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PubMed1989

Nutritional support in hospitalized patients with alcoholic liver disease.

The effects of a nutritional support in hospitalized patients with alcoholic cirrhosis and liver failure were studied in a controlled protocol. Thirty-six patients were included, 17 were randomly assigned to an experimental group and the rest to a control group. Experimentals received a diet aiming at 50 kcal (209 kJ)/kg bodyweight/d and 1.5 g protein/kg bodyweight/d (as proteins of high biological value). Controls received the standard diet prescribed by the attending physician. The severity of liver failure and the nutritional status on admission were similar in both groups. The measured energy intake in controls was 1813 +/- 121 kcal/d (7589 +/- 506 kJ/d) and 2707 +/- 71 kcal/d (1131 +/- 297 kJ/d) in experimentals (P less than 0.001). The protein intake in controls was 47 +/- 3.8 g/d and in experimentals 80 +/- 3 g/d (P less than 0.001). There were seven deaths during the study period (two experimentals and five controls). No differences were observed in the evolution of liver failure, hepatic encephalopathy or nutritional status between both study groups. It is concluded that a higher energy and protein intake in these patients does not have adverse effects and is associated with a non-significant reduction in mortality.

Body Weight↗

PubMedDate not supplied

[Hypophysial stimulation of oestradiol-17 beta secretion in Carp, Cyprinus Carpio L (author's transl)].

Using radioimmunoassays, plasma levels of carp gonadotropin (c-GTH) and oestradiol-17 beta (E2) are measured every day in Carp, during induced spawning (water temperature = 15 degrees C). Ten Carps injected twice intraperitonealy with a total extract of Carp hypophysis (0,6 mg/kg BW at Jo and 5,4 mg/kg BW at J1) are compared to a lot receiving only saline solution. No evolution is detected in that last group when in the experimental one E2 level increases with exogenous c-GTH (see table). Even if E2 levels are low at the end of vitellogenesis, steroidogenic structures remain sensitive to an exogenous hypophysial stimulation. Secretion ability differs within individuals (correlation coefficient between total estimated c-GTH and E2 = 0,15).

Animals↗

PubMed1997

[125th anniversary of Revista Médica de Chile].

The first issue of Revista Médica de Chile was printed in July, 1872. Since then, it has been published monthly, interrupted only for a few months during a Chilean civil war (1891). This medical journal has been devoted mainly to clinical topics in internal medicine, but currently it includes an increasing proportion of research papers in other biomedical and preclinical subjects. This journal is included in the most important international indexes of biomedical publications. Most issues cover also medical education, public health, the ethics of clinical and experimental research, medical administration and the history of medicine. The evolution of medicine in Chile along 125 years is clearly reflected in the contents of this journal. Revista Médica de Chile is one of the oldest medical journals in the world, particularly among those published in Spanish, and a top ranking biomedical publication in Chile.

Chile↗

PubMed2004

Nutrient enrichment and food chains: can evolution buffer top-down control?

We show how evolutionary dynamics can alter the predictions of classical models of the effects of nutrient enrichment on food webs. We compare an ecological nutrient-plant-herbivore food-chain model without evolution with the same model, including herbivore evolution, plant evolution, or both. When only herbivores are allowed to evolve, the predictions are similar to those of the ecological model without evolution, i.e., plant biomass does not change with nutrient addition. When only plants evolve, nutrient enrichment leads to an increase in the biomass of all compartments. In contrast, when plants and herbivores are allowed to coevolve, although these two classical patterns are common, a wide variety of other responses is possible. The form of the trade-offs that constrain evolution of the two protagonists is then critical. This stresses the need for experimental data on phenotypic traits, their costs and their influence on the interactions between organisms and the rest of the community.

Adaptation, Biological↗

PubMed2001

Heterogeneity affecting outcome from acute stroke therapy: making reperfusion worse.

