assess its preventive effects against the bacterial OMP arthrogenicity. PMID:22173958

  18. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries.

    PubMed

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C

    2015-10-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment. PMID:26362752

  19. Stimulation of adrenal DNA synthesis in cadmium-treated male rats

    SciTech Connect

    Nishiyama, S.; Nakamura, K.

    1984-07-01

    Cadmium chloride (CdCl2) at a dose of 1 mg/kg body wt was injected into male rats of the Wistar strain, weighing 250 g on the average, twice a day (12-hr intervals) for 7 consecutive days. DNA and RNA contents and (/sup 3/H)-thymidine and (/sup 3/H)-uridine incorporation into the acid-insoluble fraction significantly increased in the adrenals of rats treated with Cd for 2 and 7 consecutive days. Adrenal protein content and weight also significantly increased. These results indicate that continued treatment with Cd stimulates DNA and RNA synthesis in the adrenal cortex, which in turn results in the increase of the total protein contents of the adrenal gland and subsequently in the enlargement of the gland. Serum adrenocorticotrophin (ACTH) and insulin levels in Cd-treated rats were not higher than control levels, suggesting that the stimulation of DNA synthesis in the adrenals of Cd-treated rats is due to factor(s) other than serum ACTH and insulin. Treatment with Cd inhibited DNA synthesis in cultured adrenocortical cells at concentrations of 10(-4) to 10(-8) M, suggesting that Cd does not directly stimulate DNA synthesis in the adrenal gland in vivo. Although the adrenal gland became enlarged, the total adrenal corticosterone content decreased significantly. The decrease of total adrenal corticosterone content may be due to the fall in serum ACTH level of Cd-treated rats.

  20. Lipids and lipoprotein profile in doxorubicin treated rats: influence of alpha-tocopherol administration.

    PubMed

    Geetha, A; Catherine, J; Sankar, R; Devi, C S

    1990-11-01

    The effect of doxorubicin (DXR) on the levels of heart, liver and plasma lipids and plasma lipoproteins were studied in rats. Rats were treated with DXR (2.5 mg/kg body weight weekly for 8 weeks, iv) with or without alpha-tocopherol (alpha-TPL) (400 mg/kg body wt daily for 60 days) co-administration. DXR treated rats showed increase in plasma total cholesterol, triglycerides and phospholipids. The activities of lecithin cholesterol-acyl transferase and hepatic and extrahepatic lipoprotein lipase were lowered significantly with concomitant increase in liver and heart lipid peroxide levels in DXR treatment. HDL cholesterol level was found to be decreased significantly in DXR treated rats as a result of which there was an increase of LDLc/HDLc ratio. alpha-TPL coadministration brought back the enzyme activity to near normal and reduced the level of lipid peroxides. The lipid changes were minimum in rats treated with both alpha-TPL and DXR. This study suggests that the toxicity of DXR is reflected in lipids and lipoprotein profile. PMID:2283173

  1. Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia.

    PubMed

    Do Val-da Silva, Raquel Araujo; Peixoto-Santos, José Eduardo; Scandiuzzi, Renata Caldo; Balista, Priscila Alves; Bassi, Mirian; Glass, Mogens Lesner; Romcy-Pereira, Rodrigo Neves; Galvis-Alonso, Orfa Yineth; Leite, João Pereira

    2016-09-22

    Preconditioning can induce a cascade of cellular events leading to neuroprotection against subsequent brain insults. In this study, we investigated the chronic effects of hypoxic preconditioning on spontaneous recurrent seizures (SRS), neuronal death, and spatial memory performance in rats subjected to pilocarpine (Pilo)-induced status epilepticus (SE). Rats underwent a short hypoxic episode (7% O2+93% N2; 30min on two consecutive days) preceding a 4-h SE (HSE group). Control groups were rats submitted to SE only (SE), rats subjected to hypoxia only (H) or normoxia-saline (C). Animals were monitored for the occurrence of SRS, and spatial memory performance was evaluated in the radial-arm maze. Hippocampal sections were analyzed for cell death and mossy fiber sprouting at 1 or 60days after SE. Compared to SE group, HSE had increased SE latency, reduced number of rats with SRS, reduced mossy fiber sprouting at 60days, and reduced cell death in the hilus and the CA3 region 1 and 60days after SE. Additionally, HSE rats had better spatial memory performance than SE rats. Our findings indicated that short hypoxic preconditioning preceding SE promotes long-lasting protective effects on neuron survival and spatial memory. PMID:27373771

  2. Influence of acute or chronic administration of ovarian hormones on the effects of desipramine in the forced swim test in female rats

    PubMed Central

    Shah, Aparna; Frazer, Alan

    2014-01-01

    Rationale Gender may influence antidepressant (AD) treatment outcome. In order to address this pre-clinically, the potential effects of ovarian hormones on AD treatment in ovariectomized female rats were investigated. Objectives In the first study, the effect of acute administration of estrogen and progesterone on the antidepressant-like effects of desipramine (DMI), a selective norepinephrine reuptake inhibitor (SNRI), was investigated in the forced swimming test (FST). In the second study, the effect of chronic administration of these hormones on the effects of chronically administered DMI was investigated. Results In the acute study, the hormones blocked the effects of DMI in the FST as demonstrated by the absence of either a reduction in immobility or an increase in climbing behavior in animals treated with DMI in combination with the hormones. Concentration-response experiments on hippocampal synaptosomes revealed no changes in the Km or Bmax for uptake of 3H-NE in hormone-treated rats. In the chronic study, the antidepressant-like effects of DMI in the FST were not blocked by chronic administration of hormones. Interestingly, the hormones affected the serum concentrations of DMI. These levels were significantly higher in animals receiving 10 or 15 mg/kg/day in hormone-treated rats as compared to those with placebo. Conclusions Acute administration of hormones blocked the effects of DMI (given three times over 24 h) in the FST. However, chronic administration of these hormones failed to block the effects of chronically administered DMI (at a dose that produces clinically relevant serum concentrations). PMID:24590054

  3. Chronic exertional compartment syndrome of the forearm: a case series of 12 patients treated with fasciotomy.

    PubMed

    Brown, J S; Wheeler, P C; Boyd, K T; Barnes, M R; Allen, M J

    2011-06-01

    Chronic exertional compartment syndrome of the forearm is rare in the published literature. We report the outcome of a series of 12 patients treated with fasciotomy over a 14 year period. All patients underwent dynamic intra-compartmental pressure testing using a slit catheter technique before surgery. Raised intra-compartmental pressures on exercise, typical symptoms and the absence of other diagnoses were criteria for offering surgical intervention. The superficial flexor, deep flexor and extensor compartments were released. Median follow-up was 9.5 years (range 7 months to 12 years). Median patient-reported percentage improvement after surgery was 88% (range 0%-100%). Median time to return to full activity was 9 weeks. Eleven out of 12 patients were satisfied, very satisfied or extremely satisfied with the outcome of surgery. Fasciotomy can be an effective treatment for chronic exertional compartment syndrome of the forearm. PMID:21339238

  4. Evidence that chronic administration of 17β-oestradiol decreases the vasopressor responses to adrenergic system stimulation in streptozotocin-diabetic female rats.

    PubMed

    Acosta-Cota, Selene J; Sánchez-López, Araceli; Molina-Muñoz, Tzindilu; Gómez-Viquez, Norma L; Centurión, David

    2014-05-01

    In vitro studies have indicated that 17β-oestradiol exerts beneficial effects on the cardiovascular system by activating the nitric oxide pathway. However, these effects have not been demonstrated in vivo in the systemic vasculature of rats made diabetic through streptozotocin induction. Therefore, the goal of this study was to determine the effect of 17β-oestradiol on vasopressor responses induced by sympathetic stimulation or i.v. injections of noradrenaline, methoxamine and B-HT 933 in sham-operated or ovariectomised, diabetic or non-diabetic female rats. Thus, rats were ovariectomised or sham-operated for this experiment. One week later, the animals were treated with streptozotocin (60mg/kg, i.p.) or its vehicle. Two weeks later, these rats were treated daily with 17β-oestradiol (10μg/kg, s.c.) or its vehicle for five weeks. Next, under anaesthesia, the animals were pithed and prepared for blood pressure and heart rate measurements. 17β-oestradiol failed to modify the vasopressor responses to (i) sympathetic stimulation, noradrenaline, methoxamine or B-HT 933 in sham-operated non-diabetic rats; (ii) sympathetic stimulation or B-HT 933 in sham-operated diabetic rats; (iii) noradrenaline or methoxamine in ovariectomised non-diabetic rats. In contrast, 17β-oestradiol significantly decreased the vasopressor responses to (i) noradrenaline and methoxamine in sham-operated diabetic rats; (ii) sympathetic stimulation or B-HT 933 in ovariectomised non-diabetic rats; and (iii) sympathetic stimulation, noradrenaline, methoxamine or B-HT 933 in ovariectomised diabetic rats. These results suggest that chronic administration of 17β-oestradiol decreases the vasopressor responses to adrenergic system stimulation in streptozotocin-induced diabetic rats. This report describes the first in vivo study reporting this effect of 17β-oestradiol in diabetes. PMID:24513052

  5. Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

    PubMed Central

    Muntzel, Martin S.

    2013-01-01

    The sympathetic nervous system plays a pivotal role in homeostasis through its direct innervation and functional impact on a variety of end organs. In rats, a number of methods are available to assess sympathetic nervous system function. Traditionally, direct recording of sympathetic nerve activity (SNA) has been restricted to acute, anesthetized preparations or conscious animals within a few days after electrode implantation. However, these approaches provide short-term data in studies designed to investigate changes in SNA during chronic disease states. Over the last several years, chronic SNA recording has been pioneered in rabbits and more recently in rats. The purpose of this article is to provide insights and a “how to” guide for chronic SNA recordings in rats based on experiences from two independent laboratories. We will present common methodologies used to chronically record SNA, characteristics and methods to distinguish sympathetic bursts versus electrical artifacts (and provide corresponding audio clips when available), and provide suggestions for analysis and presentation of data. In many instances, these same guidelines are applicable to acute SNA recordings. Using the surgical approaches described herein, both laboratories have been able to chronically record SNA in >50% of rats for a duration >3 wk. The ability to record SNA over the time course of several weeks will, undoubtedly, greatly impact the field of autonomic and cardiovascular physiology. PMID:24014674

  6. Effects of chronic normobaric hypoxic and hypercapnic exposure in rats: Prevention of experimental chronic mountain sickness by hypercapnia

    NASA Astrophysics Data System (ADS)

    Lincoln, B.; Bonkovsky, H. L.; Ou, Lo-Chang

    1987-09-01

    A syndrome of experimental chronic mountain sickness can be produced in the Hilltop strain of Sprague-Dawley rats by chronic hypobaric hypoxic exposure. This syndrome is characterized by polycythemia, plasma hemoglobinemia, pulmonary hypertension and right ventricular hypertrophy with eventual failure and death. It has generally been assumed that these changes are caused by chronic hypoxemia, not by hypobaric exposure per se. We have now confirmed this directly by showing that chronic normobaric hypoxic exposure (10.5% O2) produces similar hematologic and hemodynamic changes. Further, the addition of hypercapnic exposure to the hypoxic exposure blunted or prevented the effects of the hypoxic exposure probably by stimulating respiration, thus increasing the rate of oxygen delivery to the cells. Changes in the rate-controlling enzymes of hepatic heme metabolism, 5-aminolevulinate synthase and heme oxygenase, and in cytochrome(s) P-450, the major hepatic hemoprotein(s), were also measured in hypoxic and hypercapnic rats. Hypoxia decreased 5-aminolevulinate synthase and increased cytochrome(s) P-450, probably by increasing the size of a “regulatory” heme pool within hepatocytes. These changes were also prevented by the addition of hypercapnic to hypoxic exposure.

  7. MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  8. Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis

    PubMed Central

    Ashcroft, Darren M; Po, Alain Li Wan; Williams, Hywel C; Griffiths, Christopher E M

    2000-01-01

    Objectives To evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis. Design Quantitative systematic review of randomised controlled trials. Subjects 6038 patients with plaque psoriasis reported in 37 trials. Main outcome measures Mean difference in percentage change in scores on psoriasis area and severity index, and response rate ratios for both patients' and investigators' overall assessments of marked improvement or better. Adverse effects were estimated with the rate ratio, rate difference, and number needed to treat. Results Calcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol. Conclusions Calcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids

  9. Acute and chronic methyl mercury poisoning impairs rat adrenal and testicular function

    SciTech Connect

    Burton, G.V.; Meikle, A.W.

    1980-05-01

    Animals poisoned with methyl mercury (CH/sub 3/Hg) exhibit stress intolerance and decreased sexual activity, which suggest both adrenal and testicular dysfunction. Adrenal and testicular function was studied in male rats after treatment with CH/sub 3/Hg. In animals treated chronically, the adrenal glands were markedly hyperplastic with enlargement of the zona fasciculata. The mean basal serum levels of corticosterone were similar in experimental (17.8 ..mu..g/dl) and control (16.8 ..mu..g/dl) groups. However, with ether stress, experimental animals had a subnormal response, and the mean serum levels of corticosterone increased to only 23.9 ..mu../dl compared to 40.6 ..mu..g/dl in the controls. Exogenous ACTH stimulation produced a mean level of 19.0 ..mu..g/dl in the CH/sub 3/Hg-treated animals and 49.7 ..mu..g/dl in the controls. In vitro studies demonstrated a defect in the conversion of cholesterol to pregnenolone. A profound impairment in swimming was partially reversed with glucocorticoid therapy. In animals treated with CH/sub 3/Hg, serum testosterone was lower than normal in the basal state. Human chorionic gonadotropin stimulation increased the mean serum concentration of testosterone to 23.4 ng/ml in controls, but it was only 4.50 ng/ml in experimental animals. The data indicate that CH/sub 3/Hg poisoning impairs adrenal and testicular steroid hormone secretion, which accounts in part for the diminished stress tolerance and decreased sexual activity observed in CH/sub 3/Hg-intoxicated animals.

  10. Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda T; Steinbusch, Harry W; van den Hove, Daniël L

    2012-03-01

    The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women. PMID:22173000

  11. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    PubMed Central

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  12. Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats.

