bluuebunny/crossref_metadata_2025 huggingface dataset:
Grafting of 2‐Hydroxypropyl‐β‐Cyclodextrin on Gum Arabic‐Modified Iron Oxide Nanoparticles as a Magnetic Carrier for Targeted Delivery of Hydrophobic Anticancer Drug
Authors: Banerjee Shashwat S. , Chen Dong‐Hwang
Published: December 2008

A new magnetic nanocarrier for the targeted delivery of hydrophobic drugs was developed by modifying magnetic nanoparticles with gum arabic and grafting with 2‐hydroxypropyl‐cyclodextrins (HCD) using hexamethylene diisocyanate (HMDI) as a linker. The size, hydrodynamic diameter, and grafting of HCD were characterized. The resultant magnetic nanocarrier exhibited an excellent capability to load all‐trans‐retinoic acid (ATRA), an anticancer agent. The better biocompatibility and the combined properties of specific targeting and complexation ability with hydrophobic drugs make the nanosystem an exciting prospect for targeted delivery of hydrophobic drugs.
Intraspecific Variation in the Fruiting of an Amazonian Timber Tree: Implications for Management
Authors: Fonseca Marisa Gesteira , Vidal Edson , Maës dos Santos Flavio Antonio
Published: December 2008

Information concerning the fruit production of timber species is important for the assessment of the effects of logging practices and for the improvement of harvesting techniques. We assessed the effects of stem diameter, crown illumination, and liana load on Chrysophyllum lucentifolium subsp. pachycarpum fruiting over a 3‐yr period in areas subjected to conventional and reduced impact logging 10–13 yr prior to the study and within a control area, in the eastern Brazilian Amazon. We further used this data set to estimate the proportion of fertile trees harvested following the adoption of 90 percent harvesting intensity and two different minimum diameter cutting limits (MDCL). Liana presence on > 50 percent of the crown was associated with a decrease in the odds of fruiting. Therefore, liana cutting aiming to increase fruiting output should target only trees in such a condition. We found no significant effects of logging treatments and crown illumination on the odds of fruiting. The percentage of reproductive trees, frequency, and intensity of fruiting increased markedly for trees > 40 cm dbh. The proportion of fertile trees harvested following the adoption of 50 cm dbh MDCL is relatively low (13–15%) and therefore, this practice is likely to have a low direct impact on C. lucentifolium fruiting at the population level. However, even for a population with relatively small fertile individuals and low proportion of trees ≥ 50 cm dbh, the MDCL should not be < 50 cm dbh, unless a lower harvest intensity is adopted.
Transforming South–North Relations? International Migration and Development
Authors: Datta Kavita
Published: December 2008

Migration is increasingly viewed as a panacea for development. While much research on the ‘migration‐development nexus’ has focused on remittances and the developmental potential of these, other work has also highlighted the importance of return migration and, increasingly, the circulation of knowledge and skills, in engendering development. This said, it is important to recognise that the general euphoria surrounding the developmental potential of migration is increasingly framed within a Northern discourse and policy framework which seeks to better manage and control migration to the developed world. As such, it is important to recognise the different, and at times contradictory, agendas pursued by migrants, home and host countries. This article aims to highlight the implications of this for South–North relations.
Assessment of Changes in Stream and Riparian Conditions of the Marys River Basin, Nevada1
Authors: Newman Sarah , Swanson Sherman
Published: December 2008

Abstract:  Stream and riparian managers must effectively allocate limited financial and personnel resources to monitor and manage riparian ecosystems. They need to use management strategies and monitoring methods that are compatible with their objectives and the response potential of each stream reach. Our objective is to help others set realistic management objectives by comparing results from different methods used to document riparian recovery across a diversity of stream types. The Bureau of Land Management Elko Field Office, Nevada, used stream survey, riparian proper functioning condition (PFC) assessment, repeat photographic analysis, and stream and ecological classification to study 10 streams within the Marys River watershed of northeast Nevada during all or parts of 20 years. Most riparian areas improved significantly from 1979 to 1992‐1993 and then additionally by 1997‐2000. Improvements were observed in riparian and habitat condition indices, bank cover, and stability, pool quality, bank angle, and depth of undercut bank. Interpretation of repeat photography generally confirmed results from stream survey and should be part of long‐term riparian monitoring. More attributes of Rosgen stream types C and E improved than of types B and F. A and Gc streams did not show significant improvement. Alluvial draws and alluvial valleys improved in more ways than V‐erosional canyons and especially V‐depositional canyons. Stream survey data could not be substituted for riparian PFC assessment. Riparian PFC assessments help interpret other data.
Applying Zonation Methods and Tabu Search to Improve the Ground‐Water Modeling1
Authors: Tan Chung‐Che , Tung Ching‐Pin , Tsai Frank T‐C.
Published: December 2008

Abstract:  An optimization procedure combining zonation methods with the Tabu Search method is proposed to identify the spatial distribution of hydraulic conductivity field. Three zonation methods, Voronoi diagram (VD), multiplicatively weighted Voronoi diagram (MWVD), and pattern zonation are adopted for the parameterization purposes. With the consideration of the homogeneity and the heterogeneity, there are four spatial distributions of hydraulic conductivity designed to test whether the parameter structure can be successfully identified. The fitting residual error is first considered to determine an adequate number of zones without over parameterization. Then, the parameter uncertainty is evaluated the decision of the number of zones. The results indicate that the MWVD performs better than other two methods because the MWVD has better flexibility in describing the zonal boundaries with small number of decision variables.
Comparison of Field Performance of Multiple Soil Moisture Sensors in a Semi‐Arid Rangeland1
Authors: Paige Ginger B. , Keefer Timothy O.
Published: December 2008

