Percentage Of Animals Research Articles

Efficacy of a Parapoxvirus ovis-based immunomodulator against equine herpesvirus type 1 and Streptococcus equi equi infections in horses

The efficacy of Zylexis®, an immunomodulator in horses based on inactivated Parapoxvirus ovis (iPPVO), was assessed using an equine herpesvirus type 1 (EHV-1) challenge model in the presence of a natural infection with Streptococcus equi equi (S. equi). Eleven horses were treated with iPPVO and twelve were kept as controls. Six horses were challenged with EHV-1 and commingled with the horses on study. Animals were dosed on Days −2, 0 (just before commingling) and Day 7. On Day 11 significantly less nasal discharge, enlarged lymph nodes, EHV-1 shedding and lower rectal temperatures were observed in the iPPVO-treated group. In addition, iPPVO-treated horses showed significantly fewer enlarged lymph nodes on Days 17 and 19, significantly less lower jaw swelling on Day 3 and significantly lower rectal temperatures on Days 12 and 13. Dyspnoea, depression and anorexia were only recorded for the control group. Following challenge seven out of 11 horses in the iPPVO treated group shed EHV-1 but on Days 11, 12, 13, 14, 15 and 16 quantitative virus detection in this group was significantly lower as compared to the controls. All animals shed S. equi but the percentage of animals with positive bacterial detection was lower in the iPPVO group than in the control group from Day 14 through Day 28. This difference was significant on Day 24. No injection site reactions or adverse events were observed. In conclusion, Zylexis administration is safe and reduced clinical signs and shedding related to both EHV-1 and S. equi infections.

Parathyroid hormone-related protein: potential therapeutic target for melanoma invasion and metastasis.

The role of PTHrP in the highly metastatic human melanoma disease is not known. This study investigates the mechanisms of action of this secreted factor through homozygous inactivation of the Pthrp gene in A375 human melanoma cells. In vitro, Pthrp-ablated cells (knockout [KO]-A375, -/-) showed decreased motility and anchorage-independent growth, rounder morphology, and a significant reduction in invasion capacity compared with nonablated A375 cells (wild-type [WT]-A375, +/+). PTHrP peptide 1-34 and conditioned medium from WT-A375 cells partially restored the invasive phenotype in KO-A375. Pthrp ablation substantially decreased actin polymerization, matrix metallopeptidase 9 expression and focal adhesion kinase phosphorylation. In vivo, green fluorescent protein-transduced ablated and nonablated A375 cells were injected intracardially or sc into nude mice to study proliferation and multiorgan metastasis. Dissemination of injected Pthrp-ablated cells to lung and liver was reduced by 85% and 50%, respectively, compared with nonablated controls (120 hours after injection). The number of metastatic lesions and the percentage of animals with metastasis were markedly lower in mice injected with Pthrp-ablated A375, and 45% of these animals survived a 7-week period compared with 15% of mice injected with nonablated WT-A375. When mice injected with WT-A375 were treated with our blocking anti-PTHrP monoclonal antibody raised against the first 33 amino acids of human PTHrP, tumor size was decreased by more than 80% over 4 weeks and survival was significantly improved over 8 months. This study provides direct evidence of the major role for PTHrP in melanoma invasion and metastasis and suggests that agents that suppress PTHrP may be beneficial against melanoma progression.

Advantages of repeated low dose against single high dose of kainate in C57BL/6J mouse model of status epilepticus: behavioral and electroencephalographic studies.

