Tissue levels, histologic changes and plasma pharmacokinetics of meta-Tetra (hydroxyphenyl) chlorin (mTHPC) in the cat.

The biodistribution and pharmacokinetics of meta-tetra(hydroxyphenyl)chlorin (mTHPC)(1) have been documented in humans, rats, dogs and rabbits. It has been demonstrated to be an effective photodynamic therapy agent for treatment of squamous cell carcinoma. Squamous cell carcinoma is a common feline neoplasm, causing significant morbidity and mortality in the feline population. The association between ultraviolet radiation exposure and occurrence of this neoplasm in the cat provides a useful model for the study of human cutaneous squamous cell carcinoma. In this study, we document the biodistribution, pharmacokinetics and toxicity of mTHPC in a group of normal cats. Four groups of cats were given the drug intravenously at dosages of 0, 0.15, 0.30 and 0.60 mg/kg. mTHPC levels were measured in plasma and tissues at 0, 24, 48, 72, 96 and 336 h after drug administration. Additionally, plasma samples were collected at 1 and 6 h post-injection and analysed. Biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other animal species. There were no clinical or pathological changes associated with administration of the drug. The biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other species studied. There were no clinical or pathological changes attributable to administration of the drug at the doses administered. mTHPC may be a useful photodynamic therapy drug in cats.

The acute and subchronic toxicity of BRB-I-28, a novel class Ib antiarrhythmic agent, in CD-1 mice.

The acute and subchronic toxic effects of BRB-I-28 (7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane HCl), a novel class Ib antiarrhythmic agent, were investigated in male and female mice. The estimated oral LD(50) for BRB-I-28 was 128 mg/kg (male mice) and 131 mg/kg (female mice). In subchronic oral studies, four groups of mice (15/sex/group/dose) were fed daily with diets containing BRB-I-28 for 90 consecutive days. The equivalent daily doses were approximately 0, 16, 32, 76 (male) and 0, 18, 37, 89 mg/kg (female). All mice survived. Food consumption per day was decreased, but water consumption per day was increased (in a non-dose-dependent manner). However, both mean body weight and mean body weight gain were not significantly changed as were true for hematological and clinical chemistry profiles, except for serum Na(+) concentration (male) and serum K(+) concentration in male and female mice (high dose levels). Hepatocellular necrosis occurred in male and female mice (in a dose-dependent fashion). Renal cortical vacuoles and myocardial necrosis with low numbers of lymphocytic infiltrations were present in female mice (middle and high doses). Lesions in the liver, kidney and heart were mild with (very small) changes in serum biochemical values. These data suggest that BRB-I-28 has limited toxic potential, and coupled with low proarrhythmic and other desirable cardiovascular effects, makes BRB-I-28 worthy of further development.

Preliminary acute and subchronic toxicity studies of GLG-V-13, a novel class III antiarrhythmic agent, in mice.

The acute and subchronic toxic effects of GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate, CAS 155029-33-7), a novel class III with some class Ib antiarrhythmic activity, were investigated in mice. The estimated LD50 for GLG-V-13 given orally were 419 mg/kg for male mice and 383 mg/kg for female mice, respectively. The acute toxic signs appeared to be of the central nervous system in origin. Four groups of mice (15 per sex, group and dose) were fed daily with diets containing GLG-V-13 for 90 consecutive days. The equivalent daily doses were 0, 22, 50 and 121 mg/kg/day and 0, 27, 60 and 136 mg/kg/day for male and female mice, respectively. All of the mice survived. Food consumption was decreased. However, mean body weight and body weight gain were not significantly changed. Gross pathological changes, especially in the lungs and liver, were found in the middle and high dose groups. Consistent increased mean corpuscular hemoglobin concentration and decreased mean corpuscular hemoglobin were observed in all dose groups. Hepatocellular necrosis was found in both male and female mice treated with the drug and was dose-dependent. Marked vacuolation of the X zone in the adrenal gland with mild to moderate deposition of ceroid pigments (brown degeneration) was observed in female mice. Lesions in the kidneys and adrenal glands may be a possible reason for changes in serum sodium and potassium ions concentrations leading to an increase in water intake. A significant reduction in cholesterol in the high dose group may be a favorable pharmacological effect of GLG-V-13. The data from the 90-day subchronic toxicity studies indicate that GLG-V-13 appears to have limited systemic toxicity potential.