    PubMed

    Oliveira, Carla de; Oliveira, Cleverson Moraes de; de Macedo, Isabel Cristina; Quevedo, Alexandre S; Filho, Paulo Ricardo Marques; Silva, Fernanda Ribeiro da; Vercelino, Rafael; de Souza, Izabel C Custodio; Caumo, Wolnei; Torres, Iraci L S

    2015-01-01

    Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity. PMID:26364693

  13. Ectopic endometrium-derived leptin produces estrogen-dependent chronic pain in a rat model of endometriosis.

    PubMed

    Alvarez, P; Bogen, O; Chen, X; Giudice, L C; Levine, J D

    2014-01-31

    Endometriosis pain is a very common and extremely disabling condition whose mechanism is still poorly understood. While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain. Rats implanted with autologous uterine tissue onto the gastrocnemius muscle developed endometriosis-like lesions and local chronic pain. Compared to eutopic uterine tissue, leptin mRNA and protein were up-regulated in the endometriosis-like lesions. Intramuscular injection of recombinant leptin in naive rats produced dose-dependent local mechanical hyperalgesia and nociceptor sensitization to mechanical stimulation. Ovariectomy attenuated the mechanical hyperalgesia induced by recombinant leptin, in rats treated with vehicle compared to those treated with 17β-estradiol replacement, at 1 and 24 h after leptin injection. Finally, intralesional injections of a pegylated leptin receptor (Ob-R) antagonist or of an inhibitor of Janus kinase2, which transduces the Ob-R signal, markedly attenuated pain in the endometriosis model. Taken together these data support the hypothesis that leptin, generated in ectopic endometrial lesions produces mechanical hyperalgesia by acting on nociceptors innervating the lesion. This sensitivity to leptin is dependent on estrogen levels. Thus, interventions targeting leptin signaling, especially in combination with interventions that lower estrogen levels, might be useful for the treatment of endometriosis pain. PMID:24239717

  14. Simultaneous impairment of passive avoidance learning and nociception in rats following chronic swim stress

    PubMed Central

    Nazeri, Masoud; Shabani, Mohammad; Parsania, Shahrnaz; Golchin, Leila; Razavinasab, Moazamehosadat; Abareghi, Fatemeh; Kermani, Moein

    2016-01-01

    Background: Stress can alter response to nociception. Under certain circumstances stress enhances nociception, a phenomenon which is called stress-induced hyperalgesia (SIH). While nociception has been studied in this paradigm, possible alterations occurring in passive avoidance (PA) learning after exposing rats to this type of stress has not been studied before. Materials and Methods: In the current study, we evaluated the effect of chronic swim stress (FS) or sham swim (SS) on nociception in both spinal (tail-flick) and supraspinal (53.5°C hot-pate) levels. Furthermore, PA task was performed to see whether chronic swim stress changes PA learning or not. Mobility of rats and anxiety-like behavior were assessed using open-field test (OFT). Results: Supraspinal pain response was altered by swim stress (hot-plate test). PA learning was impaired by swim stress, rats in SS group did not show such impairments. Rats in the FS group showed increased mobility (rearing, velocity, total distant moved (TDM) and decreased anxiety-like behavior (time spent in center and grooming) compared to SS rats. Conclusions: This study demonstrated the simultaneous impairment of PA and nociception under chronic swim stress, whether this is simply a co-occurrence or not is of special interest. This finding may implicate a possible role for limbic structures, though this hypothesis should be studied by experimental lesions in different areas of rat brain to assess their possible role in the pathophysiology of SIH. PMID:27308265

  15. Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.

    PubMed

    Mahieu, Stella T; Gionotti, Marisa; Millen, Néstor; Elías, María Mónica

    2003-11-01

    The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and

  16. Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.

    PubMed

    Ince, S; Avdatek, F; Demirel, H H; Arslan-Acaroz, D; Goksel, E; Kucukkurt, I

    2016-06-01

    Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100 mg l(-1) , approximately 1/50 of oral LD50 ) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg(-1) for 60 days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic-treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200 mg kg(-1) , reversed arsenic-induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic-induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats. PMID:26302725

  17. Chronic Deep Brain Stimulation of the Hypothalamic Nucleus in Wistar Rats Alters Circulatory Levels of Corticosterone and Proinflammatory Cytokines

    PubMed Central

    Calleja-Castillo, Juan Manuel; De La Cruz-Aguilera, Dora Luz; Manjarrez, Joaquín; Velasco-Velázquez, Marco Antonio; Morales-Espinoza, Gabriel; Moreno-Aguilar, Julia; Hernández, Maria Eugenia; Aguirre-Cruz, Lucinda

    2013-01-01

    Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-α (120%; P < 0.01) and IFN-γ (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1β (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication. PMID:24235973

  18. Combined effects of chronic hyperglycaemia and oral aluminium intoxication on testicular tissue and some male reproductive parameters in Wistar rats.

    PubMed

    Akinola, O B; Biliaminu, S A; Adedeji, O G; Oluwaseun, B S; Olawoyin, O M; Adelabu, T A

    2016-09-01

    Exposure to either environmental toxicants or chronic hyperglycaemia could impair male reproductive function. However, the extent to which exposure to such toxicants, in the presence of pre-existing metabolic dysfunction, could affect male reproduction is unclear. Streptozotocin-induced diabetic Wistar rats (12 weeks old) were exposed to oral aluminium chloride at 250 ppm for 30 days; followed by evaluation of caudal epididymal sperm count and motility, assay for serum follicle stimulating hormone (FSH), testosterone (T) and oestradiol; and assessment of testicular histology. Moreover, blood glucose was evaluated by the glucose oxidase method. In rats treated with streptozotocin (STZ) or aluminium (Al) alone, erosion of testicular parenchyma and stroma was observed. This effect was most severe in diabetic rats simultaneously exposed to Al; coupled with reduced caudal epididymal sperm count that was least in this (STZ+Al) group (18.75 × 10(6)  ml(-1) ) compared with controls (61.25 × 10(6)  ml(-1) ; P < 0.05), STZ group or Al group. Moreover, these reproductive perturbations (in the STZ+Al group) were associated with reduced sperm motility and significantly reduced serum FSH (P < 0.05); but elevated serum T and oestradiol (P < 0.05), compared with control. These suggest that diabetes-induced testicular lesion is exacerbated by simultaneous oral Al toxicity in Wistar rats. PMID:26688578

  19. Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats

    PubMed Central

    Gao, Dan-Dan; Fu, Jia; Qin, Bo; Huang, Wen-Xiang; Yang, Chun; Jia, Bei

    2016-01-01

    AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF). METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes. RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter group. CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects. PMID:27122664

  20. Curcumin Attenuates Iron Accumulation and Oxidative Stress in the Liver and Spleen of Chronic Iron-Overloaded Rats

    PubMed Central

    Badria, Farid A.; Ibrahim, Ahmed S.; Badria, Adel F.; Elmarakby, Ahmed A.

    2015-01-01

    Objectives Iron overload is now recognized as a health problem in industrialized countries, as excessive iron is highly toxic for liver and spleen. The potential use of curcumin as an iron chelator has not been clearly identified experimentally in iron overload condition. Here, we evaluate the efficacy of curcumin to alleviate iron overload-induced hepatic and splenic abnormalities and to gain insight into the underlying mechanisms. Design and Methods Three groups of male adult rats were treated as follows: control rats, rats treated with iron in a drinking water for 2 months followed by either vehicle or curcumin treatment for 2 more months. Thereafter, we studied the effects of curcumin on iron overload-induced lipid peroxidation and anti-oxidant depletion. Results Treatment of iron-overloaded rats with curcumin resulted in marked decreases in iron accumulation within liver and spleen. Iron-overloaded rats had significant increases in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver and spleen when compared to control group. The effects of iron overload on lipid peroxidation and NO levels were significantly reduced by the intervention treatment with curcumin (P<0.05). Furthermore, the endogenous anti-oxidant activities/levels in liver and spleen were also significantly decreased in chronic iron overload and administration of curcumin restored the decrease in the hepatic and splenic antioxidant activities/levels. Conclusion Our study suggests that curcumin may represent a new horizon in managing iron overload-induced toxicity as well as in pathological diseases characterized by hepatic iron accumulation such as thalassemia, sickle cell anemia, and myelodysplastic syndromes possibly via iron chelation, reduced oxidative stress derived lipid peroxidation and improving the body endogenous antioxidant defense mechanism. PMID:26230491

  1. Beneficial Effects of American Ginseng on Epididymal Sperm Analyses in Cyclophosphamide Treated Rats

    PubMed Central

    Akram, Hosseini; Ghaderi Pakdel, Firouz; Ahmadi, Abbas; Zare, Samad

    2012-01-01

    Objective: This study aims to evaluate the protective effects of American ginseng administered by gastric intubation on sperm vital quality in adult male rats treated with cyclophosphamide (CP). Materials and Methods: In this experimental study, 28 Adult male Wistar rats were assigned to four groups, seven rats in each. The animals allocated to control, CP treated, Ginseng treated and CP-Ginseng treated groups. Rats were treated with CP (6.1 mg/kg/day, i.p) for 6 weeks. American ginseng was used at a dose of 500 mg/kg/day during treatment. Sperm analysis (motion, count, morphology and viability) were evaluated at the end of the experiments. Sperm motion was assessed by Computer-Assisted Sperm Analysis (CASA). The data were analyzed using GB stat software. Probability values of p<0.05 and p<0.01 were considered significant. Results: The epididymal sperm counts in the groups that received CP showed significant decreases compared to the control group. Also dead and abnormal sperms significantly increased following CP treatment compared with control. The motility of caudal sperm was reduced significantly with CP treatment. Therefore, according to the results of this study, co-administration of CP and American ginseng can improve these parameters. Conclusion: American ginseng can prevent the cytotoxic effects of CP on sperm quality factors. PMID:23508327

  2. Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes.

    PubMed

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Nakamura, Daisuke; Nakamura, Saori; Sato, Shinobu; Yokoyama, Keisuke; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2016-09-01

    The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis. PMID:27099161

  3. Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes.

    PubMed

    DosSantos, Marcos F; Ferreira, Natália; Toback, Rebecca L; Carvalho, Antônio C; DaSilva, Alexandre F

    2016-01-01

    Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively. PMID:26903788

  4. Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes

    PubMed Central

    DosSantos, Marcos F.; Ferreira, Natália; Toback, Rebecca L.; Carvalho, Antônio C.; DaSilva, Alexandre F.

    2016-01-01

    Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively. PMID:26903788

  5. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M. V. Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications. PMID:21647314

  6. Study of mechanism in chronic simple rhinitis treated by He-Ne laser irradiation

    NASA Astrophysics Data System (ADS)

    Xin, Jiang; Fang, Chi-Oing

    1993-03-01

    Chronic rhinitis is a common disease. The patients feel troubled by nose obstruction and discharge. One-hundred-fifty cases were treated by an He-Ne laser from 1982 to 1991. Entire recovery was achieved in 16 cases; improvement was seen in 52 cases in which symptoms and signs notably declined; 41 cases were helped; and inefficacy was seen in 40 cases. The total effect rate was 73.3 percent. To study the mechanism of the disease cured with an He-Ne laser illumination experiments were performed by taking temperature, examination of blood, change of the hemostreamgraph in the brain and attenuated bacteria.

  7. [Clinical and experimental study of shengxue syrup in treating chronic aplastic anemia].

    PubMed

    Ke, W J; Wang, L; Zhou, J C

    1996-12-01

    The Shengxue Syrup (SXS) composed of Chinese medicinal herbs for invigorating the function of Spleen and resplenishing the Kidney was used in treating 115 chronic aplastic anemia patients. The SXS group consisted of 67 patients. After the median 20 months treatment the total effective rate (TER) was 97.0%. The other group was SXS + testosterone group consisted of 48 patients. After median 17.5 month treatment the TER was 95.8%. The difference of TER between two groups was insignificant. The result of animal experiment showed that SXS could markedly enhance the hematopoietic stem cells as well as progenitor cells proliferation of bone marrow in mice. PMID:9772587

  8. The cytoskeleton of digitonin-treated rat hepatocytes.

    PubMed

    Fiskum, G; Craig, S W; Decker, G L; Lehninger, A L

    1980-06-01

    Treatment of isolated rat hepatocptes with low concentrations of digitonin increases the permeability of the plsma membrane to cytosolic proteins without causing release of organelles such as mitochondria into the surrounding medium. Electron microscopy showed that treatment of the cells with increasing concentations of digitonin results in a progressive loss in the continuity of the plasma membrane, while most other aspects of cellular morphology remain normal. Depletion of background staining material from the cytosol by digitonin treatment of the cells greatly enhances the visualization of the cytoskeleton. The use of this technique, together with immunofluorescent light microscopy, has verified the presence of an actin-containing filamentous network at the hepatocyte cortex as well as intermediate filaments distributed throughout the cell. Digitonin is thus useful both for selectively permeabilizing the plasma membrane and for intensifying the appearance of intracellular structures such as microfilaments that are normally difficult to observe in cells such as hepatocytes. PMID:6997878

  9. The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats.

    PubMed

    Cho, C H; Chen, B W; Hui, W M; Lam, S K

    1990-01-01

    The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol. PMID:2295286

  10. Dynamic changes of early-stage aortic lipid deposition in chronic renal failure rats and effects of decorin gene therapy

    PubMed Central

    MA, HONG-BO; WANG, RONG; YU, KE-ZHOU; YU, CHE

    2015-01-01

    The aim of the present study was to clarify the association between lipid metabolism and the atherosclerosis in early-stage chronic renal failure at the molecular level and to explore the efficacy of decorin on chronic renal failure. Sprague Dawley rats receiving 5/6 nephrectomy and Sham surgery were divided into control and experimental groups. Sprague Dawley rats receiving 5/6 nephrectomy were divided into control and experimental groups, and the experimental group was further subdivided into rats receiving treatment with fibroblasts (FBs) transfected either with empty vector and with a decorin (DCN) gene. The dynamic levels of triglyceride (TG), total cholesterol (T-Ch) and total phospholipid (T-PL) were detected on the 10th, 30th and 60th days. The body weight, blood lipid levels, renal function and renal tissue were observed after four weeks, and transforming growth factor-βl and protein expression was detected by immunohistochemistry. In total, 4 weeks after treatment, the DCN expression in the renal tissue of rats treated with DCN-transfected FBs was significantly increased compared to that in the control rats. The results showed that the levels of the three lipids in the aortic arches were slightly elevated on the 10th day compared with those in the control group, and the TG level was significantly increased on the 30th day. The levels of T-Ch, TG and T-PL in the aortic arches were significantly elevated on the 60th day. The TG and T-Ch levels in the plasma and aortic tissues of Sprague Dawley rats receiving 5/6 nephrectomy without any treatment and after receiving treatment with FBs transfected with empty vector were significantly increased compared with those in the control group. The increased T-Ch and decreased T-PL levels in the erythrocyte membrane increased the rigidity of the erythrocyte and decreased erythrocyte deformability. In conclusion, highly expressed DCN mitigated renal fibrosis and thus delayed renal failure as well as mitigating the

  11. Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats.

    PubMed

    Roşca, A E; Stoian, I; Badiu, C; Gaman, L; Popescu, B O; Iosif, L; Mirica, R; Tivig, I C; Stancu, C S; Căruntu, C; Voiculescu, S E; Zăgrean, L

    2016-01-01

    Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

  12. Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

    PubMed Central

    Roşca, A.E.; Stoian, I.; Badiu, C.; Gaman, L.; Popescu, B.O.; Iosif, L.; Mirica, R.; Tivig, I.C.; Stancu, C.S.; Căruntu, C.; Voiculescu, S.E.; Zăgrean, L.

    2016-01-01

    Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

  13. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression.