Abstract:  Automated electronic soil moisture sensors, such as time domain reflectometry (TDR) and capacitance probes are being used extensively to monitor and measure soil moisture in a variety of scientific and land management applications. These sensors are often used for a wide range of soil moisture applications such as drought forage prediction or validation of large‐scale remote sensing instruments. The convergence of three different research projects facilitated the evaluation and comparison of three commercially available electronic soil moisture probes under field application conditions. The sensors are all installed in shallow soil profiles in a well instrumented small semi‐arid shrub covered subwatershed in Southeastern Arizona. The sensors use either a TDR or a capacitance technique; both of which indirectly measure the soil dielectric constant to determine the soil moisture content. Sensors are evaluated over a range of conditions during three seasons comparing responses to natural wetting and drying sequences and using water balance and infiltration simulation models. Each of the sensors responded to the majority of precipitation events; however, they varied greatly in response time and magnitude from each other. Measured profile soil moisture storage compared better to water balance estimates when soil moisture in deeper layers was accounted for in the calculations. No distinct or consistent trend was detected when comparing the responses from the sensors or the infiltration model to individual precipitation events. The results underscore the need to understand how the sensors respond under field application and recognize the limitations of soil moisture sensors and the factors that can affect their accuracy in predicting soil moisture in situ.
A key and four new species of Hedysarum (Fabaceae) in Iran
Authors: Ranjbar M. , Karamian R. , Olanj N. , Johartchi M. R.
Published: December 2008

A key, descriptions and new findings are given for some species from of the short‐stemmed group Hedysarum sect. Multicaulia, which occur within the area covered by the flora of the north‐eastern part of Iran (Khorassan Province). They have short stem, becoming woody at base, standard as long as keel and pods, glabrous or densely covered with grey appressed hairs. In addition, H.longepedunculatum, H. bojnordense, H. paucifoliolatum and H. glabrifoliolatum are described and illustrated as new species. The relationships between the new species and their closest relatives are discussed. Hedysarum fallacinum Rech. f. & Aellen is reduced to a synonym of H. kopetdaghi Boriss. on the basis of their common characters such as arrangement of branches and flowers, shape of leaflet and size of calyx and corolla.
Centaurea yaltirikii sp. nov. (Asteraceae, C. sect. Pseudoseridia) from Turkey
Authors: Aksoy Necmí , Duman Hayri , Efe Asuman
Published: December 2008

A new species of Centaurea L. (Asteraeeae) from Turkey is described and illustrated. Centaurea yaltirikii N. Aksoy, H. Duman & A. Efe sp. nov. (C. sect. Pseudoseridia Wagenitz) is restricted to the rocky slopes of Elmacik Daği (A3: Düzce–Gölyaka). It is morphologically most similar to C. drabifolioides Hub.‐Mor. and C. cheirolepidoides Wagenitz, but differs in stem, leaves and phyllary appendange characters. The diagnostic morphological characters are discussed. The habitat and conservation status of the species are presented, and the geographical distribution of the new species and other related species is given.
Muscari babachii sp. nov. (Hyacinthaceae) from south Anatolia
Authors: Eker İsmail , Koyuncu Mehmet
Published: December 2008

A new species, Muscari babachii Eker & Koyuncu sp. nov. (Hyacinthaceae) from south Anatolia is described. Diagnostic characters, description, detailed illustration, geographical distribution, IUCN extinction risk, observations and taxonomic comments on the new species are given. It is also compared with the closely related M. tenuiflorum Tausch.
The Use of Contralateral Masking Noise in the Detection of Unilateral Deafness in Dalmatian Puppies
Authors: Gonçalves R. , Freeman J. , Penderis J.
Published: December 2008

Background: The brainstem auditory‐evoked response (BAER) is currently the standard evaluation method of hearing in dogs. In asymmetrical hearing loss in human patients, simultaneous presentation of masking noise to the nontest ear is routinely performed during BAER to eliminate the crossover effect.

Hypothesis: The crossover effect occurs during canine BAER, and masking noise of 20 decibels (dB) below click stimulus intensity is sufficient to abolish this effect.

Animals: Fifty‐six Dalmatian puppies with confirmed unilateral deafness.

Methods: The BAER was elicited with 80 and 100 dB normalized hearing level (dBnHL) stimulus intensity in the deaf ear. The 100 dBnHL stimulus was repeated while simultaneously applying 80 dBnHL white masking noise to the nontest ear.

Results: Ten dogs were excluded because of BAER trace baseline fluctuation. In the remaining 46 dogs, 8 dogs had no waveforms, but 38 dogs had an identifiable wave‐V in the deaf ear BAER at 80 dBnHL intensity stimulus. At 100 dBnHL intensity stimulus, all but 1 dog had a discernible wave‐V in the deaf ear BAER. The deaf ear BAER waveforms were abolished by white masking noise at 80 dBnHL in the nontest ear in all dogs.

Conclusions and Clinical Importance: Abolition of BAER wave‐V in the deaf ear by white masking noise in the nontest ear suggests that this wave is caused by the crossover effect. β distribution indicates 95% confidence that white masking noise, at 20 dB below click stimulus intensity, would abolish this crossover effect in over 90% of the dogs. This supports using masking noise in the nontest ear during canine BAER.
In Vivo and In Vitro Efficacy of Zoledronate for Treating Oral Squamous Cell Carcinoma in Cats
Authors: Wypij J.M. , Fan T.M. , Fredrickson R.L. , Barger A.M. , De Lorimier L.P. , Charney S.C.
Published: December 2008

Background:Feline oral squamous cell carcinoma (OSCC) may cause painful bone destruction. Given the local invasiveness and rapid clinical progression of OSCC, conventional therapies are often palliative. In human cancer patients, zoledronate exerts anticancer effects by inhibiting tumor‐induced angiogenesis and malignant osteolysis.

