Use of activated protein C has no avail in the early phase of acute pancreatitis

PubMed Central

Ozutemiz, Omer; Yenisey, Cigdem; Genc Simsek, Nilufer; Yuce, Gul; Batur, Yucel

2008-01-01

Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435±432 U/L vs. 27,426±118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970±323 pg/mL vs. 330±368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions. PMID:19088933

Efficacy of Vesicular Stomatitis Virus-Ebola Virus Postexposure Treatment in Rhesus Macaques Infected With Ebola Virus Makona.

PubMed

Marzi, Andrea; Hanley, Patrick W; Haddock, Elaine; Martellaro, Cynthia; Kobinger, Gary; Feldmann, Heinz

2016-10-15

The Ebola virus (EBOV) epidemic in West Africa increased the focus on vaccine development against this hemorrhagic fever-causing pathogen, and as a consequence human clinical trials for a few selected platforms were accelerated. One of these vaccines is vesicular stomatitis virus (VSV)-EBOV, also known as rVSV-ZEBOV, a fast-acting vaccine against EBOV and so far the only vaccine with reported efficacy against EBOV infections in humans in phase III clinical trials. In this study, we analyzed the potential of VSV-EBOV for postexposure treatment of rhesus macaques infected with EBOV-Makona. We treated groups of animals with 1 dose of VSV-EBOV either in a single injection at 1 or 24 hours after EBOV exposure or with 2 injections, half the dose at each time point; 1 control group received the same dose of the VSV-based Marburg virus vaccine at both time points; another group remained untreated. Although all untreated animals succumbed to EBOV infection, 33%-67% of the animals in each treatment group survived the infection, including the group treated with the VSV-based Marburg virus vaccine. This result suggests that protection from postexposure vaccination may be antigen unspecific and due rather to an early activation of the innate immune system. In conclusion, VSV-EBOV remains a potent and fast-acting prophylactic vaccine but demonstrates only limited efficacy in postexposure treatment. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Enrofloxacin and Macrolides Alone or in Combination with Rifampicin as Antimicrobial Treatment in a Bovine Model of Acute Chlamydia psittaci Infection

PubMed Central

Prohl, Annette; Lohr, Markus; Ostermann, Carola; Liebler-Tenorio, Elisabeth; Berndt, Angela; Schroedl, Wieland; Rothe, Michael; Schubert, Evelyn; Sachse, Konrad; Reinhold, Petra

2015-01-01

Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6–8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e. cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks. PMID:25768665

Estrogen Deprivation in Primate Pregnancy Leads to Insulin Resistance in Offspring

PubMed Central

Maniu, Adina; Aberdeen, Graham W.; Lynch, Terrie J.; Nadler, Jerry L.; Kim, Soon OK; Quon, Michael J.; Pepe, Gerald J.; Albrecht, Eugene D.

2016-01-01

This study tested the hypothesis that estrogen programs mechanisms within the primate fetus that promote insulin sensitivity and glucose homeostasis in offspring. Glucose tolerance tests were performed longitudinally in prepubertal offspring of baboons untreated or treated on days 100 to 165/175 of gestation (term is 184 days) with the aromatase inhibitor letrozole which decreased fetal estradiol levels by 95%. Basal plasma insulin levels were over 2-fold greater in offspring delivered to letrozole-treated than untreated animals. Moreover, the peak 1 min, average of the 1, 3 and 5 min, and area under the curve blood glucose and plasma insulin levels after an iv bolus of glucose were greater (P<0.05 and P<0.01, respectively) in offspring deprived of estrogen in utero than in untreated animals and partially or completely restored in letrozole plus estradiol-treated baboons. The value for the homeostasis model assessment of insulin resistance was 2.5-fold greater (P<0.02) and quantitative insulin sensitivity check index lower (P<0.01) in offspring of letrozole-treated versus untreated animals and returned to almost normal in letrozole plus estradiol-treated animals. The exaggerated rise in glucose and insulin levels after glucose challenge in baboon offspring deprived of estrogen in utero indicates that pancreatic beta cells had the capacity to secrete insulin, but that peripheral glucose uptake and/or metabolism were impaired, indicative of insulin resistance and glucose intolerance. We propose that estrogen normally programs mechanisms in utero within the developing primate fetus that lead to insulin sensitivity, normal glucose tolerance and the capacity to metabolize glucose after birth. PMID:27207093

Complement activation promotes muscle inflammation during modified muscle use

NASA Technical Reports Server (NTRS)

Frenette, J.; Cai, B.; Tidball, J. G.

2000-01-01

Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

Losartan increases NO release in afferent arterioles during regression of L-NAME-induced renal damage.

PubMed

Helle, Frank; Iversen, Bjarne M; Chatziantoniou, Christos

2010-05-01

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of N(G)-nitro-L-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10(-7) M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10(-9) M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10(-7) M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10(-9), 10(-8), 10(-7) M) were enhanced by NOS inhibition and blunted by exogenous NO (10(-2) mM S-nitroso-N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT(1a)R antagonism during the recovery of renal function after long-term NOS inhibition in rats.

Sources of Dietary Protein in Relation to Blood Pressure in a General Dutch Population

PubMed Central

Altorf - van der Kuil, Wieke; Engberink, Mariëlle F.; Vedder, Moniek M.; Boer, Jolanda M. A.; Verschuren, W. M. Monique; Geleijnse, Johanna M.

2012-01-01

Background Little is known about the relation of different dietary protein types with blood pressure (BP). We examined whether intake of total, plant, animal, dairy, meat, and grain protein was related to BP in a cross sectional cohort of 20,820 Dutch adults, aged 20–65 y and not using antihypertensive medication. Design Mean BP levels were calculated in quintiles of energy-adjusted protein with adjustment for age, sex, BMI, education, smoking, and intake of energy, alcohol, and other nutrients including protein from other sources. In addition, mean BP difference after substitution of 3 en% carbohydrates or MUFA with protein was calculated. Results Total protein and animal protein were not associated with BP (ptrend = 0.62 and 0.71 respectively), both at the expense of carbohydrates and MUFA. Systolic BP was 1.8 mmHg lower (ptrend<0.01) in the highest (>36 g/d) than in the lowest (<27 g/d) quintile of plant protein. This inverse association was present both at the expense of carbohydrates and MUFA and more pronounced in individuals with untreated hypertension (−3.6 mmHg) than in those with normal (+0.1 mmHg) or prehypertensive BP (−0.3 mmHg; pinteraction<0.01). Meat and grain protein were not related to BP. Dairy protein was directly associated with systolic BP (+1.6 mmHg, ptrend<0.01), but not with diastolic BP (ptrend = 0.24). Conclusions Total protein and animal protein were not associated with BP in this general untreated Dutch population. Plant protein may be beneficial to BP, especially in people with elevated BP. However, because high intake of plant protein may be a marker of a healthy diet and lifestyle in general, confirmation from randomized controlled trials is warranted. PMID:22347387

78 FR 37779 - Notice of Request for Extension of Approval of an Information Collection; Untreated Oranges...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... Washington, DC, this 19th day of June 2013. Kevin Shea, Administrator, Animal and Plant Health Inspection... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2013-0029..., and Grapefruit From Mexico Transiting the United States to Foreign Countries AGENCY: Animal and Plant...

Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3.

PubMed

de Rozières, Sohela; Swan, Christina H; Sheeter, Dennis A; Clingerman, Karen J; Lin, Ying-Chuan; Huitron-Resendiz, Salvador; Henriksen, Steven; Torbett, Bruce E; Elder, John H

2004-11-19

The protease inhibitor, TL-3, demonstrated broad efficacy in vitro against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very strong protective effects on early neurologic alterations in the CNS of FIV-PPR infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with high early mortality rates. Twenty cats were infected with uncloned FIV-C and half were treated with TL-3 while the other half were left untreated. Two uninfected cats were used as controls. The general health and the immunological and virological status of the animals was monitored for eight weeks following infection. All infected animals became viremic independent of TL-3 treatment and seven of 20 FIV-C infected animals developed severe immunodepletive disease in conjunction with significantly (p < or = 0.05) higher viral RNA loads as compared to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes in animals surviving acute phase infection was noted, which was not evident in symptomatic animals (p < or = 0.05). Average viral loads were lower in TL-3 treated animals and of the 6 animals requiring euthanasia, four were from the untreated cohort. At eight weeks post infection, half of the TL-3 treated animals and only one of six untreated animals had viral loads below detection limits. Analysis of protease genes in TL-3 treated animals with higher than average viral loads revealed sequence variations relative to wild type protease. In particular, one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type protease. The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at eight weeks post infection is indicative of a therapeutic effect of the compound on virus infection.

Bioavailability and Efficacy of Levofloxacin against Francisella tularensis in the Common Marmoset (Callithrix jacchus)▿

PubMed Central

Nelson, Michelle; Lever, Mark S.; Dean, Rachel E.; Pearce, Peter C.; Stevens, Daniel J.; Simpson, Andrew J. H.

2010-01-01

Pharmacokinetic and efficacy studies with levofloxacin were performed in the common marmoset (Callithrix jacchus) model of inhalational tularemia. Plasma levofloxacin pharmacokinetics were determined in six animals in separate single-dose and multidose studies. Plasma drug concentrations were analyzed using liquid chromatography-tandem mass spectrometry-electrospray ionization. On day 7 of a twice-daily dosing regimen of 40 mg/kg, the levofloxacin half-life, maximum concentration, and area under the curve in marmoset plasma were 2.3 h, 20.9 μg/ml, and 81.4 μg/liter/h, respectively. An efficacy study was undertaken using eight treated and two untreated control animals. Marmosets were challenged with a mean of 1.5 × 102 CFU of Francisella tularensis by the airborne route. Treated animals were administered 16.5 mg/kg levofloxacin by mouth twice daily, based on the pharmacokinetic parameters, beginning 24 h after challenge. Control animals had a raised core body temperature by 57 h postchallenge and died from infection by day 5. All of the other animals survived, remained afebrile, and lacked overt clinical signs. No bacteria were recovered from the organs of these animals at postmortem after culling at day 24 postchallenge. In conclusion, postexposure prophylaxis with orally administered levofloxacin was efficacious against acute inhalational tularemia in the common marmoset. The marmoset appears to be an appropriate animal model for the evaluation of postexposure therapies. PMID:20625157

Kinetics of Coxiella burnetii excretion in a commercial dairy sheep flock after treatment with oxytetracycline.

PubMed

Astobiza, Ianire; Barandika, Jesús F; Hurtado, Ana; Juste, Ramón A; García-Pérez, Ana L

2010-05-01

The kinetics of Coxiella burnetii excretion were studied in dairy sheep using a flock that had a previous history of abortion and a positive polymerase chain reaction (PCR) test for C. burnetii in milk from the bulk-tank. An ELISA used to test sera antibodies revealed a high within-flock seroprevalence (54%). Fifty individual milk samples analysed by PCR showed a high number of milk shedders in the flock (38%). In the following breeding cycle, 75% of the animals in the flock were double treated with oxytetracycline (OTC) at days +100 and +120 of gestation, while the remaining 25% of the animals were kept as untreated controls. The percentage of shedders at lambing was similar between groups. Of the treated ewes, 82% shed the bacteria in their vaginal fluids vs. 72% of the untreated ewes. Shedding was also high in faeces (61% of treated vs. 77% of untreated ewes) and milk (57% of treated vs. 50% of untreated ewes). At 2 and 6 weeks later, treated animals continued shedding the bacteria and there were no significant differences in the number of shedders between treated and control groups. Moreover, the bacteria were excreted in faeces for 5 months after parturition, for 3 months in vaginal discharges and for 4 months in milk, which suggested that OTC treatment neither prevented the shedding of bacteria, nor limited the duration of bacterial excretion. Copyright 2009 Elsevier Ltd. All rights reserved.

Influence of manual therapy on functional mobility after joint injury in a rat model.

PubMed

Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

2013-10-01

Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; P<.001). Injured rats gradually returned to running levels equal to controls over 10 days. Neither manual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy.

PubMed

Kearney, Mary F; Anderson, Elizabeth M; Coomer, Charles; Smith, Luke; Shao, Wei; Johnson, Nicholas; Kline, Christopher; Spindler, Jonathan; Mellors, John W; Coffin, John M; Ambrose, Zandrea

2015-11-11

Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT-SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART.

Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone.

PubMed

Kokkinos, Alexander; Mourouzis, Iordanis; Kyriaki, Despoina; Pantos, Constantinos; Katsilambros, Nicholas; Cokkinos, Dennis V

2007-08-01

Thyroid hormone plays a critical role in energy homeostasis through mechanisms, which are not fully understood. In the present study, we investigated possible alterations of important energy regulators such as leptin, adiponectin, and ghrelin in relation to changes in thyroid hormones. Thyroid hormone (250 microg/kg) was administered in male Wistar rats for 2 weeks (THYR), while hypothyroidism (HYPO) was induced by propylthiouracil administration (0.05% in drinking water) for 3 weeks. Untreated animals served as controls (NORM). Leptin and adiponectin were measured in plasma by ELISA, while total ghrelin was measured with RIA. Body weight was significantly reduced both in THYR and HYPO rats, while food intake was significantly increased in THYR and decreased in HYPO. This response was associated with various changes in leptin, adiponectin, and ghrelin in plasma. In fact, in THYR rats, leptin levels (mean +/- SEM) were 240 +/- 55 pg/ml as compared to 819 +/- 70 pg/ml in untreated rats (P < 0.05), while no changes were observed in ghrelin and adiponectin. In HYPO rats, leptin levels were 1400 +/- 200 pg/ml vs. 819 +/- 70 pg/ml in untreated rats (P < 0.05), while ghrelin and adiponectin were significantly increased in HYPO rats as compared to untreated rats (P < 0.05). Furthermore, T(3) and T(4) levels were inversely correlated to leptin (P = 0.014), while ghrelin and adiponectin were inversely correlated to weight changes (P = 0.05 and P = 0.03, respectively). In conclusion, leptin seems mainly to be involved in the thyroid hormone effects on energy homeostasis. Ghrelin and adiponectin may serve a compensatory physiological role in hypothyroidism.

Insulin induces the correlation between renal blood flow and glomerular filtration rate in diabetes: implications for mechanisms causing hyperfiltration.

PubMed

Pihl, Liselotte; Persson, Patrik; Fasching, Angelica; Hansell, Peter; DiBona, Gerald F; Palm, Fredrik

2012-07-01

Glomerular filtration rate (GFR) and renal blood flow (RBF) are normally kept constant via renal autoregulation. However, early diabetes results in increased GFR and the potential mechanisms are debated. Tubuloglomerular feedback (TGF) inactivation, with concomitantly increased RBF, is proposed but challenged by the finding of glomerular hyperfiltration in diabetic adenosine A(1) receptor-deficient mice, which lack TGF. Furthermore, we consistently find elevated GFR in diabetes with only minor changes in RBF. This may relate to the use of a lower streptozotocin dose, which produces a degree of hyperglycemia, which is manageable without supplemental suboptimal insulin administration, as has been used by other investigators. Therefore, we examined the relationship between RBF and GFR in diabetic rats with (diabetes + insulin) and without suboptimal insulin administration (untreated diabetes). As insulin can affect nitric oxide (NO) release, the role of NO was also investigated. GFR, RBF, and glomerular filtration pressures were measured. Dynamic RBF autoregulation was examined by transfer function analysis between arterial pressure and RBF. Both diabetic groups had increased GFR (+60-67%) and RBF (+20-23%) compared with controls. However, only the diabetes + insulin group displayed a correlation between GFR and RBF (R(2) = 0.81, P < 0.0001). Net filtration pressure was increased in untreated diabetes compared with both other groups. The difference between untreated and insulin-treated diabetic rats disappeared after administering N(ω)-nitro-l-arginine methyl ester to inhibit NO synthase and subsequent NO release. In conclusion, mechanisms causing diabetes-induced glomerular hyperfiltration are animal model-dependent. Supplemental insulin administration results in a RBF-dependent mechanism, whereas elevated GFR in untreated diabetes is mediated primarily by a tubular event. Insulin-induced NO release partially contributes to these differences.

Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kageyama, Ken, E-mail: kageyamaken0112@gmail.com; Yamamoto, Akira, E-mail: loveakirayamamoto@gmail.com; Okuma, Tomohisa, E-mail: o-kuma@msic.med.osaka-cu.ac.jp

Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at amore » single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.« less

Side effects of pain and analgesia in animal experimentation.

PubMed

Jirkof, Paulin

2017-03-22

This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility in animal experiments involving laboratory rodents.

Sources of variation in baseline gene expression levels from toxicogenomics study control animals

EPA Science Inventory

The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization ofvariance due to individual, environmental, and technical factors. Meta-analysis ofmicroarray data from untreated or vehicle-treated animals within the con...

Amitriptyline and phenytoin prevents memory deficit in sciatic nerve ligation model of neuropathic pain.

PubMed

Abdulmajeed, Wahab Imam; Ibrahim, Ridwan Babatunde; Ishola, Azeez Olakunle; Balogun, Wasiu Gbolahan; Cobham, Ansa Emmanuel; Amin, Abdulbasit

2016-03-01

Phenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain. Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both 'Y' maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin. There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the 'Y' maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals. The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.

Changes in preferences of gestating heifers fed untreated or ammoniated straw in different flavors.

PubMed

Atwood, S B; Provenza, F D; Wiedmeier, R D; Banner, R E

2001-12-01

We determined how a food's flavor and digestibility, along with an animal's recent experiences, influenced food preference and intake. In three experiments, pregnant heifers were fed a basal ration (7.75 kg/animal) of alfalfa, barley, corn silage, and a vitamin/mineral supplement from 1500 to 2200. Exp. 1 determined the influence of recent exposure to flavored straw. Animals were divided into two groups (n = 16/group) and fed either untreated or ammoniated straw with digestibilities of 43 and 58%, respectively. Within each group, half of the heifers were fed maple-flavored straw and the other half were fed coconut-flavored straw from 1100 one day to 0900 the next day, with no base ration. We then offered straw in both flavors from 1000 to 1200 for the next 5 d. Animals fed maple-flavored straw for 1 d generally preferred coconut- over maple-flavored straw for the next 5 d, whereas animals previously fed coconut-flavored straw preferred maple-flavored straw (P < 0.001). The change in preference was stronger when animals were fed untreated compared with ammoniated straw. Experiments 2 and 3 determined the influence of offering straw in different flavors, either in sequence (Exp. 2) or simultaneously (Exp. 3). In Exp. 2, we offered heifers (n = 16) straw in three flavors (maple from 0900 to 1100, coconut from 1100 to 1300, and unflavored from 1300 to 1500) and compared their intake with that of heifers (n = 16) offered unflavored straw throughout the day. In Exp. 3, we compared intake of heifers (n = 16) simultaneously offered straw in three flavors (coconut, maple, and unflavored) with that of heifers (n = 16) offered only unflavored straw from 1000 to 1500. In both experiments, straw intake and preference differed between heifers offered straw in a variety of flavors as opposed to only unflavored straw (P < 0.05), but animals fed a variety of flavors did not consistently eat more than those fed only one flavor. During a post-trial preference test, heifers previously restricted to straw in one flavor for 5 d preferred straw in alternative flavors, whereas heifers fed straw in all three flavors preferred unflavored straw. Changes in preference were stronger for heifers fed untreated compared with ammoniated straw. Collectively, our results suggest that palatability, as evidenced by changes in preference and intake, is dynamic and depends on a food's flavor and nutritional quality and an animal's recent experiences with the food.

Ethanol modifies the effect of handling stress on gene expression: problems in the analysis of two-way gene expression studies in mouse brain.

PubMed

Rulten, Stuart L; Ripley, Tamzin L; Manerakis, Ektor; Stephens, David N; Mayne, Lynne V

2006-08-02

Studies analysing the effects of acute treatments on animal behaviour and brain biochemistry frequently use pairwise comparisons between sham-treated and -untreated animals. In this study, we analyse expression of tPA, Grik2, Smarca2 and the transcription factor, Sp1, in mouse cerebellum following acute ethanol treatment. Expression is compared to saline-injected and -untreated control animals. We demonstrate that acute i.p. injection of saline may alter gene expression in a gene-specific manner and that ethanol may modify the effects of sham treatment on gene expression, as well as inducing specific effects independent of any handling related stress. In addition to demonstrating the complexity of gene expression in response to physical and environmental stress, this work raises questions on the interpretation and validity of studies relying on pairwise comparisons.

Wound healing potential of Pterocarpus santalinus linn: a pharmacological evaluation.

PubMed

Biswas, Tuhin Kanti; Maity, Lakshmi Narayan; Mukherjee, Biswapati

2004-09-01

The need for new therapeutics for wound healing has encouraged the drive to examine the nature and value of plant products. Ayurveda, the Indian traditional system of medicine, mentions the values of medicinal plants for wound healing. One of these is Pterocarpus santalinus. This article describes a pharmacological study to evaluate its toxicity as well as wound-healing potential in animal studies. Powder made from the wood of the P. santalinus tree was used to make up an ointment in a petroleum jelly base. No toxic effects were observed in 72 hours. Studies were done on punch and burn wound models on normal and diabetic rats using the test ointment, untreated and vehicle controls, and standard therapy. Physical and biochemical measurements were made. The test ointment-treated wounds healed significantly faster. On healing, collagenesis and biochemical measurements yielded supportive data. These studies permit the conclusion that the P. santalinus ointment is safe and effective in treating acute wounds in animal models.

Investigation of the Diversity of Antibiotic Resistance Genes and Mobile Genetic Elements in Salmonella associated with U.S. Food Animals

USDA-ARS?s Scientific Manuscript database

With the emergence of antibiotic resistance (AR), multidrug resistance (MDR), and carbapenem resistant Enterobacteriaceae (CRE), the specter of widespread untreatable bacterial infections threatens human and animal health. The ability of these emerging resistances to transfer between bacteria on mob...

Investigation of the diversity of antibiotic resistance genes and mobile genetic elements in Salmonella associated with U.S. food animals

USDA-ARS?s Scientific Manuscript database

With the emergence of antibiotic resistance (AR), multidrug resistance (MDR), and carbapenem resistant Enterobacteriaceae (CRE), the specter of widespread untreatable bacterial infections threatens human and animal health. The ability of these emerging resistances to transfer between bacteria on mob...

9 CFR 166.6 - Swine feeding area standards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Swine feeding area standards. 166.6... AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.6 Swine feeding area standards. Untreated garbage shall not be allowed into swine feeding areas. Any equipment or material...

9 CFR 166.6 - Swine feeding area standards.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Swine feeding area standards. 166.6... AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.6 Swine feeding area standards. Untreated garbage shall not be allowed into swine feeding areas. Any equipment or material...

9 CFR 166.6 - Swine feeding area standards.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Swine feeding area standards. 166.6... AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.6 Swine feeding area standards. Untreated garbage shall not be allowed into swine feeding areas. Any equipment or material...

9 CFR 166.6 - Swine feeding area standards.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Swine feeding area standards. 166.6... AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.6 Swine feeding area standards. Untreated garbage shall not be allowed into swine feeding areas. Any equipment or material...

9 CFR 166.6 - Swine feeding area standards.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Swine feeding area standards. 166.6... AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.6 Swine feeding area standards. Untreated garbage shall not be allowed into swine feeding areas. Any equipment or material...

Tracing heavy metals in 'swine manure - maggot - chicken' production chain.

PubMed

Wang, Wanqiang; Zhang, Wenjuan; Wang, Xiaoping; Lei, Chaoliang; Tang, Rui; Zhang, Feng; Yang, Qizhi; Zhu, Fen

2017-08-21

With the development of large-scale livestock farming, manure pollution has drawn much attention. Conversion by insects is a rapid and cost-effective new method for manure management. Swine manure conversion with maggots (Musca domestica larvae) has developed, and the harvested maggots are often used as animal feed. However, the flow of heavy metals from manure to downstream processes cannot be ignored, and therefore, heavy metal content was measured in untreated raw manure, maggot-treated manure, harvested maggots and maggot-eating chickens (chest muscle and liver) to evaluate potential heavy metal risks. The levels of zinc, copper, chromium, selenium, cadmium and lead had significant differences between untreated raw manure and maggot-treated manure. The concentrations of all detected heavy metals, except for cadmium and selenium, in maggots met the limits established by the feed or feed additive standards of many countries. The bioaccumulation factor (BAF) of heavy metals decreased with the increase of the maggot instar, indicating that heavy metals were discharged from the bodies of maggots with the growth of maggots. Also, the contents of overall heavy metals in chickens fed harvested maggots met the standards for food. In conclusion, regarding heavy metals, it is eco-safe to use maggots in manure management.

Persistence of Viral Reservoirs in Multiple Tissues after Antiretroviral Therapy Suppression in a Macaque RT-SHIV Model

PubMed Central

Franks, Tamera; Kiser, Rebecca; Coalter, Vicky; Smedley, Jeremy; Piatak, Michael; Mellors, John W.; Lifson, Jeffrey D.; Ambrose, Zandrea

2013-01-01

Although antiretroviral therapy (ART) can suppress HIV-1 replication sufficiently to eliminate measurable plasma viremia, infected cells remain and ensure viral recrudescence after discontinuation of ART. We used a macaque model of HIV-1/AIDS to evaluate the location of infected cells during ART. Twelve macaques were infected with RT-SHIVmne, a SIV containing HIV-1 reverse transcriptase, conferring sensitivity to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten to fourteen weeks post-infection, 6 animals were treated with 3 or 4 antiretroviral drugs for 17-20 weeks; 6 control animals remained untreated. Viral DNA (vDNA) and RNA (vRNA) were measured in peripheral blood mononuclear cells (PBMC) and at necropsy in multiple tissues by quantitative PCR and RT-PCR. The majority of virally infected cells were located in lymphoid tissues with variable levels in the gastrointestinal tract of both treated and untreated animals. Tissue viral DNA levels correlated with week 1 plasma viremia, suggesting that tissues that harbor proviral DNA are established within the first week of infection. PBMC vDNA levels did not correlate with plasma viremia or tissue levels of vDNA. vRNA levels were high in lymphoid and gastrointestinal tissues of the untreated animals; animals on ART had little vRNA expressed in tissues and virus could not be cultured from lymph node resting CD4+ cells after 17-20 weeks on ART, indicating little or no ongoing viral replication. Strategies for eradication of HIV-1 will need to target residual virus in ART suppressed individuals, which may not be accurately reflected by frequencies of infected cells in blood. PMID:24367650

Survival of rats bearing advanced intracerebral F 98 tumors after glutathione depletion and microbeam radiation therapy: conclusions from a pilot project.

PubMed

Schültke, E; Bräuer-Krisch, E; Blattmann, H; Requardt, H; Laissue, J A; Hildebrandt, G

2018-05-10

Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time. BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 μM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 μm with a center-to-center distance of ≈400 μm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31. After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain. In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time.

In vitro and in vivo leishmanicidal activity of Astronium fraxinifolium (Schott) and Plectranthus amboinicus (Lour.) Spreng against Leishmania (Viannia) braziliensis.

PubMed

de Lima, Silvio César Gomes; Teixeira, Maria Jania; Lopes, José Evaldo Gonçalves; de Morais, Selene Maia; Torres, Alba Fabiola; Braga, Milena Aguiar; Rodrigues, Raphael Oliveira; Santiago, Gilvandete Maria Pinheiro; Martins, Alice Costa; Nagao-Dias, Aparecida Tiemi

2014-01-01

The aim of the present work was to evaluate antileishmanial activity of Astronium fraxinifolium and Plectranthus amboinicus. For the in vitro tests, essential oil of P. amboinicus (OEPA) and ethanolic extracts from A. fraxinifolium (EEAF) were incubated with 10(6) promastigotes of L. (Viannia) braziliensis. The OEPA was able to reduce the parasite growth after 48 h; nonetheless, all the EEAFs could totally abolish the parasite growth. For the in vivo studies, BALB/c mice were infected subcutaneously (s.c.) with 10(7) L. braziliensis promastigotes. Treatment was done by administering OEPA intralesionally (i.l.) for 14 days. No difference was found in lesion thickness when those animals were compared with the untreated animals. Further, golden hamsters were infected s.c. with 10(6) L. braziliensis promastigotes. The first protocol of treatment consisted of ethanolic leaf extract from A. fraxinifolium (ELEAF) administered i.l. for 4 days and a booster dose at the 7th day. The animals showed a significant reduction of lesion thickness in the 6th week, but it was not comparable to the animals treated with Glucantime. The second protocol consisted of 15 daily intralesional injections. The profiles of lesion thickness were similar to the standard treatment. In conclusion, in vivo studies showed a high efficacy when the infected animals were intralesionally treated with leaf ethanolic extract from A. fraxinifolium.

Immunomodulatory properties and anti-apoptotic effects of zinc and melatonin in an experimental model of chronic Chagas disease.

PubMed

Brazão, Vânia; Filipin, Marina Del Vecchio; Santello, Fabricia Helena; Azevedo, Angela Palamin; Toldo, Míriam Paula Alonso; de Morais, Fabiana Rossetto; do Prado, José Clóvis

2015-05-01

The immunomodulatory effects of melatonin and zinc during chronic experimental Chagas' disease were studied. Early and late apoptosis by Annexin V-propidium iodide staining were evaluated. The expression of CD28, CD80, CD86, CD45RA and CD4(+)T and CD8(+)T cells were also evaluated by flow cytometry analysis. The combination of zinc and melatonin notably reduced the apoptotic ratios of splenic cells in the infected and treated animals when compared to untreated rats, during early and late stages of apoptosis. The percentages of CD8(+)T cells in Zn, Mel or Zn and Mel treated rats were reduced when compared to infected and untreated animals. Higher percentages of CD28 expression in CD4(+) and CD8(+) T cell populations were observed in control and infected Zn-treated group as compared to untreated ones. Zn, Mel or the combination of both did not induce any statistically significant differences for B cells when comparing to treated control and infected groups. Zinc or Mel-treated animals presented a lower expression of CD86 when compared to untreated counterparts. According to our data, this work strongly suggest that the modulation of the immune system operated by zinc and melatonin administration affected the balance among T cell immune response, apoptosis and expression of co-stimulatory molecules during chronic Trypanosoma cruzi infection, inducing important changes in the host's immune response against the parasite. Future experiments in this field should be focused in improving our understanding of the key mechanisms underlying the involvement of melatonin and zinc in the immune response during chronic Chagas' disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase.

PubMed Central

Baker, G L; Corry, R J; Autor, A P

1985-01-01

Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIG. 3. FIG. 4. FIG. 5. FIG. 6. FIG. 7. PMID:3840348

Analysis of baseline gene expression levels from toxicogenomics study control animals to identify sources of variation and predict responses to chemicals

EPA Science Inventory

The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control ...

Aqueous 2% geraniol as a mosquito repellent failed against Aedes aegypti on ponies.

PubMed

Reeves, Will K; Miller, Myrna M

2010-09-01

Organic insect repellents are of interest to many agricultural producers and animal owners. Geraniol, a plant-derived alcohol, is naturally produced by a wide range of plants and is a US Environmental Protection Agency minimum risk pesticide. Previous studies have shown various concentrations of geraniol repel or kill mosquitoes; however, geraniol might cause allergic contact dermatitis in humans or animals. We tested a commercially available 2% aqueous solution of geraniol on ponies as a mosquito repellent. Five trials were conducted on ponies treated with a 60-ml aerosol mist (30 ml per side) of 2% geraniol or as untreated controls. Animals were observed 3 h postapplication to check for skin irritation. Aedes aegypti, in feeding tubes, were held on the ponies for 7 min. The average percent of biting on control animals was 56%, with a range of 16-90%, and the average for the treatments was 13%, with a range of 0-86%. Based on statistical models, there was no significant difference (P = 0.081) in the percent bites between treated and untreated animals after 3 h. Based on our data, 2% geraniol was not an adequate mosquito repellent for horses. We did not observe any skin irritation on the animals treated with 2% geraniol.

Neural changes in periapical lesions after systemic steroids in the ferret.

PubMed

Holland, G R

1993-06-01

This study was intended to clarify the relationship between the neural changes which occur around the apex of the ferret canine after pulpectomy and the inflammatory process induced by the procedure. In 12 young adult ferrets, under general anesthesia, the pulps in the mandibular canine teeth were removed and replaced with gutta percha and Grossman's sealer. Six of the animals were treated with dexamethasone to reduce the inflammatory response. Three months later, the animals, again under general anesthesia, were perfused with a fixative mixture. Three unoperated animals that had not been treated with dexamethasone were also perfused. The mandibular canine teeth and their supporting tissues were removed, processed, and serially sectioned. Three-dimensional reconstructions of the periapical lesions in each animal were assembled and their volumes measured. The density of innervation in the periapical region was estimated. The mean lesion volume in the pulpectomized animals not treated with dexamethasone was 3.54 (+/- 2.27) mm3 and in the dexamethasone-treated animals 1.33 (+/- 1.31) mm3. The differences were statistically significant when tested by the Mann-Whitney U test (p < 0.01). Bacteria were not seen within any of the lesions. The innervation density beneath the canines in the pulpectomized animals not treated with dexamethasone was 164 units per mm2 (+/- 80) and in the steroid-treated animals 151 +/- 68 units per mm2. In the control, untreated animals, the innervation density was 22 +/- 10 units per mm2. The difference between the steroid-treated pulpectomized animals and the untreated pulpectomized animals was not statistically significant (p > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice, subjected to subacute lead intoxication.

PubMed

Ivanova, Juliana; Gluhcheva, Yordanka; Dimova, Donika; Pavlova, Ekaterina; Arpadjan, Sonja

2016-01-01

In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys>spleen>liver>brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs. Copyright © 2015 Elsevier GmbH. All rights reserved.

Assessment of eosinophil peroxidase as a potential diagnostic and prognostic marker in dogs with inflammatory bowel disease.

PubMed

Bastan, Idil; Robinson, Nicholas A; Ge, Xiao Na; Rendahl, Aaron K; Rao, Savita P; Washabau, Robert J; Sriramarao, P

2017-01-01

OBJECTIVE To evaluate a method for identifying intact and degranulated eosinophils in the small intestine of dogs with inflammatory bowel disease (IBD) by use of a monoclonal antibody (mAb) against eosinophil peroxidase (EPX). ANIMALS 11 untreated dogs with IBD, 5 dogs with IBD treated with prednisolone, and 8 control dogs with no clinical evidence of gastrointestinal tract disease and no immunosuppressive treatment. PROCEDURES 4-μm-thick sections of paraffin-embedded tissues from necropsy specimens were immunostained with EPX mAb. Stained intact and degranulated eosinophils in consecutive microscopic fields (400X magnification) of the upper (villus tips) and lower (between the muscularis mucosae and crypts) regions of the lamina propria of the jejunum were manually counted. RESULTS Compared with control and treated IBD dogs, untreated IBD dogs had a significantly higher number of degranulated eosinophils in the lower region of the lamina propria. However, no significant differences were detected in the number of intact eosinophils in this region among groups. In the upper region of the lamina propria, untreated IBD dogs had a significantly higher number of degranulated and intact eosinophils, compared with control and treated IBD dogs. Number of degranulated and intact eosinophils did not differ significantly between control and treated IBD dogs. CONCLUSIONS AND CLINICAL RELEVANCE Immunohistologic analysis with EPX mAb yielded prominent granule staining that allowed reliable morphological identification of degranulated and intact eosinophils, which may provide a strategy for quantitative and selective evaluation of eosinophils in gastrointestinal biopsy specimens and a potential method to diagnose IBD and evaluate treatment outcome.

Role of Purified Anthocyanins in Improving Cardiometabolic Risk Factors in Chinese Men and Women with Prediabetes or Early Untreated Diabetes-A Randomized Controlled Trial.

PubMed

Yang, Liping; Ling, Wenhua; Yang, Yan; Chen, Yuming; Tian, Zezhong; Du, Zhicheng; Chen, Jianying; Xie, Yuanling; Liu, Zhaomin; Yang, Lili

2017-10-10

Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40-75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day, n = 80) or placebo ( n = 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial. Results: A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%; p = 0.005), low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01, p = 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01; p = 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers. Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings.

Microbial shifts in the swine distal gut in response to the treatment with antimicrobial growth promoter, tylosin

PubMed Central

Kim, Hyeun Bum; Borewicz, Klaudyna; White, Bryan A.; Singer, Randall S.; Sreevatsan, Srinand; Tu, Zheng Jin; Isaacson, Richard E.

2012-01-01

Antimicrobials have been used extensively as growth promoters (AGPs) in agricultural animal production. However, the specific mechanism of action for AGPs has not yet been determined. The work presented here was to determine and characterize the microbiome of pigs receiving one AGP, tylosin, compared with untreated pigs. We hypothesized that AGPs exerted their growth promoting effect by altering gut microbial population composition. We determined the fecal microbiome of pigs receiving tylosin compared with untreated pigs using pyrosequencing of 16S rRNA gene libraries. The data showed microbial population shifts representing both microbial succession and changes in response to the use of tylosin. Quantitative and qualitative analyses of sequences showed that tylosin caused microbial population shifts in both abundant and less abundant species. Our results established a baseline upon which mechanisms of AGPs in regulation of health and growth of animals can be investigated. Furthermore, the data will aid in the identification of alternative strategies to improve animal health and consequently production. PMID:22955886

Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol and Lipid Peroxidation in the Rat Plasma.

PubMed

Olayaki, L A; Sulaiman, S O; Anoba, N B

2015-12-20

Sleep deprivation (SD) is biological stressor that alters metabolic parameters, induced oxidative stress and lipid peroxidation. Previous studies have shown that antioxidants substances such as melatonin, tryptophan, vitamin E and vitamin C improved stress tolerance in laboratory animals. In this study, we examined the potential protective effects of administration of vitamin C on acute and chronic sleep deprivation-induced metabolic derangement. In addition, possible processes involved in vitamin C effects on acute and chronic sleep deprivation-induced metabolic derangement were determined. Thirty-five rats (120-250g) were used. The rats were divided into 7 groups of 5 rats each as Control (CTRL), Acute sleep deprived untreated with vitamin C (AC), Acute sleep deprived treated with vitamin C (AWC), Chronic sleep deprived untreated with vitamin C (CC), Chronic sleep deprived treated with vitamin C (CWC), Chronic sleep deprived + Recovery untreated with vitamin C (RC), and Chronic sleep deprived + Recovery treated with vitamin C (RWC). The SD was carried out for 20h for 1 day on the acute groups, and for 20h/day for 5 days on the chronic group, using the Multiple Modified Platforms (MMP) after oral administration of 300mg/kg of vitamin C to all vitamin C-treated groups. The recovery groups were further observed for five days after SD. The control group were treated with vitamin C and without stress in their home cages. At the end of the experiment, the animals were sacrificed and blood was collected for estimation of plasma glucose, insulin, cortisol and malondialdehyde (MDA). The results showed that acute and chronic SDs significantly  increased MDA and cortisol levels, while significantly reduced the levels of insulin. Treatment with vitamin C reversed the changes in the MDA, cortisol and plasma insulin levels. Additionally, allowing the rats to recover for 5 days after sleep deprivation corrected the observed changes. Plasma glucose was significantly reduced in all the sleep deprived groups compared to the control. In conclusion, sleep deprivation induced metabolic, hormonal and lipid peroxidation derangement, and treatment with vitamin C prevented these impairments. Thus, the effects of vitamin C could improve stress tolerance in rats.

Does footprint preparation influence tendon-to-bone healing after rotator cuff repair in an animal model?

PubMed

Ficklscherer, Andreas; Loitsch, Thomas; Serr, Michaela; Gülecyüz, Mehmet F; Niethammer, Thomas R; Müller, Hans-Helge; Milz, Stefan; Pietschmann, Matthias F; Müller, Peter E

2014-02-01

The aim of this study was to investigate the influence of footprint spongialization and radiofrequency ablation on rotator cuff repair outcomes compared with an untreated group in a rat model. We randomly assigned 189 Sprague-Dawley rats to either a spongialization, radiofrequency ablation, or untreated group. After separation of the supraspinatus tendon from the greater tubercle, the footprint was prepared by removing the cortical bone with a burr (spongialization), was prepared by ablating soft tissue with a radiofrequency ablation device, or was left unaltered (untreated). Biomechanical testing (after 7 weeks, n = 165) and histologic analysis after 1 and 7 weeks (n = 24) followed reinsertion. The mean load to failure was 17.51 ± 4.46 N/mm(2) in the spongialization group, 15.56 ± 4.85 N/mm(2) in the radiofrequency ablation group, and 19.21 ± 5.19 N/mm(2) in the untreated group. A significant difference was found between the spongialization and radiofrequency ablation groups (P = .0409), as well as between the untreated and radiofrequency ablation groups (P = .0014). There was no significant difference between the spongialization and untreated groups (P = .2456). The mean area of fibrocartilage transition, characterized by the presence of type II collagen, was larger after 1 and 7 weeks in the spongialization group (0.57 ± 0.1 mm(2) and 0.58 ± 0.1 mm(2), respectively) and untreated group (0.51 ± 0.1 mm(2) and 0.51 ± 0.2 mm(2), respectively) than in the radiofrequency ablation group (0.11 ± 0.1 mm(2) and 0.4 ± 0.1 mm(2), respectively) with P < .05 and P < .01. The results of this study show that radiofrequency ablation of the footprint results in a poor biomechanical and histologic outcome in an animal model. No preparation of the footprint has the same effect as spongialization. Different techniques of footprint preparation in rotator cuff repair may influence tendon-to-bone healing. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Salmonella organisms in garden fertilizers of animal origin.

PubMed Central

Smith, H. W.; Tucker, J. F.; Hall, M. L.; Rowe, B.

1982-01-01

Of 120 specimens of garden fertilizers of animal origin purchased in retail shops, 40 (33.3%) were found to be contaminated with salmonella organisms. Untreated bone meal (53.1%) was the most heavily contaminated but 25% of specimens of this product classed as heat-treated or sterilized were positive. In all, 32 serotypes were identified. PMID:6284835

Aflatoxin Toxicity Reduction in Feed by Enhanced Binding to Surface-Modified Clay Additives

PubMed Central

Jaynes, William F.; Zartman, Richard E.

2011-01-01

Animal feeding studies have demonstrated that clay additives, such as bentonites, can bind aflatoxins in ingested feed and reduce or eliminate the toxicity. Bentonite deposits are found throughout the world and mostly consist of expandable smectite minerals, such as montmorillonite. The surfaces of smectite minerals can be treated with organic compounds to create surface-modified clays that more readily bind some contaminants than the untreated clay. Montmorillonites treated with organic cations, such as hexadecyltrimethylammonium (HDTMA) and phenyltrimethylammonium (PTMA), more effectively remove organic contaminants, such as benzene and toluene, from water than untreated clay. Similarly, montmorillonite treated with PTMA (Kd = 24,100) retained more aflatoxin B1 (AfB1) from aqueous corn flour than untreated montmorillonite (Kd = 944). Feed additives that reduced aflatoxin toxicity in animal feeding studies adsorbed more AfB1 from aqueous corn flour than feed additives that were less effective. The organic cations HDTMA and PTMA are considered toxic and would not be suitable for clay additives used in feed or food, but other non-toxic or nutrient compounds can be used to prepare surface-modified clays. Montmorillonite (SWy) treated with choline (Kd = 13,800) and carnitine (Kd = 3960) adsorbed much more AfB1 from aqueous corn flour than the untreated clay (Kd = 944). A choline-treated clay prepared from a reduced-charge, high-charge montmorillonite (Kd = 20,100) adsorbed more AfB1 than the choline-treated high-charge montmorillonite (Kd = 1340) or the untreated montmorillonite (Kd = 293). Surface-modified clay additives prepared using low-charge smectites and nutrient or non-toxic organic compounds might be used to more effectively bind aflatoxins in contaminated feed or food and prevent toxicity. PMID:22069725

Aflatoxin toxicity reduction in feed by enhanced binding to surface-modified clay additives.

PubMed

Jaynes, William F; Zartman, Richard E

2011-06-01

Animal feeding studies have demonstrated that clay additives, such as bentonites, can bind aflatoxins in ingested feed and reduce or eliminate the toxicity. Bentonite deposits are found throughout the world and mostly consist of expandable smectite minerals, such as montmorillonite. The surfaces of smectite minerals can be treated with organic compounds to create surface-modified clays that more readily bind some contaminants than the untreated clay. Montmorillonites treated with organic cations, such as hexadecyltrimethylammonium (HDTMA) and phenyltrimethylammonium (PTMA), more effectively remove organic contaminants, such as benzene and toluene, from water than untreated clay. Similarly, montmorillonite treated with PTMA (K(d) = 24,100) retained more aflatoxin B1 (AfB1) from aqueous corn flour than untreated montmorillonite (K(d) = 944). Feed additives that reduced aflatoxin toxicity in animal feeding studies adsorbed more AfB1 from aqueous corn flour than feed additives that were less effective. The organic cations HDTMA and PTMA are considered toxic and would not be suitable for clay additives used in feed or food, but other non-toxic or nutrient compounds can be used to prepare surface-modified clays. Montmorillonite (SWy) treated with choline (K(d) = 13,800) and carnitine (K(d) = 3960) adsorbed much more AfB1 from aqueous corn flour than the untreated clay (K(d) = 944). A choline-treated clay prepared from a reduced-charge, high-charge montmorillonite (K(d) = 20,100) adsorbed more AfB1 than the choline-treated high-charge montmorillonite (K(d) = 1340) or the untreated montmorillonite (K(d) = 293). Surface-modified clay additives prepared using low-charge smectites and nutrient or non-toxic organic compounds might be used to more effectively bind aflatoxins in contaminated feed or food and prevent toxicity.

Therapeutic efficacy induced by the oral administration of Agaricus blazei Murill against Leishmania amazonensis.

PubMed

Valadares, Diogo G; Duarte, Mariana C; Ramírez, Laura; Chávez-Fumagalli, Miguel A; Lage, Paula S; Martins, Vivian T; Costa, Lourena E; Ribeiro, Tatiana G; Régis, Wiliam C B; Soto, Manuel; Fernandes, Ana Paula; Tavares, Carlos A P; Coelho, Eduardo A F

2012-10-01

The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dose-titration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg(-1) day(-1). In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg(-1) day(-1)) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological and immunological parameters were analyzed. Mice treated with the AbM presented a 60% reduction in the inflammation of infected footpads as compared to untreated control-infected mice. Moreover, in the treated mice, as compared to the untreated controls, approximately 60 and 66% reductions could be observed in the parasite burdens of the footpad and draining lymph nodes, respectively. In addition, no parasites could be detected in the spleen of treated mice at week 14 postinfection. These treated animals produced significantly higher levels of interferon gamma (IFN-γ) and nitric oxide (NO), higher levels of parasite-specific IgG2a isotype antibodies, and lower levels of interleukin (IL)-4, and IL-10 in the spleen and lymph node cell cultures than did the controls. Differences could be observed by comparing animals treated with AbM to those treated with AmpB, as indicated by a significant reduction in tissue parasitism, higher levels of IFN-γ and NO, and lower levels of IL-4 and IL-10, as well as by a decreased hepatic toxicity. In conclusion, the present study's data show that the A. blazei Murill water extract presents a high potential for the treatment of leishmaniasis, although additional studies on mice, as well as on other mammal hosts, are warranted in an attempt to determine this extract's true efficacy as compared to other known therapeutic products.

Autonomic control of heart rate during orthostasis and the importance of orthostatic-tachycardia in the snake Python molurus.

PubMed

Armelin, Vinicius Araújo; da Silva Braga, Victor Hugo; Abe, Augusto Shinya; Rantin, Francisco Tadeu; Florindo, Luiz Henrique

2014-10-01

Orthostasis dramatically influences the hemodynamics of terrestrial vertebrates, especially large and elongated animals such as snakes. When these animals assume a vertical orientation, gravity tends to reduce venous return, cardiac filling, cardiac output and blood pressure to the anterior regions of the body. The hypotension triggers physiological responses, which generally include vasomotor adjustments and tachycardia to normalize blood pressure. While some studies have focused on understanding the regulation of these vasomotor adjustments in ectothermic vertebrates, little is known about regulation and the importance of heart rate in these animals during orthostasis. We acquired heart rate and carotid pulse pressure (P PC) in pythons in their horizontal position, and during 30 and 60° inclinations while the animals were either untreated (control) or upon muscarinic cholinoceptor blockade and a double autonomic blockade. Double autonomic blockade completely eradicated the orthostatic-tachycardia, and without this adjustment, the P PC reduction caused by the tilts became higher than that which was observed in untreated animals. On the other hand, post-inclinatory vasomotor adjustments appeared to be of negligible importance in counterbalancing the hemodynamic effects of gravity. Finally, calculations of cardiac autonomic tones at each position revealed that the orthostatic-tachycardia is almost completely elicited by a withdrawal of vagal drive.

Even Four Minutes of Poor Quality of CPR Compromises Outcome in a Porcine Model of Prolonged Cardiac Arrest

PubMed Central

Li, Heng; Zhang, Lei; Yang, Zhengfei; Huang, Zitong; Chen, Bihua; Li, Yongqin; Yu, Tao

2013-01-01

Objective. Untrained bystanders usually delivered suboptimal chest compression to victims who suffered from cardiac arrest in out-of-hospital settings. We therefore investigated the hemodynamics and resuscitation outcome of initial suboptimal quality of chest compressions compared to the optimal ones in a porcine model of cardiac arrest. Methods. Fourteen Yorkshire pigs weighted 30 ± 2 kg were randomized into good and poor cardiopulmonary resuscitation (CPR) groups. Ventricular fibrillation was electrically induced and untreated for 6 mins. In good CPR group, animals received high quality manual chest compressions according to the Guidelines (25% of animal's anterior-posterior thoracic diameter) during first two minutes of CPR compared with poor (70% of the optimal depth) compressions. After that, a 120-J biphasic shock was delivered. If the animal did not acquire return of spontaneous circulation, another 2 mins of CPR and shock followed. Four minutes later, both groups received optimal CPR until total 10 mins of CPR has been finished. Results. All seven animals in good CPR group were resuscitated compared with only two in poor CPR group (P < 0.05). The delayed optimal compressions which followed 4 mins of suboptimal compressions failed to increase the lower coronary perfusion pressure of five non-survival animals in poor CPR group. Conclusions. In a porcine model of prolonged cardiac arrest, even four minutes of initial poor quality of CPR compromises the hemodynamics and survival outcome. PMID:24364028

Bony integration of titanium implants with a novel bioactive calcium titanate (Ca4Ti3O10) surface treatment in a rabbit model.

PubMed

Haenle, Maximilian; Lindner, Tobias; Ellenrieder, Martin; Willfahrt, Manfred; Schell, Hanna; Mittelmeier, Wolfram; Bader, Rainer

2012-10-01

Nowadays total joint replacement is an indispensable component of modern medicine. The surfaces characteristics of cementless prostheses may be altered to achieve an accelerated and enduring bony integration. Classic surface coatings bear the risk of loosening or flaking from the implant body. This risk is excluded by the chemical conversion of the naturally existing TiO(2) surface layer into calcium titanate. The aim of this experimental animal study was to investigate the bony integration of implants with a new calcium titanate surface (Ca(4)Ti(3)O(10)) compared with a conventional standard Ti6Al4V surface. Cylindrical implants, made of titanium alloy (Ti6Al4V) were implanted in both lateral femoral condyles of New Zealand white rabbits. In each animal, an implant with and without surface treatment was inserted in a blinded manner. Animals were sacrificed after 4, 12, and 36 weeks, respectively. The axial pull-off forces were determined for 25 animals using a universal testing machine (Zwick Z010, Ulm, Germany). Furthermore, a histological analysis of the bony integration of the implants was performed in 12 specimens. In general, the pull-off forces for untreated and treated implants increased with longer survival times of the rabbits. No significant difference could be shown after 4 weeks between treated and untreated implants. After 12 weeks, the treated implants revealed a statistical significant higher pull-off force. After 36 weeks, the pull-off forces for treated and untreated implants aligned again. Titanium implants treated with calcium titanate, may offer an interesting and promising implant surface modification for endoprosthetic implants. They might lead to an accelerated osseointegration of total hip and knee replacements. Copyright © 2012 Wiley Periodicals, Inc.

The Synthetic Antimicrobial Peptide 19-2.5 Interacts with Heparanase and Heparan Sulfate in Murine and Human Sepsis.

PubMed

Martin, Lukas; De Santis, Rebecca; Koczera, Patrick; Simons, Nadine; Haase, Hajo; Heinbockel, Lena; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias

2015-01-01

Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan sulfate-fragments (HS-fragments) and triggers the fatal and excessive inflammatory response in sepsis. As a potential anti-inflammatory agent for sepsis therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative bacterial infection. We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in murine and human sepsis. Our data indicate that the treatment of septic mice with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic mice treated with peptide 19-2.5 compared to untreated control animals. In humans, plasma heparanase level and activity are elevated in septic shock. The ex vivo addition of peptide 19-2.5 to plasma of septic shock patients decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in murine and human sepsis and consecutively attenuates the generation of circulating HS-fragments in systemic inflammation. Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in sepsis.

Glucagon-like peptide-2 treatment improves glucose dysmetabolism in mice fed a high-fat diet.

PubMed

Baldassano, Sara; Amato, Antonella; Caldara, Gaetano Felice; Mulè, Flavia

2016-12-01

Previous studies suggested that endogenous glucagon-like peptide 2 (GLP-2) is dispensable for the regulation of glucose homeostasis under normal conditions, while it can play a beneficial role in obesity conditions. The purpose of the present study was to investigate whether chronic treatment with Gly 2 -GLP-2, a stable analogue of GLP-2, can have an impact on glycaemic and lipid control in mice fed a high-fat diet (HFD), an animal model of human obesity and insulin resistance. HFD mice were treated once a day with Gly 2 -GLP-2 for 4 weeks. Body weight, food intake, fasting glucose, intraperitoneal glucose tolerance, insulin-induced glucose clearance, glucose-stimulated insulin secretion, β-cell mass, plasma lipid metabolic profile, and lipid deposition in the liver were examined. In untreated HFD mice, fasting glucose levels, glucose tolerance, glucose-stimulated plasma insulin and sensibility to exogenous insulin were deteriorating with time and β-cell mass increased. In Gly 2 -GLP-2-treated mice, we found significant increase in glucose tolerance and exogenous insulin sensitivity, reduction in glucose-stimulated plasma insulin and in the increase in β-cell mass in comparison with pair-aged HFD untreated animals. The chronic treatment with the peptide was not associated with remarkable improvements of dyslipidemia and it did not prevent liver fat accumulation and the presence of microvesicular steatosis. In conclusion, the results of the present study suggest, for the first time, that Gly 2 -GLP-2 may produce glucose metabolic benefits in mice with diet-induced obesity. The mechanisms underlying the beneficial impact of GLP-2 on glucose metabolism remain to be established.

Biological Effect of Leaf Aqueous Extract of Caesalpinia pyramidalis in Goats Naturally Infected with Gastrointestinal Nematodes

PubMed Central

Borges-dos-Santos, Roberto Robson; López, Jorge A.; Santos, Luciano C.; Zacharias, Farouk; David, Jorge Maurício; David, Juceni Pereira; Lima, Fernanda Washington de Mendonça

2012-01-01

Forty-eight goats naturally infected with gastrointestinal nematodes were randomly divided into four groups (n = 12): negative control (G1) (untreated), positive control (G2) (treated with doramectin, 1 mL/50 Kg b.w.), and G3 and G4 treated with 2.5 and 5 mg/Kg b.w. of a leaf aqueous extract of Caesalpinia pyramidalis (CP). Fecal and blood samples were regularly collected for the evaluation of fecal egg count (FEC), hematological and immunological parameters to assess the anthelmintic activity. In treated animals with CP, there was noted a significant reduction of 54.6 and 71.2% in the mean FEC (P < 0.05). An increase in IgA levels was observed in G3 and G4 (P < 0.05), during the experimental period, suggesting that it was stimulated by the extract administration. In conclusion, the results showed that CP provoked a protective response in infected animals treated with them. This response could be partly explained by the CP chemical composition. PMID:22548117

Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

PubMed Central

Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

2011-01-01

Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

Responses of Juvenile Black-tailed Prairie Dogs ( Cynomys ludovicianus ) to a Commercially Produced Oral Plague Vaccine Delivered at Two Doses.

PubMed

Cárdenas-Canales, Elsa M; Wolfe, Lisa L; Tripp, Daniel W; Rocke, Tonie E; Abbott, Rachel C; Miller, Michael W

2017-10-01

We confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (RCN-F1/V307) expressing Yersinia pestis V and F1 antigens. Forty-five juvenile black-tailed prairie dogs ( Cynomys ludovicianus ) were randomly divided into three treatment groups (n=15 animals/group). Animals in the first group received one standard-dose vaccine bait (5×10 7 plaque-forming units [pfu]; STD). The second group received a lower-dose bait (1×10 7 pfu; LOW). In the third group, five animals received two standard-dose baits and 10 were left untreated but in contact. Two vaccine-treated and one untreated prairie dogs died during the study, but laboratory analyses ruled out vaccine involvement. Overall, 17 of 33 (52%; 95% confidence interval for binomial proportion [bCI] 34-69%) prairie dogs receiving vaccine-laden bait showed a positive anti-V antibody response on at least one sampling occasion after bait consumption, and eight (24%; bCI 11-42%) showed sustained antibody responses. The STD and LOW groups did not differ (P≥0.78) in their proportions of overall or sustained antibody responses after vaccine bait consumption. Serum from one of the nine (11%; bCI 0.3-48%) surviving untreated, in-contact prairie dogs also had detectable antibody on one sampling occasion. We did not observe any adverse effects related to oral vaccination.

Morphological study of the effects of aqueous leaf extract of Xylopia aethiopica on the pancreas in diabetic rats.

PubMed

Ofusori, David A; Komolafe, Omobola A; Adewole, Olarinde S; Arayombo, Babatunde E; Margolis, Denise; Naicker, Thajasvarie

2016-01-01

To investigate the histological and immunohistochemical effects of aqueous leaf extract of Xylo- pia aethiopica on the pancreas in streptozotocin-induced diabetic rats, 30 adult Wistar rats were divided into three groups (n=10). Group A was the control (administered with equivalent vol- ume of citrate buffer), group B animals were made diabetic by a single intraperitoneal injection of streptozotocin dissolved in citrate buffer (65 mg/kg), group C animals were made diabetic as above and treated with 200mg/kg body weight of aqueous leave extract of Xylopia aethiop- ica for 25 days. Upon animal sacrifice, the pancreas were excised, fixed in 10% formol saline and processed for light microscopy and immunohistochemistry.. The results revealed destruc- tion of the islet cells in the untreated diabetic group as compared with the controls. The extract treated group was characterized by recovery/regenerative processes indicated by improvement in islet morphology. In untreated diabetic rats immunoreactive P-cells were sparse, at variance from the controls. The group treated with aqueous leaf extract of Xylopia aethiopica revealed more intense staining for insulin and significant (p<0.05) increase in the percentage of immuno- labelled surface area when compared with the untreated diabetic group, suggesting the ability of P-cells to secrete insulin in the extract treated rats. We conclude that the aqueous leaf extract of Xylopia aethiopica improves recovery process of P-cells in streptozotocin-induced diabetic rats and might become useful in the management of diabetes related complications.

PVA-chitosan composite hydrogel versus alginate beads as a potential mesenchymal stem cell carrier for the treatment of focal cartilage defects.

PubMed

Dashtdar, Havva; Murali, Malliga Raman; Abbas, Azlina Amir; Suhaeb, Abdulrazzaq Mahmod; Selvaratnam, Lakshmi; Tay, Liang Xin; Kamarul, Tunku

2015-05-01

To investigate whether mesenchymal stem cells (MSCs) seeded in novel polyvinyl alcohol (PVA)-chitosan composite hydrogel can provide comparable or even further improve cartilage repair outcomes as compared to previously established alginate-transplanted models. Medial femoral condyle defect was created in both knees of twenty-four mature New Zealand white rabbits, and the animals were divided into four groups containing six animals each. After 3 weeks, the right knees were transplanted with PVA-chitosan-MSC, PVA-chitosan scaffold alone, alginate-MSC construct or alginate alone. The left knee was kept as untreated control. Animals were killed at the end of 6 months after transplantation, and the cartilage repair was assessed through Brittberg morphological score, histological grading by O'Driscoll score and quantitative glycosaminoglycan analysis. Morphological and histological analyses showed significant (p < 0.05) tissue repair when treated with PVA-chitosan-MSC or alginate MSC as compared to the scaffold only and untreated control. In addition, safranin O staining and the glycosaminoglycan (GAG) content were significantly higher (p < 0.05) in MSC treatment groups than in scaffold-only or untreated control group. No significant difference was observed between the PVA-chitosan-MSC- and alginate-MSC-treated groups. PVA-chitosan hydrogel seeded with mesenchymal stem cells provides comparable treatment outcomes to that of previously established alginate-MSC construct implantation. This study supports the potential use of PVA-chitosan hydrogel seeded with MSCs for clinical use in cartilage repair such as traumatic injuries.

Responses of juvenile black-tailed prairie dogs (Cynomys ludovicianus) to a commercially produced oral plague vaccine delivered at two doses

USGS Publications Warehouse

Cárdenas-Canales, Elsa M.; Wolfe, Lisa L.; Tripp. Daniel W.,; Rocke, Tonie E.; Abbott, Rachel C.; Miller, Michael W.

2017-01-01

We confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (RCN-F1/V307) expressing Yersinia pestis V and F1 antigens. Forty-five juvenile black-tailed prairie dogs (Cynomys ludovicianus) were randomly divided into three treatment groups (n=15 animals/group). Animals in the first group received one standard-dose vaccine bait (5×107 plaque-forming units [pfu]; STD). The second group received a lower-dose bait (1×107 pfu; LOW). In the third group, five animals received two standard-dose baits and 10 were left untreated but in contact. Two vaccine-treated and one untreated prairie dogs died during the study, but laboratory analyses ruled out vaccine involvement. Overall, 17 of 33 (52%; 95% confidence interval for binomial proportion [bCI] 34−69%) prairie dogs receiving vaccine-laden bait showed a positive anti-V antibody response on at least one sampling occasion after bait consumption, and eight (24%; bCI 11–42%) showed sustained antibody responses. The STD and LOW groups did not differ (P≥0.78) in their proportions of overall or sustained antibody responses after vaccine bait consumption. Serum from one of the nine (11%; bCI 0.3–48%) surviving untreated, in-contact prairie dogs also had detectable antibody on one sampling occasion. We did not observe any adverse effects related to oral vaccination.

Effects of ceftiofur treatment on the susceptibility of commensal porcine E.coli--comparison between treated and untreated animals housed in the same stable.

PubMed

Beyer, Anne; Baumann, Sven; Scherz, Gesine; Stahl, Jessica; von Bergen, Martin; Friese, Anika; Roesler, Uwe; Kietzmann, Manfred; Honscha, Walther

2015-10-15

Healthy farm animals have been found to act as a reservoir of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli). Therefore, the objective of the study was to determine the input of antimicrobial active ceftiofur metabolites in the stable via faeces and urine after intramuscular administration of the drug to pigs and the elucidation of the Escherichia coli ESBL resistance pattern of treated and untreated pigs housed in the same barn during therapy. For determination of the minimal inhibitory concentration (MIC) the method of microdilutionaccording to the recommended procedure of the Clinical and Laboratory Standards Institute was used. Inaddition to that, a qualitative determination was performed by agar dilution. Unsusceptible E. coli speciesselected via agar dilution with cefotaxime were confirmed by MALDI-TOF and ESBL encoding genes wereidentified by PCR. The amounts of ceftiofur measured as desfuroylceftiofur (DFC) in the different probes (plasma, urine, faeces and dust) were analysed by UPLC-MS/MS. In a first experiment two groups of pigs (6 animals per group) were housed in the same barn in two separated boxes. One group (group B) were treated with ceftiofur according to the licence (3 mg/kg administered intramuscularly (i.m.) on three consecutive days, day 1-3). During a second treatment period (day 29-31) an increased rate of ESBL resistant E. coli was detectable in these treated pigs and in the air of the stable. Moreover, the second group of animals (group A) formerly untreated but housed for the whole period in the same stable as the treated animals revealed increased resistance rates during their first treatment (day 45-47) with ceftiofur. In order to investigate the environmental input of ceftiofur during therapy and to simulate oral uptake of ceftiofur residues from the air of the stable a second set of experiments were performed. Pigs (6 animals) were treated with an interval of 2 weeks for 3 days with different doses of ceftiofur (3 mg/kg, 1 mg/kg and 0.3 mg/kg i.m.) as well as with 3 mg/kg per os) and the renal and biliary excretion of ceftiofur as its active metabolite were measured in comparison to the plasma levels. In addition to that, probes of the sedimentation dust and the air of the stable were analysed for drug residues. The present study shows that treatment of several animals in a stable with ceftiofur influences the resistance pattern of intestinal Escherichia coli of the treated as well as untreated animals housed in the same stable. During therapy with the drug which was administered by injection according to the licence we detected nameable amounts of ceftiofur and its active metabolites in the dust and air of the stable.

