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PubMed1997

[Endocrine function of the testicle in the Mexican crossbred ram at different times of the year and its opioidergic control during anoestrus].

This work was carried out with the objective of studying the endocrine function of the testes in the Mexican Crossbred Ram (Suffolk x Hampshire) during the different seasons of the year in a latitude of 19 degrees 13' N. Also studied was the opioidergic control of this gland during anoestrus. For this purpose 8 rams were used, from which 3 ml of jugular blood were obtained three times a week to study the seasonal fluctuations in plasma testosterone. The experiment was carried out from May 1993 until June 1994. The androgen was determined by radioimmunoassay. To study the opioidergic control of androgen secretion during seasonal anoestrous (May-June) four of the rams were selected at random and treated with 0.5 mg naloxone at 12 h intervals during 3 continuous weeks. It was observed that blood testosterone was lowest during long days, and concentration was highest during the breeding season. Chronic naloxone medication during anoestrus resulted in a significant increase in blood testosterone (P < 0.001), an effect that was evident after the first week of treatment. When naloxone administration was discontinued, blood testosterone levels returned to basal. With this experiment it was demonstrated that an opioid antagonist such as naloxone administered in low doses, is capable of altering plasma testosterone concentration in the anoestrus ram, giving further support to endogenous opioids as important modulators of reproduction in seasonal breeders such as sheep.

Anestrus↗
PubMed2006

Rasagiline: A second-generation monoamine oxidase type-B inhibitor for the treatment of Parkinson's disease.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, and safety of rasagiline are reviewed. SUMMARY: Rasagiline is a novel, investigational propargylamine that irreversibly and selectively inhibits monoamine oxidase type B (MAO-B). Rasagiline demonstrates complete and selective inhibition of MAO-B and is at least five times more potent than selegiline. Unlike selegiline, which is metabolized to amphetamine derivatives, rasagiline is biotransformed to the nonamphetamine compound aminoindan. Clinical studies have revealed that rasagiline is associated with improved outcomes in patients with early Parkinson's disease (PD) and also reduces "off" time in patients with moderate to advanced PD with motor fluctuations. Rasagiline is rapidly absorbed by the gastrointestinal tract and readily crosses the blood-brain barrier. The optimal therapeutic dosage is 0.5-1 mg administered orally once daily. Rasagiline appears to be well tolerated, although elderly patients may be more prone to treatment-emergent adverse cardiovascular and psychiatric effects. At the recommended therapeutic dosage of up to 1 mg once daily, tyramine restriction is unnecessary. In addition to MAO-B inhibition, rasagiline has demonstrated neuroprotective properties in experimental laboratory models. The mechanisms whereby rasagiline exerts neuroprotective effects are multifactorial and include upregulation of cellular antioxidant activity and antiapoptotic factors. CONCLUSION: Rasagiline is an investigational selective and irreversible inhibitor of MAO-B that has demonstrated efficacy and safety for the treatment of PD. Whether rasagiline is associated with clinically significant neuroprotection is the subject of ongoing clinical trials.

Clinical Trials as Topic↗
PubMed2002

Seasonal variation in the niche, habitat availability and population fluctuations of a bivoltine thermophilous insect near its range margin.

We investigated the niche requirements of the summer and autumn/spring generations of the bivoltine butterfly, Polyommatus bellargusRott., and their implications for population dynamics at sites occurring near its northern range margin. The larvae of this species are sedentary, and the turf height and shelter of Hippocrepis comosa foodplants selected for egg-laying accurately predict larval distributions within United Kingdom (UK) sites. We found a significant shift between the plants used for egg-laying in each generation, with the niche occupied by summer-feeding larvae being broader and different to the autumn one. Measurements of soil temperature confirmed that the short, sheltered foodplants selected by ovipositing females in autumn placed the autumn/spring-feeding generation of larvae in the warmest available microclimates within sites. In late spring, egg-laying females avoided the hottest spots but extended egg-laying into taller, less sheltered (relatively cool) turf where the microclimate was similar to that experienced by autumn/spring-feeding larvae. Using each generations' definition of niche requirement, we analysed surveys of foodplant populations available on 24 UK sites for P. bellargus, and estimated that nearly twice as many plants were available to the summer-feeding larvae compared to those feeding in the autumn. Annual adult population counts match these seasonal differences in site carrying capacity; first generation counts (from autumn-laid eggs) were generally half as abundant as in the second generation, and more variable. These results suggest that the seasonal cycle of niche switches represents an annual (autumn-spring) bottleneck for populations of this butterfly at its northern range margin. Under climate warming we predict that the inter-generational difference in niche availability, carrying capacity and population size will be reduced. We recommend revised management requirements for this threatened species under current and predicted climates in northern Europe.