BACKGROUND: Stroke patients are heterogeneous not only with respect to etiology but also in terms of preexisting clinical conditions. Approximately one fifth of patients with acute stroke are hyperglycemic and/or have had a recent infectious or inflammatory condition. Summary of Review-- Experimental research indicates that these factors can alter and accelerate the evolution of stroke and reperfusion injury, although these effects are complex and some may have a favorable impact. Both conditions involve activation of inflammatory and reactive oxygen mechanisms. In addition, hyperglycemia has concomitant deleterious vascular and metabolic effects that worsen infarct size and encourage hemorrhagic transformation in reperfusion models. Clinical data are less extensive but in general support an adverse impact on outcome. CONCLUSIONS: After examining these data in detail, we concluded that the presence of these clinical conditions could assist in identification of those at increased risk for complications of reperfusion therapy. Furthermore, consideration of these factors may provide a rational basis for combination therapy and improve the clinical relevance of experimental stroke models.

Acute Disease↗

PubMedDate not supplied

[Biventricular infarctions].

Posterior biventricular myocardial infarctions are more frequent than anterior ones. Unipolar right and high abdominal leads are necessary for the diagnosis. These supplementary leads are dependable, can be repeated as many times as necessary and show the evolution from signs of injury to those of inactivable tissue (Q waves of 0.04 sec or more). This information on evolution increases the diagnostic value of the electrocardiogram since signs of an injury current can be observed in other conditions as well. The diagnosis of right ventricular infarction can be established even in the presence of RBBB, but the differential diagnosis with acute cor pulmonale must be established on clinical as well on laboratory basis. The signs of an inactivable zone of the free right ventricular wall are more frequently observed in posterior biventricular infarctions than in the anterior ones. In the latter, signs of subepicardial injury are more accentuated in right thoracic leads than in V2 and V3, which indicate anterior right ventricular involvement. The same signs are also observed in experimental studies. A review of medical literature concerning the prognosis and evolution of biventricular myocardial infarctions is presented.

Electrocardiography↗

PubMed1989

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with simian immunodeficiency virus (SIVsm).

Five healthy cynomolgus monkeys were inoculated intravenously with simian immunodeficiency virus (SIVsm) propagated in human lymphocytes. All five animals became infected. Virus was recovered from blood mononuclear cells and viral antigen was detected in serum 12 days postinoculation (PI) in all inoculated animals. Virus was also isolated in all five animals tested 74 to 226 days PI. Antibodies to different structural proteins of SIV and HIV-2 were demonstrated by ELISA, Western blot, and radioimmunoprecipitation assay from day 31 PI concomitantly with a reduction of viral proteins in the serum. Reappearance of antigen accompanied by a fall in antibody to gag products (p26) was observed in two monkeys 69 days PI. All SIV-infected monkeys showed a pronounced decrease in CD4+ lymphocytes demonstrable already 12 days PI. They also developed persistent lymphadenopathy. Thus, infection of cynomolgus monkeys with SIVsm mimics events in human immunodeficiency virus infection in humans but the course of evolution of pathogenic events in the monkey is markedly compressed. This experimental model will be useful for evaluation of HIV vaccines and antiviral testing.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Evolution of immune surveillance and tumor immunity: studies in Xenopus.

We have developed a novel experimental model of cancer immunity in the frog, Xenopus, which may provide a useful alternative to murine tumor models and a way to assess whether the control of tumor development is a fundamental function of the immune system of vertebrates. In Xenopus, tumor immunity can be studied in two developmentally distinct immune systems. The larval immune system reflects characteristics of an ancestral system that appears to function without classical MHC class I antigen presentation and an efficient effector mechanism. The adult system appears more highly evolved in that it is remarkably similar to that of mammals and is able to generate a potent antitumor response. This amphibian model also provides a unique system with which to investigate a postulated role of heat shock proteins as components of an ancestral system of antigen presentation and/or immune surveillance that predates the antigen presentation pathway that exclusively involves MHC molecules.

Animals↗

PubMed1999

Trophoblast interferons.

The mechanisms responsible for prevention of corpus luteum regression during early pregnancy are diverse and appear to have arisen in concert with the evolutionary divergence of placental structure. That used by the sub-order Ruminantia is unique and involves the production of a Type I interferon (IFN), IFN-tau (tau). Although IFN-tau resembles other Type I IFNs (such as IFN-alpha, -beta, and -omega) in structure as well as in many of its biological properties, it is not virally inducible and is instead produced constitutively by embryonic trophectoderm during the period immediately prior to implantation. The transcription factor Ets-2 is a component of the regulatory mechanism involved in transcription of IFN-tau. These genes probably arose as the result of a duplication of an IFN-omega gene, 36 million years ago, at about the time the Ruminantia sub-order emerged. They have duplicated extensively since then and there may be 10 or more genes in some present-day species. The expression of different IFN-tau is unequal and they differ in biological potency. The rapid evolution of IFN-tau genes possibly reflects the placenta as a site of considerable genetic experimentation.