Treated and untreated rock dust: Quartz content and physical characterization.

PubMed

Soo, Jhy-Charm; Lee, Taekhee; Chisholm, William P; Farcas, Daniel; Schwegler-Berry, Diane; Harper, Martin

2016-11-01

Rock dusting is used to prevent secondary explosions in coal mines, but inhalation of rock dusts can be hazardous if the crystalline silica (e.g., quartz) content in the respirable fraction is high. The objective of this study is to assess the quartz content and physical characteristics of four selected rock dusts, consisting of limestone or marble in both treated (such as treatment with stearic acid or stearates) and untreated forms. Four selected rock dusts (an untreated and treated limestone and an untreated and treated marble) were aerosolized in an aerosol chamber. Respirable size-selective sampling was conducted along with particle size-segregated sampling using a Micro-Orifice Uniform Deposit Impactor. Fourier Transform Infrared spectroscopy and scanning electron microscopy with energy-dispersive X-ray (SEM-EDX) analyses were used to determine quartz mass and particle morphology, respectively. Quartz percentage in the respirable dust fraction of untreated and treated forms of the limestone dust was significantly higher than in bulk samples, but since the bulk percentage was low the enrichment factor would not have resulted in any major change to conclusions regarding the contribution of respirable rock dust to the overall airborne quartz concentration. The quartz percentage in the marble dust (untreated and treated) was very low and the respirable fractions showed no enrichment. The spectra from SEM-EDX analysis for all materials were predominantly from calcium carbonate, clay, and gypsum particles. No free quartz particles were observed. The four rock dusts used in this study are representative of those presented for use in rock dusting, but the conclusions may not be applicable to all available materials.

Mycoplasma and associated bacteria isolated from ovine pink-eye.

PubMed

Langford, E V

1971-01-01

A mycoplasma was recovered from the untreated conjunctival membranes of nine sheep affected by Pink-eye. It was neither isolated from the conjunctiva of treated animals which were affected nor from the conjunctiva of normal animals either in contact or not in contact with affected animals. Bacteria found on normal conjunctival membranes were Neisseria ovis, Escherichia coli, Staphylococcus epidermididis, Streptococcus and Bacillus spp. Bacteria found in clinical cases of Pink-eye were N. ovis, E. coli, a Streptococcus and Pseudomonas spp.

Efficacy of Four Solanum spp. Extracts in an Animal Model of Cutaneous Leishmaniasis.

PubMed

Cos, Paul; Janssens, Jo; Piñón, Abel; Cuesta-Rubio, Osmany; Yglesias-Rivera, Arianna; Díaz-García, Alexis; Vilegas, Wagner; Monzote, Lianet

2018-06-05

Background: Leishmaniasis is a complex protozoa disease caused by Leishmania genus (Trypanosomatidae family). Currently, there have been renewed interests worldwide in plants as pharmaceutical agents. In this study, the in vivo efficacy of Solanum spp. is assessed in an L. amazonensis BALB/c mice model for experimental cutaneous leishmaniasis. Methods: Animals were infected with 5 × 10⁶ metacyclic promastigotes and 30-day post-infection, a treatment with 30 mg/kg of Solanum extracts or Glucantime ® (GTM) was applied intralesionally every four days to complete 5 doses. Results: Neither death nor loss of weight higher than 10% was observed. All the tested extracts were able to control the infection, compared with the infected and untreated group. Solanum havanense Jacq. extract showed the highest efficacy and was superior ( p < 0.05) to GTM. Solanum myriacanthum Dunal., S. nudum Dunal. and S. seaforthianum Andr. extracts demonstrated a similar effect ( p > 0.05) to GTM. An increase of IFN-γ ( p < 0.05) was displayed only by animals treated with S. nudum compared to the group treated with a vehicle, while no differences ( p > 0.05) were observed for IL-12. Conclusions: In vivo effects of Solanum extracts were demonstrated, suggesting that this genus could be further explored as a new antileishmanial alternative.

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model.

PubMed

Guido, Maria C; Debbas, Victor; Salemi, Vera M; Tavares, Elaine R; Meirelles, Thayna; Araujo, Thaís L S; Nolasco, Patricia; Ferreira-Filho, Julio C A; Takimura, Celso K; Pereira, Lygia V; Laurindo, Francisco R

2018-01-01

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔ loxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

Occurrence of bacteriophages infecting Aeromonas, Enterobacter, and Klebsiella in water and association with contamination sources in Thailand.

PubMed

Wangkahad, Bencharong; Bosup, Suchada; Mongkolsuk, Skorn; Sirikanchana, Kwanrawee

2015-06-01

The co-residence of bacteriophages and their bacterial hosts in humans, animals, and environmental sources directed the use of bacteriophages to track the origins of the pathogenic bacteria that can be found in contaminated water. The objective of this study was to enumerate bacteriophages of Aeromonas caviae (AecaKS148), Enterobacter sp. (EnspKS513), and Klebsiella pneumoniae (KlpnKS648) in water and evaluate their association with contamination sources (human vs. animals). Bacterial host strains were isolated from untreated wastewater in Bangkok, Thailand. A double-layer agar technique was used to detect bacteriophages. All three bacteriophages were detected in polluted canal samples, with likely contamination from human wastewater, whereas none was found in non-polluted river samples. AecaKS148 was found to be associated with human fecal sources, while EnspKS513 and KlpnKS648 seemed to be equally prevalent in both human and animal fecal sources. Both bacteriophages were also present in polluted canals that could receive contamination from other fecal sources or the environment. In conclusion, all three bacteriophages were successfully monitored in Bangkok, Thailand. This study provided an example of bacteriophages for potential use as source identifiers of pathogen contamination. The results from this study will assist in controlling sources of pathogen contamination, especially in developing countries.

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

PubMed Central

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-01-01

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model. PMID:19638223

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet.

PubMed

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-07-28

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.

Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

PubMed Central

Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong

2015-01-01

Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

The anti-caries activity and toxicity of an experimental propolis-containing varnish.

PubMed

DE Luca, Mariana Passos; Freires, Irlan Almeida; Gala-García, Alfonso; Santos, Vagner Rodrigues; Vale, Miriam Pimenta; Alencar, Severino Matias de; Rosalen, Pedro Luiz

2017-06-05

We investigated the anti-caries effects of an experimental propolis varnish in vivo, and further tested its toxicity against fibroblasts. Fifty-six SPF female Wistar rats were infected with Streptococcus mutans UA159 (SM) and allocated into four groups (n = 14/group): G1, propolis varnish (15%/PV); G2, chitosan varnish (CV/vehicle); G3, gold standard (GS/Duraphat®); and G4, untreated. The animals received a single varnish application on their molars and were submitted to a high cariogenic challenge (Diet-2000, 56% sucrose, and 5% sucrose-added water, ad libitum) for 4 weeks. Total cultivable microbiota and SM were counted, and smooth-surface and sulcal caries were scored. PV, CV and GS cytotoxic effects were tested against fibroblasts. The data were analyzed using ANOVA with the Tukey-Kramer test (p ≤ 0.05). Total microbiota and SM counts did not differ among the treatments (p = 0.78), or in relation to the untreated group (p = 0.52). PV reduced development of smooth-surface enamel caries compared with the untreated group (p = 0.0018), with no significant difference from GS (p = 0.92); however, the PV effects were no longer observed when the dentin was affected. Neither PV nor GS prevented enamel sulcal lesion onset, but GS significantly reduced the severity of dentinal sulcal lesions (p < 0.0001). No significant difference was observed in fibroblast viability between PV and GS (p < 0.0001). In conclusion, PV prevented smooth-surface enamel caries and showed low cell toxicity. Nevertheless, due to the high cariogenic challenge, its effects were not sustained throughout the experiment. Further studies are encouraged to establish a protocol to sustain the long-term anti-caries activity of PV in the oral cavity.

Effect of aminoguanidine and albendazole on inducible nitric oxide synthase (iNOS) activity in T. spiralis-infected mice muscles.

PubMed

Zeromski, Jan; Boczoń, Krystyna; Wandurska-Nowak, Elzbieta; Mozer-Lisewska, Iwona

2005-01-01

The aim of this study was to provide evidence for the expression of iNOS in the cells of inflammatory infiltrates around larvae in skeletal muscles of T. spiralis infected mice. The BALB/c mice (n = 8) divided into subgroups, received either aminoguanidine (AMG)--a specific iNOS inhibitor or albendazole (ALB)--an antiparasitic drug of choice in trichinellosis treatment. Control animals (n = 2 in each subgroup) were either uninfected and treated or uninfected and untreated. Frozen sections of hind leg muscles from mice sacrificed at various time intervals after infection were cut and subjected to immunohistochemistry, using monoclonal anti-iNOS antibody. The ALB-treated mice revealed stronger iNOS staining in the infiltrating cells around larvae than the infected and untreated animals. On the contrary, in the AMG-treated animals, the infiltrating cells did not show any specific iNOS reaction. These data confirm the specificity of iNOS staining in the cellular infiltrates around T. spiralis larvae and shed some light on the role of nitric oxide during ALB treatment in experimental trichinellosis.

The properties of red seaweed (Kappaphycus alvarezii) and its effect on mammary carcinogenesis.

PubMed

Chang, Vi-Sion; Okechukwu, Patrick N; Teo, Swee-Sen

2017-03-01

The edible red seaweed (Kappaphycus alvarezii) is one of the algae species which was found to be rich in nutrients and nutraceutical. Hence, K. alvarezii may have the ability to suppress cancer through its antiproliferative properties. The aim of this study was to investigate the potential compounds of K. alvarezii, cytotoxicity properties of K. alvarezii extract on breast cancer cell line (MCF-7), investigated toxicity effect of high dosage K. alvarezii extract in rats and determined the effect of K. alvarezii on 7, 12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis in rats. The method of LCMS/MS and MTT assay were used. For animal study, sub-chronic toxicity method was used, the rats were supplemented with 2000mg/kg body weight daily of K. alvarezii crude extracts by oral gavage. For the anticancer effect of K. alvarezii crude extracts, this study consisted of three groups of the experimental, untreated and normal group of rats. The experimental and untreated groups of rats were induced with mammary tumour with DMBA. The experimental group of rats was given with K. alvarezii crude extracts orally. The results were being used to compare with the untreated group of rats and normal group of rats. All the rats were fed with standard diet and water ad libitum. Mortality, behavior changes and tumour sizes were observed specifically. The differences between the three groups of rats were evaluated by using the ANOVA test. By using LCMS/MS method, six unknown compounds were analysed. K. alvarezii crude extract reduced the cell viability of MCF-7 from 84.91% to 0.81% and the IC 50 value is 4.1±0.69mg/mL. For sub-chronic and heavy metal toxicity studies, no significant difference was found in haematological and biochemical values of the control group and experimental group. The growth rate of tumours in the untreated group of rats was found significantly higher than the experimental group of rats. Besides that, the white blood cells level in untreated group was found significantly higher than the experimental group and the normal group. In conclusion, K. alvarezii extract might able to slow down the growth rate of the tumour cells, therefore, identification of an active compound of inhibition growth rate of the tumour cells can be positively carried out in the future. Copyright © 2016. Published by Elsevier Masson SAS.

Tyrosine - Effects on catecholamine release

NASA Technical Reports Server (NTRS)

Acworth, Ian N.; During, Matthew J.; Wurtman, Richard J.

1988-01-01

Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.

Effect of a controlled-release albendazole capsule on parasitism and productivity of sheep.

PubMed

Corba, J; Krupicer, I; Legény, J; Juris, P; Veselý, L

1991-11-01

The efficacy of intraruminal albendazole (ABZ) capsules (Profitril-Captec) and the effect of treatment on productivity were studied in 300 ewes infected with gastrointestinal nematodes and the trematode Dicrocoelium dendriticum. Coprological tests revealed that treated animals remained negative for 10 weeks after the administration of capsules. Contamination of pasture with nematode larvae was significantly reduced during the whole experiment. Necropsy of 14 animals (seven treated and seven untreated) showed 96.9-99.2% efficacy against the nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis, while efficacy was 88.5% against D. dendriticum. During the 6 month pasture season (May-October 1989), treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls. Our study confirms the reliability of the ABZ slow-release capsules over 90 days and the positive effect of treatment on nematode contamination of pasture and ewe productivity.

[Effect of melatonin instillations on the clinical course of experimental uveitis and biochemical processes in tears and aqueous humor].

PubMed

Chesnokova, N B; Beznos, O V; Lozinskaya, N A; Beyshenova, G A; Nesterova, T V

2016-01-01

Acute immunogenic uveitis was modeled in rabbits via the subcutaneous and intravitreal injections of normal horse serum. We studied the effect of instillations of 0.1% melatonin solution on the clinical course of uveitis and biochemical parameters of tear fluid and aqueous humor: antioxi-dant activity, protein concentration and α(2)-macroglobulin level. Melatonin instillations decreased clinical manifestations of uveitis. We found that the antioxidant activity in tears of the rabbits treated with melatonin was substantially higher and the α(2)-macroglobulin level lower than in untreated animals. Antioxidant activity in aqueous humor taken on day 10 of uveitis was also twice higher while protein and α(2)-macroglobulin levels were 1.5-2 times lower than in untreated animals. These data indicate that instillations of melatonin increase the local antioxidant activity and decrease the acuity of inflammation and permeability of hematoophthalmic barrier in uveitis.

Differential application of lambda-cyhalothrin to control the sandfly Lutzomyia longipalpis.

PubMed

Kelly, D W; Mustafa, Z; Dye, C

1997-01-01

To study the impact of residual pyrethroid insecticide on the abundance and distribution of peridomestic Lutzomyia longipalpis, the sandfly vector of visceral leishmaniasis in Brazil, lambda-cyhalothrin was applied at 20 mg a.i.m-2 in the following interventions: (i) spraying of all animal pens in a village (blanket coverage); (ii) treatment of a subset of animal pens, either by spraying, or by installation of insecticide-impregnated 1 m2 cotton sheets as 'targets' (focal coverage). By sampling with CDC light traps, and using a novel analytical approach, we detected a 90% reduction in Lu.longipalpis abundance in sprayed sheds of the focal intervention. However, there was no discernible effect on the abundance of other phlebotomines trapped in sheds, or on the abundance of Lu.longipalpis in untreated dining-huts and houses. This differential impact on Lu.longipalpis abundance is explained in terms of the disruption of male pheromone production. Treated targets were approximately half as effective as residual spraying in reducing the abundance of Lu.longipalpis in sheds. Following blanket intervention, the abundance of Lu.longipalpis in traps fell by only 45% (not significant): catches at untreated dining-huts actually increased, possibly because the blanket coverage diverted Lu.longipalpis away from major aggregation sites at animal pens. It is recommended that care be taken during vector control programmes to ensure that all potential aggregation sites are treated. The possible consequences of leaving some sites untreated include poor control of peridomestic sandfly abundance and an increase in the biting rate on dogs and humans.

Service life of treated and untreated fence posts on the Pringle Falls Experimental Forest.

Treesearch

Walter G. Dahms

1952-01-01

The service life of lodgepole pine fence posts can be greatly extended by a good preservative treatment, After more than 15 years, however, little or no difference can be found between treated lodgepole pine posts and untreated Western redcedar posts. These conclusions have been reached as a result of observations on 517 lodgepole pins posts for 16 years and 355 cedar...

The Webcam system: a simple, automated, computer-based video system for quantitative measurement of movement in nonhuman primates.

PubMed

Togasaki, Daniel M; Hsu, Albert; Samant, Meghana; Farzan, Bijan; DeLanney, Louis E; Langston, J William; Di Monte, Donato A; Quik, Maryka

2005-06-30

Investigations using models of neurologic disease frequently involve quantifying animal motor activity. We developed a simple method for measuring motor activity using a computer-based video system (the Webcam system) consisting of an inexpensive video camera connected to a personal computer running customized software. Images of the animals are captured at half-second intervals and movement is quantified as the number of pixel changes between consecutive images. The Webcam system allows measurement of motor activity of the animals in their home cages, without devices affixed to their bodies. Webcam quantification of movement was validated by correlation with measures simultaneously obtained by two other methods: measurement of locomotion by interruption of infrared beams; and measurement of general motor activity using portable accelerometers. In untreated squirrel monkeys, correlations of Webcam and locomotor activity exceeded 0.79, and correlations with general activity counts exceeded 0.65. Webcam activity decreased after the monkeys were rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but the correlations with the other measures of motor activity were maintained. Webcam activity also correlated with clinical ratings of parkinsonism. These results indicate that the Webcam system is reliable under both untreated and experimental conditions and is an excellent method for quantifying motor activity in animals.

Long-term AICAR administration and exercise prevents diabetes in ZDF rats.

PubMed

Pold, Rasmus; Jensen, Lasse S; Jessen, Niels; Buhl, Esben S; Schmitz, Ole; Flyvbjerg, Allan; Fujii, Nobuharu; Goodyear, Laurie J; Gotfredsen, Carsten F; Brand, Christian L; Lund, Sten

2005-04-01

Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

Effect of subretinal injection on retinal structure and function in a rat oxygen-induced retinopathy model.

PubMed

Becker, Silke; Wang, Haibo; Stoddard, Gregory J; Hartnett, M Elizabeth

2017-01-01

Subretinal injections are used to deliver agents in experimental studies of retinal diseases, often through viral vectors. However, few studies have investigated the effects of subretinal injections alone on the structure and function of the healthy or diseased retina, particularly in models of oxygen-induced retinopathy (OIR). We report on the effects of subretinal injections in a rat OIR model, which is used to study mechanisms of retinopathy of prematurity. Within 6 h of birth, neonatal rat pups were exposed to repeated cycles of oxygen between 50% and 10% O 2 every 24 h for 14 days and subsequently moved to room air. On postnatal day 8 (P8), animals were treated in both eyes with advancement of the injection needle into the vitreous (pilot-treated) or with a subretinal PBS injection (sPBS-treated) or were left untreated (untreated). Additional control animals were exposed to microscope light after eyelid opening only (light-treated). Retinal fundus images were recorded on P26. Areas of the avascular retina and intravitreal neovascularization were determined in flat mounted retinas stained with isolectin B4 on P32. Retinal function of the respective eyes was assessed with the Ganzfeld electroretinogram (ERG) on P31 or P32 and with focal ERG in the central retina on P28 or P29. The thickness of the retinal layers was measured with spectral domain optical coherence tomography (OCT) on P30 and in opsin- and TO-PRO 3-stained retinal cryosections from pups euthanized on P32. Two sections were analyzed in each pup. For each section, three images of three different locations were analyzed accounting for 18 thickness measurements per pup. Compared to untreated animals, the avascular area of the retina was greater in the pilot-treated (p<0.05) and sPBS-treated eyes (p<0.01), and the sPBS-treated eyes had a greater avascular retinal area compared to the pilot-treated eyes (p<0.01). The intravitreal neovascular area was larger in the sPBS-treated eyes compared to the untreated eyes (p<0.01). The outer nuclear and outer segment layers were thinner in the pilot- (p<0.01) and sPBS-treated eyes (p<0.05) compared to the untreated eyes as measured with OCT and immunohistochemical staining of the retinal cryosections. Compared to the untreated eyes, the amplitudes of the scotopic a- and b-waves in the Ganzfeld ERG were reduced in the pilot-treated eyes (p<0.001 and p<0.01, respectively), but only the a-wave was reduced in the sPBS-treated eyes (p<0.001). The a-wave amplitude in the focal ERG was reduced in the pilot- and sPBS-treated eyes, and no difference was seen in the b-wave amplitude between any of the groups. There was no difference between the light-treated and untreated eyes in the areas of the avascular retina or intravitreal neovascularization or Ganzfeld or focal ERG. Pilot injections alone without injection into the subretinal space resulted in an increased avascular retinal area, reduced thickness of the photoreceptors, and reduced ERG function compared to the untreated animals. Although subretinal PBS injections further increased the areas of avascular retina and intravitreal neovascularization and resulted in similar retinal thinning compared to the pilot treatment, inner retinal function was improved, as evidenced by higher Ganzfeld b-wave amplitudes. Differences in the Ganzfeld and focal ERGs may indicate that the peripheral retina is more susceptible to remote beneficial effects from potential protective mechanisms induced by subretinal injection. This study stresses the importance of appropriate controls in experiments with subretinal delivery of agents.

Do adult men with untreated hypospadias have adverse outcomes? A pilot study using a social media advertised survey

PubMed Central

Schlomer, Bruce; Breyer, Benjamin; Copp, Hillary; Baskin, Laurence; DiSandro, Michael

2014-01-01

Objective Hypospadias is usually treated in childhood. Therefore, the natural history of untreated mild hypospadias is unknown. We hypothesized that men with untreated hypospadias, especially mild, do not have adverse outcomes. Materials Facebook was used to advertise an electronic survey to men older than 18 years. Men with untreated hypospadias identified themselves and indicated the severity of hypospadias with a series of questions. Outcomes included: Sexual Health Inventory for Men (SHIM), penile curvature and difficulty with intercourse, International Prostate Symptom Score (IPSS), Penile Perception Score (PPS), psychosexual milestones, paternity, infertility, sitting to urinate, and the CDC HRQOL-4 module. Results 736 men completed self-anatomy questions and 52 (7.1%) self-identified with untreated hypospadias. Untreated hypospadias participants reported worse SHIM (p < 0.001) and IPSS scores (p = 0.05), more ventral penile curvature (p = 0.003) and resulting difficulty with intercourse (p < 0.001), worse satisfaction with meatus (p = 0.011) and penile curvature (p = 0.048), and more sitting to urinate (p = 0.07). When stratified by mild and severe hypospadias, severe hypospadias was associated with more adverse outcomes than mild hypospadias. Conclusion Men with untreated hypospadias reported worse outcomes compared with non-hypospadiac men. Mild untreated hypospadias had fewer adverse outcomes than severe hypospadias. Research is needed to determine if treatment of childhood hypospadias improves outcomes in adults, especially for mild hypospadias. PMID:24613143

Anti-arthritic activity of a lipophilic woad (Isatis tinctoria) extract.

PubMed

Recio, María-Carmen; Cerdá-Nicolás, Miguel; Hamburger, Matthias; Ríos, José-Luis

2006-06-01

A dichloromethane extract of Isatis tinctoria was tested in the adjuvant-induced arthritis model in rats. The extract (150 mg/kg p. o.) leads to a significant reduction of paw oedema. Radiographic, histological and clinical assessment confirmed reduced damage of cartilage and signs of inflammatory response in comparison to untreated control. No significant differences were observed in the tissular levels of cyclooxygenases 1 and -2, and of inducible nitric oxide synthase in Isatis treated and untreated animals. High dose treatment with Isatis extract for two weeks did not result in macroscopic lesions of the gastric mucosa.

Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats.

PubMed

Saddiq, Amna Ali; Mohamed, Azza Mostafa

2016-07-01

The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo-pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents.

In Vitro and In Vivo Anti-Helicobacter Activities of Eryngium foetidum (Apiaceae), Bidens pilosa (Asteraceae), and Galinsoga ciliata (Asteraceae) against Helicobacter pylori.

PubMed

Kouitcheu Mabeku, Laure Brigitte; Eyoum Bille, Bertrand; Nguepi, Eveline

2016-01-01

This study was performed to evaluate the antimicrobial activities of extracts of Bidens pilosa, Galinsoga ciliata, and Eryngium foetidum against 6 clinical strains of Helicobacter pylori in vitro and in vivo. Broth microdilution method was used in vitro. In vivo, Swiss mice were inoculated with H. pylori and divided into 5 groups; the control group received the vehicle and the four others received 125, 250, and 500 mg/kg of methanol extract of Eryngium foetidum and ciprofloxacin (500 mg/kg) for 7 days, respectively. Helicobacter pylori colonization and number of colonies in gastric biopsies culture were assessed on days 1 and 7 after treatment. The lowest MIC value (64 μg/mL) and the best spectrum of bactericidal effect (MBC/MIC = 1) were obtained with the methanol extract of Eryngium foetidum. The number of H. pylori infected animals was 17% (plant-extract) and 0% (ciprofloxacin) compared to 100% for the infected untreated group. Plant-extract (381.9 ± 239.5 CFU) and ciprofloxacin (248 ± 153.2 CFU) significantly reduced bacterial load in gastric mucosa compared to untreated, inoculated mice (14350 ± 690 CFU). Conclusion. The present data provided evidence that methanol extract of Eryngium foetidum could be a rich source of metabolites with antimicrobial activity to fight Helicobacter pylori infections.

Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs

PubMed Central

Chiaro, Joseph A; O’Donnell, Patricia; Shore, Eileen M; Malhotra, Neil R; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

2014-01-01

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kypho-scoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT+SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT treated; and MPS I ERT+SIM treated. Animals were euthanized at one year-of-age. Intervertebral disc condition and spinal cord compression were evaluated from MRIs and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using microcomputed tomography, and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT+SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, while ERT treatment resulted in partial preservation of these properties. ERT+SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not provide a significant additional benefit over ERT alone. PMID:24898323

Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

PubMed Central

Lin, Philana Ling; Coleman, Teresa; Carney, Jonathan P. J.; Lopresti, Brian J.; Tomko, Jaime; Fillmore, Dan; Dartois, Veronique; Scanga, Charles; Frye, L. James; Janssen, Christopher; Klein, Edwin; Barry, Clifton E.

2013-01-01

Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with Mycobacterium tuberculosis develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials. PMID:23796926

Relationship between parents' occupational characteristics and untreated dental caries in offspring: A population-based study of data from the Korean National Health and Nutrition Examination Survey, 2008-2015.

PubMed

Lim, Sung-Shil; Kim, Byurira; Yoon, Jin-Ha; Song, Je Seon; Park, Eun-Cheol; Jang, Sung-In

2018-05-01

Objectives We investigated the association between parents' occupational characteristics and untreated dental caries in their children. Methods We analyzed the data of 4764 and 5862 children merged with data of their mothers and fathers, respectively, derived from the Korean National Health and Nutrition Examination Survey, 2008-2015. Dentists assessed untreated dental caries, and occupational characteristics were self-reported. The associations between untreated dental caries in children and their parents' occupational characteristics were assessed with logistic regression analysis. Results The prevalence of untreated dental caries was 18.58% and 16.39% in the mother- and father-matched data, respectively. Compared to children whose mothers worked regular hours, those whose mothers worked overtime had increased odds of untreated dental caries [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.02-1.39]. Children of female self-employed workers/employers/unpaid family workers had higher odds of untreated dental caries than those of wage earners (OR 1.18, 95% CI 1.00-1.39). The OR of untreated dental caries was higher among children with shift-working parents than those whose parents worked daytime hours (mother: OR 1.29, 95% CI 1.11-1.51; father: OR 1.36, 95% CI 1.18-1.58). Conclusions The children of non-white-collar workers, non-wage earners, and workers working overtime or doing shift work had higher odds of untreated dental caries. The effects of parental occupational characteristics on untreated dental caries differed by sex (mother versus father). Public health programs targeting the prevention of dental caries among children should consider parental occupational characteristics.

Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.

PubMed

Gardiner, T A; Anderson, H R; Degenhardt, T; Thorpe, S R; Baynes, J W; Archer, D B; Stitt, A W

2003-09-01

To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p< or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p< or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p< or =0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.

Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

PubMed Central

Comer, Jason E.; Stark, Gregory V.; Ray, Bryan D.; Tordoff, Kevin P.; Knostman, Katherine A. B.; Meister, Gabriel T.

2012-01-01

Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of Bacillus anthracis Ames spores. Specific diagnostic parameters were detected relatively early in disease progression, i.e., by blood culture (∼37 h postchallenge) and the presence of circulating protective antigen (PA) detected by electrochemiluminescence (ECL) ∼38 h postchallenge, whereas nonspecific clinical signs of disease, i.e., changes in body temperature, hematologic parameters (ca. 52 to 66 h), and clinical observations, were delayed. To determine whether the presentation of antigenemia (PA in the blood) was an appropriate trigger for therapeutic intervention, a monoclonal antibody specific for PA was administered to 12 additional animals after the circulating levels of PA were detected by ECL. Seventy-five percent of the monoclonal antibody-treated animals survived compared to 17% of the untreated controls, suggesting that intervention at the onset of antigenemia is an appropriate treatment trigger for this model. Moreover, the onset of antigenemia correlated with bacteremia, and NHPs were treated in a therapeutic manner. Interestingly, brain lesions were observed by histopathology in the treated nonsurviving animals, whereas this observation was absent from 90% of the nonsurviving untreated animals. Our results support the use of the cynomolgus macaque as an appropriate therapeutic animal model for assessing the efficacy of medical countermeasures developed against anthrax when administered after a confirmation of infection. PMID:22956657

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

PubMed

Garcia, Camila Araújo Bernardino; Catalão, Carlos Henrique Rocha; Machado, Hélio Rubens; Júnior, Ivair Matias; Romeiro, Thais Helena; Peixoto-Santos, José Eduardo; Santos, Marcelo Volpon; da Silva Lopes, Luiza

2017-03-01

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Protective role of parnaparin in reducing systemic inflammation and atherosclerotic plaque formation in ApoE-/- mice.

PubMed

Artico, Marco; Riganò, Rachele; Buttari, Brigitta; Profumo, Elisabetta; Ionta, Brunella; Bosco, Sandro; Rasile, Manuela; Bianchi, Enrica; Bruno, Moira; Fumagalli, Lorenzo

2011-04-01

Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.

Histopathological and biochemical assessment of d-limonene-induced liver injury in rats.

PubMed

Ramos, Carlos Alberto F; Sá, Rita de Cássia da S; Alves, Mateus F; Benedito, Rubens B; de Sousa, Damião P; Diniz, Margareth de Fátima F M; Araújo, Maria Salete T; de Almeida, Reinaldo N

2015-01-01

The aim of the present work was to develop a biochemical, histologic and immunohistochemical study about the potential hepatotoxic effect of d-limonene - a component of volatile oils extracted from citrus plants. Blood alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) from d-limonene-treated animals were determined and compared to morphologic hepatic lesions in order to investigate the possible physiopathologic mechanisms involved in the liver toxicity, in experimental animals treated with d-limonene. Wistar rats were randomly divided into seven groups: two control groups (untreated or receiving only vehicle, tween-80); one positive control (vehicle); two experimental groups treated with d-limonene at doses of 25 mg/kg/day and 75 mg/kg/day for 45 days, and two other groups treated with the same doses for 30 days and kept under observation during 30 more days. Biochemical data showed significant reduction in ALT levels in the animals treated with 75 mg/kg of d-limonene. Histological analysis revealed some hepatocyte morphological lesions, including hydropic degeneration, microvesicular steatosis and necrosis, Kupffer cell hyperplasia and incipient fibrosis. By immunohistochemistry, influx of T (CD3+) and cytotoxic (CD8+) lymphocytes was observed in the rats treated with d-limonene at both dose levels. In conclusion, it is possible that d-limonene has been directly responsible for hepatic parenchymal and matrix damage following subchronic treatment with d-limonene.

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

PubMed Central

Debbas, Victor; Salemi, Vera M.; Tavares, Elaine R.; Meirelles, Thayna; Ferreira-Filho, Julio C. A.; Takimura, Celso K.; Pereira, Lygia V.; Laurindo, Francisco R.

2018-01-01

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture. PMID:29765495

Sources of Variance in Baseline Gene Expression in the Rodent Liver

EPA Science Inventory

The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variation due to individual, environmental, and technical factors. Analysis of microarray data from untreated or vehicle-treated animals within the contro...

Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

PubMed

Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed

2012-10-01

Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Evaluation of mosquito responses to pyrethroid insecticides topically applied to sheep.

PubMed

Johnson, G D; Goosey, H B; Rolston, M G; Miller, W L; Hokit, D G; Redden, R R; Kott, R W

2013-06-01

A rise in the incidence of mosquito-transmitted Cache Valley virus (CVV) in lambs in 2011 prompted a study to evaluate on-animal pyrethroid insecticides to reduce mosquito attacks on sheep. Using enclosure traps for 1 night per wk for 6 wk, we compared engorgement rates of mosquitoes given the opportunity to feed on untreated sheep and sheep treated with 1 Python insecticide ear tag (containing 10% zeta-cypermethrin and 20% piperonyl butoxide) per animal or 2 synergized permethrin body spray treatments (containing 2.5% permethrin and 2.5% piperonyl butoxide). During the 6-wk study, 18,920 mosquitoes were collected in the animal-baited enclosure traps. Thirteen species were identified from these collections with the floodwater species Aedes increpitus and Ae. idahoensis making up 68% of the total. Potential CVV vector species, making up 25% of the samples, included Ae. vexans, Ae. dorsalis, Culex tarsalis, and Culiseta inornata. Traps baited with untreated sheep collected 9,701 mosquitoes with 65% of these engorged. Traps baited with sheep treated with Python ear tags or permethrin spray collected 4,034 and 4,555, respectively, with engorgement rates of 23% and 35%. Blood feeding on ear-tagged sheep was significantly reduced by as much as 90% compared to the untreated sheep, and protection lasted 4 wk or longer. Permethrin spray treatments were most effective within 24 h after application and provided better protection against Ae. dorsalis than the Python tag. Effectiveness of the permethrin spray diminished 1 wk after the 2nd application was made. The effect of these treatments appeared to be repellency because negligible mosquito mortality was observed at the time of collection. Further evaluation of these insecticides under conditions of natural exposure to a mosquito-borne pathogen is warranted.

Elevated levels of liver methylglyoxal and d-lactate in early-stage hepatitis in rats.

PubMed

Wang, Wen-Chuang; Chou, Chu-Kuang; Chuang, Ming-Cheng; Li, Yi-Chieh; Lee, Jen-Ai

2018-02-01

Methylglyoxal (MGO) is highly cytotoxic and its levels are elevated in diabetes, nephropathy and atherosclerosis. However, it has never been studied in liver disease. For this reason, we aimed to assess the levels of MGO and its metabolite d-lactate in an early hepatitis model. Wistar rats were administered CCl 4 (0.75 mL/kg, i.p.) to induce hepatitis. In either CCl 4 -treated or untreated rats, alanine transaminase and aspartate transaminase levels did not change over the course of the study, indicating that significant liver damage did not occur following CCl 4 treatment. However, the levels of MGO and d-lactate were higher in the livers of CCl 4 -treated animals than in untreated animals (MGO: 128.2 ± 18.8 and 248.1 ± 64.9 μg/g protein, p < 0.01; d-lactate: 0.860 ± 0.040 and 1.293 ± 0.078 μmol/g protein, respectively p < 0.01). Furthermore, in untreated and treated animals, serum d-lactate levels were 57.65 ± 2.59 and 92.16 ± 16.69 μm and urine d-lactate levels were 1.060 ± 0.007 and 1.555 ± 0.366 μmol/mg UCr, respectively (p < 0.01). These data show that in this model of early-stage liver damage, the levels of MGO and its metabolite d-lactate are elevated and that d-lactate could be useful as a reference marker for the early stage of hepatitis. Copyright © 2017 John Wiley & Sons, Ltd.

Rat liver endothelial and Kupffer cell-mediated mutagenicity and polycyclic aromatic hydrocarbons and aflatoxin B sub 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberg, P.; Schlemper, B.; Molitor, E.

The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B{sub 1} (AFB{sub 1}) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB{sub 1} and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB{sub 1} showed a slight increase. BP andmore » DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells form untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB{sub 1}. The reduced mutagenicity of AFB{sub 1} correlates with the decrease in the amount of 2{alpha}-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2{alpha}-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB{sub 1}. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activated several carcinogens to mutagenic metabolites.« less

Understanding Gulf War Illness: An Integrative Modeling Approach

DTIC Science & Technology

2017-10-01

group (Task 2; Subtask1). The latest iteration of this analysis focused on n=11 animals control and n=11 DFP exposed animals without corticosterone... Groups : 1 – Control Group (Male and Female Intact) 2 – GWI Model – Cort+DFP (Male and Female OVX) 3 – Control OVX (Female) 4 – GWI Model + Enbrel...The designed protocol counts with five basic experimental groups : Group 1 (Untreated Control no toxic exposure); Group 2 (Toxic exposed, no

Decision tree analysis to evaluate dry cow strategies under UK conditions.

PubMed

Berry, Elizabeth A; Hogeveen, Henk; Hillerton, J Eric

2004-11-01

Economic decisions on animal health strategies address the cost-benefit aspect along with animal welfare and public health concerns. Decision tree analysis at an individual cow level highlighted that there is little economic difference between the use of either dry cow antibiotic or an internal teat sealant in preventing a new intramammary infection in a cow free of infection in all quarters of the mammary gland at drying off. However, a potential net loss of over ł20 per cow might occur if the uninfected cow was left untreated. The only economically viable option, for a cow with one or more quarters infected at drying off, is antibiotic treatment, although a loss might still be incurred depending on the pathogen concerned and the cure rates achievable. There was a net loss for cows with quarters infected with Corynebacterium spp. at drying off, for both the teat sealant and untreated groups (ł22 and ł48, respectively) with only antibiotic-treated cows showing a gain.

Effectiveness of a short-term treatment with progesterone injections on synchrony of lambing and fertility in tropical hair sheep.

PubMed

Knights, Marlon; Ramgattie, Reeza; Siew, Narendra; Singh-Knights, Doolarie; Bourne, Gregory

2011-06-01

The efficacy of using a low cost system for delivering progesterone as part of an estrous synchronization protocol in sheep was evaluated. In experiment 1, Barbados Black Belly ewes (n=34) and ewe lambs (n=35; 37.5±0.9 kg) were assigned to be untreated, control animals (C), or to receive PGF(2α) on d0 (PG), or receive two injections of progesterone (200mg, i.m. each) on D -5 and on D -2.5, prior to PGF(2α), on D 0 (2PPG). Treatment with 2PPG increased the proportion of animals lambing to the first service (P<0.05), an effect that was greater in ewe lambs than ewes (treatment × parity; P<0.05). The interval from ram introduction to lambing and the mean lambing day was less (P=0.04) in the 2PPG-treated animals compared to control animals. In Experiment 2, lactating ewes from experiment 1 (n=61) 60-85 days postpartum were assigned within parity and number of lambs reared to remain nursing (S; n=29) or weaned (W; n=32) 3 weeks prior to treatment with the 2PPG protocol. There was no effect of treatment on the proportion of animals lambing to the first service or overall, interval from ram introduction to lambing and lambing interval. An 8-month lambing interval was observed in ewes in which estrus was synchronized regardless of physiological state. In conclusion, the two-progesterone injection synchronization protocol may be used as a practical low cost and efficient method of synchronizing estrus to reduce the lambing interval and maximize productivity in tropical breeds of sheep. Copyright © 2011 Elsevier B.V. All rights reserved.

Reference genes for quantitative PCR in the adipose tissue of mice with metabolic disease.

PubMed

Almeida-Oliveira, Fernanda; Leandro, João G B; Ausina, Priscila; Sola-Penna, Mauro; Majerowicz, David

2017-04-01

Obesity and diabetes are metabolic diseases and they are increasing in prevalence. The dynamics of gene expression associated with these diseases is fundamental to identifying genes involved in related biological processes. qPCR is a sensitive technique for mRNA quantification and the most commonly used method in gene-expression studies. However, the reliability of these results is directly influenced by data normalization. As reference genes are the major normalization method used, this work aims to identify reference genes for qPCR in adipose tissues of mice with type-I diabetes or obesity. We selected 12 genes that are commonly used as reference genes. The expression of these genes in the adipose tissues of mice was analyzed in the context of three different experimental protocols: 1) untreated animals; 2) high-fat-diet animals; and 3) streptozotocin-treated animals. Gene-expression stability was analyzed using four different algorithms. Our data indicate that TATA-binding protein is stably expressed across adipose tissues in control animals. This gene was also a useful reference when the brown adipose tissues of control and obese mice were analyzed. The mitochondrial ATP synthase F1 complex gene exhibits stable expression in subcutaneous and perigonadal adipose tissue from control and obese mice. Moreover, this gene is the best reference for qPCR normalization in adipose tissue from streptozotocin-treated animals. These results show that there is no perfect stable gene suited for use under all experimental conditions. In conclusion, the selection of appropriate genes is a prerequisite to ensure qPCR reliability and must be performed separately for different experimental protocols. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sodium Nitroprusside Enhanced Cardiopulmonary Resuscitation Improves Short Term Survival in a Porcine Model of Ischemic Refractory Ventricular Fibrillation

PubMed Central

Yannopoulos, Demetris; Bartos, Jason A.; George, Stephen A.; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P.

2017-01-01

Introduction Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. Hypothesis SNPeCPR will increase short term (4-hour) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Methods Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5 minutes. Basic life support was performed for 10 minutes. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3 minutes. CPR continued for a total of 45 minutes, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60 minutes, if unsuccessful. SNPeCPR animals received 2 mg of SNP at minute 10 followed by 1 mg every 5 minutes until ROSC. Standard ACLS animals received 0.5 mg epinephrine every 5 minutes until ROSC. Primary endpoints were ROSC and 4-hour survival. Results All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-hour survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. Conclusion SNPeCPR significantly improved ROSC and 4-hour survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. PMID:27771299

Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration

PubMed Central

Prokopiou, Ekatherine; Kolovos, Panagiotis; Kalogerou, Maria; Neokleous, Anastasia; Papagregoriou, Gregory; Deltas, Constantinos; Malas, Stavros; Georgiou, Tassos

2017-01-01

Purpose To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2−/− model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1–1.5). Methods Nine-month-old animals were allocated to different groups: (A) C57BL/6 untreated , (B) CCL2−/− untreated, (C) CCL2−/− treated with ω-3+ω-6, and (D) CCL2−/− treated with ω-3. Treatment was daily administered by gavage for 3 months. Fatty acids analysis was performed and retinas were histologically examined. Three-month-old wild type mice were used for comparison purposes. Real-time PCR and Western blot were performed for retinal inflammatory mediators. Results Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment groups. The outer nuclear layer thickness was increased in groups C (45.0±3.9 µm) and D (62.8±4.9 µm), compared with groups B (65.6±3.0 µm) and A (71.1±4.2 µm), and in younger mice, it was 98.0±3.9 µm. A decrease in NF-κB expression was noted in the treatment groups. Interleukin (IL) 18 protein levels demonstrated a significant reduction in the ω-3-treated group only. Conclusion Supplementation with ω-3+ω-6 or ω-3 alone (AA/EPA=1–1.5) suggests a protective mechanism in the CCL2−/− animal model of dry AMD, with a more beneficial effect when ω-3 are used alone. Our findings indicated that inflammation is not the only determining factor; perhaps a regenerative process might be involved following administration of ω-3 fatty acids. PMID:29354704

Radial pressure waves mediate apoptosis and functional angiogenesis during wound repair in ApoE deficient mice.

PubMed

Contaldo, Claudio; Högger, Dominik C; Khorrami Borozadi, Meisam; Stotz, Michael; Platz, Uwe; Forster, Natasha; Lindenblatt, Nicole; Giovanoli, Pietro

2012-07-01

This study aims to quantify by intravital microscopy and histological wound scoring the effect of radial pressure wave treatment (RPWT) on murine incisional wound healing. The dorsal skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. RPWT to the wound was carried out using a ballistic pressure wave source (EMS Swiss DolorClast). Animals received a dose of 500 pulses at an energy flux rate of 0.1mJ/mm(2) and a frequency of 3Hz at day 1, 3, 5, 7, 9, and 11 post wounding. RPW treated and untreated ApoE depleted mice (ApoE(-/-)) were compared to normal healing wild type animals (WT). The microcirculation of the wound was analyzed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Tissue samples were examined ex vivo for wound scoring and immunohistochemistry. Upon RPWT total wound score in ApoE(-/-) mice was increased by 13% (not significant) on day 3, by 37% on day 7 (P<0.05), and by 39% on day 13 (P<0.05) when compared to untreated ApoE(-/-) mice. Improved wound healing was associated with an increase of functional angiogenetic density by 23% (not significant) on day 5, by 36% on day 7 (P<0.05), and by 41% on day 9 (P<0.05). Following RPWT, on day three we observed enhanced expression of capase-3 (2-fold), proliferating cell nuclear antibody (PCNA, 1,6-fold), and endothelial nitric oxide synthase (eNOS, 2.6-fold), all P<0.05. In conclusion repetitive RPWT accelerated wound healing in ApoE(-/-) mice by increasing functional neovascular density. In addition our findings strongly suggest that RPW may facilitate the linear progression of wound healing phases by fostering apoptosis. Copyright © 2012 Elsevier Inc. All rights reserved.

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

Treated and Untreated Remission from Problem Drinking in Late Life: Post-Remission Functioning and Health-Related Quality of Life

PubMed Central

Schutte, Kathleen K.; Brennan, Penny L.; Moos, Rudolf H.

2009-01-01

Objective To evaluate the post-remission status of older remitted problem drinkers who achieved stable remission without treatment. Method The post-remission drinking behavior, health-related functioning, life context, coping, and help-seeking of older, untreated (n = 330) and treated (n = 120) former problem drinkers who had been remitted for a minimum of six years were compared twice over the course of six-years to each other and to lifetime nonproblem drinkers (n = 232). Analyses considered the impact of severity of drinking problem history. Results Untreated remitters were more likely than treated remitters to continue to drink, exhibited fewer chronic health problems and less depressive symptomatology, and were less likely to smoke. Untreated remitters’ life contexts were somewhat more benign than those of treated ones, and they were less likely to describe a coping motive for drinking and engage in post-remission help-seeking. Although untreated remitters more closely resembled lifetime nonproblem drinkers than did treated remitters, both untreated and treated remitter groups exhibited worse health-related functioning, more financial and interpersonal stressors, and more post-remission help-seeking than did lifetime nonproblem drinkers. Conclusions Regardless of whether late-life remission was gained without or with treatment, prior drinking problems conveyed a legacy of health-related and life context deficits. PMID:18829184

The Effect of UV-C Pasteurization on Bacteriostatic Properties and Immunological Proteins of Donor Human Milk

PubMed Central

Christen, Lukas; Lai, Ching Tat; Hartmann, Ben; Hartmann, Peter E.; Geddes, Donna T.

2013-01-01

Background Human milk possesses bacteriostatic properties, largely due to the presence of immunological proteins. Heat treatments such as Holder pasteurization reduce the concentration of immunological proteins in human milk and consequently increase the bacterial growth rate. This study investigated the bacterial growth rate and the immunological protein concentration of ultraviolet (UV-C) irradiated, Holder pasteurized and untreated human milk. Methods Samples (n=10) of untreated, Holder pasteurized and UV-C irradiated human milk were inoculated with E. coli and S. aureus and the growth rate over 2 hours incubation time at 37°C was observed. Additionally, the concentration of sIgA, lactoferrin and lysozyme of untreated and treated human milk was analyzed. Results The bacterial growth rate of untreated and UV-C irradiated human milk was not significantly different. The bacterial growth rate of Holder pasteurized human milk was double compared to untreated human milk (p<0.001). The retention of sIgA, lactoferrin and lysozyme after UV-C irradiation was 89%, 87%, and 75% respectively, which were higher than Holder treated with 49%, 9%, and 41% respectively. Conclusion UV-C irradiation of human milk preserves significantly higher levels of immunological proteins than Holder pasteurization, resulting in bacteriostatic properties similar to those of untreated human milk. PMID:24376898

Monitoring of drug resistance amplification and attenuation with the use of tetracycline-resistant bacteria during wastewater treatment

NASA Astrophysics Data System (ADS)

Harnisz, Monika; Korzeniewska, Ewa; Niestępski, Sebastian; Osińska, Adriana; Nalepa, Beata

2017-11-01

The objective of this study was to monitor changes (amplification or attenuation) in antibiotic resistance during wastewater treatment based on the ecology of tetracycline-resistant bacteria. The untreated and treated wastewater were collected in four seasons. Number of tetracycline-(TETR) and oxytetracycline-resistant (OTCR) bacteria, their qualitative composition, minimum inhibitory concentrations (MICs), sensitivity to other antibiotics, and the presence of tet (A, B, C, D, E) resistance genes were determined. TETR and OTCR counts in untreated wastewater were 100 to 1000 higher than in treated effluent. OTCR bacterial counts were higher than TETR populations in both untreated and treated wastewater. TETR isolates were not dominated by a single bacterial genus or species, whereas Aeromonas hydrophila and Aeromonas sobria were the most common in OTCR isolates. The treatment process attenuated the drug resistance of TETR bacteria and amplified the resistance of OTCR bacteria. In both microbial groups, the frequency of tet(A) gene increased in effluent in comparison with untreated wastewater. Our results also indicate that treated wastewater is a reservoir of multiple drug-resistant bacteria as well as resistance determinants which may pose a health hazard for humans and animals when released to the natural environment.

Immune Dysfunctions and Abrogation of the Inflammatory Response by Environmental Chemicals.

DTIC Science & Technology

1981-08-01

vitro effects in cats, mice, and humans. Materials and Methods: Animals: Mice: Young adult Swiss outbred mice and C57BL/6 (for skin graft donors) were...was used to determine significant differences between control (untreated) and MNU-treated cell cultures or animal groups. Results: Skin grafts : The...MNU-treated mice showed a dose-related increase in skin graft retention time, which was significant at 25 and 50 mg/kg MNU (p<.001). This is compared

Effects of epithalon on activities gastrointestinal enzymes in young and old rats.

PubMed

Khavinson, V Kh; Malinin, V V; Timofeeva, N M; Egorova, V V; Nikitina, A A

2002-03-01

Peroral administration of Epithalon (Ala-Glu-Asp-Gly) to male and female Wistar rats aging 3 and 11 months changed activity of enzymes hydrolyzing carbohydrates, proteins, and phosphoric acid esters in various portions of the gastrointestinal tract. The most pronounced activation of enzymes was observed in 11-month-old animals. This effect diminished the differences in enzyme activities between young and old rats (compared to untreated animals). Our results indicate that Epithalon modulates activity of gastrointestinal enzymes during aging.

Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice.

PubMed

Sanchez, Benjamin; Li, Jia; Yim, Sung; Pacheck, Adam; Widrick, Jeffrey J; Rutkove, Seward B

2015-01-01

Non-invasive and effort independent biomarkers are needed to better assess the effects of drug therapy on healthy muscle and that affected by muscular dystrophy (mdx). Here we evaluated the use of multi-frequency electrical impedance for this purpose with comparison to force and histological parameters. Eight wild-type (wt) and 10 mdx mice were treated weekly with RAP-031 activin type IIB receptor at a dose of 10 mg kg-1 twice weekly for 16 weeks; the investigators were blinded to treatment and disease status. At the completion of treatment, impedance measurements, in situ force measurements, and histology analyses were performed. As compared to untreated animals, RAP-031 wt and mdx treated mice had greater body mass (18% and 17%, p < 0.001 respectively) and muscle mass (25% p < 0.05 and 22% p < 0.001, respectively). The Cole impedance parameters in treated wt mice, showed a 24% lower central frequency (p < 0.05) and 19% higher resistance ratio (p < 0.05); no significant differences were observed in the mdx mice. These differences were consistent with those seen in maximum isometric force, which was greater in the wt animals (p < 0.05 at > 70 Hz), but not in the mdx animals. In contrast, maximum force normalized by muscle mass was unchanged in the wt animals and lower in the mdx animals by 21% (p < 0.01). Similarly, myofiber size was only non-significantly higher in treated versus untreated animals (8% p = 0.44 and 12% p = 0.31 for wt and mdx animals, respectively). Our findings demonstrate electrical impedance of muscle reproduce the functional and histological changes associated with myostatin pathway inhibition and do not reflect differences in muscle size or volume. This technique deserves further study in both animal and human therapeutic trials.

Research on preparation of phosphate-modified animal glue binder for foundry use

NASA Astrophysics Data System (ADS)

Wang, Tian-Shu; Liu, Wei-Hua; Li, Ying-Min

2018-03-01

In this paper, three phosphates were used as modifiers to modify animal glue binder. The structural characteristics and thermal properties of animal glue binder treated with phosphates were studied by Fourier transform-infrared spectroscopy, gel permeation chromatography and derivative thermogravimetric analysis. The results showed that the modified animal glue binder had better sand tensile strength and lower viscosity than untreated animal glue binder. The best modification process was as follows: the optimal amount of sodium carbonate was 4 wt% to animal glue; the optimal weight ratio of the modifiers was sodium pyrophosphate : sodium tripolyphosphate : sodium hexametaphosphate : animal glue = 3 : 3 : 4 : 100, and the optimal reaction should be performed at 80°C for a reaction time of 120 min. A final tensile strength of approximately 3.20 MPa was achieved and the viscosity value was approximately 880 mPa s.

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2250 - Dermal toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... animals scheduled to be sacrificed before completion of the study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If the toxic properties of the...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2250 - Dermal toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... animals scheduled to be sacrificed before completion of the study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If the toxic properties of the...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2250 - Dermal toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... animals scheduled to be sacrificed before completion of the study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If the toxic properties of the...

40 CFR 798.2250 - Dermal toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... animals scheduled to be sacrificed before completion of the study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If the toxic properties of the...

40 CFR 798.2250 - Dermal toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... animals scheduled to be sacrificed before completion of the study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If the toxic properties of the...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

Persistence of Escherichia coli in manure-amended soil in Pennsylvania

USDA-ARS?s Scientific Manuscript database

Potential for pathogen transfer from soils amended with untreated animal manure to crops and the frequent occurrence of foodborne illness outbreaks involving Escherichia coli O157:H7 prompted the FDA proposal requiring a 9-month waiting period before harvesting produce from manure-amended fields. A...

Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress

PubMed Central

Adebiyi, Olubunmi A.; Adebiyi, Oluwafeyisetan O.; Owira, Peter M. O.

2016-01-01

Introduction Hyperglycemia promotes myocardial fibrotic lesions through upregulation of PKC and p38 in response to redox changes. The effects of naringin on hyperglycemia-induced myocardial fibrotic changes and its putative effects on PKC-β and p38 protein expression in type 1 rat model of diabetes are hereby investigated. Methods Male Sprague-Dawley rats were divided into six groups I-VI. Groups I and II, were orally treated with distilled water {3.0 ml/kg body weight (BW)} and naringin (50 mg/kg BW), respectively. Groups III, IV, V and VI were rendered diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg, BW) and were similarly treated with subcutaneous insulin (8.0 I.U/kg BW, twice daily), naringin (50 mg/kg BW), distilled water (3.0 ml/Kg BW) and ramipril (3.0 mg/kg/BW), respectively. The animals were sacrificed after 56 days by halothane overdose; blood and heart samples removed for further analysis. Results The untreated diabetic rats exhibited significantly increased oxidative stress, NADPH oxidase activity, increased cardiac fibrosis, PKC-β and p38 mitogen activated protein kinase expression compared to controls. Naringin treatment significantly ameliorated these changes in diabetic rats compared to the untreated diabetic controls. Conclusions Naringin’s amelioration of myocardial fibrosis by modulating p38 and PKC-β protein expression possibly through its known antioxidant actions and may therefore be useful in retarding the progression of fibrosis in a diabetic heart. PMID:26967518

Effects of the Hematoregulatory Peptide SK&F 107647 Alone and in Combination with Amphotericin B against Disseminated Candidiasis in Persistently Neutropenic Rabbits

PubMed Central

Lyman, Caron A.; Gonzalez, Corina; Schneider, Mark; Lee, James; Walsh, Thomas J.

1999-01-01

The effects of the hematoregulatory peptide SK&F 107647 were examined in a persistently and profoundly neutropenic rabbit model of disseminated candidiasis in order to determine its potential to enhance resistance against infection and its role as an adjunct to conventional antifungal chemotherapy. In healthy animals, SK&F 107647 elicited a time-dependent increase in CD11b-positive monocytes and neutrophils. When administered to neutropenic rabbits infected with Candida albicans, no significant differences in the number of CFU per gram in any of the tissues tested compared with the number in untreated control rabbits were detected. However, when SK&F 107647 was administered in combination with low doses of amphotericin B, there was a significant reduction in organism burden in the lungs, liver, spleen, and kidneys compared with the burdens in the organs of untreated control animals and in the lungs and kidneys compared with the burdens in the lungs and kidneys of animals treated with amphotericin B alone. These data suggest a potential role for this peptide as adjunctive therapy in combination with conventional antifungal agents in the treatment of disseminated candidiasis in the setting of profound and persistent neutropenia. PMID:10471559

Set-up of a multivariate approach based on serum biomarkers as an alternative strategy for the screening evaluation of the potential abuse of growth promoters in veal calves.

PubMed

Pirro, Valentina; Girolami, Flavia; Spalenza, Veronica; Gardini, Giulia; Badino, Paola; Nebbia, Carlo

2015-01-01

A chemometric class modelling strategy (unequal dispersed classes - UNEQ) was applied for the first time as a possible screening method to monitor the abuse of growth promoters in veal calves. Five serum biomarkers, known to reflect the exposure to classes of compounds illegally used as growth promoters, were determined from 50 untreated animals in order to design a model of controls, representing veal calves reared under good, safe and highly standardised breeding conditions. The class modelling was applied to 421 commercially bred veal calves to separate them into 'compliant' and 'non-compliant' with respect to the modelled controls. Part of the non-compliant animals underwent further histological and chemical examinations to confirm the presence of either alterations in target tissues or traces of illegal substances commonly administered for growth-promoting purposes. Overall, the congruence between the histological or chemical methods and the UNEQ non-compliant outcomes was approximately 58%, likely underestimated due to the blindness nature of this examination. Further research is needed to confirm the validity of the UNEQ model in terms of sensitivity in recognising untreated animals as compliant to the controls, and specificity in revealing deviations from ideal breeding conditions, for example due to the abuse of growth promoters.

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

PubMed

Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

2013-07-15

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

PubMed Central

Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

2011-01-01

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not Improve Renal Function and Structural Remodeling

PubMed Central

Westerweel, Peter E.; Joles, Jaap A.; den Ouden, Krista; Goldschmeding, Roel; Rookmaaker, Maarten B.; Verhaar, Marianne C.

2012-01-01

Background/Aims ACE inhibitor (ACE-I) treatment effectively inhibits proteinuria and ameliorates the course of various renal diseases. In experimental glomerulonephritis, however, angiotensin II (AngII) infusion has also been shown to be renoprotective. We evaluated the long-term (28 days) course of anti-Thy1 glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment. Methods Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12), dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6) or were left untreated (n = 14). All animals were monitored for blood pressure, proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology was assessed at day 7 and 28. Results Systolic blood pressure was equally reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance. After resolution of the microaneurysms, animals with suppressed AngII production showed a modest increase in glomerulosclerosis and vasculopathic thickening of intrarenal vessels. Conclusions In anti-Thy1 glomerulonephritis, suppression of AngII formation does not protect against the induction of glomerular damage and is associated with mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is effectively prevented by ACE-I treatment. Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent. PMID:22479264

Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

PubMed Central

Al-Obaidi, Mazen M. Jamil; Al-Bayaty, Fouad Hussain; Hussaini, Jamal; Khor, Goot Heah

2014-01-01

Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Methods. Twenty-four Sprague Dawley male rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction. PMID:25485304

Pharmacological Investigation of the Wound Healing Activity of Cestrum nocturnum (L.) Ointment in Wistar Albino Rats

PubMed Central

Nagar, Hemant Kumar; Srivastava, Amit Kumar; Srivastava, Rajnish; Kurmi, Madan Lal; Chandel, Harinarayan Singh; Ranawat, Mahendra Singh

2016-01-01

Objectives. The present study was aimed at investigating the wound healing effect of ethanolic extract of Cestrum nocturnum (L.) leaves (EECN) using excision and incision wound model. Methods. Wistar albino rats were divided into five groups each consisting of six animals; group I (left untreated) considered as control, group II (ointment base treated) considered as negative control, group III treated with 5% (w/w) povidone iodine ointment (Intadine USP), which served as standard, group IV treated with EECN 2% (w/w) ointment, and group V treated with EECN 5% (w/w) ointment were considered as test groups. All the treatments were given once daily. The wound healing effect was assessed by percentage wound contraction, epithelialization period, and histoarchitecture studies in excision wound model while breaking strength and hydroxyproline content in the incision wound model. Result. Different concentration of EECN (2% and 5% w/w) ointment promoted the wound healing activity significantly in both the models studied. The high rate of wound contraction (P < 0.001), decrease in the period for epithelialization (P < 0.01), high skin breaking strength (P < 0.001), and elevated hydroxyproline content were observed in animal treated with EECN ointments when compared to the control and negative control group of animals. Histopathological studies of the EECN ointments treated groups also revealed the effectiveness in improved wound healing. Conclusions. Ethanolic extract of Cestrum nocturnum (EECN) leaves possesses a concentration dependent wound healing effect. PMID:27018126

Use of a Bioactive Scaffold to Stimulate ACL Healing Also Minimizes Post-traumatic Osteoarthritis after Surgery

PubMed Central

Murray, Martha M.; Fleming, Braden C.

2013-01-01

Background While ACL reconstruction is the treatment gold standard for ACL injury, it does not reduce the risk of post-traumatic osteoarthritis. Therefore, new treatments that minimize this postoperative complication are of interest. Bio-enhanced ACL repair, in which a bioactive scaffold is used to stimulate healing of an ACL transection, has shown considerable promise in short term studies. The long-term results of this technique and the effects of the bio-enhancement on the articular cartilage have not been previously evaluated in a large animal model. Hypothesis 1) The structural (tensile) properties of the porcine ACL at 6 and 12 months after injury are similar when treated with bio-enhanced ACL repair, bio-enhanced ACL reconstruction, or conventional ACL reconstruction, and all treatments yield results superior to untreated ACL transection. 2) After one year, macroscopic cartilage damage following bio-enhanced ACL repair is similar to bio-enhanced ACL reconstruction and less than conventional ACL reconstruction and untreated ACL transection. Study Design Controlled laboratory study (porcine model) Methods Sixty-two Yucatan mini-pigs underwent ACL transection and randomization to four experimental groups: 1) no treatment, 2) conventional ACL reconstruction, 3) “bio-enhanced” ACL reconstruction using a bioactive scaffold, and 4) “bio-enhanced” ACL repair using a bioactive scaffold. The biomechanical properties of the ligament or graft and macroscopic assessments of the cartilage surfaces were performed after 6 and 12 months of healing. Results The structural properties (i.e., linear stiffness, yield and maximum loads) of the ligament following bio-enhanced ACL repair were not significantly different from bio-enhanced ACL reconstruction or conventional ACL reconstruction, but were significantly greater than untreated ACL transection after 12 months of healing. Macroscopic cartilage damage after bio-enhanced ACL repair was significantly less than untreated ACL transection and bio-enhanced ACL reconstruction, and there was a strong trend (p=.068) that it was less than conventional ACL reconstruction in the porcine model at 12 months. Conclusions Bio-enhanced ACL repair produces a ligament that is biomechanically similar to an ACL graft and provides chondroprotection to the joint following ACL surgery. Clinical Relevance Bio-enhanced ACL repair may provide a new less invasive treatment option that reduces cartilage damage following joint injury. PMID:23857883

Suitability of hair type for dermatophytes perforation and differential diagnosis of T. mentagrophytes from T. verrucosum.