A refined kainate (KA) C57BL/6J mouse model of status epilepticus (SE) using a repeated low dose (RLD) of KA (5 mg/kg, intraperitoneal; at 30 min intervals) was compared with the established single high dose (SHD) of KA (20 mg/kg, intraperitoneal) model. In the RLD group, increased duration of convulsive motor seizures (CMS, Racine scale stage ≥3) with a significant reduction in mortality from 21% to 6% and decreased variability in seizure severity between animals/batches were observed when compared to the SHD group. There was a significant increase in the percentage of animals that reached stage-5 seizures (65% versus 96%) in the RLD group. Integrated real-time video-EEG analysis of both groups, using NeuroScore software, revealed stage-specific spikes and power spectral density characteristics. When the seizures progressed from non-convulsive seizures (NCS, stage 1–2) to CMS (stage 3–5), the delta power decreased which was followed by an increase in gamma and beta power. A transient increase in alpha and sigma power marked the transition from NCS to CMS with characteristic ‘high frequency trigger’ spikes on the EEG, which had no behavioral expression. During SE the spike rate was higher in the RLD group than in the SHD group. Overall these results confirm that RLD of KA is a more robust and consistent mouse model of SE than the SHD of KA mouse model.

Photodynamic therapy of experimental sarcoma M-1 with boronated chlorine as a photosensitizer.

Using rat model of experimental sarcoma M-1 we studied the efficacy of photodynamic therapy with boronated chlorine as a photosensitizer in doses of 1.25, 2.5, 5.0, and 10.0 mg/ kg body weight. Laser irradiation was performed at energy densities of 150, 300 J/cm(2) and power density of 0.25 and 0.42 W/cm(2). Treatment efficacy was evaluated by the percentage of animals with complete tumor regression, percentage of tumor recurrence and, in cases of its growth, by tumor growth coefficient. The efficacy of photodynamic therapy depended on the dose of boronated chlorine and parameters of the laser irradiation. Optimal conditions were the dose of 2.5 mg/kg at laser energy density of 300 J/cm(2) and power density of 0.42 W/cm(2) and a dose of 5.0 mg/kg at 150 J/cm(2) and 0.25 W/cm(2).

Effect of Maternal Care on Hearing Onset Induced by Developmental Changes in the Auditory Periphery

Handling (H) and cross-fostering (CF) rodent pups during postnatal development triggers changes in maternal behavior which in turn trigger long-term physiological changes in the offspring. However, less is known about the short-term effects of H and CF on infant development. In this study we hypothesized that manipulations of maternal care affect the onset of hearing in Wistar rats. To test this hypothesis we obtained auditory brainstem responses (ABRs) and micro-CT x-ray scans to measure changes in the development of the auditory periphery in H and CF pups manipulated at postnatal day (P)1, P5, or P9. We found evidence of changes in hearing development in H and CF pups compared with naive pups, including changes in the percentage of animals with ABRs during development, a decrease in ABR thresholds between P13 and P15, and anatomical results consistent with an accelerated formation of the middle ear cavity and opening of the ear canal. Biochemical measurements showed elevated levels of thyroid hormone in plasma from naive and CF pups. These results provide evidence that manipulations of maternal care accelerate hearing onset in Wistar rats. Understanding the mechanisms by which maternal care affects hearing onset opens new opportunities to study experience-dependent development of mammalian hearing.

Mineral Levels in Pyrenean Chamois (Rupicapra pyrenaica)

The effects of mineral deficiencies are often sub-clinical, and the importance of mineral status is often underestimated in wildlife populations. To our knowledge, this is the first study that gives reference intervals of hepatic minerals for Pyrenean chamois (Rupicapra pyrenaica). We determined macro and trace mineral concentrations in liver samples from 100 animals (44 healthy and 56 sick) collected in the Catalan Pyrenees (NE Spain) from 1995 to 2008. After wet digestion, we determined Na, K, Ca, P, Mg, S, and Fe concentrations by inductively coupled plasma optical emission spectrometry (ICP-OES) and Cu, Zn, and Mo concentrations by inductively coupled plasma mass spectrometry (ICP-MS). We observed low hepatic concentrations of Cu in a considerable percentage of chamois, without evidences that these low concentrations increased their susceptibility to infectious diseases. The group of sick chamois had very similar percentage of animals (10/56) with low concentration of Cu (<20 ppm DW) than the group of healthy chamois (9/44). On the other hand, we observed that infectious diseases increased significantly the hepatic concentrations of Na, Ca, Mg, Fe and Zn, very likely, as a consequence of processes associated with the acute phase inflammatory response. The obtained values of liver mineral levels and their sources of variation, such as sex, age and disease, mostly fall within the range of those described for other ruminants, but possible deficiencies and differences between individuals and populations require further study.