Hypothesis:Zoledronate will exert in vitro and in vivo anti‐angiogenic and antiresorptive effects in feline OSCC.

Animals:Eight cats with OSCC were prospectively treated with zoledronate and conventional treatment modalities.

Methods:In vitro, zoledronate's effects in modulating soluble vascular endothelial growth factor (VEGF) secretion and receptor activator of nuclear factorkB (NF‐κB) ligand (RANKL) expression were investigated in a feline OSCC cell line (SCCF1). In vivo, basal serum C‐telopeptide (CTx) concentrations were compared among normal and OSCC‐bearing cats, and the biologic effects of zoledronate administration in cats with naturally occurring OSCC were quantified by serially assessing circulating serum VEGF and CTx concentrations.

Results:In vitro, zoledronate concentrations greater than 3 μM reduce soluble VEGF secretion in the SCCF1 cell line. The expression of RANKL in the SCCF1 cell line was also modulated by zoledronate, with low concentrations (3 μM) decreasing but higher concentrations (30 μM) increasing RANKL expression in comparison with untreated cells. In vivo, cats with bone‐invasive OSCC had greater serum CTx concentrations in comparison with geriatric, healthy controls. Treatment with zoledronate rapidly decreased circulating serum VEGF and CTx concentrations in cats with spontaneously occurring OSCC.

Conclusions and Clinical Importance:Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor growth and pathologic bone turnover associated with OSCC.
BartonellaDNA in the Blood and Lymph Nodes of Golden Retrievers with Lymphoma and in Healthy Controls
Authors: Duncan A.W. , Marr H.S. , Birkenheuer A.J. , Maggi R.G. , Williams L.E. , Correa M.T. , Breitschwerdt E.B.
Published: December 2008

Background:Although lymphoma is the most common neoplastic process reported in dogs, its precise etiology is unknown. Golden Retrievers are more likely to develop lymphoma, suggesting a breed predisposition; however, other factors, including environment, immunity, and infection, are likely contributors to oncogenesis.

Hypothesis:We hypothesized that the development of lymphoma in Golden Retrievers may be associated with vector‐borne infections, specificallyBartonella,Anaplasma, orEhrlichiaspecies infections.

Animals:Golden Retrievers with lymphoma and healthy Golden Retrievers from across the United States were recruited for study participation.

Methods:A matched, case‐control study was performed to determine the association of lymphoma and the presence ofBartonella, Anaplasma, andEhrlichiaspecies in serum, blood, and lymph node aspirates.

Results:Using PCR analyses and DNA sequencing, single and coinfections withBartonella henselae,Bartonella elizabethae, Bartonella quintana, and/orBartonella vinsonii(berkhoffii) were detected in the blood and lymph node aspirates of Golden Retrievers with lymphoma (5/28 dogs, 18%) and in healthy Golden Retrievers (10/56 dogs, 18%); noAnaplasmaorEhrlichiaDNA was detected in any dog. When compared with dogs with lymphoma, a higher (P<.001) proportion of healthy Golden Retrievers were receiving monthly acaricide treatments (2.6 times higher).

Conclusions and Clinical Importance:BartonellaDNA can be detected in blood and lymph nodes; importantly, in this report,Bartonellawas detected in the same proportion of clinically healthy dogs and dogs with lymphoma. Longitudinal studies should be conducted to determine the mode of transmission ofBartonellain dogs, whether lymphatic infection is persistent, or whether these bacteria may contribute to the development of lymphoma.
Circulating Natriuretic Peptides in Cats with Heart Disease
Authors: Connolly D.J. , Soares Magalhaes R.J. , Syme H.M. , Boswood A. , Luis Fuentes V. , Chu L. , Metcalf M.
Published: December 2008

Background:Circulating natriuretic peptide concentrations are increased in cats with myocardial dysfunction.

Hypothesis:Serum N‐terminal fragment of proatrial natriuretic peptide (NT‐proANP) and NT‐probrain natriuretic peptide (proBNP) concentrations may predict the presence of heart disease (HD) and congestive heart failure (CHF). A positive relationship is also predicted among natriuretic peptide (NP) concentrations, a noninvasive estimate of left ventricular filling pressure (E/Ea), and an echocardiographic measure of left atrial (LA) size (LA/aortic diameter [Ao]).

Methods:Serum NP concentrations were measured in 28 healthy control and 50 study cats using sandwich enzyme immunoassays. The study group comprised cats, with HD but no CHF (HD − CHF, n = 17) and cats with CHF (HD + CHF, n = 33). The relationship among NP concentrations, LA size, andE/Eawas examined. The ability of NP to distinguish control from study cats, and HD − CHF from HD + CHF cats, was explored using receiver operator curve analysis.

Results:NP concentrations were significantly lower in control than in study cats (P= .0001). The NT‐proBNP concentrations were positively correlated with LA/Ao ratio (ρ= 0.34;P= .02) and withE/Earatio (ρ= 0.68;P< .05). An NT‐proBNP concentration of 49 fmol/mL gave a sensitivity and specificity of 100 and 89.3%, respectively, for correctly distinguishing 96.2% of control from study cats. Pairwise comparisons of the areas under the curve identified a statistically significant difference (P= .011) between NT‐proANP and NT‐proBNP to distinguish control from study cats. NT‐proANP and NT‐proBNP concentrations were significantly higher in HD + CHF cats than in HD − CHF cats (P= .0023 and .0001, respectively).