PubMed

Al-Janabi, Ali Abdul Hussein S; Ai-Tememi, Nabaa N; Ai-Shammari, Rabab A; Ai-Assadi, Abdul Hadi A

2016-04-01

Most of the dermatophyte species have the ability to perforate hair structure and consume its contents of keratin through secretion of keratinase enzyme. Two clinical isolated species of dermatophytes were diagnosed as Trichophyton mentagrophytes var. granulosum and Trichophyton verrucosum. To determine the perforation ability, the isolated fungi were incubated with the hair of four different animals (rabbit, rat, cow and cat) and human hairs with three different colours (black, albino and bleached yellow) for different periods. Variable perforating ability of T. mentagrophytes was shown in rat hair and all types of human hair after 15 days, while other mammalian hairs exhibited resistance to this fungal activity. On the other hand, T. verrucosum was revealed a slow perforating ability, which needed a long time (60 days) for most of tested hairs. Perforation of human black hair could be considered a diagnostic test for differentiation between T. mentagrophytes and T. verrucosum. In conclusion, the treated or untreated human hair was considered more suitable to use as a source of keratin for the growth of dermatophytes than animal hairs. The human black hair was a best type of hair to use in the perforating test for differentiation between T. mentagrophytes and T. verrucosum. © 2016 Blackwell Verlag GmbH.

A multi-species model to assess the effect of refugia on worm control and anthelmintic resistance in sheep grazing systems.

PubMed

Dobson, R J; Barnes, E H; Tyrrell, K L; Hosking, B C; Larsen, J W A; Besier, R B; Love, S; Rolfe, P F; Bailey, J N

2011-06-01

Develop a computer simulation model that uses daily meteorological data and farm management practices to predict populations of Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia (Ostertagia) circumcincta and the evolution of anthelmintic resistance within a sheep flock. Use the model to explore if increased refugia, provided by leaving some adult sheep untreated, would delay development of anthelmintic resistance without compromising nematode control. Compare model predictions with field observations from a breeding flock in Armidale, NSW. Simulate the impact of leaving 1-10% of adult sheep untreated in diverse sheep-grazing systems. Predicted populations of Tr. colubriformis and T. circumcincta were less than those observed in the field, attributed to nutritional stress experienced by the sheep during drought and not accounted for by the model. Observed variation in faecal egg counts explained by the model (R(2) ) for these species was 40-50%. The H. contortus populations and R(2) were both low. Leaving some sheep untreated worked best in situations where animals were already grazing or were moved onto pastures with low populations of infective larvae. In those cases, anthelmintic resistance was delayed and nematode control was maintained when 1-4% of adult stock remained untreated. In general, the model predicted that leaving more than 4% of adults untreated did not sufficiently delay the development of anthelmintic resistance to justify the increased production risk from such a strategy. The choice of a drug rotation strategy had an equal or larger effect on nematode control, and selection for resistance, than leaving 1-10% of adults untreated. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

PubMed Central

Carvalho, Ana Teresa; Souza, Heitor; Carneiro, Antonio Jose; Castelo-Branco, Morgana; Madi, Kalil; Schanaider, Alberto; Silva, Flavia; Pereira Jứnior, Fernando Antonio; Pereira, Márcia G; Tortori, Cláudio; Dines, Ilana; Carvalho, Jane; Rocha, Eduardo; Elia, Celeste

2007-01-01

AIM: To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α (TNF-α), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohn’s disease (CD). METHODS: Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS: Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells. CONCLUSION: Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD. PMID:17465495

40 CFR 799.9130 - TSCA acute inhalation toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of the substance in the atmosphere, a vehicle control group should be used when historical data are... system to assign animals to test groups and control groups randomly is required. (2) Control groups. A concurrent untreated control group is not necessary. Where a vehicle other than water is used to generate an...

40 CFR 799.9130 - TSCA acute inhalation toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of the substance in the atmosphere, a vehicle control group should be used when historical data are... system to assign animals to test groups and control groups randomly is required. (2) Control groups. A concurrent untreated control group is not necessary. Where a vehicle other than water is used to generate an...

40 CFR 799.9130 - TSCA acute inhalation toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of the substance in the atmosphere, a vehicle control group should be used when historical data are... system to assign animals to test groups and control groups randomly is required. (2) Control groups. A concurrent untreated control group is not necessary. Where a vehicle other than water is used to generate an...

Whole Genome Sequencing and Plasmid Genomics of Antimicrobial Resistance – Salmonella’s mobile genetic elements and the antimicrobial resistance genes they carry

USDA-ARS?s Scientific Manuscript database

With the emergence of antibiotic resistance (AR), multidrug resistance (MDR), and carbapenem resistant Enterobacteriaceae (CRE), the specter of widespread untreatable bacterial infections threatens human and animal health. The ability of these emerging resistances to transfer between bacteria on mob...

40 CFR 799.9380 - TSCA reproduction and fertility effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... nonpregnant. (iv) Number of animals. Each control group shall contain a sufficient number of mating pairs to... should be randomly assigned to the control and treatment groups, in a manner which results in comparable... group. (A) A concurrent control group shall be used. This group shall be an untreated or sham treated...

40 CFR 799.9380 - TSCA reproduction and fertility effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... nonpregnant. (iv) Number of animals. Each control group shall contain a sufficient number of mating pairs to... should be randomly assigned to the control and treatment groups, in a manner which results in comparable... group. (A) A concurrent control group shall be used. This group shall be an untreated or sham treated...

40 CFR 799.9380 - TSCA reproduction and fertility effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... nonpregnant. (iv) Number of animals. Each control group shall contain a sufficient number of mating pairs to... should be randomly assigned to the control and treatment groups, in a manner which results in comparable... group. (A) A concurrent control group shall be used. This group shall be an untreated or sham treated...

40 CFR 799.9380 - TSCA reproduction and fertility effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... nonpregnant. (iv) Number of animals. Each control group shall contain a sufficient number of mating pairs to... should be randomly assigned to the control and treatment groups, in a manner which results in comparable... group. (A) A concurrent control group shall be used. This group shall be an untreated or sham treated...

Evaluation of the efficacy of a posaconazole and anidulafungin combination in a murine model of pulmonary aspergillosis due to infection with Aspergillus fumigatus.

PubMed

Bedin Denardi, Laura; Pantella Kunz de Jesus, Francielli; Keller, Jéssica Tairine; Weiblen, Carla; de Azevedo, Maria Isabel; Oliveira, Vanessa; Morais Santurio, Janio; Hartz Alves, Sydney

2018-01-01

Posaconazole (PSC) in combination with anidulafungin (AFG) was evaluated in a murine model of pulmonary aspergillosis. Immunosuppressed animals were infected via the nasal cavity with 2 different A. fumigatus strains. The animals received PSC (oral, 20mg/kg per day) and/or AFG (i.p., 10mg/kg per day) for 7days. On Day 8, the mice were euthanized and fungal burdens were determined from the lungs. Survival curves were constructed for mortality analysis. Compared to untreated groups, groups singly treated with PSC or AFG showed a reduced fungal burden in the lungs (P=0.0001-0.006) and prevention of mortality (66.66-83.33% of survival). Combination treatment with PSC and AFG significantly reduced the fungal burden (or sterilized the lungs) compared to the findings in the untreated and monotherapy groups and improved the survival rate to 100%. The PSC and AFG combination therapy was highly effective and should be evaluated in larger-scale experiments. Copyright © 2017 Elsevier Inc. All rights reserved.

Large animal evaluation of riboflavin and ultraviolet light-treated whole blood transfusion in a diffuse, nonsurgical bleeding porcine model.

PubMed

Okoye, Obi T; Reddy, Heather; Wong, Monica D; Doane, Suzann; Resnick, Shelby; Karamanos, Efstathios; Skiada, Dimitra; Goodrich, Raymond; Inaba, Kenji

2015-03-01

The Mirasol system has been demonstrated to effectively inactivate white blood cells (WBCs) and reduce pathogens in whole blood in vitro. The purpose of this study was to compare the safety and efficacy of Mirasol-treated fresh whole blood (FWB) to untreated FWB in an in vivo model of surgical bleeding. A total of 18 anesthetized pigs (40 kg) underwent a 35% total blood volume bleed, cooling to 33°C, and a standardized liver injury. Animals were then randomly assigned to resuscitation with either Mirasol-treated or untreated FWB, and intraoperative blood loss was measured. After abdominal closure, the animals were observed for 14 days, after which the animals were euthanized and tissues were obtained for histopathologic examination. Mortality, tissue near-infrared spectroscopy, red blood cell (RBC) variables, platelets (PLTs), WBCs, and coagulation indices were analyzed. Total intraoperative blood loss was similar in test and control arms (8.3 ± 3.2 mL/kg vs. 7.7 ± 3.9 mL/kg, p = 0.720). All animals survived to Day 14. Trended values over time did not show significant differences-tissue oxygenation (p = 0.605), hemoglobin (p = 0.461), PLTs (p = 0.807), WBCs (p = 0.435), prothrombin time (p = 0.655), activated partial thromboplastin time (p = 0.416), thromboelastography (TEG)-reaction time (p = 0.265), or TEG-clot formation time (p = 0.081). Histopathology did not show significant differences between arms. Mirasol-treated FWB did not impact survival, blood loss, tissue oxygen delivery, RBC indices, or coagulation variables in a standardized liver injury model. These data suggest that Mirasol-treated FWB is both safe and efficacious in vivo. © 2015 AABB.

Effects of hyperthermia and calcium channel blocker co-therapy on mice injected with Meth A solid of Meth A ascites tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prince, R.N.

1986-01-01

A study was made to determine the effectiveness of treating tumor-injected mice with verapamil, a calcium antagonist, and hyperthermia. The co-treatment reduced the incidence of tumors in animals injected with Meth A solid cells. It was shown that the decrease in tumors corresponded to increases in natural killer (NK) cell activity measured in a /sup 51/Cr release assay, in the amount of anti-Meth A antibody measured in an immunofluorescence assay, and a decrease in the amount of intra-tumor cyclic AMP measured by radioimmunoassay in co-treated compared to untreated sarcoma-injected animals. A role of the immune system for mediating the preventionmore » of sarcoma growth was indicated by Winn assays. Splenocytes sensitized in vivo against Meth A solid cells for 14 days exhibited an enhanced cytotoxic activity against syngeneic target cells compared to untreated tumor-sensitized splenocytes following heat-drug co-treatment. It was established that the stimulation of cytotoxic T cells against a histocompatibility antigen (H-2/sup d/) present on Meth A sarcoma cells resulted in tumor cell lysis. Animals bearing established Meth A solid sarcomas did not manifest tumor regressions following the administration of co-treatment alone or the adoptive transfer of co-treated tumor-sensitized splenocytes. The growth of Meth A ascites and Meth A ascites-derived solid sarcomas, unlike Meth A solid cell tumors, were not prevented in Winn assays. Additionally, the lifespan of animals injected with Meth A ascites cells was reduced by 50% compared to animals injected with Meth A solid sarcoma cells.« less

[Efficacy evaluation of epsiprantel (Cestex) against Echinococcus mutilocularis in dogs and cats].

PubMed

Eckert, J; Thompson, R C; Bucklar, H; Bilger, B; Deplazes, P

2001-01-01

Helminth-free dogs and cats were experimentally infected with protoscoleces of Echinococcus multilocularis and used in controlled trials for efficacy evaluation of the cestodicide epsiprantel. In two separate trials each 4 dogs were treated at day 20 post infection (p.i.) with average oral dosages of 5.1 (4.9-5.3) and 5.4 (5.2-5.8) mg/kg body weight (b.w.) epsiprantel, respectively, and necropsied at day 24 p.i. Among each 4 dogs of the two untreated control groups all animals were infected and had high intestinal worm burdens with averages of 33.575 and 100.725 E. multilocularis specimens per animal (individual worm burdens in group Ib 59,500-149,800, group IIb 20,500-43,200); in the two groups of treated dogs the average worm burdens were reduced by 99.6 and 99.9%. Among 8 treated dogs 4 were helminth-free, the other 4 had residual worm burdens (10-70 in 3 dogs, 1480 in 1 dog). In each 5 cats single oral treatments with average doses of 2.7 (2.7-2.8) and 5.5 (5.5-5.5) mg/kg b.w. epsiprantel were 100% effective against E. multilocularis 20 days p.i. and eliminated the worm burdens from all 10 animals. In the untreated group of 5 cats the average worm burden was 2864 per animal (individual worm burdens 20-6830). Side effects of the drug treatment were not observed. The results of the study show that in single therapeutic dosages recommended by the producer (dogs 5.5 mg, cats 2.75 mg/kg b.w.) epsiprantel eliminates E. multilocularis to over 99% or completely, but residual worm burdens may persist in some animals.

Immunization with Eimeria ninakohlyakimovae-live attenuated oocysts protect goat kids from clinical coccidiosis.

PubMed

Ruiz, Antonio; Muñoz, María Carmen; Molina, José Manuel; Hermosilla, Carlos; Andrada, Marisa; Lara, Pedro; Bordón, Elisa; Pérez, Davinia; López, Adassa María; Matos, Lorena; Guedes, Aránzazu Carmen; Falcón, Soraya; Falcón, Yaiza; Martín, Sergio; Taubert, Anja

2014-01-17

Caprine coccidiosis, affecting mainly young goat kids around the weaning period, is worldwide the most important disease in the goat industry. Control of caprine coccidiosis is increasingly hampered by resistances developed against coccidiostatic drugs leading to an enhanced need for anticoccidial vaccines. In the current study we conducted an oral immunization trial with live attenuated sporulated Eimeria ninakohlyakimovae oocysts. Sporulated E. ninakohlyakimovae oocysts were attenuated by X-irradiation technique. The experimental design included a total of 18 goat kids divided into the following groups: (i) animals immunized with attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-irradiated homologous oocysts (group 1); (ii) animals infected with non-attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-attenuated homologous oocysts (group 2); (iii) animals primary-infected with untreated E. ninakohlyakimovae oocysts at 8 weeks of age (control of the challenge infection, group 3); (iv) non-infected control animals (group 4). Goat kids immunized with live attenuated E. ninakohlyakimovae oocysts (group 1) excreted significantly less oocysts in the faeces (95.3% reduction) than kids infected with non-attenuated ones (group 2). Furthermore, immunization with live but attenuated oocysts resulted in ameliorated clinical coccidiosis compared to goat kids infected with untreated oocysts (group 2) and resulted in equally reduced signs of coccidiosis after challenge infection compared to acquired immunity driven by non-attenuated oocysts. Overall, the present study demonstrates for the first time that live attenuated E. ninakohlyakimovae oocysts orally administered showed almost no pathogenicity but enough immunogenicity in terms of immunoprotection. Importantly, vaccinated animals still shed low amounts of oocysts, guaranteeing environmental contamination and consecutive booster infections to sustain ongoing immunity. Copyright © 2013 Elsevier B.V. All rights reserved.

Blood–brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV

PubMed Central

Yilmaz, Aylin; Hagberg, Lars; Zetterberg, Henrik; Nilsson, Staffan; Brew, Bruce J.; Fuchs, Dietmar; Price, Richard W.; Gisslén, Magnus

2016-01-01

Objective: Although blood–brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined. Methods: BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART). Results: The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis. Conclusions: BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals. PMID:27868081

Duration of Untreated Cardiac Arrest and Clinical Relevance of Animal Experiments: The Relationship Between the "No-Flow" Duration and the Severity of Post-Cardiac Arrest Syndrome in a Porcine Model.

PubMed

Babini, Giovanni; Grassi, Luigi; Russo, Ilaria; Novelli, Deborah; Boccardo, Antonio; Luciani, Anita; Fumagalli, Francesca; Staszewsky, Lidia; Fiordaliso, Fabio; De Maglie, Marcella; Salio, Monica; Zani, Davide D; Letizia, Teresa; Masson, Serge; Luini, Mario V; Pravettoni, Davide; Scanziani, Eugenio; Latini, Roberto; Ristagno, Giuseppe

2018-02-01

The study investigated the effect of untreated cardiac arrest (CA), that is, "no-flow" time, on postresuscitation myocardial and neurological injury, and survival in a pig model to identify an optimal duration that adequately reflects the most frequent clinical scenario. An established model of myocardial infarction followed by CA and cardiopulmonary resuscitation was used. Twenty-two pigs were subjected to three no-flow durations: short (8-10 min), intermediate (12-13 min), and long (14-15 min). Left ventricular ejection fraction (LVEF) was assessed together with thermodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT). Neurological impairment was evaluated by neurological scores, serum neuron specific enolase (NSE), and histopathology. More than 60% of animals survived when the duration of CA was ≤13 min, compared to only 20% for a duration ≥14 min. Neuronal degeneration and neurological scores showed a trend toward a worse recovery for longer no-flow durations. No animals achieved a good neurological recovery for a no-flow ≥14 min, in comparison to a 56% for a duration ≤13 min (P = 0.043). Serum NSE levels significantly correlated with the no-flow duration (r = 0.892). Longer durations of CA were characterized by lower LVEF and CO compared to shorter durations (P < 0.05). The longer was the no-flow time, the higher was the number of defibrillations delivered (P = 0.043). The defibrillations delivered significantly correlated with LVEF and plasma hs-cTnT. Longer no-flow durations caused greater postresuscitation myocardial and neurological dysfunction and reduced survival. An untreated CA of 12-13 min may be an optimal choice for a clinically relevant model.

The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases

PubMed Central

2011-01-01

Background Over 95% of rare diseases lack treatments despite many successful treatment studies in animal models. To improve access to treatments, the Accelerated Approval (AA) regulations were implemented allowing the use of surrogate endpoints to achieve drug approval and accelerate development of life-saving therapies. Many rare diseases have not utilized AA due to the difficulty in gaining acceptance of novel surrogate endpoints in untreated rare diseases. Methods To assess the potential impact of improved AA accessibility, we devised clinical development programs using proposed clinical or surrogate endpoints for fifteen rare disease treatments. Results We demonstrate that better AA access could reduce development costs by approximately 60%, increase investment value, and foster development of three times as many rare disease drugs for the same investment. Conclusion Our research brings attention to the need for well-defined and practical qualification criteria for the use of surrogate endpoints to allow more access to the AA approval pathway in clinical trials for rare diseases. PMID:21733145

Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats.

PubMed

Pomjunya, Atchariya; Ratthanophart, Jasada; Fungfuang, Wirasak

2017-03-23

The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats.

Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats

PubMed Central

POMJUNYA, Atchariya; RATTHANOPHART, Jasada; FUNGFUANG, Wirasak

2017-01-01

The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats. PMID:28190818

Remodeling of atrial ATP-sensitive K+ channels in a model of salt-induced elevated blood pressure

PubMed Central

Lader, Joshua M.; Vasquez, Carolina; Bao, Li; Maass, Karen; Qu, Jiaxiang; Kefalogianni, Eirini; Fishman, Glenn I.; Coetzee, William A.

2011-01-01

Hypertension is associated with the development of atrial fibrillation; however, the electrophysiological consequences of this condition remain poorly understood. ATP-sensitive K+ (KATP) channels, which contribute to ventricular arrhythmias, are also expressed in the atria. We hypothesized that salt-induced elevated blood pressure (BP) leads to atrial KATP channel activation and increased arrhythmia inducibility. Elevated BP was induced in mice with a high-salt diet (HS) for 4 wk. High-resolution optical mapping was used to measure atrial arrhythmia inducibility, effective refractory period (ERP), and action potential duration at 90% repolarization (APD90). Excised patch clamping was performed to quantify KATP channel properties and density. KATP channel protein expression was also evaluated. Atrial arrhythmia inducibility was 22% higher in HS hearts compared with control hearts. ERP and APD90 were significantly shorter in the right atrial appendage and left atrial appendage of HS hearts compared with control hearts. Perfusion with 1 μM glibenclamide or 300 μM tolbutamide significantly decreased arrhythmia inducibility and prolonged APD90 in HS hearts compared with untreated HS hearts. KATP channel density was 156% higher in myocytes isolated from HS animals compared with control animals. Sulfonylurea receptor 1 protein expression was increased in the left atrial appendage and right atrial appendage of HS animals (415% and 372% of NS animals, respectively). In conclusion, KATP channel activation provides a mechanistic link between salt-induced elevated BP and increased atrial arrhythmia inducibility. The findings of this study have important implications for the treatment and prevention of atrial arrhythmias in the setting of hypertensive heart disease and may lead to new therapeutic approaches. PMID:21724863

Influence of poisoned prey on foraging behavior of ferruginous hawks

USGS Publications Warehouse

Vyas, Nimish B.; Kuncir, Frank; Clinton, Criss C.

2017-01-01

We recorded 19 visits by ferruginous hawks (Buteo regalis) over 6 d at two black–tailed prairie dog (Cynomys ludovicianus) subcolonies poisoned with the rodenticide Rozol® Prairie Dog Bait (0.005% chlorophacinone active ingredient) and at an adjacent untreated subcolony. Before Rozol® application ferruginous hawks foraged in the untreated and treated subcolonies but after Rozol® application predation by ferruginous hawks was only observed in the treated subcolonies. We suggest that ferruginous hawks' preference for hunting in the treated subcolonies after Rozol® application was influenced by the availability of easy-to-capture prey, presumably due to Rozol® poisoning. The energetically beneficial behavior of favoring substandard prey may increase raptor encounters with rodenticide exposed animals if prey vulnerability has resulted from poisoning.

Set-up of a multivariate approach based on serum biomarkers as an alternative strategy for the screening evaluation of the potential abuse of growth promoters in veal calves

PubMed Central

Pirro, Valentina; Girolami, Flavia; Spalenza, Veronica; Gardini, Giulia; Badino, Paola; Nebbia, Carlo

2015-01-01

A chemometric class modelling strategy (unequal dispersed classes – UNEQ) was applied for the first time as a possible screening method to monitor the abuse of growth promoters in veal calves. Five serum biomarkers, known to reflect the exposure to classes of compounds illegally used as growth promoters, were determined from 50 untreated animals in order to design a model of controls, representing veal calves reared under good, safe and highly standardised breeding conditions. The class modelling was applied to 421 commercially bred veal calves to separate them into ‘compliant’ and ‘non-compliant’ with respect to the modelled controls. Part of the non-compliant animals underwent further histological and chemical examinations to confirm the presence of either alterations in target tissues or traces of illegal substances commonly administered for growth-promoting purposes. Overall, the congruence between the histological or chemical methods and the UNEQ non-compliant outcomes was approximately 58%, likely underestimated due to the blindness nature of this examination. Further research is needed to confirm the validity of the UNEQ model in terms of sensitivity in recognising untreated animals as compliant to the controls, and specificity in revealing deviations from ideal breeding conditions, for example due to the abuse of growth promoters. PMID:25730172

Methyl Gallate from Galla rhois Successfully Controls Clinical Isolates of Salmonella Infection in Both In Vitro and In Vivo Systems

PubMed Central

Choi, Jang-Gi; Mun, Su-Hyun; Chahar, Harendra S.; Bharaj, Preeti; Kang, Ok-Hwa; Kim, Se-Gun; Shin, Dong-Won; Kwon, Dong-Yeul

2014-01-01

Galla rhois is a commonly used traditional medicine for the treatment of pathogenic bacteria in Korea as well as in other parts of Asia. Methyl gallate (MG), a major component of Galla Rhois, exhibits strong antibacterial activity, but its mechanism of action against Salmonella spp. is unclear. In the present study, we investigated the antibacterial actions of MG against Salmonella. The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of MG against Salmonella strains ranged from 3.9 to 125 µg/ml. In vitro bacterial viability test indicated that MG significantly decreased the viability of Salmonella over 40% when combined with ATPase inhibitors. The time-kill curves showed that a combined MG and ATPase inhibitors (DCCD and NaN3) treatment reduced the bacterial counts dramatically after 24 h. Oral administration of MG showed a strong anti-bacterial activity against WS-5 infected BALB/c mice. In contrast to the untreated Salmonella infected control animals, MG treated groups showed no clinical symptoms of the disease, such as lethargy and liver damage. It was observed that MG treatment significantly increased the survival of animals from Salmonella infection, while in untreated groups all animal succumbed to disease by the sixth day post infection. Thus, the present study demonstrates the therapeutic ability of MG against Salmonella infections. PMID:25048362

Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

PubMed Central

Young, Rebeccah F.; Leiker, Merced M.; Suzuki, Takayuki

2016-01-01

A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure. PMID:27738436

Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome.

PubMed

Mikolka, P; Kopincová, J; Košútová, P; Čierny, D; Čalkovská, A; Mokrá, D

2016-12-22

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-alpha) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

Methyl gallate from Galla rhois successfully controls clinical isolates of Salmonella infection in both in vitro and in vivo systems.

PubMed

Choi, Jang-Gi; Mun, Su-Hyun; Chahar, Harendra S; Bharaj, Preeti; Kang, Ok-Hwa; Kim, Se-Gun; Shin, Dong-Won; Kwon, Dong-Yeul

2014-01-01

Galla rhois is a commonly used traditional medicine for the treatment of pathogenic bacteria in Korea as well as in other parts of Asia. Methyl gallate (MG), a major component of Galla Rhois, exhibits strong antibacterial activity, but its mechanism of action against Salmonella spp. is unclear. In the present study, we investigated the antibacterial actions of MG against Salmonella. The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of MG against Salmonella strains ranged from 3.9 to 125 µg/ml. In vitro bacterial viability test indicated that MG significantly decreased the viability of Salmonella over 40% when combined with ATPase inhibitors. The time-kill curves showed that a combined MG and ATPase inhibitors (DCCD and NaN3) treatment reduced the bacterial counts dramatically after 24 h. Oral administration of MG showed a strong anti-bacterial activity against WS-5 infected BALB/c mice. In contrast to the untreated Salmonella infected control animals, MG treated groups showed no clinical symptoms of the disease, such as lethargy and liver damage. It was observed that MG treatment significantly increased the survival of animals from Salmonella infection, while in untreated groups all animal succumbed to disease by the sixth day post infection. Thus, the present study demonstrates the therapeutic ability of MG against Salmonella infections.

Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study.

PubMed

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369.

Shigellosis Outbreak Associated with Contaminated Well Water in a Rural Elementary School: Sichuan Province, China, June 7–16, 2009

PubMed Central

Sun, Wei; Zhang, Lijie; Zhu, Baoping; Ma, Huilai

2012-01-01

Objectives We investigated a shigellosis outbreak in an elementary school to identify the source of infection, mode of transmission and risk factors for illness. Methods In a case-control investigation, we compared the source of drinking water, consumption of untreated well water and suspected food items, and hygienic habits between case-students and randomly selected asymptomatic control-students, frequency-matched by class on a 1∶1 ratio. Results 18% of the 533 students and no teachers developed Shigella. 52%(44/85) of case-students and 17% (12/71) of control-students drank untreated well water (OR = 2.3, 95% CI = 1.1–5.8); 47% (n = 40/85) of case-students and 14% (10/71) of control-students drank untreated water from Well A (OR = 3.7, 95% CI = 1.3–11). The odds ratio increased with the amount of untreated Well A water consumed (p = 0.035, χ2 test for trend). Rectal swabs from 5 of 6 case-students and water from Well A yielded Shigella flexneri 2b. Conclusions This shigellosis outbreak was caused by drinking untreated water from a well polluted by Shigella flexneri 2b. PMID:23071767

Age and exposure to arsenic alter base excision repair transcript levels in mice.

PubMed

Osmond, Megan J; Kunz, Bernard A; Snow, Elizabeth T

2010-09-01

Arsenic (As) induces DNA-damaging reactive oxygen species. Most oxidative DNA damage is countered by base excision repair (BER), the capacity for which may be reduced in older animals. We examined whether age and consumption of As in lactational milk or drinking water influences BER gene transcript levels in mice. Lactating mothers and 24-week-old mice were exposed (24 h or 2 weeks) to As (2 or 50 p.p.m.) in drinking water. Lung tissue was harvested from adults, neonates (initially 1 week old) feeding from lactating mothers and untreated animals 1-26 weeks old. Transcripts encoding BER proteins were quantified. BER transcript levels decreased precipitously with age in untreated mice but increased in neonates whose mothers were exposed to 50 p.p.m. As for 24 h or 2 weeks. Treatment of 24-week-old mice with 2 or 50 p.p.m. As for 2 weeks decreased all transcript levels measured. Exposure to As attenuated the age-related transcript level decline for only one BER gene. We conclude that aging is associated with a rapid reduction of BER transcript levels in mice, which may contribute to decreased BER activity in older animals. Levels of As that can alter gene expression are transmitted to neonatal mice in lactational milk produced by mothers drinking water containing As, raising concerns about breastfeeding in countries having As-contaminated groundwater. Reduction of BER transcript levels in 24-week-old mice exposed to As for 2 weeks suggests As may potentiate sensitivity to itself in older animals.

Efficacy of PLD-118, a Novel Inhibitor of Candida Isoleucyl-tRNA Synthetase, against Experimental Oropharyngeal and Esophageal Candidiasis Caused by Fluconazole-Resistant C. albicans

PubMed Central

Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M.; Sarafandi, Alia A.; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H.; Walsh, Thomas J.

2004-01-01

PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring β-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 μg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P ≤ 0.05, P ≤ 0.01, P ≤ 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis. PMID:15388459

Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.

PubMed

Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M; Sarafandi, Alia A; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H; Walsh, Thomas J

2004-10-01

PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P

Dosage-Dependent Antifungal Efficacy of V-Echinocandin (LY303366) against Experimental Fluconazole-Resistant Oropharyngeal and Esophageal Candidiasis

PubMed Central

Petraitis, Vidmantas; Petraitiene, Ruta; Groll, Andreas H.; Sein, Tin; Schaufele, Robert L.; Lyman, Caron A.; Francesconi, Andrea; Bacher, John; Piscitelli, Stephen C.; Walsh, Thomas J.

2001-01-01

V-echinocandin (VER-002; LY303366) is a semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1, 3)-β-d-glucan synthase. We studied the antifungal efficacy, the concentrations in saliva and tissue, and the safety of VER-002 at escalating dosages against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant Candida albicans in immunocompromised rabbits. Study groups consisted of untreated controls, animals treated with VER-002 at 1, 2.5, and 5 mg/kg of body weight/day intravenously (i.v.), animals treated with fluconazole at 2 mg/kg/day i.v., or animals treated with amphotericin B at 0.3 mg/kg/day. VER-002-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, esophagus, stomach, and duodenum in comparison to that for untreated controls. VER-002 also was superior to amphotericin B and fluconazole in clearing the organism from all sites studied. These in vivo findings are consistent with the results of in vitro time-kill assays, which demonstrated that VER-002 has concentration-dependent fungicidal activity. Esophageal tissue VER-002 concentrations were dosage proportional and exceeded the MIC at all dosages. Echinocandin concentrations in saliva were greater than or equal to the MICs at all dosages. There was no elevation of serum hepatic transaminase, alkaline phosphatase, bilirubin, potassium, or creatinine levels in VER-002-treated rabbits. In summary, the echinocandin VER-002 was well tolerated, penetrated the esophagus and salivary glands, and demonstrated dosage-dependent antifungal activity against fluconazole-resistant esophageal candidiasis in immunocompromised rabbits. PMID:11158743

40 CFR 798.4700 - Reproduction and fertility effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (iv) Number of animals. Each test and control group shall contain at least 20 males and a sufficient number of females to yield at least 20 pregnant females at or near term. (2) Control groups. (i) A concurrent control group shall be used. This group shall be an untreated or sham treated control group or if...

40 CFR 798.4700 - Reproduction and fertility effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (iv) Number of animals. Each test and control group shall contain at least 20 males and a sufficient number of females to yield at least 20 pregnant females at or near term. (2) Control groups. (i) A concurrent control group shall be used. This group shall be an untreated or sham treated control group or if...

40 CFR 798.4700 - Reproduction and fertility effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (iv) Number of animals. Each test and control group shall contain at least 20 males and a sufficient number of females to yield at least 20 pregnant females at or near term. (2) Control groups. (i) A concurrent control group shall be used. This group shall be an untreated or sham treated control group or if...

40 CFR 798.4700 - Reproduction and fertility effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (iv) Number of animals. Each test and control group shall contain at least 20 males and a sufficient number of females to yield at least 20 pregnant females at or near term. (2) Control groups. (i) A concurrent control group shall be used. This group shall be an untreated or sham treated control group or if...

40 CFR 798.4700 - Reproduction and fertility effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (iv) Number of animals. Each test and control group shall contain at least 20 males and a sufficient number of females to yield at least 20 pregnant females at or near term. (2) Control groups. (i) A concurrent control group shall be used. This group shall be an untreated or sham treated control group or if...

Steroids reduce the periapical inflammatory and neural changes after pulpectomy.

PubMed

Holland, G R

1996-09-01

Root canal treatment, including obturation with gutta-percha and a zinc oxide and eugenol sealer, was conducted, under general anesthesia, on the canine teeth of 12 young ferrets. Six of the ferrets were given 0.5 mg/kg dexamethasone daily. Three months after the root canal treatment, under general anesthesia, the animals were perfused with fixative and the canine periapical tissues prepared for histological examination. The extent of periapical inflammation was measured and the degree of neural sprouting in the periodontal and subapical regions estimated. Periapical lesions in steroid-treated animals were 30% of the size of those in untreated animals. Innervation density in the subapical region of the steroid-treated animals was lower than that in the animals who did not receive steroids and not significantly different from controls. Reduction in periapical inflammation induced by systemic steroids is accompanied by a reduction in neural sprouting.

The effect of topical mitomycin C on full-thickness burns.

PubMed

Tennyson, Heath; Helling, Eric R; Wiseman, Joseph; Dick, Edward; Lyons, Robert C

2007-09-15

Burns result in substantial morbidity because of fibroblast proliferation and contracture. Mitomycin C is a chemotherapeutic agent known to suppress fibroblast proliferation. It is used in ophthalmologic disorders and reduces scarring in upper aerodigestive surgery. No study of the effect of mitomycin C on cutaneous burns has been performed. This study examined burn healing in the presence of topical mitomycin C by evaluation of wound appearance, contraction, and histology in a pig model. Standardized full-thickness burns were produced on the flanks of three pigs. One animal received no further therapy and was an external control. Two animals underwent placement of topical mitomycin C, 0.4 mg/ml, on selected burn sites for 5 minutes. This was repeated 2 and 4 weeks after injury. Evaluation was performed at 2 and 6 months using a clinical assessment scale and a visual analogue scale. Scar length and histologic analysis were also evaluated. Clinical assessment scale and visual analogue scale scores showed improved appearance in the untreated external control wounds versus the untreated internal control and treated wounds (p < 0.001). Wound contraction was not significantly different between groups. Histologic characteristics between groups were similar except for epidermal hyperplasia, which was decreased in the untreated external control (p < 0.05) at 2 months after treatment. Topical mitomycin C treatment of full-thickness burn wounds at 0.4 mg/cc for three courses does not improve, and may worsen, clinical appearance and scarring during early healing. There is no difference in histology during the long-term healing process. Scar contraction was unchanged.

Effect of pH, Dosage and Concentration on the Adsorption of Congo Red onto Untreated and Treated Aluminium Dross

NASA Astrophysics Data System (ADS)

Zakaria Mohamad Zulfika, Hazielim B.; Baini, Rubiyah; Zauzi, Nur Syuhada Ahmad

2017-06-01

The adsorption of congo red onto aluminium dross was studied in batch process. The objective of this study is to adsorption capacity between untreated and treated aluminium dross in the removal of congo red. Aluminium dross was leached with 250 ml of 1% of NaOH and and precipitated with 30% H2O2. The treated aluminium dross being calcined at 600°C for 3 hours. The surface area for untreated and treated aluminium dross was 10.06 m2/g and 79.80 m2/g respectively. Then the adsorption process was carried out on an orbital shaker at 200 rpm for 4 hours. In the effect of pH, it was found that untreated removes more congo red compared to the treated while in the effect of concentration solution and dosage of adsorbent, treated aluminium dross removes more congo red. In conclusion, this adsorbent was found to be effective and economically viable in the removal of congo red in waste water treatment.

Automated registration of tail bleeding in rats.

PubMed

Johansen, Peter B; Henriksen, Lars; Andresen, Per R; Lauritzen, Brian; Jensen, Kåre L; Juhl, Trine N; Tranholm, Mikael

2008-05-01

An automated system for registration of tail bleeding in rats using a camera and a user-designed PC-based software program has been developed. The live and processed images are displayed on the screen and are exported together with a text file for later statistical processing of the data allowing calculation of e.g. number of bleeding episodes, bleeding times and bleeding areas. Proof-of-principle was achieved when the camera captured the blood stream after infusion of rat whole blood into saline. Suitability was assessed by recording of bleeding profiles in heparin-treated rats, demonstrating that the system was able to capture on/off bleedings and that the data transfer and analysis were conducted successfully. Then, bleeding profiles were visually recorded by two independent observers simultaneously with the automated recordings after tail transection in untreated rats. Linear relationships were found in the number of bleedings, demonstrating, however, a statistically significant difference in the recording of bleeding episodes between observers. Also, the bleeding time was longer for visual compared to automated recording. No correlation was found between blood loss and bleeding time in untreated rats, but in heparinized rats a correlation was suggested. Finally, the blood loss correlated with the automated recording of bleeding area. In conclusion, the automated system has proven suitable for replacing visual recordings of tail bleedings in rats. Inter-observer differences can be eliminated, monotonous repetitive work avoided, and a higher through-put of animals in less time achieved. The automated system will lead to an increased understanding of the nature of bleeding following tail transection in different rodent models.

Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice

PubMed Central

Burnett, Colin M. L.

2013-01-01

Substantial research efforts have been aimed at identifying novel targets to increase resting metabolic rate (RMR) as an adjunct approach to the treatment of obesity. Respirometry (one form of “indirect calorimetry”) is unquestionably the dominant technique used in the obesity research field to assess RMR in vivo, although this method relies upon a lengthy list of assumptions that are likely to be violated in pharmacologically or genetically manipulated animals. A “total” calorimeter, including a gradient layer direct calorimeter coupled to a conventional respirometer, was used to test the accuracy of respirometric-based estimations of RMR in laboratory mice (Mus musculus Linnaeus) of the C57Bl/6 and FVB background strains. Using this combined calorimeter, we determined that respirometry underestimates RMR of untreated 9- to 12-wk-old male mice by ∼10–12%. Quantitative and qualitative differences resulted between methods for untreated C57Bl/6 and FVB mice, C57Bl/6 mice treated with ketamine-xylazine anesthesia, and FVB mice with genetic deletion of the angiotensin II type 2 receptor. We conclude that respirometric methods underestimate RMR in mice in a magnitude that is similar to or greater than the desired RMR effects of novel therapeutics. Sole reliance upon respirometry to assess RMR in mice may lead to false quantitative and qualitative conclusions regarding the effects of novel interventions. Increased use of direct calorimetry for the assessment of RMR and confirmation of respirometry results and the reexamination of previously discarded potential obesity therapeutics are warranted. PMID:23964071

Evaluation of renal nerve morphological changes and norepinephrine levels following treatment with novel bipolar radiofrequency delivery systems in a porcine model

PubMed Central

Cohen-Mazor, Meital; Mathur, Prabodh; Stanley, James R.L.; Mendelsohn, Farrell O.; Lee, Henry; Baird, Rose; Zani, Brett G.; Markham, Peter M.; Rocha-Singh, Krishna

2014-01-01

Objective: To evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model. Methods: A porcine model (N = 46) was used to investigate renal norepinephrine levels and changes to renal artery tissues and nerves following percutaneous renal denervation with radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of the radiofrequency system (i.e. electrode length and energy delivery algorithm), and the effects of single and longitudinal treatments along the artery were studied with a 7-day model in which swine received unilateral radiofrequency treatments. Additional sets of animals were used to examine norepinephrine and histological changes 28 days following bilateral percutaneous radiofrequency treatment or surgical denervation; untreated swine were used for comparison of renal norepinephrine levels. Results: Seven days postprocedure, norepinephrine concentrations decreased proportionally to electrode length, with 81, 60 and 38% reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes, respectively. Applying a temperature-control algorithm with the 4-mm electrodes increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s treatment at 68°C. Applying this treatment along the entire artery length affected more nerves vs. a single treatment, resulting in superior norepinephrine reduction 28 days following bilateral treatment. Conclusion: Percutaneous renal artery application of bipolar radiofrequency energy demonstrated safety and resulted in a significant renal norepinephrine content reduction and renal nerve injury compared with untreated controls in porcine models. PMID:24875181

The effect of methamphetamine on an animal model of erectile function

PubMed Central

Tar, Moses T.; Martinez, Luis R.; Nosanchuk, Joshua D.; Davies, Kelvin P.

2014-01-01

In the U.S. methamphetamine is considered a first-line treatment for attention-deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine (2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)) i.p. daily for three weeks and erectile function compared to untreated controls. The effect of co-administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals the ICP/BP ratio following 4 and 6mA stimulation decreased by approximately 50% compared to untreated animals and erectile dysfunction was also reversed by tadalafil. Overall our data suggests that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for treating patients that report erectile dysfunction associated with therapeutics containing methamphetamine or amphetamine with PDE5i. PMID:24706617

Effect of hydroalcoholic extract from Copaifera langsdorffii leaves on urolithiasis induced in rats.

PubMed

Brancalion, Ana Paula S; Oliveira, Rejane B; Sousa, João Paulo B; Groppo, Milton; Berretta, Andresa A; Barros, Marcio E; Boim, Mirian A; Bastos, Jairo K

2012-10-01

Copaifera langsdorffii Desf. commonly known as "copaíba", produce a commercially valuable oil-resin that is extensively used in folk medicine for anti-inflammatory, antimicrobial and antiseptic purposes. We have found the hydroalcoholic extract of this plant leaf has the potential to treat urolithiasis, a problem affecting ~7% of the population. To isolate the functional compounds C. langsdorffii leaves were dried, ground, and macerated in a hydroalcoholic solution 7:3 to produce a 16.8% crude extract after solvent elimination. Urolithiasis was induced by introduction of a calcium oxalate pellet (CaOx) into the bladders of adult male Wistar rats. The treated groups received the crude extract by oral gavage at 20 mg/kg body weight daily for 18 days. Extract treatment started 30 days after CaOx seed implantation. To monitor renal function sodium, potassium and creatinine concentrations were analyzed in urine and plasma, and were found to be in the normal range. Analyses of pH, magnesium, phosphate, calcium, uric acid, oxalate and citrate levels were evaluated to determine whether the C. langsdorffii extract may function as a stone formation prevention agent. The HPLC analysis of the extract identified flavonoids quercitrin and afzelin as the major components. Animals treated with C. langsdorffii have increased levels of magnesium and decreased levels of uric acid in urinary excretions. Treated animals have a significant decrease in the mean number of calculi and a reduction in calculi mass. Calculi taken from extract treated animals were more brittle and fragile than calculi from untreated animals. Moreover, breaking calculi from untreated animals required twice the amount of pressure as calculi from treated animals (6.90 ± 3.45 vs. 3.00 ± 1.51). The extract is rich in flavonoid heterosides and other phenolic compounds. Therefore, we hypothesize this class of compounds might contribute significantly to the observed activity.

Correlation between Histological Status of the Pulp and Its Response to Sensibility Tests

PubMed Central

Naseri, Mandana; Khayat, Akbar; Zamaheni, Sara; Shojaeian, Shiva

2017-01-01

Introduction: The purpose of this study was to assess the accuracy of sensibility tests by correlating it with histologic pulp condition. Methods and Materials: Assessment of clinical signs and symptoms were performed on 65 permanent teeth that were scheduled to be extracted for periodontal, prosthodontic or orthodontic reasons. The normal pulp and reversible pulpitis were considered as treatable tooth conditions while irreversible pulpitis and necrosis were considered as untreatable conditions. The teeth were then extracted and sectioned for histological analysis of dental pulp. Histologic status and classification corresponded to the treatable or untreatable pulp condition. Comparisons between histological treatable and untreatable pulp condition were performed with chi-square analysis for sensibility test responses. The positive predictive value (PPV), negative predictive value (NPV) and accuracy to detect untreatable from treatable pulp condition were calculated for each test. Results: A significant difference was detected in the normal and a sharp lingered response to heat and cold tests. There was significant difference in the negative response to EPT between histological groups. The kappa agreement coefficient between clinical and histological diagnosis of pulp condition was about 0.843 (P<0.001). The accuracy of cold and heat tests and EPT to detect treatable pulp or untreatable pulp states were 78, 74 and 62%, respectively. The sensibility tests diagnosed untreatable pulpitis with a higher probability (NPV=63%-67% -54%, PPV=83%-91% -95% for heat, cold and EPT, respectively). Conclusion: Sensibility test results were more likely to diagnose pulpal disease or untreatable pulp conditions. However, to increase the diagnostic accuracy patient history, clinical signs and symptoms and also radiographic findings in conjunction with sensibility tests must be used. The result of this small study demonstrated a good agreement between clinical and histological pulp diagnosis. PMID:28179918

Fenoterol Enantiomers do not Possess Beneficial Therapeutic Properties of Their Racemic Mixture in the Rat Model of Post Myocardial Infarction Dilated Cardiomyopathy

PubMed Central

Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G.; Talan, Mark I.

2015-01-01

Purpose A salutary effect of β2 adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM. Methods Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography. Results Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first two months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective. Conclusion The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM. PMID:22328006

Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.

PubMed

Guedes, R M C; França, S A; Machado, G S; Blumer, M A; da Costa Cruz, E C

2009-09-19

The effect of an oral treatment with the tartrate salt of tylvalosin on the development of proliferative enteropathy in 60 experimentally challenged pigs was studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and 30 were fed the unmedicated diet. The treated animals started to receive the medicated feed the day before they were inoculated, and continued to receive it for 14 days. The pigs' bodyweight, feed consumption and clinical signs were evaluated, and they were examined postmortem 20 days after inoculation, and samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia intracellularis. Clinical signs of the disease were more evident in the untreated group than in the treated group. The average daily weight gain, average daily feed consumption and feed conversion efficiency were better in the treated group. The combined length of intestine with lesions was 2847 cm in the untreated group and 183 cm in the treated group. The tylvalosin treatment significantly reduced the level of L intracellularis infection; almost half of the treated pigs were IHC-negative compared with 3.3 per cent of the untreated pigs.

Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging.

PubMed

O'Reilly, Meaghan Anne; Jones, Ryan Matthew; Barrett, Edward; Schwab, Anthony; Head, Elizabeth; Hynynen, Kullervo

2017-01-01

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits. Methods: Aged dogs naturally accumulate plaques and show associated cognitive declines. Low-frequency ultrasound was used to open the BBB unilaterally in aged beagles (9-11yrs, n=10) in accordance with institutionally approved protocols. Animals received either a single treatment or four weekly treatments. Magnetic resonance imaging(MRI) was used to guide the treatments and assess the tissue effects. The animals underwent neurological testing during treatment follow-up, and a follow-up MRI exam 1 week following the final treatment. Results: The permeability of the BBB was successfully increased in all animals (mean enhancement: 19±11% relative to untreated hemisphere). There was a single adverse event in the chronic treatment group that resolved within 24 hrs. Follow-up MRI showed the BBB to be intact with no evidence of tissue damage in all animals. Histological analysis showed comparable levels of microhemorrhage between the treated and control hemispheres in the prefrontal cortex (single/repeat treatment: 1.0±1.4 vs 0.4±0.5/5.2±1.8 vs. 4.0±2.0). No significant differences were observed in beta-amyloid load (single/repeat: p=0.31/p=0.98) although 3/5 animals in each group showed lower Aβ loads in the treated hemisphere. Conclusion: Whole-hemisphere opening of the BBB was well tolerated in the aged large animal brain. The treatment volumes and frequencies used are clinically relevant and indicate safety for clinical translation. Further study is warranted to determine if FUS has positive effects on naturally occurring amyloid pathology.

Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats.

PubMed Central

Larsson, L; Li, X; Teresi, A; Salviati, G

1994-01-01

1. The effects of 4 weeks of thyroid hormone treatment on contractile, enzyme-histochemical and morphometric properties and on the myosin isoform composition were compared in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscle in young (3-6 months) and old (20-24 months) male rats. 2. In the soleus of untreated controls, contraction and half-relaxation times of the isometric twitch increased by 19-32% with age. The change in contractile properties was paralleled by an age-related increase in the proportions of type I fibres and type I myosin heavy chain (MHC) and slow myosin light chain (MLC) isoforms. 3. In the EDL of controls, contraction and half-relaxation times were significantly prolonged (21-38%) in the post-tetanus twitch in the old animals. No significant age-related changes were observed in enzyme-histochemical fibre-type proportions, although the number of fibres expressing both type IIA and IIB MHCs and of fibres expressing slow MLC isoforms was increased in the old animals. 4. Serum 3,5,3',5'-tetraiodothyronine (T4) levels were lower (34%) in the old animals, but the primary byproduct of T4, 3,5,3'-triiodothyronine (T3), did not differ between young and old animals. 5. The effects of 4 weeks of thyroid hormone treatment were highly muscle specific, and were more pronounced in soleus than in EDL, irrespective of animal age. In the soleus, this treatment shortened the contraction and half-relaxation times by 35-57% and decreased the number of type I fibres by 66-77% in both young and old animals. In EDL, thyroid hormone treatment significantly shortened the contraction time by 24%, but the change was restricted to the old animals. 6. In conclusion, the ability of skeletal muscle to respond to thyroid hormone treatment was not impaired in old age and the age-related changes in speed of contraction and enzyme-histochemical properties and myosin isoform compositions were diminished after thyroid hormone treatment in both the soleus and EDL. Images Figure 3 Figure 4 PMID:7853237

Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging

PubMed Central

O'Reilly, Meaghan Anne; Jones, Ryan Matthew; Barrett, Edward; Schwab, Anthony; Head, Elizabeth; Hynynen, Kullervo

2017-01-01

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits. Methods: Aged dogs naturally accumulate plaques and show associated cognitive declines. Low-frequency ultrasound was used to open the BBB unilaterally in aged beagles (9-11yrs, n=10) in accordance with institutionally approved protocols. Animals received either a single treatment or four weekly treatments. Magnetic resonance imaging(MRI) was used to guide the treatments and assess the tissue effects. The animals underwent neurological testing during treatment follow-up, and a follow-up MRI exam 1 week following the final treatment. Results: The permeability of the BBB was successfully increased in all animals (mean enhancement: 19±11% relative to untreated hemisphere). There was a single adverse event in the chronic treatment group that resolved within 24 hrs. Follow-up MRI showed the BBB to be intact with no evidence of tissue damage in all animals. Histological analysis showed comparable levels of microhemorrhage between the treated and control hemispheres in the prefrontal cortex (single/repeat treatment: 1.0±1.4 vs 0.4±0.5/5.2±1.8 vs. 4.0±2.0). No significant differences were observed in beta-amyloid load (single/repeat: p=0.31/p=0.98) although 3/5 animals in each group showed lower Aβ loads in the treated hemisphere. Conclusion: Whole-hemisphere opening of the BBB was well tolerated in the aged large animal brain. The treatment volumes and frequencies used are clinically relevant and indicate safety for clinical translation. Further study is warranted to determine if FUS has positive effects on naturally occurring amyloid pathology. PMID:28912896

Hemodynamic and metabolic parameters during prolonged cardiac arrest and reperfusion by extracorporeal circulation.

PubMed

Mlček, M; Ošťádal, P; Bělohlávek, J; Havránek, Š; Hrachovina, M; Huptych, M; Hála, P; Hrachovina, V; Neužil, P; Kittnar, O

2012-01-01

Extracorporeal membranous oxygenation (ECMO) is increasingly used in the management of refractory cardiac arrest. Our aim was to investigate early effects of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18) ventricular fibrillation (VF) was induced and untreated period (20 min) of cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium, tissue oximetry (StO(2)) and cardiac (EGM) and cerebral (BIS) electrophysiological parameters were continuously recorded and analyzed. Within 3 minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic parameters destabilize gradually over 20 minutes peaking at pH 7.04 ± 0.05, pCO(2) 89 ± 14 mmHg, K(+) 8.5 ± 1.6 mmol/l. During reperfusion most parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40 mmHg, StO(2)>50 %, paO(2)>100 mmHg, pCO(2)<50 mmHg, K(+)<5 mmol/l. EGMs mean amplitude peaks at 4.5 ± 2.4 min. Cerebral activity (BIS>60) reappeared in 5 animals after 87 ± 21 min. In 12/18 animals return of spontaneous circulation was achieved. In conclusions, ECMO provides rapid restitution of internal milieu even after prolonged arrest. However, despite normalization of global parameters full recovery was not guaranteed since cardiac and cerebral electrical activities were sufficiently restored only in some animals. More sensitive and organ specific indicators need to be identified in order to estimate adequacy of cardiac support devices.

The Efficacy, Longevity, and Safety of Combined Radiofrequency Treatment and Hyaluronic Acid Filler for Skin Rejuvenation

PubMed Central

Kim, Hyuk; Park, Kui Young; Choi, Sun Young; Koh, Hyun-Ju; Park, Sun-Young; Park, Won-Seok; Bae, Il-Hong

2014-01-01

Background Recent advances in hyaluronic acid (HA) fillers and radiofrequency (RF) devices have been made in the context of skin rejuvenation and cosmetic surgery. Moreover, combination regimens with both techniques are currently being developed. Objective The present study was designed to examine the clinical and histologic effects of a new needle that incorporates an RF device for HA injections. Methods A new intradermal needle RF device (INNOfill; Pacific Pharma, Korea) was assessed in the present study. In the animal arm, procollagen production was measured by using enzyme-linked immunosorbent assay, the filler volume was quantified by incorporating a dye with filler, and the filler distribution was assessed through the changes in tissue structure. In the human arm, the efficacy of the combination regimen was assessed by using the wrinkle severity rating scale (WSRS). Results In the animal study, RF treatment increased procollagen production in a time-dependent fashion. The total volume was significantly increased with the RF treatment when compared with the filler injections alone, and lasted for up to 7 weeks after treatment. Additionally, the filler distribution was reduced in animals treated with RF when compared with the untreated group. In the human study, the nasolabial folds of subjects treated with RF before filler injections exhibited a significantly greater change in the WSRS score from baseline when compared with the nasolabial folds treated with filler injections alone. Conclusion A new device incorporating RF treatment before HA filler injection may represent a biocompatible and long-lasting advance in skin rejuvenation. PMID:25143672

Lentiviral Expression of Retinal Guanylate Cyclase-1 (RetGC1) Restores Vision in an Avian Model of Childhood Blindness

PubMed Central

Haire, Shannon E; Aleman, Tomas S; Cideciyan, Artur V; Sokal, Izabel; Palczewski, Krzysztof; Jacobson, Samuel G; Semple-Rowland, Susan L

2006-01-01

Background Leber congenital amaurosis (LCA) is a genetically heterogeneous group of retinal diseases that cause congenital blindness in infants and children. Mutations in the GUCY2D gene that encodes retinal guanylate cyclase–1 (retGC1) were the first to be linked to this disease group (LCA type 1 [LCA1]) and account for 10%–20% of LCA cases. These mutations disrupt synthesis of cGMP in photoreceptor cells, a key second messenger required for function of these cells. The GUCY1*B chicken, which carries a null mutation in the retGC1 gene, is blind at hatching and serves as an animal model for the study of LCA1 pathology and potential treatments in humans. Methods and Findings A lentivirus-based gene transfer vector carrying the GUCY2D gene was developed and injected into early-stage GUCY1*B embryos to determine if photoreceptor function and sight could be restored to these animals. Like human LCA1, the avian disease shows early-onset blindness, but there is a window of opportunity for intervention. In both diseases there is a period of photoreceptor cell dysfunction that precedes retinal degeneration. Of seven treated animals, six exhibited sight as evidenced by robust optokinetic and volitional visual behaviors. Electroretinographic responses, absent in untreated animals, were partially restored in treated animals. Morphological analyses indicated there was slowing of the retinal degeneration. Conclusions Blindness associated with loss of function of retGC1 in the GUCY1*B avian model of LCA1 can be reversed using viral vector-mediated gene transfer. Furthermore, this reversal can be achieved by restoring function to a relatively low percentage of retinal photoreceptors. These results represent a first step toward development of gene therapies for one of the more common forms of childhood blindness. PMID:16700630

A pilot study of an anti-MRSA bio-engineered lacteal complex (anti-MRSA BLC) in a murine septicemia model.

PubMed

Stoff, Jesse A; Nix, David E; DeYoung, D W

2006-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen of humans and other animals, causing septicemia, abcessation, toxemia, and other infectious diseases. Refined bioengineered lacteal complex (BLC), made specifically against MRSA, is a novel complex of low molecular weight immunogenic and antimicrobial molecules. It was evaluated in vivo using a mouse model of MRSA-induced peritonitis. Intraperitoneal dosing of anti-MRSA BLC demonstrated a therapeutic effect (83% survival) against an intraperitoneal MRSA challenge that caused 100% mortality in untreated animals. Anti-MRSA BLC is a promising therapeutic modality for MRSA infection.

Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

PubMed Central

Randazzo, James; Zhang, Peng; Makita, Jun; Blessing, Karen; Kador, Peter F.

2011-01-01

Background Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation. Methods/Principal Findings Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic “sugar” cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic “sugar” cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress. Conclusions/Significance Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed. PMID:21541328

Protection of the aged substantia nigra of the rat against oxidative damage by (-)-deprenyl.

PubMed Central

de la Cruz, C. P.; Revilla, E.; Steffen, V.; Rodríguez-Gómez, J. A.; Cano, J.; Machado, A.

1996-01-01

1. We have studied the effect of (-)-deprenyl on the oxidative damage that the rat substantia nigra suffers during aging. 2. (-)-Deprenyl (2 mg kg-1, three times a week) administered for two months, beginning at 22 months of age, produced a significant increase in tyrosine hydroxylase (TH) activity (2.67 +/- 0.40 and 3.64 +/- 0.38 nmol mg-1 protein h-1 in untreated aged rats and treated aged rats respectively, P < 0.05) and in TH amount (0.072 +/- 0.012 and 0.128 +/- 0.38 absorbance 405 nm in untreated aged and treated aged rats respectively, P < 0.05). 3. The proteins of aged rat substantia nigra showed a significant decrease of carbonyl groups in treated animals compared with saline-injected control rats (136.2 +/- 21.8 and 71.5 +/- 13.2 c.p.m. microgram-1 protein in untreated aged and treated aged rats respectively, P < 0.05). 4. The carbonyl groups measured in TH enzyme showed a statistically significant decrease (42.3%) after (-)-deprenyl treatment (471.4 +/- 73.0 and 271.9 +/- 50.00 c.p.m. in untreated aged and treated aged rats respectively, P < 0.001). 5. All these results suggest that oxidative damage produced during aging is prevented by (-)-deprenyl treatment and could explain the effect of this drug in Parkinson's disease (PD) and other degenerative diseases such as Alzheimer's disease. PMID:8732287

Protective effects of oleuropein against renal injury oxidative damage in alloxan-induced diabetic rats; a histological and biochemical study.

PubMed

Ahmadvand, Hassan; Shahsavari, Gholamreza; Tavafi, Majid; Bagheri, Shahrokh; Moradkhani, Mohamad Reza; Kkorramabadi, Reza Mohammadrezaei; Khosravi, Peyman; Jafari, Maryam; Zahabi, Khadije; Eftekhar, Reza; Soleimaninejad, Maryam; Moghadam, Sanaz

2017-07-01

Oleuropein is a potent antioxidant and free-radical scavenger with antiinflammatory properties. In the present study, we evaluated the protective effects of oleuropein on myeloperoxidase (MPO) activity, nitrite, urea, creatinine and glomerulosclerosis in alloxan-induced type 1 diabetic rats. Thirty Sprague-Dawley male rats were randomly divided into 3 groups: group 1 as control; group 2 as untreated diabetic; and group 3 as treated with oleuropein 15 mg/kg i.p daily. Diabetes was induced in the second and third groups by subcutaneous alloxan injection. After 48 days, the animals were anaesthetized and then the livers and kidneys were removed immediately and used fresh or kept frozen until MPO activity analysis. Blood samples were also collected before sacrificing to measure nitrite, urea, and creatinine. Kidney paraffin sections were prepared to estimate glomerular volume, leukocyte infiltration, and glomerulosclerosis. Oleuropein significantly decreased leukocyte infiltration and glomerulosclerosis in the treated group compared with the diabetic untreated group. Oleuropein significantly decreased the levels of urea, nitrite, and creatinine in the treated group compared with the diabetic untreated group. Moreover, oleuropein significantly decreased MPO activity in the treated group compared with the diabetic untreated group. Oleuropein has antioxidative and antiatherogenic activities and exerts beneficial effects on inflammation and kidney function test and decreases diabetic complication in diabetic rats.

A transgenic male-only strain of the New World screwworm for an improved control program using the sterile insect technique

USDA-ARS?s Scientific Manuscript database

The New World screwworm (NWS), Cochliomyia hominivorax, is a devastating pest of livestock endemic to sub-tropical and tropical regions of the Western Hemisphere. The larvae feed on the tissue of living animals, including man, and can cause death if untreated. Over 60 years ago the sterile insect te...

Chemotherapeutic Studies on Schistosomiasis.

DTIC Science & Technology

1978-10-01

sick ’ wor m s posses sing little movement is evidence of possible activity requiring further testing. Untreated control animal s will norma lly show...be re- peated for confirmation . a ;‘~~~~. . t 4 . -.. -...~~~~~~~~~~~~ -.-- .~~ -- L ITE RAT U RE C ITED 1 . Radke , 11. G., Berrios- Duran , L. A

Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver.

PubMed

Francis, Sheena; Laurieri, Nicola; Nwokocha, Chukwuemeka; Delgoda, Rupika

2016-05-31

The effect of apocynin on the activity of arylamine N-acetyltransferases (NATs) in excised liver samples was examined using eighteen Sprague-Dawley rats. Three groups of six animals each were fed a normal diet alone or a treatment of 50 or 100 mg/kg/day of apocynin via gavages for eight (8) weeks. Chronic in vivo administration of apocynin led to significant (p < 0.001) reduction of in vitro liver NAT activity up to 93% as compared with untreated rats (18.80 ± 2.10 μmols p-anisidine/min/μg liver protein). In vitro exposure of untreated liver homogenates to apocynin led to a dose-dependent inhibition of NAT activity with IC50 = 0.69 ± 0.02 mM. In silico modelling of apocynin tautomers and radical species into human NAT crystal structures supported the hypothesis that thiol functionalities in NAT enzymes may be crucial in apocynin binding. The involvement of human NAT enzymes in different pathological conditions, such as cancer, has encouraged the research for selective NAT inhibitors in both humans and animal models with possible chemopreventive properties.

Antioxidant effects of açaí seed ( Euterpe oleracea ) in anorexia-cachexia syndrome induced by Walker-256 tumor.

PubMed

Nascimento, Vitor Hugo Nunes do; Lima, Carla Dos Santos; Paixão, Jorge Tadeu Campos; Freitas, Jofre Jacob da Silva; Kietzer, Katia Simone

2016-09-01

To assess antioxidant effects of açaí seed extract on anorexia-cachexia induced by Walker-256 tumor. A population of 20 lab rats were distributed into four groups (n=5): Control Group (CG), which only received tumor inoculation. Experimental Group-100 (EG-100), with animals submitted to tumor inoculation and treated with seed extract in a 100 mg / ml concentration through gavage. Experimental Group-200 (EG-200), with animals submitted to tumor inoculation and treated with seed extract in a 200 mg / ml concentration. Placebo Group (GP), which received tumor inoculation and ethanol-water solution. We analyzed proteolysis, lipid peroxidation, tumor diameter and weight. Lipid peroxidation was representative only in the cerebral cortex, where there was more oxidative stress in rats treated with the extract (p = 0.0276). For proteolysis, there was less muscle damage in untreated rats (p = 0.0312). Only tumor diameter in treated rats was significantly lower (p = 0.0200) compared to untreated ones. The açaí seed extract showed no beneficial effect on the general framework of the cachectic syndrome in lab rats. However, some anticarcinogenic effects were observed in the tumor diameter and weight.