Reappearance ofMecistocirrus digitatusin Cattle from the Mexican Tropics: Prevalence, Molecular, and Scanning Electron Microscopy Identification

Mecistocirrus digitatus is a hematophagous abomasal nematode which causes significant blood and production losses in cattle. The objectives of the present study were to: (1) report the reappearance of M. digitatus in cattle from the Mexican tropics using microscopy, scanning electron microscopy (SEM), and molecular identification, and (2) determine the prevalence of M. digitatus in slaughtered adult cattle from the Mexican tropics. Gastroinestinal nematodes (GIN) were recovered from the abomasum of an 8-yr-old cow (Holstein × Zebu) previously diagnosed with Johne's disease. Of 1,254 GIN, 98.8% were identified as M. digitatus and 1.2% as Haemonchus sp. SEM was used to identify ultrastructure features of M. digitatus (oral cavity, cervical papillae, bursa, bursa lobes papillae, male spicules, anus, and female vulva). A conventional PCR method was used to corroborate the morphological findings. The prevalence of adult cattle infected with M. digitatus and Haemonchus sp., determined from 68 adult cattle from different grazing tropical herds, was 38.2% and 8.8%, respectively. Ninety-eight percent of animals infected with M. digitatus presented lesions in their abomasum such as mucosal inflammation, hemorrhage, and ulcers; some of them had necrosis. The current reappearance of M. digitatus in a Mexican herd suggests the possibility of an underestimated prevalence of this nematode amongst grazing cattle.

Field clinical study evaluating the efficacy and safety of an oral formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of the zoonotic canine infection by Dirofilaria repens.

BackgroundDirofilaria repens is the causative agent of subcutaneous dirofilariosis of dogs, other animals and humans. This nematode is transmitted by mosquitoes of Aedes, Anopheles and Culex genera. In dogs, the parasite may cause subclinical infection or cutaneous signs. Recently, D. repens has emerged and spread in different geographical areas, with an increase of cases in dogs and humans. Chemoprevention in dogs in endemic areas is the most reliable approach for controlling this infection. This paper describes a randomized, blocked and multicentric clinical field study investigating the efficacy of an oral, chewable formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of subcutaneous dirofilariosis in dogs.MethodsThis study was conducted in endemic areas of Italy. A total of 249 dogs, at two sites, negative for D. repens, were allocated into two groups (i.e. Treated -T1 vs Untreated-T2) with a ratio of 1:1, and subjected to clinical visits and blood sampling once monthly until the end of the study. All blood samples were microscopically and genetically examined. Animals belonging to T1 group received a minimum target dose of 0.5 mg/kg bodyweight of milbemycin oxime and 5 mg/kg of praziquantel in commercial tablets (Milbemax®) according body weight once every 4 weeks. Animals of group T2 were not treated with Milbemax® but received, when necessary, specific parasiticide treatments. The study duration was 336 ± 2 days for each dog.ResultsA total of 219 dogs completed the study (i.e. 111 in T1 and 108 in T2), while 30 dogs (i.e. 13 in T1, 17 in T2) were withdrawn for a variety of reasons unrelated to administration of Milbemax®. The percentages of animals not showing microfilariae of D. repens were 100% (111 animals) in T1 and 94.7% (108 animals out of 114) in group T2. Milbemax® was shown to be safe in treated dogs.ConclusionsThe results of this study confirm that the monthly use of Milbemax® in dogs is effective and safe for the prevention of subcutaneous dirofilariosis in endemic areas.