Animals↗
PubMed1992

Respiratory and cardiac rhythms as windows to central and autonomic biobehavioral regulation: selection of window frames, keeping the panes clean and viewing the neural topography.

Respiratory and cardiovascular processes figure importantly in biobehavioral regulation. Various cardiac and respiratory measures may, furthermore, index the activity of relatively distinct central and autonomic mechanisms. In this regard, I consider ventilatory indices of central drive and timing of respiration, and rhythmic cardiac-interval fluctuations as reflections of parasympathetic and sympathetic cardiac influences. Particular emphasis is placed upon the phenomenon of respiratory sinus arrhythmia (RSA). A number of conceptual and methodological questions are addressed concerning quantification and inference. Among others, these include the following issues: (1) What is the evidence that the three cardiac periodicities slower than heart rate reflect distinct autonomic mechanisms? (2) Does RSA reflect tonic or phasic parasympathetic regulation of heart rate? (3) Do specific quantification procedures for measuring these rhythms provide superior estimates? (4) What are some potential pitfalls for quantification and inference.

Arousal↗
PubMed1984

[Fluctuations in the "evenly hovering attention" and their therapeutic processing].

For epistemological and empirical reasons, Freud's "evenly hovering attention" has to be understood as an advice that the analyst should remain open for new observation. It is a recommendation against having preconceived ideas and biases. In fact, the analyst's attention is regulated by conscious and unconscious selections. It is subject to considerable changes in the analyst's cognitive processes. His countertransference influences his attention. The patient in turn reacts consciously or unconsciously to the variations of the analyst's attention. It is therefore necessary to interpret those changes and sometimes to admit them. This recognition supports the reality testing of the patient in the analytic situation. Otherwise malign regressions or denials and other defensive processes might occur. We give an example of the changes in the "evenly hovering attention" of an analyst and their handling.

Adaptation, Psychological↗
PubMed2002

Evolution of ageing.

Explaining why ageing occurs is a solution to the longstanding enigma of the role of senescence in nature. Even after half a century of progress, this solution continues to unfold. Evolution theory argues strongly against programmed ageing, suggesting instead that organisms are programmed for survival, not death. In the current view, ageing results from the twin principles that (i) the force of natural selection declines with age, and (ii) longevity requires investments in somatic maintenance and repair that must compete against investments in growth, reproduction and activities that might enhance fitness. In addition to explaining why ageing occurs, the evolutionary theory also provides insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence, as well as an array of testable predictions. Some of the most interesting current problems are to understand how the genetic factors influencing ageing and longevity are predicted to respond to fluctuating environments, such as temporary periods of famine, as well as to other kinds of spatial and/or temporal heterogeneity. Rapid progress in human genomics raises the prospect of greatly increasing our knowledge of the determinants of human longevity. To make progress in understanding the role and evolution of genetic and non-genetic factors in human longevity, we need more detailed theoretical studies of how intra-population variables, such as socio-economic status, influence the selection forces that shape the life history.

Aged↗
PubMed1999

Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process.