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

PubMed

Kent, Tiffany L; Glybina, Inna V; Abrams, Gary W; Iezzi, Raymond

2008-01-01

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

On-command drug release from nanochains inhibits growth of breast tumors

PubMed Central

Peiris, Pubudu M.; Tam, Morgan; Vicente, Peter; Abramowski, Aaron; Toy, Randall; Bauer, Lisa; Mayer, Aaron; Pansky, Jenna; Doolittle, Elizabeth; Tucci, Samantha; Schmidt, Erik; Shoup, Christopher; Rao, Swetha; Murray, Kaitlyn; Gopalakrishnan, Ramamurthy; Keri, Ruth A.; Basilion, James P.; Griswold, Mark A.; Karathanasis, Efstathios

2013-01-01

Purpose To evaluate the ability of radiofrequency (RF)-triggered drug release from a multicomponent chain-shaped nanoparticle to inhibit the growth of an aggressive breast tumor. Methods A two-step solid phase chemistry was employed to synthesize doxorubicin-loaded nanochains, which were composed of three iron oxide nanospheres and one doxorubicin-loaded liposome assembled in a 100-nm-long linear nanochain. The nanochains were tested in the Luc-GFP-4T1 orthotopic mouse model, which is a highly aggressive breast cancer model. The Luc-GFP-4T1 cell line stably expresses firefly luciferase, which allowed the non-invasive in vivo imaging of tumor response to the treatment using bioluminescence imaging (BLI). Results Longitudinal BLI imaging showed that a single nanochain treatment followed by application of RF resulted in an at least 100-fold lower BLI signal compared to the groups treated with nanochains (without RF) or free doxorubicin followed by RF. A statistically significant increase in survival time of the nanochain-treated animals followed by RF (64.3 days) was observed when compared to the nanochain-treated group without RF (35.7 days), free doxorubicin-treated group followed by RF (38.5 days), and the untreated group (30.5 days; n=5 animals per group). Conclusions These studies showed that the combination of RF and nanochains has the potential to effectively treat highly aggressive cancers and prolong survival. PMID:23934254

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

Rebamipide Improves Chronic Inflammation in the Lesser Curvature of the Corpus after Helicobacter pylori Eradication: A Multicenter Study

PubMed Central

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369. PMID:26060821

Enhanced antioxidant capacity following selenium supplemented antimalarial therapy in Plasmodium berghei infected mice

NASA Astrophysics Data System (ADS)

Adebayo, Abiodun Humphrey; Olasehinde, Grace Iyabo; Egbeola, Oluwaseun Ayodimeji; Yakubu, Omolara Faith; Adeyemi, Alaba Oladipupo; Adekeye, Bosede Temitope

2018-04-01

The effect of the co-administration of artemether, lumefantrine and selenium was studied in mice infected with Plasmodium bergheiparasite. The mice were divided into seven groups of six animals per group. All groups except A were parasitized. Group A (unparasitized/untreated) and B (parasitized/untreated) served as the positive and negative control respectively, these were administered with olive oil. Animals in groups C and D were treated with 8 and 48 mg/kg/bw of artemether and lumefantrine respectively while group E was treated with a combination of artemether and lumefantrine (8: 48 mg/kg/bw). Animals in group F were treated with 0.945 mg/kg/bw of selenium only and group G was treated with a combination of artemether, lumefantrine and selenium (8:48:0.945 mg/kg/bw). All the treatment was done for a three day period. These animals were subsequently anaesthetized and the organs were excised. Homogenates were prepared for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, reduced Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) assays. The results showed a significant (p<0.05) difference in the levels of ALP and MDA in group B, while a significant difference was observed in the levels of ALP, total protein, CAT and MDA in group G when compared with the parasitized group. Histopathological analysis showed no presence of inflammatory cells in group G when compared with group B. It may be concluded that the combination of artemether, lumefantrine and selenium showed a more potent effect against the parasite than the group treated with artemether and lumefantrine, thus, helps to combat post-infection oxidative stress in susceptible cells.

Use of activated protein C has no avail in the early phase of acute pancreatitis.

PubMed

Akay, Sinan; Ozutemiz, Omer; Yenisey, Cigdem; Simsek, Nilufer Genc; Yuce, Gul; Batur, Yucel

2008-01-01

Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

Toxicity of chromated copper arsenate (CCA)-treated wood to non-target marine fouling communities in Langstone Harbour, Portsmouth, UK.

PubMed

Brown, C J; Eaton, R A

2001-04-01

The effect of the anti-marine-borer timber preservative chromated copper arsenate (CCA) (a pressure impregnated solution of copper, chromium and arsenic compounds) on non-target marine fouling animals was investigated during a subtidal exposure trial. Panels of Scots pine treated to target retentions of 12, 24 and 48 kg CCA per m-3 of wood, plus untreated controls were submerged at a coastal site on the south coast of the UK for 6, 12 and 18 months. After each exposure period the fouling communities that formed on the surface of panels were assessed both qualitatively and quantitatively. Community structure was similar on panels treated to the three CCA loadings, but was significantly different from community structure on untreated panels. The total number of species (species richness) was similar on all panels, although the number of individual organisms attached to the surface of panels was significantly higher on CCA-treated panels than on untreated panels. k-dominance curves revealed that the difference in numbers of individuals between CCA-treated and untreated panels was caused by higher numbers of the dominant species (Elminius modestus, Hydroides ezoensis, and Electra pilosa) on CCA-treated panels. Other species were present in similar numbers on panels of all treatments. Results indicate that there are no detrimental toxic effects to epibiota caused by the presence of CCA preservative within the matrix of the wood at any of the treatment levels. Differences in community structure between CCA-treated and untreated panels may be due to enhanced larval settlement on CCA-treated timber by some species as a result of modifications to the surface properties of the timber by the CCA preservative.

Evaluation of the efficacy of oxytetracycline treatment followed by vaccination against Q fever in a highly infected sheep flock.

PubMed

Astobiza, Ianire; Barandika, Jesús F; Juste, Ramón A; Hurtado, Ana; García-Pérez, Ana L

2013-04-01

The aim of this research was to evaluate the efficacy of oxytetracycline treatment following an outbreak of Q fever in a sheep flock when gestation is too advanced for vaccination to be used. In such cases, immediate application of antibiotics is needed and vaccination postponed until the next breeding season. Seventy-five per cent of ewes from a dairy sheep flock affected by Q fever were treated with oxytetracycline at approximately days 100 and 120 of gestation, with the remaining 25% of the animals kept as untreated controls. Vaginal swabs, faeces and milk samples from 81 ewes (57 treated, 24 untreated) were analysed by PCR within 30 days of lambing and revealed a high percentage of Coxiella burnetii shedders. No significant differences were found between groups in either the percentage of shedders or in the mean amount of bacteria shed. In the following season 75% of the ewes and 50% of the replacement ewe lambs were vaccinated with a phase I vaccine prior to artificial insemination. Both vaccinated and control groups were homogeneously composed of ewes treated and untreated with antibiotics in the previous season. The number of shedders and the bacterial excretion load decreased significantly compared to the previous season but no statistically significant differences were found between vaccinated and control groups. In addition, no significant effect derived from the application of oxytetracycline in the previous season was observed. Vaccination was repeated for the following two seasons, and the percentage of animal shedders was reduced to minimal levels highlighting the importance of vaccination over the longer term. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regulation of Baboon Fetal Ovarian Development by Placental Estrogen: Onset of Puberty Is Delayed in Offspring Deprived of Estrogen In Utero1

PubMed Central

Pepe, Gerald J.; Lynch, Terrie J.; Albrecht, Eugene D.

2013-01-01

ABSTRACT Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen. PMID:24132960

Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero.

PubMed

Pepe, Gerald J; Lynch, Terrie J; Albrecht, Eugene D

2013-12-01

Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen.

Does metaphyseal cement augmentation in fracture management influence the adjacent subchondral bone and joint cartilage?: an in vivo study in sheep stifle joints.

PubMed

Goetzen, Michael; Hofmann-Fliri, Ladina; Arens, Daniel; Zeiter, Stephan; Stadelmann, Vincent; Nehrbass, Dirk; Richards, R Geoff; Blauth, Michael

2015-01-01

Augmentation of implants with polymethylmethacrylate (PMMA) bone cement in osteoporotic fractures is a promising approach to increase implant purchase. Side effects of PMMA for the metaphyseal bone, particularly for the adjacent subchondral bone plate and joint cartilage, have not yet been studied. The following experimental study investigates whether subchondral PMMA injection compromises the homeostasis of the subchondral bone and/or the joint cartilage.Ten mature sheep were used to simulate subchondral PMMA injection. Follow-ups of 2 (4 animals) and 4 (6 animals) months were chosen to investigate possible cartilage damage and subchondral plate alterations in the knee. Evaluation was completed by means of high-resolution peripheral quantitative computed tomography (HRpQCT) imaging, histopathological osteoarthritis scoring, and determination of glycosaminoglycan content in the joint cartilage. Results were compared with the untreated contralateral knee and statistically analyzed using nonparametric tests.Evaluation of the histological osteoarthritis score revealed no obvious cartilage damage for the treated knee; median histological score after 2 months 0 (range 4), after 4 months 1 (range 5). There was no significant difference when compared with the untreated control site after 2 and 4 months (P = 0.23 and 0.76, respectively). HRpQCT imaging showed no damage to the metaphyseal trabeculae. Glycosaminoglycan measurements of the treated joint cartilage after 4 months revealed no significant difference compared with the untreated cartilage (P = 0.24).The findings of this study support initial clinical observation that PMMA implant augmentation of metaphyseal fractures appears to be a safe procedure for fixation without harming the subchondral bone plate and adjacent joint cartilage.

In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat.

PubMed

Jones, Michael D; Tran, Charles W; Li, Guang; Maksymowych, Walter P; Zernicke, Ronald F; Doschak, Michael R

2010-09-01

To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA). We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam. Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury. Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.

Characterisation of the biochemical methane potential (BMP) of individual material fractions in Danish source-separated organic household waste.

PubMed

Naroznova, Irina; Møller, Jacob; Scheutz, Charlotte

2016-04-01

This study is dedicated to characterising the chemical composition and biochemical methane potential (BMP) of individual material fractions in untreated Danish source-separated organic household waste (SSOHW). First, data on SSOHW in different countries, available in the literature, were evaluated and then, secondly, laboratory analyses for eight organic material fractions comprising Danish SSOHW were conducted. No data were found in the literature that fully covered the objectives of the present study. Based on laboratory analyses, all fractions were assigned according to their specific properties in relation to BMP, protein content, lipids, lignocellulose biofibres and easily degradable carbohydrates (carbohydrates other than lignocellulose biofibres). The three components in lignocellulose biofibres, i.e. lignin, cellulose and hemicellulose, were differentiated, and theoretical BMP (TBMP) and material degradability (BMP from laboratory incubation tests divided by TBMP) were expressed. Moreover, the degradability of lignocellulose biofibres (the share of volatile lignocellulose biofibre solids degraded in laboratory incubation tests) was calculated. Finally, BMP for average SSOHW composition in Denmark (untreated) was calculated, and the BMP contribution of the individual material fractions was then evaluated. Material fractions of the two general waste types, defined as "food waste" and "fibre-rich waste," were found to be anaerobically degradable with considerable BMP. Material degradability of material fractions such as vegetation waste, moulded fibres, animal straw, dirty paper and dirty cardboard, however, was constrained by lignin content. BMP for overall SSOHW (untreated) was 404 mL CH4 per g VS, which might increase if the relative content of material fractions, such as animal and vegetable food waste, kitchen tissue and dirty paper in the waste, becomes larger. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rumen fermentation and liveweight gain in beef cattle treated with monensin and grazing lush forage.

PubMed

Packer, E L; Clayton, E H; Cusack, P M V

2011-09-01

To determine the prevalence of subacute rumen acidosis (SARA) in beef cattle grazing lush pasture and the effect of monensin on reducing SARA and improving animal performance. Commercial Angus and Murray Grey steers received a monensin slow-release capsule (n = 19) or remained untreated (n = 19). Cattle grazed an oats crop or tetraploid ryegrass pasture for a total of 91 days. Rumen fluid pH, volatile fatty acids (VFA) and lactic acid concentrations and body weight data were collected prior to treatment and again 28, 56 and 91 days after treatment. Changes in measures over time were analysed using mixed model repeated measures analysis. Differences in average daily gain between treatment groups were determined. The prevalence of SARA was low during the study, with only one animal satisfying criteria for SARA at one time point. Cattle treated with monensin capsules were 11.9 kg heavier at the completion of the study compared with untreated controls (414.5 ± 3.88 kg vs 402.6 ± 4.03 kg, P = 0.04). Rumen VFA and L- and D-lactate levels did not differ between cattle treated with monensin and untreated cattle. However, the ratio of propionate to acetate plus two times butyrate was higher (P < 0.001) when cattle were treated with monensin. Subacute rumen acidosis was not consistently detected under the conditions of the study. The higher body weight of cattle treated with monensin may have been due to improved energy utilisation of the pasture, indicated by increased propionate proportions in the rumen, rather than prevention of SARA. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta

PubMed Central

Meganck, J.A.; Begun, D.L.; McElderry, J.D.; Swick, A.; Kozloff, K.M.; Goldstein, S.A.; Morris, M.D.; Marini, J.C.; Caird, M.S.

2014-01-01

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5 weeks of healing, tibiae were assessed using microcomputed tomography (μCT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5 weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl/+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture. PMID:23774443

A new anti-glioma therapy, AG119: pre-clinical assessment in a mouse GL261 glioma model.

PubMed

Towner, Rheal A; Ihnat, Michael; Saunders, Debra; Bastian, Anja; Smith, Nataliya; Pavana, Roheeth Kumar; Gangjee, Aleem

2015-07-17

High grade gliomas (HGGs; grades III and IV) are the most common primary brain tumors in adults, and their malignant nature ranks them fourth in incidence of cancer death. Standard treatment for glioblastomas (GBM), involving surgical resection followed by radiation and chemotherapy with temozolomide (TMZ) and the anti-angiogenic therapy bevacizumab, have not substantially improved overall survival. New therapeutic agents are desperately needed for this devastating disease. Here we study the potential therapeutic agent AG119 in a pre-clinical model for gliomas. AG119 possesses both anti-angiogenic (RTK inhibition) and antimicrotubule cytotoxic activity in a single molecule. GL261 glioma-bearing mice were either treated with AG119, anti-VEGF (vascular endothelial growth factor) antibody, anti c-Met antibody or TMZ, and compared to untreated tumor-bearing mice. Animal survival was assessed, and tumor volumes and vascular alterations were monitored with morphological magnetic resonance imaging (MRI) and perfusion-weighted imaging, respectively. Percent survival of GL261 HGG-bearing mice treated with AG119 was significantly higher (p < 0.001) compared to untreated tumors. Tumor volumes (21-31 days following intracerebral implantation of GL261 cells) were found to be significantly lower for AG119 (p < 0.001), anti-VEGF (p < 0.05) and anti-c-Met (p < 0.001) antibody treatments, and TMZ-treated (p < 0.05) mice, compared to untreated controls. Perfusion data indicated that both AG119 and TMZ were able to reduce the effect of decreasing perfusion rates significantly (p < 0.05 for both), when compared to untreated tumors. It was also found that IC50 values for AG119 were much lower than those for TMZ in T98G and U251 cells. These data support further exploration of the anticancer activity AG119 in HGG, as this compound was able to increase animal survival and decrease tumor volumes in a mouse GL261 glioma model, and that AG119 is also not subject to methyl guanine transferase (MGMT) mediated resistance, as is the case with TMZ, indicating that AG119 may be potentially useful in treating resistant gliomas.

Deuterated methoxyflurane anesthesia and renal function in Fischer 344 rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baden, J.M.; Rice, S.A.; Mazze, R.I.

1982-03-01

Inorganic fluoride (F-) production and renal function were assessed in six groups of Fischer 344 rats administered either methoxyflurane (MOF) or deuterated methoxyflurane (d4-MOF). One untreated and one phenobarbital (PB)-treated group were exposed for two hours to either air, 0.5 per cent (V/v) MOF, or 0.5 per cent (v/v) d4-MOF. Serum and urinary F- and serum urea nitrogen and creatinine were measured. Urine volume and urinary F- excretion were only slightly greater among MOF than among d4-MOF exposed animals. Pretreatment with PB, however, greatly enhanced F- production in MOF-exposed animals leading to marked renal impairment but only slightly enhanced F-more » production in d4-MOF animals leading to mild renal impairment. Thus, only in PB-pretreated animals could a biologically significant difference in nephrotoxicity be demonstrated for MOF and d4-MOF.« less

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

PubMed

Trivillin, Verónica A; Pozzi, Emiliano C C; Colombo, Lucas L; Thorp, Silvia I; Garabalino, Marcela A; Monti Hughes, Andrea; González, Sara J; Farías, Rubén O; Curotto, Paula; Santa Cruz, Gustavo A; Carando, Daniel G; Schwint, Amanda E

2017-11-01

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Interventions to improve cardiopulmonary hemodynamics during laparoscopy in a porcine sepsis model.

PubMed

Grief, W M; Forse, R A

1999-11-01

Laparoscopy is increasingly used in severely ill and acutely septic patients. In animals undergoing laparoscopy, the hemodynamic response to sepsis is blunted. Specific interventions to augment the hemodynamic potential may make laparoscopic intervention a safer alternative in septic patients. We compared different interventions to improve hemodynamic performance during exploratory laparoscopy in a porcine endotoxic shock model. Domestic pigs (n = 12) received intravenous lipopolysaccharide injection and underwent surgical abdominal exploration using either laparoscopy or conventional laparotomy. For comparison, pigs exposed to endotoxin underwent laparoscopy with these interventions: intravenous infusions of prostacyclin (n = 5) or indomethacin (n = 4), intravenous crystalloid resuscitation (n = 5), pulmonary hyperventilation (n = 4), or abdominal insufflation with air (n = 5). Hemodynamic measurements and blood gas analyses were obtained using Swan-Ganz and arterial catheters. Septic animals treated with prostacyclin undergoing laparoscopy had a higher cardiac index (CI, p < 0.01), stroke volume (SV; p < 0.001) and oxygen delivery (p < 0.05) than the untreated group. Likewise, treatment with indomethacin was associated with a higher CI (p < 0.001), SV (p < 0.005), and oxygen delivery (p < 0.005) compared with the untreated group. These effects may be secondary to a decreased pulmonary vascular resistance, demonstrated in the animals that received either prostacyclin (p < 0.05) or indomethacin (p < 0.05). In addition, animals given aggressive fluid resuscitation had a significantly higher CI (p < 0.05) and SV (p < 0.001) than those with normal fluid resuscitation during laparoscopy. Manipulation of arterial pH by insufflation of the abdomen with air to create the pneumoperitoneum, or by aggressively hyperventilating the animals, did not improve CI. Adverse effects of laparoscopy on cardiovascular hemodynamics in the septic state may be mediated by increased pulmonary vascular resistance, diminished venous return, or both. Specific interventions to reverse these variables may ameliorate hemodynamic changes seen.

Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury.

PubMed

Mikolka, P; Kopincova, J; Tomcikova Mikusiakova, L; Kosutova, P; Antosova, M; Calkovska, A; Mokra, D

2016-02-01

Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free radicals compared to controls (P < 0.05). Surfactant therapy, but particularly combined surfactant + budesonide therapy reduced markers of oxidative stress versus untreated animals (P < 0.05). In conclusion, budesonide added into surfactant enhanced effect of therapy on oxidative damage of the lung.

Cutaneous anthrax associated with drum making using goat hides from West Africa--Connecticut, 2007.

PubMed

2008-06-13

On August 29, 2007, the Connecticut Department of Public Health was notified by a physician of suspect cutaneous anthrax involving a drum maker and one of his three children. The drum maker had been working with untreated goat hides from Guinea in West Africa. This report summarizes results of the joint epidemiologic and environmental investigation conducted by public health officials, environmental agencies, and law enforcement authorities. The investigation revealed that the drum maker was exposed while working with a contaminated goat hide from Guinea and that his workplace and home were contaminated with anthrax. His child was most likely exposed from cross-contamination of the home. The findings underscore the potential hazard of working with untreated animal hides from areas with epizootic anthrax and the potential for secondary cases from environmental contamination.

Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pieper, Claus C., E-mail: claus.christian.pieper@ukb.uni-bonn.de; Meyer, Carsten, E-mail: Carsten.Meyer@ukb.uni-bonn.de; Vollmar, Brigitte, E-mail: brigitte.vollmar@med.uni-rostock.de

BackgroundThis study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.MethodsIn four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.ResultsHepatic arterial embolization using DSMs was technically successfulmore » in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.ConclusionTemporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study.« less

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

PubMed

Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

2005-10-01

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

Joint instability leads to long-term alterations to knee synovium and osteoarthritis in a rabbit model.

PubMed

Egloff, C; Hart, D A; Hewitt, C; Vavken, P; Valderrabano, V; Herzog, W

2016-06-01

Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the in vivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model. Ten 1-year-old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90 days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system. Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-β, IL-1 and IL-6 compared to the healthy controls. BTX-A induced joint instability in a muscle weakness model uniquely leads to alterations in gene expression and histological changes in the synovial membranes and cartilage in otherwise intact knee joints. These results lead to the conclusion that joint instability may promote an inflammatory intraarticular milieu, thereby contributing to the development of OA. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Cryptosporidium spp. and Giardia duodenalis as pathogenic contaminants of water in Galicia, Spain: the need for safe drinking water.

PubMed

Castro-Hermida, José Antonio; González-Warleta, Marta; Mezo, Mercedes

2015-01-01

The objectives of this cross-sectional study were to detect the presence of Cryptosporidium spp. and Giardia duodenalis in drinking water treatments plants (DWTPs) in Galicia (NW Spain) and to identify which species and genotype of these pathogenic protozoans are present in the water. Samples of untreated water (surface or ground water sources) and of treated drinking water (in total, 254 samples) were collected from 127 DWTPs and analysed by an immunofluorescence antibody test (IFAT) and by PCR. Considering the untreated water samples, Cryptosporidium spp. were detected in 69 samples (54.3%) by IFAT, and DNA of this parasite was detected in 57 samples (44.8%) by PCR, whereas G. duodenalis was detected in 76 samples (59.8%) by IFAT and in 56 samples (44.0%) by PCR. Considering the treated drinking water samples, Cryptosporidium spp. was detected in 52 samples (40.9%) by IFAT, and the parasite DNA was detected in 51 samples (40.1%) by PCR, whereas G. duodenalis was detected in 58 samples (45.6%) by IFAT and in 43 samples (33.8%) by PCR. The percentage viability of the (oo)cysts ranged between 90.0% and 95.0% in all samples analysed. Cryptosporidium andersoni, C. hominis, C. parvum and assemblages A-I, A-II, E of G. duodenalis were identified. The results indicate that Cryptosporidium spp. and G. duodenalis are widespread in the environment and that DWTPs are largely ineffective in reducing/inactivating these pathogens in drinking water destined for human and animal consumption in Galicia. In conclusion, the findings suggest the need for better monitoring of water quality and identification of sources of contamination. Copyright © 2014 Elsevier GmbH. All rights reserved.

Seroepidemiology of Hepatitis E Virus Infection in General Population in Rural Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus

2014-01-01

Background: The seroepidemiology of hepatitis E virus (HEV) infection in rural areas in Mexico has been poorly studied. Objectives: The aim of the study was to determine the seroprevalence and correlates of anti-HEV IgG antibodies in adults in rural areas in Durango, Mexico. Materials and Methods: We performed a cross-sectional study to determine the frequency of anti-HEV IgG antibodies in 273 adults living in rural Durango, Mexico using an enzyme-linked immunoassay. In addition, we searched for an association of HEV exposure with the socio-demographic and behavioral characteristics of the subjects studied. Results: One hundred (36.6%) of the 273 rural adults (mean age: 39.85 ± 17.15 years) had anti-HEV IgG antibodies. Multivariate analysis of socio-demographic and behavioral characteristics of the participants showed that HEV exposure was associated with increasing age (OR = 1.04; 95% CI: 1.04-1.05; P < 0.001), consumption of untreated water (OR = 1.92; 95% CI: 1.06-3.46; P = 0.03), and availability of water at home (OR = 1.87; 95% CI: 1.07-3.27; P = 0.02). In contrast, other socio-demographic and behavioral characteristics including educational level, occupation, socio-economic status, foreign travel, consumption of unwashed raw fruits, consumption of raw or undercooked meat and raising animals did not show associations with HEV exposure. Conclusions: The seroprevalence of HEV infection found in rural Durango is higher than those reported in other Mexican populations. Consumption of untreated water is an important factor for HEV exposure in rural areas in Durango. The correlates of HEV seropositivity found in the present study can be used for an optimal planning of preventive measures against HEV infection. PMID:24976837

Endothelin Receptor-A Antagonist Attenuates Retinal Vascular and Neuroretinal Pathology in Diabetic Mice

PubMed Central

Chou, Jonathan C.; Rollins, Stuart D.; Ye, Minghao; Batlle, Daniel; Fawzi, Amani A.

2014-01-01

Purpose. We sought to determine the effects of atrasentan, a selective endothelin-A receptor antagonist, on the retinal vascular and structural integrity in a db/db mouse, an animal model of type 2 diabetes and diabetic retinopathy. Methods. Diabetic mice, 23 weeks old, were given either atrasentan or vehicle treatment in drinking water for 8 weeks. At the end of the treatment period, eyes underwent trypsin digest to assess the retinal vascular pathology focusing on capillary degeneration, endothelial cell, and pericyte loss. Paraffin-embedded retinal cross sections were used to evaluate retinal sublayer thickness both near the optic nerve and in the retinal periphery. Immunohistochemistry and TUNEL assay were done to evaluate retinal cellular and vascular apoptosis. Results. Compared with untreated db/db mice, atrasentan treatment was able to ameliorate the retinal vascular pathology by reducing pericyte loss (29.2% ± 0.4% vs. 44.4% ± 2.0%, respectively, P < 0.05) and capillary degeneration as determined by the percentage of acellular capillaries (8.6% ± 0.3% vs. 3.3% ± 0.41%, respectively, P < 0.05). A reduction in inner retinal thinning both at the optic nerve and at the periphery in treated diabetic mice was also observed in db/db mice treated with atrasentan as compared with untreated db/db mice (P < 0.05). TUNEL assay suggested that atrasentan may decrease enhanced apoptosis in neuroretinal layers and vascular pericytes in the db/db mice. Conclusions. Endothelin-A receptor blockade using atrasentan significantly reduces the vascular and neuroretinal complications in diabetic mice. Endothelin-A receptor blockade is a promising therapeutic target in diabetic retinopathy. PMID:24644048

Significant Improvement in Cloning Efficiency of an Inbred Miniature Pig by Histone Deacetylase Inhibitor Treatment after Somatic Cell Nuclear Transfer1

PubMed Central

Zhao, Jianguo; Ross, Jason W.; Hao, Yanhong; Spate, Lee D.; Walters, Eric M.; Samuel, Melissa S.; Rieke, August; Murphy, Clifton N.; Prather, Randall S.

2009-01-01

The National Institutes of Health (NIH) miniature pig was developed specifically for xenotransplantation and has been extensively used as a large-animal model in many other biomedical experiments. However, the cloning efficiency of this pig is very low (<0.2%), and this has been an obstacle to the promising application of these inbred swine genetics for biomedical research. It has been demonstrated that increased histone acetylation in somatic cell nuclear transfer (SCNT) embryos, by applying a histone deacetylase (HDAC) inhibitor such as trichostatin A (TSA), significantly enhances the developmental competence in several species. However, some researchers also reported that TSA treatment had various detrimental effects on the in vitro and in vivo development of the SCNT embryos. Herein, we report that treatment with 500 nM 6-(1,3-dioxo-1H, 3H-benzo[de]isoquinolin-2-yl)-hexanoic acid hydroxyamide (termed scriptaid), a novel HDAC inhibitor, significantly enhanced the development of SCNT embryos to the blastocyst stage when NIH inbred fetal fibroblast cells (FFCs) were used as donors compared with the untreated group (21% vs. 9%, P < 0.05). Scriptaid treatment resulted in eight pregnancies from 10 embryo transfers (ETs) and 14 healthy NIH miniature pigs from eight litters, while no viable piglets (only three mummies) were obtained from nine ETs in the untreated group. Thus, scriptaid dramatically increased the cloning efficiency when using inbred genetics from 0.0% to 1.3%. In contrast, scriptaid treatment decreased the blastocyst rate in in vitro fertilization embryos (from 37% to 26%, P < 0.05). In conclusion, the extremely low cloning efficiency in the NIH miniature pig may be caused by its inbred genetic background and can be improved by alteration of genomic histone acetylation patterns. PMID:19386991

Significant improvement in cloning efficiency of an inbred miniature pig by histone deacetylase inhibitor treatment after somatic cell nuclear transfer.

PubMed

Zhao, Jianguo; Ross, Jason W; Hao, Yanhong; Spate, Lee D; Walters, Eric M; Samuel, Melissa S; Rieke, August; Murphy, Clifton N; Prather, Randall S

2009-09-01

The National Institutes of Health (NIH) miniature pig was developed specifically for xenotransplantation and has been extensively used as a large-animal model in many other biomedical experiments. However, the cloning efficiency of this pig is very low (<0.2%), and this has been an obstacle to the promising application of these inbred swine genetics for biomedical research. It has been demonstrated that increased histone acetylation in somatic cell nuclear transfer (SCNT) embryos, by applying a histone deacetylase (HDAC) inhibitor such as trichostatin A (TSA), significantly enhances the developmental competence in several species. However, some researchers also reported that TSA treatment had various detrimental effects on the in vitro and in vivo development of the SCNT embryos. Herein, we report that treatment with 500 nM 6-(1,3-dioxo-1H, 3H-benzo[de]isoquinolin-2-yl)-hexanoic acid hydroxyamide (termed scriptaid), a novel HDAC inhibitor, significantly enhanced the development of SCNT embryos to the blastocyst stage when NIH inbred fetal fibroblast cells (FFCs) were used as donors compared with the untreated group (21% vs. 9%, P < 0.05). Scriptaid treatment resulted in eight pregnancies from 10 embryo transfers (ETs) and 14 healthy NIH miniature pigs from eight litters, while no viable piglets (only three mummies) were obtained from nine ETs in the untreated group. Thus, scriptaid dramatically increased the cloning efficiency when using inbred genetics from 0.0% to 1.3%. In contrast, scriptaid treatment decreased the blastocyst rate in in vitro fertilization embryos (from 37% to 26%, P < 0.05). In conclusion, the extremely low cloning efficiency in the NIH miniature pig may be caused by its inbred genetic background and can be improved by alteration of genomic histone acetylation patterns.

Increased Platelet Concentration does not Improve Functional Graft Healing in Bio-Enhanced ACL Reconstruction

PubMed Central

Fleming, Braden C.; Proffen, Benedikt L.; Vavken, Patrick; Shalvoy, Matthew R.; Machan, Jason T.; Murray, Martha M.

2014-01-01

Purpose The use of an extra-cellular matrix scaffold (ECM) combined with platelets to enhance healing of an ACL graft (“bio-enhanced ACL reconstruction”) has shown promise in animal models. However, the effects of platelet concentration on graft healing remains unknown. The objectives of this study were to determine if increasing the platelet concentration in the ECM scaffold would; 1) improve the graft biomechanical properties, and 2) decrease cartilage damage after surgery. Methods Fifty-five adolescent minipigs were randomized to 5 treatment groups; untreated ACL transection (n=10), conventional ACL reconstruction (n=15), and bio-enhanced ACL reconstruction using 1X (n=10), 3X (n=10) or 5X (n=10) platelet-rich plasma. The graft biomechanical properties, anteroposterior (AP) knee laxity, graft histology and macroscopic cartilage integrity were measured at 15 weeks. Results The mean linear stiffness of the bio-enhanced ACL reconstruction procedure using the 1X preparation was significantly greater than traditional reconstruction while the 3X and 5X preparations were not. The failure loads of all the ACL reconstructed groups were equivalent but significantly greater than untreated ACL transection. There were no significant differences in the ligament maturity index or AP laxity between reconstructed knees. Macroscopic cartilage damage was relatively minor, though significantly less when the ECM-platelet composite was used. Conclusions Only the 1X platelet concentration improved healing over traditional ACL reconstruction. Increasing the platelet concentration from 1X to 5X in the ECM scaffold did not further improve the graft mechanical properties. The use of an ECM-platelet composite decreased the amount of cartilage damage seen after ACL surgery. PMID:24633008

Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats

PubMed Central

Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

2017-01-01

Background Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. Objectives This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. Methods In this experimental study, 16 male Wistar rats weighing 200 – 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Results Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P < 0.01). Treatment with 400 mg/kg of the extract reduced arginase I activity and expression (P < 0.05). A significant elevation in body weight was observed in diabetic rats treated with the extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P < 0.05). Conclusions Our results suggest that the Z. officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina. PMID:28835766

A new feature extraction method and classification of early stage Parkinsonian rats with and without DBS treatment.

PubMed

Iravani, B; Towhidkhah, F; Roghani, M

2014-12-01

Parkinson Disease (PD) is one of the most common neural disorders worldwide. Different treatments such as medication and deep brain stimulation (DBS) have been proposed to minimize and control Parkinson's symptoms. DBS has been recognized as an effective approach to decrease most movement disorders of PD. In this study, a new method is proposed for feature extraction and separation of treated and untreated Parkinsonan rats. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5 μg/5 μl of saline-ascorbate)-lesioned rats were treated with DBS. We performed a behavioral experiment and video tracked traveled trajectories of rats. Then, we investigated the effect of deep brain stimulation of subthalamus nucleus on their behavioral movements. Time, frequency and chaotic features of traveled trajectories were extracted. These features provide the ability to quantify the behavioral movements of Parkinsonian rats. The results showed that the traveled trajectories of untreated were more convoluted with the different time/frequency response. Compared to the traditional features used before to quantify the animals' behavior, the new features improved classification accuracy up to 80 % for untreated and treated rats.

Peripheral lymphocyte subsets in chronic hepatitis C: Effects of 12 weeks of antiviral treatment with interferon-alpha plus ribavirin.

PubMed

Oliveira, Isabela S; Carvalho, Lucas P; Schinoni, Maria Isabel; Paraná, Raymundo; Atta, Ajax M; Atta, Maria Luiza B Sousa

2016-02-01

Chronic infection with hepatitis C virus (HCV) causes a quantitative and functional alteration in innate and adaptative immunity. In the present work, we determined by flow-cytometry the profile of blood lymphocyte of untreated HCV patients and in subjects of this group that achieved or not an early virologic response at 12-weeks of treatment with interferon-α plus ribavirin. Twenty-six untreated HCV patients and 20 control healthy individuals were enrolled in the study. Untreated HCV patients had a higher proportion of B cell and a lower proportion of CD8(+) T cell and NK cells than healthy individuals did, but the proportions of CD4(+) T cells and Treg cells (CD4(+)CD25(+)Foxp3(+)) were similar in these patients and controls. Untreated HCV patients presenting cryoglobulinemia had a lower proportion of Treg cells and a lower Treg/NK cell ratio when compared with those without cryoglobulins. Nineteen out of 26 untreated HCV patients remained in the study and were treated with Interferon-α plus ribavirin. At 12-weeks of treatment, 10 of them achieved early virologic response (EVR), whereas 9 were non-responders (NR). EVR patients differed from NR patients in the increase of their proportion of NK cells at 12 weeks of treatment. In conclusion, untreated HCV patients exhibit an altered profile of blood lymphocyte subsets, including a reduction in the proportion of CD4(+)CD25(+)FoxP3(+)T regulatory cells in patients that present cryoglobulinemia. An early virological response at 12-weeks of treatment with IFN-α plus ribavirin seems to be associated a significant improvement in the proportion of NK cells of HCV treated patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

PubMed Central

Kamb, Mary L; Newman, Lori M; Mark, Jennifer; Broutet, Nathalie; Hawkes, Sarah J

2013-01-01

Abstract Objective To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Methods PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Findings Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0–74.1]; I2 = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8–17.2]; I2 = 95.9%; P < 0.001). Conclusion Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women. PMID:23476094

Health Services Determinants of the Duration of Untreated Psychosis Among African-American First-Episode Patients

PubMed Central

Compton, Michael T.; Ramsay, Claire E.; Shim, Ruth S.; Goulding, Sandra M.; Gordon, Tynessa L.; Weiss, Paul S.; Druss, Benjamin G.

2018-01-01

Objective The duration of untreated psychosis is associated with poor outcomes in multiple domains in the early course of nonaffective psychotic disorders, although relatively little is known about determinants of this critical period, particularly health services–level determinants. This study examined three hypothesized predictors of duration of untreated psychosis (lack of insurance, financial problems, and broader barriers) among urban, socioeconomically disadvantaged African Americans, while controlling for the effects of three patient-level predictors (mode of onset of psychosis, living with family versus alone or with others before hospitalization, and living above versus below the federally defined poverty level). Methods Analyses included data from 42 patient–family member dyads from a larger sample of 109 patients with a first episode of nonaffective psychosis. The duration of untreated psychosis and all other variables were measured in a rigorous, standardized fashion in a study designed specifically to examine determinants of treatment delay. Survival analyses and Cox regression assessed the effects of the independent predictors on time from onset of psychosis to hospital admission for initial evaluation and treatment. Results The median duration of untreated psychosis was 24.5 weeks. When the analyses controlled for the three patient-level covariates, patients without health insurance, with financial problems, or with barriers to seeking help had a significantly longer duration of untreated psychosis. Conclusions Health services–related factors, such as lack of insurance, are predictive of longer treatment delay. Efforts to eliminate uninsurance and underinsurance, as well as minimize barriers to treatment, would be beneficial for improving the prognosis of young patients with emerging nonaffective psychotic disorders. (Psychiatric Services 60:1489–1494, 2009) PMID:19880467

Sexual odor discrimination and physiological profiles in adult male rats after a neonatal, short term, reversible nasal obstruction.

PubMed

Thornton, S N; Padzys, G S; Trabalon, M

2014-05-01

The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult. Copyright © 2014 Elsevier Inc. All rights reserved.

Dental caries among children visiting a mobile dental clinic in South Central Kentucky: a pooled cross-sectional study

PubMed Central

2013-01-01

Background Dental caries is one of the most common chronic childhood diseases affecting a large portion of children in the United States. The prevalence of childhood dental caries in Kentucky is among the highest in the nation. The purposes of this study are to (1) compare sociodemographic differences between caries and no caries groups and (2) investigate factors associated with untreated dental caries among children who visited a mobile dental clinic in South Central Kentucky. Methods Study subjects were children aged 6 to 15 years who participated in the school-based dental sealant program through the mobile dental clinic operated by the Institute for Rural Health at Western Kentucky University between September 2006 and May 2011 (n = 2,453). Descriptive statistics were calculated for sociodemographic factors (age, gender, race/ethnicity, insurance status, and urban versus rural residential location) and caries status. We used chi-square tests to compare sociodemographic differences of children stratified by caries and no caries status as well as three levels of caries severity. We developed a logistic regression model to investigate factors associated with untreated dental caries while controlling for sociodemographic characteristics. Results The proportion of children having untreated dental caries was 49.7% and the mean number of untreated dental caries was 2.0. The proportion of untreated dental caries was higher in older children, children with no insurance and living in rural residential locations, and caries severity was also higher in these groups. Odds ratio indicated that older ages, not having private insurance (having only public, government-sponsored insurance or no insurance at all) and rural residential location were associated with having untreated dental caries after controlling for sociodemographic characteristics of children. Conclusions Untreated dental caries was more likely to be present in older children living in rural areas without insurance. Health interventionists may use this information and target rural children without having proper insurance in order to reduce geographic disparities in untreated dental caries in South Central Kentucky. PMID:23639250

Islet transplantation under the kidney capsule fully corrects the impaired skeletal muscle glucose transport system of streptozocin diabetic rats.

PubMed Central

Napoli, R; Davalli, A M; Hirshman, M F; Weitgasser, R; Weir, G C; Horton, E S

1996-01-01

Chronic insulin therapy improves but does not restore impaired insulin-mediated muscle glucose uptake in human diabetes or muscle glucose uptake, transport, and transporter translocation in streptozocin diabetic rats. To determine whether this inability is due to inadequate insulin replacement, we studied fasted streptozocin-induced diabetic Lewis rats either untreated or after islet transplantation under the kidney capsule. Plasma glucose was increased in untreated diabetics and normalized by the islet transplantation (110 +/- 5, 452 +/- 9, and 102 +/- 3 mg/dl in controls, untreated diabetics, and transplanted diabetics, respectively). Plasma membrane and intracellular microsomal membrane vesicles were prepared from hindlimb skeletal muscle of basal and maximally insulin-stimulated rats. Islet transplantation normalized plasma membrane carrier-mediated glucose transport Vmax, plasma membrane glucose transporter content, and insulin-induced transporter translocation. There were no differences in transporter intrinsic activity (Vmax/Ro) among the three groups. Microsomal membrane GLUT4 content was reduced by 30% in untreated diabetic rats and normal in transplanted diabetics, whereas the insulin-induced changes in microsomal membrane GLUT4 content were quantitatively similar in the three groups. There were no differences in plasma membrane GLUT1 among the groups and between basal and insulin stimulated states. Microsomal membrane GLUT1 content was increased 60% in untreated diabetics and normalized by the transplantation. In conclusion, an adequate insulin delivery in the peripheral circulation, obtained by islet transplantation, fully restores the muscle glucose transport system to normal in streptozocin diabetic rats. PMID:8617870

Bone Mineral Density in Adolescent Females Using Injectable or Oral Contraceptives: A 24 Month Prospective Study

PubMed Central

Cromer, Barbara A.; Bonny, Andrea E.; Stager, Margaret; Lazebnik, Rina; Rome, Ellen; Ziegler, Julie; Camlin-Shingler, Kelly; Secic, Michelle

2008-01-01

Study Objective To determine whether bone mineral density (BMD) is lower in hormonal contraceptive users than that in an untreated, comparison group. Design Observational, prospective cohort; duration: 24 months. Setting Adolescent clinics in a midwestern, metropolitan setting. Patients 433 postmenarcheal girls, aged 12–18 years, on depot medroxyprogesterone acetate (DMPA) [n=58], oral contraceptives (OC) [n=187], or untreated (n=188). Intervention DMPA and OC containing 100 mcg levonorgestrel and 20 mcg ethinyl estradiol. Main Outcome Measure BMD measurements at spine and femoral neck were obtained with dual x-ray absorptiometry (DXA) at baseline and 6-month intervals. Results Over 24 months, mean percent change in spine BMD was: DMPA −1.5%, OC +4.2%, and untreated +6.3%. Mean percent change in femoral neck BMD was: DMPA −5.2%, OC +3.0%, untreated +3.8%. Statistical significance was found between the DMPA group and other two groups (p<.001). In the DMPA group, mean percent change in spine BMD over the first 12 months was −1.4%; the rate of change slowed to −0.1% over the second 12 months. No bone density loss reached the level of osteopenia. Conclusions Adolescent girls receiving DMPA had significant loss in BMD compared with bone gain in the OC and untreated group. However, its clinical significance is mitigated by slowed loss after the first year of DMPA use and general maintenance of bone density values within the normal range. PMID:18222431

Tyraminergic modulation of agonistic outcomes in crayfish.

PubMed

Momohara, Yuto; Aonuma, Hitoshi; Nagayama, Toshiki

2018-05-01

Octopamine, a biogenic amine, modulates various behaviors, ranging from locomotion and aggression to learning and memory in invertebrates. Several studies recently demonstrated that tyramine, the biological precursor of octopamine, also affects behaviors independent of octopamine. Here we investigated the involvement of tyramine in agonistic interaction of the male crayfish Procambarus clarkii. When male crayfish fight, larger animals (3-7% difference in body length) are more likely to win. By contrast, direct injection of tyramine or octopamine counteracted the physical advantage of larger animals. Tyramine or octopamine-injected naive large animals were mostly beaten by untreated smaller naive animals. This pharmacological effect was similar to the loser effect in which subordinate larger animals are frequently beaten by smaller animals. Furthermore, loser effects were partly eliminated by either injection of epinastine, an octopamine blocker, or yohimbine, a tyramine blocker, and significantly diminished by injection of a mixture of both blockers. We also observed that tyramine levels in the subesophageal ganglion were remarkably increased in subordinate crayfish after losing a fight. These results suggest that tyramine modulates aggressive levels of crayfish and contributes to the loser effect in parallel with octopamine.

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity.

PubMed

Yasasvini, S; Anusa, R S; VedhaHari, B N; Prabhu, P C; RamyaDevi, D

2017-03-01

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of methamphetamine on an animal model of erectile function.

PubMed

Tar, M T; Martinez, L R; Nosanchuk, J D; Davies, K P

2014-07-01

In the US methamphetamine is considered a first-line treatment for attention-deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies, we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine [2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)] i.p. daily for 3 weeks and erectile function compared with untreated controls. The effect of co-administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies, we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6 mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals, the ICP/BP ratio following 4 and 6 mA stimulation decreased by approximately 50% compared with untreated animals and erectile dysfunction (ED) was also reversed by tadalafil. Overall, our data suggest that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for treating patients that report ED associated with therapeutics-containing methamphetamine or amphetamine with PDE5i. © 2014 American Society of Andrology and European Academy of Andrology.

Magnolol attenuates sepsis-induced gastrointestinal dysmotility in rats by modulating inflammatory mediators

PubMed Central

Yang, Tie-Cheng; Zhang, Shu-Wen; Sun, Li-Na; Wang, Hong; Ren, Ai-Min

2008-01-01

AIM: To investigate the protective effects of magnolol on sepsis-induced inflammation and intestinal dysmotility. METHODS: Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide (LPS). Male Wistar rats were randomly assigned to one of three treatment groups: magnolol prior to LPS injection (LPS/Mag group); vehicle prior to LPS injection (LPS/Veh group); vehicle prior to injection of saline (Control/Veh). Intestinal transit and circular muscle mechanical activity were assessed 12 h after LPS injection. Tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS) mRNA in rat ileum were studied by RT-PCR 2 h after LPS injection. Nuclear factor-κB (NF-κB) activity in the intestine was also investigated at this time using electrophoretic mobility shift assay. In addition, antioxidant activity was determined by measuring malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity in the intestine 2 h after LPS injection. RESULTS: Magnolol significantly increased intestinal transit and circular muscle mechanical activity in LPS-treated animals. TNF-α, MCP-1 and iNOS mRNA expression in the small intestine were significantly reduced after magnolol treatment in LPS-induced septic animals, compared with untreated septic animals. Additionally, magnolol significantly increased IL-10 mRNA expression in septic rat ileum. Magnolol also significantly suppressed NF-κB activity in septic rat intestine. In addition, magnolol significantly decreased MDA concentration and increased SOD activity in rat ileum. CONCLUSION: Magnolol prevents sepsis-induced suppression of intestinal motility in rats. The potential mechanism of this benefit of magnolol appears to be modulation of self-amplified inflammatory events and block of oxidative stress in the intestine. PMID:19109869

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo.

PubMed

Tuvshintulga, Bumduuren; AbouLaila, Mahmoud; Davaasuren, Batdorj; Ishiyama, Aki; Sivakumar, Thillaiampalam; Yokoyama, Naoaki; Iwatsuki, Masato; Otoguro, Kazuhiko; Ōmura, Satoshi; Igarashi, Ikuo

2016-05-01

The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC50s) of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 μM, respectively. In mice infected with B. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Protective Efficacy of a Pseudoalteromonas Strain in European Abalone, Haliotis tuberculata, Infected with Vibrio harveyi ORM4.

PubMed

Offret, Clément; Rochard, Vincent; Laguerre, Hélène; Mounier, Jérôme; Huchette, Sylvain; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

2018-02-06

The hemolymph of healthy marine invertebrates is known to harbor antibiotic-producing bacteria belonging to the genus Pseudoalteromonas. Such strains are potential probiotics to control infectious diseases in aquaculture. In the present study, we screened a collection of Pseudoalteromonas strains isolated from the hemolymph of oyster and mussel for antimicrobial activity against Vibrio harveyi, a pathogenic species responsible for high mortality in abalone. Subsequently, the protective efficacy of the most active strain named hCg-6 was investigated in abalone culture faced with a Vibrio harveyi ORM4 infection. First, we have controlled the Pseudoalteromonas hCg-6 safety for abalone health. To that end, animals were immersed for 4 h in Pseudoalteromonas hCg-6 suspensions in seawater. The abalone viability was monitored and Pseudoalteromonas hCg-6 was tracked by quantitative-PCR in abalone hemolymph. After immersion, no abalone death occurred while the strain hCg-6 was significantly detected in hemolymph. Therefore, the strain hCg-6 was considered safe for abalone and evaluated for its ability to protect abalone against V. harveyi (injection of 1 × 10 3 Vibrio per animal). A 4-h long immersion of abalone in a seawater suspension of Pseudoalteromonas hCg-6 (1 × 10 6  CFU mL -1 ) prior to infection with Vibrio harveyi significantly improved the abalone viability. Indeed, 15 days post infection, the hCg-6 treatment used increased the abalone survival rate from 16% in untreated animals to 40% in treated abalone. We hypothesized that Pseudoalteromonas hCg-6 antibacterial activity increased the hemomicrobiota shielding effect. In conclusion, Pseudoalteromonas hCg-6 is a promising anti-Vibrio strain for abalone culture.

Microbiological Implications of Periurban Agriculture and Water Reuse in Mexico City

PubMed Central

Mazari-Hiriart, Marisa; Ponce-de-León, Sergio; López-Vidal, Yolanda; Islas-Macías, Pilar; Amieva-Fernández, Rosa Isabel; Quiñones-Falconi, Francisco

2008-01-01

Background Recycled treated or untreated wastewater represents an important health challenge in developing countries due to potential water related microbiological exposure. Our aim was to assess water quality and health implications in a Mexico City periurban agricultural area. Methodology/Principal Findings A longitudinal study in the Xochimilco wetland area was conducted, and 42 sites were randomly selected from 211, including irrigation water canals and effluents of treatment plants. Sample collection took place during rainy and dry seasons (2000–2001). Microbiological parameters (total coliforms, fecal coliforms, streptococci/enterococci, and bacteria other than Vibrio grown on TCBS), Helicobacter pylori, and physicochemical parameters including trihalomethanes (THM) were determined. Fecal coliforms and fecal streptococci are appropriate indicators of human or animal fecal contamination. Fecal coliform counts surpass Mexican and World Health Organization irrigation water guidelines. Identified microorganisms associated with various pathologies in humans and domestic animals comprise Escherichia coli, Klebsiella spp., Salmonella spp., Enterobacter spp., Enterococcus spp., and Pseudomonas spp; H. pylori was also present in the water. An environmental characteristic of the canal system showed high Total Organic Carbon content and relatively low dissolved oxygen concentration; residual chlorine as a disinfection control is not efficient, but THMs do not represent a problem. During the rainy season, temperature and conductivity were higher; in contrast, pH, dissolved oxygen, ammonia, and residual chlorine were lower. This is related with the continuous load of feces from human and animal sources, and to the aquatic systems, which vary seasonally and exhibit evidence of lower water quality in effluents from treatment plants. Conclusions/Significance There is a need for improvement of wastewater treatment systems, as well as more efficient monitoring, regulation, and enforcement procedures for wastewater disposal into bodies of water. PMID:18509453

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

PubMed Central

Tuvshintulga, Bumduuren; AbouLaila, Mahmoud; Davaasuren, Batdorj; Ishiyama, Aki; Sivakumar, Thillaiampalam; Yokoyama, Naoaki; Iwatsuki, Masato; Otoguro, Kazuhiko; Ōmura, Satoshi

2016-01-01

The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC50s) of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 μM, respectively. In mice infected with B. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti. On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis. PMID:26883713

Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques.

PubMed

Guedj, Jérémie; Piorkowski, Géraldine; Jacquot, Frédéric; Madelain, Vincent; Nguyen, Thi Huyen Tram; Rodallec, Anne; Gunther, Stephan; Carbonnelle, Caroline; Mentré, France; Raoul, Hervé; de Lamballerie, Xavier

2018-03-01

Despite repeated outbreaks, in particular the devastating 2014-2016 epidemic, there is no effective treatment validated for patients with Ebola virus disease (EVD). Among the drug candidates is the broad-spectrum polymerase inhibitor favipiravir, which showed a good tolerance profile in patients with EVD (JIKI trial) but did not demonstrate a strong antiviral efficacy. In order to gain new insights into the antiviral efficacy of favipiravir and improve preparedness and public health management of future outbreaks, we assess the efficacy achieved by ascending doses of favipiravir in Ebola-virus-infected nonhuman primates (NHPs). A total of 26 animals (Macaca fascicularis) were challenged intramuscularly at day 0 with 1,000 focus-forming units of Ebola virus Gabon 2001 strain and followed for 21 days (study termination). This included 13 animals left untreated and 13 treated with doses of 100, 150, and 180 mg/kg (N = 3, 5, and 5, respectively) favipiravir administered intravenously twice a day for 14 days, starting 2 days before infection. All animals left untreated or treated with 100 mg/kg died within 10 days post-infection, while animals receiving 150 and 180 mg/kg had extended survival (P < 0.001 and 0.001, respectively, compared to untreated animals), leading to a survival rate of 40% (2/5) and 60% (3/5), respectively, at day 21. Favipiravir inhibited viral replication (molecular and infectious viral loads) in a drug-concentration-dependent manner (P values < 0.001), and genomic deep sequencing analyses showed an increase in virus mutagenesis over time. These results allowed us to identify that plasma trough favipiravir concentrations greater than 70-80 μg/ml were associated with reduced viral loads, lower virus infectivity, and extended survival. These levels are higher than those found in the JIKI trial, where patients had median trough drug concentrations equal to 46 and 26 μg/ml at day 2 and day 4 post-treatment, respectively, and suggest that the dosing regimen in the JIKI trial was suboptimal. The environment of a biosafety level 4 laboratory introduces a number of limitations, in particular the difficulty of conducting blind studies and performing detailed pharmacological assessments. Further, the extrapolation of the results to patients with EVD is limited by the fact that the model is fully lethal and that treatment initiation in patients with EVD is most often initiated several days after infection, when symptoms and high levels of viral replication are already present. Our results suggest that favipiravir may be an effective antiviral drug against Ebola virus that relies on RNA chain termination and possibly error catastrophe. These results, together with previous data collected on tolerance and pharmacokinetics in both NHPs and humans, support a potential role for high doses of favipiravir for future human interventions.

The Effect of Pycnogenol on Wound Healing in Diabetic Rats.

PubMed

Dogan, Elif; Yanmaz, Latif; Gedikli, Semin; Ersoz, Ugur; Okumus, Zafer

2017-04-01

Pycnogenol (PYC), an extract of pine bark, is known to have photoprotective, antimicrobial, antioxidant, and anti-inflammatory properties. An in vivo study was conducted to evaluate the effects of PYC treatment on wound healing in 48 adult male Sprague-Dawley rats, of which 24 were injected with a single dose of alloxan to induce diabetes. Three (3) excisional skin wounds (1.3 cm x 1.3 cm x 2 mm) were created in each healthy and diabetic animal. One (1) wound in each animal was left untreated, 1 was treated daily with a cleanser (ethacridine lactate) and covered with silver sulfadiazine (SSD), and 1 was treated with PYC powder (30 mg). After measuring wound size, 6 animals from both groups were sacrificed on days 3, 7, 14, and 21 and tissue samples were taken for histopathological evaluation of acute and chronic inflammation, granulation tissue, fibroblast maturation, collagen deposition, epithelialization, and neovascularization using a scoring system of 0 = none, 1 = mild, 2 = moderate, and 3 = abundant. Because the wounds created were not uniform in size within and among the animals, healing was expressed as a percentage of the initial wound size for each animal. Data were compared using 2-way analysis of variance; histopathological lesion scores were reported in median values in univariate analysis, with P <.05 denoting statistical significance. The mean initial wound surface area was 1.69 ± 0.44 cm². On day 21, the average reduction in wound size was lower in diabetic than in healthy rats (47.42% versus 50.91%, P <.0001) and, in both groups combined, the average reduction was 45.73% in untreated, 48.73% in cleanser/SSD-treated, and 58.03% in PYC-treated wounds (P <.0001). Wound size reduction was also significantly different between PYC and the cleanser/SSD treatment depending on the rats' health status (P <.0001): 49.68% and 47.84% using cleanser/SSD and 56.17% and 49.84% using PYC in healthy and diabetic rats, respectively. After 3 weeks, wound size for the healthy rats had decreased more than in the diabetic rats (mean 50.91% versus 47.42%). Although reepithelialization was complete in both groups by day 21, complete neovascularization was evident in the healthy rats but not in the diabetic rats. Overall, compared to the untreated control wounds, treatments with cleanser/SSD and PYC were equally effective in lowering acute and chronic inflammation scores on days 7 and 21. In diabetic rat wounds, collagen deposition and neovascularization scores were higher in wounds treated with PYC than cleanser/SSD-treated wounds (1.5 versus 1.0 and 2.0 versus 1.5, respectively). PYC appears to be a viable option to accelerate wound healing. Further in vivo and human research is warranted.

Cochlear hearing loss in patients with Laron syndrome.

PubMed

Attias, Joseph; Zarchi, Omer; Nageris, Ben I; Laron, Zvi

2012-02-01

The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age <2 years, and 1 adolescent who started replacement therapy at bone age 4.6 years. The auditory evaluation included pure tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic emissions, loudness dynamics, auditory brain stem responses and a hyperacusis questionnaire. All untreated patients and the patient who started treatment late had various degrees of sensorineural hearing loss and auditory hypersensitivity; acoustic middle ear reflexes were absent in most of them. All treated children had normal hearing and no auditory hypersensitivity; most had recordable middle ear acoustic reflexes. In conclusion, auditory defects seem to be associated with Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age.

[Improving Mental Health Care in People at Risk for Getting Homeless].

PubMed

Salize, Hans Joachim; Arnold, Maja; Uber, Elisa; Hoell, Andreas

2017-01-01

Objective: Overall aim was to reduce the untreated prevalence in persons with untreated mental disorders and at risk for loosing accommodation and descending into homelessness. Primary aim was treatment initiation and treatment adherence by motivational interviewing. Secondary aims were to reduce social or financial problems. Methods: Persons at risk were identified in social welfare services or labour agencies, diagnosed and motivated to initiate treatment in a community mental health service. Results: 58 persons were included, 24 were referred to regular mental health care, 8 were stabilized enough after the initial motivational to refrain from acute treatment, 26 dropped out. During a 6-month follow-up quality of life and social support was improved (partly statistically significant) and psycho-social needs for care decreased. Conclusion: Motivational interviewing is likely to increase insight into illness and acceptance of mental health care in untreated persons with mental disorders at risk for social decline. © Georg Thieme Verlag KG Stuttgart · New York.

Small Molecule Inhibitors of ERG and ETV1 in Prostate Cancer

DTIC Science & Technology

2016-06-01

transition associated genes in ERG treated tumors. However, immunohistochemical analyses of these proteins in the tumors of treated and untreated animals...10). We determined that epithelial- mesenchymal transition (EMT) associated proteins RASAL2, VIM, NREP, and BCL11A were decreased among others. ERG...35 and 86.2 xenografts. RNASeq was performed to identify genes that were suppressed by YK-4-279. Epithelial- mesenchymal transition associated

Febrile response to infection in the American alligator (Alligator mississippiensis).

PubMed

Merchant, Mark; Williams, Stephanie; Trosclair, Phillip L; Elsey, Ruth M; Mills, Kaili

2007-12-01

Temperature probes were inserted into the stomachs of juvenile American alligators (Alligator mississippiensis) maintained outdoors at ambient fluctuating temperatures. Internal body temperatures (T(b)) were measured every 15 min for two days, and then the alligators were injected with bacterial lipopolysaccharide (LPS), pyrogen-free saline, or left untreated. Alligators injected intraperitoneally with LPS exhibited maximum T(b)s 2.6+/-1.1 degrees C and 3.5+/-1.2 degrees C higher than untreated control animals on days one and two after treatment, respectively. T(b)s for these animals fell to within control ranges by day three postinjection. Similarly, mean preferred body temperatures (MPBTs) were significantly higher for LPS-injected alligators on days one (4.2+/-1.8 degrees C) and two (3.5+/-1.6 degrees C) after treatment. Intraperitoneal injection of heat-killed Aeromonas hydrophila, a gram-negative bacterium known to infect crocodilians, resulted in a fever while injection of Staphylococcus aureus (gram positive) did not elicit a febrile response. Injection of LPS in alligators maintained indoors in a constant temperature environment resulted in no increase in internal T(b). These results indicate that alligators did not exhibit a febrile response in the absence of a thermal gradient, and suggest that febrile responses observed are probably behavioral in nature.

Maternal effects and cancer risk in the progeny of mice exposed to X-rays before conception.

PubMed

Dasenbrock, Clemens; Tillmann, Thomas; Ernst, Heinrich; Behnke, Wolfgang; Kellner, Rupert; Hagemann, Gerd; Kaever, Volkhard; Kohler, Manfred; Rittinghausen, Susanne; Mohr, Ulrich; Tomatis, Lorenzo

2005-04-01

To investigate in an animal model whether preconceptual X-ray exposure leads to an altered tumor rate and spectrum in the offspring, a transgeneration carcinogenesis study was carried out. Female mice received X-ray irradiation (2 x 2 Gray) 2 weeks prior to mating with untreated males. After weaning, half of the descendants were exposed for 6 months to the immunomodulating and tumor-promoting compound cyclosporine A (CsA) by diet, the others remained untreated. The animals were maintained for their entire lifespan, terminal sacrifices were carried out after 28 months. Complete autopsy was performed, and three protocol organs (lung, liver and spleen) were examined histologically, together with any suspicious lesions in other organs. Fertility and the lifetime of the maternal mice were reduced by the X-ray irradiation, and their incidence of lung and liver tumors was increased as compared to non-irradiated mice. The descendants of all groups revealed comparable body weights and mortality rates. The incidence of hematopoietic/lymphoreticular tissue tumors increased in the female hybrids by 6 months of CsA-treatment. A higher incidence of lung and liver tumors in the sham-treated male progeny of irradiated mothers was detected, pointing to a possible germ cell-transmitted alteration initiated by the preconceptual maternal X-ray exposure.

Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribeiro-Filho, Jaime; Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba; Calheiros, Andrea Surrage

Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effectsmore » of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine mechanisms involve inhibition of Ca{sup 2+} influx, and IL-13 and eotaxin secretion. • No significant toxicity was observed in mice orally treated with curine for 7 days. • Curine has the potential for the development of anti-asthmatic drugs.« less

Molecular Detection and Species-Specific Identification of Medically Important Aspergillus Species by Real-Time PCR in Experimental Invasive Pulmonary Aspergillosis ▿

PubMed Central

Walsh, Thomas J.; Wissel, Mark C.; Grantham, Kevin J.; Petraitiene, Ruta; Petraitis, Vidmantas; Kasai, Miki; Francesconi, Andrea; Cotton, Margaret P.; Hughes, Johanna E.; Greene, Lora; Bacher, John D.; Manna, Pradip; Salomoni, Martin; Kleiboeker, Steven B.; Reddy, Sushruth K.

2011-01-01

Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species-specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan-Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P < 0.0007) and treated (P ≤ 0.008) animals, respectively. For infections caused by A. terreus and A. niger, culture and PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients. PMID:21976757

Normal milk microbiome is reestablished following experimental infection with Escherichia coli independent of intramammary antibiotic treatment with a third-generation cephalosporin in bovines.

PubMed

Ganda, Erika K; Gaeta, Natalia; Sipka, Anja; Pomeroy, Brianna; Oikonomou, Georgios; Schukken, Ynte H; Bicalho, Rodrigo C

2017-07-12

The use of antimicrobials in food animals and the emergence of antimicrobial resistance are global concerns. Ceftiofur is the only third-generation cephalosporin labeled for veterinary use in the USA, and it is the drug of choice in the majority of dairy farms for the treatment of mastitis. Here, we use next-generation sequencing to describe longitudinal changes that occur in the milk microbiome before, during, and after infection and treatment with ceftiofur. Twelve animals were intramammary challenged with Escherichia coli in one quarter and randomly allocated to receive intramammary treatment with ceftiofur (5d) or untreated controls. Serial samples were collected from -72 to 216 h relative to challenge from the challenged quarter, an ipsilateral quarter assigned to the same treatment group, and from a third quarter that did not undergo intervention. Infection with E. coli dramatically impacted microbial diversity. Ceftiofur significantly decreased LogCFUs but had no significant effect on the milk microbiome, rate of pathogen clearance, or somatic cell count. At the end of the study, the microbial profile of infected quarters was indistinguishable from pre-challenge samples in both treated and untreated animals. Intramammary infusion with ceftiofur did not alter the healthy milk (i.e., milk devoid of clots or serous appearance and collected from a mammary gland that shows no clinical signs of mastitis) microbiome. Our results indicate that the mammary gland harbors a resilient microbiome, capable of reestablishing itself after experimental infection with E. coli independent of antimicrobial treatment.