Molecular and serological prevalence of Anaplasma marginale in water buffaloes in northern Brazil

Bovine anaplasmosis, caused by Anaplasma marginale, occurs in tropical and subtropical regions throughout the world and is a major constraint on cattle production in many countries. Approximately 60% of the buffalo herds in South America are located in northern Brazil. However, compared with the research on cattle, research on buffaloes has been neglected. Therefore, the present study was conducted to investigate the distribution of A. marginale in water buffaloes in northern Brazil. A total of 500 buffalo blood samples was randomly collected from 16 provinces and was analyzed using both nPCR assay and ELISA techniques. The percentage of animals that were seropositive for A. marginale according to ELISA was 49% (245/500). The main risk factors associated with seroprevalence were the region (p=0.021; OR=1.2) and the reproductive status (p=0.0001; OR=1.6). Anaplasma marginale DNA was detected in 5.4% (27/500) of the sampled buffaloes. Our data provide information about the incidence of A. marginale infection in water buffaloes and may guide future programs aimed at controlling the disease in the northern region of Brazil. Although these water buffaloes are exposed to A. marginale, a low rate of A. marginale PCR-positive animals was found, which could be explained by the habitat in which the sampled animals live because they exhibited a low rate of attached ticks on their skin.

Evolution of Specific Antibodies and Proviral DNA in Milk of Small Ruminants Infected by Small Ruminant Lentivirus

The diagnosis of Small Ruminant Lentivirus (SRLV) is based on clinical signs, pathological lesions and laboratory testing. No standard reference test for the diagnosis of maedi visna has been validated up to the present, and it is puzzling that tests which detect antibodies against the virus and tests which detect the proviral genome may render opposite results. The aim of this study was to evaluate the presence in milk throughout a lactation period of specific antibodies by ELISA and of SRLV proviral DNA by a PCR of the highly conserved pol region. A six-month study was conducted with the milk of 28 ewes and 31 goats intensively reared. The percentage of animals with antibodies against SRLV increased throughout the study period. Seroprevalence in sheep was 28% at the beginning of the study and by the end it had increased up to 52.4%. In goats, initial seroprevalence of 5.6% increased to 16%. The percentage of PCR positive ewes was stable throughout the study period. Of the positive sheep, 21.4% were PCR-positive before antibodies could be detected and most of them became PCR-negative shortly after the first detection of antibodies. This might suggest that antibodies have a neutralizing effect. In addition, an equal percentage of sheep were always PCR-negative but either became ELISA-positive or was always ELISA-positive, which might support this hypothesis. On the other hand, the PCR results in goats did not follow any pattern and oscillated between 35.3% and 55.6% depending on the month. Most goats positive by PCR failed to develop antibodies in the 6 months tested. We may conclude that the infection and the antibody response to it follow a different trend in sheep and goats.

