Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs.

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 µg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 µg/kg intravenously for 10 min), followed by CRI at 40 µg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 µg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 µg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Case Report: Ultrasonography and Magnetic Resonance Imaging of Anterior Segment Dysgenesis in a Calf.

This study includes diagnostic efficacy of the antemortem, combined use of ultrasonography and magnetic resonance imaging (MRI) for the diagnosis of anterior segment dysgenesis. A 7-day-old male Holstein calf presented with progressive unilateral exophthalmos associated with enlargement of the right eyeball soon after birth. Ultrasonography of the enlarged right eyeball showed (1) a 2-cm-thick echogenic parenchymal lesion filling the anterior region of the right eyeball, (2) excess accumulation of the anechoic vitreous humor, and (3) absence of the lens structure. Antemortem examination using T2-weighted and fluid-attenuated inversion recovery MRI revealed a thickened, hyperintense anterior lesion and absence of the lens structure. These imaging findings were suggestive of anterior segment dysgenesis. Antemortem imaging showed no abnormalities other than the abnormal structure and size of the right eyeball; therefore, enucleation of the right eye was performed, which allowed intact healing without suppuration. Ocular ultrasonography enhanced the diagnostic accuracy due to the characteristic ultrasonographic findings of a thickened anterior lesion and absence of the lens structure in the eyeball, suggestive of anterior segment dysgenesis.

Imaging findings and outcomes after traumatic cerebellar injury: a canine case report.

BACKGROUND: Traumatic brain injury (TBI) is a structural injury or physiological disruption of the brain induced by an external force. The cerebellum facilitates movement coordination and provides a sense of equilibrium; damage to this structure can cause a wide variety of symptoms, including ataxia or dystaxia, ocular motor dysfunction, and disequilibrium. TBIs localised to the cerebellum are rare in dogs, and the prognosis following this type of injury remains unclear. CASE PRESENTATION: A 10-year-old female Chihuahua/Dachshund-cross dog weighing 2.8 kg presented after a fall of approximately 1 m the preceding night. The dog exhibited paresis of all limbs and was recumbent with constant extensor rigidity with opisthotonos. The bilateral thoracic limb and right pelvic limb spinal reflexes were exaggerated, while the left pelvic limb spinal reflexes were normal. The menace response was decreased, and vertical nystagmus was observed. Magnetic resonance imaging (MRI) revealed a hyperintense lesion on T2weighted (W) images, fluid-attenuated inversion recovery, and diffusion-weighted imaging (DWI). Mannitol and prednisolone were administered, and the dog recovered. The bilateral pelvic limb postural reactions improved by Day 16. On Day 22, MRI revealed a decrease in the hyperintense area of the T2W images, and this lesion appeared isointense on DWI. CONCLUSIONS: In this case report, a dog with localised injury to the cerebellum that comprised a post-tentorial lesion recovered with a favourable outcome. Moreover, similar to reports in humans, DWI can help diagnose and evaluate TBI in dogs.

Detection of squamous cell carcinoma of presumed pancreatic origin and its metastasis in a spotted seal (Phoca largha) using ultrasonography and computed tomography.

A 21-year-old female spotted seal (Phoca largha), with a swollen abdomen, had a five-month history of anorexia and vomiting. Ultrasonography revealed an extended mass with central necrotic foci in the right cranial abdomen. Computed tomography revealed an abdominal mass with a low-density central lumen and a pulmonary nodular lesion. Cytology of an abdominal specimen collected through fine-needle aspiration indicated a malignant tumor with round, atypical cells with large nuclei. Three days after diagnosis, necropsy revealed a 10-cm large, solid, whitish mass in the pancreatic parenchyma and multiple small nodules in the liver, spleen, mesentery, lungs, and mediastinal lymph nodes. Histopathological analysis showed prolific neoplastic cells with marked atypia and occasional keratinization. Immunohistochemistry revealed that the neoplastic cells were positive for cytokeratin AE1/AE3 antibody. Thus, the seal was diagnosed with squamous cell carcinoma, of presumed pancreatic origin, which had metastasized to multiple organs.

Genetic Characterization of CTX-M-2-Producing Klebsiella pneumoniae and Klebsiella oxytoca Associated With Bovine Mastitis in Japan.