    PubMed

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V; Christiansen, Sofie; Christensen, Trine; Andreasen, Jesper T; Palme, Rupert; Lichota, Jacek; Wiborg, Ove

    2012-12-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant tendency towards higher total cytosine methylation in rats from low maternal care dams. Assessment of methylation in the resilient versus anhedonic-like rat phenotypes, revealed only minor differences. Thus, maternal care status seems to be a strong predictor or trait marker for the behavioural phenotype. PMID:23075705

  14. Renal toxicity after chronic inhalation exposure of rats to trichloroethylene.

    PubMed

    Mensing, Thomas; Welge, Peter; Voss, Bruno; Fels, Lüder M; Fricke, Hajo Hennig; Brüning, Thomas; Wilhelm, Michael

    2002-03-10

    Male Long-Evans rats were exposed to 0 (controls) or 500 ppm trichloroethylene (TRI) for 6 months, 6 h daily, and 5 days a week. The TRI metabolites trichloroethanol (TCE) in blood and trichloroacetic acid (TCA) in urine were measured. Specific parameters related to the renal damage were determined in urine [biomarker for glomerular damage: high molecular weight proteins (HMW), albumin (ALB); for proximal tubular damage: N-acetyl-beta-D-glucosaminidase (NAG), low-molecular-weight-proteins (LMW)]. Significantly increased concentrations of NAG and LMW in urine of exposed rats were detected. No DNA-strand breaks in kidney cells could be detected using the comet assay, and histological examinations were performed. Histological alterations were observed in glomeruli and tubuli of exposed rats. The release of biomarkers for nephrotoxicity suggested alterations preferably in the proximal tubules of the exposed rats. PMID:11869834

  15. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism

    PubMed Central

    LI, SHUANG; WANG, SU; GUO, ZHI-GANG; HUANG, NING; ZHAO, FAN-RONG; ZHU, MO-LI; MA, LI-JUAN; LIANG, JIN-YING; ZHANG, YU-LIN; HUANG, ZHONG-LIN; WAN, GUANG-RUI

    2015-01-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism. PMID:26640531

  16. Fructus mume Ethanol Extract Prevents Inflammation and Normalizes the Septohippocampal Cholinergic System in a Rat Model of Chronic Cerebral Hypoperfusion

    PubMed Central

    Kim, Min-Soo; Bang, Ji Hye; Lee, Jun; Han, Jung-Soo; Kang, Hyung Won

    2016-01-01

    Abstract Fructus mume (F. mume), the unripe fruit of Prunus mume, has long been used in Asian countries to treat cough and chronic diarrhea. We previously reported that F. mume exerts anti-inflammatory effects in a model of chronic cerebral hypoperfusion (CCH), a key etiological factor of vascular dementia (VaD). The present study was performed to investigate the protective effects of an ethanolic extract of F. mume on the inflammatory response and cholinergic dysfunction in a model of CCH induced by bilateral common carotid artery occlusion (BCCAo) in Wistar rats. Rats were assigned to three treatment groups: sham plus vehicle, BCCAo plus vehicle, and BCCAo plus F. mume extract (200 mg/kg). F. mume was administered by oral gavage from days 21 to 42 following BCCAo. Glial cell numbers were measured in the white matter and hippocampus. The hippocampal expressions of proinflammatory cytokines, angiotensin-II (Ang-II), receptor for advanced glycation end products (RAGE), and mitogen-activated protein kinase (MAPKs) were also evaluated. Choline acetyltransferase (ChAT) levels in the hippocampus and basal forebrain were examined. Rats with BCCAo showed an increase in the number of glial cells and levels of proinflammatory cytokines, Ang-II, RAGE, and MAPKs, all of which were significantly attenuated by F. mume treatment. F. mume administration also restored ChAT expression in the basal forebrain and hippocampus following chronic BCCAo. These results suggest that F. mume is a potentially valuable drug or nutraceutical for the treatment of VaD. PMID:26714236

  17. Differential effects of acute and chronic nicotine on dopamine output in the core and shell of the rat nucleus accumbens.

    PubMed

    Nisell, M; Marcus, M; Nomikos, G G; Svensson, T H

    1997-01-01

    Like several drugs of abuse, nicotine increase dopamine (DA) release in the nucleus accumbens (NAC). In the present study, the effects of acute and chronic nicotine on DA output in two subdivisions of the NAC, the core and the shell, which are largely associated with motor control and limbic functions, respectively, were examined by means of in vivo differential normal pulse voltammetry in anesthetized, pargyline-treated rats. In the first experiment, acute administration of nicotine (25, 50 and 100 micrograms/kg, cumulative doses; i.v.) was found to increase DA levels in the NACshell to 163% of baseline, whereas DA output in the NACcore was not significantly affected. In the second experiment, animals were pretreated with twelve daily injections of saline or nicotine (0.5 mg/kg, i.p.); about 24 hours after the last injection, the animals were challenged with nicotine (50 micrograms/kg and 100 micrograms/kg, cumulative doses; i.v.). Under these conditions, nicotine increased DA output in the NACshell in saline-pretreated animals to 248% and in nicotine-pretreated rats to 180%. Also, nicotine increased DA output in the NACcore in saline-pretreated animals to 185%, whereas no significant effect was observed in nicotine-pretreated rats. The results of the present experiments indicate (i) that acutely administered nicotine or nicotine challenge in chronically pretreated animals with either saline or nicotine consistently increases DA release to a greater extent in the NACshell than in the NACcore, and (ii) that chronic nicotine pretreatment reduces the stimulatory-action of nicotine on DA output in either the shell or the core subdivision of the NAC. PMID:9085189

  18. Chronic parenterally administered nicotine and stress- or ethanol-induced gastric mucosal damage in rats.

    PubMed

    Wong, D; Ogle, C W

    1995-01-13

    Mini-osmotic pumps containing solutions of either 0.9% NaCl (infused at the rate of 0.5 microliter/h) or nicotine (infused in doses of 0.224, 1.03 or 1.88 mg/kg per day) were implanted s.c. into rats 12 days before experimentation. The alkaloid increased solid food consumption, but fluid intake and average weight gain were similar among the animals given saline or nicotine. Chronic nicotine treatment dose dependently intensified cold (4 degrees C)-restraint stress-induced ulceration and increased mast cell degranulation. Oral administration of 40% ethanol to nicotine-treated animals also produced greater mucosal damage; mast cell degranulation by ethanol was significantly worsened after alkaloid treatment. These findings show that the stress ulcer-intensifying action of the alkaloid is mainly through a systemic mechanism. In the case of ethanol-evoked mucosal damage, in addition to a topical effect, stimulation of the stomach wall ganglia is likely to participate in the exaggerated post-vagal ulcerogenic responses as seen in stress. PMID:7720788

  19. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  20. Effects of Acupuncture, RU-486 on the Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Adult Male Rats.

    PubMed

    Eshkevari, Ladan; Mulroney, Susan E; Egan, Rupert; Lao, Lixing

    2015-10-01

    We have recently reported that pretreatment with electroacupuncture (EA) at stomach meridian point 36 (St36) prevents the chronic cold-stress increase in the hypothalamus-pituitary-adrenal axis (HPA), an action that may be under central control. Given that treatment for stress-related symptoms usually begins after onset of the stress responses, the objectives of the present study were to determine the efficacy of EA St36 on HPA hormones when EA St36 is given after stress was initiated, if the results are long lasting, and if blocking the glucocorticoid receptor (GR) using RU-486 had the same effects as EA St36. Adult male rats were placed in 4 groups of animals, 3 of which were exposed to cold and 1 of which was a nontreatment control group. After exposure to the cold stress, 2 groups were treated with either EA St36 or sham-EA, repeated over 10 days. The increase in ACTH and corticosterone observed in stress-only rats was prevented in EA St36 animals, and the effects remained intact 4 days after withdrawal of EA but continuation of cold stress. When the GR was blocked with RU-486, the efficacy of EA St36 remained unchanged. GR blockade did significantly elevate ACTH, which is not seen with EA St36, suggesting that EA St36 does act centrally. The elevated HPA hormones in stress-only rats were associated with a significant increase in depressive and anxious behavior; this was not observed in the stressed EA St36 animals. The results indicate that EA specifically at St36 vs sham-EA is effective in treating chronic poststress exposure. PMID:26196540

  1. Systematic approach to treat chronic osteomyelitis through localized drug delivery system: bench to bed side.

    PubMed

    Bhattacharya, Rupnarayan; Kundu, Biswanath; Nandi, Samit Kumar; Basu, Debabrata

    2013-10-01

    Chronic osteomyelitis is a challenging setback to the orthopedic surgeons in deciding an optimal therapeutic strategy. Conversely, patients feel frustrated of the therapeutic outcomes and development of adverse drug effects, if any. Present investigation deals with extensive approach incorporating in vivo animal experimentation and human application to treat chronic osteomyelitis, using antibiotic loaded porous hydroxyapatite scaffolds. Micro- to macro-porous hydroxyapatite scaffolds impregnated with antibiotic ceftriaxone-sulbactam sodium (CFS) were fabricated and subsequently evaluated by in vivo animal model after developing osteomyelitis in rabbit tibia. Finally 10 nos. of human osteomyelitis patients involving long bone and mandible were studied for histopathology, radiology, pus culture, 3D CT etc. up to 8-18 months post-operatively. It was established up to animal trial stage that 50N50H samples [with 50-55% porosity, average pore size 110 μm, higher interconnectivity (10-100 μm), and moderately high drug adsorption efficiency (50%)] showed efficient drug release up to 42 days than parenteral group based on infection eradication and new bone formation. In vivo human bone showed gradual evidence of new bone formation and fracture union with organized callus without recurrence of infection even after 8 months. This may be a new, alternative, cost effective and ideal therapeutic strategy for chronic osteomyelitis treatment in human patients. PMID:23910305

  2. Structural Biology Contributions to the Discovery of Drugs to Treat Chronic Myelogenous Leukemia

    NASA Astrophysics Data System (ADS)

    Cowan-Jacob, Sandra W.; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W.

    This case study illustrates how the determination of multiple co-crystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery efforts leading to the design of nilotinib, a newly approved therapy for imatinib-intolerant and - resistant chronic myelogenous leukemia. Chronic myelogenous leukemia (CML) results from the BCR-Abl onco-protein, which possesses a constitutively activated Abl tyrosine kinase domain. Although many chronic-phase CML patients treated with imatinib as first-line therapy maintain excellent, durable responses, patients who have progressed to advanced-stage CML frequently fail, or lose their response to therapy, often due to the emergence of drug-resistant mutants of the protein. More than 60 such point mutations have been detected in imatinib-resistant patients. We determined the crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small molecule Abl inhibitors, with the aim of understanding the molecular basis for resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way this information is used to support drug discovery.

  3. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    SciTech Connect

    Cowan-Jacob, Sandra W. Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W.

    2007-01-01

    A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.

  4. Chronic acromioclavicular joint dislocations treated by the GraftRope device

    PubMed Central

    Nordin, Jonas S; Aagaard, Knut E; Lunsjö, Karl

    2015-01-01

    Background and purpose Surgical treatment of chronic acromioclavicular joint dislocations is challenging, and no single procedure can be considered to be the gold standard. In 2010, the GraftRope method (Arthrex Inc., Naples, FL) was introduced in a case series of 10 patients, showing good clinical results and no complications. We wanted to evaluate the GraftRope method in a prospective consecutive series. Patients and methods 8 patients with chronic Rockwood type III–V acromioclavicular joint dislocations were treated surgically using the GraftRope method. The patients were clinically evaluated and a CT scan was performed to assess the integrity of the repair. Results and interpretation In 4 of the 8 patients, loss of reduction was seen within the first 6 weeks postoperatively. A coracoid fracture was the reason in 3 cases and graft failure was the reason in 1 case. In 3 of the 4 patients with intact repairs, the results were excellent with no subjective shoulder disability 12 months postoperatively. It was our intention to include 30 patients in this prospective treatment series, but due to the high rate of complications the study was discontinued prematurely. Based on our results and other recent reports, we cannot recommend the GraftRope method as a treatment option for chronic acromioclavicular joint dislocations. PMID:25323800

  5. Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats

    SciTech Connect

    Adair, Blakely M.; Moore, Tanya; Conklin, Sean D.; Creed, John T.; Wolf, Douglas C.; Thomas, David J. . E-mail: thomas.david@epa.gov

    2007-07-15

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P < 0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P < 0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.

  6. Chronic desipramine treatment alters tyrosine hydroxylase but not norepinephrine transporter immunoreactivity in norepinephrine axons in the rat prefrontal cortex

    PubMed Central

    Erickson, Susan L.; Gandhi, Anjalika R.; Asafu-Adjei, Josephine K.; Sampson, Allan R.; Miner, LeeAnn; Blakely, Randy D.; Sesack, Susan R.

    2011-01-01

    Pharmacological blockade of norepinephrine (NE) reuptake is clinically effective in treating several mental disorders. Drugs that bind to the NE transporter (NET) alter both protein levels and activity of NET and also the catecholamine synthetic enzyme tyrosine hydroxylase (TH). We examined the rat prefrontal cortex (PFC) by electron microscopy to determine whether the density and subcellular distribution of immunolabeling for NET and colocalization of NET with TH within individual NE axons were altered by chronic treatment with the selective NE uptake inhibitor desipramine (DMI). Following DMI treatment (21 days, 15 mg/kg/day), NET-immunoreactive (-ir) axons were significantly less likely to colocalize TH. This finding is consistent with reports of reduced TH levels and activity in the locus coeruleus after chronic DMI and indicates a reduction of NE synthetic capacity in the PFC. Measures of NET expression and membrane localization, including the number of NET-ir profiles per tissue area sampled, the number of gold particles per NET-ir profile area, and the proportion of gold particles associated with the plasma membrane, were similar in DMI and vehicle treated rats. These findings were verified using two different antibodies directed against distinct epitopes of the NET protein. The results suggest that chronic DMI treatment does not reduce NET expression within individual NE axons in vivo or induce an overall translocation of NET protein away from the plasma membrane in the PFC as measured by ultrastructural immunogold labeling. Our findings encourage consideration of possible postranslational mechanisms for regulating NET activity in antidepressant-induced modulation of NE clearance. PMID:21208501

  7. Pixe analysis of trace elements in tissues of rats treated with anticonvulsants

    NASA Astrophysics Data System (ADS)

    Hurd, R. W.; Van Rinsvelt, H. A.; Kinyua, A. M.; O'Neill, M. P.; Wilder, B. J.; Houdayer, A.; Hinrichsen, P. F.

    1987-04-01

    Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

  8. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib.

    PubMed

    Castagnetti, F; Gugliotta, G; Breccia, M; Stagno, F; Iurlo, A; Albano, F; Abruzzese, E; Martino, B; Levato, L; Intermesoli, T; Pregno, P; Rossi, G; Gherlinzoni, F; Leoni, P; Cavazzini, F; Venturi, C; Soverini, S; Testoni, N; Alimena, G; Cavo, M; Martinelli, G; Pane, F; Saglio, G; Rosti, G; Baccarani, M

    2015-09-01

    For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients. PMID:26088952

  9. CHRONIC ETHANOL INTAKE IMPAIRS INSULIN SIGNALING IN RATS BY DISRUPTING AKT ASSOCIATION WITH THE CELL MEMBRANE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic and excessive alcohol consumption is an important and modifiable risk factor for type 2 diabetes. We previously reported elevations in Class 1 Alcohol Dehydrogenase (ADH) expression in ethanol-fed rats that were coincident with reduced levels of mature, nuclear SREBP-1, suggesting that this ...