BPM 31510 decreases doxorubicin-induced cardiomyopathy

Doxorubicin is a commonly used antineoplastic agent for treatment of cancers in adults and children. Despite its high efficacy in the treatment of various cancers, doxorubicin confers dose-limiting cardiogenic toxicity in both populations and associated with EKG changes. In a subset of patients, this effect on EKG is transient, however a significant number of patients will develop cardiomyopathy refractory to conventional treatment. Mitochondrial damage in the cardiomyocytes is the first hallmark of doxorubicin-induced cardiomyopathy. It has been suggested that lipid peroxidation may play a pivotal role in its pathophysiology by affecting the mitochondria through formation of reactive oxygen species. This theory is supported by the presence of markers of lipid peroxidation after doxorubicin administration in the blood. Coenzyme Q10 is found within the membranes of the mitochondria, lysosomes and the Golgi apparatus, and also acts as a powerful antioxidant and inhibitor of lipid peroxidation. BPM 31510 is an intravenous formulation of coenzyme Q10 in a proprietary nanodispersion formulation with ability to selectively deliver high concentrations of Coenzyme Q10 to targets tissues and organelles including the mitochondria. In this study, Sprague Dawley rats were used as model system to determine the effect of intravenous BPM31510 on doxorubicin-mediated cardiomyopathy. Lethality of doxorubicin was observed when rats were injected intraperitoneally 20 mg total dose, with a schedule of 10 mg/kg/day for two days. On day 30, signs of morbidity were present, such as cachexia and a decrease in the size of the heart was documented following necropsy. Concomitant administration of BPM31510 resulted in a modest but significant increase in lifespan in the doxorubicin treated animals (p 0.025). In contrast, pretreatment with intravenous BPM31510 followed by doxorubicin dosing was associated with significant decline in mortality, with as many as sixty percent of animals surviving past 30 days (p<0.01). The potential mechanism(s) underlying the effect of long-term use of BPM31510 on doxorubicin-induced cardiotoxicity was investigated. Rats with a protracted regimen of doxorubicin died between days 25 and 30, whereas as previously observed, BPM 31510 had a significant impact on survival (p=0.005). Increased survival in the BPM31510 treated group was associated with significant decreases in alterations of heart morphology and biochemical parameters of oxidative stress. Taken together, the data suggests that intravenous BPM31510 has the potential to mitigate doxorubicin-mediated mortality

Effects of conditions of an experimental model to evaluate methods of electric-fence strand addition to barbed-wire fence to contain goats1

Growing meat goats of 4 types (Boer and Spanish of both wethers and doelings) were used to evaluate conditions for a method of testing efficacy of electric-fence strand additions to barbed-wire fence used for cattle to also contain goats. Animals were allocated to 8 sets, with each set consisting of 5 groups. There was 1 goat of each of the 4 types in a group. One side of five 2.4- × 3.7-m evaluation pens consisted of barbed-wire strands at 30, 56, 81, 107, and 132 cm from the ground. Evaluation pens were adjacent to a pasture with abundant vegetation. Fence treatments (FT) were electrified strands (6 kV) at 15- and 43- (LowHigh), 15- and 23- (LowMed), 15- (Low), 23- (Med), and 43-cm (High), where Low, Med, and High abbreviations are for low, medium, and high heights from the ground, respectively. For adaptation, there were 4-wk and sequential exposures to evaluation pens: wk 1, no electric strands; wk 2, 1 strand at 0 kV; wk 3, LowHigh; and wk 4, LowHigh. There were 6 periods for measurements, each separated by 1 wk. During the 1-wk intervals on pasture, sets were exposed to 1 interval treatment without and another with 2 electric strands (6 kV) positioned next to supplement troughs, to potentially affect familiarity with electrified strands and influence subsequent behavior. All animal sets were used for measurements in period 1 in a completely randomized design (CRD). Four sets were also used in 4-wk subsequent measurement periods for a 5 × 5 Latin square (LS). All animal sets were exposed to the same FT in period 6 as in period 1. Behavior in evaluation pens was observed for 1 h with a video surveillance system in the 6 periods. There were no effects of gender and few and minor effects of preliminary and interval treatments. The percentage of animals that exited evaluation pens differed (P < 0.05) among FT, with the CRD approach in period 1 (25%, 47%, 38%, 66%, and 84%; SEM = 8.0) and with repeated measures in periods 1 and 6 (6%, 22%, 22%, 63%, and 81% for LowHigh, LowMed, Low, High, and Med, respectively; SEM = 4.9), and between breeds in periods 1 (34% and 70%) and 1 and 6 (28% and 50% for Boer and Spanish, respectively). For the LS approach, FT affected exit (31%, 23%, 16%, 35%, and 30%; SEM = 5.3) and breeds differed (P < 0.05), as well (12% and 43%). Exit decreased as period advanced (60%, 35%, 23%, 10%, and 8%, for 1, 2, 3, 4, and 5, respectively; SEM = 5.3). In conclusion, breed should be considered in the model being developed. A LS approach was not suitable, but a CRD experiment after these adaptation procedures appears promising.

Preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII

The preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII, was assessed in a series of animal studies. In the tail-clip bleeding model, hemophilia A mice were injected with escalating doses (1-150 IU/kg) of rVIII-SingleChain, B-domain deleted (BDD) rFVIII (ReFacto AF(®)), or full-length rFVIII products (Advate(®), Helixate(®)). Total blood loss and the percentage of animals in which hemostasis occurred were assessed in this observer-blinded, randomized study. In a second non-randomized study in hemophilia A mice, thromboelastographic analysis, thrombin generation, and activated partial thromboplastin time assays were performed. General safety and toxicity were assessed in three animal species, including determination of the prothrombotic potential of rVIII-SingleChain in a rabbit venous thrombosis model. Under acute bleeding conditions, the effect of rVIII-SingleChain on total blood loss and hemostasis was indistinguishable from BDD and full-length rFVIII. rVIII-SingleChain and full-length rFVIII (both 20 IU/kg) corrected thromboelastographic parameters, activated partial thromboplastin time, and thrombin generation to a similar degree in hemophilia A mice. In a thrombosis model, the effect of rVIII-SingleChain on thrombus incidence was non-significant and comparable to BDD rFVIII at doses up to 500 IU/kg. Treatment with rVIII-SingleChain did not cause anaphylactic reaction or local intolerance in safety and toxicity studies, and demonstrated an excellent overall safety profile. rVIII-SingleChain showed convincing hemostatic efficacy and excellent tolerability in animal studies, warranting continued investigation in human Phase I/III trials (AFFINITY).

Forage and breed effects on behavior and temperament of pregnant beef heifers

BackgroundIntegration of behavioral observations with traditional selection schemes may lead to enhanced animal well-being and more profitable forage-based cattle production systems. Brahman-influenced (BR; n = 64) and Gelbvieh × Angus (GA; n = 64) heifers consumed either toxic endophyte-infected tall fescue (E+) or one of two nontoxic endophyte-infected tall fescue (NT) cultivars during two yr. Heifers were weighed at midpoint and termination of grazing. Grazing behavior (grazing, resting in the shade, lying, or standing without grazing) was recorded (n = 13 visual observations per yr in June and July) for each pasture. During yr 2, exit velocity (EV) and serum prolactin (PRL) were determined.ResultsGrazing behavior was influenced (P < 0.05) by an interaction between fescue cultivar and breed type. Gelbvieh × Angus heifers assigned to E+ pastures had the lowest percentage of animals grazing and the largest percentage of animals resting in the shade. Brahman-influenced heifers had faster EV (P < 0.001) than GA heifers (0.52 vs. 0.74 ± 0.04 s/m, respectively). Body weight (BW) was affected (P < 0.01) by an interaction of tall fescue cultivar and d, and an interaction of tall fescue cultivar and breed type. Heifers grazing NT pastures were heavier (P < 0.01) than heifers grazing E+ pastures at midpoint and termination. Gelbvieh × Angus heifers grazing NT pastures were heavier (P < 0.01) than GA and BR heifers grazing E+ and BR heifers grazing NT pastures. An interaction of forage cultivar and breed type occurred on serum PRL (P < 0.01).ConclusionCollectively fescue cultivar, EV, and concentrations of serum PRL were associated with grazing behavior. Heifers grazing NT pastures were observed to be grazing more than heifers assigned to E+ pastures, regardless of breed type, which may have contributed to changes in BW and average daily gain (ADG) in heifers. Integration of behavioral observations along with traditional selection schemes may lead to enhanced animal well-being and more profitable forage-based cattle production systems.