CTX-M-2-producing Klebsiella oxytoca (K. oxytoca) has not received much attention in animal husbandry compared with Klebsiella pneumoniae (K. pneumoniae), a major reservoir of extended-spectrum ß-lactamase (ESBL) genes. Bacteriological examinations of 1,466 mastitic milk samples between October 2012 and December 2014 were conducted. Ninety-five K. pneumoniae isolates (total prevalence: 6.5%) and 81 K. oxytoca isolates (total prevalence: 5.5%) were obtained. Seventeen K. pneumoniae isolates obtained from 15 animals reared on 11 farms and 9 K. oxytoca isolates obtained from 9 animals reared on the same farm were phenotypically confirmed to be ESBL producers. All nine ESBL-producing K. oxytoca isolates were obtained from one farm between June and November 2013 and related to a significantly (p < 0.05) higher monthly prevalence of mild mastitis (in June, August, September, October, and November 2013). Pulsed-field gel electrophoresis (PFGE) patterns of ESBL-producing K. pneumoniae isolates were distinguished from each other by more than 6-band differences except for two isolates from two animals, whereas all nine K. oxytoca isolates showed an identical PFGE pattern. Transferability of the bla CTX-M-2 gene was found in 14 K. pneumoniae and 9 K. oxytoca isolates by conjugation analysis. Of these isolates, the bla CTX-M-2 gene was detected on plasmids belonging to the incompatibility (Inc) groups P and N derived from five K. pneumoniae and nine K. oxytoca isolates, respectively, although the plasmids from the remaining nine K. pneumoniae were untypeable. All the transconjugants exhibited elevated minimum inhibitory concentrations of ampicillin, cefotaxime, and ceftiofur compared with those in the wild-type, recipient strain. Restriction fragment length polymorphism analysis demonstrated that the IncN plasmids extracted from eight of nine transconjugants, which received resistance against ß-lactams from K. oxytoca, showed an identical DraI digestion pattern. These results suggest that the CTX-M-2-producing K. oxytoca strain with the above-mentioned characteristics may have clonally spread within a farm, whereas the bla CTX-M-2 gene in K. pneumoniae possibly disseminated among the farms through different plasmids. Thus, monitoring of ESBL genes, including the bla CTX-M-2 gene, among causative agents of bacterial mastitis in cows can help to develop relevant treatments and control practices.

Cardiovascular and renal effects of constant rate infusions of remifentanil, dexmedetomidine and their combination in dogs anesthetized with sevoflurane.

We evaluated changes in cardiovascular and renal functions as well as arginine vasopressin (AVP) secretion, with remifentanil and dexmedetomidine administration alone or in combination in sevoflurane-anesthetized dogs. Six healthy adult Beagle dogs received one of the following four treatments in a randomized crossover study: saline (C), remifentanil alone at successively increasing doses (R; 0.15, 0.60, and 2.40 µg/kg/min), dexmedetomidine alone (D; 0.5 µg/kg intravenously for initial 10 min followed by a constant rate infusion at 0.5 µg/kg/hr), and a combination of remifentanil and dexmedetomidine at the above-mentioned doses (RD). Sevoflurane doses were adjusted to 1.5 times of minimum alveolar concentration (MAC) equivalent according to MAC-sparing effects with remifentanil and dexmedetomidine as previously reported. Cardiovascular measurements, renal function data, and plasma AVP concentrations were determined before and every 60 min until 180 min after drug administration as per each treatment. In the R, D and RD, heart rate significantly decreased and mean arterial pressure significantly increased from baseline or with C. Cardiac index significantly decreased and systemic vascular resistance index increased with D and RD. Oxygen extraction ratio, renal blood flow, and glomerular filtration rate were not affected. The plasma AVP concentrations significantly decreased in D and RD, but increased in R. Only in D, the natriuresis was elicited. The combination of remifentanil and dexmedetomidine in sevoflurane-anesthetized dogs was acceptable in terms of the hemodynamics, oxygenation, and renal function. Remifentanil may interfere with dexmedetomidine-induced diuresis and inhibition of AVP secretion.

Triple nostrils in a calf.