Conclusions:Serum concentrations of NT‐proANP and particularly NT‐proBNP were different in healthy control cats, asymptomatic cats with HD, and cats with CHF, suggesting that measurement of NP concentrations may prove clinically useful as an initial screening test for cats with suspected cardiac disease.
Effect of Erythromycin and Gentamicin on Abomasal Emptying Rate in Suckling Calves
Authors: Nouri M. , Hajikolaee M.R. , Constable P.D. , Omidi A.
Published: December 2008

Background:Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying.

Hypothesis:Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying.

Animals:Five male Holstein‐Friesian calves (8–15 days of age).

Methods:Calves received each of the following 4 IM treatments in random order: control, 2 mL of 0.9% NaCl; erythromycin, 8.8 mg/kg; low‐dose gentamicin, 4.4 mg/kg; high‐dose gentamicin, 6.6 mg/kg. Abomasal emptying rate was assessed by acetaminophen and glucose absorption. Calves were fed 2 L of cow's milk containing acetaminophen (50 mg/kg body weight) 30 minutes after each treatment was administered, and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma acetaminophen concentration (actualCmax) and time of actualCmax(actualTmax) were determined, and pharmacokinetic modeling was used to calculate modelCmaxand modelTmax.

Results:Erythromycin increased abomasal emptying rate, as indicated by a shorter time to actualTmaxand modelTmax(P< .05). Abomasal emptying rate after injection of low‐dose gentamicin was similar to that of control. Administration of high‐dose gentamicin resulted in a longer time to actualTmax(P= .021) but did not change modelTmax(P= .62).

Conclusions and Clinical Relevance:IM injection of erythromycin increased abomasal emptying rate in dairy calves, whereas low‐dose and high‐dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption. The clinical relevance of these findings remains to be determined.
Clinical Efficacy of Intravenous Hypertonic Saline Solution or Hypertonic Bicarbonate Solution in the Treatment of Inappetent Calves with Neonatal Diarrhea
Authors: Koch A. , Kaske M.
Published: December 2008

Background:The clinical efficacy of IV administered hypertonic saline solution and hypertonic bicarbonate solution (HBS) in the treatment of inappetent diarrheic calves has not been compared yet.

Hypothesis:HBS is more advantageous than hypertonic saline in the treatment of calves with severe metabolic acidosis.

Animals:Twenty‐eight dehydrated, inappetent calves with neonatal diarrhea.

Methods:In 2 consecutive clinical studies, calves were initially treated with saline (5.85%; 5 mL/kg body weight [BW] over 4 minutes; study I: N = 16) or bicarbonate solution (8.4%; 10 mL/kg BW over 8 minutes; study II: N = 12), respectively, followed by oral administration of 3 L isotonic electrolyte solution 5 minutes after injection. Clinical and laboratory variables were monitored for 72 hours.

Results:Treatment failed in 6 calves of study I and in 1 calf of study II as indicated by a deterioration of the general condition. All treatment failures had more severe metabolic acidosis compared with successfully treated calves before treatment. In the latter, rehydration was completed within 18 hours after injection; metabolic acidosis was corrected within 24 hours (study I) and 6 hours (study II) after injection.

Conclusions and Clinical Importance:Diarrheic calves with slight metabolic acidosis (base excess [BE] >−10 mM) can be treated successfully with hypertonic saline. HBS is appropriate in calves without respiratory problems with more severe metabolic acidosis (BE up to −20 mM). Intensive care of the calves is required to ensure a sufficient oral fluid intake after the initial IV treatment.
Efficacy and Toxicosis of VELCAP‐C Treatment of Lymphoma in Cats
Authors: Hadden A.G. , Cotter S.M. , Rand W. , Moore A.S. , Davis R.M. , Morrissey P.
Published: December 2008

Background: Lymphoma is the most common malignancy affecting cats. A protocol employing vincristine, l‐asparaginase, cyclophosphamide, doxorubicin, and prednisone (VELCAP‐S) is effective and well tolerated in dogs with lymphoma. A 24‐week variation of this protocol (VELCAP‐C) was developed for treatment of cats.

Hypothesis: That VELCAP‐C will result in survival times for cats with lymphoma that are similar to those obtained when cats are treated with a protocol that includes fewer chemotherapy agents.

Animals: Sixty‐one cats with lymphoma.

Methods: Retrospective study. Outcomes evaluated were response to VELCAP‐C therapy, toxicosis, and survival time. The effect of signalment, staging, CBC, and serum chemistry profile and dosage on these outcomes was examined.

Results: Six cats (10%) completed the protocol with a median survival of 1189 days. Forty‐three percent (23 of 61) of the cats achieved complete response (CR) with a median survival time of 62 days. Cats that required a dose reduction of any drug during induction were more likely to achieve CR. Weight loss and hepatomegaly at diagnosis were negatively associated with response to treatment. Increased lactate dehydrogenase (LDH) serum activity at the time of initial treatment correlated with decreased survival times.

