Effects of pupil dilation with topical 0.5% tropicamide on retinal vascular parameters assessed by VAMPIRE® software in healthy cats.

Our study investigates the effects of mydriasis obtained with topical 0.5% tropicamide on retinal vascular parameters evaluated in cats using the retinal imaging software: Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE®). Forty client-owned healthy adult cats were included in the study.

Ocular fundus abnormalities in cats affected by systemic hypertension: Prevalence, characterization, and outcome of treatment.

Objectives: To determine the prevalence of ocular fundus abnormalities in cats with a diagnosis of systemic hypertension, to characterize the abnormalities observed, and to evaluate ophthalmoscopic evolution during treatment with amlodipine besylate.

Animals Studied: Cats diagnosed as affected by SHP in a 2-year period.

Procedures: Systemic hypertension was assessed by oscillometric blood pressure measurement, and its etiology was also established.

Discovery of Stereospecific PARP-1 Inhibitor Isoindolinone NMS-P515.

Poly(ADP-ribose) polymerase-1 (PARP-1) is an enzyme involved in signaling and repair of DNA single strand breaks. PARP-1 employs NAD to modify substrate proteins via the attachment of poly(ADP-ribose) chains. PARP-1 is a well established target in oncology, as testified by the number of marketed drugs (e.

Exophthalmos associated to orbital zygomatic mucocele and complex maxillary malformation in a puppy.

A case of exophthalmos due to zygomatic mucocele in a puppy with ipsilateral segmental maxillary atrophy is reported. A 7-month-old, mixed breed, male dog suffered the sudden-onset of unilateral painful exophthalmos and a gradual swelling of the right temporal region. A compressing, right retrobulbar mass was observed by ultrasound.

Automated tru-cut imaging-guided core needle biopsy of canine orbital neoplasia. A prospective feasibility study.

The purpose of this study was to evaluate the diagnostic value of imaging-guided core needle biopsy for canine orbital mass diagnosis. A second excisional biopsy obtained during surgery or necropsy was used as the reference standard. A prospective feasibility study was conducted in 23 canine orbital masses at a single centre.

Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy.

The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by).

Discovery of 2-(cyclohexylmethylamino)pyrimidines as a new class of reversible valosine containing protein inhibitors.

Valosine-containing protein (VCP), also known as p97 or cdc48 in yeast, is a highly abundant protein belonging to the AAA ATPase family involved in a number of essential cellular functions, including ubiquitin-proteasome mediated protein degradation, Golgi reassembly, transcription activation, and cell cycle control. Altered expression of VCP has been detected in many cancer types sometimes associated with poor prognosis. Furthermore, VCP mutations are causative of some neurodegenerative disorders.

Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors.

We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile.

[Painting in construction and exposure to carcinogenic chemical agents: an Italian study in Lombardy].

The risk associated with exposure to chemical carcinogens (as classified by International Agency for Research on Cancer and/or the European Union), during painting activities in construction seems controversial. This study included all 43 activities of professional painting in this sector existing in the area of Cremona, in Lombardy region. The aim was to consider and promote preventive technical and medical solutions, basing on efficacy.

[Nickel dermatitis, systemic nickel allergy syndrome, immuno-genesis, immune-tolerance: an Italian study].

Subjects with Nickel sensitization proved by patch test may suffer of contact eczema, but also of a Sistemic Nickel Allergy Syndrome (SNAS) consisting of urticaria-like troubles, itch, erythema, cutaneous rush, headache, intestinal symptoms, recurrent vesicular palmar dermatitis. 160 subjects (130 F, 30 M) were classified into three groups and underwent dosage of Nickel in urines (U-Ni) and blood (B-Ni). The two groups with SNAS showed an higher indicators of Nickel absorption, while the only-eczema group did not.

PARP inhibitors in cancer therapy: an update.

Introduction: Inhibitors of the poly(ADP-ribose) polymerases (PARPs) family of proteins are currently being evaluated as potential anticancer medicines at both preclinical and clinical levels. They have the peculiarity to increase the efficacy of DNA-damaging agents and to selectively target tumor cells with specific DNA repair defects. This later development of these drugs should make it possible, in principle, to selectively target neoplastic vs healthy cells, thus realizing the Ehrlich's magic bullet concept of a personalized and tailored cure of diseases.

Alkylsulfanyl-1,2,4-triazoles, a new class of allosteric valosine containing protein inhibitors. Synthesis and structure-activity relationships.

Valosine containing protein (VCP), also known as p97, is a member of AAA ATPase family that is involved in several biological processes and plays a central role in the ubiquitin-mediated degradation of misfolded proteins. VCP is an ubiquitously expressed, highly abundant protein and has been found overexpressed in many tumor types, sometimes associated with poor prognosis. In this respect, VCP has recently received a great deal of attention as a potential new target for cancer therapy.

[Leather dust and sensitizing agents. A study on occupational indoor allergenic pollution in shoes].

The study was aimed to ascertain a possible pollution by allergenic Mites in 15 samples of leather dust belonging to occupational environments of 4 Italian shoes factories. All dosages were both performed by a quantitative immunologic and ELISA method (Indoor Biotechnology Lmd) and a semi-quantitative colorimetric method (Aclotest Lofarma) and the results were compared according to a five steps risk-evaluation. In all factories allergenic components of Mites were documented.

