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PubMed2001

Desensitization of type 1 angiotensin II receptor subtypes in the rat kidney.

Differences involving serine residues in the sequence of the carboxyl-terminal tail of type 1 angiotensin II (Ang II) receptor subtypes AT(1A) and AT(1B) suggest differences in desensitization ability. We examined the Ang II-induced homologous desensitization patterns of both receptor subtypes in freshly isolated renal structures: glomerulus (Glom), afferent arteriole, and cortical thick ascending limb (CTAL), whose content in each subtype mRNA is different, by measuring variations in intracellular calcium concentration. A preexposure to a maximal dose of Ang II, followed by a second application of the same concentration, induced: 1) a complete desensitization in Glom, where AT(1A) and AT(1B) mRNAs were expressed in similar proportions, and 2) no or partial desensitization in afferent arteriole and CTAL, where AT(1A) mRNA was predominant. In the absence of nephron structure containing only AT(1B) mRNA, we studied rat anterior pituitary cells that exhibit high content in this subtype and observed that desensitization was not complete. In Glom, CTAL, and pituitary cells, desensitization proceeded in a dose-dependent manner. In Glom and CTAL, desensitization occurred via a PKC-independent mechanism. These results suggest that desensitization does not depend on the nature of Ang II receptor subtype but either on the proportion of each subtype in a given cell and/or on cell specific type. This could allow adaptive biological responses to Ang II appropriate to the specific function of a given cell type.

Angiotensin II↗
PubMed2003

Age and aerobic performance in deer mice.

Age impacts the phenotype of all multicellular animals, but lifetime changes in physiological traits are poorly understood for all but a few species. Here, we describe a cross-sectional study of age effects on body composition, aerobic performance and ventilation in deer mice Peromyscus maniculatus. This species lives considerably longer in captivity (in excess of 5 years) than most laboratory rodents, and the adaptational biology of its aerobic physiology is well studied. Our deer mice grew throughout life, and, as is typical for mammals, their basal metabolic rate (BMR) and maximal oxygen consumption in exercise ((VO(2)max)) and thermogenesis ((VO(2)sum)) increased as power functions of mass. Age did not affect BMR, but we found abrupt decreases in growth rate, (VO(2)max) and (VO(2)sum) at approximately 485 days of age, and the mass-adjusted maximal aerobic performance of old mice (5 years of age) was 20% ((VO(2)max)) to 35% ((VO(2)sum)) less than that of young animals. Breathing frequency (f) and oxygen extraction (E(O(2))) also declined with age but did not change abruptly. However, there were no consistent age-related changes in tidal volume (V(T)) or minute volume ((Vmin)) after accounting for the effects of mass and (VO(2)sum). Age influenced several aspects of body composition (lean and fat mass). However, these changes were insufficient to explain the age-related declines in aerobic performance, suggesting that mass-specific oxidative capacity of lean tissue decreased with age. The performance changes we found could engender substantial reductions in the mobility and thermal tolerances of old deer mice. However, very few wild mice are likely to survive to ages where substantial performance decreases occur, so these declines are probably not subjected to strong selection in natural populations.

Acclimatization↗
PubMed2001

Effects of chronic exposure to simulated microgravity on skeletal muscle cell proliferation and differentiation.

Cell culture models that mimic long-term exposure to microgravity provide important insights into the cellular biological adaptations of human skeletal muscle to long-term residence in space. We developed insert scaffolding for the NASA-designed rotating cell culture system (RCCS) in order to study the effects of time-averaged microgravity on the proliferation and differentiation of anchorage-dependent skeletal muscle myocytes. We hypothesized that prolonged microgravity exposure would result in the retardation of myocyte differentiation. Microgravity exposure in the RCCS resulted in increased cellular proliferation. Despite shifting to media conditions promoting cellular differentiation, 5 d later, there was an increase in cell number of approximately 62%, increases in total cellular protein (52%), and cellular proliferating cell nuclear antigen (PCNA) content (2.7 times control), and only a modest (insignificant) decrease (10%) in sarcomeric myosin protein expression. We grew cells in an inverted orientation on membrane inserts. Changes in cell number and PCNA content were the converse to those observed for cells in the RCCS. We also grew cells on inserts at unit gravity with constant mixing. Mixing accounted for part, but not all, of the effects of microgravity exposure on skeletal muscle cell cultures (53% of the RCCS effect on PCNA at 4-6 d). In summary, the mechanical effects of simulated microgravity exposure in the RCCS resulted in the maintenance of cellular proliferation, manifested as increases in cell number and expression of PCNA relative to control conditions, with only a modest reciprocal inhibition of cellular differentiation. Therefore, this model provides conditions wherein cellular differentiation and proliferation appear to be uncoupled.

Animals↗
PubMed2006

Detecting non-Brownian trait evolution in adaptive radiations.

