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PubMed1999

Transgenic rats expressing the human ET-2 gene: a model for the study of endothelin actions in vivo.

Previous studies have characterized the endothelin peptides (ET-1, ET-2, ET-3) as strong vasoconstrictors which are possibly involved in the pathogenesis of cardiovascular disease. Whereas ET-1 and ET-3 have been characterized using a number of approaches, little is known about the function of ET-2. The aim of this study was to define the role of ET-2 in physiology and pathophysiology using a transgenic approach. Transgenic rats expressing a genomic construct of the human ET-2 gene were generated by microinjection of fertilized oocytes from Sprague-Dawley rats. Two transgenic lines were generated, and one line was further characterized in detail. Studies on mRNA expression demonstrated that the transgene is expressed predominantly in kidney, gastrointestinal tract, adrenal gland, lung, and brain. Plasma endothelin levels were elevated 2-fold, and big-endothelin levels were elevated 2.5-fold. Despite these alterations blood pressure in transgenic rats remained normal. Further analysis of transgenic animals revealed that endothelin receptors were not downregulated, and that infusion of exogenous human ET-2 results in an enhanced blood pressure response. These observations suggest the presence of counterregulatory mechanisms influencing the effects of endothelin on blood pressure. One of these mechanisms may involve the nitric oxide system since infusion of an inhibitor of nitric oxide synthase resulted in a greater blood pressure response than in non-transgenic littermates. Despite unchanged blood pressure, alterations were observed in organ development and function, namely of hearts and kidneys, indicating an interference between transgene expression and growth processes. Male rats seem to be more susceptible to endothelin actions. These data show that the elevation in endothelin-2 expression in this transgenic model does not induce hypertension but leads to changes at the end-organ level. Normotension is most likely due to compensatory mechanisms such as increased nitric oxide formation.

Animals↗
PubMed1993

Big-endothelin-1 contracts rat isolated uterus via a phosphoramidon-sensitive endothelin ETA receptor-mediated mechanism.

The presence of a phosphoramidon-sensitive endothelin-1-converting enzyme was investigated in the rat isolated uterus. Endothelin-1 and its precursor, big-endothelin-1, increased the rate of spontaneous contractions and caused tonic contractions. Responses to big-endothelin-1 had a slower start than those to endothelin-1. The tonic contraction induced by big-endothelin-1 (10 nM) was nearly abolished by phosphoramidon (100 microM), but the response to an equieffective concentration of endothelin-1 (3 nM) was not affected. Big-endothelin-1 (EC50 6.7 nM) was only 7-fold less potent than endothelin-1 (EC50 0.9 nM), whereas endothelin-3 was much less potent (EC50 > 100 nM). The endothelin ETA receptor antagonist, BQ-123 (40, 150 and 600 nM), induced graded rightward shifts of the concentration-response curve for endothelin-1. Schild analysis yielded a straight line with a slope not different from unity, and a pA2 value of 7.76. At 100 nM, BQ-123 specifically blocked responses to both endothelin-1 (3 nM) and big-endothelin-1 (10 nM), without modifying those to oxytocin (5 nM), acetylcholine (3 microM) or bradykinin (0.5 nM). Our results suggest the presence of phosphoramidon-sensitive endothelin-converting enzyme and demonstrate the occurrence of functional endothelin ETA receptors in the rat uterus.

Amino Acid Sequence↗
PubMed1998

Design and synthesis of potent, selective inhibitors of endothelin-converting enzyme.

