Genetic and environmental risk indicators in canine non-Hodgkin's lymphomas: breed associations and geographic distribution of 608 cases diagnosed throughout France over 1 year.

BACKGROUND: The etiology of non-Hodgkin's lymphomas (NHL) is multifactorial. Environmental and genetic factors are frequently incriminated both in humans and dogs. OBJECTIVES: Our purpose was to study the geographic distribution of canine NHL (CNHL) in France and to evaluate genetic and environmental influences. ANIMALS: Six hundred and eight cases of CNHL, diagnosed throughout France over 1 year, were collected from 7 Veterinary Histopathologic Laboratories. METHODS: Retrospective study. Breeds affected by lymphomas were compared with the national population and associations between breed and immunophenotype were studied. The distribution of CNHL and canine T-cell NHL per 100,000 dogs per department was compared with the distribution of waste incinerators, polluted sites, and radioactive waste. RESULTS: The breeds significantly overrepresented among lymphoma cases were Boxer, Setter, and Cocker Spaniel (P < .001). There was a significant association between Boxer and T-cell NHL (P < .001), and between German Shepherd and Rottweiler and B-cell NHL (P < .01). The geographic distribution of CNHL and canine T-cell NHL indicated significant heterogeneity. Significant association between distributions of CNHL and waste incinerators (rho= 0.25, P < .05), polluted sites (rho= 0.36, P < .001), and radioactive waste (rho= 0.51, P < .001) was found. CONCLUSIONS AND CLINICAL IMPORTANCE: Influence of genetics in the development of CNHL was supported by the existence of an association between breed and immunophenotype. Waste incinerators, polluted sites, and radioactive waste could just be considered as risk indicators of CNHL, but not as risk factors. Case-control studies around critical sites are necessary to confirm the implication of those environmental factors in the development of CNHL.

Ecotoxicological risk assessment of hospital wastewater: a proposed framework for raw effluents discharging into urban sewer network.

In hospitals a large variety of substances are in use for medical purposes such as diagnostics and research. After application, diagnostic agents, disinfectants and excreted non-metabolized pharmaceuticals by patients, reach the wastewater. This form of elimination may generate risks for aquatic organisms. The aim of this study was to present: (i) the steps of an ecological risk assessment and management framework related to hospital effluents evacuating into wastewater treatment plant (WWTP) without preliminary treatment; and (ii) the results of its application on wastewater from an infectious and tropical diseases department of a hospital of a large city in southeastern France. The characterization of effects has been made under two assumptions, which were related to: (a) the effects of hospital wastewater on biological treatment process of WWTP, particularly on the community of organisms in charge of the biological decomposition of the organic matter; (b) the effects on aquatic organisms. COD and BOD5 have been measured for studying global organic pollution. Assessment of halogenated organic compounds was made using halogenated organic compounds absorbable on activated carbon (AOX) concentrations. Heavy metals (arsenic, cadmium, chrome, copper, mercury, nickel, lead and zinc) were measured. Low most probable number (MPP) for faecal coliforms has been considered as an indirect detection of antibiotics and disinfectants presence. For toxicity assessment, bioluminescence assay using Vibrio fischeri photobacteria, 72-h EC50 algae growth Pseudokirchneriella subcapitata and 24-h EC50 on Daphnia magna were used. The scenario allows to a semi-quantitative risk characterization. It needs to be improved on some aspects, particularly those linked to: long term toxicity assessment on target organisms (bioaccumulation of pollutants, genotoxicity, etc.); ecotoxicological interactions between pharmaceuticals, disinfectants used both in diagnostics and in cleaning of surfaces, and detergents used in cleaning of surfaces; the interactions into the sewage network, between the hospital effluents and the aquatic ecosystem.

The first directed reduction of beta-alkoxy ketones to anti-1,3-diol monoethers: identification of spectator and director alkoxy groups.

A new reduction procedure for the stereoselective reduction of certain beta-alkoxy ketones is described. The method relies upon electron-transfer reduction using samarium diiodide in THF with MeOH as an additive. Reduction is facile for a number of alkoxy groups that can complex samarium effectively but is not observed with TBS or benzyl protecting groups. Experiments with deuterated methanol show that the stereoselectivity arises from protonation of a samarium carbanion intermediate.

Catalytic asymmetric allylation reactions using BITIP catalysis and 2-substituted allylstannanes as surrogates for beta-keto ester dianions.

[formula: see text] Catalytic asymmetric allylation (CAA) reactions using the indicated allylstannane and the BITIP catalysts previously described by us give high yields and enantioselectivities in additions to aldehydes. The products are convertible to beta-keto esters by oxidative cleavage of the olefin. These reactions thus provide a useful catalytic enantioselective method for chain extension with introduction of a versatile four-carbon unit.

Total synthesis of the immunosupressant (-)-pironetin (PA48153C).