Conclusions and Clinical Importance: This multi agent protocol did not provide improved survival over historical data using protocols with fewer agents. Serum LDH activity levels might provide useful prognostic information for cats with lymphoma.
Innate Immunity and Host Defense Peptides in Veterinary Medicine
Authors: Linde A. , Ross C.R. , Davis E.G. , Dib L. , Blecha F. , Melgarejo T.
Published: December 2008

Recent years have witnessed a surge in interest directed at innate immune mechanisms. Proper conceptualization of the key elements of innate immunity, however, is still a work in progress, because most research in immunology traditionally has been focused on components of the acquired immune response. The question of why an animal stays healthy in a world filled with many dangers is perhaps as interesting as why it sometimes surrenders to disease. Consequently, studies with an increased focus on inborn mechanisms of animal host defense may help further the development of appropriate preventative and therapeutic measures in veterinary medicine. Host defense peptides (HDPs) are central effector molecules of innate immunity, and are produced by virtually all living species throughout the plant and animal kingdoms. These gene‐encoded peptides play a central role in multiple, clinically relevant disease processes. Imbalances in the expression of HDPs can lead to overt pathology in different organ systems and cell types in all species studied. In addition, HDPs are an ancient group of innate chemical protectors, which are now evaluated as model molecules for the development of novel natural antibiotics and immunoregulatory compounds. This review provides an overview of HDPs and is aimed at veterinary practitioners as well as basic researchers with an interest in comparative immunology involving small and large animal species.
The Effects of Hydrocortisone on Systemic Arterial Blood Pressure and Urinary Protein Excretion in Dogs
Authors: Schellenberg S. , Mettler M. , Gentilini F. , Portmann R. , Glaus T.M. , Reusch C.E.
Published: December 2008

Background:Hypertension and proteinuria are commonly recognized in dogs with spontaneous hypercortisolism. There is, however, little information regarding the effect of exogenous glucocorticoids on blood pressure (BP) and proteinuria and whether these changes are reversible.

Hypothesis:Hydrocortisone administration increases systemic BP and urinary protein excretion, and these effects are reversible after hydrocortisone withdrawal.

Animals:Six control dogs and 6 dogs treated with hydrocortisone.

Methods:BP, urine protein : creatinine ratio (UPC), microalbuminuria (MALB), urine albumin : creatinine ratio (UAC), and urine gel electrophoresis were evaluated before, during, and after administration of hydrocortisone (8 mg/kg PO q12h for 12 weeks) or placebo.

Results:BP and UPC increased substantially during hydrocortisone administration from 123 mmHg (range 114–136 mmHg) and 0.17 (0.15–0.28) to a maximum of 143 mmHg (128–148 mmHg) and 0.38 (0.18–1.78), respectively, on day 28. MALB developed in 4 dogs and UAC significantly increased in all dogs during hydrocortisone administration with the maximum on day 84. Both increases in BP and proteinuria were reversible and completely resolved within 1 month after stopping hydrocortisone administration. SDS‐AGE revealed the proteinuria to be primarily albuminuria with a pronounced increase during hydrocortisone treatment. Furthermore, a protein of 25–30 kDa was found in male dogs, identified by mass spectrometry to be arginine esterase, the major secretory prostatic protein.

Conclusions and Clinical Importance:Long‐term hydrocortisone treatment results in significant but only mild increases in systemic BP and urinary protein excretion, which are both reversible within 1 month after discontinuation of hydrocortisone.
Feline Visceral Hemangiosarcoma
Authors: Culp W.T.N. , Drobatz K.J. , Glassman M.M. , Baez J.L. , Aronson L.R.
Published: December 2008

Background:Feline visceral hemangiosarcoma (HSA) is an uncommon tumor, and the clinical progression and outcome are rarely reported.

Hypothesis:The prognosis of feline visceral HSA is poor because of severe clinical signs, anemia, and a high rate of metastasis.

Animals:The medical records of 26 client‐owned cats with visceral HSA were reviewed.

Methods:Multi‐institutional retrospective study.

Results:The most common historical findings and clinical signs included lethargy, anorexia, respiratory difficulty, collapse, and vocalizing. Eighty‐two percent of cats were anemic, and aspartate transaminase was increased in 53% of the study population. Metastatic lung disease was noted in 33% of affected cats. In 75% of the cats, abdominal ultrasonography identified a specific location of HSA. However, ultrasound identification of all multifocal lesions was successful only in 3/9 cats (33%). Tumor location was identified in the following organs: liver (35%), small intestine (31%), large intestine (31%), abdominal lymph node (31%), mesentery (27%), spleen (23%), lung (19%), omentum (12%), brain (8%), pancreas (8%), and diaphragm (8%). Multifocal HSA was noted in 77% of cats. Three cats received adjuvant chemotherapy (doxorubicin). Seventy‐one percent of euthanized cats were euthanized within 1 day of diagnosis. The median survival time of the remaining cats (n = 6) was 77 days (range, 23–296 days).

Conclusion and Clinical Importance:Feline visceral HSA is most often multifocal at the time of diagnosis. The prognosis appears poor, and the number of cats receiving chemotherapy is low.
Portal Vein Thrombosis in Cats: 6 Cases (2001–2006)
Authors: Rogers C.L. , O'Toole T.E. , Keating J.H. , Penninck D.G. , Webster C.R.L.
Published: December 2008

Background: Portal vein thrombosis (PVT) in cats is sparsely reported.

Purpose of Study: To evaluate the clinical signs and diseases associated with PVT in cats.

Animals: 6 client‐owned cats.

Methods: Medical records for cats with a portal vein thrombus diagnosed on abdominal ultrasound or at necropsy were reviewed. Signalment, historical data, underlying disorders, clinical findings, clinicopathologic and histopathologic data, diagnostic imaging findings, treatment, and outcome were recorded.