Endothelin-1 is the most potent peptidic vasoconstrictor discovered to date. The final step of posttranslational processing of this peptide is the conversion of its precursor by endothelin-converting enzyme-1 (ECE-1), a metalloprotease which displays high amino acid sequence identity with neutral endopeptidase 24.11 (NEP) especially at the catalytic center. A series of potent and selective arylacetylene-containing ECE-1 inhibitors have been prepared. (S, S)-3-Cyclohexyl-2-[[5-(2, 4-difluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino] propio nic acid (47), an arylacetylene amino phosphonate dipeptide, was found to inhibit ECE-1 and NEP with IC50 values of 14 nM and 2 microM, respectively. Similarly, (S)-[[1-[(2-biphenyl-4-ylethyl)carbamoyl]-4-(2-fluorophenyl)but-3- yny l]amino]methyl]phosphonic acid (56), an arylacetylene amino phosphonate amide, had IC50's of 33 nM and 6.5 microM for ECE-1 and NEP, respectively. Slight modification of the aryl moiety was found to have dramatic effects on ECE-1/NEP selectivity. The 2-fluoro dipeptide analogue, (S, S)-2-[[5-(2-fluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]+ ++amin o]-4-methylpentanoic acid (40), showed a 72-fold selectivity for ECE-1 over NEP, while the 3-fluoro dipeptide analogue, (S, S)-2-[[5-(3-fluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]+ ++amin o]-4-methylpentanoic acid (22), was equipotent for ECE-1 and NEP. Several of these inhibitors were shown to be potent in blocking ET-1 production in vivo as demonstrated by the big ET-1-induced pressor response in rats. These potent inhibitors are the most selective for ECE-1 reported to date and are envisaged to have a variety of therapeutic applications.

Acetylene↗
PubMed2006

[Internal Medicine hospital departments of Andalucian Public Health System. A description of the clinical activity in 2002].

BACKGROUND: Description of the patients admitted in the general Internal Medicine (IM) departments of the Public Health System in Andalusia (Spain) (PHSA) during 2002. PATIENTS AND METHODS: It is an analysis of the Minimum Basic Set of Data (MBSD) and its management by the Diagnostic Related Groups (DRG) of admission episodes in Andalusian public hospitals. We divided the hospitals into group 1: more than 600 beds; group 2: between 200 and 600 beds, and group 3: less than 200 beds. RESULTS: IM services discharged 80,514 patients (total in PHSA, 558,114); 25.9%, 29.6% and 44.5% from groups 1, 2 y 3, respectively; 87.4% were admitted from the emergency room. Gross mortality rate was 10.23%. Average age was 72 years, 8 years more than in the other medical departments. Mean diagnosis per episode was 5.4. The most frequent pathologies (33%) were chronic obstructive pulmonary disease, congestive heart failure, brain stroke and coronary heart disease. Adjusted length of stay was 9.35 days, this being somewhat longer in big hospitals. Mean weight of the episodes (DRG weight) of IM services was 20% higher than the mean of the rest and it accumulates 18.02% of the total weight. Real hours of outpatient clinics was 5.45% of the total. CONCLUSIONS: The activity of the general IM services is very high in relative and absolute terms. Higher age and the multiple pathologies are typical characteristics of IM patients in Andalusia. Author claim it is very important to be careful with the clinical and administrative records. Interventions on prevalent diseases in IM services may produce positive and valuable results due to their high volume.

Adult↗
PubMedDate not supplied

Does employee fitness decrease employee absenteeism and medical cost?

In recent years American have become increasingly interested in physical fitness and optimum health care. Health care is big business in the United States. American industry has lead the nation in a quest for wellness by establishing wellness programs for it's employees. This article will attempt to determine: 1) if employees on a fitness program facilitate cost containment for industry when compared to employees not participating in a fitness program; and 2) if employees on a fitness program experience reduced absenteeism due to health reasons and reduced medical costs compared to employees not participating in a fitness program.

Absenteeism↗
PubMed1998

Just how big is the pulmonary granulocyte pool?