Animals↗

PubMed2004

Simulation as experiment: a philosophical reassessment for biological modeling.

Some scientific modelers suggest that complex simulation models that mimic biological processes should have a limited place in ecological and evolutionary studies. However, complex simulation models can have a role that is different from that of simpler models that are designed to be fit to data. Simulation can be viewed as another kind of experimental system and should be analyzed as such. Here, I argue that current discussions in the philosophy of science and in the physical sciences fields about the use of simulation as an experimental system have important implications for biology, especially complex sciences such as evolution and ecology. Simulation models can be used to mimic complex systems, but unlike nature, can be manipulated in ways that would be impossible, too costly or unethical to do in natural systems. Simulation can add to theory development and testing, can offer hypotheses about the way the world works and can give guidance as to which data are most important to gather experimentally.

Journal Article↗

PubMed2001

Pollinator-mediated selection on a flower color polymorphism in experimental populations of Antirrhinum (Scrophulariaceae).

We quantified pollinator visit behavior, pollen receipt and export, and changes in allele and genotype frequencies from initial Hardy- Weinberg conditions in experimental arrays of two color morphs of snapdragons (Antirrhinum majus) visited by freely foraging bumble bees (Bombus appositus and B. flavifrons). The number of pollen grains received by a flower depended most on the number of pollinator visits to the flower, whereas the number of grains exported was best predicted by the total time pollinators spent inside the flower. The pattern of mating generally was assortative with respect to color, as bees tended to overvisit one color or the other within a foraging bout. In arrays where nectar was augmented in one color, the augmented color received both more visits and longer visits. Allele and genotype frequencies in offspring samples were in accord with qualitative expectations based on the pollinator observations, demonstrating that pollinators can directly influence the evolution of single-locus floral traits, at least under simplified experimental conditions.

Journal Article↗

PubMed2005

Clinical evaluation of drug-induced hepatitis.

OBJECTIVE: To ascertain the epidemiological characteristics, clinical symptoms, and evolution of drug-induced hepatitis over the last 22 years. EXPERIMENTAL DESIGN AND SUBJECTS: An observational, retrospective study between 1982 and 1993, and prospective study between 1994 and 2003. All patients in our department diagnosed with having drug-induced hepatitis were studied analyzing epidemiological (age, sex, cases per year, hospitalization) and clinical features (previous liver disease, hepatic symptoms, laboratory results), and follow-up (complete recovery or chronicity). RESULTS: A total of 61 patients were diagnosed as having drug-induced hepatitis, 26 men and 35 women (57%), mean age 52.4 years +/- 17 years, of which 72.2% were older than 40 years. A total of 43% were admitted to hospital. In 87% of cases, two or more drugs were involved, the most frequent being antituberculosis (19 cases), psychotropic (26 cases), and non-steroidal anti-inflammatory drugs (45 cases). Evolution showed that 94% of patients recovered after the withdrawal of suspected causal drugs. CONCLUSIONS: The incidence of drug-induced hepatitis is higher in patients over 40 years of age, it being more common in females. Non-steroidal anti-inflammatory, psychotropic, and anti-tuberculosis agents were the main drugs involved. Most patients made a complete recovery after withdrawal of the suspected causal drug.

Adult↗

PubMedDate not supplied

Inhibition of caspases improves bacterial clearance in experimental peritonitis.