[Assessment of exposure to cancerogenic aromatic hydrocarbon during controlled-access highways management activities].

The purpose of this study was an integrated assessment of exposure to benzene and Polycyclic Aromatic Hydrocarbons (PAH) in 29 workers employed to manage a controlled-access highways. A campaign was performed in summertime by environmental monitoring (active and passive airborne personal sampler), as well as by biological monitoring (urine samples of the beginning and of the end of daily shift, baseline after two days of vacation). The measured environmental levels did not differ from background environmental concentrations found in a metropolitan area (i.

[Nickel risk in metal processing workers. Highlights on toxic and allergic effects].

Nowadays nickel is a global problem, related to occupations (mainly metalworkers) and to life habits. The dietary intake, more than environments, is the source of a basic immune identification and also of possible complications after occupational inhalation or contact. Nickel insoluble compounds are proved to be cancerogenic.

[Asthma and baker's allergy: experience with health programs].

Wheat flour sensitization may lead to several occupational diseases: persistent rhinitis, intermittent or persistent asthma, conjunctivitis, urticaria, and contact dermatitis. The main allergenic components of wheat have been identified, the prevalent mechanism is IgE-mediated, the worsening after starting of sensitization shows the characters of the "allergy march" till the respiratory functional impairment and disability. Nowadays the occupational rhinitis is the first important step to begin to start prevention, but its relevance is also for quality of life of subjects.

Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding.

Cdc7 serine/threonine kinase is a key regulator of DNA synthesis in eukaryotic organisms. Cdc7 inhibition through siRNA or prototype small molecules causes p53 independent apoptosis in tumor cells while reversibly arresting cell cycle progression in primary fibroblasts. This implies that Cdc7 kinase could be considered a potential target for anticancer therapy.

[The medical management of the allergic worker in small industries and for craftsmen].

This report is aimed to suggest how allergic subjects can be admitted to activities at risk and how workers affected by occupational allergy can be relocated. Allergy is a mechanism strictly joined with the individuality trough the immunologic system of protection of the organism Works are the background of a possible exposure to agents able to rouse a specific hypersensitivity, but also the purposes of everyone for having a normal way of life. Population studies demonstrated that 70% of adults that present themselves for working as craftsmen or in small industries are normally reactive, but about 30% have a condition of a diagnosed allergy or are hyperreactive to the environment.

First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery.

Cdc7 kinase is a key regulator of the S-phase of the cell cycle, known to promote the activation of DNA replication origins in eukaryotic organisms. Cdc7 inhibition can cause tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 inhibitors for the treatment of cancer. In this paper, we conclude the structure-activity relationships study of the 2-heteroaryl-pyrrolopyridinone class of compounds that display potent inhibitory activity against Cdc7 kinase.

Comparison of conservative management and juvenile pubic symphysiodesis in the early treatment of canine hip dysplasia.

Objectives: To evaluate the efficacy of juvenile pubic symphysiodesis (JPS) in a clinical setting for the early treatment of canine hip dysplasia (CHD), and to identify its indications and contraindications.

Methods: The final degree of CHD using the FCI (Fédération Cynologique Internationale) CHD classification in 5 Grades (A, B, C, D, E) was assessed at skeletal maturity in two homogeneous groups of dogs assessed at the age of 14 to 22 weeks and selected according to their susceptibility to CHD; one group was treated with JPS and one group was conservatively managed. Two hundred seventeen puppies completed the study; 81 were treated with JPS (group 1) and 76 were conservatively managed (group 2).

[Specific immunotherapy and relocation in occupational allergic bakers].

Occupational allergy to components of wheat flour is the main cause of rhinitis and asthma of workers in bakeries and similar activities. An immunological mechanism IgE-mediated is involved and the sensitising properties of some proteins of wheat where assessed. Nowadays it is possible to have an extract to be used for specific immunotherapy.

[Analysis of work accidents during the years 1999-2006 in a hospital company in Lombardia].

This study describe accidents occurred in the period between 1999 and 2006 in the Hospital of Cremona, in which about 2400 subjects operate. The analysis of Accident Register showed a reduction of about 30% of the total number of accidents during the examined period and a non homogeneous distribution of the various types of accidents. The most frequent accidents were prick (25.

[Rubber industry and exposure to carcinogenic chemical agents: an Italian Multicentric Study in Lombardy].

Evaluating the chemical risks at the workplaces, the potential carcinogenic risk is a primary interest. Particularly, in the rubber forming industry the main attention was directed to the hot processing as a possible source of exposure to chemical agents, several of which were classified as carcinogens by the International Agency for Research on Cancer (IARC) and/or the European Union (EU). A study on occupational exposure to chemical carcinogens in the rubber forming industry was planned during last two years, involving a representative sample of firms.

[Biological monitoring in the molding of plastics and rubbers].

This survey was carried out in the molding of plastics and rubbers, in the "Professional Cancer Prevention Project" sponsored by the Lombardy region with the objective of developing and implementing protocols for evaluating exposure to carcinogens through the biological monitoring. The realities of molding the thermoplastic polymer ABS, rubber, and thermosetting plastics containing formaldehyde were examined. The carcinogenic substances identified in these processes were: 1,3-butadiene, acrylonitrile and styrene in molding ABS, polycyclic aromatic hydrocarbons (PAH) in molding rubber, and formaldehyde in molding the thermosetting plastics.