[reaction: see text]. Total synthesis of the immunosuppresant pironetin has been achieved by a synthetic route in which the connections between starting materials and the desired structure are readily discerned. Key steps include a diastereoselective Lewis acid mediated crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction, an anti-selective SmI2 reduction of a beta-hydroxyketone, and finally a lactone annulation reaction.

A versatile preparation of alpha,beta-unsaturated lactones from homoallylic alcohols.

[formula: see text] A new method for the synthesis of alpha,beta-unsaturated lactones from beta-acetoxy aldehydes by reaction with the lithium enolate of methyl acetate was developed. The reaction is relatively insensitive to structural changes in the aldehyde substrates. The process was extended to the synthesis of five-ring lactones from alpha-acetoxy aldehydes. Experimental evidence regarding the mechanism of this one-pot transformation was obtained. The observations are consistent with a pathway involving an initial aldol condensation with subsequent acyl migration, lactonization, and beta-elimination and not an enolate equilibration-aldol mechanism.

Sequestration of the lung arising from the circumflex coronary artery.

Sequestration is an unusual pulmonary malformation. Systemic blood supply is commonly from the thoracic aorta, but arteries may occasionally arise from other sites including the abdominal aorta or the intercostal vessels. We report a rare form of sequestration with origin from the circumflex coronary artery. Knowledge of uncommon vascular origins, particularly from coronary arteries, is important to avoid injury and possible ischemia, infarction, exsanguination, or death.

MR imaging of the spinal cord in 23 subjects with ALD-AMN complex.

Twenty-three subjects from two family groups with the adrenoleukodystrophy (ALD)-adrenomyeloneuropathy (AMN) complex were examined with MR imaging at 1.5 T to determine the presence and extent of brain and spinal cord abnormalities. Nineteen individuals were identified as having ALD or AMN, or as having carrier status on the basis of pedigree analysis and/or evaluation of serum very-long-chain fatty acids. In addition to the expected intracranial white matter changes for this disorder, decreased spinal cord diameter was found in seven (30%) of the 23 subjects. In three of these cases, atrophy was limited to the thoracic spinal cord, while atrophy of both the cervical and thoracic cord was identified in four patients. Two patients who did not have MR imaging of the spine were found to have spinal cord atrophy at autopsy. The finding of decreased spinal cord diameter on MR examinations in individuals who are heterozygous for ALD-AMN, in patients with ALD or AMN, and in asymptomatic ALD-AMN patients may represent a new anatomic marker for the variable clinical presentations of this condition. In addition to cranial MR examination, MR imaging of the spine may be indicated in patients with suspected ALD or AMN, or in women with carrier status.

Veterinary pharmacovigilance in the European context.

Pharmacovigilance (or pharmaco-surveillance) is the surveillance of adverse drug reactions (ADRs) which are noxious and of unintended reactions which occur at doses normally used in animals in accordance with the terms of the marketing authorization. From this definition, the scope of veterinary pharmacovigilance should be clearly defined, especially with regard to associated problems of lack of efficacy, resistance, effects in man, residues, etc. Priorities should be established concerning adverse effects in animals in order to set up an operational system. Methodological tools are being developed such as causality assessment, thesaurus, data banks, alert systems. The situation of veterinary pharmacovigilance in countries is very different. The existing systems are based on two different conceptions: a pharmacovigilance of the administrative type, made by authorities; a pharmacovigilace of the interactive type, made in veterinary universities, linked with the authorities. In industry, the importance of pharmacovigilance is increasing; collaborations have been set up but should certainly be developed. Finally, the sensitization of the veterinary practitioners, which play a key-role in the system of spontaneous reporting of ADRs, is to be developed in many ways: interaction during or after the report, publication of data, concrete actions, improvement of side-effect warnings and prevention, etc. Veterinary pharmacovigilance should be a very interesting area of cooperation between the field, universities, industry and regulation authorities.

Review and prospect of emerging contaminants in waste--key issues and challenges linked to their presence in waste treatment schemes: general aspects and focus on nanoparticles.

The presence in waste of emerging pollutants (EPs), whose behaviours and effects are not well understood, may present unexpected health and environmental risks and risks for the treatment processes themselves. EP may include substances that are newly detected in the environment, substances already identified as risky and whose use in items is prohibited (but which may be present in old or imported product waste) or substances already known but whose recent use in products can cause problems during their future treatment as waste. Several scientific studies have been conducted to assess the presence of EP in waste, but they are mostly dedicated to a single category of substance or one particular waste treatment. In the absence of a comprehensive review focused on the impact of the presence of EP on waste treatment schemes, the authors present a review of the key issues associated with the treatment of waste containing emerging pollutants. This review presents the typologies of emerging pollutants that are potentially present in waste along with the major challenges for each treatment scheme (recycling, composting, digestion, incineration, landfilling and wastewater treatment). All conventional treatment processes are affected by these new pollutants, and they were almost never originally designed to consider these substances. In addition to these general aspects, a comprehensive review of available data, projects and future R&D needs related to the impact of nanoparticles on waste treatment is presented as a case study.