BACKGROUND: Nasal abnormalities are rare in bovines. In humans, nasal deformities are mainly classified as proboscis lateralis or supernumerary nostrils. This report discusses the etiology of triple nostrils in a calf, based on computed tomography, magnetic resonance imaging, and endoscopy. CASE PRESENTATION: A female Holstein calf presented with triple nostrils. The following abnormalities were observed: (1) formation of a small and flat blind-ended middle nostril between the right and left nostrils; (2) presence of a hair-bearing surface on the muzzle; (3) abnormal curvature of the nasal septum, resulting in a narrower right nasal cavity due to transformation of the nasal bones; and (4) formation of a bone-like structure within the nasal septum. These findings were similar to those of supernumerary nostrils in humans. CONCLUSIONS: To the best of our knowledge, this represents the first description of a calf with triple nostrils. The use of imaging modalities is necessary for investigating the etiology of triple nostrils.

Photohyperthermal therapy using liposomally formulated indocyanine green for feline nasal lymphoma: A case report.

Our previous research has focused on the development of a novel cancer therapy by using photohyperthermal therapy (PHT) with indocyanine green (ICG) as an optical sensitizer. ICG-Lipo is a liposomally formulated ICG derivative in which ICG is tagged with an octadeca-alkyl chain to incorporate into liposome bilayers, and contains antitumor drugs such as carboplatin and paclitaxel within the inner membrane space. The present study reported a case of feline nasal lymphoma that was treated with combination therapy of PHT with ICG-Lipo. An antitumour effect was observed, and the patient entered remission. Complications from the radiation treatment included skin burns and bleeding from the irradiated hard palate. Serious side effects related to the drugs were not observed. This report suggested that PHT using ICG-Lipo enabled efficient and safe treatment of lymphoma, and that treatment with a liposomal drug delivery system was enhanced by PHT.

Ultrasonography of sudden swollen tongue in a calf.

BACKGROUND: In cattle, the lingual diseases are primarily diagnosed postmortem by histopathological examination of the affected tongues obtained after the death or during necropsy. In humans, ultrasonography has been used to provide differential diagnoses, and for preoperative or intraoperative planning of glossectomy in various lingual diseases. This is a bovine clinical case report, in which ultrasonography for sudden swelling of the tongue, which was possibly caused by snake bite, was utilized as a preoperative indication to perform a glossectomy. CASE PRESENTATION: An eight-month-old female Japanese black calf presented with sudden swelling of the tongue with well-defined discoloration in the cranial region. A 10-MHz linear probe on a portable-type ultrasound machine (MyLabOne VET, Esaote Co., Genova, Italy) was applied to the ventral surface of the tongues in the affected case, and also in five healthy calves under sedation to observe normal tongues. Ultrasonography of the swollen tongue in this case revealed that the ventral lingual muscular layers were severely thickened compared with those of normal tongues. However, the muscle layers were regularly aligned with the echogenic muscular fibers. This resembled the lingual muscular architectures of normal tongues. Color-flow Doppler ultrasonography revealed that blood flow was weakened in the small peripheral vessels in the spaces between the lingual muscular structures, and was lacking in the deep lingual artery between the apex and base of the tongue. This finding was very different than that of normal tongues, which exhibited weakened or rich blood flows. Based on ultrasonographic findings, this case was treated with glossectomy. After recovery, the calf grew up normally with a normal appetite and rumination, and did not exhibit mouth pain behavior. Histopathologically, hemorrhagic necrotic changes, together with focal formation of fibrin thrombus in the lingual blood vessels in the affected tongue, were noted. CONCLUSIONS: To the best of our knowledge, the present report is the first description of lingual ultrasonography performed in cattle. In this case, ultrasonography enabled visualization of decreased vascularity, which might be associated with hemorrhage or formation of fibrin thrombus in the suddenly swollen tongue presented.

Effects of constant rate infusions of dexmedetomidine, remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg. METHODS: Anesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg-1 hour-1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 µg kg-1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 µg kg-1 hour-1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 µg kg-1 minute-1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 µg kg-1 hour-1, obtained using log-linear regression analysis. RESULTS: The sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline-remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 µg kg-1 hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: Combined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.

Photodynamic detection of a feline meningioma using 5-aminolaevulinic acid hydrochloride.