  10. CHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The chronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 (F344) rats was evaluated by feeding a diet containing 0, 5, 60 and 300 ppm of TNB for 2 years. The calculated average TNB intake over 2 years for males and females was 0.22, 2.64, 13.44 and 0.23,...

  11. BEHAVIOR, PHYSIOLOGY, AND ENERGY DEPOSITION IN RATS CHRONICALLY EXPOSED TO 2450 MHZ RADIATION

    EPA Science Inventory

    The research program was initiated to determine both the specific absorption rate (SAR) and the behavioral and physiological consequences of chronic CW microwave radiation exposure at 2450 MHz in the laboratory rat. Whole-body average and local SARs at discrete sites within the b...

  12. SOME EFFECTS OF CHRONIC TRITIUM EXPOSURE DURING SELECTED AGES IN THE RAT

    EPA Science Inventory

    To assess the implication of age at the time of exposure to chronic irradiation, rats were exposed to constant tritium (HTO) activities of 10 microcuries/ml of body water for 42 days beginning either on the first day of pregnancy or at birth, or at 42 days or 74 days of age. This...

  13. THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

    EPA Science Inventory

    Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

  14. EFFECTS OF CHRONIC EXERCISE CONDITIONING ON THERMAL RESPONSES TO LIPOPOLYSACCHARIDE AND TURPENTINE ABSCESS IN FEMALE RATS.

    EPA Science Inventory

    Chronic exercise conditioning has been shown to alter basal thermoregulatory processes as well as the response to inflammatory agents. Two such agents, lipopolysaccharide (LPS) and turpentine (TPT) are inducers of fever in rats. LPS, given intraperitoneally (i.p.), involves a sys...

  15. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  16. Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

    PubMed Central

    Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

    2014-01-01

    Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

  17. Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

    PubMed

    Burda-Malarz, Kinga; Kus, Krzysztof; Ratajczak, Piotr; Czubak, Anna; Hardyk, Szymon; Nowakowska, Elżbieta

    2014-07-01

    Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs. PMID:24215604

  18. Neuroprotective and hepatoprotective effects of micronized purified flavonoid fraction (Daflon®) in lipopolysaccharide-treated rats.

    PubMed

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Abd-Elmoniem, Mehrevan; Omara, Enayat; Sleem, Amany A

    2012-12-01

    Micronized purified flavonoid fraction (MPFF, Daflon®) is a phlebotonic drug widely used in chronic venous or lymphatic insufficiency. We aimed to investigate the effects of MPFF on hepatic and brain oxidative stress and on liver injury caused by lipopolysaccharide (LPS) in rats. MPFF (4.5, 9, or 18 mg/kg) or saline was administered orally for two days prior to intraperitoneal (i.p.) LPS (300 μg/kg) and at time of LPS administration. Rats were euthanized 4 h after LPS injection. The administration of LPS increased oxidative stress in brain and liver tissue. Malondialdehyde (MDA) increased by 193.5 and 191.8%, reduced glutathione (GSH) decreased by 73.8 and 70.8% and nitric oxide increased by 118.2 and 151.7% in the brain and liver, respectively. Serum paraoxonase 1 (PON1) activity decreased by 42.6%. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were raised by 101.8, 93.6, and 223.2%, respectively. Rats treated with MPFF at 9 and 18 mg/kg showed decreased brain MDA (27.5-34%), nitrite (25.5-41%) and increased GSH (27.2-74.1%). In the liver, MDA decreased by 16.4-59.8%, nitrite decreased by 54.7-56.7%, and GSH increased by 15.2-70.5% with MPFF at 4.5, 9, or 18 mg/kg, respectively. Serum PON1 activity showed 41-65.9% increments with MPFF. Significant reductions in serum AST, ALT, and ALP were seen after treatment with MPFF. Moreover, the degree of histological damage, expression of the inducible form of nitric oxide synthase and the apoptotic enzyme caspase-3 in the liver were substantially reduced. MPFF thus prevented the increased oxidative stress and inflammation in brain and liver as well as the liver dysfunction caused by endotoxemia in the rat. PMID:23337818

  19. Plasma metabonomics study on toxicity biomarker in rats treated with Euphorbia fischeriana based on LC-MS.

    PubMed

    Wang, Yingfeng; Man, Hongxue; Gao, Jian; Liu, Xinfeng; Ren, Xiaolei; Chen, Jianxin; Zhang, Jiayu; Gao, Kuo; Li, Zhongfeng; Zhao, Baosheng

    2016-09-01

    Lang-du (LD) has been traditionally used to treat human diseases in China. Plasma metabolic profiling was applied in this study based on LC-MS to elucidate the toxicity in rats induced by injected ethanol extract of LD. LD injection was given by intraperitoneal injection at doses of 0.1, 0.05, 0.025 and 0 g kg(-1) body weight per day to rats. The blood biochemical levels of alanine aminotransferase, direct bilirubin, creatinine, serum β2-microglobulin and low-density lipoprotein increased in LD-injected rats, and the levels of total protein and albumin decreased in these groups. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structures discriminate analysis (OPLS-DA). The metabolic characters in rats injected with LD were perturbed in a dose-dependent manner. By OPLS-DA, 18 metabolites were served as the potential toxicity biomarkers. Moreover, LD treatment resulted in an increase in the p-cresol, p-cresol sulfate, lysophosphatidylethanolamine (LPE) (18:0), LPE (16:0), lysophosphatidylcholine (16:0) and 12-HETE concentrations, and a decrease in hippuric acid, cholic acid and N-acetyl-l-phenylalanine. These results suggested that chronic exposure to LD could cause a disturbance in lipids metabolism and amino acids metabolism, etc. Therefore, an analysis of the metabolic profiles can contribute to a better understanding of the adverse effects of LD. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26856302

  20. Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in L-NAME-treated rats.

    PubMed

    Dhaliwal, Jasdeep S; Casey, David B; Greco, Anthony J; Badejo, Adeleke M; Gallen, Thomas B; Murthy, Subramanyam N; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2007-11-01

    The small GTP-binding protein and its downstream effector Rho kinase play an important role in the regulation of vasoconstrictor tone. Rho kinase activation maintains increased pulmonary vascular tone and mediates the vasoconstrictor response to nitric oxide (NO) synthesis inhibition in chronically hypoxic rats and in the ovine fetal lung. However, the role of Rho kinase in mediating pulmonary vasoconstriction after NO synthesis inhibition has not been examined in the intact rat. To address this question, cardiovascular responses to the Rho kinase inhibitor fasudil were studied at baseline and after administration of an NO synthesis inhibitor. In the intact rat, intravenous injections of fasudil cause dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and increases in cardiac output. L-NAME caused a significant increase in pulmonary and systemic arterial pressures and a decrease in cardiac output. The intravenous injections of fasudil after L-NAME caused dose-dependent decreases in pulmonary and systemic arterial pressure and increases in cardiac output, and the percent decreases in pulmonary arterial pressure in response to the lower doses of fasudil were greater than decreases in systemic arterial pressure. The Ca(++) entry blocker isradipine also decreased pulmonary and systemic arterial pressure in L-NAME-treated rats. Infusion of sodium nitroprusside restored pulmonary arterial pressure to baseline values after administration of L-NAME. These data provide evidence in support of the hypothesis that increases in pulmonary and systemic vascular resistance following L-NAME treatment are mediated by Rho kinase and Ca(++) entry through L-type channels, and that responses to L-NAME can be reversed by an NO donor. PMID:17766587

  1. Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia.

    PubMed

    Chung, Danielle; Dzal, Yvonne A; Seow, Allison; Milsom, William K; Pamenter, Matthew E

    2016-03-30

    Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH). Conversely, naked mole rats do not hyperventilate in acute hypoxia and their response to CSH has not been examined. In this study, we explored mechanisms of plasticity in the control of the hypoxic ventilatory response (HVR) and hypoxic metabolic response (HMR) of freely behaving naked mole rats following 8-10 days of chronic sustained normoxia (CSN) or CSH. Specifically, we investigated the role of the major inhibitory neurotransmitter γ-amino butyric acid (GABA) in mediating these responses. Our study yielded three important findings. First, naked mole rats did not exhibit ventilatory plasticity following CSH, which is unique among adult animals studied to date. Second, GABA receptor (GABAR) antagonism altered breathing patterns in CSN and CSH animals and modulated the acute HVR in CSN animals. Third, naked mole rats exhibited GABAR-dependent metabolic plasticity following long-term hypoxia, such that the basal metabolic rate was approximately 25% higher in normoxic CSH animals than CSN animals, and GABAR antagonists modulated this increase. PMID:27009224

  2. Effect of chronic stress and mifepristone treatment on voltage-dependent Ca2+ currents in rat hippocampal dentate gyrus.

    PubMed

    van Gemert, N G; Joëls, M

    2006-10-01

    Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the present study, we examined: (i) whether these changes in expression are accompanied by altered Ca2+ currents in rat dentate granule cells recorded on day 22 and (ii) whether treatment with the glucocorticoid receptor antagonist mifepristone during the last 4 days of the stress protocol normalises the putative stress-induced effects. Three weeks of unpredictable stress did not affect Ca2+ current amplitude in dentate granule cells under basal conditions (i.e. after incubation with vehicle solution). However, the sustained Ca2+ current component (which largely depends on the alpha1C subunit) was significantly increased in amplitude after chronic stress when slices had been treated with corticosterone 1-4 h before recording. These findings suggest that dentate granule cells are exposed to an increased calcium load after exposure to an acute stressor when they have a history of chronic stress, potentially leading to increased vulnerability of the cells. The present results are in line with the molecular data on Ca2+ channel alpha1C subunit expression. A significant three-way interaction between chronic stress, corticosterone application and mifepristone treatment was found, indicating that the combined effect of stress and corticosterone depends on mifepristone cotreatment. Interestingly, current density (defined as total current divided by capacitance) did not differ between the groups. This indicates that the observed changes in Ca2+ current amplitude could be attributable to changes in cell size. PMID:16965291

  3. Impact of chronic stressors on the anxiety profile of pregnant rats.

    PubMed

    de Brito Guzzo, Soliani Flaviane Cristina; Rafael, Cabbia; Matheus Fitipaldi, Batistela; Amarylis Garcia, Almeida; Vinícius Dias, Kümpel; Luiz, Yamauchi Junior; Fernando, Frei; Telma Gonçalves Carneiro Spera de, Andrade

    2015-04-01

    The manifestation of anxiety during pregnancy can be caused by multiple factors and may have emotional and physical consequences for both the mother and the fetus. The prevalence of gestational anxiety has grown in recent years, making the development of studies for its comprehension essential. Thus, the aim of this investigation was to evaluate the effects of predictable and unpredictable chronic stressors on the anxiety profile of rats in three distinct stages of pregnancy (1st, 2nd and 3rd weeks). Wistar dams were divided into three groups: control, social separation and unpredictable chronic stress. Behavioral assessments were conducted in the Elevated Plus-Maze at the end of the 1st, 2nd and 3rd weeks of gestation. The results showed that there was increased anxiety in the proximity of parturition in control dams. Chronic stressors differentially affected the behavior of pregnant rats according to the gestational period where they were applied: social separation decreased anxiety at the end of the 3rd week, while unpredictable chronic stress caused increased anxiety, especially at the end of the 2nd gestational week. These results show that there is a critical time during pregnancy for the onset of anxiety in control rats, depending on the gestational stage. The exposure to different types of chronic stressors may result in distinct behaviors related to this disorder. PMID:25665962

  4. [Chronic bronchial dilatations in different colonies of laboratory rats].

    PubMed

    Miguel, Juan Carlos; Erazo, Ariana; Beduino, Fernanda; Picena, Juan Carlos; Luciano, María Isabel; Pizzutti, Gustavo; Tarrés, María Cristina; Montenegro, Silvana; Martínez, Stella Maris

    2002-06-01

    Bronchiectasis occurred naturally in 12-month-old spontaneously diabetic eSS male rats. The lungs of 3 and 6-month-old eSS rats were compared in eumetabolic eSS rats from three inbred lines consisting of inbred spontaneously diabetic eSS derived from IIM strain; these were compared with eumetabolic, outbred Wistar rats, paired by sex and age. Acrylic casts of bronchial tree were obtained after injection of a plastic substance. The casts were pruned to focus on the first four bronchial branchings. Diameter and volume of the conductive bronchial tree were determined using a binocular magnifier. Histological sections were obtained. All lines showed multiple bronchiectasis, mostly fusiform, bronchial dilatation and inflammatory response with lymphocytic infiltrates. These symptoms were much more severe in 180-day-old eSS males. Bacteria were isolated from the lungs in 70% of cases (n = 32), except in eSS rats. Pseudomonas spp. (38%) and Gram-positive cocci as coagulase-negative Staphylococcus spp. (20%) were detected. Neither pathogenic bacteria nor saprophyte fungi were found. Although all lines were affected, diabetes in eSS appears to be an aggravating factor. PMID:12152476

  5. Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats

    SciTech Connect

    Evans, E.B.; Seifen, E.; Kennedy, R.H.; Kafiluddi, R.; Paule, M.G.; Scallet, A.C.; Ali, S.F.; Slikker, W. Jr.

    1987-10-01

    This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)(/sup 3/H)dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

  6. Atypical dissemination of the highly neurotropic Borna disease virus during persistent infection in cyclosporine A-treated, immunosuppressed rats.

