Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy

BACKGROUND: Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. AIM: The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. ANIMALS: Eighteen client-owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. METHODS: PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. RESULTS: No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1-year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 +/-87.1) days. CONCLUSIONS AND CLINICAL IMPORTANCE: A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.     

Evaluation of electroacupuncture treatment for thoracolumbar intervertebral disk disease in dogs

OBJECTIVE: To evaluate use of electroacupuncture combined with standard Western medical treatment versus Western medical treatment alone for treatment of thoracolumbar intervertebral disk disease in dogs. DESIGN: Prospective controlled study. ANIMALS: 50 dogs with signs of thoracolumbar intervertebral disk disease. PROCEDURES: Dogs were randomly allocated to 1 of 2 treatment groups and classified as having grade 1 to 5 neurologic dysfunction. Dogs in group 1 received electroacupuncture stimulation combined with standard Western medical treatment; those in group 2 received only standard Western medical treatment. A numeric score for neurologic function was evaluated at 4 time points to evaluate effects of treatments. RESULTS: Time (mean +/- SD) to recover ambulation in dogs with grade 3 and 4 dysfunction in group 1 (10.10 +/- 6.49 days) was significantly lower than in group 2 (20.83 +/- 11.99 days). Success (able to walk without assistance) rate for dogs with grade 3 and 4 dysfunction in group 1 (10/10 dogs) was significantly higher than that of similarly affected dogs in group 2 (6/9 dogs). Dogs without deep pain perception (grade 5 dysfunction) had a success (recovery of pain sensation) rate of 3 of 6 and 1 of 8 in groups 1 and 2, respectively, but the difference was not significant. Overall success rate (all dysfunction grades) for group 1 (23/26; 88.5%) was significantly higher than for group 2 (14/24; 58.3%). CONCLUSIONS AND CLINICAL RELEVANCE: Electroacupuncture combined with standard Western medical treatment was effective and resulted in shorter time to recover ambulation and deep pain perception than did use of Western treatment alone in dogs with signs of thoracolumbar intervertebral disk disease.     

The Effects of Selenium Source on Measures of Selenium Status of Mares and Selenium Status and Immune Function of Their Foals

The effect of organic and inorganic sources of selenium (Se) on measures of Se status of mares and their foals, Se concentrations of colostrum and milk, and indices of immune function of foals was studied. Twenty late-gestation Standardbred mares were randomly assigned to one of two groups. All mares received an identical balanced ration, except for the source of supplementary Se: one group received organic Se (Se yeast) and the other group received inorganic Se (sodium selenite), fed to deliver 0.3 mg/kg supplementary Se based on total ration dry matter. Mares received the experimental diet from 2 months before estimated due date until 1 month after foaling. Source of Se did not affect Se concentrations in maternal plasma, red blood cells, colostrum, or milk. At 1 month of age, foals from mares fed organic Se had higher red blood cell Se concentration than foals from mares fed inorganic Se (P < .05). Measures of immunity included serum immunoglobulin G concentration, lymphocyte proliferation in response to concanavalin A, and relative cytokine gene expression of stimulated lymphocytes (interferon gamma [IFNγ], interleukin [IL]-2, IL-5, IL-10, tumor necrosis factor alpha [TNFα]) and neutrophils (IL-1, IL-6, IL-8, IL-12, TNFα). Relative gene expression of IL-2, TNFα, and IFNγ by foal lymphocytes was associated with the source of Se supplementation provided to the mares. We conclude that the source of dietary Se provided to mares may influence the immune function of foals at 1 month of age through changes in relative gene expression of certain lymphocyte cytokines.     

A longitudinal study of Neospora caninum infection on three dairy farms in Brazil

Neospora caninum is an apicomplexan protozoan parasite that is one of the most important infectious causes of abortion in both dairy and beef cattle in many countries. The objectives of this longitudinal study were to determine the prevalence, rates of vertical and horizontal transmission of N. caninum and hazard for culling of N. caninum-seropositive animals in three Brazilian dairy herds. Blood samples from all animals were collected nine times at each of the three farms over a two-year period. Serum was tested for antibodies against N. caninum using the indirect fluorescent antibody test with a cutoff value of 1:100. The percentage of N. caninum-positive samples at each sampling time ranged at Farm I from 3.32% to 11.71%, at Farm II from 3.90% to 22.06% and at Farm III from 3.90% to 22.06%. The number of positive serological reactions varied in relation to the number of repeated samples taken from individual animals at each farm. In all herds, there was a high degree (P<0.05) of association between the N. caninum serological status of dams and daughters. The seropositive conversion rate was estimated as 0.37%, 3.00% and 6.94% per 100 cow-years at Farms I, II and III, respectively. The seronegative conversion rate was estimated as 31.58% and 11.11% per 100 cow-years at Farms I and III, respectively. In all herds, there was no difference (P>0.05) in the culling rate between the cattle that were seropositive cattle and seronegative for N. caninum infection. The results from this study confirm the importance of vertical transmission in the epidemiology of N. caninum. Although a few positive seroconversions indicated horizontal transmission, it does not appear to be the major route of infection for N. caninum.     