Many phylogenetic comparative methods that are currently widely used in the scientific literature assume a Brownian motion model for trait evolution, but the suitability of that model is rarely tested, and a number of important factors might affect whether this model is appropriate or not. For instance, we might expect evolutionary change in adaptive radiations to be driven by the availability of ecological niches. Such evolution has been shown to produce patterns of change that are different from those modelled by the Brownian process. We applied two tests for the assumption of Brownian motion that generally have high power to reject data generated under non-Brownian niche-filling models for the evolution of traits in adaptive radiations. As a case study, we used these tests to explore the evolution of feeding adaptations in two radiations of warblers. In one case, the patterns revealed do not accord with Brownian motion but show characteristics expected under certain niche-filling models.

Adaptation, Biological↗
PubMed2000

Psychoanalysis and the moral high ground.

The author reflects on the power and ubiquity of moral issues in the human psyche and thus inevitably in psychoanalysis, and suggests that our moral sense may be an adaptive biological strategy. Goodness is sought in others and aspired to in the self, as part of an innate need to build the ego upon experiences of good objects. Kleinian theory suggests a 'natural morality' that can be discerned in the move towards the 'depressive position', involving increasing care and concern for others. The hunger for goodness within is experienced as a moral quest, with strivings both to approve of, and to be approved of by, one's objects. Goodness, felt as moral rightness, is highly prized, and may be claimed falsely for the self or for objects in the form of the 'moral high ground'. Derailments of the analytic standpoint easily occur, away from the search for objective truth towards assumption of the moral high ground, on the part of the patient, the analyst or both. The author shows this occurring clinically and reflects also on how psychoanalytic theory can be misused in the pursuit of moral superiority.

Adult↗
PubMed1998

Nur77, a member of the steroid receptor superfamily, antagonizes negative feedback of ACTH synthesis and secretion by glucocorticoid in pituitary corticotrope cells.

Nur77 is a member of the steroid receptor superfamily and is known to be expressed in animals under stress. We studied the role of nur77 in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis during the stress response using a murine pituitary corticotrope cell line, AtT-20. Corticotropin-releasing hormone (CRH), a stress mediator in the HPA axis, induced the expression of nur77 transiently in AtT-20 cells. Gel shift assay showed that nur77 bound to negative glucocorticoid responsive element (nGRE) in the promoter of the human proopiomelanocortin (POMC) gene and the formation of the nur77-nGRE complex increased after treatment of the cells with CRH. Negative GRE is known to be necessary for the negative regulation by glucocorticoid of the POMC gene expression. In stable transformants of AtT-20 cells expressing a human homolog of nur77, NAK-1, at a high level, glucocorticoid-mediated inhibition of both POMC mRNA induction and ACTH secretion was significantly lower than that in the NAK-1-non-expressing cells (P < 0.001). These results strongly suggest that nur77 antagonizes the negative feedback effect of glucocorticoid on the synthesis and secretion of ACTH in pituitary corticotropes. This suggests that nur77 plays an important role in the pituitary gland in the biological adaptation to overcome stress.

Adaptation, Physiological↗
PubMed2006

Induction of apoptosis via the modulation of reactive oxygen species (ROS) production in the treatment of myeloid leukemia.

Recent advances in genetic and molecular biology have provided greater insight into the biology of acute myeloid leukemia (AML). These investigations have shown that AML is a heterogeneous disease of biologically different entities. Current therapeutic approaches to AML are based on chemotherapy, but the side effects of the drugs used and various complications, including infections and bleeding, are sometimes fatal. In addition, responses to therapy and long-term outcome differ depending on the subentity in question. Therefore, it is essential to develop new therapeutic strategies such as biology adapted treatment based on the individual molecular pathogenesis of AML. Natural compounds appear to be safer than the current chemotherapeutic drugs, and we have therefore sought new potential agents among various natural compounds with the ability to induce the apoptosis of myeloid leukemic cells. Recently, we found that a highly toxic reactive oxygen species (ROS) generated via the hydrogen peroxide/myeloperoxidase [H(2)O(2)/MPO/halide] system by natural compounds induces apoptosis in MPO-positive leukemic cells. This result is of great interest in establishing novel therapeutic approaches to AML mediated through ROS-induced apoptosis of leukemic cells.

Antineoplastic Agents↗
PubMed2004

Regulation of blood flow by prostaglandins.

Prostaglandins (PGs) belong to the family of prostanoids together with thromboxanes and are produced mainly from arachadonic acid by the enzyme cyclooxygenase. PGs are known to stimulate platelet aggregation, mediate inflammation and edema, play a role in bone metabolism and in biological adaptation of connective tissues e.g. tendon. This review covers the role of PG for mediating tissue blood flow at rest and during increases in metabolic demand such as exercise and reactive hyperaemia. There is strong evidence that PGs contribute to elevate blood flow at rest and during reactive hyperaemia in a variety of tissues. Their role for regulating the large increases in muscle blood flow during exercise is less clear which may be explained by redundant mechanisms. Several interactions are known to exist between specific vasodilator substances, and therefore PGs can act in synergy with other substances and contribute to functional hyperaemia. Furthermore, there is evidence for differential, tissue-specific influences of PGs where their influence on blood flow during exercise may be profound.