1. It is widely believed that a large fraction of the blood granulocyte population is located in the pulmonary circulation. 2. Evidence in favour of this belief is based on several independent and complementary techniques including studies of granulocyte deformability in relation to pulmonary capillary diameter, isolated perfused lungs, direct videomicroscopic observations, cellular and capillary morphometry, physiological studies and labelled blood cell kinetics. 3. Inconsistencies in this body of evidence can be identified and traced in many cases to doubts concerning the physiological integrity of labelled granulocytes. 4. In addition to the lungs, other regions of the body undoubtedly pool granulocytes, and there is good quantitative evidence, based mainly on clinical studies, pointing to the liver, bone marrow and especially the spleen. 5. Clinical studies, furthermore, have generally not supported major granulocyte pooling in the lung, except in association with systemic inflammatory diseases, such as inflammatory bowel disease and systemic vasculitis. 6. Compromises based on technical considerations permit reconciliation of the literature, and an overall whole-body model of granulocyte distribution is proposed with which all the existing data are broadly compatible.

Animals↗
PubMed2004

Critical closing pressure in subarachnoid hemorrhage: effect of cerebral vasospasm and limitations of a transcranial Doppler-derived estimation.

BACKGROUND AND PURPOSE: Critical closing pressure (CCP) is thought to be jointly influenced by intracranial pressure and cerebrovascular tone. We examined how CCP is affected by cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: In 15 patients with vasospasm of the middle cerebral artery, CCP was calculated using 2 methods previously reported (ad modem Aaslid and Michel, indexed CCP(Aaslid) and CCP(Michel), respectively) based on data of arterial blood pressure and flow velocity (FV) as assessed by transcranial Doppler. RESULTS: CCP decreased significantly (P<0.05) during vasospasm (CCP(Aaslid)=6.3+/-22.9 mm Hg, CCP(Michel)=14.9+/-16.5 mm Hg, mean+/-SD) as compared with baseline (CCP(Aaslid)=24.4+/-20.3 mm Hg, CCP(Michel)=27.8+/-19.4 mm Hg). This was not attributable to ICP, which remained unaffected by vasospasm. In addition, CCP was significantly lower on the side of vasospasm (CCP(Aaslid)=11.9+/-24.2 mm Hg, CCP(Michel)=18.4+/-19.6 mm Hg) as compared with the contralateral nonvasospastic side (CCP(Aaslid)=24.7+/-22.3 mm Hg, CCP(Michel)=28.2+/-18.0 mm Hg). CONCLUSIONS: Assuming that autoregulation-related distal vasodilatation outweighs proximal vasospasm, CCP should decrease. Alternatively, CCP might have increased during vasospasm as the tension of big vessels increase, but the turbulence occurring during vasospasm may have impaired the linear relationship between pressure and FV, thus leading to a marked underestimation of CCP. In conclusion, interpretation of CCP in vasospasm is difficult and may be overshadowed by nonlinear hemodynamic effects.

Adult↗
PubMed2005

Evaluation of noise-induced hearing loss in young people using a web-based survey technique.

OBJECTIVE: Many adolescents and young adults consciously expose themselves to loud music for entertainment. We hypothesized that these individuals might not be aware that exposure to loud music could result in hearing loss. Furthermore, we wished to assess the feasibility of a web-based survey to collect health information from this group. METHODS: A 28-question survey was designed to target adolescents and young adults. The survey contained questions about views toward general health issues, including hearing loss, and was presented to random visitors at the MTV web site. RESULTS: In 3 days, 9693 web surveys were completed. Hearing loss was defined on a Likert scale as "a very big problem" by 8% of respondents compared with other health issues: sexually transmitted diseases, 50%; alcohol/drug use, 47%; depression, 44%; smoking, 45%; nutrition and weight issues, 31%; and acne, 18%. Notably, most respondents had experienced tinnitus or hearing impairment attending concerts (61%) and clubs (43%). Only 14% of respondents had used earplugs; however, many could be motivated to try ear protection if they were aware of the potential for permanent hearing loss (66%) or were advised by a medical professional (59%). CONCLUSIONS: A majority of young adults have experienced tinnitus and hearing impairment after exposure to loud music. Fortunately, many of these individuals could be motivated to wear ear protection. This novel web-based survey technique rapidly generated a large database and is a feasible method to obtain health data from this group.