    PubMed Central

    Stitz, L; Schilken, D; Frese, K

    1991-01-01

    In adult rats infected with Borna disease virus, the virus was found exclusively in the brain, whereas in cyclosporine A-treated rats, infectious virus was also detected in peripheral nerve fibers and, unexpectedly, in adjacent organ-specific cells. In contrast to untreated virus-infected rats, no major histocompatibility complex class II expression was found in the brain of cyclosporine A-treated animals. Images PMID:1985209

  7. Defining the Role of Cognitive Behavioral Therapy in Treating Chronic Low Back Pain: An Overview.

    PubMed

    Hanscom, David A; Brox, Jens Ivar; Bunnage, Ray

    2015-12-01

    Study Design Narrative review of the literature. Objectives Determine if the term cognitive behavioral therapy (CBT) is useful in clinical care and research. What literature supports these variables being relevant to the experience of chronic pain? What effects of CBT in treating these factors have been documented? What methods and platforms are available to administer CBT? Methods Chronic low back pain (CLBP) is a complex neurologic disorder with many components. CBT refers to a broad family of therapies that address both maladaptive thoughts and behaviors. There are several ways to deliver it. CLBP was broken into five categories that affect the perception of pain, and the literature was reviewed to see the effects of CBT on these variables. Results The term cognitive behavioral therapy has little use in future research because it covers such a wide range of therapies. CBT should always be defined by the problem it is intended to solve. The format and method of delivery should be defined because they have implications for outcomes. They are readily available even at the primary care level. The effectiveness of CBT is unquestioned regarding its effectiveness in treating each of the variables that affect CLBP. It is unclear why it is not more widely implemented. Conclusions CBT represents a family of therapies that are effective for a wide range of problems, many of which coexist with and influence CLBP. Each of the variables can be improved with focused CBT. Early, widespread adoption of CBT in treating and preventing CLBP is recommended. Future research and clinical care should focus on strategies to operationalize these well-documented treatments utilizing a public health approach. PMID:26682100

  8. Defining the Role of Cognitive Behavioral Therapy in Treating Chronic Low Back Pain: An Overview

    PubMed Central

    Hanscom, David A.; Brox, Jens Ivar; Bunnage, Ray

    2015-01-01

    Study Design Narrative review of the literature. Objectives Determine if the term cognitive behavioral therapy (CBT) is useful in clinical care and research. What literature supports these variables being relevant to the experience of chronic pain? What effects of CBT in treating these factors have been documented? What methods and platforms are available to administer CBT? Methods Chronic low back pain (CLBP) is a complex neurologic disorder with many components. CBT refers to a broad family of therapies that address both maladaptive thoughts and behaviors. There are several ways to deliver it. CLBP was broken into five categories that affect the perception of pain, and the literature was reviewed to see the effects of CBT on these variables. Results The term cognitive behavioral therapy has little use in future research because it covers such a wide range of therapies. CBT should always be defined by the problem it is intended to solve. The format and method of delivery should be defined because they have implications for outcomes. They are readily available even at the primary care level. The effectiveness of CBT is unquestioned regarding its effectiveness in treating each of the variables that affect CLBP. It is unclear why it is not more widely implemented. Conclusions CBT represents a family of therapies that are effective for a wide range of problems, many of which coexist with and influence CLBP. Each of the variables can be improved with focused CBT. Early, widespread adoption of CBT in treating and preventing CLBP is recommended. Future research and clinical care should focus on strategies to operationalize these well-documented treatments utilizing a public health approach. PMID:26682100

  9. Chronic toxicity of phosalone to rats: Effect on erythropoiesis

    SciTech Connect

    Reddy, S.J.; Reddy, D.C.; Kalarani, V.; Ramamurthi, R. )

    1989-12-01

    It is well known that organophosphorus insecticides (OPI) act as nerve poisons by blocking synaptic transmission in cholinergic part of the nervous system. Phosalone (0,0-diethyl-S-(6-chloro-1,3-benzoxozol-2(3H)-onylmethyl)phosphorodithioate), an OPI, is being extensively used to kill insect crop pests in this part of India. Studies on the effects of phosalone on physiology of vertebrates are very few. Prolonged exposure to phosalone has been reported to cause marked changes in body weight, liver weight and RBC of rats. Others reported a decrease in brain SDH activity of rat dosed with phosalone, and a decrease in brain acetylcholinesterase (AchE) activity of fish exposed to phosalone. However, the effect of multiple sublethal doses of phosalone on haemopoietic system of rat has not yet been fully evaluated. The present investigation is one such attempt over a 60 day period.

  10. Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats.

    PubMed

    Niknazar, Somayeh; Nahavandi, Arezo; Peyvandi, Ali Asghar; Peyvandi, Hassan; Akhtari, Amin Shams; Karimi, Mohsen

    2016-08-01

    Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats' hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development. PMID:26189832

  11. Erythropoietin promotes deleterious cardiovascular effects and mortality risk in a rat model of chronic sports doping.

    PubMed

    Piloto, Nuno; Teixeira, Helena M; Teixeira-Lemos, Edite; Parada, Belmiro; Garrido, Patrícia; Sereno, José; Pinto, Rui; Carvalho, Lina; Costa, Elísio; Belo, Luís; Santos-Silva, Alice; Teixeira, Frederico; Reis, Flávio

    2009-12-01

    Athletes who abuse recombinant human erythropoietin (rhEPO) consider only the benefit to performance and usually ignore the potential short and long-term liabilities. Elevated haematocrit and dehydratation associated with intense exercise may reveal undetected cardiovascular risk, but the mechanisms underlying it remain to be fully explained. This study aimed to evaluate the cardiovascular effects of rhEPO in rats under chronic aerobic exercise. A ten week protocol was performed in four male Wistar rat groups: control--sedentary; rhEPO--50 IU kg(-1), 3 times/wk; exercised (EX)--swimming for 1 h, 3 times/wk; EX + rhEPO. One rat of the EX + rhEPO group suffered a sudden death episode during the week 8. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertrophy, sympathetic and serotonergic overactivation. The suddenly died rat's tissues presented brain with vascular congestion; left ventricular hypertrophy, together with a "cardiac-liver", suggesting the hypothesis of heart failure as cause of sudden death. In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected RBC count increment, suggesting hyperviscosity, but also other serious deleterious cardiovascular and thromboembolic modifications, including mortality risk, which might be known and assumed by all sports authorities, including athletes and their physicians. PMID:19859831

  12. Metabolic and behavioral effects of chronic olanzapine treatment and cafeteria diet in rats.

    PubMed

    Muller, Alexandre P; Tort, Ana H; Gnoatto, Jussânia; Moreira, Julia D; Vinadé, Elsa R; Perry, Marcos L; Souza, Diogo O; Lara, Diogo R; Portela, Luis V

    2010-10-01

    Olanzapine and highly palatable diets can alter metabolism and brain function. We investigated the interaction of chronic treatment (4 months) with olanzapine and a cafeteria diet on metabolic parameters, memory tasks (spatial and aversive), the elevated plus maze and locomotor activity induced by d-amphetamine. Male Wistar rats were separated into the following groups: standard diet vehicle, standard diet and olanzapine, cafeteria diet vehicle and cafeteria diet and olanzapine. Olanzapine was administered in the drinking water (approximately 1.5 mg/kg/day), and after 3 days of treatment, the rats exhibited an expected anxiolytic effect and reduced amphetamine-induced hyperlocomotion. After 4 months of treatment, cafeteria diet vehicle and cafeteria diet olanzapine rats exhibited an increased body weight and heavier fat pads compared with the standard diet groups. Olanzapine increased only the epididymal and mesenteric fat pads. The cafeteria diet and olanzapine group showed greater glucose intolerance compared with all other groups. The cafeteria diet altered the effects of chronic olanzapine on the performance in the water maze and inhibitory avoidance tasks. Chronic olanzapine treatment failed to affect amphetamine-induced locomotion and to produce anxiolytic effects in the elevated plus maze task, regardless of the diet. Our results suggest that chronic olanzapine caused an increase in fat pads, which is putatively involved in the etiology of many metabolic diseases. Rats on the cafeteria diet were overweight and exhibited glucose intolerance. We did not observe these effects with olanzapine treatment with the standard diet. Moreover, the chronic treatment regimen caused tolerance to the antipsychotic and anxiolytic effects of olanzapine and seemed to potentiate some of the metabolic effects of the cafeteria diet. The cafeteria diet also modified the effects of chronic treatment with olanzapine on cognitive tasks, which may represent an undesirable effect of

  13. Risk of Hip Fracture Associated with Untreated and Treated Chronic Hepatitis B Virus Infection

    PubMed Central

    Byrne, Dana D.; Newcomb, Craig W.; Carbonari, Dena M.; Nezamzadeh, Melissa S.; Leidl, Kimberly B. F.; Herlim, Maximilian; Yang, Yu-Xiao; Hennessy, Sean; Kostman, Jay R.; Leonard, Mary B.; Localio, A. Russell; Lo Re, Vincent

    2014-01-01

    Background & Aims Chronic hepatitis B (CHB) infection is associated with reduced bone mineral density, but its association with fractures is unknown. Our objectives were to determine whether untreated or treated CHB-infected persons are at increased risk for hip fracture compared to uninfected persons. Methods We conducted a cohort study among 18,796 untreated CHB-infected, 7,777 treated CHB-infected, and 979,751 randomly sampled uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999 – 2007). CHB infection was defined by two CHB diagnoses recorded >6 months apart and was classified as treated if a diagnosis was recorded and antiviral therapy was dispensed. After propensity score matching of CHB-infected and uninfected persons, Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture in: 1) untreated CHB-infected versus uninfected, and 2) treated CHB-infected versus uninfected patients. Results Untreated CHB-infected patients of black race had a higher rate of hip fracture than uninfected black persons (HR, 2.55 [95% CI, 1.42 – 4.58]). Compared to uninfected persons, relative hazards of hip fracture were increased for untreated white (HR, 1.26 [95% CI, 0.98 – 1.62]) and Hispanic (HR, 1.36 [95% CI, 0.77 – 2.40]) CHB-infected patients, and treated black (HR, 3.09 [95% CI, 0.59 – 16.22) and white (HR, 1.90 [95% CI, 0.81 – 4.47]) CHB-infected patients, but these associations were not statistically significant. Conclusions Among U.S. Medicaid enrollees, untreated CHB-infected patients of black race had a higher risk of hip fracture than uninfected black persons. PMID:24713185

  14. The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression.

    PubMed

    Liu, Lanxiang; Zhou, Xinyu; Zhang, Yuqing; Liu, Yiyun; Yang, Lining; Pu, Juncai; Zhu, Dan; Zhou, Chanjuan; Xie, Peng

    2016-05-15

    Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography-mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression. PMID:26947756

  15. Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: role of pharmaceutical formulation.

    PubMed

    Fretellier, Nathalie; Salhi, Mariem; Schroeder, Josef; Siegmund, Heiko; Chevalier, Thibaut; Bruneval, Patrick; Jestin-Mayer, Gaëlle; Delaloge, Francette; Factor, Cécile; Mayer, Jean-François; Fabicki, Jean-Michel; Robic, Caroline; Bonnemain, Bruno; Idée, Jean-Marc; Corot, Claire

    2015-05-25

    While not acutely toxic, chronic hepatic effect of certain gadolinium chelates (GC), used as contrast agent for magnetic resonance imaging, might represent a risk in renally-impaired patients due to free gadolinium accumulation in the liver. To answer this question, this study investigated the consequences of the presence of small amounts of either a soluble gadolinium salt ("free" Gd) or low-stability chelating impurity in the pharmaceutical solution of gadoteric acid, a macrocyclic GC with high thermodynamic and kinetic stabilities, were investigated in renally-impaired rats. Renal failure was induced by adding 0.75% adenine in the diet for three weeks. The pharmaceutical and commercial solution of gadoteric acid was administered (5 daily intravenous injections of 2.5 mmol Gd/kg) either alone or after being spiked with either "free" gadolinium (i.e., 0.04% w/v) or low-stability impurity (i.e., 0.06 w/v). Another GC, gadodiamide (low thermodynamic and kinetic stabilities) was given as its commercial solution at a similar dose. Non-chelated gadolinium was tested at two doses (0.005 and 0.01 mmol Gd/kg) as acetate salt. Gadodiamide induced systemic toxicity (mortality, severe epidermal and dermal lesions) and substantial tissue Gd retention. The addition of very low amounts of "free", non-chelated gadolinium or low thermodynamic stability impurity to the pharmaceutical solution of the thermodynamically stable GC gadoteric acid resulted in substantial capture of metal by the liver, similar to what was observed in "free" gadolinium salt-treated rats. Relaxometry studies strongly suggested the presence of free and soluble gadolinium in the liver. Electron microscopy examinations revealed the presence of free and insoluble gadolinium deposits in hepatocytes and Kupffer cells of rats treated with gadoteric acid solution spiked with low-stability impurity, free gadolinium and gadodiamide, but not in rats treated with the pharmaceutical solution of gadoteric acid. The

  16. Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

    PubMed

    Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

    2015-06-01

    There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. PMID:25922423

  17. Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat

    PubMed Central

    Mul, Joram D.; la Fleur, Susanne E.; Toonen, Pim W.; Afrasiab-Middelman, Anthonieke; Binnekade, Rob; Schetters, Dustin; Verheij, Michel M. M.; Sears, Robert M.; Homberg, Judith R.; Schoffelmeer, Anton N. M.; Adan, Roger A. H.; DiLeone, Ralph J.; De Vries, Taco J.; Cuppen, Edwin

    2011-01-01

    Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh) form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH). MCH promotes feeding behavior via MCH receptor-1 (MCH1R) in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding. Here we show that chronic loss of the rat MCH-precursor Pmch decreased food intake predominantly via a reduction in meal size during rat development and reduced high-fat food-reinforced operant responding in adult rats. Moreover, acute AcbSh administration of Neuropeptide-GE and Neuropeptide-EI (NEI), both additional neuropeptides derived from Pmch, or chronic intracerebroventricular infusion of NEI, did not affect feeding behavior in adult pmch+/+ or pmch−/− rats. However, acute administration of MCH to the AcbSh of adult pmch−/− rats elevated feeding behavior towards wild type levels. Finally, adult pmch−/− rats showed increased ex vivo electrically evoked dopamine release and increased limbic dopamine transporter levels, indicating that chronic loss of Pmch in the rat affects the limbic dopamine system. Our findings support the MCH-MCH1R system as an amplifier of consummatory behavior, confirming this system as a possible target for the treatment of obesity. We propose that MCH-mediated signaling in the AcbSh positively mediates motivational aspects of feeding behavior. Thereby it provides a crucial signal by which hypothalamic neural circuits control energy balance and guide limbic brain areas to enhance motivational or incentive-related aspects of food consumption. PMID

  18. The influence of chronic ethanol administration on adriamycin-induced nephrotic syndrome in rats.

    PubMed

    Tesar, V; Zima, T; Poledne, R; Stejskalová, A; Stípek, S; Tĕmínová, J

    1995-01-01

    Alcoholic liver disease may be frequently complicated by mesangial proliferation with the deposition of IgA in glomeruli and glomerulosclerosis, but these glomerular lesions are usually mild and without greater impact on renal function. To evaluate the putative role of ethanol in glomerular pathology we studied the influence of chronic ethanol administration on the development of experimental adriamycin nephropathy in rats. Nephrotic syndrome was induced by a single i.v. dose of adriamycin (5 mg/kg body wt) both in rats given ethanol at a dose of 4 g/day for 3 months and control rats given standard chow. Further controls on both diets without adriamycin administration were also studied. Blood and urine were examined before and 3 and 6 weeks after adriamycin administration. All rats were killed and examined histologically 6 weeks after adriamycin administration. Ethanol fed nephrotic rats were more catabolic than control nephrotic rats (with higher free fatty acids, lower glycaemia, higher urea with similar creatinine) and had lower proteinuria (0.55 +/- 0.34 versus 5.79 +/- 3.15 g of protein/nmol of creatinine, P < 0.05), higher albuminaemia (5.41 +/- 2.62 versus 1.92 +/- 1.94 g/l, P < 0.01), lower plasma cholesterol (6.54 +/- 2.6 versus 10.57 +/- 2.92 mmol/l, P < 0.01) and triglycerides. The development of nephrotic syndrome and renal morphological changes after adriamycin administration in rats seemed to be ameliorated, or at least delayed by chronic ethanol feeding with much milder and focal glomerulosclerosis as compared with more severe and diffuse glomerulosclerosis in control nephrotic animals. The mechanism of this effect of chronic ethanol feeding remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7748275

  19. Chronic Δ9-Tetrahydrocannabinol during Adolescence Differentially Modulates Striatal CB1 Receptor Expression and the Acute and Chronic Effects on Learning in Adult Rats.