Factors associated with gastrointestinal parasite infection in dogs in Rio de Janeiro, Brazil

Factors associated with parasitism by helminths and protozoans in 500 dogs presented to three veterinary clinics in the municipality of Rio de Janeiro from November 2003 to September 2004 were evaluated. Dogs were submitted to physical examination and owners were interviewed about the animal's management. One fecal sample from each dog was examined by centrifugal flotation and sedimentation methods followed by the safranin–methylene blue staining technique. Positive results for gastrointestinal parasites were detected in 46.4% of the examined samples. Infection with protozoans (29.6%) was more frequent than with helminths (23.2%). Cryptosporidium sp. (26.2%) and Ancylostoma sp. (15.2%) were the most frequent parasites. Logistic regression analysis showed that age (p < 0.001), access to soil (p < 0.001), hygiene of the environment (p = 0.001), illness (p = 0.007), owner's level of education (p < 0.006) and veterinary clinic (p = 0.043) were associated with gastrointestinal parasite infections in dogs. Treatment and control are especially important for puppies. Adult dogs should be submitted to fecal examination before treatment, placing special emphasis on those that present one or more factors associated with infection.     

Variation in E(rns) viral glycoprotein associated with failure of immunohistochemistry and commercial antigen capture ELISA to detect a field strain of bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) affects cattle populations causing clinical signs that range from subclinical immunosuppression to severe reproductive and respiratory problems. Detection and removal of persistently infected (PI) calves is the single most important factor for control and eradication of BVDV. Current testing strategies to detect PI calves rely heavily on immunohistochemistry (IHC) and a commercially available antigen capture ELISA (ACE) assay. These viral assays depend on 1 or 2 monoclonal antibodies which target the E(rns) glycoprotein of BVDV. The sensitivity and specificity of these two tests have been reported previously. The purpose of this research was to characterize a strain of BVDV (AU501) that was undetectable using IHC and ACE based on a single monoclonal antibody, but was consistently detected in samples from a Holstein steer using virus isolation and PCR testing. Sequencing of this AU501 viral isolate revealed a unique mutation in the portion of the genome coding for the E(rns) glycoprotein. This unique field strain of BVDV demonstrates the risk of relying on a single monoclonal antibody for detection of BVDV. Multiple testing strategies, including polyclonal or pooled monoclonal antibodies that detect more than one viral glycoprotein may be necessary to detect all PI calves and facilitate eradication of BVDV.     

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) progress to date and future plans

The INHAND Proposal (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) has been operational since 2005. A Global Editorial Steering Committee (GESC) manages the overall objectives of the project and the development of harmonized terminology for each organ system is the responsibility of the Organ Working Groups (OWG), drawing upon experts from North America, Europe and Japan.Great progress has been made with 9 systems published to date – Respiratory, Hepatobiliary, Urinary, Central/Peripheral Nervous Systems, Male Reproductive and Mammary, Zymbals, Clitoral and Preputial Glands in Toxicologic Pathology and the Integument and Soft Tissue and Female Reproductive System in the Journal of Toxicologic Pathology as supplements and on a web site – www.goreni.org. INHAND nomenclature guides offer diagnostic criteria and guidelines for recording lesions observed in rodent toxicity and carcinogenicity studies. The guides provide representative photo-micrographs of morphologic changes, information regarding pathogenesis, and key references. During 2012, INHAND GESC representatives attended meetings with representatives of the FDA Center for Drug Evaluation and Research (CDER), Clinical Data Interchange Standards Consortium (CDISC), and the National Cancer Institute (NCI) Enterprise Vocabulary Services (EVS) to begin incorporation of INHAND terminology as preferred terminology for SEND (Standard for Exchange of Nonclinical Data) submissions to the FDA. The interest in utilizing the INHAND nomenclature, based on input from industry and government toxicologists as well as information technology specialists, suggests that there will be wide acceptance of this nomenclature. The purpose of this publication is to provide an update on the progress of INHAND.