Prostate cancers require androgen for growth but progress to an androgen-independent stage under the selective pressure of androgen ablation therapy. Here we describe a novel human prostate cancer xenograft (LAPC-9) propagated by serial passage in male severe combined immunodeficient mice that expresses prostate-specific antigen and wild-type androgen receptor. In response to castration, LAPC-9 cells undergo growth arrest and persist in a dormant, androgen-responsive state for at least 6 months. After prolonged periods of androgen deprivation, spontaneous androgen-independent outgrowths develop. Thus, prostate cancers progress to androgen independence through two distinct stages, initially escaping dependence on androgen for survival and, subsequently, for growth. Through the use of serial dilution and fluctuation analysis, we provide evidence that the latter stage of androgen independence results from clonal expansion of androgen-independent cells that are present at a frequency of about 1 per 10(5)-10(6) androgen-dependent cells. We conclude that prostate cancers contain heterogeneous mixtures of cells that vary in their dependence on androgen for growth and survival and that treatment with antiandrogen therapy provides selective pressure and alters the relative frequency of these cells, thereby leading to outgrowths of androgen-independent cancers.

Androgens↗
PubMed1992

Allometry and prediction in hominoids: a solution to the problem of intervening variables.

To avoid misinterpretation of allometric exponents determined from interspecific allometric comparisons, specific conditions must be met with respect to the common reference variable. Body weight is considered to be the best general indication of overall size and is hence widely acknowledged to be the most suitable reference variable. However, because of the paucity of recorded body weights for museum specimens, various comparative studies have used other size indicators as intervening variables, although the allometric relationships to body size/weight were often unknown and possibly differed between species. Because of differences in the scaling properties of alternative intervening variables across the species investigated, conflicting conclusions may be drawn if different variables are chosen as substitutes for overall size. This is illustrated with two examples. In this study, series of skeletons with associated body weights of Gorilla, Pan, Pongo, and Homo were investigated. Both ontogenetic and static adult allometric relationships between several widely used reference variables and body weight were determined. Neither these variables nor additional estimators investigated in this study displayed allometric exponents and coefficients similar enough across species to justify direct interspecific comparison. To generate an alternative size estimator for both ontogenetic and static interspecific investigations, equations for combined sexes were derived to predict body weight from various long bone dimensions for individual hominoid species. From a total of 25 predictors, 12 prediction equations per species (six for nonadults and six for adults) were selected according to their relative suitability for reliable prediction of body weight. It is shown that the derived reference variable "predicted body weight" avoids problems of intervening variables, is valid for any interspecific ontogenetic and static allometric comparison, and displays less fluctuation in comparison to actual body weight.

Animals↗
PubMed1990

A model of empathic understanding and adherence to treatment regimens in practitioner-patient relationships.

Empathic understanding in practitioner relationships is postulated as necessary for adherence to therapeutic regimens. It is considered to be one of the most important practitioner relationship skills leading ultimately to patient health benefit. Research literature from a wide-range of health disciplines including personality theory, social psychology, psychotherapy, psycho-analysis, and practitioner-patient communication highlights the key role of empathic processes in personal health care. A model of empathic understanding is described which attempts to integrate the substantive findings in the research literature and seeks to generate new ideas for further investigation. The model addresses theoretical relationships between practitioners' empathic understanding, patients' knowledge of their illness and motivation to get better, adherence to treatment advice, and outcome. Recent work on the selection and training of medical and nursing staff in empathic skills is reviewed. A number of areas for future research are outlined including the effect of individual practitioner differences in the components of empathy, empathic compatibility in practitioner-patient dyads, fluctuations in levels of practitioner empathy during long-term care, specific practitioner behaviours which communicate empathy, and the relationship between factors of patient satisfaction and the perception of empathic understanding.

Communication↗
PubMed2001

The electronic nose as a rapid sensor for volatile compounds in treated domestic wastewater.

An electronic nose consisting of 12 metal oxide sensors was used to monitor volatile compounds in effluent of a domestic wastewater treatment plant. Effluent and reference (deionized water) samples were heated to 60 and 90 degrees C to promote the volatilization and to increase the sensitivity. An effluent measuring campaign of 12 weeks was conducted and the repeatability and reproducibility of the procedure and the apparatus were determined. Processing the obtained fingerprints with principal component analysis (PCA) allowed interpretation and differentiation of the samples in terms of origin and quality, relative to the reference. To minimize the variance due to sensitivity fluctuations of the apparatus and to detect effluents with deviating qualities, two new concepts were defined, i.e. the relative sensorial odour perception (in short: rSOP) and the relative fingerprint. Correlations between the relative overall electronic nose output, expressed as rSOP, and selected routine parameters were weak except for the parameter "volatile suspended solids" (VSS), indicating adsorption of volatile organic compounds (VOCs) onto the organic particles. The results clearly demonstrate the possibility to use the electronic nose as a rapid alarm generator towards volatile compounds, e.g. in specific advanced treatment processes to produce reclaimed water from effluent of the domestic wastewater treatment plant under scrutiny.

