Reference intervals for transthoracic echocardiographic measurements in adult Dachshunds.

The aim of this study was to establish reference values for 2D and M-mode measurements in Dachshunds. Basic echocardiographic data, including M-mode, 2D and spectral Doppler mea- surements, was collected, analyzed and compared between 41 healthy Dachshunds and 50 other healthy dogs of similar weight. Echocardiographic reference intervals were prepared for Dachs- hunds. Dachshunds had a smaller left ventricular diameter in diastole and systole and a thicker septum than other dog breeds. Male Dachshunds had larger diastolic and systolic left ventricular diameter than females. Reference intervals for 2D and M-mode measurements in healthy Dachs- hunds differ from other dogs of similar weight and should be used for this breed to assess cham- ber enlargement.

Serum paraoxonase 1 activity and lipid metabolism parameter changes in Dachshunds with chronic mitral valve disease. Assessment of its diagnostic usefulness.

Chronic mitral valve disease, which is frequently diagnosed in Dachshunds, leads to structural, hemodynamic and redox state changes in dogs. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity and lipid metabolism in different disease stages. Standardized PON1 activity (PON1/HDL ratio) was lower in asymptomatic dogs, B1 and B2 Stages when compared to healthy ones and symptomatic Dachshunds in Stage C (ACVIM classfication). PON1 paraoxonase activity was elevated in Stage C dogs, with no changes found in PON1 activity towards phenyl acetate. Dachshunds in Stage B2 and C showed increased triglyceride levels, with no changes in cholesterol and lipoprotein concentration in comparison to healthy ones. Our data suggest that standardized PON1 activity changes could be used in laboratory diagnostics to differentiate the CMVD of affected asymptomatic (Stage B1 and B2) dogs from healthy (Stage A) and clinically affected (Stage C) dogs. Also, a standardized PON1 activity increase might be a prognostic progression signal of the disease to Stage C.

Amorphous Protic Ionic Systems as Promising Active Pharmaceutical Ingredients: The Case of the Sumatriptan Succinate Drug.

In this article, we highlight the benefits coming from the application of amorphous protic ionic systems as active pharmaceutical ingredients (APIs). Using the case of the sumatriptan (STR) drug, we show that the conversion of nonionic API to partially ionized amorphous protic succinate salt (STR SUCC) brings a substantial improvement in apparent solubility. Since in general the disordered systems reveal a tendency to self-arrangement during storage, the dominant part of this article is dedicated to the physical stability issue of sumatriptan and its ionic counterpart. To recognize the crystallization tendency of the studied systems, the calorimetric measurements were performed. Additionally, the role of ion dynamics in spontaneous nucleation of amorphous sumatriptan succinate is discussed. The differential scanning calorimetry analysis of ionic and nonionic sumatriptan reveals many similarities in thermal properties of these APIs as well as distinct differences in their resistance against crystallization in the supercooled liquid state. To determine the long-term physical stability of STR SUCC at room temperature conditions, the time scale of structural relaxation below their glass transition temperatures is estimated. We show that in contrast to nonionic materials, τα predictions of STR SUCC are much more complex and require aging experiments.

Immunosuppression in Dogs During Mammary Cancer Development.

Cancer immunosuppression that facilitates tumor progression and metastasis evolves by development of an immunosuppressive network. The aim of this study was to assess this network in dogs with benign or malignant tumors with or without confirmed metastasis. The authors showed that the number of various T cell subpopulations was constant during tumor development; however the number of regulatory T cells (Tregs) was significantly higher in tumor-bearing dogs than in healthy individuals. The number of myeloid-derived suppressor cells (MDSCs) and their p-STAT3 expression (which is a negative regulator of hematopoiesis and regulates VEGF expression) were higher in cancer patients than in control dogs, however their number increased significantly in late-stage cancer patients. Canine mammary carcinomas with confirmed metastases to either lymph nodes or internal organs had greater MDSCs and Treg infiltration than benign mammary tumors or malignant mammary tumors for which metastases had not been detected. Similarly, expression of p-STAT3 and VEGF-C was the highest in tumors with confirmed metastases. This research shows changes occurring in the blood (n = 30 patients) and tumor tissue of patients (n = 100) during canine mammary tumor development. The findings should be considered preliminary because of the small number of samples. Nonetheless, the findings suggest that a high level of Tregs and MDSCs as well as high expression of p-STAT3 and VEGF-C may significantly contribute to mammary tumor progression and metastasis in dogs.

ProANP as a screening biomarker for hypertrophic cardiomyopathy in Maine coon cats.