Animals↗
PubMed1993

Energy metabolism of growing pigs after transportation, regrouping, and exposure to new housing conditions as affected by feeding level.

An experiment was performed to evaluate alterations of energy metabolism with time in 10 groups of 16 barrows just after transportation. Ten-week-old pigs were fed at once (four groups; LF) or twice (three groups; MF) maintenance level (35 and 75 g.kg-.75.d-1, respectively), or allowed ad libitum access to feed (three groups; HF). The 13.5-d experimental period was divided into two balance periods. Heat production (HP) decreased with time. The changes in HP with time were different among feeding level groups (P < .001); the LF group had the greatest decrease. Metabolizable energy intake remained constant with time for the LF and MF groups and decreased for the HF group. Requirements for maintenance energy and efficiency of ME for growth decreased with time. Feeding level influenced (P < .001) energy retention (ER) during the total experimental period. The LF group had a negative ER (-65 kJ.kg-.75.d-1), whereas in the MF and HF groups positive values for ER were obtained (346 and 757 kJ.kg-.75.d-1, respectively). At all feeding levels, animals had a positive protein gain. The level differed between feeding levels (P < .001). Differences among groups (P < .001) were observed in energy retained as fat. Data from the present experiment show that young pigs are not in a steady state of energy metabolism during the 2 wk after transportation. During this period, the relationship between metabolic rate and feed intake alters with time.

Adaptation, Biological↗
PubMed1976

[Comparison of the pharmacokinetic profiles of clenbuterol in rat and dog during toxicological studies (author's transl)].

The pharmacokinetics of the beta-sympathomimetic 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) have been investigated in two animal species during the chronic toxicological studies after single and multiple dosing. After oral administration of 2.5 mg/kg (dog) and 5 mg/kg (rat) the plasma levels showed significant differences. Moreover, a marked sex difference was to be seen in the plasma levels of the rat. The excretion, established only in the dog, showed no difference after single or multiple administration. The elimination occurs predominantly via the kidneys, and the main urinary elimination product is the unchanged clenbuterol. Each of the 8 metabolites is formed only in minor quantities. The biotransformation is not altered by long-term administration. The differences in the plasma levels that are observed with larger doses can be explained by the biological adaptation of the gastrointestinal tract during multiple administration.

Animals↗
PubMed1999

[In Process Citation]

The monograph embraces high number of Bulgarian, Russian, English, American, German, etc. literature sources by most distinguished surgeons--scientists and lecturers, as well as proper long- year operative, scientific and tuition experience. The author treats 93 topics of the abdominal surgery. They are presented in accessible manner with emphasis laid on the most essential, necessary for the favourable outcome of the operation. Therapeutic results are reported, comparable to the best, published by internationally renowned authors. Many single and group illustrations--drawings and photos--are applied. The problems of abdominal surgery are discussed in accessible manner for physicians (specialisilising surgery, internal diseases, anaesthesiology, urology and orthopaedics) and scientific workers, as well as for medical nurses, rehabilitators and kinesitherapeutists. The trend emerges for organ-sparing reconstructive operations, etio-pathogenetically expedient, with biologic adaption of the patients, but also extended blockoperations and simultaneous operations in synchronic diseases.

Journal Article↗
PubMed1991

Issues in human gravitational physiology: a medical perspective on gravity and the cell.

There are many interacting factors that contribute to understanding the effects of gravity and microgravity on human gravitational physiology. Medical practitioners are interested in maintaining human health and performance in the space environment and thus have concerns regarding what biological questions should be addressed during human space excursions. Communication between disciplines and subdisciplines and creation of a common language and perspective must be determined for knowledge to progress. There is a need for increased experimentation supplying a solid data bank to aid in answering biological questions. Perhaps simple things may be as important as complicated discoveries when learning how biological adaptation has occurred.

Adaptation, Physiological↗
PubMed1992

[Stress related immune regulation].

The immune system ist capable of producing factors, which apart from playing a crucial role during the immune response, serve to integrate immune-neuroendocrine circuits with immunoregulatory and metabolic consequences for the organism. Hormones and neuropeptides on the other hand exert direct effects on immune cells via specific surface receptors on such cells. Therefore, there is strong evidence for a bidirectional communication between the immune, endocrine, and central nervous systems mediated by peptide hormones and receptors common to these systems. One element of the immune system's response to stress factors may involve the activation of the hypothalamo-pituitary-adrenal axis and other neuroendocrine circuits. A complex network of neuroendocrine immune systems is able to sustain biologic adaptation and homeostasis in response to stresses and needs to be taken into account in every clinical context of stress responses.

Adaptation, Psychological↗