In vitro neutralization of HoBi-like viruses by antibodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea viruses 1 and 2

HoBi-like viruses are an emerging species of pestiviruses with genetic and antigenic similarities to bovine viral diarrhea viruses 1 and 2 (BVDV1 and BVDV2). Vaccines for HoBi-like viruses are not yet available. However, both modified live virus (MLV) and killed virus (KV) vaccines against BVDV are widely used worldwide. This study evaluated the cross reactive antibody response against HoBi-like pestiviruses in sera of cattle immunized with BVDV1 and BVDV2 vaccines. Groups "KV" and "MLV", with 25 calves each, received killed or modified live vaccines, respectively, containing both BVDV1 and BVDV2 antigens. The antibody response was evaluated by virus neutralization test. The average of geometric mean titers (GMTs) of neutralizing antibodies in serum against HoBi-like viruses in the MLV group was 12.9, whereas GMTs to BVDV1, BVDV2 and border disease virus (BDV) were 51.1, 23.5, and 12.4, respectively. In this group, neutralizing antibodies against BVDV1, BVDV2, HoBi-like viruses and BDV were detected in 100%, 94%, 68% and 68% of calves, respectively. The GMT of neutralizing antibodies in serum against BVDV1, BVDV2, HoBi-like viruses and BDV in the KV group were 24.7, 14.5, 10.4 and 11, respectively. Similarly, the percentage of animals with neutralizing antibodies against BVDV1, BVDV2, HoBi-like viruses and BDV were 84%, 56%, 34% and 44%, respectively. These results indicate that MLV or killed BVDV1 and BVDV2 vaccines induce a cross reactive antibody response comparatively weak to HoBi-like viruses, and this response would likely not suffice to confer protection.

Abstract 1577: Subtype dependent carcinoma initiation by Rb tumor suppressor inactivation in multiple epithelial tissues.

Abstract Carcinomas arise in a complex microenvironment consisting of multiple distinct epithelial lineages surrounded by mesenchymal cells. Of major importance is to understand the relationship among cell types, initiation event, and ultimate cancer outcome. Mouse models facilitate the prospective examination of early oncogenic events, which is not feasible in humans, permitting an analysis of epithelial subtype susceptibility. Since most solid tumors harbor aberrations in the pRb network, we assessed the susceptibility of epithelial subtypes expressing cytokeratin (K) 18 or K19 to the disruption of Rb tumor suppression (Rb-TS) in vivo. Tumorigenesis could be initiated in either K18- or K19-expressing cells. However, the susceptibility of epithelial tissues was subtype-dependent. K19 cells were more prone to hyperplasia and neoplasia than K18 targeted cells. Given that a single genetic event was engineered, a small percentage of animals developed carcinoma/adenocarcinoma, providing the opportunity to define progression events via engineering or spontaneous evolution. To extend our analysis to a specific tissue, we employed a prostate-specific Cre line to target either K18- or K19-expressing prostate epithelial cells. Differential responses observed in the frequency and extent of premalignant hyperplastic lesions strongly supported the notion of cell type-dependent susceptibility to Rb-TS inactivation. Our data suggest that the tumorigenic consequences of a single initiation event are dictated by cellular subtype distinctiveness, underscoring the importance of the tumor cell of origin. Citation Format: Yurong Song, Chunyu Yang, Wenqi Pan, Alisan Fathalizadeh, Lucy Lu, Debra Gilbert, T. Norene O'Sullivan, Diana C. Haines, Philip L. Martin, Terry Van Dyke. Subtype dependent carcinoma initiation by Rb tumor suppressor inactivation in multiple epithelial tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1577. doi:10.1158/1538-7445.AM2013-1577

Comportamento de ovinos da raça Santa Inês em ambientes com e sem disponibilidade de sombra