Adolescent↗
PubMed1992

Chronic liver disease in Ethiopia: a clinical study with emphasis on identifying common causes.

Between July 1986 and April 1989, 334 hospitalized adult Ethiopian patients with chronic liver disease were studied according to a protocol to define their clinical features and to identify risk factors with the aim of preventive intervention. Of these, 14 had chronic hepatitis, 208 cirrhosis and 112 hepatocellular carcinoma (HCC). Both clinical and histological diagnostic criteria were employed. A detailed questionnaire was used to document demographic and clinical data. A common clinical presentation among patients with chronic hepatitis was darkening of the face and hands with or without hypertrichosis of the face and blisters over the dorsi of the hands. This overt or latent form of porphyrea cutanea tarda (PCT) responds to chloroquine. Patients with cirrhosis of the liver commonly present for the first time with ascites, splenomegaly, haematemesis and/or melena from oesophageal varices, and mental changes due to hepatic encephalopathy. Overt or latent forms of PCT are also common features. Peculiar to these cirrhotics is the rarity of spider naevi, gynaecomastia, testicular atrophy, Dupuytren's contracture, parotid gland enlargement and clubbing of the fingers. Exhaustion, loss of appetite, rapid loss of weight, right upper quadrant and/or epigastric pain (all often of less than 6 months' duration, a big, hard, tender and grossly nodular liver with bruit, signs of portal hypertension, and/or hepatic encephalopathy, in a young male with a rapid down hill course characterize the Ethiopian patient with HCC. Serum anti-nuclear factor, anti-mitochondrial anti-bodies and anti-smooth muscle anti-bodies were absent in those with chronic hepatitis and were uncommon in the cirrhotics and HCC cases. One or more hepatitis B virus markers were found in 86% of chronic hepatitis, 88% cirrhosis and 78% HCC and the HBsAg carrier state was found in 36%, 29% and 23%, respectively. Among the HBsAg carriers, HBeAg positivity was less common than anti-HBe but anti-HDV was significantly higher than in the healthy general population. Alphafetoprotein (AFP) levels greater than 500 mg/ml were present in 16 (8%) cirrhotics and 58 (52%) patients with HCC. Histologically, 3 of the chronic hepatitis patients had progressed to cirrhosis, 8 of the cirrhotic patients had chronic active hepatitis and 85% of HCC cases occurred in a background of macronodular cirrhosis. Three cirrhotics developed HCC during follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2005

Leadership, collective personality, and performance.

By viewing behavior regularities at the individual and collective level as functionally isomorphic, a referent-shift compositional model for the Big 5 personality dimensions is developed. On the basis of this compositional model, a common measure of Big 5 personality at the individual level is applied to the collective as a whole. Within this framework, it is also hypothesized that leadership (i.e., transformational, transactional, and passive) would predict collective personality and that collective personality would be significantly related to collective performance. The results supported these hypotheses using a sample of franchised units. On the basis of recent research at the individual level, several interactions among the various personality dimensions were hypothesized and supported. Implications are discussed.

Adolescent↗
PubMed1990

Item factor structure of the Personality Adjective Check List.

This study reports on a principal-components analysis of the Personality Adjective Check List (PACL) at the item level. Data came from a national sample of normal adults and included the responses of 1,058 men and 1,194 women (N = 2,252). Analyses were conducted separately for men and women, and for the sexes combined. The scree test was applied to decide on the number of factors to extract. Retained factors were rotated by varimax and direct oblimin procedures. Results were very similar for each analysis, with coefficients of congruence for the five orthogonal factors obtained from men and women separately being .95, .92, .94, .94, and .92. The five unipolar personality dimensions isolated were interpreted as Aggressive/Dominant, Neurotic, Conscientious, Detached/Introverted, and Surgent/Extraverted. These were compared to item factors of the Million Clinical Multiaxial Inventory (MCMI-I), MCMI-II, Adjective Check List (ACL), and to Norman's Big Five dimensions.

