Evaluation of adverse reactions in dogs following intravenous mesenchymal stem cell transplantation

Background

Recent studies have assessed the therapeutic potential and drawbacks of mesenchymal stem cells (MSCs). The adverse reactions of intravenous transplantation of bone marrow (BM)-derived MSCs were examined at varying doses and frequencies of administration.Nine healthy beagle dogs were purchased from a commercial laboratory. The dogs were distributed equally (n = 3 per group) and randomly into three groups. All dogs received allogeneic BM-derived MSCs: 2 × 10⁶ once (group A), 2 × 10⁷ once (group B), and 2 × 10⁶ for three consecutive days (group C). Various laboratory examinations, multi-detector computed tomography features and histopathology were evaluated to clarify the clinical and diagnostic features of adverse reactions of MSCs administration, prior to receiving MSCs (pre procedure) and on days 1, 3, and 7 post transplantation.

Results

Only one dog had clinical signs during and after MSCs transplantation. Dogs receiving 2 × 10⁶ MSCs showed increased numbers of lymphocytes but the total white blood cell counts were not elevated (P < 0.01). Multi-detector computed tomography (MDCT) revealed pulmonary parenchymal changes in one dog and histopathologic examination revealed pulmonary parenchymal edema and hemorrhage in four dogs. The presence of pulmonary thromboembolism was not detected in either examination.

Conclusions

We considered the presence of pulmonary edema and hemorrhage as possible adverse reactions after intravenous MSCs transplantation; however these results should be cautiously interpreted.     

Comparison of response to immunotherapy by intradermal skin test and antigen-specific IgE in canine atopy

The intradermal skin test (IDST) and serologic allergy test (SAT) has been developed for confirming a diagnosis of canine atopy and determining allergens for immunotherapy. To determine the prevalence of causative allergens for canine atopic dermatitis in Japan, IDST and SAT were performed with the CMG Immunodot strips on 95 atopic dogs using 9 allergens. In addition, we compared agreement rate, sensitivity and specificity between them (using IDST as the standard). The allergen most commonly positive in both tests was house dust mites (IDST: 69.5%, SAT: 48.4%). Moreover, Japanese cedar, mugwort and grass mix were detected as attendant causative allergens. Agreement rates between the two tests ranged from 67.4% to 96.8%; the overall mean agreement rate were 81%. SAT was shown to have sensitivity to IDST ranging from 16.7 to 68.2%. The specificities were very high for all allergens, on the order of 94.9-100% (median=98.7%). Finally, the efficacy of immunotherapy was evaluated on 27 atopic dogs based on IDST (15 dogs) and SAT (12 dogs) results. Overall, 60% (9/15) of the IDST group and 66.8% (8/12) of the SAT group experienced a 50% to 100% reduction in their symptomatology. No significant differences were found in response to immunotherapy during the follow-up period between allergen selection methods. These results indicate the value of serologic tests as an aid to identifying an allergen solution for immunotherapy.     

Development of a multiplex PCR assay to detect Edwardsiella tarda,Streptococcus parauberis,and Streptococcus iniae in olive flounder (Paralichthys olivaceus)

A multiplex PCR protocol was established to simultaneously detect major bacterial pathogens in olive flounder (Paralichthys olivaceus) including Edwardsiella (E.) tarda, Streptococcus (S.) parauberis, and S. iniae. The PCR assay was able to detect 0.01 ng of E. tarda, 0.1 ng of S. parauberis, and 1 ng of S. iniae genomic DNA. Furthermore, this technique was found to have high specificity when tested with related bacterial species. This method represents a cheaper, faster, and reliable alternative for identifying major bacterial pathogens in olive flounder, the most important farmed fish in Korea.     

Cutaneous Serratia marcescens infection in two dogs

We describe two canine cases of cutaneous infection caused by Serratia marcescens. A 2-year-old castrated male mixed dog (Case 1) presented with multiple ulcerations on the dorsal trunk, which were observed 4 days after shampooing. A 4-year-old male wolf shepherd mix dog (Case 2) presented with ulceration and purulent discharge on the nasal bridge. Cytological examination of both cases revealed pyogranulomatous inflammatory cells with rod-like infectious agents identified as S. marcescens in aerobic bacterial culture. Both patients were treated with oral antibiotics and topical chlorhexidine. Case 1 received enrofloxacin 10 mg/kg once daily for 1 week, followed by trimethoprim/sulfamethoxazole 15 mg/kg twice daily for 3 weeks. Case 2 received doxycycline 10 mg/kg twice daily for 4 weeks. No skin lesions were detected 2 weeks after the initial administration. The antibiotics were discontinued after a total 4 weeks of administration, and the skin lesions did not reappear.     