Adsorption↗
PubMed1998

Emergency room visits of asthmatic children, relation to air pollution, weather, and airborne allergens.

BACKGROUND: The worldwide increase in the incidence, prevalence, and severity of asthma may suggest that environmental factors play a role in these epidemiologic changes. OBJECTIVE: To examine the correlations between air pollutants, weather conditions, airborne allergens, and the incidence of emergency room (ER) visits of children with acute asthma attacks. DESIGN: One-year prospective study. Data of daily concentration of air pollutants, weather conditions, and selective airborne allergens were collected and compared with the number of ER visits of asthmatic children. SUBJECTS: 1076 asthmatic children (aged 1 to 18 years) who presented at the Pediatric ER between January 1 and December 31, 1993. RESULTS: Correlations between fluctuations in ER visits of asthmatic children and various environmental parameters were more relevant for weekly than for daily values. Emergency room visits correlated positively with concentrations of NOx, SO2 and with high barometric pressure; and negatively with O3 concentration and minimal and maximal temperature. There were no significant correlations with concentrations of particulates, humidity, or airborne pollen and spores. An exceptionally high incidence of ER visits of asthmatic children was observed during September. This peak coincided with the beginning of the school year and the Jewish holidays. The correlations between ER visits and the environmental factors increased significantly when the September peak was excluded, revealing that 61% of the variance in ER visits was explained by NOx, SO2, and 03 concentrations, 46% by weather parameters, 66% by NOx, SO2 and barometric pressure, and 69% by the combination of air pollutants and weather parameters. CONCLUSION: The major factors found to be associated with ER visits of asthmatic children were high NOx, high SO2, and high barometric pressure. Negative correlation was found between ER visits of asthmatic children and ozone concentrations. The particularly high number of ER visits at the beginning of the school year and the Jewish holidays was probably associated with an increase in the number of viral infections and/or emotional stress.

Adolescent↗
PubMed2000

Evidence for phase-separated quantum dots in cubic InGaN layers from resonant raman scattering

The emission of light in the blue-green region from cubic InxGa1-xN alloys grown by molecular beam epitaxy is observed at room temperature and 30 K. By using selective resonant Raman spectroscopy (RRS) we demonstrate that the emission is due to quantum confinement effects taking place in phase-separated In-rich quantum dots formed in the layers. RRS data show that the In content of the dots fluctuates across the volume of the layers. We find that dot size and alloy fluctuation determine the emission wavelengths.

Journal Article↗
PubMed2001

Spontaneous mutations that confer antibiotic resistance in Helicobacter pylori.

In this study, we systematically examined in vitro frequencies and spectra of the spontaneous mutations in Helicobacter pylori that confer resistance to clarithromycin (Cla(r)), metronidazole (Mtz(r)), amoxicillin (Amx(r)), ciprofloxacin (Cip(r)), and rifampin (Rif(r)). The mutation rate of Rif(r) or Cip(r) determined in a fluctuation assay is 1 x 10(-8) to 2 x 10(-8) per cell per division. In contrast, the mutation rates of Cla(r), Mtz(r), and Amx(r) are much lower (<10(-9)). However, Mtz(r) mutants could be readily selected in vitro by using the serial passage method, suggesting that the mutagenic effect and selective effect of a sublethal dose of metronidazole contribute to the rapid development of Mtz(r). Analysis of spontaneous Rif(r), Cla(r), and Cip(r) mutants confirmed previous results indicating that mutations within the rpoB gene, the 23S rRNA gene, and the gyrA gene, respectively, are responsible; also, several new mutant alleles were identified. Mtz(r) mutants resulted most frequently, but not always, from mutations in the rdxA gene. DNA fragments containing each mutant allele could readily transform susceptible H. pylori strains to resistance, confirming that each mutant allele is responsible for the resistance phenotype.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Gabapentin in the treatment of epilepsy in the elderly].