Adolescent↗
PubMed2005

[The influence of Janicki cercomer theory on the development of platyhelminthes systematics and evolution investigations].

The aim of this article was to present the development of ideas about the provenience of parasitic helminths and the phylogenetical relationships within this taxon, since the publication of the "cercomer theory" just to nowadays. The following essentials of the Janicki theory are outlined: main differences between free-living Turbellaria and parasitic platyhelminths (ciliated epithelium in Turbellaria versus unciliated surface in the others); universality of the cercomer presence in Monogenea, Digenea and Cestoda; evolutionary changes in the morphology and function of the cercomer; homology of the caudal appendices of all parasitic helminths; the subsequent evolution of parasitic platyhelminthes from the ancestor to Monogena, Digenea and Cestoda; proposition to establish a new common taxon--Cercomerophora--for these three groups. In this background the evolution of evolutionary ideas is reviewed, divided into two periods: up to the eighties of the XX century, and up to date. The first period can be characterised by the criticism of some points of the "cercomer theory" and formulation of some new hypotheses; these are those of Fuhrmann, Bychovsky, Llewellyn, Price and Malmberg, which: questioned the homology of the cercarial tail with the caudal appendices of Monogenea and Cestoda; rejected Digenea from the common group; established the common taxon--Cercomeromorpha--comprising only Monogenea and Cestoda; opposed the idea of radial evolution of three main groups of Platyhelmithes (Turbellaria, Digenea and Cercomeromorpha) to the idea of subsequent evolution presented by Janicki. The differences between these last hypotheses are also underlined, arising mainly from the different ideas on the importance of particular features as the evolutionary indicators of affinities between and within the taxons. As to the hypotheses dealing with the evolution of particular groups of parasitic platyhelminths formulated at the same period, the publications of Freeman and Jarecka (Cestoda), Heynemann, Ginetsinskaja, Pearson, Cable, Rhode and Gibson (Trematoda), Bychovsky, Lambert and Malmberg (Monogenea) are referred, with special emphasises on the differences in the ideas presented by their authors. In the second period two points are underlined: a dynamic development of new techniques and methods (including molecular investigations) allowing to gather more and more different data on the parasites, and, as a consequence of this phenomenon, a new approach to the evolutionary problems--the birth of numeric and phylogenetic systematics. In this period "the cercomer theory", as well as supporting the group Cercomeromorphae generally are not accepted (exception: Brooks et al.). In contrast, the new taxon--Neodermata has been created by Ehlers. The importance of this publication for further evolutionary study is stressed. In this background some publications are quoted, especially those, presenting the results of searching for monophyletic groups and joining them in hieratic kladograms (Brooks and al., Rohde at al., Littlewood at al., and the others). It is stated, that in spite of some differences in the kladograms builded by various authors (resulting mainly from the set of features being analysed) the monophyly of big taxons of Neodermata (Trematoda, Monogenea, Cestoda) is fairly well documented. In conclusion several points connected with the "cercomer theory" are emphasized. It is now obvious, that the base of this theory--homology of caudal appendices of Janicki's Cercomerophora has to be rejected, as well as his concept of subsequent evolution of Platyhelminthes. But the base of his joining of Monogena, Trematoda (in his theory--Digenea) and Cestoda in one group (lack of cilia on the body surface), opposite to the Turbellaria (ciliary ephitelium) is maintained by the creation of Neodermata, undoubtedly documented better and in a different way. Also his idea (after many years of rejecting) on close affinity of Digenea and Cestoda seems to have returned due to the study of Lockyer at al., who write: "Among the Neodermata, the Cercomeromorphae (Cestoda + Monogenea) was not supported, whereas Cestoda + Trematoda was supported".

Animals↗
PubMed2003

Long-term infection with Helicobacter felis and inactivation of the tumour suppressor gene p53 cumulatively enhance the gastric mutation frequency in Big Blue transgenic mice.