CASE SUMMARY: The present study describes the case of a feline meningioma that was detected using 5-aminolaevulinic acid hydrochloride (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence at surgery. An extra-axial mass in the temporoparietal region was observed by MRI. Following craniectomy and durotomy, photodynamic detection (PDD) was performed for detection of the tumour. Intratumour PpIX was detected using fluorescence spectrum evaluation and high-performance liquid chromatography. PDD revealed bright fluorescence of PpIX induced by 5-ALA, facilitating fluorescence-guided resection of the tumour tissue. Postoperative examination demonstrated an intratumour PpIX protein concentration of 16.8 nmol/g, and based on histopathological findings we diagnosed the mass as meningioma. RELEVANCE AND NOVEL INFORMATION: PDD using 5-ALA has been used to identify the surgical margins during resection of primary human brain tumours. Recently, we have reported post-mortem PDD using 5-ALA for a canine glioblastoma. To our knowledge, this technique has not been previously used for the detection and resection of feline brain tumours. Our findings suggest that PDD using 5-ALA is useful for intraoperative fluorescence-guided resection of malignant meningioma in cats.

Imaging and pathological findings of intramedullary inflammatory pseudotumour in a miniature dachshund: a case report.

BACKGROUND: Inflammatory pseudotumours (IPTs) are distinctive lesions consisting of myofibroblastic spindle cells and a variety of inflammatory cells. The aetiology of IPTs is unknown. Reports of IPTs in veterinary medicine have been scarse. Moreover, only one case of intradural extramedullary IPT has been previously reported. In this report, we introduce the first known case of canine IPT, which occurred in the parenchyma of the spinal cord. CASE PRESENTATION: A 10-year-old female Miniature Dachshund presented with a 2-month-long history of progressively worsening ataxia and tetraparesis. Neurological examination was consistent with a lesion involving the cervical spinal cord. Magnetic resonance imaging revealed an intradural space-occupying lesion in the region of the fourth cervical vertebra. Dorsal laminectomy and resection of the mass were performed. Histopathological examination revealed the proliferation of immature spindle cells (fibroblasts/myofibroblasts and glial cells) and a highly cellular mixture of neutrophils, macrophages and lymphocytic cells. The mass was located in the parenchyma of the spinal cord and was diagnosed as an IPT occurring in the parenchyma of the spinal cord. No causative pathogen was detected. The dog's symptoms improved, during the first month after surgery. However, neurological symptoms, such as laboured breathing and dysuria, subsequently worsened and the dog died 42 days after surgery. CONCLUSIONS: The present study describes a canine case of IPT occurring in the parenchyma of the spinal cord. The diagnosis and determination of the site of the mass was difficult solely based on preoperative imaging in the present case. The outcome of this case was poorer than that observed in cases of canine extramedullary IPT and human intramedullary IPT, in which the patients exhibited recovery. The prognosis after surgical resection cannot be decided from the present case alone. However, patients should be monitored for potential serious complications and recurrence.

Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine.

5-Aminolevulinic acid (5-ALA), a commonly used photosensitizer in photodynamic detection (PDD) and therapy (PDT), is converted in situ to the established photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. To extend 5-ALA-PDT application, we evaluated the PpIX fluorescence induced by exogenous 5-ALA in various veterinary tumors and treated canine and feline tumors. 5-ALA-PDD sensitivity and specificity in the whole sample group for dogs and cats combined were 89.5 and 50%, respectively. Notably, some small tumors disappeared upon 5-ALA-PDT. Although single PDT application was not curative, repeated PDT+/-chemotherapy achieved long-term tumor control. We analyzed the relationship between intracellular PpIX concentration and 5-ALA-PDT in vitro cytotoxicity using various primary tumor cells and determined the correlation between intracellular PpIX concentration and 5-ALA transporter and metabolic enzyme mRNA expression levels. 5-ALA-PDT cytotoxicity in vitro correlated with intracellular PpIX concentration in carcinomas. Ferrochelatase mRNA expression levels strongly negatively correlated with PpIX accumulation, representing the first report of a correlation between mRNA expression related to PpIX accumulation and PpIX concentration in canine tumor cells. Our findings suggested that the results of 5-ALA-PDD might be predictive for 5-ALA-PDT therapeutic effects for carcinomas, with 5-ALA-PDT plus chemotherapy potentially increasing the probability of tumor control in veterinary medicine.