Lipid Profile and Electrolyte Composition in Diabetic Rats Treated With Leaf Extract of Musa sapientum.

PubMed

Adewoye, E O; Ige, A O

2016-01-01

Diabetes mellitus affects lipid levels resulting in diabetic dyslipidemia as well as electrolyte loss from the body. Musa sapientum has been reported to possess antidiabetic properties. This study assessed the lipid profile and electrolyte composition in alloxan-induced diabetic rats treated with methanol leaf extract of M. sapientum (cMEMSL). Diabetes was induced with alloxan (120 mg/kg i.p.). Seventy-five male albino rats were divided into 5 groups of 15 rats each. Group 1 was control; groups 2-5 were made diabetic and treated with 0.2 ml 0.9% NaCl, cMEMSL (250 mg/kg and 500 mg/kg), and glibenclamide (5 mg/kg), respectively, for 14 days. Blood samples were obtained from the retro orbital sinus after light anesthesia from 5 animals in each group on days 2, 7, and 14 for lipids and electrolyte analysis. Lipid profile of diabetic treated (cMEMSL and glibenclamide) animals showed significant reduction (p < .05) in total cholesterol, triglyceride, and low density lipoprotein (LDL) levels. The high density lipoprotein (HDL) level in the treatment groups increased significantly (p < .05) compared with diabetic untreated. Sodium, potassium, and phosphate ions significantly increased in all diabetic treatment groups while chloride ion significantly decreased compared with diabetic untreated. There was no significant difference in calcium and bicarbonate ion concentration in all the groups. This study has showed additional properties of Musa sapientum to include its ability to restore electrolyte balance, reduce cholesterol, triglyceride, LDL, and increase the HDL levels in diabetic animals.

Role of neutrophilic elastase in ethanol induced injury to the gastric mucosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kvietys, P.R.; Carter, P.R.

1990-02-26

Intragastric administration of ethanol (at concentrations likely to be encountered by the mucosa during acute intoxication) produces gastritis. Recent studies have implicated neutrophils in the gastric mucosal injury induced by luminal ethanol. The objective of the present study was to assess whether neutrophilic elastase contributes to the ethanol-induced gastric mucosal injury. Sprague-Dawley rats were instrumented for perfusion of the gastric lumen with saline or ethanol. Mucosal injury was quantitated by continuously measuring the blood-to-lumen clearance of {sup 51}Cr-EDTA. The experimental protocol consisted of a 40 minute control period (saline perfusion) followed by three successive 40 minute experimental periods (ethanol perfusion).more » During the three experimental periods the concentration of ethanol was progressively increased to 10, 20, and 30%. The experiments were performed in untreated animals and in animals pretreated with either Eglin c (an inhibitor of elastase and cathepsin G activity) or L 658 (a specific inhibitor of elastase activity). The effects of ethanol on EDTA clearance (x control) in untreated (n = 9) and L658 treated (n = 5) animals are shown in the Table below. Pretreatment with L 658 significantly attenuated the ethanol-induced increases in EDTA clearance. Pretreatment with Eglin c (n = 6) also provided some protection against ethanol-induced injury, but not to the extent as that provided by L658. The results of the authors studies suggest that neutrophilic elastase contributes to a gastric mucosal injury induced by luminal perfusion of the stomach with physiologically relevant concentrations of ethanol.« less

Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

PubMed Central

Schuurhuis, J M; Span, L F R; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

2016-01-01

Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. Methods: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. Results: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. Conclusions: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy. PMID:27002936

Evaluation of materials proposed for use in space flight

NASA Technical Reports Server (NTRS)

Duncan, W. C.

1981-01-01

The cutaneous primary irritancy and allergenicity potential of cotton shirts/fabrics treated with flame retardants were evaluated in order to establish their suitability for spacecraft crew use. Twenty-five volunteer human subjects were patch tested on the back utilizing standard methodology, with both treated and untreated cotton fabric. The fabric was treated with tetrakis (hydroxymethyl) phosphonium hydroxide and subsequently cured with gaseous ammonia. The final treatment comprised adding on dicyandiamine phosphoric acid. None of the individuals experienced primary irritant or allergic reactions attributable to the fabric during induction or challenge patch testing. Likewise, there were no reactions to treated or untreated fabric patches placed on ten subjects of the usage panel at the conclusion of the study.

Comparative gastrointestinal blood loss associated with placebo, aspirin, and nabumetone as assessed by radiochromium (/sup 51/Cr)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lussier, A.; Davis, A.; Lussier, Y.

Nabumetone differs from most other nonsteroidal anti-inflammatory drugs. It is presented to the gut as a nonacidic prodrug, and is metabolized to its active form after absorption. Studies in animals and humans suggest it is less irritating to the gastrointestinal mucosa. This study compared the gastrointestinal microbleeding induced by nabumetone to aspirin (acetylsalicylic acid, ASA), and placebo in a double blind parallel study using chromium /sup 51/Cr labelled red cells to quantitate fecal blood loss (FBL) in healthy volunteers. Thirty subjects were randomized to treatment with nabumetone (2000 mg), ASA (3.6 g) or placebo for 21 days following a 7more » day placebo period. Six subjects served as untreated controls. FBL in nabumetone treated subjects was not significantly different to placebo or untreated subjects. In contrast, ASA-treated subjects exhibited significantly increased FBL than the other 3 groups (P less than .0001).« less

Assessment of Tumoricidal Efficacy and Response to Treatment with 18F-FDG PET/CT After Intraarterial Infusion with the Antiglycolytic Agent 3-Bromopyruvate in the VX2 Model of Liver Tumor

PubMed Central

Liapi, Eleni; Geschwind, Jean-Francois H.; Vali, Mustafa; Khwaja, Afsheen A.; Prieto-Ventura, Veronica; Buijs, Manon; Vossen, Josephina A.; Ganapathy, Shanmugasudaram; Wahl, Richard L.

2015-01-01

The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with 18F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Methods Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of 18F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUVmax), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Results Intense 18F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUVmax was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor–to–liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUVmax increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r2 = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUVmax on 18F-FDG PET at 7 d after treatment with 3-BrPA. Conclusion Intraarterial injection of 3-BrPA resulted in markedly decreased 18F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA. PMID:21233194

Temporal patterns of inflammatory gene expression in local tissues after banding or burdizzo castration in cattle

PubMed Central

Pang, Wanyong; Earley, Bernadette; Sweeney, Torres; Gath, Vivian; Crowe, Mark A

2009-01-01

Background Castration of male cattle has been shown to elicit inflammatory reactions and acute inflammation is initiated and sustained by the participation of cytokines. Methods Sixty continental × beef bulls (Mean age 12 ± (s.e.) 0.2 months; Mean weight 341 ± (s.e.) 3.0 kg) were blocked by weight and randomly assigned to one of three treatments (n = 20 animals per treatment): 1) untreated control (Con); 2) banding castration at 0 min (Band); 3) Burdizzo castration at 0 min (Burd). Samples of the testis, epididymis and scrotal skin were collected surgically from 5 animals from each group at 12 h, 24 h, 7 d, and 14 d post-treatment, and analysed using real-time PCR. A repeated measurement analysis (Proc GLM) was performed using SAS. If there was no treatment and time interaction, main effects of treatment by time were tested by ANOVA. Results Electrophoresis data showed that by 7 d post-castration RNA isolated from all the testicle samples of the Burd castrated animals, the epididymis and middle scrotum samples from Band castrates were degraded. Transitory effects were observed in the gene expression of IFN-γ, IL-6, IL-8 and TNF-α at 12 h and 24 h post treatment. Burd castrates had greater (P < 0.05) testicular IFN-γ mRNA levels compared with Band and Con animals, but lower (P < 0.05) testicular TNF-α mRNA levels compared with Con animals. Band castrates had greater (P < 0.05) testicular IL-6 mRNA levels than Burd castrates at 12 h post-castration. Burd castrates had greater (P < 0.05) testicular IL-8 mRNA levels than Band and Con animals at 24 h post-castration. In the epididymis, Burd castrates had greater (P < 0.05) IL-6 mRNA (both at 12 h and 24 h post treatment) and IL-8 mRNA (12 h post treatment) levels compared with Band and Con animals; Burd castrates had greater (P = 0.049) IL-10 mRNA levels than Band castrates at 12 h post-castration. Conclusion Banding castration caused more inflammatory associated gene expression changes to the epididymis and scrotum than burdizzo. Burdizzo caused more severe acute inflammatory responses, in terms of pro-inflammatory cytokine gene expression, in the testis and epididymis than banding. PMID:19775432

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Lerner, Aaron; Coran, Arnold G; Lurie, Michael; Miselevich, Iness; Shiloni, Eitan

2005-06-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Shamir, Raanan; Shehadeh, Naim; Bejar, Jacob; Hirsh, Mark; Coran, Arnold G

2005-03-01

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

A Preclinical Study of the Safety and Efficacy of Occlusin Trade-Mark-Sign 500 Artificial Embolization Device in Sheep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owen, Richard J., E-mail: drrichardowen@tbwifi.ca; Nation, Patrick N.; Polakowski, Robert

Introduction: This study evaluated the safety, effectiveness, and biodegradation of a new embolic agent, Occlusin Trade-Mark-Sign 503 Artificial Embolization Device (OCL 503). The agent consists of biodegradable poly-lactic-co-glycolic acid microspheres (150-212 {mu}m) coated with type I bovine collagen and was compared with Embosphere{sup Registered-Sign} Microspheres (300-500 {mu}m) in this controlled study of uterine artery embolization (UAE) in sheep. Methods: Unilateral UAE was performed in 32 adult ewes randomly assigned. Vessels were embolized to effective stasis. The cohort was divided into four groups, which were sacrificed at 1, 3, 6, and 12 months. Results: Both agents were 100% effective in achievingmore » stasis. At 6 months, all OCL 503-treated arteries were occluded, the microspheres degraded with time, and at 12 months all four animals examined demonstrated recanalization. OCL 503 was found in the untreated uterine artery in one animal with no other evidence of non target embolization. In the Embosphere-treated group, all vessels remained occluded and microspheres were detected in the contralateral uterine artery in 6 of 15 examined vessels and in 10 vaginal, 2 ovarian, and 1 vesical artery. No procedural-related complications were seen in either group. Conclusions: OCL 503 is as effective an embolic agent as Embosphere{sup Registered-Sign} Microspheres when embolizing ovine uterine arteries and resorbs with time, allowing recanalization of the treated arteries. No device-related issues or adverse events were observed.« less

Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

PubMed Central

Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M.; Longatto-Filho, Adhemar; Castro, António G.; Pedrosa, Jorge; Fraga, Alexandra G.

2015-01-01

Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

American College of Sports Medicine Roundtable on Exertional Heat Stroke - Return to Duty/Return to Play: Conference Proceedings

DTIC Science & Technology

2010-01-01

individuals with EHS experience long-term complica- tions that may include multisystem organ (liver, kidney, muscle ) and neurologic damage, as well as... reduced exercise capacity and heat intolerance (12,52,57,69). Animal and human research suggest late or untreated EHS may result in organ damage that...collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and

Alterations in Pain Responses in Treated and Untreated Patients with Restless Legs Syndrome: Associations with Sleep Disruption

PubMed Central

Edwards, Robert R; Quartana, Phillip J.; Allen, Richard P; Greenbaum, Seth; Earley, Christopher J; Smith, Michael T

2011-01-01

Objective There has been recent interest in characterizing potential abnormalities of pain processing in patients with sleep disorders such as Restless Legs Syndrome (RLS). The aim of this study was to evaluate psychophysical responses to noxious heat and pressure stimuli in both treated and untreated RLS patients, compared to matched controls. Methods This study is a cross-sectional group comparison of RLS patients with matched controls. A total of 31 patients (15 treated, 16 untreated) with a confirmed diagnosis of RLS were compared to 18 controls with no history of RLS or related sleep disorders. Results RLS patients (both treated and untreated) demonstrated reduced pain thresholds and reported greater clinical pain relative to controls. Moreover, RLS patients demonstrated enhanced temporal summation of heat pain (p< .05), which may reflect aberrant central nervous system facilitation of pain transmission. Both treated and untreated RLS patients reported disrupted sleep relative to controls, and mediation analyses suggested that the reduced pain thresholds in RLS were attributable to sleep disturbance. However, the effect of RLS on the magnitude of temporal summation of heat pain was independent of sleep disturbance. Conclusions These findings suggest that central nervous system pain processing may be amplified in RLS, perhaps partially as a consequence of sleep disruption. RLS patients, even those whose symptoms are managed pharmacologically, may be at elevated long-term risk for the development or maintenance of persistent pain conditions. Further studies in larger samples could help to improve the prospects for pain management in RLS patients. PMID:21570347

Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo

PubMed Central

Hrgovic, Igor; Glavic, Zeljko; Kovacic, Zeljko; Mulic, Smaila; Zunic, Lejla; Hrgovic, Zlatko

2014-01-01

ABSTRACT Introduction: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. Material and methods: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. Results: After termination of the experiments the mean tumor diameter in the control group was 12.4±0.8mm, in group A it was 6.9±0.6mm, and in group B we measured 6.6±3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. Conclusion: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options. PMID:24937925

Implications from distinct sulfate-reducing bacteria populations between cattle manure and digestate in the elucidation of H2S production during anaerobic digestion of animal slurry.

PubMed

St-Pierre, Benoit; Wright, André-Denis G

2017-07-01

Biogas produced from the anaerobic digestion of animal slurry consists mainly of methane (CH 4 ) and carbon dioxide (CO 2 ), but also includes other minor gases, such as hydrogen sulfide (H 2 S). Since it can act as a potent corrosive agent and presents a health hazard even at low concentrations, H 2 S is considered an undesirable by-product of anaerobic digestion. Sulfate-reducing bacteria (SRBs) have been identified as the main biological source of H 2 S in a number of natural, biological, and human-made habitats, and thus represent likely candidate microorganisms responsible for the production of H 2 S in anaerobic manure digesters. Phylogenetically, SRBs form a divergent group of bacteria that share a common anaerobic respiration pathway that allows them to use sulfate as a terminal electron acceptor. While the composition and activity of SRBs have been well documented in other environments, their metabolic potential remains largely uncharacterized and their populations poorly defined in anaerobic manure digesters. In this context, a combination of in vitro culture-based studies and DNA-based approaches, respectively, were used to gain further insight. Unexpectedly, only low to nondetectable levels of H 2 S were produced by digestate collected from a manure biogas plant documented to have persistently high concentrations of H 2 S in its biogas (2000-3000 ppm). In contrast, combining digestate with untreated manure (a substrate with comparatively lower sulfate and SRB cell densities than digestate) was found to produce elevated H 2 S levels in culture. While a 16S rRNA gene-based community composition approach did not reveal likely candidate SRBs in digestate or untreated manure, the use of the dsrAB gene as a phylogenetic marker provided more insight. In digestate, the predominant SRBs were found to be uncharacterized species likely belonging to the genus Desulfosporosinus (Peptococcaceae, Clostridiales, Firmicutes), while Desulfovibrio-related SRBs (Desulfovibrionaceae, Desulfovibrionales, Proteobacteria) were the most highly represented in untreated manure. Intriguingly, the same species-level OTUs with a similar pattern of opposite relative abundance were also found in two other digesters with lower H 2 S levels in their biogas. Together, our results suggest that elevated H 2 S production in anaerobic digesters requires the combination of biological and nutritional factors from both untreated manure and digestate.

Protective effect of zoledronic acid on articular cartilage and subchondral bone of rabbits with experimental knee osteoarthritis

PubMed Central

She, Guorong; Zhou, Ziqi; Zha, Zhengang; Wang, Fei; Pan, Xiaoting

2017-01-01

Subchondral bone reabsorption and remodeling are responsible for the initiation and progression of osteoarthritis (OA). Zoledronic acid (ZOL), a third-generation bisphosphonate (BIS), is an inhibitor of bone reabsorption. However, the intervention effect of ZOL on OA has not been fully characterized and remains to be directly demonstrated in animal experiments. The present study examined the microscopic and macroscopic changes in the anterior cruciate ligament transection (ACLT) model of OA in rabbits and evaluated the effects of ZOL on cartilage degeneration and subchondral bone loss. A total of 32 New Zealand white rabbits were randomly divided into four groups: High-, medium- and low-dose ZOL groups, which received an intravenous injection of 250, 50 and 10 µg/kg ZOL, respectively, after modeling, as well as an untreated group. The bone mineral density (BMD) of the knee joint was evaluated by dual-energy X-ray absorptiometry scanning immediately after modeling and at 4 and 8 weeks. At week 8, quantitative measurement of cartilage was performed by a specialized magnetic resonance imaging (MRI) technique, including three-dimensional fat-suppressed spoil gradient-recalled sequence and T2 mapping. The rabbits were sacrificed by air embolism after anesthesia and both knee joints were harvested and evaluated by general and histological observation. Toluidine blue and hematoxylin and eosin staining were used to assess histological changes in the articular cartilage. Quantitative analysis of cartilage histopathology was performed according to the Mankin scoring system. The BMD of ACLT joints dropped after modeling, which was effectively suppressed by ZOL at the high and medium dose but not the low dose. MRI scans demonstrated that in the untreated group, articular cartilages on ACLT knees were thinner than those on normal knees. The high dose of ZOL preserved the cartilage tissue thickness more efficiently than the medium and low doses. Observation of specimens and pathological slices revealed that the articular cartilage degeneration in the high-dose ZOL group was lightest, while that in the medium- and low-dose ZOL group was moderate, and the untreated group exhibited the most severe defect. The untreated group had the highest Mankin score, whereas the high-dose ZOL group had the lowest score. In conclusion, ZOL increased the subchondral bone density, improved the microstructure and reduced the degeneration of articular cartilage in OA according to morphological as well as quantitative observation. ZOL exerted significant chondroprotective effects in a dose-dependent manner. A favorable chondroprotective effect was induced at the dose of 250 µg/kg. ZOL may represent a novel promising drug to complement the treatment of OA. PMID:29201194

Effects of tick infestation and tick-borne disease infections (heartwater, anaplasmosis and babesiosis) on the lactation and weight gain of Mashona cattle in south-eastern Zimbabwe.

PubMed

Meltzer, M I; Norval, R A; Donachie, P L

1995-08-01

The effects of ticks and tick-borne disease infections on the lactation and weight gain of Mashona cattle were studied at Mbizi Quarantine Station in the south-eastern lowveld of Zimbabwe. Twenty-nine Mashona cows were allocated to 2 balanced groups and kept in separate paddocks at a stocking rate of one animal per 8 ha. One group received regular acaricide treatment to control bont (Amblyomma hebraeum) and other ticks. The other group was left untreated. The cows were artificially inseminated. The acaricide-treated cows and calves were essentially tick free throughout the experiment, while the untreated cows and calves were continuously tick infested. There was a drought-related decline in tick infestations in the second year of the experiment. Antibodies to Cowdria ruminantium, Babesia bigemina and Anaplasma marginale were detected in cows and calves from both groups, though the untreated group had significantly higher titres to C. ruminantium (P < 0.001). The total, measured amount of milk suckled by untreated calves was significantly more than treated calves (273 kg vs. 241 kg, P < or = 0.05). By interpolating between the twice weekly measurements, it was calculated that over the entire lactation untreated calves suckled an average of 935 kg/hd vs. 837 kg/hd for the treated group. There were no statistical differences in the weights of the 2 groups of calves at birth, weaning, 180 and 210 days post partum (P < 0.05). For cows, there were no statistically significant differences in gestation periods (288 vs. 279 days), reconception rates or weight patterns over time (P < 0.05). The results show that intensive acaricide treatment in areas of Zimbabwe where heartwater is enzootically stable is uneconomical. The maintenance of enzootic stability for tick-borne diseases through minimal tick control is clearly a more economic and practical control option.

Characterization of antibiotic resistant enterococci isolated from untreated waters for human consumption in Portugal.

PubMed

Macedo, Ana S; Freitas, Ana R; Abreu, Cristina; Machado, Elisabete; Peixe, Luísa; Sousa, João C; Novais, Carla

2011-01-31

Untreated drinking water is frequently overlooked as a source of antibiotic resistance in developed countries. To gain further insight on this topic, we isolated the indicator bacteria Enterococcus spp. from water samples collected in wells, fountains and natural springs supplying different communities across Portugal, and characterized their antibiotic resistance profile with both phenotypic and genetic approaches. We found various rates of resistance to seven antibiotic families. Over 50% of the isolates were resistant to at least ciprofloxacin, tetracyclines or quinupristin-dalfopristin and 57% were multidrug resistant to ≥3 antibiotics from different families. Multiple enterococcal species (E. faecalis, E. faecium, E. hirae, E. casseliflavus and other Enterococcus spp) from different water samples harbored genes encoding resistance to tetracyclines, erythromycin or gentamicin [tet(M)-46%, tet(L)-14%, tet(S)-5%, erm(B)-22%, aac(6´)-Ie-aph(2″)-12%] and putative virulence factors [gel-28%, asa1-16%]. The present study positions untreated drinking water within the spectrum of ecological niches that may be reservoirs of or vehicles for antibiotic resistant enterococci/genes. These findings are worthy of attention as spread of antibiotic resistant enterococci to humans and animals through water ingestion cannot be dismissed. Copyright © 2010 Elsevier B.V. All rights reserved.

Small animal magnetic resonance imaging: an efficient tool to assess liver volume and intrahepatic vascular anatomy.

PubMed

Melloul, Emmanuel; Raptis, Dimitri A; Boss, Andreas; Pfammater, Thomas; Tschuor, Christoph; Tian, Yinghua; Graf, Rolf; Clavien, Pierre-Alain; Lesurtel, Mickael

2014-04-01

To develop a noninvasive technique to assess liver volumetry and intrahepatic portal vein anatomy in a mouse model of liver regeneration. Fifty-two C57BL/6 male mice underwent magnetic resonance imaging (MRI) of the liver using a 4.7 T small animal MRI system after no treatment, 70% partial hepatectomy (PH), or selective portal vein embolization. The protocol consisted of the following sequences: three-dimensional-encoded spoiled gradient-echo sequence (repetition time per echo time 15 per 2.7 ms, flip angle 20°) for volumetry, and two-dimensional-encoded time-of-flight angiography sequence (repetition time per echo time 18 per 6.4 ms, flip angle 80°) for vessel visualization. Liver volume and portal vein segmentation was performed using a dedicated postprocessing software. In animals with portal vein embolization, portography served as reference standard. True liver volume was measured after sacrificing the animals. Measurements were carried out by two independent observers with subsequent analysis by the Cohen κ-test for interobserver agreement. MRI liver volumetry highly correlated with the true liver volume measurement using a conventional method in both the untreated liver and the liver remnant after 70% PH with a high interobserver correlation coefficient of 0.94 (95% confidence interval, 0.80-0.98 for untreated liver [P < 0.001] and 0.90-0.97 after 70% PH [P < 0.001]). The diagnostic accuracy of magnetic resonance angiography for the occlusion of one branch of the portal vein was 0.95 (95% confidence interval, 0.84-1). The level of agreement between the two observers for the description of intrahepatic vascular anatomy was excellent (Cohen κ value = 0.925). This protocol may be used for noninvasive liver volumetry and visualization of portal vein anatomy in mice. It will serve the dynamic study of new strategies to enhance liver regeneration in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.

PubMed

Burgess, Alison; Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

2014-12-01

To validate whether repeated magnetic resonance (MR) imaging-guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease ( AD Alzheimer disease ), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging-guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging-guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging-guided focused ultrasound-treated animals (P < .01). Further, after MR imaging-guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging-guided focused ultrasound, as well (P < .01). Repeated MR imaging-guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of AD Alzheimer disease . The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal plasticity. © RSNA, 2014.

Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules.

PubMed

Datta, Sanchita; Roy, Syamal; Manna, Madhumita

2015-01-01

Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model. The T-cell proliferation level, the mRNA expression level of inducible nitric oxide synthase (iNOS) and tumor growth factor-beta (TGF-β) genes and finally the phosphorylation levels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) and p38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c mice model immunized with radio-attenuated Leishmania donovani parasites through I.M. route. Higher T-cell proliferation, increased iNOS level, and suppressed TGF-β level were found in treated infected animal groups (100 and 150Gy) in relation to untreated infected animals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groups were increased when compared to untreated infected controls. The clearance of the parasites from treated infected groups of animals may be mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovani parasites. The killing of parasites was mediated by increase in nitric oxide release through PDK1, PI3K and p38MAPK signaling pathways. A lower TGF-β expression has augmented the restored Th1 ambience in the 100 and 150Gy treated animal groups proving further the efficacy of the candidate vaccine. Copyright © 2015. Published by Elsevier Editora Ltda.

Efficacy of nitazoxanide to treat natural Giardia infections in dogs.

PubMed

Moron-Soto, Mario; Gutierrez, Lilia; Sumano, Héctor; Tapia, Graciela; Alcala-Canto, Yazmin

2017-01-31

Giardia parasites cause gastrointestinal disease in humans, dogs, and many other animals worldwide. The treatment of dogs for giardiasis requires further investigation to ascertain levels of drug efficacy and the possibility of adverse side effects. Nitazoxanide (NTZ) has shown good clinical anti-Giardia activity in humans, yet it has not been evaluated for the treatment of giardiasis in dogs. Thirty-five dogs, naturally infected with Giardia were divided into five groups (n = 7): dogs in group NTZ1, NTZ2, and NTZ3 were treated with a single oral dose of 37.5 mg/kg, 75 mg/kg, and 150 mg/kg, respectively, of NTZ on days 0 and 14. The fourth group was treated with a commercially available regimen that includes a combination of pyrantel, praziquantel, and febantel (FEB) administered orally for three consecutive days. Additionally, an untreated control group was established. Giardia cysts from the stool of each dog were quantified on days -3, 0, 5, 7, 9, 11, 14, 18, 25, and 28. Biochemical parameters were evaluated in all dogs, before the first treatment and after concluding the experiment. Shedding of Giardia cysts was reduced in all treated groups when compared to untreated controls (P < 0.01). However, NTZ2, NTZ3, and FEB had a lower risk during the study. Furthermore, NTZ was also effective against another protozoan, Cryptosporidium spp. at doses of 75 mg/kg and 150 mg/kg, in contrast to the combination of febantel + pyrantel + praziquantel. Biochemical parameters of treated animals, namely, aspartate transaminase and alanine transaminase enzymes, remained within physiological ranges. Based on these results, the implementation of NTZ as a treatment for giardiasis in dogs is proposed. The administration of a single dose is an important advantage of NTZ because it reduces workload, particularly in animals placed in shelters and kennels, where handling of large numbers of animals is required, and personnel is frequently scarce.

Chronic Giardia muris infection in anti-IgM-treated mice. I. Analysis of immunoglobulin and parasite-specific antibody in normal and immunoglobulin-deficient animals.

PubMed

Snider, D P; Gordon, J; McDermott, M R; Underdown, B J

1985-06-01

To investigate the role of B cells and antibody in the immune response of mice to the murine intestinal parasite Giardia muris, we used mice treated from birth with rabbit anti-IgM antisera (aIgM). Such mice developed in serum and in gut secretions extreme Ig deficiency (IgM, IgA, and IgG) relative to control animals. The aIgM-treated mice showed no anti-G. muris antibody in serum or in gut wash material. Infections of G. muris in these mice were chronic, with a high load of parasite present in the small bowel, as reflected by prolonged cyst excretion (greater than 11 wk) and high trophozoite counts. In contrast, normal, untreated mice or NRS-treated animals developed anti-parasite IgA and IgG antibody in serum, demonstrated IgA antibody against the parasite in gut washings, and expelled the parasite within 9 wk. These effects of aIgM treatment on the murine response to primary infection with G. muris were demonstrated in two strains of mice: BALB/c and (C57BL/6 X C3H/He) F1. It was also observed that the response to G. muris infection in untreated animals was characterized by higher than normal total secretion of IgA into the gut and a concomitant increase in the serum polymeric IgA level. Mice treated with aIgM had a marked decrease of both monomeric and polymeric IgA in serum, and little detectable IgA in the intestinal lumen. These experiments provide the first demonstration that anti-IgM treatment suppresses a specific intestinal antibody response to antigen, and provide evidence that B cells and antibody play a role in the development of an effective response to a primary infection with G. muris in mice.

Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group streptococcus experimental endocarditis.

PubMed Central

Rouse, M S; Steckelberg, J M; Brandt, C M; Patel, R; Miro, J M; Wilson, W R

1997-01-01

The efficacy of azithromycin or clarithromycin was compared to that of amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no antibiotics or two doses of amoxicillin at 25 mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg, clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at 10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after bacterial inoculation, the rabbits were killed and aortic valve vegetations were aseptically removed and cultured for bacteria. Infective endocarditis occurred in 88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals receiving clarithromycin, and 1% of animals receiving azithromycin. All five regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis in this model. PMID:9257739

Newly postulated neurodevelopmental risks of pediatric anesthesia.

PubMed

Hays, Stephen R; Deshpande, Jayant K

2011-04-01

Recent animal and human studies have raised concern that exposure to anesthetic agents in children may cause neuronal damage and be associated with adverse neurodevelopmental outcomes. Exposure of young animals to anesthetic agents above threshold doses and durations during a critical neurodevelopmental window in the absence of concomitant painful stimuli causes widespread neuronal apoptosis and subsequent abnormal behaviors. The relevance of such animal data to humans is unknown. Untreated neonatal pain and stress also are associated with enhanced neuronal death and subsequent maladaptive behaviors, which can be prevented by exposure to these same anesthetic agents. Retrospective observational human studies have suggested a dose-dependent association between multiple anesthetic exposures in early childhood and subsequent learning disability, the causality of which is unknown. Ongoing prospective investigations are underway, the results of which may clarify if and what neurodevelopmental risks are associated with pediatric anesthesia. No change in current practice is yet indicated.

Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellender, M.; Hodgson, A.; Wood, K.L.

Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with [sup 57]CO. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of [sup 57]CO at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and [sup 57]Comore » activity of the washings. The subsequent fractional clearance rate of [sup 57]Co from lavaged animals was not significantly different from that in a group of untreated control animals. 30 refs., 2 figs., 2 tabs.« less

Schistosoma japonicum: An ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Y.E.; Jiang, C.F.; Han, J.J.

1990-07-01

Water buffaloes were vaccinated three times with 10,000 Schistosoma japonicum cercariae irradiated with ultraviolet (uv) light at a dose of 400 microW x min/cm2. The irradiation was performed with cheap, simple, and portable equipment in a rural area of Hubei Province (People's Republic of China). A challenge infection of 1000 untreated cercariae was given to six vaccinated and six naive control buffaloes, while two vaccinated animals were not challenged. The experiment was terminated 6 weeks after the challenge. Control animals had lost body weight and harbored a mean of 110 worms and 37 eggs per gram of liver. The vaccinatedmore » animals gained weight after the challenge and developed 89% resistance to infection with S. japonicum. Since schistosomiasis japonica is nowadays transmitted in China predominantly by domestic livestock, a uv-attenuated cercarial vaccine for bovines may contribute to the control of this disease.« less

Effects of osteochondral defect size on cartilage regeneration using a double-network hydrogel.

PubMed

Higa, Kotaro; Kitamura, Nobuto; Goto, Keiko; Kurokawa, Takayuki; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

2017-05-22

There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O'Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p < 0.05). The 2.5-mm and 4.3-mm DN gel implanted defects maintained relatively high macroscopic and histological scores for the 12-week implantation period, while the histological score of the 5.8-mm DN gel implanted defect had decreased somewhat but statistically significantly at 12 weeks (p = 0.0057). The DN gel induced cartilage regeneration in defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of osteochondral defects.

Topical anesthesia mitigates the pain of castration in beef calves.

PubMed

Lomax, S; Windsor, P A

2013-10-01

Castration involves the removal of the testes and is performed to improve product quality and management of male calves. The procedure has been proven to cause significant pain and stress, and despite several attempts to reduce the impact of castration on animal welfare, there has yet to be a practical and affordable option made available for farmer application. To address this issue, we conducted 2 trials (n = 18 and 27) to examine the efficacy of topical anesthetic Tri-Solfen (TA) to alleviate the pain of surgical castration. Angus bull calves (135.8 ± 5.7 kg) aged 3 to 4 mo were randomly allocated to 3 treatment groups, including surgical castration, castration in combination with TA, and uncastrated controls. In Trial 1, pain-related behavior was assessed using a customized numerical rating scale (NRS) over 4 h. In Trial 2, pre- and postoperative skin sensitivity of the wound and periwound areas was assessed using an electronic von Frey anesthesiometer (IITC Life Sciences, Woodland Hills, CA) and von Frey monofilaments (300 g). Sampling was repeated at 1 min and 2, 4, 6, and 24 h after castration. Pain threshold was measured as maximum pressure (g) exerted by the electronic anesthesiometer to invoke animal reflex, and responses to the von Frey monofilaments were scored from 0 to 3 using a NRS on the basis of local and central motor reflexes. Calves treated with TA displayed significantly less pain-related behaviors up to 3.5 h after castration than untreated calves (P < 0.001) and did not differ from uncastrated controls. Topical anesthetic-treated calves also exhibited significantly greater pain threshold of the wound (559.2 ± 14.3 g) and surrounding skin (602.8 ± 16.5 g) than untreated calves (446.0 ± 18.9 and 515.3 ± 20.4 g, respectively; P < 0.001). Control and TA-treated calves had significantly lower mean response scores to von Frey stimulation than untreated calves (0.333, 0.978, and 4.289, respectively; P < 0.001). Results indicate that TA effects rapid and prolonged pain alleviation in calves up to 24 h after castration. Topical anesthesia may present a cost-effective, practical, on-farm approach to pain alleviation and is proposed as a potential tool for reducing the welfare impact on the beef animal in routine husbandry procedures.

Side effects of anastrozole in the experimental pre-menopausal mammary carcinogenesis.

PubMed

Sadlonova, V; Kubatka, P; Kajo, K; Ostatnikova, D; Nosalova, G; Adamicova, K; Sadlonova, J

2009-01-01

The aim of this study was to assess side effects of aromatase inhibitor anastrozole in the prevention of N-methyl-N-nitrosourea - induced pre-menopausal mammary carcinogenesis in female Sprague-Dawley rats. This model mimicked situation in healthy, but from the point of view of the development of breast cancer, high-risk pre-menopausal women.

Aromatase inhibitor anastrozole was used as a chemopreventive agent taken by the animals in the food during the whole period of time of the experiment. Group 1 - the control group had taken food without anastrozole, the groups 2 and 3 with anastrozole in various concentrations - 0.05 mg/1 kg of food (ANA 0.05) and 0.5 mg/1 kg of food (ANA 0.5).

In anastrozole-treated animals in comparison with untreated animals, macroscopic changes of uterus and vagina were not found. The values of absolute and relative wet weight of uterus and vagina in the groups ANA 0.05 and ANA 0.5 were comparable with the control. Histological examination did not show atrophic changes in endometrium of uterus and in epithelium of vagina in anastrozole-treated animals. In the group ANA 0.5 myometrium was significantly grosser than in the group ANA 0.05 (P<0.05). Anastrozole neither affects parameters of plasma lipid metabolism (triacylglycerols, total cholesterol, low - density lipoprotein cholesterol and high - density lipoprotein cholesterol) nor serum levels of sex hormones (estradiol, testosterone, dehydroepiandrosterone). Compact bone thickness in the groups with anastrozole was significantly increased in comparison with untreated animals (P<0.001). A significant increase in body weight was found in the group ANA 0.5 compared with the control group (P<0.01). The significant increase in body weight gain was not attended by the significant increase in food intake.

The side effects of aromatase inhibitor anastrozole in the prevention of N-methyl-N-nitrosourea - induced pre-menopausal mammary carcinogenesis in female Sprague-Dawley rats on myometrium, compact bone thickness and body weight gain were observed.

Do adult men with untreated ventral penile curvature have adverse outcomes?

PubMed Central

Menon, Vani; Breyer, Benjamin; Copp, Hillary L.; Baskin, Laurence; Disandro, Michael; Schlomer, Bruce J.

2016-01-01

Summary Introduction Congenital ventral penile curvature without hypospadias is often treated surgically in childhood. The history of untreated ventral curvature is unknown. Objective This study’s aim was to examine the association of untreated ventral penile curvature with various sexual and psychosexual outcomes. Study design An electronic survey was advertised to men older than 18 years on Facebook. Men with possible ventral penile curvature identified themselves by choosing sketches that most closely represented their anatomy. Outcomes assessed included: Sexual Health Inventory for Men, difficulty of intercourse because of curvature, International Prostate Symptom Score, Penile Perception Score, psychosexual milestones, paternity, infertility, sitting to urinate, and the CDC HRQOL-4 module. Results Among participants, 81 out of 684 men (11.8%) reported untreated ventral penile curvature. Participants with self-reported curvature noted more difficulty with intercourse because of curvature (4.5 vs 4.9, p < 0.001), more unhealthy mental days (8.6 vs 6.2, p = 0.02), and increased dissatisfaction with penile self-perception compared with men without reported curvature (8.6 vs 9.5, p < 0.001). Discussion Men with possible untreated ventral curvature reported worse penile perception scores, more mentally unhealthy days, and increased difficulty with intercourse secondary to curvature compared with men without curvature. A limitation to this study is selection bias; responses collected were self-reported from survey volunteers. Additionally, the question identifying ventral penile curvature is not validated but performed well in pretesting. Most questions were from validated surveys, but some were modeled after validated surveys and/or contained high face validity types of questions. Conclusion Men with possible untreated ventral penile curvature reported more dissatisfaction with penile appearance, increased difficulty with intercourse, and more unhealthy mental days. Given high success rates, low complications, and improved outcomes after surgical correction of penile curvature reported in the literature, our results support correction of congenital penile curvature in childhood. PMID:26776946

Decision Modeling in Sleep Apnea: The Critical Roles of Pretest Probability, Cost of Untreated Obstructive Sleep Apnea, and Time Horizon

PubMed Central

Moro, Marilyn; Westover, M. Brandon; Kelly, Jessica; Bianchi, Matt T.

2016-01-01

Study Objectives: Obstructive sleep apnea (OSA) is associated with increased morbidity and mortality, and treatment with positive airway pressure (PAP) is cost-effective. However, the optimal diagnostic strategy remains a subject of debate. Prior modeling studies have not consistently supported the widely held assumption that home sleep testing (HST) is cost-effective. Methods: We modeled four strategies: (1) treat no one; (2) treat everyone empirically; (3) treat those testing positive during in-laboratory polysomnography (PSG) via in-laboratory titration; and (4) treat those testing positive during HST with auto-PAP. The population was assumed to lack independent reasons for in-laboratory PSG (such as insomnia, periodic limb movements in sleep, complex apnea). We considered the third-party payer perspective, via both standard (quality-adjusted) and pure cost methods. Results: The preferred strategy depended on three key factors: pretest probability of OSA, cost of untreated OSA, and time horizon. At low prevalence and low cost of untreated OSA, the treat no one strategy was favored, whereas empiric treatment was favored for high prevalence and high cost of untreated OSA. In-laboratory backup for failures in the at-home strategy increased the preference for the at-home strategy. Without laboratory backup in the at-home arm, the in-laboratory strategy was increasingly preferred at longer time horizons. Conclusion: Using a model framework that captures a broad range of clinical possibilities, the optimal diagnostic approach to uncomplicated OSA depends on pretest probability, cost of untreated OSA, and time horizon. Estimating each of these critical factors remains a challenge warranting further investigation. Citation: Moro M, Westover MB, Kelly J, Bianchi MT. Decision modeling in sleep apnea: the critical roles of pretest probability, cost of untreated obstructive sleep apnea, and time horizon. J Clin Sleep Med 2016;12(3):409–418. PMID:26518699

Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients

PubMed Central

Price, Richard W.; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Background Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. Methods With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. Results While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Conclusions Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use. PMID:24523921

Bilirubin Level is Associated with Left Ventricular Hypertrophy Independent of Blood Pressure in Previously Untreated Hypertensive Patients

PubMed Central

Ayaz, Teslime; Kocaman, Sinan Altan; Durakoğlugil, Tuğba; Erdoğan, Turan; Şahin, Osman Zikrullah; Şahin, Serap Baydur; Çiçek, Yüksel; Şatiroğlu, Ömer

2014-01-01

Background and Objectives Left ventricular hypertrophy (LVH), a sign of subclinical cardiovascular disease, is an important predictor of cardiovascular morbidity and mortality. The aim of our study was to determine the association of left ventricular mass (LVM) with possible causative anthropometric and biochemical parameters as well as carotid intima-media thickness (CIMT) and brachial flow-mediated dilation (FMD) as surrogates of atherosclerosis and endothelial dysfunction, respectively, in previously untreated hypertensive patients. Subjects and Methods Our study included 114 consecutive previously untreated hypertensive patients who underwent echocardiography and ultrasonography to evaluate their vascular status and function via brachial artery CIMT and FMD. Results Among all study parameters, age, systolic blood pressure (BP), diastolic BP, pulse pressure, plasma glucose, uric acid, total bilirubin, direct bilirubin, hemoglobin, and CIMT were positively correlated with the LVM index. Multiple logistic regression analysis revealed that office systolic BP, age, male gender, and total bilirubin were independent predictors of LVH. Conclusion Bilirubin seems to be related to LVM and LVH. The positive association of bilirubin with these parameters is novel and requires further research. PMID:25278987

Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families

PubMed Central

Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L.; Drilling, Amy

2016-01-01

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was –7.5 SDs with a very delayed bone age of –13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (–5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. PMID:27244801

The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

PubMed Central

Tanuma, Yasushi

2017-01-01

Objectives The persistence of silodosin and the reasons for withdrawal from treatment of previously untreated Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in real-life clinical practice. Methods A total of 81 previously untreated Japanese patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and prospectively followed for 4 years. The persistence rate was estimated using the Kaplan-Meier method. If silodosin had to be terminated or a patient did not come to the hospital, the reason was determined. Results The 6-month, 1-year, 2-year, 3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%, respectively. The most frequent reason (22.2%) for withdrawal was symptom resolution. After silodosin treatment, the international prostate symptom score and the quality of life index were significantly improved and maintained for 4 years. Conclusions 35.8% of previously untreated Japanese patients continued silodosin for 4 years. Many patients terminated silodosin for various reasons, the most frequent of which was symptom resolution. The effects of silodosin were maintained when the patients continued treatment. Trial Registration This study was approved by the institutional review board of Hokkaido Prefectural Esashi Hospital (number 2007-2) and was registered in a public trial registry (UMIN000026910). PMID:28694823

Modest Improvement of Untreated Severe Sleep-Disordered Breathing in the Middle-Aged and Elderly

PubMed Central

Jeon, Hong Jun; Bang, Young Rong; Jeon, Soyeon; Lee, Tae Young; Park, Hye Youn

2017-01-01

Objective It has been reported that untreated sleep-disordered breathing (SDB) deteriorates over time, however this remains contentious. The aim of the present study is to evaluate the clinical course of SDB in middle-aged and older SDB patients, and to identify how relevant factors contribute to the change in SDB severity. Methods Baseline and follow-up polysomnographic data of 56 untreated SDB patients (mean age, 61.2±5.71) were obtained retrospectively and the mean interval was 62.4±22.0 months. Subgroup analysis was performed based on the baseline severity, and the factors associated with the course of SDB were analyzed. Results At the baseline, 13 subjects were simple snorers, 15 had mild to moderate SDB, and 28 were severe SDB patients. While there was no significant change in apnea-hypopnea index (AHI) as a whole, subgroup analysis showed decrease of AHI in severe SDB patients (43.9±10.6 to 35.6±20.0, p=0.009). The change in supine time percent and baseline AHI were associated with the change in AHI (β=0.387, p=0.003; β=-0.272, p=0.037). Conclusion Untreated SDB did not deteriorate over time with modest improvement in severe SDB. A proportion of severe SDB patients might expect decrease in SDB severity irrespective of changes in sleep position or body weight. PMID:29042892

Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families.

PubMed

Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L; Drilling, Amy; Petryk, Anna

2016-05-01

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was -7.5 SDs with a very delayed bone age of -13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (-5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. Copyright © 2016 by the American Academy of Pediatrics.

Effect of antithyroid drug on chick embryos during the last week of development: delayed hatching and decreased cerebellar acetylcholinesterase activity.

PubMed

Haba, Gen; Nishigori, Hidekazu; Tezuka, Yu; Kagami, Keisuke; Sugiyama, Toru; Nishigori, Hideo

2011-11-01

Hypothyroid state during embryogenesis disturbs normal growth and brain development, influencing later life. To evaluate the harmful consequences of the state during embryogenesis using an animal model, we inhibited thyroid hormone biosynthesis in chick embryos by using methimazole (MMI). Typically, embryos were treated with MMI (20 µmol/egg) on day 14, and examined on specific days.  Of the control embryos, 94% hatched on day 21, whereas 0% and 60% of MMI-treated embryos hatched on days 21 and 24, respectively. MMI retarded the rates of bodyweight gain as well as liver and heart development, and delayed hatching. However, the external differences in appearance and differences in the weights of the newly hatched control chicks on day 21 and the MMI-treated chicks on day 24 were less obvious. Embryos treated with MMI exhibited increased mass in their brain parts on day 24. Most notably, the treatment resulted in a 1.35-fold increase in cerebellum weight compared to that of the untreated animals. Acetylcholinesterase activity in the cerebellum on the day of hatching decreased significantly to 0.85-fold that of the untreated controls. Thyroid hormone receptor β mRNA was detected from day 12 and dramatically expressed from day 19 to the day of hatching. The 'fertilized hen's egg-chick embryo-chick system' is an appropriate animal model for investigating the hypothyroid state during embryogenesis. Decreased cerebellar acetylcholinesterase activity after MMI treatment was assumed to relate to a mechanism of motor and cognitive deficits in congenital hypothyroidism. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Inactivation of Orientia tsutsugamushi in red blood cells, plasma, and platelets with riboflavin and light, as demonstrated in an animal model.

PubMed

Rentas, Francisco; Harman, Ronald; Gomez, Charlotte; Salata, Jeanne; Childs, Joseph; Silva, Tonya; Lippert, Lloyd; Montgomery, Joshua; Richards, Allen; Chan, Chye; Jiang, Ju; Reddy, Heather; Li, John; Goodrich, Raymond

2007-02-01

Treatment of blood products with riboflavin and light has been used to reduce the number of certain pathogens. Orientia (formerly Rickettsia) tsutsugamushi, the scrub typhus agent, is an obligate intracellular bacterium that grows free in the cytoplasm of infected cells. This study evaluated the capability of riboflavin and light to inactivate O. tsutsugamushi in red blood cells (RBCs), platelets (PLTs), and plasma, as measured by mouse infectivity. A total of 108 mice, equally divided into groups receiving RBCs, plasma, and PLTs, received untreated products infected with 10(0) to 10(5) organisms. Eighteen mice received products infected with 10(5) organisms and were subsequently treated with riboflavin and light. Mice were monitored daily for up to 17 days for signs and symptoms of infection (e.g., lethargy, labored breathing, rough coat) and killed upon appearance of symptoms or on Day 17 after infection. Real-time polymerase chain reaction (PCR) on blood and Giemsa stains from peritoneal exudates were performed. A total of 102 of 108 mice receiving the untreated products developed signs and symptoms of infection and had positive PCR and Giemsa stain results. None of the 18 animals receiving riboflavin and light-treated blood products exhibited signs or symptoms of infection, nor was infection observed by PCR testing or Giemsa staining. Riboflavin and light are effective in reducing O. tsutsugamushi. Mice injected with blood products inoculated with 10(5) organisms and treated with riboflavin and light did not experience any signs or symptoms of infection, 17 days after inoculation. A 5-log reduction of this organism in blood was achieved as assayed in an animal model.

Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression.

PubMed

Baka, Judith; Csakvari, Eszter; Huzian, Orsolya; Dobos, Nikoletta; Siklos, Laszlo; Leranth, Csaba; MacLusky, Neil J; Duman, Ronald S; Hajszan, Tibor

2017-02-20

Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague-Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals. After 'postpartum' withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during 'postpartum' stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during 'postpartum' stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated 'postpartum' females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging 'synaptogenic hypothesis' of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Stress Induces Equivalent Remodeling of Hippocampal Spine Synapses in a Simulated Postpartum Environment and in a Female Rat Model of Major Depression

PubMed Central

Baka, Judith; Csakvari, Eszter; Huzian, Orsolya; Dobos, Nikoletta; Siklos, Laszlo; Leranth, Csaba; MacLusky, Neil J; Duman, Ronald S; Hajszan, Tibor

2017-01-01

Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague-Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn ‘postpa rtum’, simulated proestrus, and hormone-treated ‘postpartum’ animals. After ‘postpartum’ withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn ‘postpartum’ females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during ‘postpartum’ stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during ‘postpartum’ stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated ‘postpartum’ females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging ‘synaptogenic hypothesis’ of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness. PMID:28012870

Mutagen and Oncogen Study on N-Phenyl-Alpha-Naphthylamine

DTIC Science & Technology

1976-12-01

several dose levels of the test compound for five days and then sequentially mated to two virgin untreated females each week over the period of...Stock Solutions The compound was prepared daily from stock solutions. N-phenyl-alpha-naphthylamine pellets were ground with a mortor and pestle ...five animals to a cage during the five days of dosing. After two days of rest, each male was caged with two virgin females from Monday through Friday

Synthesis and preliminary antileukemic studies of cyclic mitoguazone analogues.

PubMed

Krezel, I; Graczyk, J

1998-03-01

Analogues of mitoguazone bearing a terminal amidino group as a part of the seven-membered ring of 1,3-diazepine and six-membered ring of pyrimidine were prepared in order to evaluate in vivo antileukemic action towards L1210 leukemia in mice. Preliminary pharmacological screening showed that the investigated compounds increase the life span (T/C%) of the treated mice in comparison with the untreated animals. The strongest antineoplastic effect was exhibited by compound 8.

Unveiling the potential of novel yeast protein extracts in white wines clarification and stabilization

PubMed Central

Fernandes, Joana P.; Neto, Rodrigo; Centeno, Filipe; De Fátima Teixeira, Maria; Gomes, Ana Catarina

2015-01-01

Fining agents derived from animal and mineral sources are widely used to clarify and stabilize white wines. Nevertheless, health and environmental problems are being raised, concerning the allergenic and environmental impact of some of those fining products. In this study, our aim is to validate the potential of yeast protein extracts, obtained from an alternative and safe source, naturally present in wine: oenological yeasts. Three untreated white wines were used in this work in order to evaluate the impact of these novel yeast protein extracts (YPE) in terms of the wine clarification and stabilization improvement. Two separated fining trials were thus conducted at laboratory scale and the yeast alternatives were compared with reference fining agents, obtained from mineral, animal and vegetable origins. Our results indicate that YPE were capable to promote (i) brilliance/color improvement, (ii) turbidity reduction (76–89% comparing with the untreated wines), and (iii) production of compact and homogeneous lees (44% smaller volume than obtained with bentonite). Additionally, after submitting wines to natural and forced oxidations, YPE treatments revealed (iv) different forms of colloidal stabilization, by presenting comparable or superior effects when particularly compared to casein. Altogether, this study reveals that YPE represent a promising alternative for white wine fining, since they are resultant from a natural and more sustainable origin, at present not regarded as potential allergenic according to Regulation (EC) No. 1169/2011. PMID:25853122

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

PubMed

Coetzee, J F; Gehring, R; Bettenhausen, A C; Lubbers, B V; Toerber, S E; Thomson, D U; Kukanich, B; Apley, M D

2007-08-01

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was <10 microg/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5 microg/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

PubMed Central

Chandran, Preethi K.; Kuttan, Ramadasan

2008-01-01

Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

How should we respond to the emergence of plasmid-mediated colistin resistance in humans and animals?

PubMed

Al-Tawfiq, Jaffar A; Laxminarayan, Ramanan; Mendelson, Marc

2017-01-01

The widespread use of antibiotics in humans and animals has contributed to growing rates of antibiotic resistance. Previously treatable bacterial infections now require the last line of antibiotics or are untreatable. The current antibiotic of last resort for carbapenem-resistant Gram-negative bacterial infections is often colistin. Evidence for the shifting pattern of colistin resistance and how the international community should respond are discussed in this review. The literature on colistin resistance was reviewed. Plasmid-mediated colistin resistance encoded by mcr-1 was first documented in China during the routine surveillance of food animals. This has been followed by similar reports across a wide geographic area, in humans, animals, and the environment. The mcr-1 gene has been reported among human isolates in 29 countries, related to environmental samples in four countries, and in food animals and other animals in 28 countries. More recently, a second gene encoding resistance, mcr-2, has been isolated from porcine and bovine Escherichia coli. The emergence and horizontal transmission of colistin resistance highlights the need for heightened stewardship efforts across the One Health platform for this antibiotic of last resort, and indeed for all antibiotics used in animals and humans. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Catheter-directed Gastric Artery Chemical Embolization Suppresses Systemic Ghrelin Levels in Porcine Model

PubMed Central

Arepally, Aravind; Barnett, Brad P.; Patel, Tarek T.; Howland, Valerie; Boston, Ray C.; Kraitchman, Dara L.; Malayeri, Ashkan A.

2008-01-01

Purpose: To prospectively test, in a porcine model, the hypothesis that catheter-directed gastric artery chemical embolization (GACE) can result in suppression of systemic ghrelin levels and affect weight gain. Materials and Methods: This study, which had Animal Care and Use Committee approval, was performed in healthy, growing swine (weight range, 40–45 kg; n = 10). GACE was performed in five swine with the infusion of sodium morrhuate (125 μg) selectively into the gastric arteries that supply the fundus. Five control animals underwent a sham procedure with 5 mL of saline. Weight and fasting plasma ghrelin levels were obtained in animals at baseline and in weeks 1–4. Statistical testing for substantial differences in ghrelin blood levels over time and between treated and untreated animals was performed by using a cross-sectional time-series linear model with feasibility generalized least squares. Results: The pattern of the change in ghrelin levels over time was significantly different between control and treated animals (P < .004). In treated animals, ghrelin levels were significantly reduced at week 1 (mean, 664.1 pg/mL ± 103.1 [standard error of the mean], P < .02), week 2 (mean, 618.1 pg/mL ± 180.4, P < .001), week 3 (mean, 578.4 pg/mL ± 214.9, P < .001), and week 4 (mean, 876.6 pg/mL ± 228.6, P < .03) relative to baseline (mean, 1006.3 pg/mL ± 190.1). The percentage change in serum ghrelin values in swine treated with GACE decreased from baseline to −34%, −38.6%, −42.5%, and −12.9% during weeks 1–4, respectively. In control swine, percentage change in serum ghrelin was −1.7%, −9.7%, +2.6%, and +18.2% during weeks 1–4, respectively. At the end of 4 weeks, control swine continued to gain weight, with a 15.1% increase from their original weight, while the weight in swine treated with GACE plateaued at an increase of 7.8% from the original weight. Conclusion: Catheter-directed GACE can suppress the appetite hormone ghrelin and affect weight gain. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/249/1/127/DC1 © RSNA, 2008 PMID:18796671

Hyperglycemia in BALB/c mice after pretreatment with one subdiabetogenic dose of streptozotocin and subsequent infection with a Coxsackie B4 strain.

PubMed

Wegner, U; Kewitsch, A; Madauss, M; Döhner, L; Zühlke, H

1985-01-01

Male BALB/c mice were injected with one subdiabetogenic dose of streptozotocin followed by Coxsackie B4 virus infection 7 days later. The animals developed a transient hyperglycemia after streptozotocin-pretreatment and infection with a human Coxsackie B4 isolate. Frozen sections of pancreata stained with FITC-labeled antibodies showed an intensive infection of the exocrine tissue. Immunofluorescence studies with isolated islets obtained from streptozotocin-treated or untreated animals demonstrated virus antigen in about 20% of the islets 5 days after in vivo virus infection. It is supposed that the hyperglycemia measured in our experiments was caused by a cumulative effect of streptozotocin and virus infection.

Application of Adipose-Derived Stem Cells on Scleral Contact Lens Carrier in an Animal Model of Severe Acute Alkaline Burn

PubMed Central

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2015-01-01

Purpose To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. Materials and Methods After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Results Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Conclusion Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits. PMID:24901976

Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities.

PubMed

Mastrangelo, Peter; Norris, Michael J; Duan, Wenming; Barrett, Edward G; Moraes, Theo J; Hegele, Richard G

2017-09-19

Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target.

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency

PubMed Central

Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio

2014-01-01

Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2−/−) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2−/− mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2−/−200dCMP/dTMP) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. Subject Categories Genetics, Gene Therapy & Genetic Disease; Metabolism PMID:24968719

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency.

PubMed

Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio

2014-08-01

Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2(-/-)) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2(-/-) mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2(-/-200dCMP/) (dTMP)) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Radiofrequency ablation of liver tumors in combination with local OK-432 injection prolongs survival and suppresses distant tumor growth in the rabbit model with intra- and extrahepatic VX2 tumors.

PubMed

Kageyama, Ken; Yamamoto, Akira; Okuma, Tomohisa; Hamamoto, Shinichi; Takeshita, Toru; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio

2013-10-01

To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

The role of three-dimensional pure bovine gelatin scaffolds in tendon healing, modeling, and remodeling: an in vivo investigation with potential clinical value.

PubMed

Oryan, Ahmad; Sharifi, Pardis; Moshiri, Ali; Silver, Ian A

2017-09-01

Large tendon defects involving extensive tissue loss present complex clinical problems. Surgical reconstruction of such injuries is normally performed by transplanting autogenous and allogenous soft tissues that are expected to remodel to mimic a normal tendon. However, the use of grafts has always been associated with significant limitations. Tissue engineering employing artificial scaffolds may provide acceptable alternatives. Gelatin is a hydrolyzed form of collagen that is bioactive, biodegradable, and biocompatible. The present study has investigated the suitability of gelatin scaffold for promoting healing of a large tendon-defect model in rabbits. An experimental model of a large tendon defect was produced by partial excision of the Achilles tendon of the left hind leg in adult rabbits. To standardize and stabilize the length of the tendon defect a modified Kessler core suture was anchored in the sectioned tendon ends. The defects were either left untreated or filled with three-dimensional gelatin scaffold. Before euthanasia 60 days after injury, the progress of healing was evaluated clinically. Samples of healing tendon were harvested at autopsy and evaluated by gross, histopathologic, scanning, and transmission electron microscopy, and by biomechanical testing. The treated animals showed superior weight-bearing and physical activity compared with those untreated, while frequency of peritendinous adhesions around the healing site was reduced. The gelatin scaffold itself was totally degraded and replaced by neo-tendon that morphologically had significantly greater numbers, diameters, density, and maturation of collagen fibrils, fibers, and fiber bundles than untreated tendon scar tissue. It also had mechanically higher ultimate load, yield load, stiffness, maximum stress and elastic modulus, when compared to the untreated tendons. Gelatin scaffold may be a valuable option in surgical reconstruction of large tendon defects.

Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation.

PubMed

Scheer, Sebastian; Medina, Tiago S; Murison, Alex; Taves, Matthew D; Antignano, Frann; Chenery, Alistair; Soma, Kiran K; Perona-Wright, Georgia; Lupien, Mathieu; Arrowsmith, Cheryl H; De Carvalho, Daniel D; Zaph, Colby

2017-04-01

The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades-a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4 + T cells using an experimental T cell transfer model of IBD. Our results show that CD4 + T cells isolated from adult mice that had been treated with Abx during gestation and in early life induced a faster onset of IBD in Rag1 -deficient mice compared with CD4 + T cells of untreated mice. Ex vivo functional analyses of IBD-inducing CD4 + T cells did not show significant differences in their immunologic potential ex vivo, despite their in vivo phenotype. However, genome-wide gene-expression analysis revealed that these cells displayed dysregulated expression of genes associated with cell-cycle regulation, metabolism, and cellular stress. Analysis of Abx-treated CD4 + T cell donors showed systemically elevated levels of the stress hormone corticosterone throughout life compared with untreated donors. The cohousing of Abx-treated mice with untreated mice decreased serum corticosterone, and a consequent transfer of the cells from cohoused mice into Rag1 -deficient mice restored the onset and severity of disease to that of untreated animals. Thus, our results suggest that early-life Abx treatment results in a stress response with high levels of corticosterone that influences CD4 + T cell function. © Society for Leukocyte Biology.

Evaluation of Veriox as a Skin Decontamination Product after Dermal Exposure to the Nerve Agent VX

DTIC Science & Technology

2016-09-01

in hair -clipped, unanesthetized guinea pigs. Efficacy was established by generating VX dose-lethality curves for each DC product based on 24 survival...This study compared the effectiveness of Veriox® to RSDL when each was used as a DC product 2 min after dermal exposure to VX in hair -clipped...by the dermal LD90 of VX in untreated animals. A LD90 value of 188 μg/kg generated in hair -clipped, unanesthetized guinea pigs (Clarkson, personal

Breast Cancer Therapy Using Antibody-Endostatin Fusion Proteins

DTIC Science & Technology

2008-04-01

animal tumor and/or human xenograft models. Task 9. Anti-tumor activity in human tumor xenografts (Months 18 -24) Anti-tumor efficacy in human...breast cancer SK-BR-3 xenografts in SCID mice. SK-BR-3 was implanted on the flank of SCID mice.9 The treatment was repeated (shown below in Fig. 18 ...untreated group (p=0.0141) (Fig. 18 ). KEY RESEARCH ACCOMPLISHMENTS o Treatment of established SK-BR-3 xenografts in SCID mice with the αHER2

Exposure of Creosote-Naive and Creosote-Conditioned Limnoria tripunctata (Menzies) of Untreated and Creosote-Treated Wood.

DTIC Science & Technology

1983-06-13

contents, and within the space between the peritrophic membrane and the intestinal lining. Zachery and Colwell [24] and Emery [251 suggested that...seawater, each containing a piece of Whatman #42 filter paper as a food source. Those animals that did not appear to be healthy at the end of this...Parrish and .D. Bultman, "Navy reserach on marine borers and the laboratory culturing of limnorians," Proc. 4th Annual Combined MTS-IEEE Conference

Modification of the actions of some neuroactive drugs by growth hormone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, L.C.; Cotzias, G.C.

The flat serum growth hormone (GH) patterns of untreated parkinsonian patients develop diurnal rises during treatment with levodopa. This chronic exposure to excesses of GH might lead to the eventual emergence of the ''on-off'' phenomenon, which would indicate a need for animal experiments. Pretreatment of mice with GH increased (1) cerebral dopa and dopamine concentrations in levodopa-treated mice, (2) cerebral accumulation of injected tritiated apomorphine and tritiated thymidine, and (3) behavioral responses to levodopa, L-m-tyrosine, apomorphine hydrochloride, and oxotremorine. (auth)

A multifactorial anti‐cachectic approach for cancer cachexia in a rat model undergoing chemotherapy

PubMed Central

Toledo, Míriam; Penna, Fabio; Oliva, Francesc; Luque, Melania; Betancourt, Angelica; Marmonti, Enrica; López‐Soriano, Francisco J.; Argilés, Josep M.

2015-01-01

Abstract Background The effectiveness of drugs aimed at counteracting cancer cachexia is generally tested in pre‐clinical rodent models, where only the tumour‐induced alterations are taken into account, excluding the co‐presence of anti‐tumour molecules that could worsen the scenario and/or interfere with the treatment. Methods The aim of the present investigation has been to assess the efficacy of a multifactorial treatment, including formoterol and megestrol acetate, in cachectic tumour‐bearing rats (Yoshida AH‐130, a highly cachectic tumour) undergoing chemotherapy (sorafenib). Results Treatment of cachectic tumour‐bearing rats with sorafenib (90 mg/kg) causes an important decrease in tumour cell content due to both reduced cell proliferation and increased apoptosis. As a consequence, animal survival significantly improves, while cachexia occurrence persists. Multi‐factorial treatment using both formoterol and megestrol acetate is highly effective in preventing muscle wasting and has more powerful effects than the single formoterol administration. In addition, both physical activity and grip strength are significantly improved as compared with the untreated tumour‐bearing animals. The effects of the multi‐factorial treatment include increased food intake (likely due to megestrol acetate) and decreased protein degradation, as shown by the reduced expression of genes associated with both proteasome and calpain proteolytic systems. Conclusions The combination of the two drugs proved to be a promising strategy for treating cancer cachexia in a pre‐clinical setting that better resembles the human condition, thus providing a strong rationale for the use of such combination in clinical trials involving cachectic cancer patients. PMID:27066318

Fenoterol enantiomers do not possess beneficial therapeutic properties of their racemic mixture in the rat model of post myocardial infarction dilated cardiomyopathy.