    PubMed

    Weed, Peter F; Filipeanu, Catalin M; Ketchum, Myles J; Winsauer, Peter J

    2016-01-01

    The purpose of this study was to determine whether chronic administration of Δ(9)-tetrahydrocannabinol (THC) during adolescence would (1) modify any sex-specific effects of THC on learning and (2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35-75, yielding four groups (female/saline, female/THC, male/saline, and male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32-18 mg/kg of THC acutely as adults (experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, female rats were more sensitive than male rats were to the rate-decreasing effects. Rats were then chronically administered 10 mg/kg of THC (experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than did rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males did. Western blot analysis of brain tissue indicated long-term changes in hippocampal and striatal cannabinoid type-1 receptor (CB1R) levels despite levels that were indistinguishable immediately after chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than male rats were to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC. PMID:26462539

  20. The Effects and Possible Mechanisms of Puerarin to Treat Endometriosis Model Rats

    PubMed Central

    Zhao, Li; Zhang, Danying; Zhai, Dongxia; Shen, Wei; Bai, Lingling; Liu, Yiqun; Cai, Zailong; Li, Ji; Yu, Chaoqin

    2015-01-01

    Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β-hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic. PMID:25815028

  1. Chronic exposure to MDMA (Ecstasy) elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

    PubMed Central

    Modi, Gunjan M; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2006-01-01

    Background The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA. Methods The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg) and a saline control group (N = 9/group). All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13). Rats were then given an additional 25-day washout period, and re-challenged (day 38) with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39). Open-field locomotor activity was recorded using a computerized automated activity monitoring system. Results Acute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group), while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change in locomotor activity

  2. Expression of Serotonin Receptors in the Colonic Tissue of Chronic Diarrhea Rats

    PubMed Central

    Zhu, Tong; Qiu, Juanjuan; Wan, Jiajia; Wang, Fengyun; Tang, Xudong; Guo, Huishu

    2016-01-01

    Background/Aims: This study aimed to investigate the difference among the expression of serotonin receptors (5-HT3, 5-HT4, and 5-HT7 receptors) in colonic tissue of chronic diarrhea rats. Materials and Methods: A rat model of chronic diarrhea was established by lactose diet. The expression of 5-HT3, 5-HT4, and 5-HT7 receptors in the colonic tissue was detected using immunohistochemistry, real-time PCR and Western blotting techniques. Results: There is no significant difference on the protein expression of 5-HT3 receptor between the normal group and the chronic diarrhea model group. The mRNA expression of 5-HT3 receptor in the chronic diarrhea model group was significantly lower than that in the normal group (n = 10; P < 0.01). The protein and mRNA expression of 5-HT4 receptor in the chronic diarrhea model group were significantly higher than those in the normal group (n = 10; P < 0.05, P < 0.01). On the contrary, the protein and mRNA expressions of 5-HT7 receptor in the chronic diarrhea model group were significantly decreased compared with the normal group (n = 10; P < 0.01, P < 0.01). Conclusions: The results suggested the receptors of 5-HT4 and 5-HT7 may be involved in inducing diarrhea by lactose diet. PMID:27184643

  3. Ultrastructural Changes of Caudate Nucleus in Mice Chronically Treated with Manganese.

    PubMed

    Villalobos, Virginia; Hernández-Fonseca, Juan Pablo; Bonilla, Ernesto; Medina-Leendertz, Shirley; Mora, Marylu; Mosquera, Jesús

    2015-01-01

    Manganese (Mn) is able to cross the blood-brain barrier and induces functional and structural alterations during the intoxication by this metal. Therefore, the effects of chronic administration of Mn in the caudate nucleus of mice were evaluated by electron microscopy. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/kg/d) 5 d per week during 9 weeks. The control group received only 0.9% of NaCl solution. The caudate nuclei were extracted and subsequently processed to be observed on a conventional transmission electron microscope at 2, 4, 6, and 9 weeks after treatment. A high percentage of vacuolated and swollen mitochondria were found throughout all the analyzed periods. Myelin disarrangement and ultrastructural alterations related to edema were observed increased in Mn-treated mice at week 9. Granular degeneration of myelin at week 9 accompanied with deposition of electron dense granules in the neuropil was also observed. Edema in neuropil and glial cells was detected from week 2 to week 9 accompanied by swollen mitochondria. Neuronal bodies, synaptic terminals, and perivascular cells were found swollen. Decreased electron density in postsynaptic areas and decreased and dispersed synaptic vesicles in presynaptic areas were noted in Mn-treated animals. Some neurons from Mn-treated mice showed cisternae dilation of the Golgi apparatus. These results suggest that Mn-treatment produces structural alterations in the caudate nucleus that could be responsible for some of the neurotoxic effects of this metal. PMID:25569534

  4. Anterior vitrectomy and partial capsulectomy via anterior approach to treat chronic postoperative endophthalmitis

    PubMed Central

    Güler, Mete; Yılmaz, Turgut

    2013-01-01

    AIM To describe the results of vitrectomy and partial capsulectomy via anterior approach surgical technique in treatment of chronic postoperative endophthalmitis (CPE). METHODS Clinical records of 9 patients treated for CPE between 2006 and 2010 were reviewed retrospectively. All of these patients were treated with vitrectomy and partial capsulectomy via anterior approach. RESULTS Six of 9 patients were male. The average patients' age was (60±8.1) years. The average period between cataract extraction and onset of signs and symptoms was (3.6±1.3) weeks. The average presenting visual acuity was 0.3±0.1 and the average final post operative visual acuity was 0.7±0.2. The mean follow-up period was (28.1±8.9) weeks. In all patients, the inflammation subsided after surgery. CONCLUSION Our results suggest that anterior vitrectomy and partial capsulectomy via anterior approach may be considered as potentially useful and relatively less invasive technique to treat CPE. PMID:23550103

  5. Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats.

    PubMed

    Min, Jung-Ah; Lee, Hye-Ryeon; Kim, Jae-Ick; Ju, Anes; Kim, Dai-Jin; Kaang, Bong-Kiun

    2011-08-01

    Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF-Alcohol (O-A, n=5) and the OLETF-Control (O-C, n=5). The rats in the O-A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42±2.52g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O-A group showed significantly lower fasting and postprandial glucose (P<0.01 and P=0.02, respectively), the hippocampal LTP was more significantly attenuated in the O-A group than the O-C group (P=0.032). The results of this study suggested that chronic heavy alcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes. PMID:21683761

  6. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  7. Injected tryptophan increases brain but not plasma tryptophan levels more in ethanol treated rats

    SciTech Connect

    Haleem, D.J. )

    1990-01-01

    In the present study ethanol treatment given for two weeks decreased hepatic apo-tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation.

  8. Antihyperuricemic effects of thiadiazolopyrimidin-5-one analogues in oxonate treated rats.

    PubMed

    Sathisha, Kadanuru R; Gopal, Shubha; Rangappa, Kanchugarakoppal S

    2016-04-01

    Hyperuricemia is a risk factor for not only gout, but also to a variety of disorders that affect the vital organ systems of the human body. The xanthine oxidase (XO) is the key enzyme in the production of uric acid and its inhibition can inhibit hyperuricemia. Although, XO inhibitor allopurinol is widely prescribed antigout agent but its use is not without any side effects. Previously, we described the synthesis of four novel thiadiazolopyrimidin-5-one analogues as effective XO inhibitors and molecular docking studies also confirmed this. When these analogues were tested in potassium oxonate treated rats, their serum uric acid and creatinine levels were dropped significantly from 4.85±0.03mg/dl to 1.21±0.01mg/dl and 0.92±0.02mg/dl to 0.40±0.02mg/dl respectively. Among the pyrimidine analogues tested, 6a was most potent. Histological examinations of both liver and kidney tissues exhibited severe necrosis in oxonate treated rats and pyrimidine analogues could significantly attenuate this with a correlative inhibitory profile of hepatic XO from the same rats. Our results demonstrate antihyperuricemic effect of novel thiadiazolopyrimidin-5-one analogues in oxonate treated rats, which can be further explored not only as antigout therapeutics but also in other systems where hyperuricemia is the driving cause of the disease. PMID:26875636

  9. Zinc improves the immune function and the proliferation of lymphocytes in Cadmium-treated rats

    PubMed Central

    Hassan, Iftekhar; Bashandy, Samir; Taha, Nael Abu; Mahmood, Amer; Alomar, Suliman; Alhazza, Iibrahim; Mashaly, Ashraf; Rady, Ahmed

    2014-01-01

    The effects of Cadmium (Cd) exposure and the treatment with Zinc (Zn) on immune functions of splenocytes and cultured lymphocytes of rats were studied. The exposure of rats to Cd was at a dose of 2.2 mg/kg CdCl2, injected subcutaneously four times weekly for 2 months. Rats were supplemented with Zn (2.2 mg/kg ZnCl2, injected subcutaneously four times weekly for 2 months) one hour prior to Cd exposure. Spleens were removed and splenocytes were isolated and cultured. The proliferation capacity of lymphocytes and their homing to the spleen were studied. Ribonucleic acid (RNA) was extracted from stimulated lymphocytes in order to analyse gene expressions using RT-PCR. Accordingly, proliferation of lymphocytes was found to be suppressed in Cd-treated rats, both in vivo and in vitro. Zinc served to activate the proliferation of B and T lymphocytes in Cd-treated rats both in vivo and in vitro. Antigen-activated lymphocytes showed that Cd impaired the mRNA expression of CD68, Ccl22 and CXCL10. Zinc was not found to restore mRNA expression of these genes to the normal levels. Zinc was found to decrease the MDA level with replenishment of activity of key antioxidant enzymes and proteins in Cd-pre-treated animals significantly. Moreover, the histopathological examination of spleen samples also agreed with the molecular, immunological and redox findings. Hence, Zn is able to restore the normal structure, redox status and immunity in Cd-induced damage in the rat model system. PMID:26155160

  10. Histomorphometric changes in the perirenal adipocytes of adrenalectomized rats treated with dexamethasone

    PubMed Central

    Ahmad, Fairus; Soelaiman, Ima Nirwana; Ramli, Elvy Suhana Mohd; Hooi, Tan Ming; Suhaimi, Farihah H

    2011-01-01

    INTRODUCTION: Prolonged steroid treatment administered to any patient can cause visceral obesity, which is associated with metabolic disease and Cushing's syndrome. Glucocorticoids have a profound negative effect on adipose tissue mass, giving rise to obesity, which in turn is regulated by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Adrenalectomized rats treated with dexamethasone exhibited an increase in visceral fat deposition but not in body weight. OBJECTIVES: The main aim of this study was to determine the effect of dexamethasone on the histomorphometric characteristics of perirenal adipocytes of adrenalectomized, dexamethasone-treated rats (ADR+Dexa) and the association of dexamethasone treatment with the expression and activity of 11β-hydroxysteroid dehydrogenase type 1 (11β- hydroxysteroid dehydrogenase type 1). METHODS: A total of 20 male Sprague Dawley rats were divided into 3 groups: a baseline control group (n = 6), a sham-operated group (n = 7) and an adrenalectomized group (n = 7). The adrenalectomized group was given intramuscular dexamethasone (ADR+Dexa) 2 weeks post adrenalectomy, and the rats from the sham-operated group were administered intramuscular vehicle (olive oil). RESULTS: Treatment with 120 µg/kg intramuscular dexamethasone for 8 weeks resulted in a significant decrease in the diameter of the perirenal adipocytes (p<0.05) and a significant increase in the number of perirenal adipocytes (p<0.05). There was minimal weight gain but pronounced fat deposition in the dexamethasone-treated rats. These changes in the perirenal adipocytes were associated with high expression and dehydrogenase activity of 11β-hydroxysteroid dehydrogenase type 1. CONCLUSIONS: In conclusion, dexamethasone increased the deposition of perirenal fat by hyperplasia, which causes increases in the expression and dehydrogenase activity of 11β-hydroxysteroid dehydrogenase type 1 in adrenalectomized rats. PMID:21789391

  11. Spleen-Specific Development of Germinal Centers in Rats Treated with Antithyroid Drugs

    PubMed Central

    Fukui, Motoko; Fukui, Norio; Sakai, Kuniyoshi; Hasegawa, Yuko; Nagasaki, Shuji; Shibata, Seiji; Araki, Sei-ichi; Isobe, Mitsui; Hisada, Shigeru

    2013-01-01

    The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in the immune system in male and female rats given MMI (2, 20 and 200 mg/kg/day, p.o., in experiment 1; 200 mg/kg/day, p.o., in experiment 3) or PTU (25 and 250 mg/kg/day, p.o., in experiment 2; 200 mg/kg/day, p.o., in experiment 3) for two weeks. In experiments 1 and 2, highest doses of MMI and PTU induced histopathologic changes in the spleen consistent with those in experiment 3 without any changes in the other peripheral lymphoid organs and tissues. In experiment 3, histopathological evaluation of the spleen along with hematological and bone marrow examinations were performed. In both male and female rats, MMI or PTU induced histopathological changes in the spleen characterized by development of germinal centers and an increase in the number of IgG-positive plasma cells in the red pulp; these changes were most prevalent in the MMI-treated female rats. Total red and white blood cell counts were decreased in the MMI-treated male and female rats; lymphocytes and monocytes were lower in male and female rats, respectively. Bone marrow nucleated cells were significantly lower in the MMI-treated males. This is the first study to demonstrate that ATDs induce spleen specific B-cell reactions in rats PMID:24526810

  12. Development of tolerance to the inhibitory effects of ethanol in the rat isolated vas deferens: effect of acute and chronic ethanol administration in vivo.

    PubMed Central

    DeTurck, K. H.; Pohorecky, L. A.

    1986-01-01

    Contractions of the rat vas deferens elicited by the addition of noradrenaline (NA), K+-depolarizing solutions or by electrical stimulation were recorded before and after incubation with ethanol 181 mM. In tissues from untreated rats, the contractions were inhibited 40-50% by such exposure. Injection of ethanol (2 g kg-1) significantly attenuated ethanol's reduction of peak tension generated by the lowest concentration of NA (10(-4) mM). Chronic administration of ethanol, 18-14 g kg-1 daily for two weeks, resulted in significant tolerance to ethanol. Tissues of treated animals demonstrated ethanol-induced decreases of roughly one-half those of the maltose dextrin (isocaloric) and water (fluid control) groups. This tolerance persisted for at least 48 h after ethanol treatment had been terminated. Overall, the data suggest that ethanol acts both pre- and postsynaptically to produce acute inhibition of smooth muscle contractions or tolerance to these actions upon chronic exposure. PMID:3730699

  13. Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats

    PubMed Central

    Marfà, Santiago; Morales-Ruiz, Manuel; Oró, Denise; Ribera, Jordi; Fernández-Varo, Guillermo; Jiménez, Wladimiro

    2016-01-01

    ABSTRACT At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis. PMID:27230648

  14. Studies on organ weights in naproxen treated rats after intermittent exposure to simulated high altitude

    NASA Astrophysics Data System (ADS)

    Saha, R. C.; Biswas, H. M.