The aim of this study was to determine if atrial natriuretic peptide can be used as an early screening tool for hypertrophic cardiomyopathy in Maine coon cats. ANIMALS: The study was performed in 43 Maine coon cats of both sexes, aged 11 to 92 months. Clinical and echocardiographic examinations were done and proANP serum concentrations were measured every three months over a period of one year (each cat had a total of five examinations). Cats were divided into 3 groups based on echocardiographic results: group 1 - healthy cats, group 2 - cats with unequivocal hypertrophic cardiomyopathy results, group 3 - cats with HCM. The study showed that the concentration of atrial natriuretic peptide correlates with the severity of HCM. A significant increase in serum concentration of this peptide was observed in cats from group 3, but it did not differ significantly between cats from group 2 and the healthy animals (p>0.05). A correlation was also found between proANP and age of the cats (p<0.01, r=0.5578) as well as between the ejection fraction (p=0.0285, r=0.5305) and end-systolic left ventricular diameter (p=0.05, r=0.48) in the affected animals. Atrial natriuretic peptide may be used to help in the diagnosis of advanced stages of HCM in Maine coon cats. Cats with high levels of proANP should be assigned to echocardiographic studies to confirm the disease.

Correlation between peripheral blood cell transcriptomic profile and clinical parameters of chronic mitral valve disease in Dachshunds.

Studies identifying specific pathologically expressed genes have been performed on diseased myocardial tissue samples, however less invasive studies on gene expression of peripheral blood mononucleated cells give promising results. This study assessed transcriptomic data that may be used to evaluate Dachshunds with chronic mitral valve disease. Dachshunds with different stages of heart disease were compared to a control, healthy group. Microarray data analysis revealed clusters of patients with similar expression profiles. The clusters were compared to the clinical classification scheme. Unsupervised classification of the studied groups showed three clusters. Clinical and laboratory parameters of patients from the cluster 1 were in accordance with those found in patients without heart disease. Data obtained from patients from the cluster 3 were typical of advanced heart failure patients. Comparison of the cluster 1 and 3 groups revealed 1133 differentially expressed probes, 7 significantly regulated process pathways and 2 significantly regulated Ariadne Metabolic Pathways. This study may serve as a guideline for directing future research on gene expression in chronic mitral valve disease.

Anomalous origin of the right coronary artery from the pulmonary artery in a Staffordshire bull terrier.

An asymptomatic 17-month-old, 18.5-kg, male Staffordshire bull terrier was referred due to a heart murmur. Examination revealed a grade 3/6 left apical systolic and right apical 3/6 heart murmur. Echocardiography showed volume overload of the left ventricle and mild systolic dysfunction with a left-right flow over the interventricular septal region. Cardiac gated computed tomography revealed anomalous origin of the right coronary artery from the pulmonary artery, an extensive network of collateral blood vessels connected the right and left coronary arteries, with bronchial and left intercostal arteries also connected to the network of collateral blood vessels, markedly enlarged right and left coronary arteries and left coronary sinus. With varied presentation, coronary anomalies are difficult to recognise and classify and to the best of our knowledge this is the first case of anomalous origin of the right coronary artery from the pulmonary artery diagnosis in the dog.

The influence of age, gender and weight on transthoracic echocardiographic evaluation of transmitral and left ventricular outflow tract diastolic parametersin healthy dogs.

The aim of this study was to obtain reference values for diastolic cardiac function parameters in healthy dogs and to ascertain if significant differences exist between dogs of various age, weight and sex. The study was performed on 82 healthy dogs of different age and breed. Eleven param- eters were analyzed: peak velocity during early diastolic filling, acceleration time of early diastol- ic filling, deceleration time of early diastolic filling, total time of early diastolic filling, peak veloc- ity during late diastolic filling, acceleration time of late diastolic filling, deceleration time of late diastolic filling, total time of late diastolic filling, total time of early and late diastolic filling, ratio of peak velocities during early and late diastolic filling, isovolumetric relaxation time. The Dop- pler measurements used for general assessment of diastolic function in healthy dogs were signifi- cantly influenced by body weight, heart rate and age. No significant differences were found be- tween males and females. This study described the value of non-invasive echocardiographic assessment of diastolic function in healthy dogs.

Effect of pollen extract on the development of experimental atherosclerosis in rabbits.

Our previous studies have shown that the pollen extract, Cernitin, reveals lipid-lowering properties in animals and humans. The present study was designed to investigate the influence of Cernitin on the development of experimental atherosclerosis in rabbits over a period of 12 weeks. Forty male mongrel rabbits were divided into 4 equal groups: (1) controls, (2) animals receiving high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + pollen extract, and (4) HFD + clofibrate. The most pronounced reduction in lipid metabolism and in the severity of plaque formation occurred after the pollen extract had been applied. The total cholesterol content in serum and liver homogenate was depressed by 67% and 45%, respectively, while the serum HDL cholesterol and alpha-lipoproteins level was increased by 19% and from 7.73% to 21.73% respectively. The cytochrome P-450 content in the liver microsomes was elevated by 98% (nmol/g liver). Atherosclerotic plaque intensity at 12 weeks, measured planimetrically, averaged 85.5% in HFD-fed animals vs 33.7% in pollen extract-treated rabbits. These findings suggest that Cernitin, in addition to significantly lowering serum lipid levels in rabbits on an experimental diet, may modify lipid deposition in major arteries.

Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal features. Comparative genomic hybridization evidence for a mesothelioma subgroup.

Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart from the three classical patterns, predominantly epithelioid, sarcomatoid, and biphasic, some rare variants do exist. In some cases, one can find uncommon additional mesodermal tumor components. These tumors have previously been called "mesodermomas" and, like regular mesotheliomas, are usually associated with a previous asbestos exposure. We examined eight cases of mesodermomas by light microscopy, immunohistochemistry and comparative genomic hybridization (CGH). Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous, or even angioblastic elements may be found to varying degrees. Immunohistochemical analysis shows similar staining results as with regular mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per case; range, 11-27). In 10 classical biphasic mesotheliomas that served as a control, defects of comparable number and severity could not be detected (8 per case; range, 2-16). The most frequent defects of mesodermomas (losses on 1p, 4pq, 9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in mesotheliomas of the classical type. Thus, our results support the classification of the so-called mesodermomas as a separate tumor subgroup while maintaining the relationship to the classical mesotheliomas. Therefore, we propose to use the term mesodermoma for this subgroup.

Patterns of chromosomal imbalances in benign solitary fibrous tumours of the pleura.

Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise 12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible genes involved in early tumorigenesis.

Capillary electrophoretic separation of N-acetylcysteine and its impurities as a method for quality control of pharmaceuticals.

Capillary electrophoresis has been applied to separate and determine N-acetylcysteine (NAC) and related impurities. Determination conditions were found to be optimum with 100 mmol/l borate as the buffer, pH 8.40. The limit of detection was established for each substance examined. The method has been validated by examining linearity ranges, precision and repeatability. The method was used to determine the content of NAC in, and purity of, pharmaceutical preparations. The major impurities (N,N-diacetylcystine, N,S-diacetylcysteine and cystine) were determined at levels of 0.1%.

Nacystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro.

Nacystelyn (NAL), a recently-developed lysine salt of N-acetylcysteine (NAC), and NAG, both known to have excellent mucolytic capabilities, were tested for their ability to enhance cellular antioxidant defence mechanisms. To accomplish this, both drugs were tested in vitro for their capacity: (1) to inhibit O2- and H2O2 in cell-free assay systems; (2) to reduce O2- and H2O2 released by polymorphonuclear leukocytes (PMN); and (3) for their cellular glutathione (GSH) precursor effect. In comparison with GSH, NAL and NAC inhibited H2O2, but not O2-, in cell-free, in vitro test systems in a similar manner. The anti-H2O2 effect of these drugs was as potent as that of GSH, an important antioxidant in mammalian cells. To enhance cellular GSH levels, increasing concentrations (0-2 x 10(-4) mol l-1) of both substances were added to a transformed alveolar cell line (A549 cells). After NAC administration (2 x 10(-4) mol l-1), total intracellular GSH (GSH + 2GSSG) levels reached 4.5 +/- 1.1 x 10(-6) mol per 10(6) cells, whereas NAL increased GSH to 8.3 +/- 1.6 x 10(-6) mol per 10(6) cells. NAC and NAL administration also induced extracellular GSH secretion; about two-fold (NAC), and 1.5-fold (NAL), respectively. The GSH precursor potency of cystine was about two-fold higher than that of NAL and NAC, indicating that the deacetylation process of NAL and NAC slows the ability of both drugs to induce cellular glut production and secretion. Buthionine-sulphoximine, which is an inhibitor of GSH synthetase, blocked the cellular GSH precursor effect of all substances. In addition, these data demonstrate that NAC and NAL reduce H2O2 released by freshly-isolated cultured blood PMN from smokers with chronic obstructive pulmonary disease (COPD) (n = 10) in a similar manner (about 45% reduction of H2O2 activity by NAC or NAL at 4 x 10(-6) mol l-1). In accordance with the results obtained from cell-free, in vitro assays, O2- released by PMN was not affected. Ambroxol (concentrations: 10(-9)-10(-3) mol l-1) did not reduce activity levels of H2O2 and O2- in vitro. Due to the basic effect of dissolved lysine, which separates easily in solution from NAL, the acidic function of the remaining NAC molecule is almost completely neutralized [at concentration 2 x 10(-4) M: pH 3.6 (NAC), pH 6.4 (NAL)]. Due to their function as H2O2 scavengers, and due to their ability to enhance cellular glutathione levels, NAL and NAC both have potent antioxidant capabilities in vitro. The advantage of NAL over NAC is two-fold; it enhances intracellular GSH levels twice as effectively, and it forms neutral pH solutions whereas NAC is acidic. Concluding from these in vitro results, NAL could be an interesting alternative to enhance the antioxidant capacity at the epithelial surface of the lung by aerosol administration.