Citrate inhibition of snake venom proteases.

Thirty snake venoms had a citrate content of 2.3 to 12.9%, dry basis, by an aconitase isocitric dehydrogenase coupled enzyme assay. This is a venom concentration range of approximately 30 to 150 mM citrate assuming 25% venom solids content. Inhibition of snake venom protease activity by the addition of exogenous citrate was obtained using azure blue hide powder and azocasein as substrates. Protease inhibitions of 7.5% for Crotalus atrox venom to 78% for Bothrops picadoi venom were observed with citrate. Complete inhibition of snake venom protease activity by citrate was not observed. Bothrops asper (Pacifico) venom showed a 41% protease inhibition by citrate with azocasein as the substrate and 46% inhibition of Bothrops asper (Alantico) venom protease with azure blue hide power as a substrate. Trypsin was not inhibited in this system. Citrate may inhibit some venom protease activity by forming a complex with the zinc of zinc-dependent enzymes. reserved.

Metastatic carcinoma presenting as hind-limb lameness: diagnosis by synovial fluid cytology.

A dog presented for evaluation of left hind-limb lameness and pain associated with manipulation of the tail. Synovial metastasis of a carcinoma was diagnosed by joint fluid examination. A primary bronchiolar-alveolar carcinoma with widespread (including synovial and skeletal) metastases was diagnosed on postmortem examination. Metastasis to synovial surfaces is uncommon, but when it occurs, the metastasis-induced arthritis may be the initial presenting complaint for which medical attention is sought. Although rarely reported, cytological examination of synovial fluid may be diagnostic. This paper presents an interesting clinical case and reviews the literature concerning metastatic disease of the synovium.

Survival of a domestic cat with naturally acquired cytauxzoonosis.

A cat with acute onset of febrile systemic illness was determined to be infected with Cytauxzoon felis. The diagnosis was made on the basis of cytologic morphology of erythroparasites seen in blood smears and results of microfluorometric immunoassay for serum antibody directed against C felis-parasitized RBC. Treatment consisted of parenteral administration of fluids and antibiotics. The cat recovered within 2 weeks. Circulating erythroparasites were not detected on blood smears from samples collected during follow-up examinations. However, high serum antibody titer persisted for at least 15 weeks after infection. The cat continued to be free of clinical disease 2.5 years after the initial diagnosis. Whether C felis infection persists in this cat has yet to be determined. This case indicates that some domestic cats can recover from naturally acquired cytauxzoonosis.

Pneumocystis carinii pneumonia in foals.

Pneumocystis carinii pneumonia was diagnosed in 3 foals. In 2 foals (No. 1 and 2), diagnosis was by histologic evaluation of pulmonary tissue. On retrospective evaluation, P carinii cysts were found on sediment smears of bronchoalveolar lavage fluid in 1 foal (No. 1). A different foal (No. 3) was diagnosed as having pneumocytosis by finding P carinii cysts in bronchoalveolar lavage fluid, and was treated successfully. Definitive diagnosis of pneumocytosis in animals is usually made at necropsy. However, careful cytologic evaluation in bronchoalveolar lavage fluid sediment can provide a diagnosis in some cases, allowing for initiation of appropriate treatment.

Pulse-length scaling of laser damage at 249 nm in oxide and fluoride multilayer coatings.

We have measured laser damage thresholds of a variety of fluoride-based multilayer coatings at 249 nm by using pulse lengths between 450 fs and 25 ns. Rare-earth fluoride materials yield coatings with damage resistance approximately three times greater than conventional oxide multilayers. In the scaling law, where the damage threshold is proportional to the nth power of the pulse length, the value of n changed between 1 and 0.25 over the range of pulse lengths employed.

Myxosarcoma in a Sinaloan milksnake.