Results: All 6 cats identified with PVT also had hepatic disease. Evidence of a congenital portosystemic shunt was present in 3/6 cats. Two cats had primary or metastatic hepatic neoplasia. One cat had acute cholangitis, acute pancreatitis, and locally extensive acute centrilobular hepatic necrosis. Two cats were suspected to have acute thrombi and 4 cats had chronic thrombi.

Conclusion and Clinical Significance: PVT might be an important concurrent finding in cats with hepatic disease.
Thromboelastographic Tracings in Retired Racing Greyhounds and in Non‐Greyhound Dogs
Authors: Vilar P. , Couto C.G. , Westendorf N. , Iazbik C. , Charske J. , Marín L.
Published: December 2008

Background:Bleeding disorders in patients with normal coagulation test results are frequently reported in Greyhounds. The purpose of this study was to compare Greyhounds to non‐Greyhounds by thromboelastography (TEG).

Hypothesis:TEG parameters in Greyhounds are different from those in non‐Greyhounds.

Animals:Forty‐three healthy dogs (28 Greyhounds and 15 non‐Greyhounds) based on the results of physical examination, CBC, activated partial thromboplastin time, prothrombin time, fibrinogen, and platelet count.

Materials and Methods:Recalcified citrated native TEGs were performed in both groups; data were compared using Student's, Mann‐Whitney, and Pearson's statistical tests.

Results:In Greyhounds, mean ± SD were as follows: R‐time 4.3 ± 1.7 minutes, K‐time 3.8 ± 1.4 minutes, angle (α) 50.0 ± 8.0°, maximum amplitude (MA) 47.6 ± 5.6 mm, clot strength (G) 4,647 ± 1,097 dyn/cm2, and percent lysis at 60 minutes (LY60) 2.8 ± 5.0%. In the non‐Greyhounds they were R‐time 3.7 ± 1.6 minutes, K‐time 2.5 ± 0.9 minutes, angle 59.8 ± 7.0°, MA 53.1 ± 5.6 mm, G 5,811 ± 1,256 dyn/cm2, and LY60 3.1 ± 2.5%. All parameters were significantly different between the groups, except for R‐time and LY60.

Conclusion:In Greyhounds, clotting kinetics are slower and clot strength are weaker than in non‐Greyhounds, supporting the increased tendency to bleed observed after minor trauma or surgical procedures in the breed. The findings may also be attributed to blood viscosity or to the concentration of citrate in the sample (ie, Greyhounds have higher hematocrit and less plasma per unit volume).
Association of Body Weight and Body Condition with Survival in Dogs with Heart Failure
Authors: Slupe J.L. , Freeman L.M. , Rush J.E.
Published: December 2008

Background:Obesity is a risk factor for cardiovascular disease in people, but overweight and obese human heart failure patients have improved survival compared with normal‐ or underweight controls—the obesity paradox. The purpose of this study was to determine if there is an association of body weight and body condition with survival in dogs with heart failure.

Hypothesis:That body condition and changes in body weight are predictors of survival in dogs with heart failure.

Animals:One hundred and eight dogs with heart failure (International Small Animal Cardiac Health Council stages 2, 3a, or 3b) secondary to dilated cardiomyopathy or chronic valvular disease.

Methods:Medical records were reviewed, and data regarding initial body weight and body condition score (BCS), subsequent changes in body weight, and treatment were collected. Survival times were determined for dogs that were discharged from the hospital and lived >24 hours.

Results:Survival was significantly different between dogs that gained, lost, or maintained body weight over the course of their disease (P= .04), with dogs that gained weight surviving the longest. BCS and medications were not significantly associated with survival time; however, n‐3 fatty acid intake was associated with longer survival time (P= .009).

Conclusions and Clinical Importance:These results suggest that changes in body weight might be an important consideration in the survival of dogs with heart failure.
Mutation in β1‐Tubulin Correlates with Macrothrombocytopenia in Cavalier King Charles Spaniels
Authors: Davis B. , Toivio‐Kinnucan M. , Schuller S. , Boudreaux M.K.
Published: December 2008

Background: Cavalier King Charles Spaniels (CKCS) have a high prevalence of inherited macrothrombocytopenia. The purpose of this study was to determine if a mutation in β1‐tubulin correlated with presumptive inherited macrothrombocytopenia.

Hypothesis: A mutation in β1‐tubulin results in synthesis of an altered β1‐tubulin monomer. α‐β tubulin dimers within microtubule protofilaments are unstable, resulting in altered megakaryocyte proplatelet formation.

Animals: Blood samples were obtained from CKCS and non‐CKCS dogs.

Methods: DNA was used in polymerase chain reaction (PCR) assays to evaluate β1‐tubulin. Platelet numbers and mean platelet volume (MPV) were evaluated for a correlation with the presence or absence of a mutation identified in β1‐tubulin. Platelets obtained from homozygous, heterozygous, and clear CKCS were further evaluated using electron microscopy and immunofluorescence.

Results: A mutation in the gene encoding β1‐tubulin correlated with macrothrombocytopenia in CKCS. Electron microscopy and immunofluorescence studies suggest that platelet microtubules are present but most likely are unstable and decreased in number.