BACKGROUND: Inhibition of caspases improves the antibacterial capacity of leukocytes cultured with peritoneal dialysis solutions, and improves the prognosis of septic, polymicrobial experimental peritonitis. OBJECTIVE: To test whether inhibition of caspases alters the evolution of peritonitis in the presence of peritoneal dialysis solution. DESIGN: 32 mice were assigned to therapy with either the pan-caspase inhibitor zVAD or vehicle for 48 hours following infection with Staphylococcus aureus, in the presence of lactate-buffered, 4.25% glucose peritoneal dialysis solution. 16 mice received vehicle in phosphate-buffered saline. MAIN OUTCOME MEASURE: Number of bacteria recovered from the peritoneum at 48 hours. RESULTS: Peritoneal dialysis solution accelerated leukocyte apoptosis. zVAD decreased the number of apoptotic peritoneal leukocytes and the number of bacteria recovered from the peritoneum at 48 hours (zVAD 2.8 +/- 0.3 vs vehicle 3.9 +/- 0.2 log colony forming units of S. aureus, p = 0.007). CONCLUSIONS: Inhibition of caspases accelerates peritoneal bacterial clearance in the presence of peritoneal dialysis solutions in vivo in the experimental setting. Inhibition of caspases should be explored as a mean to accelerate recovery following peritonitis in the clinical setting.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Model of geometrical and smooth muscle tone adaptation of carotid artery subject to step change in pressure.

Recent experimental studies have shown significant alterations of the vascular smooth muscle (VSM) tone when an artery is subjected to an elevation in pressure. Therefore, the VSM participates in the adaptation process not only by means of its synthetic activity (fibronectins and collagen) or proliferative activity (hypertrophy and hyperplasia) but also by adjusting its contractile properties and its tone level. In previous theoretical models describing the time evolution of the arterial wall adaptation in response to induced hypertension, the contribution of VSM tone has been neglected. In this study, we propose a new biomechanical model for the wall adaptation to induced hypertension, including changes in VSM tone. On the basis of Hill's model, total circumferential stress is separated into its passive and active components, the active part being the stress developed by the VSM. Adaptation rate equations describe the geometrical adaptation (wall thickening) and the adaptation of active stress (VSM tone). The evolution curves that are derived from the theoretical model fit well the experimental data describing the adaptation of the rat common carotid subjected to a step increase in pressure. This leads to the identification of the model parameters and time constants by characterizing the rapidity of the adaptation processes. The agreement between the results of this simple theoretical model and the experimental data suggests that the theoretical approach used here may appropriately account for the biomechanics underlying the arterial wall adaptation.

Adaptation, Physiological↗

PubMed1990

Chimeric phage-bacterial enzymes: a clue to the modular evolution of genes.

Pneumococcal peptidoglycan amidase (N-acetylmuramoyl-L-alanine amidase, EC 3.5.1.28) and phage CPL1 lysozyme degrade a common substrate (choline-containing pneumococcal cell walls); the former hydrolyzes the bond between muramic acid and alanine, whereas the latter breaks down the linkage between muramic acid and glucosamine. The amino acid sequences of their C-terminal domains are homologous. Chimeric genes were constructed by site-directed mutagenesis: a unique SnaBI restriction site in the cpl1 gene, coding for the phage lysozyme, was introduced at a location equivalent to the SnaBI site present in the lytA gene, which codes for the pneumococcal amidase. The resulting genes expressed lytic activities at levels similar to those of the parental genes. The gene products, which have been purified to electrophoretical homogeneity, exhibited unusual combined biochemical properties--e.g., by exchange of protein domains, we have switched the regulatory properties of these enzymes without altering their catalytic activities. Chimeric gene construction in Streptococcus pneumoniae and its bacteriophages is an excellent model to study the modular organization of genes and proteins and to help to establish evolutionary relationships between phage and bacteria. These constructions provide an experimental approach to the molecular processes involved in cassette recruitment during evolution and contribute support to the concept of bacteria as adaptable chimeras.

Amino Acid Sequence↗

PubMed2005

A genetic interpretation of the variation in inbreeding depression.

Inbreeding depression is expected to play an important but complicated role in evolution. If we are to understand the evolution of inbreeding depression (i.e., purging), we need quantitative genetic interpretations of its variation. We introduce an experimental design in which sires are mated to multiple dams, some of which are unrelated to the sire but others are genetically related owing to an arbitrary number of prior generations of selfing or sib-mating. In this way we introduce the concept of "inbreeding depression effect variance," a parameter more relevant to selection and the purging of inbreeding depression than previous measures. We develop an approach for interpreting the genetic basis of the variation in inbreeding depression by: (1) predicting the variation in inbreeding depression given arbitrary initial genetic variance and (2) estimating genetic variance components given half-sib covariances estimated by our experimental design. As quantitative predictions of selection depend upon understanding genetic variation, our approach reveals the important difference between how inbreeding depression is measured experimentally and how it is viewed by selection.