A 2-year-old Sinaloan milksnake was examined because of a 1-cm mass attached to the lateral wall of the coelom. A diagnosis of myxosarcoma was made on the basis of histologic features and special staining characteristics.

Xylazine-induced pulmonary edema in rats.

Inhibitors of cytochrome P450, such as SK&F 525-A, prolong the duration of xylazine-ketamine anesthesia and cause pulmonary edema (PE) and death in rats. To determine the cause of PE, Sprague-Dawley rats were given a single dose of xylazine (21 mg/kg, im) alone or in combination with ketamine (45 mg/kg, im) and/or SK&F 525-A (50 mg/kg, ip) and percentage lung to body weight (%LW/BW) ratios (as an indicator of PE) were compared. The results indicated that xylazine caused PE which was independent of ketamine and was enhanced by SK&F 525-A. Subsequently, it was determined that 42 mg/kg xylazine, im, is an optimal edemagenic dose. Xylazine (42 mg/kg, im) increased the %LW/BW ratio as compared to control. Pleural effusion (PLE) of various amounts was observed in 75% of the animals. The pleural fluid to serum protein ratio for xylazine was similar to that obtained for alpha-naphthylthiourea (5 mg/kg, ip). Extensive serous PLE and alveolar edema with hemorrhage were found at necropsy in xylazine-treated rats. Pretreatment with yohimbine (4.2 mg/kg), prazosin (20 mg/kg), tolazoline (20 mg/kg), yohimbine (4.2 mg/kg) plus prazosin (20 mg/kg), atropine (20 mg/kg), dimethyl sulfoxide (DMSO) (7.8 g/kg), allopurinol (50 mg/kg), superoxide dismutase (20,000 U/kg), catalase (20,000 U/kg), BW755C (50 mg/kg), ibuprofen (50 mg/kg), cystathionine (100 mg/kg) plus taurine (100 mg/kg) did not affect the %LW/BW ratio. PLE was increased by yohimbine, yohimbine plus prazosin, and allopurinol, reduced by DMSO, and not changed in other groups. The results indicate that xylazine caused increased-permeability PE characterized by rapid onset, cellular damage and protein-rich pleural fluid. PE may not be mediated by adverse cardiovascular effects of xylazine and oxygen radicals are possibly involved in its etiology.

Severe systemic reactions to Hymenoptera stings in three dogs.

Three dogs were treated for acute severe systemic reactions following Hymenoptera stings. The reactions were characterized clinically by CNS depression, shock, and hemorrhage, and clinicopathologically by inflammation, liver injury, renal disease, hypoproteinemia, and possible disseminated intravascular coagulation. The severe systemic reaction may have resulted from allergic mechanisms, toxic, nonimmunologic mechanisms, or both. Rapid correction of hypovolemia and prevention of vascular stasis are the most important aspects of treatment.

Failure to transmit Ehrlichia canis (Rickettsiales: Ehrlichieae) with Otobius megnini (Acari: Argasidae).

An ear tick, Otobius megnini (Dugès) recovered from a child who had serologic evidence of ehrlichiosis, was examined for Ehrlichia species microscopically and by inoculation into a susceptible dog; no evidence of infection was found in the tick. Experimental transmission of E. canis by laboratory-reared O. megnini was attempted; neither transstadial nor transovarial transmission occurred.

Lymphocytic-plasmacytic enteritis in two horses.

The primary hematologic abnormalities in 2 adult horses with chronic weight loss were hypoalbuminemia and hyperglobulinemia. One horse was anemic, had subclinical disseminated intravascular coagulation, and prolonged plasma sulfobromophthalein half-life. Small-intestinal dysfunction with malabsorption was indicated by abnormal D-xylose absorption test results. Clinicopathologic and pathologic findings were consistent with a diagnosis of malabsorption and protein-losing enteropathy, attributable to lymphocytic and plasmacytic infiltration of the intestine.

Ehrlichiosis in a dog with seizures and nonregenerative anemia.