PubMed

Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G; Talan, Mark I

2012-04-01

A salutary effect of β(2) adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM. Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography. Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first 2 months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective. The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM.

HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma

PubMed Central

Hu, Ning; Du, Xiaoping; Li, Wei; West, Matthew B.; Choi, Chul-Hee; Floyd, Robert; Kopke, Richard D.

2017-01-01

Oxidative stress is considered a major cause of the structural and functional changes associated with auditory pathologies induced by exposure to acute acoustic trauma AAT). In the present study, we examined the otoprotective effects of 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), a nitrone-based free radical trap, on the physiological and cellular changes in the auditory system of chinchilla following a six-hour exposure to 4 kHz octave band noise at 105 dB SPL. HPN-07 has been shown to suppress oxidative stress in biological models of a variety of disorders. Our results show that administration of HPN-07 beginning four hours after acoustic trauma accelerated and enhanced auditory/cochlear functional recovery, as measured by auditory brainstem responses (ABR), distortion product otoacoustic emissions (DPOAE), compound action potentials (CAP), and cochlear microphonics (CM). The normally tight correlation between the endocochlear potential (EP) and evoked potentials of CAP and CM were persistently disrupted after noise trauma in untreated animals but returned to homeostatic conditions in HPN-07 treated animals. Histological analyses revealed several therapeutic advantages associated with HPN-07 treatment following AAT, including reductions in inner and outer hair cell loss; reductions in AAT-induced loss of calretinin-positive afferent nerve fibers in the spiral lamina; and reductions in fibrocyte loss within the spiral ligament. These findings support the conclusion that early intervention with HPN-07 following an AAT efficiently blocks the propagative ototoxic effects of oxidative stress, thereby preserving the homeostatic and functional integrity of the cochlea. PMID:28832600

(+)-Pentazocine Reduces NMDA-Induced Murine Retinal Ganglion Cell Death Through a σR1-Dependent Mechanism

PubMed Central

Zhao, Jing; Mysona, Barbara A.; Qureshi, Azam; Kim, Lily; Fields, Taylor; Gonsalvez, Graydon B.; Smith, Sylvia B.; Bollinger, Kathryn E.

2016-01-01

Purpose To evaluate, in vivo, the effects of the sigma-1 receptor (σR1) agonist, (+)-pentazocine, on N-methyl-D-aspartate (NMDA)-mediated retinal excitotoxicity. Methods Intravitreal NMDA injections were performed in C57BL/6J mice (wild type [WT]) and σR1−/− (σR1 knockout [KO]) mice. Fellow eyes were injected with phosphate-buffered saline (PBS). An experimental cohort of WT and σR1 KO mice was administered (+)-pentazocine by intraperitoneal injection, and untreated animals served as controls. Retinas derived from mice were flat-mounted and labeled for retinal ganglion cells (RGCs). The number of RGCs was compared between NMDA and PBS-injected eyes for all groups. Apoptosis was assessed using TUNEL assay. Levels of extracellular-signal–regulated kinases (ERK1/2) were analyzed by Western blot. Results N-methyl-D-aspartate induced a significant increase in TUNEL-positive nuclei and a dose-dependent loss of RGCs. Mice deficient in σR1 showed greater RGC loss (≈80%) than WT animals (≈50%). (+)-Pentazocine treatment promoted neuronal survival, and this effect was prevented by deletion of σR1. (+)-Pentazocine treatment resulted in enhanced activation of ERK at the 6-hour time point following NMDA injection. The (+)-pentazocine–induced ERK activation was diminished in σR1 KO mice. Conclusions Targeting σR1 activation prevented RGC death while enhancing activation of the mitogen-activated protein kinase (MAPK), ERK1/2. Sigma-1 receptor is a promising therapeutic target for retinal neurodegenerative diseases. PMID:26868747

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

PubMed Central

2014-01-01

Background WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Methods Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Results Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels. Conclusion Altogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea. PMID:25095704

Effect of steam explosion and microbial fermentation on cellulose and lignin degradation of corn stover.

PubMed

Chang, Juan; Cheng, Wei; Yin, Qingqiang; Zuo, Ruiyu; Song, Andong; Zheng, Qiuhong; Wang, Ping; Wang, Xiao; Liu, Junxi

2012-01-01

In order to increase nutrient values of corn stover, effects of steam explosion (2.5 MPa, 200 s) and Aspergillus oryzae (A. oryzae) fermentation on cellulose and lignin degradation were studied. The results showed the contents of cellulose, hemicellulose and lignin in the exploded corn stover were 8.47%, 50.45% and 36.65% lower than that in the untreated one, respectively (P<0.05). The contents of cellulose and hemicellulose in the exploded and fermented corn stover (EFCS) were decreased by 24.36% and 69.90%, compared with the untreated one (P<0.05); decreased by 17.35% and 38.59%, compared with the exploded one (P<0.05). The scanning electron microscope observations demonstrated that the combined steam explosion and fermentation destructed corn stover. The activities of enzymes in EFCS were increased. The metabolic experiment showed that about 8% EFCS could be used to replace corn meal in broiler diets, which made EFCS become animal feedstuff possible. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lack of behavioral sensitization to repeated cocaine administration from postnatal days 1 to 10.

PubMed

Meyer, J S; Yacht, A C

1993-09-01

This research determined whether sensitization (or tolerance) to the behavioral effects of cocaine in rat pups would occur following repeated cocaine administration. Rats were injected daily with 20 mg/kg of cocaine HCl s.c. from postnatal day 1 to day 10, injected with saline vehicle only, or left untreated during this period. On day 11, animals from each group were challenged with either 0, .625, 1.25, or 2.50 mg/kg of cocaine and their behavioral responses were recorded. Prior cocaine treatment did not influence the acute effects of cocaine on ultrasonic vocalizations or on any observed motor responses. In contrast, the cocaine- and saline-treated pups differed in a similar manner from the untreated control group on several behavioral measures. These results indicate that the sensitizing effects of repeated cocaine administration are not manifested during the neonatal period. However, the stimulation (stress) of handling and injection may alter the subsequent responsivity of infant rats to a cocaine challenge.

IN SITU RT-PCR DETECTION OF CYP1A MRNA IN PHARYNGEAL EPITHELIUM AND CHONDROID CELLS OF CHEMICALLY UNTREATED FISH: INVOLVEMENT IN CRANIOFACIAL SKELETAL DEVELOPMENT? (R827102)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Effect of cyanamide on toxicity and glutathione depletion in rat hepatocyte cultures: differences between two dichloropropanol isomers.

PubMed

Hammond, A H; Fry, J R

1999-09-30

The effect of aldehyde dehydrogenase inhibition by cyanamide pre-treatment in vitro on dichloropropanol-dependent toxicity and glutathione depletion was investigated in 24 h rat hepatocyte cultures. Cyanamide pre-treatment had no effect on nitrophenol hydroxylase, 7-methoxy-, 7-ethoxy- or 7-benzyloxyresorufin O-dealkylase activities in 24 h cultures from untreated rats, and had no effect on intracellular glutathione content in cultures from untreated rats, or in cultures from isoniazid-treated rats in which cytochrome P4502E1 (CYP2E1) is increased. In cultures from untreated animals the primary alcohol, 2,3-dichloropropanol, was not toxic and did not significantly deplete glutathione. Cyanamide pre-treatment however, potentiated both toxicity and glutathione depletion. Induction of CYP2E1 also potentiated the toxicity of 2,3-dichloropropanol, and in these cultures cyanamide pre-treatment significantly increased both toxicity and glutathione depletion. Cyanamide did not alter the toxicity or glutathione depletion due to the secondary alcohol, 1,3-dichloropropanol, irrespective of CYP2E1 induction. These results indicate that the primary alcohol isomer is metabolised to an aldehyde intermediate which depletes glutathione. Under basal conditions this metabolite appears to be effectively detoxified, but increased CYP2E1 activity and/or decreased aldehyde dehydrogenase activity promotes accumulation of metabolite, and therefore increases glutathione depletion and toxicity.

Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.

PubMed

Capelozzi, Marco A; Leick-Maldonado, Edna A; Parra, Edwin R; Martins, Mílton A; Tibério, Iolanda F L C; Capelozzi, Vera L

2007-05-14

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology

PubMed Central

Zhang, Bei-ying; Li, Shao-chuan; Luo, Dong-zhang; Zhan, Xiaoshu; Chen, Sheng-feng; Chen, Zhi-sheng; Liu, Can-ying; Ji, Hui-qin; Bai, Yin-shan; Li, Dong-sheng; He, Yang

2018-01-01

Objective The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Methods Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro. A suspension of allogeneic UC-MSCs (1 × 106) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF-α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF-α of the untreated control group were significantly higher than those of the treated group (P < 0.05) 7–14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference (P < 0.01). Conclusion Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response. PMID:29861739

Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

ClinicalTrials.gov

2014-05-15

Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Oligodendroglioma

Small strongyle infection: consequences of larvicidal treatment of horses with fenbendazole and moxidectin.

PubMed

Steinbach, Tanja; Bauer, Christian; Sasse, Hermann; Baumgärtner, Wolfgang; Rey-Moreno, Cecilia; Hermosilla, Carlos; Damriyasa, I Made; Zahner, Horst

2006-06-30

The study was undertaken to evaluate adverse effects of larvicidal treatment in horses naturally infected with cyathostomins. Out of 24 ponies kept on pasture, four animals were housed in September and anthelmintically cured to serve as worm-free controls (group C-0). The others were housed in December. Eight animals each were treated 8 weeks later with 5 x 7.5mg/kg fenbendazole (FBZ) or 1 x 0.4 mg/kg moxidectin (MOX). Four animals remained untreated (group C-i). Two, 4, 6 and 14 days after the end of treatment two animals of each of the treated groups were necropsied together with group C-0 and C-i animals. Infected animals before treatment showed weight loss, eosinophilia, increased plasma protein and globulin contents. Treatment was followed by weight gain and temporal plasma protein and globulin increase. Proportions of CD4+ and CD8+ T lymphocytes in the peripheral blood did not differ between the groups before treatment but dropped significantly temporally after FBZ treatment. Group C-0 was worm-free at necropsy. Group C-i animals contained variable numbers of luminal and tissue cyathostomins. Histological sections showed larval stages in the lamina propria und submucosa surrounded by macrophages. Either treatment was effective against luminal parasites and reduced the number of larvae in the bowel wall beginning 4-6 days after FBZ and 6-14 days after MOX treatment. Histologically, as a first reaction after FBZ application T lymphocytes accumulated around morphologically intact L4 in the submucosa. Subsequently T lymphocytes associated with eosinophils infiltrated the submucosa. Parasites became enclosed by granulomas with eosinophils adhering to and invading the larvae which started to disintegrate on day 4. Later on, particularly on day 14 inflammation extended into the mucosa and was frequently associated with ulcerations. Third stage larvae in general and L4 in the lamina propria, however, seemed not to be affected until day 14 and even then, parasites did usually not generate extensive inflammation. After MOX treatment severe morphologically detectable alterations of tissue larvae could not be observed earlier than day 14. Different from FBZ treatment, larvae disintegrated and were obviously resorbed without causing severe inflammation in the gut wall. In conclusion treatment with either drug was efficacious against tissue larvae of cyathostomins but there may be different clinical consequences: in contrast to MOX effects, killing of larvae due to FBZ was associated with severe tissue damage, which clinically may correspond to reactions caused by synchronous mass emergence of fourth stage larvae, i.e., may mimic larval cyathostominosis.

Genome‑wide identification of long noncoding RNAs in CCl4‑induced liver fibrosis via RNA sequencing.

PubMed

Gong, Zhenghua; Tang, Jialin; Xiang, Tianxin; Lin, Jiayu; Deng, Chaowen; Peng, Yanzhong; Zheng, Jie; Hu, Guoxin

2018-05-07

Liver fibrosis occurs as a result of chronic liver lesions, which may subsequently develop into liver cirrhosis and hepatocellular carcinoma. The involvement of long noncoding RNAs (lncRNAs) in liver fibrosis is being increasingly recognized. However, the exact mechanisms and functions of the majority of lncRNAs are poorly characterized. In the present study, the hepatotoxic substance carbon tetrachloride (CCl4) was employed to induce liver fibrosis in an animal model and agenome‑wide identification of lncRNAs in fibrotic liver tissues compared with CCl4 untreated liver tissues was performed using RNA sequencing. Sprague‑Dawley rats were treated with CCl4 for 8 weeks. Histopathogical alterations were observed in liver tissues, and serum levels of alanine aminotransferase, aspartate aminotransferase, transforming growth factor‑β1 and tumor necrosis factor‑α were significantly higher, in the CCl4‑treated group compared with the CCl4 untreated group. RNA sequencing of liver tissues demonstrated that 231 lncRNAs and 1,036 mRNAs were differentially expressed between the two groups. Furthermore, bioinformatics analysis demonstrated that the differentially expressed mRNAs were predominantly enriched in 'ECM‑receptor interaction', 'PI3K‑Akt signaling pathway' and 'focal adhesion' pathways, all of which are essential for liver fibrosis development. Validation of 12 significantly aberrant lncRNAs by reverse transcription‑quantitative polymerase chain reaction indicated that the expression patterns of 11 lncRNAs were consistent with the sequencing data. Furthermore, overexpression of lncRNA NR_002155.1, which was markedly downregulated in CCl4‑treated liver tissues, was demonstrated to inhibit HSC‑T6 cell proliferation in vitro. In conclusion, the present study determined the expression patterns of mRNAs and lncRNAs in fibrotic liver tissue induced by CCl4. The identified differentially expressed lncRNAs may serve as novel diagnostic biomarkers and therapeutic targets for liver fibrosis.

An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

PubMed Central

Daburkar, Mohan; Lohar, Vikram; Rathore, Arvind Singh; Bhutada, Pravin; Tangadpaliwar, Shrikant

2014-01-01

Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs) protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I), untreated DFUs (Group II), DFUs treated with A. vera gel ethanolic extract (Group III), DFUs treated with topical A. vera gel (Group IV), DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V). The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM). Data were analyzed using one-way analysis of variance (ANOVA) after Newman–Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ)-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs) to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats. PMID:25035641

The burden of moderate-to-heavy soil-transmitted helminth infections among rural malaysian aborigines: an urgent need for an integrated control programme

PubMed Central

2011-01-01

Background Soil-transmitted helminth (STH) infections, among the most common neglected tropical diseases, continue to be a major threat to the health and socioeconomic wellbeing of infected people especially children in developing countries. Methods A cross-sectional study among 254 aboriginal schoolchildren was conducted in order to determine the current prevalence and intensity of infections and to investigate the potential risk factors associated with moderate-to-heavy burden of STH infections among these children. Results Overall, 93.7% of children were found to be infected with one or more STH species. The prevalence of trichuriasis, ascariasis and hookworm infections were 84.6%, 47.6% and 3.9%, respectively. Almost half of the participants had heavy trichuriasis, one-quarter had heavy ascariasis whereas all hookworm infections were light infections. Overall, moderate-to-heavy STH infections accounted for 56.7% of the total infections. Univariate analysis revealed that those using untreated water supply (P = 0.013), living in houses without toilets (P = 0.027) and having domestic animals in the houses (P = 0.044) had significantly higher prevalence of moderate-to-heavy infections than others. Logistic regression analysis confirmed using untreated water for drinking (P = 0.001) and the absence of a toilet in the house (P = 0.003) as significant risk factors of moderate-to-heavy STH infections among these children. Conclusion The high proportion of moderate-to-heavy STH infections further confirms the need for serious attention towards these devastating diseases that has put lives and the future of aboriginal children in jeopardy. Introduction of more poverty alleviation schemes, proper sanitation, provision of clean and safe drinking water, health education, as well as the introduction of periodic school-based deworming programmes are imperative among these communities in order to curtail the transmission and morbidity caused by STH. PMID:22208559

The effect of platelet-rich plasma on the repair of muscle injuries in rats☆

PubMed Central

Quarteiro, Marcelo Luiz; Tognini, João Ricardo Filgueiras; de Oliveira, Everton Lucas Flores; Silveira, Izabelli

2015-01-01

Objective The need for therapeutic options for muscle injuries, which are increasingly frequent among sports practitioners, was the motivation for this experimental study, which had the aim of evaluating the histological effects of platelet-rich plasma (PRP) on repairs to muscle tissues of rats. Methods PRP was obtained by means of double centrifugation of blood from five animals. In 30 rats, an injury was produced in the middle third of the belly of the gastrocnemius muscle of each hind limb. These injuries did not receive any treatment in six rats (12 legs). In 24 rats, 0.9% physiological serum was injected into the injury in the left leg and PRP into the injury in the right leg. Samples from the treated and untreated tissue were evaluated histologically 7 and 21 days after the procedures. Results The quantity of collagen in the injuries treated with PRP was significantly lower than that in the other injuries, in the evaluation made 7 days after the procedure, but it became equal to the other groups in the evaluation done on the 21st day. There was a significant increase (p < 0.001) in the quantity of collagen from the 7th to the 21st day in the injuries treated with PRP, but this was not seen in the injuries treated using other methods. The inflammatory process was shown to be more intense in the injuries treated with PRP than in the injuries of the other treatment groups, in the evaluation done 7 days after the procedure. However, the morphological aspects of these injuries were seen to be similar to those of the untreated injuries, 21 days after the procedure. Conclusion PRP promoted complete tissue restitution between the 7th and 21st days in experimental muscle injuries. PMID:26535207

Inhibitory effect of essential oils obtained from plants grown in Colombia on yellow fever virus replication in vitro

PubMed Central

Meneses, Rocío; Ocazionez, Raquel E; Martínez, Jairo R; Stashenko, Elena E

2009-01-01

Background An antiviral drug is needed for the treatment of patients suffering from yellow fever. Several compounds present in plants can inactive in vitro a wide spectrum of animal viruses. Aim In the present study the inhibitory effect of essential oils of Lippia alba, Lippia origanoides, Oreganum vulgare and Artemisia vulgaris on yellow fever virus (YFV) replication was investigated. Methods The cytotoxicity (CC50) on Vero cells was evaluated by the MTT reduction method. The minimum concentration of the essential oil that inhibited virus titer by more than 50% (MIC) was determined by virus yield reduction assay. YFV was incubated 24 h at 4°C with essential oil before adsorption on Vero cell, and viral replication was carried out in the absence or presence of essential oil. Vero cells were exposed to essential oil 24 h at 37°C before the adsorption of untreated-virus. Results The CC50 values were less than 100 μg/mL and the MIC values were 3.7 and 11.1 μg/mL. The CC50/MIC ratio was of 22.9, 26.4, 26.5 and 8.8 for L. alba, L origanoides, O. vulgare and A. vulgaris, respectively. The presence of essential oil in the culture medium enhances the antiviral effect: L. origanoides oil at 11.1 μg/mLproduced a 100% reduction of virus yield, and the same result was observed with L. alba, O. vulgare and A. vulgaris oils at100 μg/mL. No reduction of virus yield was observed when Vero cells were treated with essential oil before the adsorption of untreated-virus. Conclusion The essential oils evaluated in the study showed antiviral activities against YFV. The mode of action seems to be direct virus inactivation. PMID:19267922

Estradiol-promoted accumulation of receptor in nuclei of porcine endometrium cells. Immunogold electron microscopy of resting and estradiol-stimulated cells.

PubMed

Sierralta, W D; Jakob, F; Thole, H; Engel, P; Jungblut, P W

1992-01-01

Endometrium was collected by curettage from castrated pigs, either untreated or exposed to estradiol in vivo by intrauterine injection, and processed for electron microscopy. The resin LR Gold was used for embedding, and sections were floated on droplets of 10 nm diameter gold particles, coated with the immunoglobulin-G1 (IgG1) fraction or its Fab2 fragment of a monospecific polyclonal antiserum raised in goats against the C-terminal half of the estradiol receptor. On average, only one gold particle per microns 2 became attached in the cytoplasmic area of untreated cells, whereas four were found over the nuclear area. These figures rose to 2-3/microns 2 and 15-26/microns 2, respectively, within 10 min after exposure to estradiol. The labeling intensities of nuclei in cell clusters and of coprocessed nuclei released from cells ruptured during curettage were identical in all situations. Nuclear pores were frequently tagged after estradiol treatment. The proportions of tagging densities in nuclei of untreated and estradiol-exposed cells corresponded to those of receptor contents measured in extracts of isolated nuclei by ligand binding. This correlation was not seen for the cytoplasmic compartment of untreated cells, the scarce tagging of which is interpreted by hidden antigenic determinants. Our morphological analyses support the conclusions drawn from biochemical data (Sierralta et al., 1992) of an estradiol-promoted translocation of receptor from the cytoplasm into the nucleus.

Effects of sarcoptic mange and its control with oil of Cedrus deodara, Pongamia glabra, Jatropha curcas and benzyl benzoate, both with and without ascorbic acid on growing sheep: assessment of weight gain, liver function, nutrient digestibility, wool production and meat quality.

PubMed

Dimri, U; Sharma, M C

2004-03-01

The aim of this study was to evaluate the therapeutic efficacy of commonly used acaricidal drugs in India and also to assess the effect of ascorbic acid as adjunct therapy in 72 growing sheep with sarcoptic mange, aged 5-6 months and weighing 20.4-31.7 kg. Eight replicates of nine animals were formed based on sex, and day 0 body weight. Drugs were applied locally on the affected parts daily and recovery changes in skin lesions were observed at the time of every application. L-ascorbic acid was administered intramuscularly. Skin scrapings were collected daily from each group and examined for the presence of mites. Body weights were measured every 10th day from day 0 to 60. Nutrient digestiblity was evaluated by studying digestibility coefficients for dry matter, crude protein, ether extract, crude fibre, nitrogen free extract, total carbohydrates and nutrient balance (nitrogen, calcium and phosphorus) for a 30-day period. The liver function was evaluated by bromosulphophthalein (BSP) dye retention time. The animals were shorn on day 60 post-treatment (PT). Meat quality assesment was carried out by killing sheep at 60 days PT and estimating pH, water-holding capacity (WHC), tenderness, muscle colour, rib eye area and fat thickness. The lambs treated with oil of Jatropha curcas ascorbic acid had significantly (P < 0.05) greater mean daily body weight gains (63.29 g) than the infected untreated control (41.10 g). This was also higher than the mean daily weight gain in other treated groups. Infected untreated sheep showed significantly (P < 0.01) reduced digestibility coefficients for dry matter, crude protein, crude fibre, ether extract and total carbohydrate, but no significant differences for nitrogen-free extract. Treated sheep had significantly higher positive nitrogen, calcium and phosphorus balances compared with infested untreated sheep. Oil of J. curcas plus ascorbic acid (OJC-AA) treated group was better over all other treated groups with respect to nutrient digestibility. The BSP test revealed significant (P < 0.05) increase in BSP retention time in sheep with sarcoptic mange. Post -treatment, the BSP retention time decreased in all treated groups and the decrease was maximum in OJC-AA treated group. The carcasses of sheep treated with OJC-AA had significantly (P < 0.01) higher water holding capacity, rib eye area and back fat thickness than the untreated infected control group. The muscle pH and tenderness values were significantly lower in OJC-AA treated group post-slaughter than infested untreated control group. Muscle colour of OJC-AA treated group was maximum bright red. The lambs treated with OJC-AA had significantly (P < 0.05) greater clean fleece weight and fleece yield than the untreated infected group. It is concluded that OJC was the better therapy for sarcoptic mange of sheep and ascorbic acid as adjunct therapy is advisable. OJC-AA therapy may be better from the point of view of improving two most important production parameters in sheep, that is, wool yield and meat production.

Ovarian factors inhibit and fetal factors stimulate the secretion of rat placental lactogen.

PubMed

Robertson, M C; Owens, R E; McCoshen, J A; Friesen, H G

1984-01-01

Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same time, a great increase in serum rPL-II levels is seen. This occurs despite a significant decrease in placental weight. When Ftx14 was performed on day 14 and Ovx was delayed 1, 2, or 3 days, the expected large increase in serum rPL-II was progressively attenuated compared to that seen when Ftx and Ovx were carried out simultaneously. Daily administration of 17 beta-estradiol (4 micrograms/rat X day) to Ftx14 Ovx14 pregnant rats resulted in a significant suppression of rPL-II and elevation of rPRL levels, a reversal of what is seen for these hormones in untreated Ftx14 Ovx14 animals. To test whether 17 beta-estradiol was acting through rat PRL (rPRL), serum levels of rPRL were elevated in Ftx13 Ovx13 animals with pimozide (0.6 mg/kg), a dopamine receptor blocker. There was no effect of this treatment on rPL-II levels. In late pregnancy (day 17) serum rPL-II levels remained high after removal of half the fetuses (1/2 Ftx), compared to the rapid fall in pregnant rats in which all fetuses were removed (Ftx17). Serum levels were also elevated in 1/2 Ftx animals compared to those in which half of the fetuses and placentas were removed by hemi-hysterectomy, suggesting that the increase in rPL-II levels in 1/2 Ftx animals was due to a stimulatory effect of the remaining fetuses on all of the placentas. These results indicate that the presence of the fetus is necessary for the normally observed increase in rPL-II levels in late pregnancy. In conclusion, fetal stimulators and ovarian inhibitors influence rPL-II secretion.

Immunomodulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in a Swine Hemi-Facial Allotransplantation Model

PubMed Central

Goto, Shigeru; Huang, Yu-Ting; Wang, Chun-Ting; Tsai, Chia-Chun; Chen, Chao-Long

2012-01-01

Background In this study, we investigated whether the infusion of bone marrow-derived mesenchymal stem cells (MSCs), combined with transient immunosuppressant treatment, could suppress allograft rejection and modulate T-cell regulation in a swine orthotopic hemi-facial composite tissue allotransplantation (CTA) model. Methodology/Principal Findings Outbred miniature swine underwent hemi-facial allotransplantation (day 0). Group-I (n = 5) consisted of untreated control animals. Group-II (n = 3) animals received MSCs alone (given on days −1, +1, +3, +7, +14, and +21). Group-III (n = 3) animals received CsA (days 0 to +28). Group-IV (n = 5) animals received CsA (days 0 to +28) and MSCs (days −1, +1, +3, +7, +14, and +21). The transplanted face tissue was observed daily for signs of rejection. Biopsies of donor tissues and recipient blood sample were obtained at specified predetermined times (per 2 weeks post-transplant) or at the time of clinically evident rejection. Our results indicated that the MSC-CsA group had significantly prolonged allograft survival compared to the other groups (P<0.001). Histological examination of the MSC-CsA group displayed the lowest degree of rejection in alloskin and lymphoid gland tissues. TNF-α expression in circulating blood revealed significant suppression in the MSC and MSC-CsA treatment groups, as compared to that in controls. IHC staining showed CD45 and IL-6 expression were significantly decreased in MSC-CsA treatment groups compared to controls. The number of CD4+/CD25+ regulatory T-cells and IL-10 expressions in the circulating blood significantly increased in the MSC-CsA group compared to the other groups. IHC staining of alloskin tissue biopsies revealed a significant increase in the numbers of foxp3+T-cells and TGF-β1 positive cells in the MSC-CsA group compared to the other groups. Conclusions These results demonstrate that MSCs significantly prolong hemifacial CTA survival. Our data indicate the MSCs did not only suppress inflammation and acute rejection of CTA, but also modulate T-cell regulation and related cytokines expression. PMID:22558153

Targeted delivery of transferrin-conjugated liposomes to an orthotopic model of lung cancer in nude rats.

PubMed

Gaspar, Maria Manuela; Radomska, Anna; Gobbo, Oliviero L; Bakowsky, Udo; Radomski, Marek W; Ehrhardt, Carsten

2012-12-01

Lung cancer is the leading cause of cancer death worldwide. Pulmonary anticancer therapy might offer several advantages over systemic delivery, leading to an increased exposure of the lung tumor to the drug, while minimizing side effects, due to regional containment. Here, we studied if a combination of inhalation therapy and drug targeting holds potential as an even more efficient lung cancer therapy. Transferrin (Tf )-conjugated PEG liposomes loaded with doxorubicin (DOX) were administered using an intracorporeal nebulizing catheter to an orthotopic lung cancer model established in athymic Rowett nude rats. Different DOX formulations and doses (0.2 and 0.4 mg/kg) were tested and the influence on tumor progression and life span of rats was evaluated in comparison with the i.v. administration of Tf-PEG-liposomes loaded with DOX at a therapeutic dose of 2 mg/kg. Rats in the untreated control group showed significant weight loss 2 weeks after tumor induction and died between days 19 and 29. Lungs of these animals showed multiple foci of neoplastic deposits, ranging up to 20 mm replacing the entire lobe. Empty Tf-liposomes showed a significant effect on survival time. This might be caused by the secondary cytotoxicity via stimulation of pulmonary macrophages. All animal treated intravenously also perished before the end of the study. No significant (p<0.05) improvement in survival was observed between the groups treated with aerosols of free drug, DOX encapsulated in plain and in Tf-modified liposomes. However, more animals survived in the Tf-liposome groups than in the other treatment regimes, and their lung tissue generally had fewer and smaller tumors. Nevertheless, the size of the groups, and the duration of the trial render it impossible to come to a definite conclusion. Drug targeting demonstrated potential for improving the aerosol treatment of lung cancer.

A study of the interaction between H. pylori mice passage strains and gastric epithelial cells.

PubMed

Rahman, Inayatur; Idrees, Muhammad; Waqas, Mohammad; Karim, Abdul

2018-05-01

Helicobacter pylori (H. pylori) infections are very serious health problem that are further worsened by increasing/developing resistance to the current antibiotics. Therefore, new therapeutic agents are needed for H. pylori eradication. Use of a CD46 derived peptide (P3) as bactericidal agent against H. pylori has shown high activity rate in vivo and this study examines the changes in H. pylori features in response to effect of P3 treatment.AGS cells were infected with H. pylori wild type strain 67:21 and its mice passage strains (P3 treated and untreated strains) and further examined using immunoblotting assay, FACS and Urease activity analysis. Comparatively we found increased level of Urease alpha subunit A (UreA) and alkyl hydroperoxide reductase C (AhpC) proteins for P3 treated strain of H. pylori than its wild type or untreated strain after infection of AGS cells. Conclusion These results suggest that there might be a high rate of adherence to host cells for the P3 treated passage strain than untreated or wild type strain. Our findings also indicate that either adhesins are being changed or H. pylori interaction to the host cells is affected after P3 treatment.

Macrophage Repolarization with Targeted Alginate Nanoparticles Containing IL-10 Plasmid DNA for the Treatment of Experimental Arthritis

PubMed Central

Jain, Shardool; Tran, Thanh-Huyen; Amiji, Mansoor

2015-01-01

In this study, we have shown for the first time the effectiveness of a non-viral gene transfection strategy to re-polarize macrophages from M1 to M2 functional sub-type for the treatment of rheumatoid arthritis (RA). An anti-inflammatory (IL-10) cytokine encoding plasmid DNA was successfully encapsulated into non-condensing alginate based nanoparticles and the surface of the nano-carriers was modified with tuftsin peptide to achieve active macrophage targeting. Enhanced localization of tuftsin-modified alginate nanoparticles was observed in the inflamed paws of arthritic rats upon intraperitoneal administration. Importantly, targeted nanoparticle treatment was successful in reprogramming macrophage phenotype balance as ~66% of total synovial macrophages from arthritic rats treated with the IL-10 plasmid DNA loaded tuftsin/alginate nanoparticles were in the M2 state compared to ~9% of macrophages in the M2 state from untreated arthritic rats. Treatment significantly reduced systemic and joint tissue pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression and prevented the progression of inflammation and joint damage as revealed by magnetic resonance imaging and histology. Treatment enabled animals to retain their mobility throughout the course of study, whereas untreated animals suffered from impaired mobility. Overall, this study demonstrates that targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state, offering a novel treatment paradigm for treatment of chronic inflammatory diseases. PMID:26004232

Photodynamic inactivation of antibiotic resistant strain of Pseudomonas aeruginosa in vivo

NASA Astrophysics Data System (ADS)

Hashimoto, M. C. E.; Toffoli, D. J.; Prates, R. A.; Courrol, Lilia C.; Ribeiro, M. S.

2009-06-01

Burns are frequently contamined by pathogenic microorganisms and the widespread occurrence of antibiotic resistant strains of Pseudomonas aeruginosa in hospitals is a matter of growing concern. Hypocrellin B (HB) is a new generation photosensitizer extracted from the fungus Hypocrella bambusae with absorption bands at 460, 546 and 584 nm. Lanthanide ions change the HB molecular structure and a red shift in the absorption band is observed as well as an increase in the singlet oxygen quantum yield. In this study, we report the use of HB:La+3 to kill resistant strain of P. aeruginosa infected burns. Burns were produced on the back of mice and wounds were infected subcutaneously with 1x109 cfu/mL of P. aeruginosa. Three-hours after inoculation, the animals were divided into 4 groups: control, HB:La+3, blue LED and HB:La+3+blue LED. PDT was performed using 10μM HB:La+3 and 500mW light-emitting diode (LED) emitting at λ=470nm+/-20nm during 120s. The animals of all groups were killed and the infected skin was removed for bacterial counting. Mice with photosensitizer alone, light alone or untreated infected wounds presented 1x108 cfu/g while mice PDT-treated showed a reduction of 2 logs compared to untreated control. These results suggest that HB:La+3 associated to blue LED is effective in diminishing antibiotic resistant strain P. aeruginosa in infected burns.

Association of Incident Obstructive Sleep Apnea with Outcomes in a Large Cohort of US Veterans

PubMed Central

Molnar, Miklos Z; Mucsi, Istvan; Novak, Marta; Szabo, Zoltan; Freire, Amado X; Huch, Kim M; Arah, Onyebuchi A; Ma, Jennie Z; Lu, Jun L; Sim, John J; Streja, Elani; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2015-01-01

Rationale There is a paucity of large cohort studies examining the association of obstructive sleep apnea(OSA) with clinical outcomes including all-cause mortality, coronary heart disease(CHD), strokes and chronic kidney disease(CKD). Objectives We hypothesized that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes. Methods, Measurements In a nationally representative cohort of over 3 million(n=3,079,514) US veterans(93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 ml/min/1.73m2, we examined the association between the diagnosis of incident OSA, treated and untreated with continuous positive airway pressure(CPAP), and: 1) all-cause mortality, 2) incident CHD, 3) incident strokes, 4)incident CKD defined as eGFR<60 ml/min/1.73m2, and 5)slopes of eGFR. Main Results Compared to OSA negative patients, untreated and treated OSA was associated with 86% higher mortality risk,(adjusted hazard ratio and 95% confidence interval: 1.86(1.81-1.91)) and 35% (1.35(1.21-1.51)), respectively. Similarly, untreated and treated OSA was associated with 3.5 times(3.54(3.40-3.69)) and 3 times(3.06(2.62-3.56)) higher risk of incident CHD; 3.5 times higher risk of incident strokes(3.48(3.28-3.64) and 3.50(2.92-4.19)) for untreated and treated OSA, respectively. The risk of incident CKD was also significantly higher in untreated(2.27(2.19-2.36)) and treated(2.79(2.48-3.13)) OSA patients. The median (interquartile range) of the eGFR slope was −0.41(−2.01 - 0.99), −0.61(−2.69 - 0.93) and −0.87(−3.00 - 0.70)ml/min/1.73m2 in OSA negative, untreated and treated OSA positive patients, respectively. Conclusions In this large and contemporary cohort of more than 3 million US veterans, a diagnosis of incident OSA was associated with higher mortality, incident CHD, stroke and CKD and with faster kidney function decline. PMID:26038534

Repeated cycles of electrical stimulation decrease vasoconstriction and axon-reflex vasodilation to noradrenaline in the human forearm

PubMed Central

Drummond, Peter D

2007-01-01

What is already known about this subject Repeated cycles of electrical stimulation inhibit cutaneous vasoconstriction to noradrenaline, but the mechanism is unknown. Investigating this is important because peripheral electrical stimulation is useful for pain modulation and appears to assist cutaneous wound healing. What this study adds Intermittent, brief electrical stimulation of the forearm over a 10-day period inhibited vasoconstriction and axon-reflex vasodilation to noradrenaline, but did not affect vasoconstriction to vasopressin or axon-reflex vasodilation to histamine. Thus, electrical stimulation may evoke a specific reduction in responsiveness to noradrenaline. Aim To investigate whether desensitization to the vasomotor effects of noradrenaline is a specific effect of electrical stimulation. Methods Three sites on the forearm of 10 healthy volunteers were stimulated with 0.2 mA direct current for 2 min twice daily for 10 days. Noradrenaline and histamine were then displaced from ring-shaped iontophoresis chambers into two of the pretreated sites and two untreated sites on the contralateral forearm. Axon-reflex vasodilation was measured from the centre of the ring described by the iontophoresis chamber with a laser Doppler flowmeter. One or two days later, noradrenaline and vasopressin were introduced into pretreated and untreated sites by iontophoresis, and vasoconstriction at sites of administration was measured in the heated forearm. Results The pretreatment blocked vasoconstriction to noradrenaline [median increase in flow 1%, interquartile range (IR) −41 to 52%; median decrease at the untreated site 53%, IR. −70 to −10%; P < 0.05], but did not block vasoconstriction to vasopressin (median decrease 42% at the untreated site and 45% at the pretreated site). Axon-reflex vasodilation to noradrenaline was diminished at the pretreated site (median increase in flow 33%, IR 2–321%; untreated site 247%, IR 31–1087%; P < 0.05). However, axon-reflex vasodilation to histamine did not differ significantly between the pretreated site (median increase 1085%) and the untreated site (median increase 1345%). Conclusions The conditioning pretreatment appears to evoke a specific decrease in responsiveness to noradrenaline. Repeated cycles of electrical stimulation may downregulate neural and vascular responses to noradrenaline by repetitively activating cutaneous sympathetic nerve fibres. PMID:17441931

Shortened Lifespan and Lethal Hemorrhage in a Hemophilia A Mouse Model.

PubMed

Staber, Janice M; Pollpeter, Molly J

2016-01-01

Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p < 0.0001). In addition, the hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated.

Ballast Water Treatment Corrosion Scoping Study

DTIC Science & Technology

2011-10-01

measurements can only be indicative and are seldom conclusive. For the maritime industry , corrosion and corrosion protection is a considerable cost element...8  Table 4. Corrosion rates of several alloys in natural and chlorinated seawater...10  Table 5. Corrosion rates of selected marine alloys in untreated seawater and seawater with 0, 0.1, 0.25, and 0.50 mg L-1 residual

18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

ClinicalTrials.gov

2017-01-30

Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain.

PubMed

Petro, Marianne; Jaffer, Hayder; Yang, Jun; Kabu, Shushi; Morris, Viola B; Labhasetwar, Vinod

2016-03-01

Inherent neuronal and circulating progenitor cells play important roles in facilitating neuronal and functional recovery post stroke. However, this endogenous repair process is rather limited, primarily due to unfavorable conditions in the infarcted brain involving reactive oxygen species (ROS)-mediated oxidative stress and inflammation following ischemia/reperfusion injury. We hypothesized that during reperfusion, effective delivery of antioxidants to ischemic brain would create an environment without such oxidative stress and inflammation, thus promoting activation and mobilization of progenitor cells in the infarcted brain. We administered recombinant human tissue-type plasminogen activator (tPA) via carotid artery at 3 h post stroke in a thromboembolic rat model, followed by sequential administration of the antioxidants catalase (CAT) and superoxide dismutase (SOD), encapsulated in biodegradable nanoparticles (nano-CAT/SOD). Brains were harvested at 48 h post stroke for immunohistochemical analysis. Ipsilateral brain slices from animals that had received tPA + nano-CAT/SOD showed a widespread distribution of glial fibrillary acidic protein-positive cells (with morphology resembling radial glia-like neural precursor cells) and nestin-positive cells (indicating the presence of immature neurons); such cells were considerably fewer in untreated animals or those treated with tPA alone. Brain sections from animals receiving tPA + nano-CAT/SOD also showed much greater numbers of SOX2- and nestin-positive progenitor cells migrating from subventricular zone of the lateral ventricle and entering the rostral migratory stream than in t-PA alone treated group or untreated control. Further, animals treated with tPA + nano-CAT/SOD showed far fewer caspase-positive cells and fewer neutrophils than did other groups, as well as an inhibition of hippocampal swelling. These results suggest that the antioxidants mitigated the inflammatory response, protected neuronal cells from undergoing apoptosis, and inhibited edema formation by protecting the blood-brain barrier from ROS-mediated reperfusion injury. A longer-term study would enable us to determine if our approach would assist progenitor cells to undergo neurogenesis and to facilitate neurological and functional recovery following stroke and reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

25-hydroxycholecalciferol stimulation of muscle metabolism.

PubMed Central

Birge, S J; Haddad, J G

1975-01-01

Intact diaphragms from vitamin D-deficient rats were incubated in vitro with [3H]leucine. Oral administration of 10 mug (400 U) of cholecalciferol 7 h before incubation increased leucine incorporation into diaphragm muscle protein by 136% (P less than 0.001) of the preparation from untreated animals. Nephrectomy did not obliterate this response. ATP content of the diaphragm muscle was also enhanced 7 h after administration of the vitamin. At 4 h after administration of cholecalciferol, serum phosphorus concentration was reduced by 0.7 mg/100 ml (P less than 0.025) and the rate of inorganic 32PO4 accumulation by diaphragm muscle was increased by 18% (P less than 0.025) over the untreated animals. Increasing serum phosphate concentration of the vitamin D-deficient animals by dietary supplementation with phosphate for 3 days failed to significantly enhance leucine incorporation into protein. However, supplementation of the rachitogenic, vitamin D-deficient diet with phosphorus for 3 wk stimulated the growth of the animal and muscle ATP levels. This increase in growth and muscle ATP content attributed to the addition of phosphorus to the diet was less than the increase in growth and muscle ATP levels achieved by the addition of both phosphorus and vitamin D to the diet. To eliminate systemic effects of the vitamin, the epitrochlear muscle of the rat foreleg of vitamin D-depleted rats was maintained in tissue culture. Addition of 20 ng/ml of 25-hydroxycholecalciferol (25-OHD3) to the medium enhanced ATP content of the muscle and increased leucine incorporation into protein. Vitamin D3 at a concentration of 20 mug/ml and 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) at a concentration of 500 pg/ml were without effect. Analysis of muscle cytosol in sucrose density gradients revealed a protein fraction which specifically bound 25-OHD3 and which demonstrated a lesser affinity for 1,25-(OH)2D3. These studies suggest that 25-OHD3 may influence directly the intracellular accumulation of phosphate by muscle and thereby play an important role in the maintenance of muscle metabolism and function. PMID:1184737

Insulin, insulin-like growth factor–1, insulin receptor, and insulin-like growth factor–1 receptor expression in the chick eye and their regulation with imposed myopic or hyperopic defocus

PubMed Central

Penha, Alexandra Marcha; Schaeffel, Frank

2011-01-01

Purpose Insulin stimulates eye growth in chicks and this effect is greatly enhanced if the retinal image is degraded by the defocus of either sign. However, it is unclear whether the insulin receptor (IR) is expressed at all in the chicken retina in animals 1–2 weeks post-hatching. We have investigated IR expression and whether IR transcript abundance varies in the fundal layers. To elucidate the possible role of insulin and insulin-like growth factor (IGF)-1 signaling in eye growth regulation, mRNA (mRNA) levels were measured for insulin, IGF-1, IR, and IGF-1 receptor (IGF-1R) during imposed negative or positive defocus. Methods Chicks were treated binocularly with positive or negative spectacle lenses for 4 or 24 h, or they remained untreated (n=6, for each treatment group). Northern blot analyses were performed to screen for transcription variants in the different fundal layers of untreated animals. Real-time PCR was used to quantify IR, IGF-1R, IGF-1, and insulin mRNA levels in the different fundal layers of the chick eye in the three treatment groups. Results IR mRNA was found in all the studied tissues, although there is evidence of tissue-specific transcript variations. Three major transcripts were detected for IR. The brain, retina, and choroid showed the longest transcript (4.3 kb), which was not present in the liver. Nevertheless, the liver and brain showed a second transcript (2.6 kb) not present in the retina and choroid. A short transcript (1.3 kb) was the predominant form in the liver and choroid, and it seems to be present in the retinal pigment epithelium (RPE) and sclera as well. In the retina, no significant gene expression changes were found when defocus was imposed. Interestingly, in the RPE, both IR and IGF-1R were already downregulated after short periods (4 h) of positive lens wear. In contrast, IR and IGF-1R were upregulated in the choroid and fibrous sclera during treatment with negative, but not positive, lenses. Conclusions Differences observed in the IR transcript length in different tissues suggest possibly different functions. The differential regulation of IR and IGF-1R in the RPE, choroid, and fibrous sclera is consistent with their involvement in a signaling cascade for emmetropization. PMID:21655358

Antibody-based in vivo PET imaging detects amyloid-β reduction in Alzheimer transgenic mice after BACE-1 inhibition.

PubMed

Meier, Silvio R; Syvänen, Stina; Hultqvist, Greta; Fang, Xiaotian T; Roshanbin, Sahar; Lannfelt, Lars; Neumann, Ulf; Sehlin, Dag

2018-05-31

Positron emission tomography (PET) used for visualizing amyloid-β (Aβ) pathology has become an important tool for specific clinical diagnosis of Alzheimer's disease (AD). However, all available amyloid PET radioligands, such as [ 11 C]PiB, reflect levels of insoluble Aβ plaques, but do not capture soluble and protofibrillar Aβ forms. When measured with current PET ligands, the plaque load appears to be fairly static during clinical stages of AD, and may not be affected by Aβ reducing treatments. The aim of the present study was to investigate if a novel PET radioligand, based on an antibody directed towards soluble aggregates of Aβ, could be used to detect changes in Aβ levels during disease progression and after treatment with a β-secretase (BACE-1) inhibitor. Methods: One set of transgenic mice (tg-ArcSwe, model of Aβ pathology) aged between 7 and 16 months were PET scanned with the Aβ protofibril selective radioligand [ 124 I]RmAb158-scFv8D3 to follow progression of Aβ pathology in the brain. A second set of tg-ArcSwe mice, aged 10 months, were treated with BACE-1 inhibitor NB-360 for 3 months and compared to an untreated control group. A set of 10 months old tg-ArcSwe mice also underwent PET scanning, acting as a baseline group. Brain tissue was isolated after PET to determine levels of Aβ by ELISA and immunohistochemistry. Results: Concentration of [ 124 I]RmAb158-scFv8D3 in tg-ArcSwe mice, measured in vivo with PET, increased with age and corresponded well with ex vivo autoradiography and Aβ immunohistochemistry. Tg-ArcSwe mice treated with NB-360 showed significantly lower in vivo PET signals than untreated animals, and were similar to the baseline 10 month old animals. The decreased [ 124 I]RmAb158-scFv8D3 concentrations in NB-360 treated mice, quantified with PET, corresponded well with decreased Aβ levels measured in post mortem brain. Conclusion: A number of treatments for AD are currently studied in phase 2 and 3 clinical trials but there are limited possibilities to study their effects on the important, non-fibrillar Aβ forms in vivo. This study demonstrates the ability of the Aβ protofibril selective radioligand [ 124 I]RmAb158-scFv8D3 to follow disease progression and detect treatment effects with PET imaging in tg-ArcSwe mice. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Auditory Brainstem Response (ABR) Abnormalities across the Life Span of Rats Prenatally Exposed to Alcohol

PubMed Central

Church, Michael W.; Hotra, John W.; Holmes, Pamela A.; Anumba, Jennifer I.; Jackson, Desmond A.; Adams, Brittany R.

2011-01-01

Background Fetal Alcohol Syndrome is a leading cause of neurodevelopmental impairments (NDI) in developed countries. Sensory deficits can play a major role in NDI, yet few studies have investigated the effects of prenatal alcohol exposure on sensory function. In addition, there is a paucity of information on the life-long effects of prenatal alcohol exposure. Thus, we sought to investigate the effects of prenatal alcohol exposure on auditory function across the life span in an animal model. Based on prior findings with prenatal alcohol exposure and other forms of adverse prenatal environments, we hypothesized that animals prenatally exposed to alcohol would show an age-dependent pattern of (A) hearing and neurological abnormalities as post-weanling pups, (B) a substantial dissipation of such abnormalities in young adulthood, and (C) a resurgence of such abnormalities in middle-aged adulthood. Method Pregnant rats were randomly assigned to an untreated control (CON), a pair-fed control (PFC) or an alcohol treated group (ALC). The ALC dams were gavaged with 6 mg/kg alcohol daily from gestation day (GD) 6 to 21. The PFC dams were gavaged daily from GD6-21 with an isocaloric and isovolumetric water-based solution of Maltose-Dextrins and pair-fed to the ALC dams. The CON dams were the untreated group to which the ALC and CON groups were compared. Hearing and neurological functions in the offspring were assessed with the Auditory Brainstem Response (ABR) at the postnatal ages of 22, 220 and 520 days of age. Results & Conclusions In accord with our hypothesis, ABR abnormalities were first observed in the post-weanling pups, largely dissipated in young adulthood, and then resurged in middle-aged adulthood. This age-related pattern suggests that the ALC pups had a developmental delay that dissipated in young adulthood and an enhanced age-related deterioration that occurred in middle-aged adulthood. Such a pattern is consistent with the fetal programming hypothesis of adult-onset diseases (the Barker Hypothesis). Our findings have important clinical implications for the assessment and management of (A) childhood hearing disorders and their co-morbidities (i.e., speech-and-language, learning, and attention deficit disorders) and (B) enhanced age-related hearing and neurological degeneration in middle-aged adulthood that can result from prenatal alcohol exposure. We recommend hearing evaluation be a part of any long-term follow-up for FAS patients and patients exposed to any adverse prenatal environment. PMID:21815896

Antihyperglycaemic effect of laser acupuncture treatment at BL20 in diabetic rats.

PubMed

Cornejo-Garrido, Jorge; Becerril-Chávez, Flavia; Carlín-Vargas, Gabriel; Ordoñez-Rodríguez, Juan Manuel; Abrajan-González, María Del Carmen; de la Cruz-Ramírez, Rosario; Ordaz-Pichardo, Cynthia

2014-12-01

To investigate the antihyperglycaemic activity of laser acupuncture stimulation at 650 and 980 nm at BL20 in streptozotocin (STZ)-induced diabetic rats. Seventy healthy adult male albino Wistar rats weighing 250±50 g were divided into seven groups of 10 animals each. Groups I-III comprised healthy control rats which were untreated (I) or stimulated with laser acupuncture at 650 nm (II) and 980 nm (III), respectively. Groups IV-VII underwent induction of diabetes with a single intraperitoneal administration of STZ at 50 mg/kg. Animals with blood glucose levels of ≥200 mg/dL on the fifth day were used for the experiments and were left untreated (group IV), treated with glibenclamide (group V) or stimulated with laser acupuncture at 650 nm (group VI) and 980 nm (group VII), respectively. Laser acupuncture was applied at BL20 on alternate days for a total of 12 sessions over a 28-day period. After 28 days of treatment, STZ-induced diabetic rats stimulated with laser acupuncture at 650 and 980 nm had significantly lower glucose levels compared with untreated diabetic rats (242.0±65.0 and 129.8±33.2 vs 376.5±10.0 mg/dL, both p≤0.05). Treatment at 980 nm also attenuated the increase in glucose between day 1 and day 28 compared with the glibenclamide-treated diabetic group (41.5±19.6 mg/dL vs 164.1±13.7 g/dL, p<0.05). Laser acupuncture treatment did not affect the blood count or biochemical profile and was not associated with any morphological changes in the pancreas, liver, kidney or spleen. Stimulation with laser acupuncture at 650 and 980 nm at BL20 in STZ-induced diabetic rats has antihyperglycaemic activity. The results support further evaluation of laser acupuncture as an alternative or complementary treatment for the control of hyperglycaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis.

PubMed

Arulkumaran, Nishkantha; Sixma, Marije L; Pollen, Sean; Ceravola, Elias; Jentho, Elisa; Prendecki, Maria; Bass, Paul S; Tam, Frederick W K; Unwin, Robert J; Singer, Mervyn

2018-03-01

Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X 7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X 7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis. Compared with sham-operated animals, septic animals had significant increases in heart rate (-1(-4 to 8)% vs. 21(12-26)%; P = 0.003), fever (37.4(37.2-37.6)°C vs. 38.6(38.2-39.0)°C; P = 0.0009), and falls in serum albumin (29(27-30)g/L vs. 26(24-28); P = 0.0242). Serum IL-1β (0(0-10)(pg/mL) vs. 1671(1445-33778)(pg/mL); P < 0.001) and renal IL-1β (86(50-102)pg/mg protein vs. 200 (147-248)pg/mg protein; P = 0.0031) were significantly elevated in septic compared with sham-operated animals at 6 h. Serum creatinine was elevated in septic animals compared with sham-operated animals at 24 h (23(22-25) μmol/L vs. 28 (25-30)μmol/L; P = 0.0321). Renal IL-1β levels were significantly lower in A-438079-treated animals compared with untreated animals at 6 h (70(55-128)pg/mg protein vs. 200(147-248)pg/mg protein; P = 0.021). At 24 h, compared with untreated animals, A-438079-treated animals had more rapid resolution of tachycardia (22(13-36)% vs. -1(-6 to 7)%; P = 0.019) and fever (39.0(38.6-39.1)°C vs. 38.2(37.6-38.7)°C; P < 0.024), higher serum albumin (23(21-25)g/L vs. (27(25-28)g/L); P = 0.006), lower arterial lactate (3.2(2.5-4.3)mmol/L vs. 1.4(0.9-1.8)mmol/L; P = 0.037), and lower serum creatinine concentrations (28(25-30)μmol/L vs. 22(17-27)μmol/L; P = 0.019). P2X 7 A treatment ameliorates the systemic inflammatory response and renal dysfunction in this clinically relevant model of sepsis-related AKI. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

ClinicalTrials.gov

2017-04-27

Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Pleomorphic Xanthoastrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Medulloblastoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilocytic Astrocytoma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Pineoblastoma; Untreated Childhood Pleomorphic Xanthoastrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

[Drug residues in untreated swine].

PubMed

Kietzmann, M; Markus, W; Chavez, J; Bollwahn, W

1995-11-01

The concentration of sulfadimidine was measured in the urine of pigs which were housed (over five days) in boxes where other pigs have been treated orally with sulfadimidine before. Sulfadimidine was measured in the urine of the unmedicated pigs in a concentration of up to 4 micrograms/ml. Considering these urine concentrations, violative sulfadimidine tissue residues would be expectable in the carcass after slaughter. The practice of fixing withdrawal times must be considered again to ensure that drug residues in tissues are below the MRL before slaughter also in unmedicated animals.

Clinical course of untreated tonic-clonic seizures in childhood: prospective, hospital based study.

PubMed Central

van Donselaar, C. A.; Brouwer, O. F.; Geerts, A. T.; Arts, W. F.; Stroink, H.; Peters, A. C.

1997-01-01

OBJECTIVE: To assess decleration and acceleration in the disease process in the initial phase of epilepsy in children with new onset tonic-clonic seizures. STUDY DESIGN: Hospital based follow up study. SETTING: Two university hospitals, a general hospital, and a children's hospital in the Netherlands. PATIENTS: 204 children aged 1 month to 16 years with idiopathic or remote symptomatic, newly diagnosed, tonic-clonic seizures, of whom 123 were enrolled at time of their first ever seizure; all children were followed until the start of drug treatment (78 children), the occurrence of the fourth untreated seizure (41 children), or the end of the follow up period of two years (85 untreated children). MAIN OUTCOME MEASURES: Analysis of disease pattern from first ever seizure. The pattern was categorised as decelerating if the child became free of seizures despite treatment being withheld. In cases with four seizures, the pattern was categorised as decelerating if successive intervals increased or as accelerating if intervals decreased. Patterns in the remaining children were classified as uncertain. RESULTS: A decelerating pattern was found in 83 of 85 children who became free of seizures without treatment. Three of the 41 children with four or more untreated seizures showed a decelerating pattern and eight an accelerating pattern. In 110 children the disease process could not be classified, mostly because drug treatment was started after the first, second, or third seizure. The proportion of children with a decelerating pattern (42%, 95% confidence interval 35% to 49%) may be a minimum estimate because of the large number of patients with an uncertain disease pattern. CONCLUSIONS: Though untreated epilepsy is commonly considered to be a progressive disorder with decreasing intervals between seizures, a large proportion of children with newly diagnosed, unprovoked tonic-clonic seizures have a decelerating disease process. The fear that tonic-clonic seizures commonly evolve into a progressive disease should not be used as an argument in favour of early drug treatment in children with epilepsy. PMID:9040384

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

PubMed Central

Hackett, Geoffrey; Jones, Peter W; Strange, Richard C; Ramachandran, Sudarshan

2017-01-01

AIM To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men. PMID:28344753

A multi-institutional analysis of the untreated course of cerebral dural arteriovenous fistulas.

PubMed

Gross, Bradley A; Albuquerque, Felipe C; McDougall, Cameron G; Jankowitz, Brian T; Jadhav, Ashutosh P; Jovin, Tudor G; Du, Rose

2017-12-15

OBJECTIVE The rarity of cerebral dural arteriovenous fistulas (dAVFs) has precluded analysis of their natural history across large cohorts. Investigators from a considerable proportion of the few reports that do exist have evaluated heterogeneous groups of untreated and partially treated lesions. In the present study, the authors exclusively evaluated the untreated course of dAVFs across a multi-institutional data set to delineate demographic, angiographic, and natural history data. METHODS A multi-institutional database of dAVFs was queried for demographic and angiographic data as well as untreated disease course. After dAVFs were stratified by Djindjian type, annual nonhemorrhagic neurological deficit (NHND) and hemorrhage rates were derived, as were risk factors for each. A multivariable Cox proportional-hazards regression model was used to calculate hazard ratios. RESULTS Two hundred ninety-five dAVFs had at least 1 month of untreated follow-up. For 126 Type I dAVFs, there were no episodes of NHND or hemorrhage over 177 lesion-years. Respective annualized NHND and hemorrhage rates were 4.5% and 3.4% for Type II, 6.0% and 4.0% for Type III, and 4.5% and 9.1% for Type IV dAVFs. The respective annualized NHND and hemorrhage rates were 2.3% and 2.9% for asymptomatic Type II-IV dAVFs, 23.1% and 3.3% for dAVFs presenting with NHND, and 0% and 46.2% for lesions presenting with hemorrhage. On multivariate analysis, NHND presentation (HR 11.49, 95% CI 3.19-63) and leptomeningeal venous drainage (HR 5.03, 95% CI 0.42-694) were significant risk factors for NHND; hemorrhagic presentation (HR 17.67, 95% CI 2.99-117) and leptomeningeal venous drainage (HR 10.39, 95% CI 1.11-1384) were significant risk factors for hemorrhage. CONCLUSIONS All Type II-IV dAVFs should be considered for treatment. Given the high risk of rebleeding, lesions presenting with NHND and/or hemorrhage should be treated expediently.

A comparison between placental and amniotic mesenchymal stem cells for transamniotic stem cell therapy (TRASCET) in experimental spina bifida.

PubMed

Feng, Christina; D Graham, Christopher; Connors, John Patrick; Brazzo, Joseph; Zurakowski, David; Fauza, Dario O

2016-06-01

We compared placental-derived and amniotic fluid-derived mesenchymal stem cells (pMSCs and afMSCs, respectively) in transamniotic stem cell therapy (TRASCET) for experimental spina bifida. Pregnant dams (n=29) exposed to retinoic acid for the induction of fetal spina bifida were divided into four groups. Three groups received volume-matched intraamniotic injections of either saline (n=38 fetuses) or a suspension of 2×10(6) cells/mL of syngeneic, labeled afMSCs (n=73) or pMSCs (n=115) on gestational day 17 (term=21-22days). Untreated fetuses served as controls. Animals were killed before term. Statistical comparisons were by Fisher's exact test (p<0.05). Survival was similar across treatment groups (p=0.08). In fetuses with isolated spina bifida (n=100), there were higher percentages of defect coverage (either partial or complete) in both afMSC and pMSC groups compared with saline and untreated groups (p<0.001-0.03 in pairwise comparisons). There were no differences in coverage rates between afMSC and pMSC groups (p=0.94) or between saline and untreated groups (p=0.98). Both pMSC and afMSC can induce comparable rates of coverage of experimental spina bifida after concentrated intraamniotic injection in the rodent model. This broadens the options for timing and cell source for TRASCET as a potential alternative in the prenatal management of spina bifida. Copyright © 2016 Elsevier Inc. All rights reserved.

[Clinical situation, diagnosis and prevention of a Streptococcus suis serotype 7 problem on a farm].

PubMed

Unterweger, Christine; Baums, Christoph Georg; Höcher, Martin; Fischer, Louis; Weiss, Astrid; Hennig-Pauka, Isabel

2014-01-01

In an Austrian piglet producing farm with 1500 sows a high incidence of meningitis, arthritis and sudden death was recorded in five to eight week old piglets. Overall losses were 1.8%. Streptococcus (S.) suis serotype 7 was detected with an intermediate to high specific bacterial load in all samples taken from brains and joints of 17 untreated piglets with typical clinical signs. All isolates showed an identical spectrum of virulence-associated genes (mrp+, epf-, ofs-, sly-) and expressed a relatively small variant of MRP (Muramidase-Released Protein) called MRPs. A bacterin was produced using four of the S. suis serotype 7 isolates. An untreated and non-vaccinated control group A with 957 piglets, a non-vaccinated but amoxicillin-treated group B with 1012 piglets and an untreated group C with 998 piglets, which was vaccinated twice in the first and third week of life, were compared. Later, an additional group D with 290 piglets was vaccinated twice in the fourth and sixth week of life. Amoxicillin treatment in group B resulted in the lowest mortality and morbidity rate. Furthermore, the incidence of lameness and losses were significantly lower in vaccinated pigs compared to the control group. In an ex vivo blood survival assay, a strong bactericidal effect of the post immune sera of group D animals was found. This is likely due to the presence of specific opsonizing antibodies against S. suis elicited through vaccination and associated with the protective efficacy of the vaccine.

Mortality in the Vertebroplasty Population

PubMed Central

McDonald, Robert J.; Achenbach, Sara; Atkinson, Elizabeth; Gray, Leigh A.; Cloft, Harry J.; Melton, L. Joseph; Kallmes, David F.

2011-01-01

Purpose Vertebroplasty is an effective treatment for painful compression fractures refractory to conservative management. Since there are limited data regarding the survival characteristics of this patient population, we compared the survival of a treated to an untreated vertebral fracture cohort to determine if vertebroplasty affects mortality rates. Materials and Methods The survival of a treated cohort, comprising 524 vertebroplasty recipients with refractory osteoporotic vertebral compression fractures, was compared to a separate, historical cohort of 589 subjects with fractures not treated by vertebroplasty who were identified from the Rochester Epidemiology Project. Mortality was compared between cohorts using Cox proportional hazard models adjusting for age, gender, and Charlson indices of co-morbidity. Mortality was also correlated with pre-, peri-, and post-procedural clinical metrics (e.g., cement volume utilization, Roland-Morris Disability Questionnaire score, analog pain scales, frequency of narcotic use, and improvements in mobility) within the treated cohort. Results Vertebroplasty recipients demonstrated 77% of the survival expected for individuals of similar age, ethnicity, and gender within the US population. When compared to individuals with both symptomatic and asymptomatic untreated vertebral fractures, vertebroplasty recipients retained a 17% greater mortality risk. However, when compared to symptomatic untreated vertebral fractures, vertebroplasty recipients had no increased mortality following adjustment for differences in age, sex and co-morbidity (HR 1.02; CI 0.82–1.25). In addition, no clinical metrics used to assess the efficacy of vertebroplasty were predictive of survival. Conclusion Vertebroplasty recipients have mortality rates similar to individuals with untreated symptomatic fractures but worse mortality compared to those with asymptomatic vertebral fractures. PMID:21998109

Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

PubMed Central

Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

2014-01-01

Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis

PubMed Central

Schmidt, André; Palaniyappan, Lena; Smieskova, Renata; Simon, Andor; Riecher-Rössler, Anita; Lang, Undine E.; Fusar-Poli, Paolo; McGuire, Philip; Borgwardt, Stefan J.