Symmetric undivided diplopagus with cardiac malformation in a Japanese wild boar (Sus scrofa leucomystax).

A captured Japanese wild boar (Sus scrofa leucomystax) fetus was dicephalic. The fetus had two heads, but one body from the cranial neck region. Computed tomography imaging revealed that the two crania merged at the occipital bone, and the vertebral bodies between the atlas and the seventh thoracic vertebra were deformed. The fetus was found to have two tongues and laryngopharynges, but its esophagus and trachea were not duplicated. Each head contained a cerebrum and cerebellum, but the brains merged at the obex of the medulla oblongata, and the cervical spinal cord had duplicated ventral clefts. The heart was composed of three atria and four ventricles. This is the first report of a dicephalus with cardiac malformation in a wild boar.

Hair growth-promoting activities of chitosan and surface-deacetylated chitin nanofibers.

In this study, the effects of chitosan and surface-deacetylated chitin nanofibrils (SDACNFs) on hair growth were evaluated. In human follicle dermal papilla cells in vitro, chitosan and SDACNFs were shown to increase cell growth on day 3 after the initiation of treatment, together with an increase in the production of fibroblast growth factor-7 (FGF-7) by these cells on day 3. Furthermore, in an in vivo study in mice, chitosan and SDACNF application promoted hair growth. The number of anagen follicles significantly increased compared with that in the control group, whereas the number of telogen follicles significantly decreased in the chitosan and SDACNF groups. In the chitosan and SDACNFs groups, moreover, the expression levels of FGF-7 and Sonic hedgehog were significantly upregulated in hair follicles. Overall, our results demonstrated that chitosan and SDACNFs promoted hair growth and therefore may have applications as novel therapeutic agents for the treatment of hair loss in patients.

Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment.

Tumor hypoxia is a severe problem affecting tumor therapy because it reduces the sensitivity of chemotherapy and radiation therapy. Ozone has been known to improve peripheral blood perfusion and oxygen partial pressure. The effect of ozonated water on tumor hypoxia, alone and in combination with an antitumor drug was studied in the present study. Following intraperitoneal administration of ozonated water to colon-26-bearing mice, the Hoechst 33342-positive area and the intratumoral oxygen partial pressure was significantly increased. The tumor growth rate was more suppressed when ozonated water was combined with cisplatin (CDDP) compared with CDDP treatment alone. The number of Ki-67-positive cells significantly decreased, whereas the number of TUNEL-positive cells significantly increased. The present study showed that ozonated water increased intratumoral blood perfusion and improved tumor hypoxia. In addition, ozonated water increased the therapeutic effect of CDDP. These findings, as well as previous reports, suggest that tumor growth is suppressed after treatment with ozonated water as the amount of CDDP reaching the tumor is increased when the intratumoral blood perfusion is increased due to the ozonated water. Thus, the administration of ozonated water may be a new therapeutic approach to solve current concerns regarding antitumor treatment.

Effects of TONS504-photodynamic therapy on mouse mammary tumor cells.

In the present study, TONS504 (C51H58N8O5I2; molecular weight, 1,116.9), a novel cationic hydrophilic photosensitizer, was synthesized from protoporphyrin IX dimethyl ester through a five-step process according to a patented method for use in photodynamic therapy (PDT). The subcellular localization of TONS504 and the cytotoxic effects of TONS504-mediated PDT in the mouse mammary tumor EMT6 cell line were investigated. TONS504 was localized primarily in the lysosomes and partially in the mitochondria. The cytotoxic effects of TONS504-mediated PDT in the mouse mammary tumor EMT6 cell line were investigated using a WST8 assay and an Oxidative Stress kit. The cell viability values following treatment with 10 µg/ml TONS504 at light energies of 0, 1, 5 and 10 J/cm2 were 92.5, 101.8, 27.7 and 1.8%, respectively. The percentages of reactive oxygen species (ROS)(+) cells following the same treatment were 8.6, 8.5, 29.2 and 70.1%, respectively, whereas the percentages of apoptotic cells were 7.1, 5.6, 24.8 and 48.7%, respectively. The percentages of ROS(+) and apoptotic cells in the group subjected to TONS504-mediated PDT increased in a manner dependent on the TONS504 concentration and light energy. Further studies are required to evaluate the in vivo pharmacokinetics, tissue distribution and photodynamic effects of TONS504.