Ehrlichia canis infection was diagnosed in a dog with a history of seizures and nonregenerative anemia. Serologic titer to E canis was greater than 1:100. Evaluation of CSF revealed a high cell count, high protein concentration, and a positive Pandy test result. Several mononuclear leukocytes in the CSF contained E canis morulae. Central nervous system lesions are commonly found on postmortem examination of animals with ehrlichiosis, although clinical reports of neurologic signs attributable to this disease are less common. Ehrlichiosis should be included in the differential diagnosis of CNS disease in dogs from enzootic areas.

Cytology of cutaneous lesions.

Cytology is a quick, easy, and inexpensive way to gain useful information concerning the process(es) or etiology of cutaneous lesions. Cutaneous lesions can be separated quickly into inflammatory or noninflammatory conditions and organisms and neoplastic cells can be identified, allowing for a definitive diagnosis. Although not all lesions can be diagnosed cytologically, recognition of the process(es) (for example, purulent inflammation, eosinophilic inflammation, cysts) allows for better therapeutic management and a more accurate prognosis.

Evaluation of pleural and peritoneal effusions.

Certain diseases cause an increase in the amount of fluid present in the pleural and/or peritoneal cavity (an effusion). Uroperitoneum subsequent to kidney, ureter, bladder, or urethra rupture also can cause an increased amount of fluid in the abdomen. Evaluation of fluid samples often is helpful in identifying the mechanism causing the effusion and, occasionally, results in a specific diagnosis. The TP, TNCC, and general cytologic examination can be performed easily, quickly, and inexpensively in-house. The TP and TNCC are used to classify effusions as transudates, modified transudates, or exudates. Transudates usually are caused by hypoalbuminemia, but also can be caused by leakage of fluid from efferent intestinal lymphatics. Cytology and culture usually are not rewarding in the evaluation of transudates. Modified transudates usually are caused by increased vascular permeability or increased intrahepatic hydrostatic pressure. Cytologic and radiographic examinations often are helpful in evaluating patients with modified transudates, while cultures usually are unrewarding. The exudate class encompasses the inflammatory exudates (septic or nonseptic), neoplastic exudates, and chylous effusions. Inflammatory exudates have a high TP and predominantly contain inflammatory cells. They may be septic or nonseptic. When septic, degeneration neutrophils often, but not always, are found. Cultures often are needed to determine whether sepsis is present, to identify the specific organism, and to determine the best therapy. Neoplastic exudates may contain numerous neoplastic cells. If there is concern that the cells are dysplastic instead of neoplastic, the cytology preparation should be referred to a consultant. Chylous effusions usually contain many small lymphocytes with a variable number of neutrophils and macrophages. In chronic chylous effusions, however, neutrophils and/or macrophages may predominate. Chylous effusions usually are differentiated easily from pseudochylous effusions by cytology. Comparison of fluid and serum triglyceride and cholesterol concentrations can be used to differentiate chylous and pseudochylous effusions when differentiation cannot be accomplished by cytology.

Disseminated histoplasmosis in dogs: 12 cases (1981-1986).

Diarrhea, intestinal blood loss, anemia, and lethargy were predominant clinical findings in 12 dogs with disseminated histoplasmosis. Young dogs were affected most commonly, with 6 dogs being 1 to 3 years old. A diagnosis of disseminated histoplasmosis was established on the basis of histologic or cytologic detection of Histoplasma organisms in intestinal or rectal mucosa in 7 dogs, in circulating leukocytes in 5 dogs, in bone marrow in 3 dogs, and in multiple tissues at necropsy in 1 dog (4 dogs had Histoplasma organisms detected in greater than 1 site). Anemia was detected in 10 dogs (PCV less than 20% in 3 dogs), and the anemia was inadequately regenerative or nonregenerative in 7. Hypoalbuminemia was detected in 9 dogs, and serum albumin concentrations were low (less than 1.0 g/dl) in 4 of the 9 dogs. Of 5 dogs treated with ketoconazole, 2 were in remission for greater than or equal to 1 year. Corticosteroid therapy may have exacerbated the disease in 4 dogs. Histoplasma infection of multiple organs was detected in 5 necropsied dogs.