Conclusions and Clinical Importance: The macrothrombocytopenia of CKCS correlated with a mutation in β1‐tubulin. α–β tubulin dimers within protofilaments most likely are unstable, leading to altered proplatelet formation by megakaryocytes. This information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart‐related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation.
Effective and Reduced-Cost Modified Selective Medium for Isolation of
Clostridium difficile
Authors: Nerandzic Michelle M. , Donskey Curtis J.
Published: December 2008

Both for epidemiologic studies and for diagnostic testing, there is a need for effective, economical, and readily available selective media for the culture of
Clostridium difficile
. We have developed a reduced-cost substitute for cycloserine-cefoxitin-fructose agar (CCFA), which is an effective but expensive selective medium for
C. difficile
. The modified medium, called
C. difficile
brucella agar (CDBA), includes an enriched brucella base as a substitute for proteose peptone no. 2, and the concentration of sodium taurocholate has been reduced from 0.1% to 0.05%. To compare the sensitivities and selectivities of CDBA and CCFA, cultures for
C. difficile
were performed using stool samples from patients with C.
difficile
-associated disease. CDBA was as sensitive as CCFA for the recovery of
C. difficile
, with a similar frequency of breakthrough growth of stool microflora (25% versus 31%, respectively). A liquid formulation of the modified medium, termed
C. difficile
brucella broth (CDBB), stimulated rapid germination and outgrowth of
C. difficile
spores, at a rate comparable to that in cycloserine-cefoxitin-fructose broth. Our results suggest that CDBA and CDBB are sensitive, selective, and reduced-cost media for the recovery of
C. difficile
from stool samples.
Rapid Emergence of
emm84
among Invasive
Streptococcus pyogenes
Infections in Finland
Authors: Siljander Tuula , Lyytikäinen Outi , Vähäkuopus Susanna , Säilä Petrus , Jalava Jari , Vuopio-Varkila Jaana
Published: December 2008

From 2005 to 2007, in Finland, the incidence of invasive
Streptococcus pyogenes
disease increased sharply, partly due to the uncommon
emm84
gene becoming more prevalent from 2006 onwards. The overall case fatality rate of infections caused by strains carrying
emm84
was not significantly different than that of infections caused by other types (7% versus 10%, respectively;
P
= 0.50).
Herpes Simplex Virus Replication: Roles of Viral Proteins and Nucleoporins in Capsid-Nucleus Attachment
Authors: Copeland Anna Maria , Newcomb William W. , Brown Jay C.
Published: December 2008

Replication of herpes simplex virus type 1 (HSV-1) involves a step in which a parental capsid docks onto a host nuclear pore complex (NPC). The viral genome then translocates through the nuclear pore into the nucleoplasm, where it is transcribed and replicated to propagate infection. We investigated the roles of viral and cellular proteins in the process of capsid-nucleus attachment. Vero cells were preloaded with antibodies specific for proteins of interest and infected with HSV-1 containing a green fluorescent protein-labeled capsid, and capsids bound to the nuclear surface were quantified by fluorescence microscopy. Results showed that nuclear capsid attachment was attenuated by antibodies specific for the viral tegument protein VP1/2 (UL36 gene) but not by similar antibodies specific for UL37 (a tegument protein), the major capsid protein (VP5), or VP23 (a minor capsid protein). Similar studies with antibodies specific for nucleoporins demonstrated attenuation by antibodies specific for Nup358 but not Nup214. The role of nucleoporins was further investigated with the use of small interfering RNA (siRNA). Capsid attachment to the nucleus was attenuated in cells treated with siRNA specific for either Nup214 or Nup358 but not TPR. The results are interpreted to suggest that VP1/2 is involved in specific attachment to the NPC and/or in migration of capsids to the nuclear surface. Capsids are suggested to attach to the NPC by way of the complex of Nup358 and Nup214, with high-resolution immunofluorescence studies favoring binding to Nup358.
Lower Levels of Gamma Interferon Expressed by a Pseudotyped Single-Cycle Simian Immunodeficiency Virus Enhance Immunogenicity in Rats
Authors: Peng Yue , Lin Fan-ching , Verardi Paulo H. , Jones Leslie A. , Yilma Tilahun D.
Published: December 2008

A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-γ) as a potential vaccine strategy. We previously showed that IFN-γ expression by pseudotyped SIVs does not alter viral single-cycle infectivity. T cells primed with dendritic cells transduced by pseudotyped SIVs expressing high levels of IFN-γ had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-γ. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-γ (dSIVLRγ) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-γ (dSIVR). Rats vaccinated with dSIVLRγalso had lower viral loads than those vaccinated with dSIVRwhen inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-γ (dSIVHRγ) did not further enhance immunity and was less protective than dSIVLRγ. In conclusion, the data indicated that IFN-γ functioned as an adjuvant to augment antigen-specific immune responses in a dose- and cell type-related manner in vivo. Thus, fine-tuning of the cytokine expression appears to be essential in designing vaccine vectors expressing adjuvant genes such as the gene for IFN-γ. Furthermore, we provide evidence of the utility of the rat model to evaluate the immunogenicities of single-cycle HIV/SIV recombinant vaccines before initiating studies with nonhuman primate models.
Role for Plasmacytoid Dendritic Cells in the Immune Control of Recurrent Human Herpes Simplex Virus Infection
Authors: Donaghy Heather , Bosnjak Lidija , Harman Andrew N. , Marsden Valerie , Tyring Stephen K. , Meng Tze-Chiang , Cunningham Anthony L.
Published: December 2008