Comparison of transcriptional response to phorbol ester, bryostatin 1, and bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into their differential mechanism of action.

Bryostatin 1, like the phorbol esters, binds to and activates protein kinase C (PKC) but paradoxically antagonizes many but not all phorbol ester responses. Previously, we have compared patterns of biological response to bryostatin 1, phorbol ester, and the bryostatin 1 derivative Merle 23 in two human cancer cell lines, LNCaP and U937. Bryostatin 1 fails to induce a typical phorbol ester biological response in either cell line, whereas Merle 23 resembles phorbol ester in the U937 cells and bryostatin 1 in the LNCaP cells. Here, we have compared the pattern of their transcriptional response in both cell lines. We examined by qPCR the transcriptional response as a function of dose and time for a series of genes regulated by PKCs. In both cell lines bryostatin 1 differed primarily from phorbol ester in having a shorter duration of transcriptional modulation. This was not due to bryostatin 1 instability, since bryostatin 1 suppressed the phorbol ester response. In both cell lines Merle 23 induced a pattern of transcription largely like that of phorbol ester although with a modest reduction at later times in the LNCaP cells, suggesting that the difference in biological response of the two cell lines to Merle 23 lies downstream of this transcriptional regulation. For a series of bryostatins and analogs which ranged from bryostatin 1-like to phorbol ester-like in activity on the U937 cells, the duration of transcriptional response correlated with the pattern of biological activity, suggesting that this may provide a robust platform for structure activity analysis.

Cryopreservation of Ovarian Tissue: Detailed Description of Methods for Transport, Freezing and Thawing.

Purpose: In many cases cancer therapy leads to an irreversible reduction or even loss of ovarian reserve. Cryopreservation of ovarian tissue with subsequent thawing and re-transplantation of tissue after the cancer is in remission constitutes a promising method to preserve fertility in women. To date, more than 25 cases of live births after re-transplantation of cryopreserved ovarian tissue have been published worldwide. In Germany the first live birth after re-transplantation of cryopreserved tissue was in 2011. Material and Methods: After surgical removal of ovarian tissue in the Gynaecological Clinic of Dresden University, the tissue was sent to the Gynaecological Clinic of Bonn University in a special transport container at 5 °C and was frozen the next day using 1.5 M dimethyl sulfoxide cryosolution. In 2010 this ovarian tissue was thawed using a sucrose solution in the Gynaecological Clinic of Erlangen University Clinical Centre and was laparoscopically re-transplanted into the patient. Results: The patient became pregnant, the pregnancy was uneventful, and she gave birth to a healthy boy. Conclusion: Freezing of ovarian tissue with subsequent re-transplantation as described here is a viable method to preserve fertility in cancer patients.

[Drug surveillance and reproduction in domestic animals]. / Pharmacovigilance et reproduction chez les animaux domestiques.

Adverse effects of veterinary drugs, on the reproductive functions of domestic animals, represent an important aspect of veterinary pharmaco-vigilance. The data presented here are coming from the cases recorded by the National Centre of Veterinary Toxicological Informations or from published cases. The substances taken in account are mainly currently used drugs (antimicrobials, anti-parasitic...) either of specific veterinary use, either used in both human and veterinary medicine.

[Species differences in pharmaco-kinetics of chemicals. Correlations with toxicity (author's transl)]. / Variations inter-spécifiques du métabolisme des substances chimiques. Relations avec la toxicité.

The species differences in kinetics of drugs or toxics were studied in laboratory and domestic animals at various stages of the fate in the body: - absorption, - distribution, blood transport, binding on plasmatic proteins, tissues; placenta passage, - elimination via the kidney, bile, and diverses secretions. Since they are very important in species differences bio-transformations of chemical substances were studied separately. The toxicological or pharmacological implications of these differences were shown from a theoretical point of view (phenomena of passage through the membranes), an experimental point of view (choice of species, extrapolation from animal to man) and from the veterinary point of view.

[Effects of the contamination by polychlorobiphenyls (PCBs) on the growth of the Ehrlich tumor in mice (author's transl)]. / Effets de la contamination par les polychlorobiphényles (PCB) sur le développement de la tumeur d'Ehrlich chez la souris Swiss.

The effects of a 3-month experimental contamination with a commercial mixture of PCBs, DP5 (corresponding to Aroclor 1254) have been studied on groups of 25 SWISS female mice, at levels of 0, 10, 50 and 250 ppm added at feeding. After subcutaneous injection of 0,2 ml of Ehrlich's tumoral ascites liquid, the evolution of tumors as well as the mortality level, were different in the treated groups as compared to the control group. The percentages of mortality due to tumors were the following: control (0 ppm) = 50% 10 ppm = 5% 50 ppm = 5% 250 ppm = 35% Thus, contamination by PCBs seems to have protected these mice against the Ehrlich tumor. No decrease in body weight was noted neither were differences in size or appearance of the thymus and the spleen in the treated mice; an evident liver hypertrophy was noted in all PCB treated mice.