The effect of remifentanil on the minimum alveolar concentration (MAC) and MAC derivatives of sevoflurane in dogs.

Remifentanil is an ultra-short-acting µ-opioid receptor agonist. The purpose of this study was to determine the relationship of the minimum alveolar concentration (MAC) of sevoflurane and other MAC derivatives, including the MAC for blocking adrenergic responses (MAC-BAR) and the MAC at which tracheal extubation is occurred (MAC-extubation), with or without remifentanil infusion. Six healthy adult beagle dogs were randomly anesthetized three times for determining the MAC-BAR (SEVMAC-BAR), MAC (SEVMAC), and MAC- extubation (SEVMAC-extubation) of sevoflurane under infusion of saline and remifentanil at rates of 0.15, 0.30, 0.60, 1.20, and 2.40 µg/kg/min. The ratio of the SEVMAC-BAR and SEVMAC and that of the SEVMAC-extubation and SEVMAC were not significantly different at baseline and during treatment. The MAC-BAR95 and MAC95 decreased in a dose-dependent manner until reaching 1.20 µg/kg/min, and the MAC-extubation5 decreased in a dose-dependent manner until reaching 0.60 µg/kg/min. The percentage reduction of SEVMAC-BAR, SEVMAC, and SEVMAC-extubation increased in a dose-dependent manner during remifentanil infusion. The heart rate significantly decreased in the MAC-BAR and MAC groups, and the systolic and mean arterial pressures increased after remifentanil infusion compared with the baseline values. Remifentanil infusion caused reduction of the SEVMAC-BAR, SEVMAC, and SEVMAC-extubation in a dose-dependent manner, and ceiling effects were observed in the dogs. Higher doses of remifentanil and sevoflurane were necessary for blocking the sympathetic response to the supramaximal stimulus to prevent movement and extubation in dogs.

Unilateral rostral mandibulectomy for gingival vascular hamartoma in two calves.

A 2-month-old female Holstein calf and a 5-month-old female Japanese black calf presented with gingival vascular hamartoma located in the interdental space between the second and third mandibular incisors in the right and left mandibles, respectively. On radiographic or computed tomographic images, osteolytic changes appeared within the mandibular bones adjacent to the masses. The masses were removed along with affected mandibular bone by using unilateral rostral mandibulectomy. After surgery, both cases exhibited a normal appetite and grew normally, with no cosmetic changes or recurrences. Unilateral rostral mandibulectomy can be applied for invasive gingival vascular hamartomas associated with osteolytic changes.

Bleomycin-Loaded pH-Sensitive Polymer⁻Lipid-Incorporated Liposomes for Cancer Chemotherapy.

Cancer chemotherapeutic systems with high antitumor effects and less adverse effects are eagerly desired. Here, a pH-sensitive delivery system for bleomycin (BLM) was developed using egg yolk phosphatidylcholine liposomes modified with poly(ethylene glycol)-lipid (PEG-PE) for long circulation in the bloodstream and 2-carboxycyclohexane-1-carboxylated polyglycidol-having distearoyl phosphatidylethanolamine (CHexPG-PE) for pH sensitization. The PEG-PE/CHexPG-PE-introduced liposomes showed content release responding to pH decrease and were taken up by tumor cells at a rate 2.5 times higher than that of liposomes without CHexPG-PE. BLM-loaded PEG-PE/CHexPG-PE-introduced liposomes exhibited comparable cytotoxicity with that of the free drug. Intravenous administration of these liposomes suppressed tumor growth more effectively in tumor-bearing mice than did the free drug and liposomes without CHexPG-PE. However, at a high dosage of BLM, these liposomes showed severe toxicity to the spleen, liver, and lungs, indicating the trapping of liposomes by mononuclear phagocyte systems, probably because of recognition of the carboxylates on the liposomes. An increase in PEG molecular weight on the liposome surface significantly decreased toxicity to the liver and spleen, although toxicity to the lungs remained. Further improvements such as the optimization of PEG density and lipid composition and the introduction of targeting ligands to the liposomes are required to increase therapeutic effects and to reduce adverse effects.