2016-01-01

Background Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored. Methods We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication. Results The model including reward-induced modulation of insula–ACC connectivity was the best fitting model in each group. Compared with healthy controls (n = 19), patients with FEP (n = 29) revealed reduced right insula–ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula–ACC connectivity relative to healthy controls was observed only in untreated patients (n = 17), not in patients treated with antipsychotics (n = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP. Limitations The modest sample size of untreated patients with FEP was a limitation of our study. Conclusion This study indicates that insula–ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction. PMID:26854756

Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

PubMed Central

2011-01-01

Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression. PMID:21831310

Experimental Paracoccidioidomycosis in Mice

PubMed Central

Linares, Leonor I.; Friedman, Lorraine

1972-01-01

Virulence and infectivity of nine strains of Paracoccidioides brasiliensis were investigated in groups of mice which were inoculated intranasally or intravenously, and some of each were treated with corticosteroids. Fatal infections were not often seen among untreated mice, but mortality usually occurred when corticosteroids were given, regardless of the route of fungus inoculation. Prior treatment did not uniformly increase the incidence of infection, however; only in the case of intranasally inoculated mice was this effect seen. Most strains appeared to be more virulent when administered intravenously, with the exception of a single strain which, under the influence of corticosteroids, repeatedly displayed greatest virulence when given intranasally. All animals that died early in the course of the disease, irrespective of route of inoculation, always had acute pulmonary lesions and usually no other organ was involved. Animals which died later or were sacrificed always had chronic lung lesions. Whether or not chronically diseased animals had additional organ involvement correlated with how the organisms were administered; intravenously inoculated animals usually had extrapulmonary as well as pulmonary lesions, but lesions of those inoculated intranasally were almost exclusively pulmonary. Corticosteroids did not alter the histologic characteristics of either the acute or the chronic type of lesion, but the lesions of treated animals were usually more extensive. Most of the survivors appeared healthy even when infection was extensive. Images PMID:4637603

Modulation of cytotoxic T lymphocyte, natural killer cell, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by Vernonia cinerea L. and vernolide-A in BALB/c mice via enhanced production of cytokines IL-2 and IFN-γ.

PubMed

Pratheeshkumar, Poyil; Kuttan, Girija

2012-02-01

Effect of Vernonia cinerea L. and vernolide-A on cell-mediated immune (CMI) response was studied in normal as well as tumor-bearing BALB/c mice. Administration of V. cinerea and vernolide-A significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were also enhanced significantly in both normal as well as tumor-bearing animals after V. cinerea and vernolide-A administration compared with untreated control tumor-bearing animals. Extract and vernolide-A showed a significant increase in cytotoxic T lymphocyte (CTL) production in both the in vivo and in vitro models. The level of cytokines such as interleukin (IL)-2 and interferon (IFN)-γ were also enhanced by the treatment of V. cinerea and vernolide-A in both normal as well as tumor-bearing animals. This study demonstrated that V. cinerea extract and vernolide-A stimulate the CTL, NK cell, ADCC, and ADCC through enhanced secretion of IL-2 and IFN-γ.

Tinnitus-provoking salicylate treatment triggers social impairments in mice.

PubMed

Guitton, Matthieu J

2009-09-01

Tinnitus (perception of sound in silence) strongly affects the quality of life of sufferers. Tinnitus sufferers and their relatives frequently complain about major social impairments. However, it is not known whether this impairment directly results from the occurrence of tinnitus or is the indirect expression of a preexisting psychological vulnerability. Using the well-characterized animal model of salicylate-induced tinnitus, we investigate in mice whether the occurrence of tinnitus can trigger social impairments. Experiments were performed on 32 male Balb/C mice. Tinnitus was induced in mice using salicylate treatment. Social behavior was assessed in experimental and control animals using social interaction paradigm. Interaction time, number of social events, and number of nonsocial events were assessed in all animals. We demonstrate for the first time that treatment known to induce tinnitus triggers complex social impairments in mice. While salicylate-treated animals present a massive decrease in their overall social interactions compared to control untreated animals, they also display a paradoxal increase in the number of conspecific followings. Tinnitus can thus trigger a complex set of modifications of behavior, which will not only find their expression at the individual level, but also at the social level. Our results suggest that tinnitus can directly be a cause of psychosocial impairment in human and have strong implications for the clinical management of tinnitus sufferers.

Models for Trypanosoma evansi (surra), its control and economic impact on small-hold livestock owners in the Philippines.

PubMed

Dobson, R J; Dargantes, A P; Mercado, R T; Reid, S A

2009-08-01

Simple demographic and infectious disease models of buffaloes and other domestic hosts for animal trypanosomosis (surra) caused by Trypanosoma evansi were developed. The animal models contained deterministic and stochastic elements and were linked to simulate the benefit of control regimes for surra in village domestic animal populations in Mindanao, Philippines. The impact of the disease on host fertility and mortality were key factors in determining the economic losses and net-benefit from the control regimes. If using a high (99%) efficacy drug in surra-moderate to high risk areas, then treating all animals twice each year yielded low prevalence in 2 years; targeted treatment of clinically sick animals, constantly monitored (monthly), required 75% fewer treatments but took longer to reach a low prevalence than treating all animals twice each year. At high drug efficacy both of these treatment strategies increased the benefit over untreated animals by 81%. If drug efficacy declined then the benefit obtained from twice yearly treatment of all animals declined rapidly compared with regular monitoring and targeting treatment to clinically sick animals. The current control regimen applied in the Philippines of annual sero-testing for surra and only treating sero-positive animals provided the lowest net-benefit of all the control options simulated and would not be regarded as effective control. The total net-benefit from effective surra control for a typical village in a moderate/high risk area was 7.9 million pesos per annum (US $158,000). The value added to buffaloes, cattle, horses, goats/sheep and pigs as a result of this control was US $88, $84, $151, $7, $114 per animal/year, respectively.

Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-exposure Application of Tenofovir Gel

PubMed Central

Cranage, Martin; Sharpe, Sally; Herrera, Carolina; Cope, Alethea; Dennis, Mike; Berry, Neil; Ham, Claire; Heeney, Jonathan; Rezk, Naser; Kashuba, Angela; Anton, Peter; McGowan, Ian; Shattock, Robin

2008-01-01

Background The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. Methods and Findings A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6) or had modified virus outcomes (n = 2), while all untreated macaques and three of four macaques given placebo gel were infected, as were two of three animals receiving tenofovir gel after challenge. Moreover, analysis of lymphoid tissues post mortem failed to reveal sequestration of SIV in the protected animals. We found a strong positive association between the concentration of tenofovir in the plasma 15 min after rectal application of gel and the degree of protection in the six animals challenged with virus at this time point. Moreover, colorectal explants from non-SIV challenged tenofovir-treated macaques were resistant to infection ex vivo, whereas no inhibition was seen in explants from the small intestine. Tissue-specific inhibition of infection was associated with the intracellular detection of tenofovir. Intriguingly, in the absence of seroconversion, Gag-specific gamma interferon (IFN-γ)-secreting T cells were detected in the blood of four of seven protected animals tested, with frequencies ranging from 144 spot forming cells (SFC)/106 PBMC to 261 spot forming cells (SFC)/106 PBMC. Conclusions These results indicate that colorectal pretreatment with ARV drugs, such as tenofovir, has potential as a clinically relevant strategy for the prevention of HIV transmission. We conclude that plasma tenofovir concentration measured 15 min after rectal administration may serve as a surrogate indicator of protective efficacy. This may prove to be useful in the design of clinical studies. Furthermore, in vitro intestinal explants served as a model for drug distribution in vivo and susceptibility to virus infection. The finding of T cell priming following exposure to virus in the absence of overt infection is provocative. Further studies would reveal if a combined modality microbicide and vaccination strategy is feasible by determining the full extent of local immune responses induced and their protective potential. PMID:18684007

Addition of a combination of onion (Allium cepa) and coconut (Cocos nucifera) to food of sheep stops gastrointestinal helminthic infections.

PubMed

Mehlhorn, Heinz; Al-Quraishy, Saleh; Al-Rasheid, Khaled A S; Jatzlau, Antje; Abdel-Ghaffar, Fathy

2011-04-01

Sheep with gastrointestinal nematodes and cestodes were fed on three farms with a combination of specially prepared extracts of onion (Allium cepa) and coconut (Cocos nucifera) for 8 days containing each 60 g coconut and onion extract, combined with milk powder and/or polyethylene glycol (PEG) propylencarbonate (PC). In all cases, the worm stages disappeared from the feces and were also not found 9 and 20 days after the end of the feeding with this plant combination. Since all treated animals increased their body weight considerably (when compared to untreated animals), worm reduction was apparently as effective as it was shown in previous laboratory trials with rats and mice (Klimpel et al., Parasitol Res, in press, 2010; Abdel-Ghaffar et al., Parasitol Res, in press, 2010; in this volume).

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

PubMed Central

Hickey, Raymond D.; Mao, Shennen A.; Glorioso, Jaime; Lillegard, Joseph B.; Fisher, James E.; Amiot, Bruce; Rinaldo, Piero; Harding, Cary O.; Marler, Ronald; Finegold, Milton J.; Grompe, Markus; Nyberg, Scott L.

2014-01-01

Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH+/− pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer. Subsequently, these animals were outbred and crossed to produce the first FAH−/− pigs. FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopthy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes. PMID:24879068

Inflammation in the Pathogenesis of Lyme Neuroborreliosis

PubMed Central

Ramesh, Geeta; Didier, Peter J.; England, John D.; Santana-Gould, Lenay; Doyle-Meyers, Lara A.; Martin, Dale S.; Jacobs, Mary B.; Philipp, Mario T.

2016-01-01

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis. PMID:25892509

Blocking pulmonary ICAM-1 expression ameliorates lung injury in established diet-induced pancreatitis.

PubMed

Lundberg, A H; Fukatsu, K; Gaber, L; Callicutt, S; Kotb, M; Wilcox, H; Kudsk, K; Gaber, A O

2001-02-01

To determine whether blocking the cell surface expression of intracellular adhesion molecules (ICAM-1) in established severe acute pancreatitis (AP) would ameliorate pulmonary injury. Lung injury in AP is in part mediated by infiltrating leukocytes, which are directed to lung tissue by ICAM-l. The authors' laboratory has previously demonstrated that AP results in overproduction of inflammatory cytokines, upregulation of pulmonary ICAM-1 expression, and a concomitant infiltration of neutrophils, which results in lung injury. Young female mice were fed a choline-deficient/ethionine-supplemented diet to induce AP and were treated with a blocking dose of monoclonal antibody specific to the ICAM-1 receptor. Antibody treatment was administered at 72, 96, and 120 hours after beginning the diet, and all animals were killed at 144 hours. The degree of pancreatitis was evaluated by serum biochemical and tumor necrosis factor alpha levels as well as histology. The dual radiolabeled monoclonal antibody method was used to quantitate ICAM-1 cell surface expression in pulmonary tissue. Lung injury was assessed histologically and by determining lung microvascular permeability by measuring accumulated 125I-radiolabeled albumin. Pulmonary neutrophil sequestration was determined by the myeloperoxidase assay. All mice developed severe AP, and pancreatic injury was equally severe in both treated and untreated groups. Pulmonary ICAM-1 expression was significantly upregulated in animals with AP compared with controls. Treatment with a blocking dose of anti-ICAM-1 antibody after the induction of AP resulted in inhibited ICAM-1 cell surface expression to near control levels. Compared to untreated animals with AP, mice treated with anti-ICAM-1 mice had significantly reduced histologic lung injury and neutrophil sequestration, and a decreased microvascular permeability by more than twofold. These results demonstrate for the first time that treatment targeting the cell surface expression of ICAM-1 after the induction of AP ameliorates pulmonary injury, even in the face of severe pancreatic disease.

Confirmation of Fasciola hepatica resistant to triclabendazole in naturally infected Australian beef and dairy cattle.

PubMed

Brockwell, Yvette M; Elliott, Timothy P; Anderson, Glenn R; Stanton, Rex; Spithill, Terry W; Sangster, Nicholas C

2014-04-01

Triclabendazole (TCBZ) is the drug of choice for Fasciola hepatica control and reports of F. hepatica resistant to this drug from a wide range of geographic regions are very concerning. This study investigated the presence of TCBZ resistance in F. hepatica in naturally infected Australian beef and dairy cattle herds and evaluated methods of measuring the levels of resistance. Faecal egg count and coproantigen reduction tests (FECRT and CRT, respectively) were conducted on 6 South-eastern Australian beef properties and one dairy property where treatment failure by triclabendazole (TCBZ) was suspected. The CRT was conducted on an additional beef property. On each property 15 animals were treated with an oral preparation of TCBZ at the recommended dose and 15 animals remained as untreated controls. Fluke eggs in faeces were counted and coproantigen levels were measured before treatment and 21 days after treatment and in the untreated control animals. These data were evaluated using three different methods to calculate % reductions compared with controls. Resistance (<90% reduction) was detected on the dairy property using both FEC and CRT, and on 3/6 beef properties using FECRT and 4/7 beef properties using CRT. Using the FECRT, reductions of 6.1-14.1% were observed in dairy cattle and 25.9-65.5% in beef cattle. Using the CRT, reductions of 0.4-7.6% were observed in dairy cattle and 27.0-69.5% in beef cattle. Live flukes were recovered at slaughter following TCBZ treatment of 6 cattle from 3 of the beef properties, confirming the TCBZ resistance status of F. hepatica in these cattle. This is the first report of F. hepatica resistant to TCBZ in cattle in Australia and the results suggest that resistance is widespread in the South-eastern region. The CRT is shown to be a robust alternative to the FECRT for evaluation of TCBZ resistance in F. hepatica in cattle.

Apical Negative Pressure irrigation presents tissue compatibility in immature teeth

PubMed Central

Pucinelli, Carolina Maschietto; da Silva, Léa Assed Bezerra; Cohenca, Nestor; Romualdo, Priscilla Coutinho; da Silva, Raquel Assed Bezerra; Consolaro, Alberto; de Queiroz, Alexandra Mussolino; Nelson, Paulo

2017-01-01

Abstract Aim: To compare the apical negative pressure irrigation (ANP) with conventional irrigation in the teeth of immature dogs with apical periodontitis. Methods: Fifty-two immature pre-molar root canals were randomly assigned into 4 groups: ANP (n=15); conventional irrigation (n=17); healthy teeth (control) (n = 10); and teeth with untreated apical periodontitis (control) (n=10). After induction of apical periodontitis, teeth were instrumented using EndoVac® (apical negative pressure irrigation) or conventional irrigation. The animals were euthanized after 90 days. The sections were stained by HE and analyzed under conventional and fluorescence microscopy. TRAP histoenzymology was also performed. Statistical analyses were performed with the significance level set at 5%. Results: There was difference in the histopathological parameters between ANP and conventional groups (p<0.05). The ANP group showed a predominance of low magnitude inflammatory infiltrate, a smaller periodontal ligament, and lower mineralized tissue resorption. There were no differences in the periapical lesion extensions between the ANP and conventional groups (p>0.05). However, a lower number of osteoclasts was observed in the ANP group (p<0.05). Conclusion: The EndoVac® irrigation system presented better biological results and more advanced repair process in immature teeth with apical periodontitis than the conventional irrigation system, confirming the hypothesis. PMID:29211282

Corpuls CPR Generates Higher Mean Arterial Pressure Than LUCAS II in a Pig Model of Cardiac Arrest.

PubMed

Eichhorn, S; Mendoza, A; Prinzing, A; Stroh, A; Xinghai, L; Polski, M; Heller, M; Lahm, H; Wolf, E; Lange, R; Krane, M

2017-01-01

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods . Pigs ( n = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO 2 , regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results . Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion . Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device.

Corpuls CPR Generates Higher Mean Arterial Pressure Than LUCAS II in a Pig Model of Cardiac Arrest

PubMed Central

Mendoza, A.; Prinzing, A.; Stroh, A.; Xinghai, L.; Polski, M.; Heller, M.; Lahm, H.; Wolf, E.; Lange, R.; Krane, M.

2017-01-01

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods. Pigs (n = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO2, regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results. Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion. Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device. PMID:29392137

A nonlethal young domesticated ferret (Mustela putorius furo) model for studying pandemic influenza virus A/California/04/2009 (H1N1).

PubMed

Lednicky, John A; Croutch, Claire R; Lawrence, Sandra J; Hamilton, Sara B; Daniels, Deirdre E; Astroff, Barry

2010-10-01

Recent events have heightened the need for the rapid development of vaccines directed against pandemic influenza H1N1 viruses circulating during 2009 to 2010. The current study was conducted to establish a virus challenge dose for a subsequent CA/04 vaccine efficacy study in 3-mo-old domesticated ferrets. An additional consideration in using CA/04 in ferrets is the selection of endpoints on which to base the challenge dose, given the potential nonlethality of this particular model. Four doses ranging from 10(4) to 10(7) TCID(50) units of CA/04 per animal were administered by intranasal instillation to groups of male and female ferrets, and virus titers in nasal washes obtained 1, 3, and 5 d thereafter were determined in MDCK cells. Dosed ferrets developed clinically mild infections. Peak virus titers occurred on day 3 after instillation regardless of dose. Virus-treated ferrets had less weight gain than did untreated ferrets. In conclusion, 3-mo-old ferrets can be infected with doses as low as 10(4) TCID(50) units of CA/04, and virus titers in nasal washes and decreased body weight gain can be used to assess the course of nonlethal infection of 3-mo-old ferrets by CA/04.

Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.

PubMed

Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

2018-03-15

The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP ( p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.

Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions

PubMed Central

Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

2018-01-01

The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP (p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP (p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP (p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions. PMID:29543727

Immunohistochemical expression of heat shock protein27 in the mouse dental pulp after immediate teeth separation

PubMed Central

2011-01-01

Aim After immediate teeth separation, expression of HSP27 in the mouse dental pulp was examined. Immunohistochemistry was performed to examine the incidence of HSP27 expression. Materials and methods A total of 36 8-week-old ddY mice were used as experimental subjects and a wedge was inserted in between maxillary right molars. The wedge was removed 30 min or 3 h after insertion. Animals were immediately sacrificed after the removal of wedge or until 1 week later and serial sections from paraffin-embedded tissues were prepared. Immunohistochemistry was carried out to examine the expression of HSP27. The untreated side served as the control. Results In the control group, the endothelial cells and some pulp fibroblasts weakly expressed HSP27 suggesting that the expression is due to mechanical stress brought about by physiological masticatory force and pressure from the tongue. In both 30 min and 3 h experimental groups, HSP27 expression was highest at 24 h after wedge removal and the expression remained the same or started to decrease thereafter. The expression decreased at the same level as that of the control group 1 week after wedge removal. Conclusion HSP27 may serve as an indicator of stimulus strong enough to show its expression. PMID:22027643

Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

PubMed Central

Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to methacholine was assessed using the in vitro living lung slice preparation. Results One week of CPAP increased AW responsiveness to methacholine in male, but not female mice, compared to untreated control animals. The AW hyper-reactivity of male mice persisted for 2 weeks (at P21) after CPAP treatment ended. 4 days of CPAP, however, did not significantly increase AW reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a delayed response to early (7 days) CPAP treatment. The effects of 7 days of CPAP on hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones were relatively unaffected. Conclusion These data may be important to our understanding of the potential long-term consequences of neonatal CPAP therapy used in the intensive care of preterm infants. PMID:25950451

Saxagliptin Prevents Increased Coronary Vascular Stiffness in Aortic-Banded Mini Swine.

PubMed

Fleenor, Bradley S; Ouyang, An; Olver, T Dylan; Hiemstra, Jessica A; Cobb, Melissa S; Minervini, Gianmaria; Emter, Craig A

2018-06-11

Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin-a DPP-4 inhibitor-on coronary stiffness in aortic-banded mini swine. We hypothesized saxagliptin would prevent increased coronary artery stiffness in a translational swine model with cardiac features of HF with preserved ejection fraction by inhibiting perivascular adipose tissue inflammation. Yucatan mini swine were divided into 3 groups: control, aortic-banded untreated HF, and aortic-banded saxagliptin-treated HF. Ex vivo mechanical testing was performed on the left circumflex and right coronary arteries, and advanced glycation end product, NF-κB (nuclear factor-κB), and nitrotyrosine levels were measured. An increase in the coronary elastic modulus of HF animals was associated with increased vascular advanced glycation end products, NF-κB, and nitrotyrosine levels compared with control and prevented by saxagliptin treatment. Aortas from healthy mice were treated with media from swine perivascular adipose tissue culture to assess its role on vascular stiffening. Conditioned media from HF and saxagliptin-treated HF animals increased mouse aortic stiffness; however, only perivascular adipose tissue from the HF group showed increased advanced glycation end products and NF-κB levels. In conclusion, our data show increased coronary conduit vascular stiffness was prevented by saxagliptin and associated with decreased advanced glycation end products, NF-κB, and nitrotyrosine levels in a swine model with potential relevance to HF with preserved ejection fraction. © 2018 American Heart Association, Inc.

Evaluation of an experimental rat model for comparative studies of bleaching agents.

PubMed

Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Louzada; Rahal, Vanessa; Ervolino, Edilson; Jacinto, Rogério de Castilho; Gomes Filho, João Eduardo; Briso, André Luiz Fraga

2016-04-01

Dental materials in general are tested in different animal models prior to the clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents, by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats' vital teeth. Material and Methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals were untreated (control). The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated through histomorphometric analysis with inflammatory cell count in the coronal and radicular thirds of the pulp. Fibroblasts were also counted. Scores were attributed to odontoblastic layer and vascular changes. Tertiary dentin area and pulp chamber central area were measured histomorphometrically. Data were compared by analysis of variance and Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the coronal pulp occlusal third up to the 15-min application groups of each bleaching gel. In the groups exposed to each concentration for 30 and 45 min, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, reduction on the pulp chamber central area and enlargement of the tertiary dentin area were observed, without the detection of inflammation areas. Conclusion The rat model of extracoronal bleaching showed to be adequate for studies of bleaching protocols, as it was possible to observe alterations in the pulp tissues and tooth structure caused by different concentrations and application periods of bleaching agents.

Evaluation of an experimental rat model for comparative studies of bleaching agents

PubMed Central

CINTRA, Luciano Tavares Angelo; BENETTI, Francine; FERREIRA, Luciana Louzada; RAHAL, Vanessa; ERVOLINO, Edilson; JACINTO, Rogério de Castilho; GOMES, João Eduardo; BRISO, André Luiz Fraga

2016-01-01

ABSTRACT Dental materials in general are tested in different animal models prior to the clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents, by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats’ vital teeth. Material and Methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals were untreated (control). The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated through histomorphometric analysis with inflammatory cell count in the coronal and radicular thirds of the pulp. Fibroblasts were also counted. Scores were attributed to odontoblastic layer and vascular changes. Tertiary dentin area and pulp chamber central area were measured histomorphometrically. Data were compared by analysis of variance and Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the coronal pulp occlusal third up to the 15-min application groups of each bleaching gel. In the groups exposed to each concentration for 30 and 45 min, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, reduction on the pulp chamber central area and enlargement of the tertiary dentin area were observed, without the detection of inflammation areas. Conclusion The rat model of extracoronal bleaching showed to be adequate for studies of bleaching protocols, as it was possible to observe alterations in the pulp tissues and tooth structure caused by different concentrations and application periods of bleaching agents. PMID:27119766

Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

PubMed Central

Kumari, Mrinalini; Singh, Poonam

2015-01-01

Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats.

PubMed

Glorie, Lorenzo; Behets, Geert J; Baerts, Lesley; De Meester, Ingrid; D'Haese, Patrick C; Verhulst, Anja

2014-09-01

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management. Copyright © 2014 the American Physiological Society.

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms & new guidelines

PubMed Central

Yeghiazaryan, Kristina; Peeva, Viktoriya; Shenoy, Aparna; Schild, Hans H.; Golubnitschaja, Olga

2013-01-01

Aims Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Methods Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using “Comet Assay”-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner. Results Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA - under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetized and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment. Conclusions This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care. PMID:21470100

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration

PubMed Central

XU, XIAOPING; LI, XIAOHUA; ZHANG, LEI; LIU, ZHAOHUI; PAN, YUAN; CHEN, DONG; BIN, DONGHUA; DENG, QUN; SUN, YU; HOFFMAN, M. ROBERT; YANG, ZHIJIAN; YUAN, HONG

2017-01-01

Background/Aim: Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. Materials and Methods: A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E2 (PGE2) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Results: Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. Conclusion: CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE2 and IL-8 may be involved in the mechanism of enhanced wound-healing. PMID:28652418

Efficacy of a combination of 10% imidacloprid and 1% moxidectin against Caparinia tripilis in African pygmy hedgehog (Atelerix albiventris)

PubMed Central

2012-01-01

Background The efficacy and safety of a combination formulation of 10% imidacloprid + 1.0% moxidectin spot-on (Advocate® for Cats, Bayer Animal Health GmbH, Leverkusen, Germany) was tested in 40 African pygmy hedgehogs (Atelerix albiventris) naturally infested with Caparinia tripilis. Methods The optimal dosage level of the combination for hedgehogs was determined by assigning 20 hedgehogs into three treatment groups (0.1, 0.4 and 1.6 ml/Kg b.w.), and one untreated control group of 5 hedgehogs each. Twenty naturally infested hedgehogs were then randomly assigned to either treatment or control group with 10 animals each, and the number of live mites was counted from 13 body regions on day 0, 3, 9, 16, and 30 after single treatment at the dosage level of 0.1 ml/Kg. Results Before the chemotherapy, the highest density of mite was observed in external ear canals followed by the dorsal and the lowest in the ventral regions of the body surface. The dosage level of 0.1 ml/Kg, which corresponded to the recommended dosage level for cats, containing 10 mg imidacloprid and 1 mg moxidectin was also the optimal dosage level for hedgehogs. No hedgehogs in the treatment group showed live mites from day 3 post treatment. Side effects such as ataxia, depression, nausea, and weight fluctuation were not observed during the whole period of study. Conclusions This report suggests that a combination formulation of 0.1 ml/Kg of 10% imidacloprid + 1% moxidectin spot-on for cats is also useful for the control of Caparinia tripilis infestation in hedgehogs. PMID:22871121

Blood Pressure and Coronary Perfusion Pressure Targeted Cardiopulmonary Resuscitation Improves 24-Hour Survival from Ventricular Fibrillation Cardiac Arrest

PubMed Central

Maryam, Y.; Sutton, Robert M.; Friess, Stuart H.; Bratinov, George; Bhalala, Utpal; Kilbaugh, Todd J.; Lampe, Joshua; Nadkarni, Vinay M.; Becker, Lance B.; Berg, Robert A.

2016-01-01

Objective Treatment algorithms for cardiac arrest are rescuer-centric and vary little from patient to patient. The objective of this study was to determine if cardiopulmonary resuscitation (CPR) targeted to arterial blood pressure and coronary perfusion pressure (CPP) rather than optimal Guideline Care would improve 24-hour survival in a porcine model of ventricular fibrillation (VF) cardiac arrest. Design Randomized interventional study Setting Preclinical animal laboratory Subjects Female 3-month old swine Interventions/Measurements After induction of anesthesia and 7 minutes of untreated VF, 16 female 3-month old swine were randomized to: 1) Blood Pressure (BP) care: titration of chest compression (CC) depth to a systolic blood pressure (SBP) of 100 mmHg and vasopressor dosing to maintain CPP >20mmHg or 2) Guideline care: CC depth targeted to 51 mm and standard Guideline vasopressor dosing. Animals received manual CPR for 10 minutes before the first defibrillation attempt and standardized post-resuscitation care for 24 hours. Main Results 24-hour survival was more likely with BP care versus Guideline care (0/8 versus 5/8, p<0.03), and all survivors had normal neurological examinations. Mean CPP prior to defibrillation was significantly higher with BP care (28±3 mmHg versus 10±6 mmHg, p<0.01). CC depth was lower with BP care (48±0.4 mmHg versus 44±0.5 mmHg, p<0.05) and number of vasopressor doses was higher with BP care (median 3 [range 1-7] versus 2 [range 2-2], p<0.01). Conclusions Individualized goal-directed hemodynamic resuscitation targeting SBP of 100 mmHg and CPP >20 mmHg improved 24-hour survival compared to Guideline care in this model of VF cardiac arrest. PMID:27414479

Population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) following an intracoelomic injection or extended immersion.

PubMed

Rosenberg, Justin F; Haulena, Martin; Phillips, Brianne E; Harms, Craig A; Lewbart, Gregory A; Lahner, Lesanna L; Papich, Mark G

2016-11-01

OBJECTIVE To determine population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) administered an intracoelomic injection of enrofloxacin (5 mg/kg) or immersed in an enrofloxacin solution (5 mg/L) for 6 hours. ANIMALS 28 sea stars of undetermined age and sex. PROCEDURES The study had 2 phases. Twelve sea stars received an intracoelomic injection of enrofloxacin (5 mg/kg) or were immersed in an enrofloxacin solution (5 mg/L) for 6 hours during the injection and immersion phases, respectively. Two untreated sea stars were housed with the treated animals following enrofloxacin administration during both phases. Water vascular system fluid samples were collected from 4 sea stars and all controls at predetermined times during and after enrofloxacin administration. The enrofloxacin concentration in those samples was determined by high-performance liquid chromatography. For each phase, noncompartmental analysis of naïve averaged pooled samples was used to obtain initial parameter estimates; then, population pharmacokinetic analysis was performed that accounted for the sparse sampling technique used. RESULTS Injection phase data were best fit with a 2-compartment model; elimination half-life, peak concentration, area under the curve, and volume of distribution were 42.8 hours, 18.9 μg/mL, 353.8 μg•h/mL, and 0.25 L/kg, respectively. Immersion phase data were best fit with a 1-compartment model; elimination half-life, peak concentration, and area under the curve were 56 hours, 36.3 μg•h/mL, and 0.39 μg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the described enrofloxacin administration resulted in water vascular system fluid drug concentrations expected to exceed the minimum inhibitory concentration for many bacterial pathogens.

Waterborne transmission ofCampylobacter enteritis.

PubMed

Taylor, D N; Brown, M; McDermott, K T

1982-12-01

Campylobacter jejuni is an important cause of human diarrheal disease throughout the world and likeSalmonella enteritidis, has a large animal reservoir which includes most of man's domestic animals. Until recently, it has been difficult to trace the chain of transmission from animals to man because of inadequate environmental sampling techniques and means to distinguish strains. Recent improvements in these techniques have made environmental studies more feasible in 2 water-related out-breaks.In 1 study,C. jejuni was found to be an important cause of sporadic, summertime diarrheal disease among hikers in national wilderness areas of Wyoming. In this setting, illness was significantly associated with drinking untreated surface water. SubsequentlyC. jejuni was isolated from surface water, including mountian streams, and from animals in the area. Some of the environmental isolates were serotypically identical to strains isolated from humans.A second study occurred as a result of an outbreak of Campylobacter enteritis in a community in northern Illinois which was epidemiologically associated with the community water system.Campylobacter jejuni was isolated from several surface water sources and from the implicated water system. These studies demonstrate that environmental isolation ofC. jejuni is now possible and may add to our understanding of disease transmission.

Efficacy of 65% permethrin applied as a topical spot-on against walking dandruff caused by the mite, Cheyletiella yasguri in dogs.

PubMed

Endris, R G; Reuter, V E; Nelson, J D; Nelson, J A

2000-01-01

The efficacy of a 65% permethrin topically applied spot-on formulation (Defend EXspot Topical Remedy for Dogs, Schering-Plough Animal Health, Union, NJ) was determined against the dog mite, Cheyletiella yasguri (Smiley, 1965). Female dogs and their litters comprised the experimental unit, and all dogs in an experimental unit were treated on the same day 4 to 6 weeks after whelping. Mites and mite eggs were counted weekly on an untreated control group of six litters (15 pups) and on a group of six litters (14 pups) treated with 65% permethrin. Pups in the untreated control group maintained high numbers of Cheyletiella yasguri throughout the 14- to 21-day observation period. No mites or mite eggs were detected on dogs within 7 to 21 days after application of 65% permethrin. No adverse reactions were noted during the study. Clinical signs of infestation with C. yasguri--which included skin irritation, thickening of the stratum corneum, scratching with resultant scabs, pruritus, and flaky, scaly skin-were eliminated when mites were killed by the 65% permethrin formulation.

Reduced dental calcium expression and dental mass in chronic sleep deprived rats: Combined EDS, TOF-SIMS, and micro-CT analysis

NASA Astrophysics Data System (ADS)

Kuo, Yi-Jie; Huang, Yung-Kai; Chou, Hsiu-Chu; Pai, Man-Hui; Lee, Ai-Wei; Mai, Fu-Der; Chang, Hung-Ming

2015-08-01

Teeth are the hardest tissue in the body. The growth of teeth is closely regulated by circadian rhythmicity. Considering that sleep deprivation (SD) is a severe condition that disrupts normal circadian rhythmicity, this study was conducted to determine whether calcium expression (the major element participating in teeth constitution), and dental mass would be significantly impaired following SD. Adolescent rats subjected to 3 weeks of SD were processed for energy dispersive spectrum (EDS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), and micro-computed tomography (micro-CT) analyses. The EDS and TOF-SIMS results indicated that high calcium intensity was detected in both the upper and lower incisors of untreated rats. Micro-CT analysis corresponded closely with spectral data in which an enhanced dental mass was calculated in intact animals. However, following SD, both calcium expression and the dental mass were remarkably decreased to nearly half those of the untreated values. Because SD plays a detrimental role in impairing dental structure, establishing satisfactory sleep behavior would therefore serve as a crucial strategy for preventing or improving prevalent dental dysfunctions.

Effects of selected Indonesian plant extracts on E. cuniculi infection in vivo.

PubMed

Sak, Bohumil; Jandová, Anna; Doležal, Karel; Kváč, Martin; Květoňová, Dana; Hlásková, Lenka; Rost, Michael; Olšanský, Milan; Nurcahyo, Wisnu; Foitová, Ivona

2017-10-01

The present study was conducted to evaluate the methanolic extracts from several plant leaves widely used in traditional medicine to cure digestive tract disorders and in the self-medication of wild animals such as non-human primates, namely Archidendron fagifolium, Diospyros sumatrana, Shorea sumatrana, and Piper betle leaves, with regard to their antimicrosporidial activity against Encephalitozoon cuniculi in immunocompetent BALB/c mice determined using molecular detection of microsporidial DNA (qPCR) in various tissues and body fluids of infected, treated mice. Of the plant extracts tested, Diospyros sumatrana provided the most promising results, reducing spore shedding by 88% compared to untreated controls. Moreover, total burden per 1 g of tissue in the D. sumatrana extract-treated group reached 87% reduction compared to untreated controls, which was comparable to the effect of the standard drug, Albendazole. This data represents the baseline necessary for further research focused on determining the structure, activity and modes of action of the active compounds, mainly of D. sumatrana, enabling subsequent development of antimicrosporidial remedies. Copyright © 2017 Elsevier Inc. All rights reserved.

[The analysis of epidemiology, clinical symptoms, serological tests in the course of borreliosis].

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Leśniak, Maciej; Garlicki, Aleksander; Mach, Tomasz

2010-01-01

Lyme disease is an animal-borne disease, caused by spirochetes of the Borrelia burgdorferi (Bb). The infection is transmitted by ticks of the Ixodes ricinus species. Humans are infected through a tick bite to the skin. The aim of the study was evaluation of epidemiology, symptoms and serologic factors in Lyme disease. We have enrolled 39 patients from Malopołska region in the study treated for Lyme borreliosis. History of tick biting, clinical signs and symptoms and serological tests were evaluated. The most common symptoms were headaches and pain of the large joints. Patients with untreated erithema migrans (EM) more often developed symptoms from nervous system (83%) than joints (54%). We found abnormalities which confirmed inflammation in CSF in 24.3% of patients. Patients with positive IgG antibodies against Bb in CSF and confirmed their intrathecal synthesis had never had EM in the past. There is low percentage of the patients who were treated due to EM. Patients with untreated EM more often developed symptoms from nervous system than joints. The most common symptoms among our patients were headaches and pain of large joints.

Inequalities in purchase of mosquito nets and willingness to pay for insecticide-treated nets in Nigeria: Challenges for malaria control interventions

PubMed Central

Onwujekwe, Obinna; Hanson, Kara; Fox-Rushby, Julia

2004-01-01

Objective To explore the equity implications of insecticide-treated nets (ITN) distribution programmes that are based on user charges. Methods A questionnaire was used to collect information on previous purchase of untreated nets and hypothetical willingness to pay (WTP) for ITNs from a random sample of householders. A second survey was conducted one month later to collect information on actual purchases of ITNs. An economic status index was used for characterizing inequity. Major findings The lower economic status quintiles were less likely to have previously purchased untreated nets and also had a lower hypothetical and actual WTP for ITNs. Conclusion ITN distribution programmes need to take account of the diversity in WTP for ITNs if they are to ensure equity in access to the nets. This could form part of the overall poverty reduction strategy. PMID:15023234

Initial study of transdermal oxybutynin for treating hyperhidrosis.

PubMed

Millán-Cayetano, José Francisco; Del Boz, Javier; Toledo-Pastrana, Tomas; Nieto-Guindo, Miriam; García-Montero, Pablo; de Troya-Martín, Magdalena

2017-06-01

Oral oxybutynin for treating hyperhidrosis is effective and safe. Its side-effects are mild but frequent so we consider whether transdermal oxybutynin (considered to have a better side-effect profile) could be an alternative for treating hyperhidrosis. During 2015, a prospective study was conducted. Epidemiological variables, effectiveness (using the Hyperhidrosis Disease Severity Scale) and tolerance to transdermal oxybutynin were compiled concerning two different groups (patients previously treated or untreated with oral oxybutynin), at baseline, and at 3 and 12 months. Seven previously treated and six previously untreated patients were included. Five patients in the first group discontinued the treatment within 3 months. Of the two remaining patients, one reported ineffectiveness and the other obtained an excellent response but discontinued due to local irritation. Among the untreated patients, two showed no response and four experienced improvement (three with "partial response" and one with "excellent response"). All patients discontinued treatment within 12 months. No major adverse effects were observed. The absence of active metabolites after transdermal oxybutynin could result in less effectiveness than oral oxybutynin, although it is usually well tolerated. In conclusion, transdermal oxybutynin could have low effectiveness for the treatment of hyperhidrosis in patients following intolerance to oral oxybutynin but could provide good results in patients who have never tried systemic drugs. © 2017 Japanese Dermatological Association.

Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis

PubMed Central

Rubin, Leah H.; Carter, C. Sue; Bishop, Jeffrey R.; Pournajafi-Nazarloo, Hossein; Harris, Margret S. H.; Hill, Scot K.; Reilly, James L.; Sweeney, John A.

2013-01-01

Background In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine-vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined. Method Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls. Results Patients demonstrated increased AVP levels compared to controls (p=0.01). Higher AVP levels were associated with greater positive symptoms (r=0.58, p=0.03) and worse verbal learning (r=−0.63, p=0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients. Conclusion Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia. PMID:23465965

Mitochondrial protection by low doses of insulin-like growth factor-Iin experimental cirrhosis

PubMed Central

Pérez, Raquel; García-Fernández, María; Díaz-Sánchez, Matías; Puche, Juan E; Delgado, Gloria; Conchillo, Marian; Muntané, Jordi; Castilla-Cortázar, Inma

2008-01-01

AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I(IGF-I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS: Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Itreatment (2 μg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups. RESULTS: Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF-Itherapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Iand III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF-Itherapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION: These results show that IGF-Iexerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production. PMID:18461658

Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

ClinicalTrials.gov

2018-03-30

Anaplastic Astrocytoma; Brain Stem Glioma; Childhood Mixed Glioma; Fibrillary Astrocytoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

Histopathology of spleen allograft rejection in miniature swine

PubMed Central

Dor, Frank J M F; Gollackner, Bernd; Kuwaki, Kenji; Ko, Dicken S C; Cooper, David K C; Houser, Stuart L

2005-01-01

Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n = 4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model. PMID:15676033

Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo

PubMed Central

Batista, Denise da Gama Jaén; Batista, Marcos Meuser; de Oliveira, Gabriel Melo; Britto, Constança Carvalho; Rodrigues, Ana Carolina Mondaine; Stephens, Chad E.; Boykin, David W.; Soeiro, Maria de Nazaré Correia

2011-01-01

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via ip route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals. PMID:21814568

Pulsed low-dose irradiation of orthotopic glioblastoma multiforme (GBM) in a pre-clinical model: effects on vascularization and tumor control.

PubMed

Dilworth, Joshua T; Krueger, Sarah A; Dabjan, Mohamad; Grills, Inga S; Torma, John; Wilson, George D; Marples, Brian

2013-07-01

To compare dose-escalated pulsed low-dose radiation therapy (PLRT) and standard radiation therapy (SRT). Intracranial U87MG GBM tumors were established in nude mice. Animals received whole brain irradiation with daily 2-Gy fractions given continuously (SRT) or in ten 0.2-Gy pulses separated by 3-min intervals (PLRT). Tumor response was evaluated using weekly CT and [(18)F]-FDG-PET scans. Brain tissue was subjected to immunohistochemistry and cytokine bead array to assess tumor and normal tissue effects. Median survival for untreated animals was 18 (SE±0.5) days. A significant difference in median survival was seen between SRT (29±1.8days) and PLRT (34.2±1.9days). Compared to SRT, PLRT resulted in a 31% (p<0.01), 38% (p<0.01), and 53% (p=0.01) reduction in normalized tumor volume and a 48% (p<0.01), 51% (p<0.01), and 70% (p<0.01) reduction in tumor growth rate following the administration of 10Gy, 20Gy, and 30Gy, respectively. Compared to untreated tumors, PLRT resulted in similar tumor vascular density, while SRT produced a 40% reduction in tumor vascular density (p=0.05). Compared to SRT, PLRT was associated with a 28% reduction in degenerating neurons in the surrounding brain parenchyma (p=0.05). Compared to SRT, PLRT resulted in greater inhibition of tumor growth and improved survival, which may be attributable to preservation of vascular density. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Study on Utilization of Detoxified Jatropha curcas Seed Cake Subjected to Solid State Fermentation as a Dietary Supplement in Wistar Rats.

PubMed

Sharath, Belame S; Muthukumar, Sevva P; Somashekar, Devappa

2017-01-01

The presence of anti-nutrients and toxins like phorbol esters in Jatropha curcas seed cake (JSC) limits its application in feeds. This study was done to assess the potential of detoxified JSC as rat feed. The rats were fed a diet containing 0-5 and 10% of detoxified fermented JSC for four weeks. For the group I, only casein diet was used in rat feed as a negative control. For the group II, untreated JSC was used in rat feed as a positive control. For the group III, fermented JSC using Saccharomyces cerevisiae MTCC-36 was used. For the group IV, the fermented JSC treated with 65% ethanol to remove the residual toxic phorbol esters was used as rat feed. The rats fed with untreated JSC showed increased levels of serum liver enzymes as an indication of the onset of liver disease resulting in mortality. In this group, rats died in week 2, confirming that the cake is not safe as feed until it is processed. The rats fed with detoxified JSC with 5 and 10% level survived with no adverse effects, and the performance was on par with the control groups, although the body weight was slightly less compared to control. Therefore, it was concluded that the detoxified JSC might be the potential and alternative source of protein in the animal feedstuffs up to 10% level. There are recent patents also suggesting the use of alternative feed supplements in the animal feed applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.

PubMed

Gallego-Delgado, Julio; Lazaro, Alberto; Gomez-Garre, Dulcenombre; Osende, Julio I; Gonzalez-Rubio, Maria L; Herraiz, Marta; Manzarbeitia, Félix; Fortes, José; Fernandez-Cruz, Arturo; Egido, Jesús

2006-01-01

Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls. Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group. Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.

Effects of N-acetylcysteine and glutathione ethyl ester drops on streptozotocin-induced diabetic cataract in rats.

PubMed

Zhang, Shu; Chai, Fei-Yan; Yan, Hong; Guo, Yong; Harding, J J

2008-05-12

To evaluate the effect of N-acetylcysteine (NAC) and glutathione ethyl ester (GSH-EE) eye drops on the progression of diabetic cataract formation induced by streptozotocin (STZ). One hundred and thirty Sprague-Dawley (SD) rats were selected, and diabetes was induced by streptozotocin (65 mg/kg bodyweight) in a single intraperitoneal injection. The control group (group I) received only vehicle. Then, 78 rats with random blood glucose above 14 mmol/l were divided into four groups (group II-V). The drug-treated rats received NAC and GSH-EE eye drops five days before STZ injection. Group I and V animals received sodium phosphate buffer drops (pH 7.4), and those in groups II, III, and IV received 0.01% NAC, 0.05% NAC, and 0.1% GSH-EE drops, respectively. Lens transparency was monitored with a slit lamp biomicroscope and classified into six stages. At the end of four weeks, eight weeks, and 13 weeks, animals were killed and components involved in the pathogenesis of diabetic cataract including thiols (from glutathione and protein), glutathione reductase (GR), catalase (CAT), and glycated proteins were investigated in the lens extracts. Blood glucose, urine glucose, and bodyweight were also determined. The progression in lens opacity induced by diabetes showed a biphasic pattern in which an initial slow increase in the first seven weeks after STZ injection was followed by a rapid increase in the next six weeks. The progression of lens opacity in the treated groups (group II-IV) was slower than that of the untreated group (group V) in the earlier period and especially in the fourth week. There were statistically significant differences between the treated groups and the untreated group (p<0.05). However, these differences became insignificant after the sixth week, and the progression of lens opacification in all diabetic groups became aggravated. The content of thiol (from glutathione and protein), glutathione reductase (GR), and catalase (CAT) were lower in the lens extracts of the diabetic rats four weeks, eight weeks, and 13 weeks after the STZ injection while the levels of thiol and CAT activity were both higher in the treated groups (group II-IV) than in the untreated group (group V) at every stage. However, there was no statistically significant difference (p>0.05). Moreover, the diabetes resulted in an increased level of glycated proteins in both the treated groups and the untreated group, but there was no statistically significant difference between all the diabetic groups (p>0.05). NAC and GSH-EE can slightly inhibit the progression of the diabetic cataract at the earlier stage. They may maintain lens transparency and function by serving as a precursor for glutathione biosynthesis and by protecting sulfhydryl groups from oxidation.

Assaying Benefits of Poly[styrene-4-(trimethylammonium)methyl Triiodide] in Respiratory Protection Devices

DTIC Science & Technology

2009-12-01

common laboratory mouse, Mus musculus , and treated and mechanically equivalent untreated filter media to measure infection rates as a function of...to determine viable counts. Data noise in the control experiment prevented drawing a firm conclusion but loss of viability in the aerosol phase ...protection, Triosyn U U U UU 35 Joseph Wander Reset iii TABLE OF CONTENTS Section Page 1.0 Overview

Effect of preoperative regional artery chemotherapy on proliferation and apoptosis of gastric carcinoma cells

PubMed Central

Tao, Hou-Quan; Zou, Shou-Chun

2002-01-01

AIM: To study the effects of preoperative regional artery chemotherapy (PRACT) in inducing growth inhibition and apoptosis of gastric carcinoma (GC) cells. METHODS: TUNEL (terminal-deoxynucleotidyl-transferase TdT-mediated dUTP-fluorescein and labeling) method and immunohistochemical techniques were used to detect the state of apoptosis and proliferation of GC cells in histopathologic sections. A total of 110 cases of GC and 68 cases of metastatic lymph node with or without PRACT were adopted. Correlations between apoptosis index (AI), proliferation index (PI) and PRACT and prognosis were analysed. RESULTS: The apoptosis index (AI) was significantly higher in the PRACT group (12.5‰ ± 4.33‰) than in the untreated group (7.1‰ ± 3.43‰, P < 0.001), whereas the proliferation index (PI) in the PRACT group (33.8% ± 8.8%) was significantly lower than that in untreated group (43.6% ± 12.8%, P < 0.01). Both AI and PI were correlated to the differentiation degree of GC in PRACT group, the AI in the differentiated group was higher than that in undifferentiated group (P < 0.001), but the PI was lower in the differentiated group than that of the undifferentiated group (P < 0.01). The AI of GC cells in metastatic lymph node was also significantly higher in the PRACT group (7.9‰ ± 3.41‰) than in the untreated group (3.6‰ ± 2.93‰, P < 0.01), though the PI of GC cells in metastatic lymph nodes in the PRACT group (17.2% ± 6.8%) was significantly lower than that in the untreated group (26.7% ± 9.3%, P < 0.01). The severity of histopathologic changes was significantly higher in the PRACT group than in the untreated group (P < 0.05). In addition, postoperative surveys demonstrated that the 5-year survival rate of GC patients in the PRACT group was significantly higher than that of patients in the untreated group (P < 0.01). CONCLUSION: Preoperative regional artery chemotherapy (PRACT) showed inhibitory action on the growth of GC cells mainly through inhibiting proliferation and inducing the apoptosis of tumor cells. PRACT can improve the prognosis of GC patients also. PMID:12046068

CHEMO-IMMUNOLOGICAL STUDIES ON LOCALIZED INFECTIONS

PubMed Central

Lamar, Richard V.

1912-01-01

Virulent pneumococci injected into the cranial or spinal cavities of monkeys produce constantly a meningitis closely resembling pneumococcus meningitis in man, except that the experimental disease pursues a more rapid course to the invariable death of the untreated animal. An homologous immune pneumococcus serum injected into the spinal canal exerts a restraining influence upon the disease to the extent that when employed early it prevented, exceptionally, the occurrence of infection and thus saved the life of the animal, and when given later it at first retarded the disease but subsequently exerted no beneficial action and was powerless to save life. A mixture of sodium oleate, immune serum, and boric acid exerted regularly a more powerful action than immune serum alone, and not only prevented the occurrence of infection but also, when administered repeatedly, arrested the progress of an actually established infection and led, often, to the enduring and perfect recovery of the inoculated animal. It is proposed to employ a similar mixture in the direct treatment of pneumococcic meningitis and possibly of still other accessible local pneumococcic infections in man. PMID:19867598

Antileishmanial activity of essential oil from Chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in BALB/c mice.

PubMed

Monzote, L; Pastor, J; Scull, R; Gille, L

2014-01-01

Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide). Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. EO prevented lesion development compared (p<0.05) with untreated animals and treated with vehicle. In addition, the efficacy of EO was also statistically superior (p<0.05) compared with the glucantime-treated animals. No potential effects were observed with pure components treatment. Mix of pure compounds cause death of animals after 3 days of treatment. Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis. Copyright © 2014 Elsevier GmbH. All rights reserved.

Sustained phenotypic reversion of junctional epidermolysis bullosa dog keratinocytes: Establishment of an immunocompetent animal model for cutaneous gene therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spirito, Flavia; Capt, Annabelle; Rio, Marcela Del

2006-01-20

Gene transfer represents the unique therapeutic issue for a number of inherited skin disorders including junctional epidermolysis bullosa (JEB), an untreatable genodermatose caused by mutations in the adhesion ligand laminin 5 ({alpha}3{beta}3{gamma}2) that is secreted in the extracellular matrix by the epidermal basal keratinocytes. Because gene therapy protocols require validation in animal models, we have phenotypically reverted by oncoretroviral transfer of the curative gene the keratinocytes isolated from dogs with a spontaneous form of JEB associated with a genetic mutation in the {alpha}3 chain of laminin 5. We show that the transduced dog JEB keratinocytes: (1) display a sustained secretionmore » of laminin 5 in the extracellular matrix; (2) recover the adhesion, proliferation, and clonogenic capacity of wild-type keratinocytes; (3) generate fully differentiated stratified epithelia that after grafting on immunocompromised mice produce phenotypically normal skin and sustain permanent expression of the transgene. We validate an animal model that appears particularly suitable to demonstrate feasibility, efficacy, and safety of genetic therapeutic strategies for cutaneous disorders before undertaking human clinical trials.« less

Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

PubMed

Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

2007-02-01

Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

Parental administration of antipyretics to children with upper respiratory tract infections without consultation with a physician

PubMed Central

Andabaka, Tea; Globočnik, Tina; Vukelić, Dalibor; Esposito, Susanna; Baršić, Bruno

2011-01-01

Aim To evaluate the administration of antipyretics to children with upper respiratory tract infections (URTI) by their parents or guardians without consultation with physicians, and compare epidemiological and clinical characteristics of patients who received antipyretics and of untreated patients. Methods A prospective observational study was performed in three pediatric clinics in Zagreb, Croatia, from March to June 2002. A total of 171 children aged from 2 to 14 years with symptoms and signs of URTI lasting more than 2 days and fever above 38°C lasting more than 2 days were included in the study. Data were collected on the usage of antipyretics, patients’ demographic and epidemiological characteristics, and clinical signs and symptoms. Results Antipyretics, predominantly paracetamol, were used in 29.8% of patients. Their usage was less frequent in children attending day-care centers (49% of treated and 70% of untreated children, P = 0.014) and in children with reiterated URTIs (33.3% of treated and 55.8% of untreated children, P = 0.008). However, it was more frequent in children with recent URTIs in the family (33.3% of treated and 7.5% of untreated children, P < 0.001). Overall, most clinical signs and symptoms of URTI were notably less pronounced in patients treated with antipyretics. Conclusions Antipyretics use correlated with less pronounced clinical signs and symptoms of infection, which indicates their anti-inflammatory activity, but also with negative effects such as lethargy. It is necessary to educate parents on the positive and negative aspects of antipyretics use and on the optimal choice of an antipyretic drug. PMID:21328720

Clarifying the Impact of Untreated and Treated Dental Caries on Oral Health-Related Quality of Life among Adolescents.

PubMed

Feldens, Carlos Alberto; Ardenghi, Thiago Machado; Dos Santos Dullius, Angela Isabel; Vargas-Ferreira, Fabiana; Hernandez, Pedro Antonio González; Kramer, Paulo Floriani

2016-01-01

The aim of the present study was to investigate the effect of dental caries experience and the components of the decayed, missing and filled teeth (DMFT) index on oral health-related quality of life (OHRQoL) among adolescents in southern Brazil. A cross-sectional study was conducted with 509 adolescents aged 11-14 years enrolled at public schools in the municipality of Osório (southern Brazil). A calibrated examiner performed the clinical examination for caries (World Health Organization: DMFT index), malocclusion (Dental Aesthetic Index) and traumatic dental injuries [Andreasen et al., 2007]. The participants answered the Brazilian version of the Child Perceptions Questionnaire (CPQ11-14) - Impact Short Form, and their parents/guardians answered a structured questionnaire addressing demographic and socioeconomic characteristics. Data analysis involved Poisson regression with robust variance, with the calculation of rate ratios adjusted for potential confounding variables. High severity of dental caries experience exerted a significant impact on OHRQoL, even after controlling for socioeconomic and clinical factors (rate ratio 1.30; 95% confidence interval, CI 1.12-1.51). All OHRQoL domains were affected by untreated dental caries. The multivariate analysis demonstrated that the CPQ11-14 scores were 33% higher among adolescents with untreated caries (rate ratio 1.33; 95% CI 1.17-1.50) and 24% higher among those with missing teeth (rate ratio 1.24; 95% CI 1.06-1.47). No difference in OHRQoL was found between adolescents with filled teeth and those without dental caries. In conclusion, dental caries experience, untreated dental caries and missing teeth exerted a negative impact on OHRQoL among the adolescents. © 2016 S. Karger AG, Basel.

Cell-wall properties contributing to improved deconstruction by alkaline pre-treatment and enzymatic hydrolysis in diverse maize ( Zea mays L.) lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Muyang; Heckwolf, Marlies; Crowe, Jacob D.

A maize (Zea mays L. subsp. mays) diversity panel consisting of 26 maize lines exhibiting a wide range of cell-wall properties and responses to hydrolysis by cellulolytic enzymes was employed to investigate the relationship between cell-wall properties, cell-wall responses to mild NaOH pre-treatment, and enzymatic hydrolysis yields. Enzymatic hydrolysis of the cellulose in the untreated maize was found to be positively correlated with the water retention value, which is a measure of cell-wall susceptibility to swelling. It was also positively correlated with the lignin syringyl/guaiacyl ratio and negatively correlated with the initial cell-wall lignin, xylan, acetate, and p-coumaric acid (pCA)more » content, as well as pCA released from the cell wall by pre-treatment. The hydrolysis yield following pre-treatment exhibited statistically significant negative correlations to the lignin content after pre-treatment and positive correlations to the solubilized ferulic acid and pCA. Several unanticipated results were observed, including a positive correlation between initial lignin and acetate content, lack of correlation between acetate content and initial xylan content, and negative correlation between each of these three variables to the hydrolysis yields for untreated maize. Also, another surprising result was that pCA release was negatively correlated with hydrolysis yields for untreated maize and, along with ferulic acid release, was positively correlated with the pre-treated maize hydrolysis yields. In conclusion, this indicates that these properties that may negatively contribute to the recalcitrance in untreated cell walls may positively contribute to their deconstruction by alkaline pre-treatment« less

Long-Term Effects of Untreated Adolescent Idiopathic Scoliosis: A Review of the Literature

PubMed Central

Karavidas, Nikos; Moramarco, Marc; Moramarco, Kathryn

2016-01-01

Currently, adolescent idiopathic scoliosis (AIS) is principally regarded as benign, but some researchers have cited serious or extreme effects, including severe pain, cardiopulmonary compromise, social isolation, and even early death. Therefore, exploration of the long-term effects of AIS, the most common type of idiopathic scoliosis, is warranted. The purpose of this review was to examine the long-term studies on the natural history of AIS and/or reviews concerning the long-term effects of untreated AIS. A PubMed search was conducted using the key words idiopathic scoliosis, long-term effects and idiopathic scoliosis, natural history. For further analysis, references cited in those studies were reviewed for additional, related evidence not retrieved in the initial PubMed search. A review of the pertinent bibliography showed that older natural history studies did not distinguish between late-onset scoliosis (referred to in this paper as AIS) and early-onset scoliosis (EOS). The more recent studies offer such important distinction and reach to the general conclusion that untreated AIS does not lead to severe consequences with respect to signs and symptoms of scoliosis. It is possible that earlier studies may have included patient populations with EOS, leading to the perception of untreated scoliosis as having an unusually high morbidity rate. Studies on the long-term effects of AIS that specifically excluded EOS patients conclude that AIS is a benign disorder. This indicates that for research and reporting purposes, it is important to distinguishing between AIS and EOS. This will allow the practitioner and patient and their families to decide on an optimal treatment plan based on the most appropriate prognosis. PMID:27994795

Post-exercise hypotension and heart rate variability response after water- and land-ergometry exercise in hypertensive patients

PubMed Central

Bocalini, Danilo Sales; Bergamin, Marco; Evangelista, Alexandre Lopes; Rica, Roberta Luksevicius; Pontes, Francisco Luciano; Figueira, Aylton; Serra, Andrey Jorge; Rossi, Emilly Martinelli; Tucci, Paulo José Ferreira

2017-01-01

Background systemic arterial hypertension is the most prevalent cardiovascular disease; physical activity for hypertensive patients is related to several beneficial cardiovascular adaptations. This paper evaluated the effect of water- and land-ergometry exercise sessions on post-exercise hypotension (PEH) of healthy normotensive subjects versus treated or untreated hypertensive patients. Methods Forty-five older women composed three experimental groups: normotensive (N, n = 10), treated hypertensive (TH, n = 15) and untreated hypertensive (UH, n = 20). The physical exercise acute session protocol was performed at 75% of maximum oxygen consumption (VO2max) for 45 minutes; systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure were evaluated at rest, peak and at 15, 30, 45, 60, 75 and 90 minutes after exercise cessation. Additionally, the heart rate variability (HRV) was analyzed by R-R intervals in the frequency domain for the assessment of cardiac autonomic function. Results In both exercise modalities, equivalent increases in SBP were observed from rest to peak exercise for all groups, and during recovery, significant PEH was noted. At 90 minutes after the exercise session, the prevalence of hypotension was significantly higher in water- than in the land-based protocol. Moreover, more pronounced reductions in SBP and DBP were observed in the UH patients compared to TH and N subjects. Finally, exercise in the water was more effective in restoring HRV during recovery, with greater effects in the untreated hypertensive group. Conclusion Our data demonstrated that water-ergometry exercise was able to induce expressive PEH and improve cardiac autonomic modulation in older normotensive, hypertensive treated or hypertensive untreated subjects when compared to conventional land-ergometry. PMID:28658266

Cell-wall properties contributing to improved deconstruction by alkaline pre-treatment and enzymatic hydrolysis in diverse maize ( Zea mays L.) lines

DOE PAGES

Li, Muyang; Heckwolf, Marlies; Crowe, Jacob D.; ...

2015-02-20

A maize (Zea mays L. subsp. mays) diversity panel consisting of 26 maize lines exhibiting a wide range of cell-wall properties and responses to hydrolysis by cellulolytic enzymes was employed to investigate the relationship between cell-wall properties, cell-wall responses to mild NaOH pre-treatment, and enzymatic hydrolysis yields. Enzymatic hydrolysis of the cellulose in the untreated maize was found to be positively correlated with the water retention value, which is a measure of cell-wall susceptibility to swelling. It was also positively correlated with the lignin syringyl/guaiacyl ratio and negatively correlated with the initial cell-wall lignin, xylan, acetate, and p-coumaric acid (pCA)more » content, as well as pCA released from the cell wall by pre-treatment. The hydrolysis yield following pre-treatment exhibited statistically significant negative correlations to the lignin content after pre-treatment and positive correlations to the solubilized ferulic acid and pCA. Several unanticipated results were observed, including a positive correlation between initial lignin and acetate content, lack of correlation between acetate content and initial xylan content, and negative correlation between each of these three variables to the hydrolysis yields for untreated maize. Also, another surprising result was that pCA release was negatively correlated with hydrolysis yields for untreated maize and, along with ferulic acid release, was positively correlated with the pre-treated maize hydrolysis yields. In conclusion, this indicates that these properties that may negatively contribute to the recalcitrance in untreated cell walls may positively contribute to their deconstruction by alkaline pre-treatment« less

Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

PubMed Central

Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

2015-01-01

Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p < 0.001). In the overall group of 24 treated plus untreated former users, 7 (29%) had experienced major depressive episodes during AAS withdrawal; 4 of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

Effects of N-[Imino(1-Piperidinyl)Methyl] Guanidine on the Intensity of Free Radical Processes, Aconitase Activity, and Citrate Level in the Tissues of Rats with Experimental Type 2 Diabetes Mellitus.

PubMed

Skliarova, E I; Popova, T N; Shulgin, K K

2016-06-01

Effects of a synthetic biguanide derivative N-[imino(1-piperidinyl)methyl] guanidine (NIPMG) on free radical homeostasis, aconitase activity, and citrate concentration were studied in the liver and blood serum of rats with type 2 diabetes mellitus. Analysis of biochemiluminescence parameters showed that administration of this agent (10 mg/kg body weight) to animals with diabetes reduced the intensity of free radical processes in study tissues relative to the increased values in untreated diabetic animals. Under these conditions, aconitase activity, a principal target of ROS effects, and citrate level in the liver and blood serum of rats approached the control levels. The results show that NIPMG can positively regulate free radical homeostasis and reduce the intensity of oxidative stress in type 2 diabetes mellitus, which was accompanied by normalization of the studied parameters.

Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case–control sample of schizophrenia

PubMed Central

Ingason, A; Giegling, I; Hartmann, A M; Genius, J; Konte, B; Friedl, M; Ripke, S; Sullivan, P F; St. Clair, D; Collier, D A; O'Donovan, M C; Mirnics, K; Rujescu, D

2015-01-01

Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders. PMID:26460480

Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia.

PubMed

Ingason, A; Giegling, I; Hartmann, A M; Genius, J; Konte, B; Friedl, M; Ripke, S; Sullivan, P F; St Clair, D; Collier, D A; O'Donovan, M C; Mirnics, K; Rujescu, D

2015-10-13

Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.