Plasmacytoid dendritic cells (pDC) are an important component of the innate immune response, producing large amounts of alpha interferon in response to viral stimulation in vitro. Under noninflammatory conditions, pDC are not found in the skin and are restricted in location to the blood and lymph nodes. Therefore, their role in mucosal and cutaneous herpes simplex virus (HSV) infection has not been well-defined. In this study we show a role for human pDC in the immune response to HSV infection. First, by confocal microscopy we showed that pDC infiltrate the dermis of recurrent genital herpes simplex lesions at early and late phases, often at the dermo-epidermal junction. We then showed that pDC in vitro are resistant to HSV infection despite expressing the entry receptors CD111, CD112, and HVE-A. Within the lesions, pDC were found closely associated with CD3+lymphocytes and NK cells, especially those which were activated (CD69+). Furthermore, these HSV-exposed pDC were able to stimulate virus-specific autologous T-lymphocyte proliferation. We conclude from this work that pDC may contribute to the immune control of recurrent herpes virus infection in vivo.
Reevaluating the CD8 T-Cell Response to Herpes Simplex Virus Type 1: Involvement of CD8 T Cells Reactive to Subdominant Epitopes
Authors: Sheridan Brian S. , Cherpes Thomas L. , Urban Julie , Kalinski Pawel , Hendricks Robert L.
Published: December 2008

In C57BL/6 (B6) mice, most herpes simplex virus (HSV)-specific CD8 T cells recognize a strongly immunodominant epitope on glycoprotein B (gB498) and can inhibit HSV type 1 (HSV-1) reactivation from latency in trigeminal ganglia (TG). However, half of the CD8 T cells retained in latently infected TG of B6 mice are not gB498specific and have been largely ignored. The following observations from our current study indicate that these gB498-nonspecific CD8 T cells are HSV specific and may contribute to the control of HSV-1 latency. First, following corneal infection, OVA257-specific OT-1 CD8 T cells do not infiltrate the infected TG unless mice are simultaneously immunized with OVA257peptide, and then they are not retained. Second, 30% of CD8 T cells in acutely infected TG that produce gamma interferon in response to HSV-1 stimulation directly ex vivo are gB498nonspecific, and these cells maintain an activation phenotype during viral latency. Finally, gB498-nonspecific CD8 T cells are expanded in ex vivo cultures of latently infected TG and inhibit HSV-1 reactivation from latency in the absence of gB498-specific CD8 T cells. We conclude that many of the CD8 T cells that infiltrate and are retained in infected TG are HSV specific and potentially contribute to maintenance of HSV-1 latency. Identification of the viral proteins recognized by these cells will contribute to a better understanding of the dynamics of HSV-1 latency.
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection
Authors: Miron Marie-Joëlle , Blanchette Paola , Groitl Peter , Dallaire Frederic , Teodoro Jose G. , Li Suiyang , Dobner Thomas , Branton Philip E.
Published: December 2008

The human adenovirus type 5 (Ad5) E4orf4 product has been studied extensively although in most cases as expressed from vectors in the absence of other viral products. Thus, relatively little is known about its role in the context of an adenovirus infection. Although considerable earlier work had indicated that the E4orf4 protein is not essential for replication, a recent study using
dl
359, an Ad5 mutant believed to produce a nonfunctional E4orf4 protein, suggested that E4orf4 is essential for virus growth in primary small-airway epithelial cells (C. O'Shea, et al., EMBO J. 24:1211-1221, 2005). Hence, to examine further the role of E4orf4 during virus infection, we generated for the first time a set of E4orf4 virus mutants in a common Ad5 genetic background. Such mutant viruses included those that express E4orf4 proteins containing various individual point mutations, those defective entirely in E4orf4 expression, and a mutant expressing wild-type E4orf4 fused to the green fluorescent protein. E4orf4 protein was found to localize primarily in nuclear structures shown to be viral replication centers, in nucleoli, and in perinuclear bodies. Importantly, E4orf4 was shown not to be essential for virus growth in either human tumor or primary cells, at least in tissue culture. Unlike E4orf4-null virus, mutant
dl
359 appeared to exhibit a gain-of-function phenotype that impairs virus growth. The
dl
359 E4orf4 protein, which contains a large in-frame internal deletion, clustered in aggregates enriched in Hsp70 and proteasome components. In addition, the late viral mRNAs produced by
dl
359 accumulated abnormally in a nuclear punctate pattern. Altogether, our results indicate that E4orf4 protein is not essential for virus growth in culture and that expression of the
dl
359 E4orf4 product interferes with viral replication, presumably through interactions with structures in the nucleus.
Epstein-Barr Virus Episome Stability Is Coupled to a Delay in Replication Timing
Authors: Zhou Jing , Snyder Andrew R. , Lieberman Paul M.
Published: December 2008

The temporal regulation of DNA replication is thought to be important for chromosome organization and genome stability. We show here that Epstein-Barr virus (EBV) genomes replicate in mid- to late S phase and that agents that accelerate replication timing of EBV reduce viral genome stability. Hydroxyurea (HU) treatment, which is known to eliminate EBV episomes, shifted EBV replication to earlier times in the cell cycle. HU treatment correlated with hyperacetylation of histone H3 and loss of telomere repeat factor 2 (TRF2) binding at the EBV origin of plasmid replication (
OriP
). Deletion of TRF2 binding sites within
OriP
or short hairpin RNA depletion of TRF2 advanced the replication timing of
OriP-
containing plasmids. Inhibitors of class I histone deacetylases (HDACs) increased histone acetylation at
OriP
, advanced the replication timing of EBV, and reduced EBV genome copy number. We also show that HDAC1 and -2 form a stable complex with TRF2 at OriP and that HU treatment inhibits HDAC activity. We propose that the TRF2-HDAC complex enhances EBV episome stability by providing a checkpoint that delays replication initiation at OriP.