Analysis of Variance↗

PubMedDate not supplied

Ultrastructural studies of the dying-back process. IV. Differential vulnerability of PNS and CNS fibers in experimental central-peripheral distal axonopathies.

A companion paper in this issue (46) described the evolution of peripheral nervous system dying-back disease of the giant axonal type in animals chronically intoxicated with the neurotoxic hexacarbons n-hexane (CH3CH2CH2CH2CH2CH3), methyl n-butyl ketone or MBK (CH3COCH2CH2CH2CH3), and 2,5-hexanedione (CH3COCH2CH2COCH3). The present study compares the distribution and pattern of peripheral (PNS) and central nervous system (CNS) dying-back disease produced by these three neurotoxic hexacarbons with that produced by acrylamide (CH2CHCONH2), and, in addition, employs these compounds to address unresolved issues in the dying-back process. In the PNS, large myelinated fibers in tibial nerve branches supplying calf muscles were especially sensitive in rats intoxicated with hexacarbons. These nerve branches and sensory plantar nerves in the hindfeet were equally vulnerable in acrylamide-treated rats. In both conditions, fibers located at these sites commenced degeneration before the distal regions of much longer and smaller diameter nerve fibers in nerve branches supplying the flexor digitorum brevis muscle and, in rats intoxicated with hexacarbons, before equivalent regions of plantar sensory branches to the digits. Pacinian corpuscles sited in the hindfeet of intoxicated cats were much less vulnerable to MBK than to acrylamide. Rats and cats intoxicated with hexacarbons displayed giant axonal swellings in vulnerable regions of the PNS degeneration in these animals was accompanied by pronounced endoneurial edema. In the CNS, rostral regions of long, ascending tracts (dorso-spino-cerebellar, gracile and, later, the cuneate) and the caudal end of long, descending tracts (lateral colums, ventrolateral and ventromedial tracts) of hexacarbon-treated animals were especially vulnerable. After prolonged intoxication of cats with MBK, giant axonal swelling was also found in preterminal and terminal axons in Rexed laminae V-VII at spinal levels C4 through S3-Neurofilament proliferation without giant axonal swelling was seen in CNS fibers of rats intoxicated with acrylamide. Taken in concert, the findings underline the importance of axon diameter and length in determining the hierarchy of fiber vulnerability and indicate the common sensitivity of selected regions of the PNS and CNS. The term central-peripheral distal axonopathy is introduced to emphasize the widespread, distal distribution of disease in these and in similar experimental conditions. It is suggested that certain human neuropathies (toxic, nutritional, uremic, diabetic and some hereditary polyneuropathies, and the neuropathy associated with multiple myeloma) are additional examples of central-peripheral distal axonopathies.

Acrylamides↗

PubMed1986

Progress of bleomycin-induced lung fibrosis in rabbits.

Progression of lung fibrosis induced in rabbits by intratracheal bleomycin (BLM, 10 mg/kg) was monitored by biochemical and morphological measurements. These indicated that the evolution of fibrosis in the rabbit was slower than in other experimental animals. Histology revealed cellular and fibrocellular lesions 4 weeks after BLM. At 8 weeks these lesions still predominated, indicating continuing active disease accompanied by a progression to fibrosis. The gradual progression of the response was reflected in alterations in lung composition. Changes in lung content of collagen, protein and DNA were evident at 8 weeks after BLM, at which time concentration (micrograms/mg dry weight) of collagen and protein were also elevated (P less than 0.05). Plasma angiotensin converting enzyme (ACE), a marker of endothelial injury, decreased 1 week after BLM (P less than 0.01) and then returned to normal, indicating that endothelial injury does not parallel the fibrotic response. In summary, the continuing active inflammation and slow progress of fibrosis induced by i.t. BLM in the rabbit suggests that this model has advantages over others for the serial study of the cellular and biochemical evolution of lung fibrosis.

Animals↗