The aims of this study were to determine whether colonization with Helicobacter felis resulted in the accumulation of mutations within murine gastric tissue and whether the degree of genetic damage was increased by p53 deficiency. Female C57BL/6 mice carrying either the lambda/lacI transgene (Big Blue transgenic mice) or the lambda/lacI transgene and deficient in one allele of the p53 tumour suppressor gene (TSG-p53/Big Blue) were inoculated with H felis. Seven months after inoculation, mutations in the target lacI gene were assessed using the Big Blue transgenic mutagenesis assay system in these animals and in controls. There was an approximately two-fold increase in lacI mutations in gastric mucosa harvested from mice infected with H felis and also from non-infected mice heterozygous for the p53 allele relative to wild-type mice. The mutation frequency in mice infected with H felis and deficient in one allele of p53 was increased approximately three-fold. Active gastric inflammation was significantly greater in H felis-infected p53 hemizygous mice compared with H felis p53 wild-type mice. Gastric epithelial proliferation was similarly increased with infection in both of these latter groups of mice. In infected mice, there was a significant correlation between the mutation frequency and the degree of active gastric inflammation. These data suggest a synergistic action between infection with H felis and p53 deficiency in the accumulation of mutations within gastric tissue. Active neutrophil infiltration in gastric Helicobacter infection may contribute to the increased levels of mutation observed.

Alleles↗
PubMed1990

One of the endothelin gene family, endothelin 3 gene, is expressed in the placenta.

A cDNA encoding human endothelin 3 (ET-3) precursor was cloned from a cDNA library from the placenta, and its nucleotide and deduced amino acid sequences were determined. This ET-3 cDNA was found to contain 2.3 kb pairs and encode prepro-ET-3 protein consisting of 224 amino acid residues. The putative big-ET-3 seems to consist of 42 amino acid residues. Two of the intron insertion sites were determined with information from nucleotide sequences of the cloned genomic ET-3 gene. This is the first direct evidence that the ET-3 gene is transcribed and expressed in the placenta.

Amino Acid Sequence↗
PubMed2004

A characteristic size of approximately 10 Mpc for the ionized bubbles at the end of cosmic reionization.

The first galaxies to appear in the Universe at redshifts z > 20 created ionized bubbles in the intergalactic medium of neutral hydrogen left over from the Big Bang. The ionized bubbles grew with time, surrounding clusters of dwarf galaxies and eventually overlapped quickly throughout the Universe over a narrow redshift interval near z approximately 6. This event signalled the end of the reionization epoch when the Universe was a billion years old. Measuring the size distribution of the bubbles at their final overlap phase is a focus of forthcoming programmes to observe highly redshifted radio emission from atomic hydrogen. Here we show that the combined constraints of cosmic variance and light travel time imply an observed bubble size at the end of the overlap epoch of approximately 10 physical Mpc, and a scatter in the observed redshift of overlap along different lines-of-sight of approximately 0.15. This scatter is consistent with observational constraints from recent spectroscopic data on the farthest known quasars. This implies that future radio experiments should be tuned to a characteristic angular scale of 0.5 degrees and have a minimum frequency bandwidth of approximately 8 MHz for an optimal detection of 21-cm flux fluctuations near the end of reionization.

Journal Article↗
PubMed1995

[Time course of amino acid absorption in growing rats after feeding of a 15N-labeled wheat/yeast ration].