Chemical stimulation of productivity and pathogenicity of entomopathogenic nematodes

Under laboratory conditions, the treatment of Steinernema carpocapsae and Heterorhabditis bacteriophora entomopathogenic nematodes with either Mg or Mn(II) ions produced an increase in their productivity and pathogenicity against Sitona lineatus weevil, pupae, and larvae. Copyright 1999 Academic Press.

Soluble L-selectin and interleukin-8 in otitis media with effusion.

OBJECTIVE: adhesion of leukocytes to vascular endothelium and their invasion into local tissues are important steps in inflammation. L-selectin plays a crucial role in leukocyte rolling and adhesion on endothelial cell surface. Interleukin-8 (IL-8) is a potent chemotactic substance toward neutrophils and lymphocytes-T and mediate their migration to local inflammation. The levels of soluble L-selectin (sL-selectin) and IL-8 were measured in middle ear effusions (MEE) from children with otitis media (OM) to estimate their role in pathogenesis of inflammation in middle ear. METHODS: MEE were collected from 113 ears of 62 children during routine myringotomy. The entire specimen was diluted with phosphate-buffered saline (PBS) to 2 ml and centrifugated at 1500 rpm for 15 min to separate cellular components. Supernatants of MEE were stored frozen at -20 degrees C for sL-selectin and at -80 degrees C for IL-8 assessment. The concentration of sL-selectin and IL-8 were estimated with ELISA and compared with total protein concentration measured by Bradford assay. RESULTS: MEEs from children with chronic mucous otitis media contained significantly higher mean concentrations of IL-8 559.4 pg/mg total protein (TP) (+/-535.6) in comparison with normal serum 17.79 pg/mg TP (+/-10.9), serous OM 40.3 pg/mg TP (+/-28.1) and purulent OM 104.4 pg/mg TP (+/-128.6). High concentration of IL-8 was found in MEE from the children with early recurrence of OMS. The levels of sL-selectin were higher in purulent effusions 77.2 ng/mg TP (+/-67.4) than those of chronic mucoid 27.6 ng/mg TP (+/-36.7) and serous OM 26.3 ng/mg TP (+/-27.1). CONCLUSION: the results support a hypothesis that IL-8 can be responsible for prolongation of inflammatory process in middle ear, therefore long-term treatment and observation of children with the high levels of IL-8 in MEE may be necessary. Elevated level of sL-selectin in acute OM suggests the involvement of L-selectin in the acute phase of OM.

Determination of oxazepam and diazepam in body fluids by HPLC.

A reversed-phase high-performance liquid chromatography method for determination of benzodiazepine derivatives has been developed. Oxazepam and diazepam was determined in serum and oxazepam in urine.

[Atypical sarcomas localized within a head and neck in children]. / Nietypowe miesaki wieku dzieciecego zlokalizowane w obrebie glowy i szyi.

Seven children treated surgically because of non-rhabdomyosarcomatous soft tissue sarcoma (NRSTS) localized extrameningeally on the head and neck were presented. Three of the patients were operated on haemangiopericytoma, two--fibrosarcoma, one child--neurofibrosarcoma and one--liposarcoma. The pre- and postoperative TNM classification was employed as a staging system. The surgical resectability--R was used to establish tumour margins. Four patients (two with fibrosarcoma and two with haemangiopericytoma) survived free of disease. The influence of the complete surgical resection on the outcome of the head and neck extrameningeal NRSTS was proved.

[Pediatric neoplasms: laryngological manifestations]. / Nowotwory wieku dzieciecego--objawy laryngologiczne.

Ten children with neoplasms of the head and neck were treated in the Clinic of Otolaryngology of Medical University in Wroclaw. In 4 children non-Hodgkin lymphoma-type B (NHL-B) primarily situated in tonsils or adenoids were diagnosed, 3 patients suffered from embryonal rhabdomyosarcoma (RMS)--2 in the nasal cavity and the paranasal sinuses and 1 in the middle ear. One boy presented histiocytosis (LCH) in the orbit. In 1 case Hodgkin disease (HD) in the preauricular lympho nodes was found and in 1 child neuroblastoma of retromandibular region was detected. Our analysis revealed unsufficient oncological awareness of the physician who had examined the children as the first one. The neoplasms were detected in advanced stage. The onset of the treatment was additionally delayed because of the long period of expecting for the histological diagnosis.