Com o objetivo de observar os efeitos do sombreamento propiciado pela tela de polipropileno sobre o comportamento de ovinos da raça Santa Inês em diferentes épocas do ano, montou-se um experimento em Petrolina, PE, no período de junho a novembro de 2010. Utilizaram-se 40 animais distribuídos em igual quantidade em dois tratamentos (Sombreado e Não sombreado) com oferta de pastagem (Tiffton 85) irrigada. Foram feitas aferições dos dados meteorológicos em todas as épocas, com a montagem de termômetros de globo negro e psicrômetros nas duas áreas e de uma mini-estação meteorológica na área sombreada. Nessas épocas foram realizados ensaios de comportamento tendo-se feito observações visuais pelo método da varredura instantânea em intervalos de 10 min no período diurno, verificando-se o percentual de animais quanto à alimentação, ruminação e ócio, a partir da metodologia proposta por Johnson &amp; Combs (1991) adaptada para o tempo de 12h. O sombreamento não influenciou no número de animais em referência às atividades avaliadas nos diferentes tratamentos. A procura por sombra foi intensa nos períodos mais quentes do dia para a atividade de ócio.

Effect of the Treatment with Alpha-Macroglobulin on the Development of Experimental Pancreatitis

Alpha-macroglobulins are proteinase inhibitors. Monofluorophosphate increases alpha-macroglobulin levels in plasma, inducing a higher survival rate and lower pancreatic damage in rats with pancreatitis. The aim of this study was to evaluate the effect of alpha-macroglobulin on the development of pancreatitis. Pancreatitis was surgically induced in Sprague-Dawley rats divided into groups of 16 rats each and -subjected to the following intravenous treatments for 3 days: pancreatitis without treatment, Enriched plasma: pancreatitis+-alpha-macroglobulin-enriched plasma, Normal plasma: pancreatitis+plasma with normal levels of alpha-macroglobulin, Saline Solution: pancreatitis+saline solution, Purified alpha-macroglobulin: pancreatitis+purified alpha-macroglobulin. After 14 days pancreatic damage was assessed using a score that measures: edema, fibrin, neutrophils, mononuclear leukocytes, necrosis, vascular congestion, thrombosis, hemorrhage and fibrosis. Pancreatic damage decreased and the percentage of animals with pancreatitis was lower in enriched-plasma and purified alpha-macroglobulin groups. We conclude that the intravenous administration of alpha-macroglobulins causes a reduction in the histological damage produced by pancreatitis.

Novel Rabbit Model for the Evaluation of Open Tibia Fractures: Effect of Delayed Surgery on Infection Rate

ABSTRACTIntroductionThe objective of this investigation was to evaluate the effects of delayed surgery on infection rates of open tibia fractures in a rabbit model. Our hypothesis was that delaying irrigation and debridement (I&amp;D) would increase the risk of bony and soft tissue infection when antibiotics were withheld.Materials and methodsA drill hole was created in the rabbit tibia and inoculated withStaphylococcus aureus. Animals underwent I&amp;D at controlled delayed times of 6 hours (n = 11), 12 hours (n = 9) and 24 hours (n = 10). A stainless steel pin was inserted to mimic definitive fracture fixation with a metal prosthesis. No antibiotics were administered. Animals were sacrificed at 4 weeks and evaluated for infection.ResultsThe percent of soft tissue infections with I&amp;D delays of 6, 12 and 24 hours were 18, 22 and 40%, respectively [p = 0.59; odds ratio (OR) = 3]. The percentage of animals with osteomyelitis with I&amp;D delays of 6, 12 and 24 hours were 9, 22 and 50%, respectively (p = 0.12; OR = 10).DiscussionIn the current model, delaying I&amp;D from 6 to 24 hours may increase the rate of postoperative osteomyelitis and further investigation is warranted.Kokko KP, Kang QK, Wen X, An YH, Barfield WR, Hartsock LA. Novel Rabbit Model for the Evaluation of Open Tibia Fractures: Effect of Delayed Surgery on Infection Rate. The Duke Orthop J 2013;3(1):48-53. I

Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.)

This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L.) as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L.), using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle), standard (diazepam) and test (Trachyspermum ammi (L.) extract). Trachyspermum ammi (L.) demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L.) and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L.) showed antiepileptic activity, which may be due to the presence of thymol.