    1990-06-01

    Rats were exposed intermittently for 8h per day over 6 days at simulated high altitude of 20 000 feet. One group of altitude-exposed animals was treated with naproxen, a prostaglandin inhibiting drug. Significant reduction in body weight gain was observed in both altitude-exposed and drug-treated altitude-exposed animals compared to the control group. Right and left ventricular weights and weights of the adrenal glands were increased significantly in altitude-exposed and altitude-exposed drug-treated animals. The weight of the spleen was increased significantly in altitude-exposed animals whereas no such increase of splenic weight was observed in drug-treated altitude-exposed group of animals. On the other hand, the weight of the liver was decreased significantly in both cases. In drug-treated altitude-exposed animals, the unaltered splenic weight was thought to be due to inhibition of the erythropoietic activity.

  15. Cytoarchitectural, behavioural and neurophysiological dysfunctions in the BCNU-treated rat model of cortical dysplasia.

    PubMed

    Inverardi, Francesca; Chikhladze, Maia; Donzelli, Andrea; Moroni, Ramona Frida; Regondi, Maria Cristina; Pennacchio, Paolo; Zucca, Ileana; Corradini, Irene; Braida, Daniela; Sala, Mariaelvina; Franceschetti, Silvana; Frassoni, Carolina

    2013-01-01

    Cortical dysplasias (CDs) include a spectrum of cerebral lesions resulting from cortical development abnormalities during embryogenesis that lead to cognitive disabilities and epilepsy. The experimental model of CD obtained by means of in utero administration of BCNU (1-3-bis-chloroethyl-nitrosurea) to pregnant rats on embryonic day 15 mimics the histopathological abnormalities observed in many patients. The aim of this study was to investigate the behavioural, electrophysiological and anatomical profile of BCNU-treated rats in order to determine whether cortical and hippocampal lesions can directly lead to cognitive dysfunction. The BCNU-treated rats showed impaired short-term working memory but intact long-term aversive memory, whereas their spontaneous motor activity and anxiety-like response were normal. The histopathological and immunohistochemical analyses, made after behavioural tests, revealed the disrupted integrity of neuronal populations and connecting fibres in hippocampus and prefrontal and entorhinal cortices, which are involved in memory processes. An electrophysiological evaluation of the CA1 region of in vitro hippocampal slices indicated a decrease in the efficiency of excitatory synaptic transmission and impaired paired pulse facilitation, but enhanced long-term potentiation (LTP) associated with hyperexcitability in BCNU-treated rats compared with controls. The enhanced LTP, associated with hyperexcitability, may indicate a pathological distortion of long-term plasticity. These findings suggest that prenatal developmental insults at the time of peak cortical neurogenesis can induce anatomical abnormalities associated with severe impairment of spatial working memory in adult BCNU-treated rats and may help to clarify the pathophysiological mechanisms of cognitive dysfunction that is often associated with epilepsy in patients with CD. PMID:23095101

  16. NMR-Based Metabolic Profiling Reveals Neurochemical Alterations in the Brain of Rats Treated with Sorafenib.

    PubMed

    Du, Changman; Shao, Xue; Zhu, Ruiming; Li, Yan; Zhao, Qian; Fu, Dengqi; Gu, Hui; Kong, Jueying; Luo, Li; Long, Hailei; Deng, Pengchi; Wang, Huijuan; Hu, Chunyan; Zhao, Yinglan; Cen, Xiaobo

    2015-11-01

    Sorafenib, an active multi-kinase inhibitor, has been widely used as a chemotherapy drug to treat advanced clear-cell renal cell carcinoma patients. In spite of the relative safety, sorafenib has been shown to exert a negative impact on cognitive functioning in cancer patients, specifically on learning and memory; however, the underlying mechanism remains unclear. In this study, an NMR-based metabolomics approach was applied to investigate the neurochemical effects of sorafenib in rats. Male rats were once daily administrated with 120 mg/kg sorafenib by gavage for 3, 7, and 28 days, respectively. NMR-based metabolomics coupled with histopathology examinations for hippocampus, prefrontal cortex (PFC), and striatum were performed. The (1)H NMR spectra data were analyzed by using multivariate pattern recognition techniques to show the time-dependent biochemical variations induced by sorafenib. Excellent separation was obtained and distinguishing metabolites were observed between sorafenib-treated and control rats. A total of 36 differential metabolites in hippocampus of rats treated with sorafenib were identified, some of which were significantly changed. Furthermore, these modified metabolites mainly reflected the disturbances in neurotransmitters, energy metabolism, membrane, and amino acids. However, only a few metabolites in PFC and striatum were altered by sorafenib. Additionally, no apparent histological changes in these three brain regions were observed in sorafenib-treated rats. Together, our findings demonstrate the disturbed metabonomics pathways, especially, in hippocampus, which may underlie the sorafenib-induced cognitive deficits in patients. This work also shows the advantage of NMR-based metabolomics over traditional approach on the study of biochemical effects of drugs. PMID:26233726

  17. Impact of acute and chronic stress hormone on male albino rat brain

    PubMed Central

    Han, Li-Li; Chen, Ling; Dong, Zhi-Ling

    2015-01-01

    The present investigation aimed to evaluate the acute and chronic effect of stress (stress hormone) in male albino rat brain. Nor-epinephrine was used for the treatment and saline used for the control. Nor-epinephrine was dissolved in the saline and administered orally to the rats. Following nor-epinephrine administration, the brain was removed surgically at 6 h, 12 h and 45 days. Alanine tansaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) were significantly altered in the rats. Lipid peroxidation was measured as malondialdehyde (MDA), showed altered lipid peroxidation. Hematological markers such as packed cell volume (PCV), white blood cells (WBC), neutrophil, lymphocytes and hemoglobin were significantly altered compared to controls. Altered serum biochemical and hematological markers, lipid peroxidation and enzyme activities leads to adverse effect in the cellular metabolism and physiological activities of rats. PMID:26261571

  18. Nourishing Yin and Promoting Blood Circulation of TCM to Treat Hemorheologic Disorder Induced by Diabetes Mellitus in Rats

    PubMed Central

    Huang, Ping; Shao, Guo-ming

    2007-01-01

    Diabetes mellitus, DM, is commonly accompanied with various stages of hemorheologic disturbances that are the main causes of the development of chronic DM. In this study, simple Chinese material medica [yang-yin jiang-tang preparation (YYJT)] was given to alloxan-induced DM rats and analyzed to compare the changes of fasting blood glucose (FBG), fasting insulin (FINS), hemorheologic parameters and insulin-like growth factor II (IGF-II) before and after administration. The results suggested that YYJT can significantly downregulate FBG (P < 0.005), improve insulin resistance and beta-cell secretion (P < 0.05), decrease whole blood viscosity at low and high shear rates, gathering of blood index test (GIT) and fibrinogen (FIB) (P < 0.05), and enlarge the function of IGF-II (P < 0.05). We concluded that YYJT could prevent and treat hemorheologic disorder in DM rats by means of reducing glucose, improving insulin resistance and elevating IGF-II. PMID:17549237

  19. Protective potential of the methanol extract of Macrothelypteris oligophlebia rhizomes for chronic non-bacterial prostatitis in rats.

    PubMed

    Han, Pan; Lai, Yong Ji; Chen, Jing; Zhang, Xue Nong; Chen, Jing Lou; Yang, Xian; Xue, Ping Ping; Ruan, Jin Lan

    2016-07-01

    The protective potential of the methanol extract of Macrothelypteris oligophlebia rhizomes (MMO) for chronic non-bacterial prostatitis (CNP) in rats was investigated in the present study. Carrageenan-induced CNP in rats was established. Fifty rats were randomly divided into sham-operated (sham-ope) group, model group, positive control group (Cernilton at a dose of 148mg/kg body weight) and two MMO-treated groups (MMO at doses of 600mg/kg and 300 mg/kg body weight). The anti-prostatitis effect was evaluated by prostate index, the levels of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), and histopathological examination. After 20 days of administration, MMO could significantly decrease prostate index and the levels of IL-10, TNF-α COX-2 and PGE2 in serum and could improve the prostate morphology in comparison with the model group. In summary, these results suggest that MMO possesses protective effects on prostate, which might be beneficial to further development for the treatment of CNP. PMID:27393434

  20. Comparative pharmacokinetics of catalpol and acteoside in normal and chronic kidney disease rats after oral administration of Rehmannia glutinosa extract.

    PubMed

    Zhao, Min; Qian, Dawei; Liu, Pei; Shang, Er-xin; Jiang, Shu; Guo, Jianming; Su, Shu-lan; Duan, Jin-ao; Du, Leyue; Tao, Jinhua

    2015-12-01

    In this study, a sensitive and robust ultra-performance liquid chromatography-mass spectrometry method with multiple-reaction monitoring mode was developed, validated, and applied to determine pharmacokinetics of catalpol and acteoside in normal and doxorubicin-induced chronic kidney disease rats after oral administration of Rehmannia glutinosa extract. The lower limits of quantification for catalpol and acteoside in rat plasma were 2.62 and 0.61 ng/mL, with a signal-to-noise ratio of ≥10. Precision and accuracy studies showed that catalpol and acteoside plasma concentrations were within the 10% range in all studies. The extraction recoveries of catalpol and acteoside were both >68.24% and the matrix effects ranged from 96.59 to 101.62%. The method was successfully applied to the pharmacokinetic study of catalpol and acteoside after oral administration of RG extract to normal and model rats, respectively. This study might further support the traditional use of RG to treat kidney diseases clinically. PMID:26031219

  1. Chronic Ethanol Exposure during Adolescence in Rats Induces Motor Impairments and Cerebral Cortex Damage Associated with Oxidative Stress

    PubMed Central

    Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex. PMID:24967633

  2. Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.

    PubMed

    Chiş, I C; Mureşan, A; Oros, A; Nagy, A L; Clichici, S

    2016-03-01

    Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue. PMID:27030627

  3. Rats with high or low sociability are differently affected by chronic variable stress.

    PubMed

    Tõnissaar, M; Herm, L; Eller, M; Kõiv, K; Rinken, A; Harro, J

    2008-04-01

    Depression is strongly related to social behavior. We have previously shown that social behavior of rats is individually stable. The purpose of the present study was to compare the sensitivity of animals with different sociability to chronic variable stress (CVS). Four social interaction tests were performed with 60 single-housed male Sprague-Dawley rats. Twenty rats with the lowest and 20 with the highest average social activity time were selected as low sociability (LS) and high sociability (HS) rats, respectively. Both groups were further divided into control and stress groups with equal average body weight. The CVS procedure lasted for 3 weeks. The stressors applied were cold water and wet bedding, imitation of injection, stroboscopic light, movement restriction in a small cage, tail pinch with a clothespin, and strong illumination during the predicted dark phase. In HS-rats, but not in LS-rats, CVS reduced sucrose intake compared with baseline after 3 weeks, suggesting that HS-rats are more vulnerable to anhedonia elicited by CVS. LS-animals were more anxious in the social interaction and open field tests, but stress eliminated differences with HS-animals in the social interaction test and increased their activity in the forced swimming test. In LS-rats stress increased ex vivo dopamine levels and reduced 5-HT levels in the frontal cortex, suggesting that the increased behavioral activity after stress may be related to increased impulsivity. This study thus revealed that animals with high sociability trait are more vulnerable to anhedonia elicited by chronic stress in conditions of single housing. PMID:18343596

  4. Chronic biliary obstruction induces pulmonary intravascular phagocytosis and endotoxin sensitivity in rats.

    PubMed Central

    Chang, S W; Ohara, N

    1994-01-01

    Endotoxin sensitivity varies among animal species and appears to correlate with the presence of pulmonary intravascular macrophage (PIM). In rats, which lack PIM, we investigated the hypothesis that chronic cholestatic liver injury leads to induction of PIM and endotoxin sensitivity. Rats were randomized to either common bile duct ligation (BDL) or sham-surgery and studied at 1 wk (acute cholestasis), 2 wk (cholestasis, early cirrhosis), and 4 wk (cholestasis, established cirrhosis) after surgery. Intravascularly injected fluorescent latex microspheres (1 micron diameter) were taken up by large phagocytic cells in lung parenchyma of BDL rats (at 2 and 4 wk), while no uptake was observed in lungs from control rats. Electronmicroscopy revealed accumulation of large, mononuclear, macrophage-like cells containing ingested latex particles within the pulmonary capillaries. Pulmonary intravascular phagocytosis, as reflected in lung uptake of 99mTc microaggregated albumin (Microlite, mean particle diameter = 1 micron), averaged 0.7 +/- 0.1% (mean +/- SEM) of total injected dose in 13 control rats and progressively increased with time after BDL (1 wk, 1.7 +/- 0.2%; 2 wk, 10.0 +/- 3.0%; 4 wk 35.1 +/- 5.9%). Rats with biliary cirrhosis were markedly sensitive to the lethal effects of low dose endotoxin and demonstrated marked lung edema at the time of death. Furthermore, the lung uptake of intravascular 125I-lipopolysaccharide was increased five-fold in cirrhotic rats. We conclude that chronic biliary obstruction leads to the induction of pulmonary intravascular phagocytes and enhances endotoxin sensitivity in rats. Pulmonary intravascular phagocytosis in patients with advanced cirrhosis may account for their increased susceptibility to sepsis-induced adult respiratory distress syndrome. Images PMID:7962547

  5. Anti-inflammatory effects of potato extract on a rat model of cigarette smoke–induced chronic obstructive pulmonary disease

    PubMed Central

    Xu, Gui Hua; Shen, Jie; Sun, Peng; Yang, Min Li; Zhao, Peng Wei; Niu, Yan; Lu, Jing Kun; Wang, Zhi Qiang; Gao, Chao; Han, Xue; Liu, Lei Lei; Liu, Chen Chen; Cong, Zhang Yue

    2015-01-01

    Highlights: (1) Potato extract (PE) exhibits non-toxic effects on mice. (2) Cigarette smoke (CS)–induced COPD rats exhibit significant thickened and disordered lung markings. (3) PE could improve the histopathological symptoms of lung tissue in COPD. (4) PE could increase the expression of IL-10 and reduce the expression of TNF-α and G-CSF in COPD rats. Objective This study aimed to evaluate the therapeutic effects of potato extract (PE) on cigarette smoke (CS)–induced chronic obstructive pulmonary disease (COPD). Methods PE was first prepared by frozen centrifugation, and its amino acid composition was detected. Toxicity of PE was analyzed by changes in morphology, behavior, routine blood indexes, and biochemical criteria of mice. Then, the COPD rat model was established by CS exposure, and PE, doxofylline, and prednisolone acetate were used to treat these rats. After 45 days of treatment, the morphology and behavior of rats were recorded. In addition, the histopathology of lung tissue was evaluated by chest x-ray and hematoxylin and eosin staining. The expression of interleukine-10 (IL-10), tumor necrosis factor-α (TNF-α), and granulocyte colony-stimulating factor (G-CSF) was detected in serum and lung tissue by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Results Various amino acids were identified in PE, and no toxicity was exhibited in mice. The CS-induced COPD rat model was successfully established, which exhibited significant thickened and disordered lung markings on 90% of the rats. After administering doxofylline and prednisolone acetate, inflammation symptoms were improved. However, side effects such as emaciation, weakness, and loosening of teeth appeared. In the PE group, obviously improved histopathology was observed in lung tissues. Meanwhile, it was revealed that PE could increase the expression of IL-10 and reduce the expression of TNF-α and G-CSF in COPD rats, and doxofylline and prednisolone acetate