The time course of AA digestion, AA balance (sV AS), and AA absorption (wV AS) was estimated on growing rats (Wistar rats, LW = 124 g) in different sections of the intestinal tract using the combination of 15N tracer and TiO2 marker techniques. The animals received once a diet of 15N labelled wheat and yeast as protein sources supplemented by TiO2 as a marker. Up to 6 h after feeding the amino acid composition the 15N excess and the TiO2 content in the digesta of stomach, small and large intestine were determinated in the relation of amino acids resp. of 15N labelled amino acids to the marker. In addition the content of amino acids and the 15N excess of these amino acids were estimated in plasma. From these data the disappearance rates and the relation of exogenous to endogenous amino acids as well as the sV and the wV values of the different amino acids were calculated for the different gut sections. The following results were obtained: The relative disappearance rate for N and TiO2 marker out of the stomach went approximately parallel but with a delay for TiO2 of about 30 minutes. The AA composition of the stomach content, the small and the large intestine content did not vary in dependence of the time. The AA composition of the stomach digesta was nearly identical to that of the diet, while that of the small intestine was between exogenous AA composition (feed) and endogenous AA composition (digesta on protein free feeding). AA composition of the large intestine digesta showed quite big differences (bacterial AA break down and AA synthesis). Considering a delay time (small intestine: 1 h, large intestine: 4 h) the exogenous portion of the different AA remained constant in both of these intestinal sections during the whole experimental time. The exogenous AA part varied for small intestine digesta between 31 and 69% (mean value: 41%), and for large intestine digesta between 13 and 39% (mean value: 22%). The sV AS values in the small intestine (AA balance resp. precaecal digestibility) differed from 61% (threonine) to 86% (proline) with an average of 73.4 +/- 7.4%, those for wV AS (AA absorption) from 81% (lysine) to 94% (proline) with an average of 88.1 +/- 4.1%. There were significant differences between AA, but they are negligible for practical purposes.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1998

Specific mutational spectrum of dimethylnitrosamine in the lacI transgene of Big Blue C57BL/6 mice.

Dimethylnitrosamine (DMN) produces tumors in mice predominantly in the liver, but also in the kidney and lung. It forms O6-methylguanine adducts in DNA, which induce G:C-->A:T transitions. We have analyzed the spectra of spontaneous and DMN-induced mutations in the lacI transgene of the Big Blue mouse (C57BL/6). In both cases, mutations in the liver, kidney and lung were predominantly base substitutions, among which G:C-->A:T transitions were the most frequent. In contrast, a high incidence of short deletions (2-23 bp) was only found in the liver of treated mice. The deletions often occurred at direct repeat sequences. Single-base deletion incidence was also higher in the liver than in the kidney and lung. These results imply that accumulation of DNA lesions or their repair in liver is different from other organs. Spontaneous and induced base substitutions and deletions appeared to be randomly distributed in the lacI gene and an apparent hotspot was not observed, except for a 4 bp deletion of a (TGGC)3 sequence at positions 621-632. The present data demonstrate, for the first time, that DMN induces short deletions especially in the liver, although the mechanism involved needs further investigation.

Animals↗
PubMed2001

In vitro comparison between a DCP and external fixator for pancarpal arthrodesis in the dog.

Many clinical reports have previously documented the advantages of plates or external fixations but surgeons prefer to use plate for better acceptance by the owner, less dressing and a decreased rate of infection. In order to address complications of carpal surgery, infections, arthritis and osteomyelitis, external fixation is warranted. Twelve canine forelimbs, free of abnormality, were tested under compression to evaluate the in vitro biomechanical behaviour of the normal carpus. This behaviour was compared with that of a stabilized carpus stabilised by panarthrodesis with either plates (8 hole 3.5 mm dynamic compression plate (DCP), or a type II external fixator. Deformation vs. load was recorded after compression with a testing machine in conjunction with a digital data acquisition system. Yield load, maximal load to failure and stiffness were then calculated. Variables were significantly greater for arthrodesis with external fixation and plates than for intact forelimbs. The stiffness and the MLF after stabilisation with plates or external fixators did not differ significantly. At MLF, fracture of the third metacarpus appeared with plates, whereas deformations of the pins and bars of the external fixators increased with load. Stabilisation with plate or external fixation allowed more load to failure than the intact carpus. The biomechanical behaviour of both methods of arthrodesis was identical during loading. However, after rupture, external fixation was more plastic. External fixation, which is less often used than plates for pancarpal arthrodesis, mainly due to the occurrence of sepsis, may be useful for arthrodesis of the carpus in big or active dogs.

Animals↗