Modulating effects in learned helplessness of dyadic dominance-submission relations.

PubMed

Díaz-Berciano, Cristina; de Vicente, Francisco; Fontecha, Elisa

2008-01-01

In this experiment, learned helplessness was studied from an ethological perspective by examining individual differences in social dominance and its influence on the effects of helplessness. Ninety animals were used, 30 randomly selected and 60 selected because of their clear dominance or submission. Each condition (dominant, submissive, and random) was distributed in three subgroups corresponding to the triadic design. The test consisted of an escape/avoidance task. The results showed that the animals in the uncontrollable condition performed worse than those in the controllable and no treatment conditions. Social submission and dominance reduced vulnerability of the subjects against learned helplessness. Submission had a facilitating effect on subsequent learning, independently of whether pretreatment was controllability or uncontrollability. Learned mastery was observed in the submissive condition, because submission benefited the subjects in the controllable condition in comparison with the untreated subjects, and dominance impaired the subjects in the controllable condition. Copyright 2007 Wiley-Liss, Inc.

Evaluation of the effects of treating dairy cows with meloxicam at calving on retained fetal membranes risk

PubMed Central

Newby, Nathalie C.; Renaud, David; Tremblay, Robert; Duffield, Todd F.

2014-01-01

Some non-steroidal anti-inflammatory drugs increase the risk of retained fetal membranes. This is the first study to investigate the effects of meloxicam on the risk of retained fetal membranes. Administration of meloxicam to dairy cattle immediately following calving revealed no differences in the incidence of retained fetal membranes between meloxicam-treated and untreated animals. There was no difference between the 2 groups in the incidence of periparturient diseases following calving. Meloxicam can be used on the day of calving in lactating cows without increasing the risk of retained fetal membranes. PMID:25477550

Effect of simulated weightlessness on the immune system in rats

NASA Technical Reports Server (NTRS)

Caren, L. D.; Mandel, A. D.; Nunes, J. A.

1980-01-01

Rats suspended in a model system designed to simulate many aspects of weightlessness were immunized with sheep red blood cells. Parameters measured on these and control rats included titers of anti-sheep red blood cell antibodies, serum immunoglobulin levels, spleen and thymus weights, hematocrits, and leukocyte differential counts on peripheral blood. No significant differences were found between test and weight-bearing, harnessed controls; however, the thymuses of animals in both these groups were significantly smaller than untreated cage controls. The lack of an effect of simulated weightlessness on the immune system is an interesting result, and its significance is discussed.

Effect of a stable prostacyclin analogue on canine renal allograft rejection.

PubMed Central

Tobimatsu, M; Ueda, Y; Toyoda, K; Saito, S; Konomi, K

1987-01-01

The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection. Images Figs. 1A and B. PMID:3545109

The potential beneficial effect of nicardipine in a rat model of transient forebrain ischemia.

PubMed

Alps, B J; Hass, W K

1987-05-01

In a rat 3-day survival model of 10-minute four-vessel occlusion, halothane anesthesia was used to attenuate the ictal blood pressure elevation of the cerebral ischemic response and thereby maintain an isoelectric EEG. Selectively vulnerable regions of the brain were protected by preischemia plus postischemia maintenance treatment with the calcium entry blocker nicardipine. Compared with untreated animals, repeated doses at 500 micrograms/kg IP were markedly more effective than doses of 50 micrograms/kg. Ongoing studies demonstrate a neurocytoprotective action of nicardipine when deferred treatment is given postischemia.

Scotopic vision deficits in young monkeys exposed to lead.

PubMed

Bushnell, P J; Bowman, R E; Allen, J R; Marlar, R J

1977-04-15

Rhesus monkeys were reared on diets designed to produce blood lead concentrations of 14 (untreated), 55, or 85 micrograms per 100 milliliters for the first year of life. Eighteen months later, blood lead levels were normal in all animals. At this time, however, visual discrimination performance in the 85-microgram group was impaired under dim light relative both to their own performance under bright light and to the performance of the other groups under all light levels used. We interpret these results to reflect a deleterious, enduring impairment of scotopic visual function (night blindness) as a result of early lead intoxication.

High speed measurement of corn seed viability using hyperspectral imaging

NASA Astrophysics Data System (ADS)

Ambrose, Ashabahebwa; Kandpal, Lalit Mohan; Kim, Moon S.; Lee, Wang-Hee; Cho, Byoung-Kwan

2016-03-01

Corn is one of the most cultivated crops all over world as food for humans as well as animals. Optimized agronomic practices and improved technological interventions during planting, harvesting and post-harvest handling are critical to improving the quantity and quality of corn production. Seed germination and vigor are the primary determinants of high yield notwithstanding any other factors that may play during the growth period. Seed viability may be lost during storage due to unfavorable conditions e.g. moisture content and temperatures, or physical damage during mechanical processing e.g. shelling, or over heating during drying. It is therefore vital for seed companies and farmers to test and ascertain seed viability to avoid losses of any kind. This study aimed at investigating the possibility of using hyperspectral imaging (HSI) technique to discriminate viable and nonviable corn seeds. A group of corn samples were heat treated by using microwave process while a group of seeds were kept as control group (untreated). The hyperspectral images of corn seeds of both groups were captured between 400 and 2500 nm wave range. Partial least squares discriminant analysis (PLS-DA) was built for the classification of aged (heat treated) and normal (untreated) corn seeds. The model showed highest classification accuracy of 97.6% (calibration) and 95.6% (prediction) in the SWIR region of the HSI. Furthermore, the PLS-DA and binary images were capable to provide the visual information of treated and untreated corn seeds. The overall results suggest that HSI technique is accurate for classification of viable and non-viable seeds with non-destructive manner.

Field and in vitro insecticidal efficacy of alphacypermethrin-treated high density polyethylene mesh against Culicoides biting midges in South Africa.

PubMed

Page, P C; Labuschagne, K; Venter, G J; Schoeman, J P; Guthrie, A J

2014-06-16

The efficacy of untreated and alphacypermethrin-treated high density polyethylene (HDPE) mesh against Culicoides biting midges (Diptera: Ceratopogonidae) was determined using Onderstepoort downdraught black light traps and a contact bioassay. Three traps were operated overnight in four replicates of a 3×3 randomised Latin square design near horses under South African field conditions. Both the untreated and alphacypermethrin-treated HDPE mesh significantly (P<0.05) reduced the numbers of Culicoides midges, predominantly Culicoides (Avaritia) imicola Kieffer, collected in the light traps by 4.2 and 7.2 times, respectively. A repellent effect of the alphacypermethrin-treated mesh was not confirmed because the number of midges collected in the light traps with untreated and alphacypermethrin-treated HDPE mesh was not significantly different (P=0.656). Bioassay of the insecticidal contact efficacy indicated median C. imicola mortality of 100% from 30 and 10 min following exposure to the alphacypermethrin-treated HDPE mesh for 1 or 3 min, respectively. In the bioassay, mortality was significantly higher (P=0.016) at 5 min post exposure in the midges exposed to the alphacypermethrin-treated mesh for 3 min (74.8%) compared to the 1 min exposure group (59.5%). The HDPE mesh could be used to reduce exposure of housed animals to Culicoides midges, specifically C. imicola, and viruses transmitted by these midges. Mesh treated with alphacypermethrin had the additional benefit of a rapid insecticidal effect on C. imicola. Copyright © 2014 Elsevier B.V. All rights reserved.

Hormonal crosstalk with calcium channel blocker during implantation.

PubMed

Banerjee, Aryamitra; Padh, Harish; Nivsarkar, Manish

2011-08-01

The site specific action of the calcium channel blocker diltiazem in blocking prostaglandin synthesis and hence causing blastocyst implantation failure has been previously described. Based on this understanding it was important to learn if this pathway was under the control of the fine balance in estradiol-progesterone (E2-P4) milieu, considered to be of the utmost significance for effective implantation. In the current study the circulating E2-P4 levels were monitored on the first 6 d of pregnancy at various time points using sensitive chemiluminescence based assays. Next, diltiazem was administered intra-luminally into the uterus at 10-20 h prior to implantation as this time has been previously implicated to be when the best anti-implantation activity of diltiazem can be observed. Following this, the E2-P4 in peripheral circulation was again monitored. On d 6 (post implantation) the implantation sites were observed in the uterus of both diltiazem treated and untreated groups using Chicago blue dye and correlated to the hormonal activity. The levels of both estradiol and progesterone were very similar in both untreated and diltiazem treated groups during and post implantation. However complete implantation failure was noted in the diltiazem treated group whereas prominent implantation sites were observed in the untreated animals. Thus, the previously reported inhibition of blastocyst implantation cascade by calcium channel blockers during the 'implantation window' seems to be an independent mechanism interfering with uterine receptivity without any direct estrogen-progesterone control and further studies to understand its regulation need to be performed.

Human brucellosis is characterized by an intense Th1 profile associated with a defective monocyte function.

PubMed

Rodríguez-Zapata, Manuel; Matías, Marlene J; Prieto, Alfredo; Jonde, Marco A; Monserrat, Jorge; Sánchez, Lorenzo; Reyes, Eduardo; De la Hera, Antonio; Alvarez-Mon, Melchor

2010-07-01

In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1beta (IL-1beta), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-gamma, IL-2, and TNF-alpha, but not that of IL-4, by phorbol myristate-activated CD4(+) CD3(+) and CD8(+) CD3(+) T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-gamma levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.

Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function▿

PubMed Central

Rodríguez-Zapata, Manuel; Matías, Marlene J.; Prieto, Alfredo; Jonde, Marco A.; Monserrat, Jorge; Sánchez, Lorenzo; Reyes, Eduardo; De la Hera, Antonio; Alvarez-Mon, Melchor

2010-01-01

In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-γ, IL-2, and TNF-α, but not that of IL-4, by phorbol myristate-activated CD4+ CD3+ and CD8+ CD3+ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-γ levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes. PMID:20404074

Efficacy, distribution and faecal excretion of copper oxide wire particles in a novel bolus in red deer (Cervus elaphus).

PubMed

Castillo-Alcala, F; Wilson, P R; Molenaar, R; Lopez-Villalobos, N

2007-04-01

To determine the efficacy of a novel copper oxide wire particle (COWP) formulation in elevating concentrations of copper (Cu) in the liver and serum of red deer (Cervus elaphus), and to investigate the distribution of particles in the gastrointestinal tract and the rate of their excretion in faeces. Mixed-age red deer hinds were allocated to three groups (n=10 per group) on the basis of pre-treatment liver Cu concentrations. Groups 1 and 2 were treated orally with a 10-g COWP bolus on Days 0 and 30, respectively, while the remaining group served as an untreated control. Animals were slaughtered on Day 60, when blood and liver samples were collected for determination of Cu concentrations. An additional group of 18-month-old red deer hinds (n=20) were treated orally with a 10-g COWP bolus, and four were slaughtered on each of Days 1, 5, 15, 30 and 60 after treatment. The gastrointestinal tract was secured between compartments below the oesophagus and contents rinsed until sedimentation of particles was complete. The sediment was oven-dried and COWP were separated and weighed. Faeces were collected continuously from four additional animals held in metabolism cages for 4 days after treatment, sub-sampled daily, and COWP recovered. Mean liver Cu concentrations at slaughter were 80, 597 and 447 micromol/kg for controls and hinds treated 30, and 60 days previously, respectively. Corresponding mean serum Cu concentrations were 7.7, 12.9 and 11.9 micromol/L, respectively. Liver and serum Cu concentrations were higher in both treatment groups than in untreated control animals (p<0.001). COWP were found in all compartments of the gastrointestinal tract measured, for at least 15 days, and in the rumen/reticulum and abomasum for at least 60 days post-administration. The highest rate of recovery overall was from the rumen/reticulum. Mean weight of COWP recovered from faeces was 0.09 g during the first 24 h and 0.94 g over the first 4 days following administration. The COWP bolus tested resulted in elevated mean liver Cu concentrations for at least 60 days compared with control animals. The majority of COWP were found in the rumen/ reticulum, where recovery was possible for at least 60 days. About 10% of particle weight was excreted in the faeces within 4 days of administration. The test bolus was efficacious in deer, elevating mean liver and serum Cu concentrations 30 and 60 days after treatment. Variation in faecal excretion may explain between-animal differences in efficacy.

Anti cancerous efficacy of Ayurvedic milk extract of Semecarpus anacardium nuts on hepatocellular carcinoma in Wistar rats.

PubMed

Joseph, Joice P; Raval, Sunant K; Sadariya, Kamlesh A; Jhala, Mayur; Kumar, Pranay

2013-01-01

The objective of the study was to determine the anticancerous efficacy of Ayurvedic preparation made of Semecarpus anacardium (SA) nuts. Five groups of rats were used for the study. Group I served as water control. Hepatocellular carcinoma (HCC) was induced in groups II, III and IV animals using N-nitrosodiethylamine as inducing agent followed by phenobarbitone as promoter for 13 weeks. Group-II animals were kept untreated as hepatocellular carcinoma control. Group-III animals were treated with Ayurvedic milk extract of Semecarpus anacardium nuts at dose mentioned in Ashtangahridaya, an authentic book of Ayurveda for 49 days and group-IV animals were treated with doxorubicin as reference drug at dose of 1mg/kg twice a week for 7 weeks. Group V animals were kept as drug (SA nut milk extract) control for studying the effect of nut milk extract on normal rats. After 154 days of experiment, all animals were subjected to screening for HCC by estimation of liver enzymes, HCC marker (alpha-2 macroglobulin) and histopathology. Both liver enzymes and HCC marker were increased in hepatocellular carcinoma control along with neoplastic changes in liver and were decreased in Semecarpus anacardium nut milk extract treated group. The Ayurvedic drug showed positive correlation with the action of doxorubicin. This study demonstrated the efficacy of Semecarpus anacardium nut milk extract for the treatment of hepatocellular carcinoma either alone or along with chemotherapy.

Long-acting oxytetracycline prophylaxis to protect susceptible cattle introduced into an area of Kenya with endemic East Coast fever.

PubMed

Chumo, R S; Irvin, A D; Morzaria, S P; Katende, J; Purnell, R E

1989-03-04

Two field trials were carried out in successive years at the Ngong Veterinary Farm, Kenya, in which young cattle, previously unexposed to tick-borne diseases, were introduced into an area with endemic East Coast fever while protected by a series of injections of a long-acting oxytetracycline. In 1984, 12 animals which received injections of 20 mg/kg of the drug on days 0, 7, 14 and 21 after introduction, together with 12 untreated controls, were exposed without tick control until clinical disease occurred. All 12 control animals contracted East Coast fever by day 24 and 10 of them died. Five of the 12 injected animals had detectable parasites, and one of them required antitheilerial treatment. In 1985, four groups of 10 calves were introduced. One group received injections of 20 mg/kg of oxytetracycline on days 7 and 14, one group received injections on days 7, 14 and 21, and a third group received injections on days 7, 12 and 17; the fourth group (controls) had no treatment until clinical disease occurred. By day 35 all the control animals had contracted the disease and one had died despite antitheilerial treatment. Three injections of oxytetracycline suppressed the disease so that mild reactions occurred in only four animals in each group, but two injections failed to prevent severe reactions in two animals and mild reactions in four others.(ABSTRACT TRUNCATED AT 250 WORDS)

Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, Damian J.; Shadman, Mazyar; Jones, Jon C.

Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls).more » In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.« less

Growth, carcass yield and meat quality attributes of Red Maasai sheep fed wheat straw-based diets.

PubMed

Safari, John G; Mushi, Daniel E; Mtenga, Louis A; Kifaro, George C; Eik, Lars O

2011-01-01

Thirty-two castrated Red Maasai sheep (12.7 kg initial body weight, aged 12-18 months), were used in an 84-day experiment to evaluate diets based on treated straw upon growth performance, carcass yield and meat quality. The animals were blocked by weight into four similar groups and randomly allotted into four dietary treatments, with eight individually fed animals per treatment. The dietary treatments were ad libitum untreated wheat straw (UTS), wheat straw treated with urea and lime (TS), straw and ad libitum hay (UTSH), and TS and ad libitum hay (TSH). In addition, each experimental animal received 220 g/day (on as fed basis) of a concentrate diet. Treatment of straw increased (P < 0.05) dry matter intake (42.3 vs. 33.7 g/kg W (75)/day), energy intake (4.6 vs. 3.7 MJ ME/d) and the average daily gain (40.7 vs. 23.1 g). Animals on TS produced heavier (P < 0.05) carcasses (6.6 vs. 5.4 kg) with superior conformation than animals on UTS. Percentage cooking loss was higher in carcasses from animals fed TS compared to those from other diets. Except M. longissimus dorsi and M. semitendinosus, tenderness of muscles was not affected by diet but ageing of meat improved (P < 0.001) tenderness. Overall, straw treatment increased carcass yields with limited effects on meat quality attributes.

The effect of taurine and enriched environment on behaviour, memory and hippocampus of diabetic rats.

PubMed

Rahmeier, Francine Luciano; Zavalhia, Lisiane Silveira; Tortorelli, Lucas Silva; Huf, Fernanda; Géa, Luiza Paul; Meurer, Rosalva Thereza; Machado, Aryadne Cardoso; Gomez, Rosane; Fernandes, Marilda da Cruz

2016-09-06

Diabetes mellitus (DM) has been studied recently as a major cause of cognitive deficits, memory and neurodegenerative damage. Taurine and enriched environment have stood out for presenting neuroprotective and stimulating effects that deserve further study. In this paper, we examined the effects of taurine and enriched environment in the context of diabetes, evaluating effects on behaviour, memory, death and cellular activity. Eighty-eight Wistar rats were divided into 2 groups (E=enriched environment; C=standard housing). Some animals (24/group) underwent induction of diabetes, and within each group, some animals (half of diabetics (D) and half of non-diabetics (ND)/group) were treated for 30days with taurine (T). Untreated animals received saline (S). In total, there were eight subgroups: DTC, DSC, NDTC, NDSC, DTE, DSE, NDTE and NDSE. During the experiment, short-term memory was evaluated. After 30th day of experiment, the animals were euthanized and was made removal of brains used to immunohistochemistry procedures for GFAP and cleaved caspase-3. As a result, we observed that animals treated with taurine showed better performance in behavioural and memory tasks, and the enriched environment had positive effects, especially in non-diabetic animals. Furthermore, taurine and enriched environment seemed to be able to interfere with neuronal apoptosis and loss of glial cells, and in some instances, these two factors seemed to have synergistic effects. From these data, taurine and enriched environment may have important neurostimulant and neuroprotective effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of isosorbide dinitrate in cyanide poisoning as a function of the administration timing.

PubMed

Lavon, Ophir; Avrahami, Amit; Eisenkraft, Arik

2017-03-14

Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders. A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 μg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH. Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved. Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.

Effect of the probiotic Enterococcus faecium SF68 on presence of diarrhea in cats and dogs housed in an animal shelter.

PubMed

Bybee, S N; Scorza, A V; Lappin, M R

2011-01-01

Beneficial effects of probiotics have never been analyzed in an animal shelter. Dogs and cats housed in an animal shelter and administered a probiotic are less likely to have diarrhea of ≥2 days duration than untreated controls. Two hundred and seventeen cats and 182 dogs. Double blinded and placebo controlled. Shelter dogs and cats were housed in 2 separate rooms for each species. For 4 weeks, animals in 1 room for each species was fed Enterococcus faecium SF68 while animals in the other room were fed a placebo. After a 1-week washout period, the treatments by room were switched and the study continued an additional 4 weeks. A standardized fecal score system was applied to feces from each animal every day by a blinded individual. Feces of animals with and without diarrhea were evaluated for enteric parasites. Data were analyzed by a generalized linear mixed model using a binomial distribution with treatment being a fixed effect and the room being a random effect. The percentage of cats with diarrhea ≥2 days was significantly lower (P = .0297) in the probiotic group (7.4%) when compared with the placebo group (20.7%). Statistical differences between groups of dogs were not detected but diarrhea was uncommon in both groups of dogs during the study. Cats fed SF68 had fewer episodes of diarrhea of ≥2 days when compared with controls suggests the probiotic may have beneficial effects on the gastrointestinal tract. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Role of tissue engineered collagen based tridimensional implant on the healing response of the experimentally induced large Achilles tendon defect model in rabbits: a long term study with high clinical relevance

PubMed Central

2013-01-01

Background Tendon injury is one of the orthopedic conditions poses with a significant clinical challenge to both the surgeons and patients. The major limitations to manage these injuries are poor healing response and development of peritendinous adhesions in the injured area. This study investigated the effectiveness of a novel collagen implant on tendon healing in rabbits. Results Seventy five mature White New-Zealand rabbits were divided into treated (n = 55) and control (n = 20) groups. The left Achilles tendon was completely transected and 2 cm excised. The defects of the treated animals were filled with collagen implants and repaired with sutures, but in control rabbits the defects were sutured similarly but the gap was left untreated. Changes in the injured and normal contralateral tendons were assessed weekly by measuring the diameter, temperature and bioelectrical characteristics of the injured area. Clinical examination was done and scored. Among the treated animals, small pilot groups were euthanized at 5, 10, 15, 20, 30, 40 and 60 (n = 5 at each time interval) and the remainder (n = 20) and the control animals at 120 days post injury (DPI). The lesions of all animals were examined at macroscopic and microscopic levels and the dry matter content, water delivery and water uptake characteristics of the lesions and normal contralateral tendons of both groups were analyzed at 120 DPI. No sign of rejection was seen in the treated lesions. The collagen implant was invaded by the inflammatory cells at the inflammatory phase, followed by fibroplasia phase in which remnant of the collagen implant were still present while no inflammatory reaction could be seen in the lesions. However, the collagen implant was completely absorbed in the remodeling phase and the newly regenerated tendinous tissue filled the gap. Compared to the controls, the treated lesions showed improved tissue alignment and less peritendinous adhesion, muscle atrophy and fibrosis. They also showed significantly better clinical scoring, indices for water uptake and water absorption, and bioelectrical characteristics than the controls. Conclusion This novel collagen implant was biodegradable, biocompatible and possibly could be considered as a substitute for auto and allografts in clinical practice in near future. PMID:23672303

Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

ClinicalTrials.gov

2018-06-19

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Brain Stem Glioma; Childhood Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Gliosarcoma

Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin

PubMed Central

Rowe, Peter S.N.; Matsumoto, Naoko; Jo, Oak D.; Shih, Remi N.J.; Oconnor, Jeannine; Roudier, Martine P.; Bain, Steve; Liu, Shiguang; Harrison, Jody; Yanagawa, Norimoto

2012-01-01

Increased expression of several osteoblastic proteases and MEPE (a bone matrix protein) occurs in X-linked hypophosphatemic rickets (hyp). This is associated with an increased release of a protease-resistant MEPE peptide (ASARM peptide), a potent inhibitor of mineralization. Cathepsin B cleaves MEPE releasing ASARM peptide and hyp osteoblast/osteocyte cells hypersecrete cathepsin D, an activator of cathepsin B. Our aims were to determine whether cathepsin inhibitors correct the mineralization defect in vivo and whether hyp-bone ASARM peptide levels are reduced after protease treatment. Normal littermates and hyp mice (n = 6) were injected intraperitoneally once a day for 4 weeks with pepstatin, CAO74 or vehicle. Animals were then sacrificed and bones plus serum removed for comprehensive analysis. All hyp mice groups (treated and untreated) remained hypophosphatemic with serum 1,25 vitamin D3 inappropriately normal. Serum PTH was significantly elevated in all hyp mice groups relative to normal mice (P = 0.0017). Untreated hyp mice had six-fold elevated levels of serum alkaline-phosphatase and two-fold elevated levels of ASARM peptides relative to normal mice (P < 0.001). In contrast, serum alkaline phosphatase and serum ASARM peptides were significantly reduced (normalized) in hyp mice treated with CA074 or pepstatin. Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining). Also, hyp animals treated with protease inhibitors showed marked and significant improvements in growth plate width (42%), osteoid thickness (40%) and cortical area (40%) (P < 0.002). The mineralization apposition rate, bone formation rate and mineralization surface were normalized by protease-treatment. High-resolution pQCT mineral histomorphometry measurements and uCT also confirmed a marked mineralization improvement. Finally, the growth plate and cortical bone of hyp femurs contained a massive accumulation of osteoblast-derived ASARM peptide(s) that was reduced in hyp animals treated with CA074 or pepstatin. This study confirms in vivo administration of cathepsin inhibitors improves bone mineralization in hyp mice. This may be due to a protease inhibitor mediated decrease in proteolytic degradation of the extracellular matrix and a reduced release of ASARM peptides (potent mineralization inhibitors). PMID:16762607

Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.

PubMed

Santos, Fabiane M; Mazzeti, Ana L; Caldas, Sérgio; Gonçalves, Karolina R; Lima, Wanderson G; Torres, Rosália M; Bahia, Maria Terezinha

2016-09-01

Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with values in non-infected dogs. These findings strongly suggest that the temporary reduction in the parasite load that was induced by benznidazole treatment was not able to prevent myocardial lesions and diastolic dysfunction for long after treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of carprofen administration during banding or burdizzo castration of bulls on plasma cortisol, in vitro interferon-gamma production, acute-phase proteins, feed intake, and growth.

PubMed

Pang, W Y; Earley, B; Sweeney, T; Crowe, M A

2006-02-01

The objective of this study was to determine the effect of carprofen (C) administration before banding or burdizzo castration of bulls on cortisol, in vitro interferon-gamma (IFN-gamma) production, acute-phase proteins, feed intake, and growth. Fifty Holstein Friesian bulls (5.5 mo old; 191 +/- 3.7 kg) were blocked by weight and assigned randomly to 1 of 5 treatments (n = 10/treatment): 1) untreated control (2) banding castration at 0 min (Band); 3) Band following an i.v. injection of 1.4 mg/kg of BW of C at -20 min (Band+C); 4) Burdizzo castration at 0 min (Burd); or 5) Burd following 1.4 mg/kg of BW of C at -20 min (Burd+C). Castration acutely increased plasma cortisol concentrations compared with control; no significant differences occurred in peak and interval to peak cortisol responses between Band and Band+C or Burd and Burd+C groups. The administration of C in Band+C reduced (P < 0.05) the cortisol concentration between 6 and 12 h postcastration compared with Band animals. Overall, the integrated cortisol response was greater (P < 0.05) in the castrates than in control, whereas C treatments tended to reduce this response compared with Band (P = 0.08) and Burd (P = 0.07), respectively. Plasma fibrinogen was elevated in Band animals on d 14 and in Burd animals on d 3 and 14. Carprofen administration reduced Band- and Burd-induced fibrinogen production on d 14 and 3, respectively. Plasma haptoglobin was elevated in Band animals on d 3 and 35 compared with control, and C administration was effective in reducing the haptoglobin elevation on d 35 in Band+C compared with Band. There were no differences among treatments in in vitro IFN-gamma production induced by concanavalin A and phytohemagglutinin on d 1 and 2. Overall from d -1 to 16, there were no DMI differences among treatments. From d -1 to 35, there were no ADG differences among treatments. In conclusion, banding and burdizzo castration increased plasma cortisol with no change in in vitro IFN-gamma production. Carprofen (1.4 mg/kg of BW) tended to reduce the integrated cortisol response, and it reduced cortisol secretion in banded animals between 6 and 12 h postcastration. There was an increased acute-phase protein production following castration; this response was effectively moderated by the administration of C before castration.

Does core mobility of lumbar total disc arthroplasty influence sagittal and frontal intervertebral displacement? Radiologic comparison with fixed-core prosthesis

PubMed Central

Delécrin, Joël; Allain, Jérôme; Beaurain, Jacques; Steib, Jean-Paul; Chataigner, Hervé; Aubourg, Lucie; Huppert, Jean; Ameil, Marc; Nguyen, Jean-Michel

2009-01-01

Background An artificial disc prosthesis is thought to restore segmental motion in the lumbar spine. However, it is reported that disc prosthesis can increase the intervertebral translation (VT). The concept of the mobile-core prosthesis is to mimic the kinematic effects of the migration of the natural nucleus and therefore core mobility should minimize the VT. This study explored the hypothesis that core translation should influence VT and that a mobile core prosthesis may facilitate physiological motion. Methods Vertebral translation (measured with a new method presented here), core translation, range of motion (ROM), and distribution of flexion-extension were measured on flexion-extension, neutral standing, and lateral bending films in 89 patients (63 mobile-core [M]; 33 fixed-core [F]). Results At L4-5 levels the VT with M was lower than with F and similar to the VT of untreated levels. At L5-S1 levels the VT with M was lower than with F but was significantly different compared to untreated levels. At M levels a strong correlation was found between VT and core translation; the VT decreases as the core translation increases. At F levels the VT increases as the ROM increases. No significant difference was found between the ROM of untreated levels and levels implanted with either M or F. Regarding the mobility distribution with M and F we observed a deficit in extension at L5-S1 levels and a similar distribution at L4-5 levels compared to untreated levels. Conclusion The intervertebral mobility was different between M and F. The M at L4-5 levels succeeded to replicate mobility similar to L4-5 untreated levels. The M at L5-S1 succeeded in ROM, but failed regarding VT and mobility distribution. Nevertheless M minimized VT at L5-S1 levels. The F increased VT at both L4-5 and L5-S1. Clinical Relevance This study validates the concept that the core translation of an artificial lumbar disc prosthesis minimizes the VT. PMID:25802632

The effect of social geographic factors on the untreated tooth decay among head start children

PubMed Central

Ferretti, Margaret; Qureshi, Mehveen; Ferretti, Gerald

2017-01-01

Background Disparities among untreated dental caries exist for children from low-income families in the United States. Understanding of the mechanism of the disparities is required to reduce it and social geographic factors are one of the important influences. Although the effect of fluoridated water has been well reported, studies of other sociogeograpic factors, such as the density of available dentists, are still very limited. The objective of this study is to explore the effect of sociogeographic factors on the number of primary teeth with untreated dental caries among children from low-income families who are enrolled in Head Start programs throughout Northeast Ohio of the United States. Material and Methods This was a cross-sectional chart review study. Three hundred-eighty-eight charts were reviewed, and the number of primary teeth with untreated dental caries (dt) and the children’s addresses were retrieved. The sociogeographic variables, including fluoridated water availability and the density of available dentists who accept a government-supported insurance (Medicaid dentists), were collected. Results The mean (standard deviation) of children’s age was 3.51 (1.14) years with a range of 7 months to 5 years. A negative binomial regression model analysis, which used dt as a dependent variable and children’s characteristic factors (i.e. age, gender, insurance type, and total number of primary teeth) and sociogeographic factors (i.e. Population, total number of Medicaid dentists, density of Medicaid dentist, and Fluoride water availability) of cities, as independent variables, demonstrated that only the density of Medicaid dentist in the sociogeographic factors indicated a significant effect (Estimated ß-Coefficients (Standard Errors)=-0.003 (0.002), p=0.030). Conclusions This study demonstrated a significant negative association between the density of available dentists and untreated dental caries among children from low-income families in Head Start programs in Northeast Ohio. Increasing available dentists may be a strategy to reduce the number of early childhood caries. Key words:Child, poverty, dental caries, Health Services Accessibility. PMID:29167713

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

PubMed Central

Almeida, Caroline de Souza; Andrade-Oliveira, Vinicius; Câmara, Niels Olsen Saraiva; Jacysyn, Jacqueline F.; Faquim-Mauro, Eliana L.

2015-01-01

Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a local anti-inflammatory profile in mice. PMID:25853847

Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse.

PubMed

Passini, Marco A; Bu, Jie; Fidler, Jonathan A; Ziegler, Robin J; Foley, Joseph W; Dodge, James C; Yang, Wendy W; Clarke, Jennifer; Taksir, Tatyana V; Griffiths, Denise A; Zhao, Michael A; O'Riordan, Catherine R; Schuchman, Edward H; Shihabuddin, Lamya S; Cheng, Seng H

2007-05-29

Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation of undegraded lipids in cells of the viscera and CNS. In this study, we tested the effect of combination brain and systemic injections of recombinant adeno-associated viral vectors encoding human ASM (hASM) in a mouse model of NPD. Animals treated by combination therapy exhibited high levels of hASM in the viscera and brain, which resulted in near-complete correction of storage throughout the body. This global reversal of pathology translated to normal weight gain and superior recovery of motor and cognitive functions compared to animals treated by either brain or systemic injection alone. Furthermore, animals in the combination group did not generate antibodies to hASM, demonstrating the first application of systemic-mediated tolerization to improve the efficacy of brain injections. All of the animals treated by combination therapy survived in good health to an investigator-selected 54 weeks, whereas the median lifespans of the systemic-alone, brain-alone, or untreated ASM knockout groups were 47, 48, and 34 weeks, respectively. These data demonstrate that combination therapy is a promising therapeutic modality for treating NPD and suggest a potential strategy for treating disease indications that cause both visceral and CNS pathologies.

The sensory but not muscular pelvic nerve branch is necessary for parturition in the rat.

PubMed

Martínez-Gómez, M; Cruz, Y; Pacheco, P; Aguilar-Roblero, R; Hudson, R

1998-03-01

In the rat the pelvic nerve consists of a viscerocutaneous (sensory) branch which receives information from pelvic viscera and the midline perineal region, and a somatomotor (muscular) branch which innervates the ilio- and pubococcygeous muscles. To investigate the contribution of these branches to the parturition process, the length of gestation and course of delivery were closely monitored in 43 pregnant, Wistar-strain rats randomly assigned to five groups: untreated control animals, animals in which the somatomotor branch of the pelvic nerve was bilaterally sectioned on Day 14 of gestation, animals in which the viscerocutaneous branch of the pelvic nerve was bilaterally sectioned on Day 14 of gestation, animals treated similarly to the previous group but with young delivered by C-section at term, and sham-operated controls. Sectioning the viscerocutaneous branch seriously disrupted parturition and resulted in major dystocia and a high percentage of stillbirths in all females. In contrast, sectioning the somatomotor branch had no apparent effect on parturition and no significant differences were found between females of this group and sham or control dams on any of the measures recorded. It is concluded that the viscerocutaneous branch of the pelvic nerve is vital for the normal course of parturition in the rat but that the somatomotor branch plays little role, if any.

Polyethylene glycol-induced motor recovery after total spinal transection in rats.

PubMed

Ren, Shuai; Liu, Ze-Han; Wu, Qiong; Fu, Kuang; Wu, Jun; Hou, Li-Ting; Li, Ming; Zhao, Xin; Miao, Qing; Zhao, Yun-Long; Wang, Sheng-Yu; Xue, Yan; Xue, Zhen; Guo, Ya-Shan; Canavero, Sergio; Ren, Xiao-Ping

2017-08-01

Despite more than a century of research, spinal paralysis remains untreatable via biological means. A new understanding of spinal cord physiology and the introduction of membrane fusogens have provided new hope that a biological cure may soon become available. However, proof is needed from adequately powered animal studies. Two groups of rats (n=9, study group, n=6 controls) were submitted to complete transection of the dorsal cord at T10. The animals were randomized to receive either saline or polyethylene glycol (PEG) in situ. After 4 weeks, the treated group had recovered ambulation vs none in the control group (BBB scores; P=.0145). One control died. All animals were studied with somatosensory-evoked potentials (SSEP) and diffusion tensor imaging (DTI). SSEP recovered postoperatively only in PEG-treated rats. At study end, DTI showed disappearance of the transection gap in the treated animals vs an enduring gap in controls (fractional anisotropy/FA at level: P=.0008). We show for the first time in an adequately powered study that the paralysis attendant to a complete transection of the spinal cord can be reversed. This opens the path to a severance-reapposition cure of spinal paralysis, in which the injured segment is excised and the two stumps approximated after vertebrectomy/diskectomies. © 2017 John Wiley & Sons Ltd.

Efficacy of celecoxib in the treatment of CNS lymphomas: an in vivo model.

PubMed

Wang, Weijun; Kardosh, Adel; Su, Yuzhuang S; Schonthal, Axel H; Chen, Thomas C

2006-11-15

The incidence of primary central nervous system lymphomas (PCNSLs) has increased over the past several decades. Unfortunately, even with the most effective therapeutic regimen (that is, methotrexate with wholebrain radiation therapy), PCNSL recurs within a few years in more than half of the treated patients and is eventually fatal. Because PCNSL usually occurs in older patients and in those with acquired immunodeficiency syndrome, combination treatments in which both chemo- and radiation therapy are used is often poorly tolerated and results in a significant reduction in the quality of life. Recently, it has been demonstrated that the selective cyclooxygenase- 2 inhibitor celecoxib (Celebrex), can block the growth of lymphoma cells in vitro. To create an experimental animal model in vivo for the PCNSL study, the authors intracranially injected a human B-cell lymphoma cell line into nude mice. Their data demonstrate that this experimental model is an excellent one for human PCNSL with brain and leptomeningeal involvement. They also evaluated the feasibility of using celecoxib as a therapeutic agent in the treatment of PCNSL. Nude mice with intracranial lymphomas were treated with celecoxib contained in the animal chow. The treated animals demonstrated significantly prolonged survival times compared with the untreated animals. Based on the authors' data, celecoxib may be a promising therapeutic agent for the treatment of PCNSL.

Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

PubMed Central

Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

2012-01-01

Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

Andromonoecy and developmental plasticity in Chaerophyllum bulbosum (Apiaceae–Apioideae)

PubMed Central

Reuther, Kerstin; Claßen-Bockhoff, Regine

2013-01-01

Background and Aims Andromonoecy, the presence of hermaphrodite and male flowers in the same individual, is genetically fixed or induced, e.g. by fruit set. Little is known about the forces triggering andromonoecy in the Apiaceae. In the present study, a natural population of the protandrous Chaerophyllum bulbosum was investigated to elucidate architectural constraints and effects of resource reallocation. Methods Three sets of plants (each n = 15) were treated by hand pollination, pollinator exclusion and removal of low-order inflorescences. Fifteen untreated plants were left as controls. Key Results Untreated plants produce umbels up to the third branch order, with increasing proportions of male flowers from 15 % (terminal umbel) to 100 % (third-order umbels). Fruit set correspondingly decreases from 70% (terminal umbel) to <10 % (second-order umbels). Insignificant differences from hand-pollinated plants do not reveal any sign of pollinator limitation at the study site. Bagged individuals show the same increase in male flowers with age as untreated plants, indicating that the presence of andromonoecy is not induced by fruit set. After umbel removal, individuals tend to present a higher number of hermaphrodite flowers and fruits in the umbels of second and third order. Three plants (25 %) produced an additional branch order composed of 100 % male umbels. Conclusions Inherited andromonoecy and the plastic response to environmental conditions are interpreted as a self-regulating system saving investment costs and optimizing fruit set at the same time. PMID:23585495

Aldehyde dehydrogenase induction in arsenic-exposed rat bladder epithelium.

PubMed

Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin

2016-01-01

Arsenic is widely distributed in the environment. Many human cancers, including urothelial carcinoma (UC), show a dose-dependent relationship with arsenic exposure in the south-west coast of Taiwan (also known as the blackfoot disease (BFD) areas). However, the molecular mechanisms of arsenic-mediated UC carcinogenesis has not yet been defined. In vivo study, the rat bladder epithelium were exposed with arsenic for 48 h. The proteins were extracted from untreated and arsenic-treated rat bladder cells and utilized two-dimensional gel electrophoresis and mass spectrometry. Selected peptides were extracted from the gel and identified by quadrupole-time of flight (Q-TOF) Ultima-Micromass spectra. The significantly difference expression of proteins in arsenic-treated groups as compared with untreated groups was confirmed by immunohistochemistry (IHC) and western blotting. We found that thirteen proteins were down-regulated and nine proteins were up-regulated in arsenic-treated rat bladder cells when compared with untreated groups. The IHC and western blotting results confirmed that aldehyde dehydrogenase (ALDH) protein was up-regulated in arsenic-treated rat bladder epithelium. Expression of ALDH protein was significantly higher in UC patients from BFD areas than those from non-BFD areas using IHC (p=0.018). In conclusion, the ALDH protein expression could be used as molecular markers for arsenic-induced transformation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area

PubMed Central

Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Nerbrand, Christina; Valdemarsson, Stig

2011-01-01

Objective To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Design Patient survey study. Setting and subjects A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. Main outcome measures ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Results Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Conclusion Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted. PMID:21323498

ANTICIPATORY POSTURAL ADJUSTMENTS PRIOR TO STEP INITIATION ARE HYPOMETRIC IN UNTREATED PARKINSON'S DISEASE: AN ACCELEROMETER-BASED APPROACH

PubMed Central

Mancini, Martina; Zampieri, Cris; Carlson-Kuhta, Patricia; Chiari, Lorenzo; Horak, Fay B.

2010-01-01

Background and purpose Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson's disease (PD) and may be one of the factors associated with ‘start hesitation’. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. Methods Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). Results Our findings show that APAs measured from the peak COP displacement towards the swing leg and the peak trunk acceleration towards the stance leg were smaller in untreated PD compared to control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. Conclusion These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes. PMID:19473350

Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

PubMed

Magnano, Laura; Montoto, Silvia; González-Barca, Eva; Briones, Javier; Sancho, Juan Manuel; Muntañola, Ana; Salar, Antonio; Besalduch, Joan; Escoda, Lourdes; Moreno, Carol; Domingo-Domenech, Eva; Estany, Cristina; Oriol, Albert; Altés, Albert; Pedro, Carmen; Gardella, Santiago; Asensio, Antoni; Vivancos, Pilar; Fernández de Sevilla, Alberto; Ribera, Josep María; Colomer, Dolors; Campo, Elias; López-Guillermo, Armando

2017-04-01

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Gut microbiota in MS: possible influence of immunomodulators

PubMed Central

Cantarel, Brandi L.; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z.; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M.; Mowry, Ellen M.

2015-01-01

Objectives Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in multiple sclerosis patients and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Methods Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Multiple sclerosis patients were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5,000 IU/day) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. Results While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in multiple sclerosis patients. Glatiramer acetate-treated MS subjects showed differences in community composition compared to untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and Other Clostridiales. Compared to the other groups, untreated multiple sclerosis subjects had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. Conclusions While overall bacterial communities were similar, specific operational taxonomic units differed between healthy and multiple sclerosis subjects. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results. PMID:25775034

Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.

PubMed

Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

2014-09-03

The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

The survival and proliferation of fibroblasts on biocomposites containing genetically modified flax fibers: an in vitro study.

PubMed

Kunert-Keil, Christiane; Gredes, Tomasz; Meyer, Annelie; Wróbel-Kwiatkowska, Magdalena; Dominiak, Marzena; Gedrange, Tomasz

2012-11-01

Natural fibers have long been used in several branches of industry. Nowadays, they are considered as composite materials in medicine with special focus on artificial tissue scaffolding, drug-release systems, cardiovascular patches and nerve cuffs. The purpose of this study has been to examine the in vitro biocompatibility of newly designed "green composites". Therefore, composites containing flax fibers from transgenic flax plants producing polyhydroxybutyrate (M50) and control (wt-NIKE) plants in a polylactid (PLA) or polycaprolactone (PCL) matrix were prepared and mice fibroblast viability and cytotoxicity determined after incubation for 12-48h and 3 weeks with those composites. After 24h and 48h, all green composites have a strong influence on cell viability and membrane stability without any differences among each other. The cell viability of treated cells is approximately 82.5-93% of those of untreated control cells, respectively. The increase in cytotoxicity ranged between 1.4 and 2.9 fold compared to untreated cells. After 3 weeks of incubation, no significant changes were detectable in the amount of dead and living cells between composite treated and untreated cells. In conclusion, the tested new "green composites" showed a good biocompatibility. The biocompatibility of composites from transgenic flax plant fibers producing PHB did not differ from composites of non-transgenic flax plant fibers. Copyright © 2012 Elsevier GmbH. All rights reserved.

Effects of supplemental L-arginine on the intestinal adaptive response after massive small-bowel resection in rats.

PubMed

Oztürk, Hayrettin; Dokucu, Ali Ihsan; Yağmur, Yusuf; Sari, Ibrahim

2002-09-01

To evaluate whether L-arginine methyl ester (L-Arg) can improve the structure of the small intestine and enhance adaptation in an experimental model of short-bowel syndrome (SBS), 40 Sprague-Dawley rats were divided randomly into four groups of 10 each. In one group only a laparotomy was performed (G1). The remaining 30 rats underwent 90% small-bowel resection (SBR) and formed the three experimental groups: the SBR/untreated group (G2), the SBR/L-NAME-treated group (G3), and the SBR/ L-Arg-treated group (G4). Rats in G2 received no therapeutic treatment. Rats in the SBR/L-NAME and SBR/L-Arg treated groups received N-G-nitro-L-arginine-methyl ester (L-NAME) and L-Arg intraperitoneally for 3 weeks, respectively. The animals were weighed daily. All rats underwent a relaparotomy on day 21 of the experiment. Remnant small bowel was excised and evaluated for villus height and crypt cell mitoses. After the 90% SBR, all animals had from diarrhea and weight loss between the 1st and 6th postoperative days (POD). The body weight of the SBR/L-Arg group showed significant increases at POD 10 and 21 in comparison to the SBR/untreated and SBR/L-NAME groups (P < 0.001). The rats treated with L-Arg had significantly greater villus height and crypt-cell mitoses compared to the other groups (P < 0.0001, P < 0.001). These observations suggest that L-Arg treatment increases villus height and crypt-cell mitoses after massive SBR and may play a considerable role in the mucosal adaptive response in SBS in rats.

Gene-activated fat grafts for the repair of spinal cord injury: a pilot study.

PubMed

Betz, Volker M; Sitoci-Ficici, K Hakan; Uckermann, Ortrud; Leipnitz, Elke; Iltzsche, Anne; Thirion, Christian; Salomon, Michael; Zwipp, Hans; Schackert, Gabriele; Betz, Oliver B; Kirsch, Matthias

2016-02-01

Spinal cord injury (SCI) is a complex disease requiring a concerted multi-target approach. The most appropriate combination of therapeutic gene, cellular vehicle, and space filling scaffold still has to be determined. We present an approach that employs syngeneic adipose tissue serving as a three-dimensional biological implant, source of progenitor cells, and delivery system for therapeutic genes. In this pilot experiment, we evaluated the feasibility and short-term effects using gene-activated autologous fat grafts after SCI. An experimental SCI model was established in syngeneic Fischer 344 rats by a T9-T10 hemimyelonectomy. Fat tissue was harvested from two donor rats. Animals were divided into four groups and treated with either (i) fat grafts activated by an adenoviral vector carrying the human NT-3 cDNA, (ii) or BDNF, (iii) or with untreated fat grafts or (iv) remained untreated. Animals were euthanized either 7 or 21 days after surgery, and spinal cord tissue was investigated by histological and immunohistochemical methods. NT-3 and BDNF were produced by gene-activated fat grafts for at least 21 days in vitro and in vivo. Fat tissue grafts remained stable at the site of implantation at 7 days and at 21 days. Neither BDNF-activated nor NT-3-activated fat graft had a detectable limiting effect on the neuronal degeneration. BDNF recruited microglia to perilesional site and attenuated their inflammatory response. Gene-activated syngeneic fat tissue serves as a three-dimensional biological material delivering therapeutic molecules to the site of SCI over an extended period of time. The BDNF-fat graft attenuated the inflammatory response. Whether these findings translate into functional recovery will require extended observation times.

Economic value of urea-treated straw fed to lactating buffaloes during the dry season in Nepal.

PubMed

Chemjong, P B

1991-08-01

An experiment was conducted to study the effects of feeding urea-treated rice straw to lactating buffaloes in the Koshi Hills. Six pairs of similar buffaloes on farms were selected. All were given a conventional diet based on rice straw for four weeks, then one of each pair was given 15 to 20 kg/day of urea-treated rice straw for a period of four weeks while the control group received untreated rice straw. In the final four week period all animals were given the conventional diet. Feeding straw treated with 4% urea increased the voluntary intake of straw by 25% and increased milk yield by 1.6 litres/day compared with buffaloes fed the conventional diet containing untreated straw. Milk production remained elevated after the four-week treatment period had finished. The results show that buffalo cows fed urea-treated straw achieved better weight gain, and milk yield increased significantly (P less than 0.01) compared with the control animals. During the treatment period the net benefit was 4.0 (i.e. US$1.16) Nepalese currency rupees (NCRs) per day and the incremental rate of return was 46 per cent. Moreover, in the four weeks following the treatment period the net benefit was 10.0 NCRs (i.e. US$0.40) per day. Ensiling rice straw with 4% urea can be recommended as a safe, economical and suitable method for improving the nutritional value of rice straw on small farms in Nepal thus increasing milk production and liveweight of lactating buffaloes. The practice of feeding urea-treated straw is economic for farmers during the dry season from January to April.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures

PubMed Central

Wu, Yuhsin; Schomisch, Steve J.; Cipriano, Cassandra; Chak, Amitabh; Lash, Richard H.; Ponsky, Jeffrey L.

2015-01-01

Background Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Methods Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. Results The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Conclusions Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy. PMID:24100858

The effect of administering a dopamine agonist (Cabergoline) on follicular and luteal development during pro-estrus and estrus in the female greyhound.

PubMed

De Rensis, F; Spattini, G; Ballabio, R; Scaramuzzi, R J

2006-09-01

To study the effect of the dopamine agonist Cabergoline, on ovarian activity in the female dog during pro-estrus and estrus, 6 greyhounds were treated with 5 microg/kg per os of Cabergoline for 20 days beginning on the first day of pro-estrus; 6 animals were left untreated (controls). Ovarian morphology was determined by ultrasound examination once a day during pro-estrus and twice a day during estrus. Follicles were divided into three classes on the basis of their diameter: F1 (<3mm), F2 (3-6mm) and F3 (>6mm). The presence and diameters of post-ovulatory follicles (F-POST) and corpora lutea (CL) were also recorded. Blood samples were taken once a day during pro-estrus and twice a day during estrus. The plasma was assayed for LH, prolactin and progesterone by radioimmunoassay. There were no differences between Cabergoline-treated and control dogs in the duration of pro-estrus or estrus. There was a progressive increase in follicle diameter from the start of pro-estrus when follicles were mainly class F1 to the day of estrus when follicles were mainly class F3. Three days after the start of estrus, the first F-POST follicles were detected. This pattern of development continued and on day 5 the first CLs were detected. By day 9, only CLs were detected. The peak of pre-ovulatory LH was within 3 days of estrus and ovulation was detected in all animals within 3 days of the LH peak. There were no differences in LH concentrations between groups. Plasma prolactin levels varied between animals and were reduced in treated dogs, however, this was not statistically significant (P=0.12). Plasma progesterone levels were below 1.0 ng/ml before the LH surge and thereafter gradually increased. There were no differences in plasma progesterone concentrations between treated and control dogs. In conclusion these results show that the administration of the dopamine agonist Cabergoline during pro-estrus and estrus did not affect the duration of pro-estrus or estrus or the pattern of follicular and luteal development in female dogs.

Banding or Burdizzo castration and carprofen administration on peripheral leukocyte inflammatory cytokine transcripts.

PubMed

Pang, W Y; Earley, B; Murray, M; Sweeney, T; Gath, V; Crowe, M A

2011-02-01

The objective was to investigate if Banding or Burdizzo castration of bulls would alter the gene expression profile of a range of peripheral leukocyte inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, interferon-γ and tumor necrosis factor-α) and to determine if the administration of carprofen (C) before castration would affect the expression of these genes. Thirty Holstein-Friesian bulls (5.5 months; Mean 191±(SEM) 3.7 kg) were blocked by weight and randomly assigned to one of five treatments: (1) untreated control (CON); (2) Banding castration at 0 min (BAND); (3) BAND following an i.v. injection of 1.4 mg/kg BW of carprofen (C) at -20 min (BAND+C); (4) Burdizzo castration at 0 min (BURD); or (5) BURD following 1.4 mg/kg BW of carprofen at -20 min (BURD+C). Blood samples were collected at 1 h before castration and 6, 24 and 48 h post-castration for routine hematology and quantitative real-time PCR analysis of cytokine gene expression analysis. Generally, there were no differences (P>0.05) among treatment groups in hematological variables following castration. Cortisol concentrations were unchanged throughout the experimental period in CON bulls. BURD animals had greater cortisol concentrations than BAND and CON animals at 6 h post treatment. Transitory effects were observed only in the expression of IL-6 and TNF-α. The relative expression of IL-6 was greater in the BURD than in the BAND treatment (P<0.05) at 24 h post-castration and was greater in the BURD+C group than in the BURD group (P<0.05) at 48 h. The relative expression of TNF-α was greater in BAND than in the BURD group (P<0.05) at 48 h. In conclusion, these findings indicate that Banding or Burdizzo castration did not have any major effect on peripheral leukocyte inflammatory cytokine gene expression; Banding castration caused a greater pro-inflammatory cytokine gene expression reaction than Burdizzo castration and carprofen administration can affect IL-6 gene expression levels in BURD castrated animals. Copyright © 2010 Elsevier Ltd. All rights reserved.

Local Vascularized Flaps for Augmentation of Reinke’s Space

PubMed Central

Dailey, Seth H.; Gunderson, McLean; Chan, Roger; Torrealba, Jose; Kimura, Miwako; Welham, Nathan V.

2011-01-01

Objectives/Hypothesis The purpose of this study is to describe and test a novel surgical strategy for augmentation of Reinke’s space using vascularized flaps: a thyroid ala perichondrium flap (TAP) and a composite thyroid ala perichondrium flap (CTAP) from the anterior larynx. We hypothesized that these specially designed vascularized flaps would remain viable once inset into the lamina propria, and that they would not disrupt rheologic, biomechanical, and histologic properties of the native vocal fold. Study Design Experimental. In vivo canine model. Methods The length and volume of test flaps harvested in six adult human cadaveric larynges were analyzed to determine suitability for use in augmentation in the lamina propria. Also, 12 beagles randomly underwent unilateral placement of either TAP or CTAP, which were designed in accordance with the human adult cadaveric experiments. Flap perfusion was measured before and after harvest with laser Doppler. After 1 month, the beagles were humanely sacrificed and their larynges subjected to aerodynamic and acoustic evaluation using an excised larynx apparatus. The vocal fold lamina propria of four larynges—two TAP and two CTAP—underwent rheologic evaluation using a simple-shear rheometer. The remaining eight larynges underwent quantitative histologic and immunohistochemical evaluation. The survival and complication (swallowing, airway, local wound) rates of all dogs were noted. Results Initial studies with adult human cadaveric larynges established that TAP and CTAP possessed length and volume greater than native lamina propria. In the canine experiments, the perfusion change in the flaps was similar between flap groups. The damping ratio (ζ), dynamic viscosity (η′), elastic shear modulus (G′), and viscous shear modulus (G″) of treated and untreated native vocal folds were not statistically different. The glottic function measures of vocal efficiency, laryngeal resistance, jitter, shimmer, and harmonics-to-noise ratio (HNR) of treated and normal larynges were not statistically different. Similarly, the values for collagen, elastin, and glycosaminoglycans (GAGs) in treated and untreated vocal folds were not statistically different. Also, neither neochrondrogenesis nor neoosteogenesis was detected in any treated vocal fold. The values for vascular and cellular proliferation in treated and untreated vocal folds were not statistically different. All test dogs survived and had no complications related to swallowing, airway distress, or the local wound. Conclusions The test flaps described and tested in this study appear to have conceptually attractive features for augmentation of Reinke’s space. When placed in an in vivo setting TAP and CTAP did not reveal unfavorable vascular, rheologic, aerodynamic, acoustic, or histologic characteristics. There was no unanticipated morbidity or mortality to the test animals. Long-term viability of these flaps is unknown. TAP and CTAP may open novel pathways for correction of glottic defects and may offer crossover opportunities with tissue engineering techniques. Level of Evidence None. PMID:21271606

Co-digestion of dairy cattle slurry and industrial meat-processing by-products--effect of ultrasound and hygienization pre-treatments.

PubMed

Luste, Sami; Heinonen-Tanski, Helvi; Luostarinen, Sari

2012-01-01

Anaerobic co-digestion of a mixture of industrial animal by-products (ABP) from meat-processing in conjunction with dairy cattle slurry (mixed in a ratio of 1:3; w.w.) was evaluated at 35 °C focusing on methane production and stabilization. Three pre-treatments were applied (1) digestion with no pre-treatment (control), (2) ultrasound, and (3) thermal hygienization (70 °C, 60 min). Methane production potentials (MPP) of the untreated, ultrasound pre-treated and hygienized feed mixtures were 300, 340, and 360 m(3) CH(4)/t volatile solids (VS) added, as determined in the batch experiments. However, the specific methane productions (SMP) achieved in reactor experiments (hydraulic retention time HRT 21 d, organic loading rate OLR 3.0±0.1 kg VS/m(3) d) were 11±2% (untreated and ultrasound pre-treated) and 22±3% (hygienized) lower than the potentials. Ultrasound with the energy input of 1000 kJ/kg total solids (TS) and hygienization of the ready-made feed were the most suitable pre-treatment modes studied. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enzyme Production by Industrially Relevant Fungi Cultured on Coproduct From Corn Dry Grind Ethanol Plants

NASA Astrophysics Data System (ADS)

Ximenes, Eduardo A.; Dien, Bruce S.; Ladisch, Michael R.; Mosier, Nathan; Cotta, Michael A.; Li, Xin-Liang

Distillers dried grain with solubles (DDGS) is the major coproduct produced at a dry grind ethanol facility. Currently, it is sold primarily as a ruminant animal feed. DDGS is low cost and relatively high in protein and fiber contents. In this study, DDGS was investigated as carbon source for extracellular hydrolytic enzyme production. Two filamentous fungi, noted for their high cellulolytic and hemicellulolytic enzyme titers, were grown on DDGS: Trichoderma reesei Rut C-30 and Aspergillus niger NRRL 2001. DDGS was either used as delivered from the plant (untreated) or after being pretreated with hot water. Both microorganisms secreted a broad range of enzymes when grown on DDGS. Higher xylanase titers were obtained when cultured on hot water DDGS compared with growth on untreated DDGS. Maximum xylanase titers were produced in 4 d for A. niger and 8 d for T. reesei in shake flask cultures. Larger amounts of enzymes were produced in bioreactors (5L) either equipped with Rushton (for T. reesei) or updraft marine impellers (A. niger). Initial production titers were lower for bioreactor than for flask cultures, especially for T. reesei cultures. Improvement of enzyme titers were obtained using fed-batch feeding schemes.

Thermal Imaging of Medical Saw Blades and Guides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinwiddie, Ralph Barton; Steffner, Thomas E

2007-01-01

Better Than New, LLC., has developed a surface treatment to reduce the friction and wear of orthopedic saw blades and guides. The medical saw blades were thermally imaged while sawing through fresh animal bone and an IR camera was used to measure the blade temperature as it exited the bone. The thermal performance of as-manufactured saw blades was compared to surface-treated blades, and a freshly used blade was used for temperature calibration purposes in order to account for any emissivity changes due to organic transfer layers. Thermal imaging indicates that the treated saw blades cut faster and cooler than untreatedmore » blades. In orthopedic surgery, saw guides are used to perfectly size the bone to accept a prosthesis. However, binding can occur between the blade and guide because of misalignment. This condition increases the saw blade temperature and may result in tissue damage. Both treated ad untreated saw guides were also studied. The treated saw guide operated at a significantly lower temperature than untreated guide. Saw blades and guides that operate at a cooler temperature are expected to reduce the amount of tissue damage (thermal necrosis) and may reduce the number of post-operative complications.« less

3-Monochloropropane-1,2-diol (alpha-chlorohydrin) disrupts spermatogenesis and causes spermatotoxicity in males of the Egyptian fruit-bat (Rousettus aegyptiacus).

PubMed

Mahmoud, Y I; Taha, A; Soliman, S

2018-03-29

We evaluated the sterilizing effect of 3-monochloropropane-1, 2-diol (3-MCPD) in male Egyptian fruit bats (Rousettus aegyptiacus). We used three groups. One was treated with 70 mg/kg 3-MCPD for 4 days. The second group was treated with 3-MCPD as a bait formulation (known concentration of 3-MCPD mixed with a known amount of food). The third group was untreated controls. We compared the weights of the reproductive organs, histology of the testes, occurrence of spermatogenesis, and the count, motility and abnormalities of epididymal sperm of treated males with those of the untreated control group. 3-MCPD caused significantly decreased weights of reproductive organs, several testicular histological alterations and spermatogenic arrest accompanied by significant decreases in sperm count and motility, and significantly increased number of abnormal sperm. 3-MCPD bait was readily accepted by the animals. 3-MCPD, even in low doses and after limited exposure, disrupted spermatogenesis in males of the Egyptian fruit bat. Our findings have potential value for public health and agricultural authorities, and for vertebrate pest managers. 3-MCPD may have application for control of this pest.

Enhanced Perfusion During Advanced Life Support Improves Survival With Favorable Neurologic Function in a Porcine Model of Refractory Cardiac Arrest

PubMed Central

Debaty, Guillaume; Metzger, Anja; Rees, Jennifer; McKnite, Scott; Puertas, Laura; Yannopoulos, Demetris; Lurie, Keith

2016-01-01

Objective To improve the likelihood for survival with favorable neurologic function after cardiac arrest, we assessed a new advanced life support approach using active compression-decompression cardiopulmonary resuscitation plus an intrathoracic pressure regulator. Design Prospective animal investigation. Setting Animal laboratory. Subjects Female farm pigs (n = 25) (39 ± 3 kg). Interventions Protocol A: After 12 minutes of untreated ventricular fibrillation, 18 pigs were randomized to group A—3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with standard cardiopulmonary resuscitation; group B—3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator; and group C—3 minutes of basic life support with active compression-decompression cardiopulmonary resuscitation plus an impedance threshold device, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator. Advanced life support always included IV epinephrine (0.05 μg/kg). The primary endpoint was the 24-hour Cerebral Performance Category score. Protocol B: Myocardial and cerebral blood flow were measured in seven pigs before ventricular fibrillation and then following 6 minutes of untreated ventricular fibrillation during sequential 5 minutes treatments with active compression-decompression plus impedance threshold device, active compression-decompression plus intrathoracic pressure regulator, and active compression-decompression plus intrathoracic pressure regulator plus epinephrine. Measurements and Main Results Protocol A: One of six pigs survived for 24 hours in group A versus six of six in groups B and C (p = 0.002) and Cerebral Performance Category scores were 4.7 ± 0.8, 1.7 ± 0.8, and 1.0 ± 0, respectively (p = 0.001). Protocol B: Brain blood flow was significantly higher with active compression-decompression plus intrathoracic pressure regulator compared with active compression-decompression plus impedance threshold device (0.39 ± 0.23 vs 0.27 ± 0.14 mL/min/g; p = 0.03), whereas differences in myocardial perfusion were not statistically significant (0.65 ± 0.81 vs 0.42 ± 0.36 mL/min/g; p = 0.23). Brain and myocardial blood flow with active compression-decompression plus intrathoracic pressure regulator plus epinephrine were significantly increased versus active compression-decompression plus impedance threshold device (0.40 ± 0.22 and 0.84 ± 0.60 mL/min/g; p = 0.02 for both). Conclusion Advanced life support with active compression-decompression plus intrathoracic pressure regulator significantly improved cerebral perfusion and 24-hour survival with favorable neurologic function. These findings support further evaluation of this new advanced life support methodology in humans. PMID:25756411

Association Between HIV-1 RNA Level and CD4 Cell Count Among Untreated HIV-Infected Individuals

PubMed Central

Lima, Viviane D.; Fink, Valeria; Yip, Benita; Hogg, Robert S.; Harrigan, P. Richard

2009-01-01

Objectives. We examined the significance of plasma HIV-1 RNA levels (or viral load alone) in predicting CD4 cell decline in untreated HIV-infected individuals. Methods. Data were obtained from the British Columbia Centre for Excellence in HIV/AIDS. Participants included all residents who ever had a viral load determination in the province and who had never taken antiretroviral drugs (N = 890). We analyzed a total of 2074 viral load measurements and 2332 CD4 cell counts. Linear mixed-effects models were used to predict CD4 cell decline over time. Results. Longitudinal viral load was strongly associated with CD4 cell decline over time; an average of 1 log10 increase in viral load was associated with a 55-cell/mm3 decrease in CD4 cell count. Conclusions. Our results support the combined use of CD4 cell count and viral load as prognostic markers in HIV-infected individuals before the introduction of antiretroviral therapy. PMID:19218172