Farmers' attitudes towards techniques for improving oestrus detection in dairy herds in South West England

Unidentified heats contribute to declining fertility rates in English dairy herds. Several techniques have been advocated to improve heat detection rates. Despite demonstrable technical efficacy and cost-effectiveness, uptake is low. A study in South West England used the Theory of Reasoned Action (TORA) to explore dairy farmers' attitudes and beliefs towards heat detection techniques. Few farmers were convinced that following prescribed observation times, milk progesterone testing and using pedometers would fit their system or improve on their current heat detection practices. Perceived difficulty of using a technique was not a constraint on adoption. Without promotion that addresses identified barriers and drivers to adoption, little change in current practice can be expected.     

Electrically driven single-cell photonic crystal laser

We report the experimental demonstration of an electrically driven, single-mode, low threshold current (approximately 260 microA) photonic band gap laser operating at room temperature. The electrical current pulse is injected through a sub-micrometer-sized semiconductor wire at the center of the mode with minimal degradation of the quality factor. The actual mode of interest operates in a nondegenerate monopole mode, as evidenced through the comparison of the measurement with the computation based on the actual fabricated structural parameters. As a small step toward a thresholdless laser or a single photon source, this wavelength-size photonic crystal laser may be of interest to photonic crystals, cavity quantum electrodynamics, and quantum information communities.     

Pathogenicity characterization of a bovine triple reassortant rotavirus in calves and piglets

Rotaviruses are important human and animal pathogens with high impact on public health and livestock industry. There is little evidence about the cross-species pathogenicity and extra-intestinal infections of animal and human reassortant rotaviruses, particularly based on all 11 genotyping data. In this study, the bovine triple reassortant KJ56-1 strain harboring two bovine-like genome segments, eight porcine-like genome segments, and one human-like genome segment was used to evaluate the cross-species pathogenicity in its parent species, calves and piglets, and to determine its abilities of causing viremia and extra-intestinal tropisms in piglets. The KJ56-1 strain isolated from a calf diarrhea fecal sample replicated without causing diarrhea and severe intestinal pathology in calves. However, piglets inoculated with this strain showed persistent severe diarrhea and marked intestinal pathology. By SYBR Green real-time RT-PCR, viral RNA was detected in the sera, mesenteric lymph node, lung, liver, choroid plexus, and cerebrospinal fluid in the experimental piglets. An immunofluorescence assay confirmed viral replication in these extra-intestinal organs and tissues. These results indicated that the bovine triple reassortant KJ56-1 strain was virulent to piglets but not to calves. Our data also demonstrated that the reassortant rotaviruses had the ability to spread to the bloodstream from the gut, enter and amplify in the mesenteric lymph node, and disseminate to the extra-intestinal organs and tissues.     

Therapeutic trial of granulocyte-colony stimulating factor for dilated cardiomyopathy in three dogs

Three dogs were presented to us for evaluation of cardiac problems. Electrocardiographic recordings revealed severe tachyarrhythmia and atrial fibrillation with ventricular tachycardia in 2 of the 3 dogs. The echocardiographic findings of the 3 dogs revealed markedly decreased fractional shortening and a marked increase in E-point septal separation. Based on the results of electrocardiographic and echocardiographic evaluation, the 3 dogs were diagnosed as dilated cardiomyopathy (DCM). The dogs were treated with conventional cardiac medication, but cardiac function did not improve and the clinical signs remained. We subsequently attempted treatment with granulocyte-colony stimulating factor (G-CSF; 10 microg/kg, subcutaneously). The specific purpose of G-CSF therapy for DCM was to improve cardiac function and a significant improvement in cardiac function was confirmed. The three dogs had no treatment side effects. This case report suggests that G-CSF might have therapeutic effects for medically refractory DCM in dogs.