  6. Chronic nifedipine dosing enhances cephalexin bioavailability and intestinal absorption in conscious rats.

    PubMed

    Berlioz, F; Lepére-Prevot, B; Julien, S; Tsocas, A; Carbon, C; Rozé, C; Farinotti, R

    2000-11-01

    Cephalexin, a beta-lactam antibiotic, is rapidly absorbed via the di-and tripeptide intestinal transporters, as for many peptidomimetic drugs. Acute nifedipine has been shown to increase intestinal absorption of several beta-lactams: amoxicillin and cefixime in humans, and cephalexin in the rat. We showed previously that the nervous system was involved in the increasing effect of nifedipine on cephalexin intestinal absorption in anesthetized rats. The aim of the present study was 2-fold: 1) to investigate whether the effect of nifedipine is maintained in conscious rats, and 2) to determine whether the nifedipine effect will persist during chronic nifedipine administration. Acute and chronic oral administration of nifedipine significantly increased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, respectively), while the distribution and elimination parameters of intra-arterial cephalexin were not affected by acute or chronic nifedipine administration. In conclusion, acute nifedipine effect on intestinal absorption of cephalexin is independent of anesthesia in rats. Since nifedipine could still enhance cephalexin intestinal absorption after a 7-day b.i.d. treatment, it can be envisaged to apply this effect to increase bioavailability of poorly absorbed peptidomimetic drugs in man. PMID:11038150

  7. Interaction between vitamin E and glutathione in rat brain: Effect of chronic ethanol administration.

    PubMed

    Marcus, S R; Chandrakala, M V; Nadiger, H A

    1998-12-01

    The protection against ethanol-induced lipid peroxidation is rendered by antioxidants such as vitamin E and glutathione (GSH) interacting with each other and also functioning independently. A study of the levels of GSH and activities of glutathione peroxidase (GP), glutathione reductase (GR) and glutathione transferase (GST) in the cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of vitamin E-supplemented and -deficient rats subjected to ethanol administration for 30 days was carried out. Chronic ethanol administration to vitamin E-supplemented rats elevated GP, GR and GST activities in the three regions and GSH levels in the CB. Chronic ethanol administration to vitamin E-deficient rats elevated GR activity in the three regions and GP activity in the CC and CB, decreased GST activity in the CC and CB, but did not alter GSH levels compared with normal rats subjected to chronic ethanol administration. The results indicate that vitamin E helps to maintain GSH levels to combat increased peroxidation while its absence has a deleterious effect. PMID:24393672

  8. Fall of zinc protoporphyrin levels in workers treated for chronic lead intoxication

    SciTech Connect

    Hryhorczuk, D.O.; Hogan, M.M.; Mallin, K.; Hessl, S.M.; Orris, P.

    1985-11-01

    A temporal fall of zinc protoporphyrin (ZPP) levels in whole blood was observed in 51 patients with occupational chronic lead intoxication who were removed from exposure, treated with intravenous calcium disodium edetate (EDTA), and followed for periods up to 2273 days. ZPP levels fell, with a mean half-life of 68 days, to a mean baseline level of 36 micrograms/dl of whole blood. The baseline ZPP level was positively associated with the length of exposure (p less than .01) and the blood lead half-life (p less than .001). The amount of EDTA received had no apparent effect on ZPP levels. These data suggest that the fall of ZPP levels is largely a function of red blood cell turnover. The baseline ZPP level appears to be a useful biologic index of the biologically active pool of lead for at least two years after removal from exposure.

  9. [An establishment of theoretical structure of PRO questionnaire in treating chronic liver disease by Chinese medicine].

    PubMed

    Wang, Li; Zhang, Hua; Yuan, Wei-An; Wang, Yi-Xing; Tang, Jie; Cui, Chen; Zeng, Jin; Miao, Ping; Jiang, Jian

    2014-11-01

    By reviewing research contents of patient-reported outcome (PRO) and discussing Chinese medicine (CM) theories related to chronic liver disease (CLD), we have followed international PRO questionnaire development specification, combined CM theories such as uniformed spirit and body, correspondence between human and the universe, yin in property and yang in function of Gan, and seven emotions, and constructed theoretical structure of PRO questionnaire of treating CLD, including four major areas as physiology, psychology, independence, and society and nature. Of them, the physiological field contained six aspects such as blood deficiency, yin deficiency, bleeding, disorder of qi movement, improper transformation and transportation of Pi-Wei, and abnormal biliary excretion. The psychological field contained two aspects: Gan-related emotions and general disease related emotions. The independence field contained two aspects: daily life and study and work. The field of society and nature contains three aspects: social relations, social environment, and natural adaptability. PMID:25566635

  10. Practicalities and challenges in re-orienting the health system in Zambia for treating chronic conditions

    PubMed Central

    2014-01-01

    Background The rapid evolution in disease burdens in low- and middle income countries is forcing policy makers to re-orient their health system towards a system which has the capability to simultaneously address infectious and non-communicable diseases. This paper draws on two different but overlapping studies which examined how actors in the Zambian health system are re-directing their policies, strategies and service structures to include the provision of health care for people with chronic conditions. Methods Study methods in both studies included semi-structured interviews with government health officials at national level, and governmental and non-governmental health practitioners operating from community-, primary health care to hospital facility level. Focus group discussions were conducted with staff, stakeholders and caregivers of programmes providing care and support at community- and household levels. Study settings included urban and rural sites. Results A series of adaptations transformed the HIV programme from an emergency response into the first large chronic care programme in the country. There are clear indications that the Zambian government is intending to expand this reach to patients with non-communicable diseases. Challenges to do this effectively include a lack of proper NCD prevalence data for planning, a concentration of technology and skills to detect and treat NCDs at secondary and tertiary levels in the health system and limited interest by donor agencies to support this transition. Conclusion The reorientation of Zambia’s health system is in full swing and uses the foundation of a decentralised health system and presence of local models for HIV chronic care which actively involve community partners, patients and their families. There are early warning signs which could cause this transition to stall, one of which is the financial capability to resource this process. PMID:25005125

  11. Effect of a chronic GSM 900 MHz exposure on glia in the rat brain.

    PubMed

    Ammari, Mohamed; Brillaud, Elsa; Gamez, Christelle; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; de Seze, René

    2008-01-01

    Extension of the mobile phone technology raises concern about the health effects of 900 MHz microwaves on the central nervous system (CNS). In this study we measured GFAP expression using immunocytochemistry method, to evaluate glial evolution 10 days after a chronic exposure (5 days a week for 24 weeks) to GSM signal for 45 min/day at a brain-averaged specific absorption rate (SAR)=1.5 W/kg and for 15 min/day at a SAR=6 W/kg in the following rat brain areas: prefrontal cortex (PfCx), caudate putamen (Cpu), lateral globus pallidus of striatum (LGP), dentate gyrus of hippocampus (DG) and cerebellum cortex (CCx). In comparison to sham or cage control animals, rats exposed to chronic GSM signal at 6 W/kg have increased GFAP stained surface areas in the brain (p<0.05). But the chronic exposure to GSM at 1.5 W/kg did not increase GFAP expression. Our results indicated that chronic exposure to GSM 900 MHz microwaves (SAR=6 W/kg) may induce persistent astroglia activation in the rat brain (sign of a potential gliosis). PMID:18424058

  12. Chronic sleep deprivation alters the myosin heavy chain isoforms in the masseter muscle in rats.

    PubMed

    Cao, Ruihua; Huang, Fei; Wang, Peihuan; Chen, Chen; Zhu, Guoxiong; Chen, Lei; Wu, Gaoyi

    2015-05-01

    To investigate the changes in myosin heavy chain (MyHC) isoforms of rat masseter muscle fibres caused by chronic sleep deprivation and a possible link with the pathogenesis of disorders of the temporomandibular joint (TMJ). A total of 180 male rats were randomly divided into three groups (n=60 in each): cage controls, large platform controls, and chronic sleep deprivation group. Each group was further divided into three subgroups with different observation periods (7, 14, and 21 days). We investigated he expression of MyHC isoforms in masseter muscle fibres by real-time quantitative polymerase chain reaction (PCR), Western blotting, and immunohistochemical staining. In rats with chronic sleep deprivation there was increased MyHC-I expression in layers of both shallow and deep muscles at 7 and 21 days compared with the control groups, whereas sleep deprivation was associated with significantly decreased MyHC-II expression. At 21 days, there were no differences in MyHC-I or MyHC-II expression between the groups and there were no differences between the two control groups at any time point. These findings suggest that chronic sleep deprivation alters the expression of MyHC isoforms, which may contribute to the pathogenesis of disorders of the TMJ. PMID:25804396

  13. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    PubMed Central

    Cowan-Jacob, Sandra W.; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W.

    2007-01-01

    Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery. PMID:17164530

  14. Strategies for treating chronic HCV infection in patients with cirrhosis: latest evidence and clinical outcomes

    PubMed Central

    Wilder, Julius M.; Muir, Andrew J.

    2015-01-01

    The burden of chronic hepatitis C virus (HCV) infection is significant and growing. HCV is considered one of the leading causes of liver disease worldwide and the leading cause of liver transplantation globally. While those infected is estimated in the hundreds of millions, this is likely an underestimation because of the indolent nature of this disease when first contracted. Approximately 20% of patients with HCV infection will progress to advanced fibrosis and cirrhosis. Those that do are at risk of decompensated liver disease including GI bleeding, encephalopathy, severe lab abnormalities, and hepatocellular carcinoma. Those individuals with advanced fibrosis and cirrhosis have historically been difficult to treat. The backbone of previous HCV regimens was interferon (IFN). The outcomes for IFN based regimens were poor and resulted in increased adverse events among those with advanced fibrosis and cirrhosis. Now, in the era of new direct acting antiviral (DAA’s) medications, there is hope for curing chronic HCV in everyone, including those with advanced fibrosis and cirrhosis. This article provides a review on the most up to date data on the use of DAA’s in patients with advanced fibrosis and cirrhosis. We are at a point where HCV could be truly eradicated, but to do so will require ensuring there are effective and safe treatments for those with advanced fibrosis and cirrhosis. PMID:26568808

  15. Photodynamic therapy (PDT) to treat a chronic skin wound in a dog

    NASA Astrophysics Data System (ADS)

    Hage, Raduan; Plapler, Hélio; Bitar, Renata A.

    2008-02-01

    Photodynamic Therapy (PDT) is an emerging and promising therapeutic modality for treatment of a wide variety of malignant and nononcologic tumors, as well as in the treatment of infected skin ulcers. This study evaluated the effectiveness of the PDT to treat a chronic skin wound that had been already subjected to several clinical and surgical type treatments in a dog. The animal with an infected chronic skin wound with 8 cm diameter in the left leg received an injection of an aqueous solution of 1% methylene blue (MB) with 2% lidocaine into the lesion. After MB injection the wound was irradiated using a LED (LED-VET MMOptics(r)) with a wavelength between 600 and 700 nm, 2 cm diameter circular light beam, of 150 mW of power, light dose of 50 J/cm2. After 3 and 6 weeks PDT was repeated and the wound was re-evaluated. Complete healing was achieved 10 weeks after the first procedure.

  16. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  17. Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection

    PubMed Central

    Hesselink, J M Keppel

    2013-01-01

    Chronic idiopathic axonal polyneuropathy is a frequent diagnosis in patients suffering from idiopathic polyneuropathy and neuropathic pain. No guidelines exist on how to treat these patients. To date, there are no results available from randomized clinical trials, and mostly classical neuropathic analgesics are prescribed, such as amitriptyline and gabapentine. However, the usefulness of these drugs is limited, as many patients remain in pain despite treatment, or suffer debilitating side effects. Palmitoylethanolamide (PEA) is a new analgesic compound, tested in more than 4,000 patients in various clinical trials in a variety of patients suffering from various neuropathic pain states. It is available in Europe and the USA as a food supplement under the brand name PeaPure, and it is available for medical purposes in Italy and Spain under brand names Normast and Pelvilen. We present a case series of seven patients with an electrophysiological confirmed diagnosis of chronic idiopathic axonal polyneuropathy, suffering from neuropathic pains, mostly refractory to previous analgesics. In all these patients, PEA reduced pain significantly, without side effects. PEA can be administered in addition to other analgesics, without negative drug–drug interactions, or can be used as a stand-alone analgesic. Due to a favorable ratio between efficacy and safety, PEA should be considered more often as a treatment for neuropathic pain. PMID:24049461

  18. Posttraumatic chronic patellar dislocation treated by distal femoral osteotomy and medial patellofemoral ligament reconstruction.

    PubMed

    Purushothaman, Balaji; Agarwal, Amit; Dawson, Matt

    2012-11-01

    Chronic patellar dislocation is a rare condition where the patella remains dislocated throughout knee range of motion during flexion and extension. In adults, the delayed presentation of this condition is often due to symptoms caused by the onset of severe secondary osteoarthritis. To the authors' knowledge, all of the cases reported in the literature have been treated by patellofemoral or total knee replacements depending on patient age and the extent of the arthritis. This article describes a rare case of a 22-year-old woman who sustained a traumatic chronic patellar dislocation for 5 months. Clinical examination revealed a valgus deformity of the left leg secondary to childhood injury and that the patella lay lateral to the lateral femoral condyle throughout flexion and extension. Radiographs of the knee revealed patellar dislocation. Long-leg radiographs of the left leg showed an anatomic tibiofemoral angle of 17° valgus. The anatomical (74°) and mechanical (80°) lateral distal femoral angles were abnormal, whereas the medial proximal tibial angle (87°) was normal, confirming that the valgus deformity was due to the abnormal distal femur. The authors performed a distal femoral osteotomy to correct the valgus deformity. Medial patellofemoral ligament reconstruction using a hamstring autograft was performed to stabilize the patella. PMID:23127463

  19. Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats.

    PubMed

    Abelaira, Helena M; Réus, Gislaine Z; Ribeiro, Karine F; Zappellini, Giovanni; Ferreira, Gabriela K; Gomes, Lara M; Carvalho-Silva, Milena; Luciano, Thais F; Marques, Scherolin O; Streck, Emilio L; Souza, Cláudio T; Quevedo, João

    2011-12-01

    The present study was aimed to investigate the behavioral and molecular effects of lamotrigine. To this aim, Wistar rats were treated with lamotrigine (10 and 20 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The behavior was assessed using forced swimming test. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Proteina Kinase B (PKB, AKT), glycogen synthase kinase 3 (GSK-3) and B-cell lymphoma 2 (Bcl-2) levels, citrate synthase, creatine kinase and mitochondrial chain (I, II, II-III and IV) activities were assessed in the brain. The results showed that both treatments reduced the immobility time. The BDNF were increased in the prefrontal after acute treatment with lamotrigine (20 mg/kg), and the BDNF and NGF were increased in the prefrontal after chronic treatment with lamotrigine in all doses. The AKT increased and Bcl-2 and GSK-3 decreased after both treatments in all brain areas. The citrate synthase and c