INTRODUCTION: Epilepsy is the third most common neurological disease in the elderly. Diagnosis of epilepsy in this age is increasing because more people are reaching older age and physician awareness about this disorder is higher than in the past. Seizures are suspected in patients with episodic impairment of consciousness and neurological function, but in addition, seizures can be the cause of fluctuating cognitive derangement and nocturnal episodes of neurological dysfunction. DEVELOPMENT: The etiological spectrum of epilepsy in the elderly is different than in younger adults because of a higher prevalence of cerebrovascular disease and degenerative disorders of the central nervous system. The selection and dosage of antiepileptic drugs requires proper attention to special pharmacokinetic and pharmacodynamic situations that are common in older individuals. Changes that occur with advanced age are responsible of distinct pharmacokinetics, decreased tolerability to antiepileptic drugs, concomitant systemic diseases. In addition poor compliance and polypharmacy can complicate therapy. CONCLUSIONS: Gabapentin has favourable pharmacokinetic properties: lack of hepatic metabolism, no protein binding, and easy to calculate regimen for patients with renal failure. For these reasons is a good candidate drug for treatment of seizures in the elderly.

Acetates↗
PubMed1978

Serotoninergic involvement in the regulation of circadian rhythms of hypothalamic-pituitary adrenal and prolactin axis.

A detailed review of their own experiments and of data existing in the literature regarding the role played by 5HT in the control of circadian rhythms of HHAA and HHPA is given by the AA. In rats, a positive correlation between 5-HT content in the limbic system and plasma corticosterone circadian rhythm has been shown to exist by means of pharmacological and neurosurgical approaches. Lesions of the raphe area result in an abolition of diurnal periodicity of plasma steroids similar to that obtained after inhibition of 5-HT synthesis by means of PCPA. A modification of the amplitude of the plasma corticosterone circadian variations also occurs after more selective destruction of some nuclei (n. centralis superior and n. raphe dorsalis) which reduced 5-HT concentration both in the hypothalamus and the hippocampus. Isolation of the mediobasal hypothalamus by a frontal cut posterior to the optic chiasma abolishes the diurnal fluctuation of plasma corticosterone, indicating that the suprachiasmatic nucleus is a focal site for the 5-HT regulation of the phasic activity of the HHAA. Evidence in favour of 5-HT mechanisms in the limbic area as the biological clock regulating the circadian variations of the adrenal axis is also provided. Restoration of the diurnal rhythm of plasma corticosterone after its abolition could be explained with the existence of a small functional pool of brain 5-HT or with the development of receptor supersensitivity. Pharmacological and surgical manipulation on central 5-HT neurons suggest the existence of two distinct serotoninergic mechanisms, a limbic one and an intrahypothalamic one, which play a modulatory role in the circadian variations of plasma PRL. Also in this case, adaptive accessory brain structures can take over in restoring the circadian hormones periodicity in conditions of impairment of the main serotoninergic mechanisms.

5,6-Dihydroxytryptamine↗
PubMed1987

A new sustained-release theophylline suspension for asthmatic children: evaluation of serum theophylline concentrations.

Theophylline level variability obtained with standard slow-release theophylline tablets was compared to that obtained with a new sustained-release theophylline suspension in asthmatic children. The sustained-release preparations were administered every 12 hours and serum samples were collected after ten days of treatment during the steady-state period. In this crossover study, the sequence of the two regimens (slow-release tablets versus slow-release suspension) was selected at random. Both preparations of theophylline were administered at a mean dosage (+/- s.d.) of 19.3 +/- 1 mg/kg/day. The results of our study demonstrated that theophylline serum levels remain within the therapeutic range for both preparations, but there was a greater fluctuation with theophylline suspension compared to the tablets. The tolerability of the two drugs was satisfactory.

Adolescent↗
PubMed1985

Translational control of the circadian rhythm of liver sterol carrier protein. Analysis of mRNA sequences with a specific cDNA probe.

The striking changes in amount of rat liver SCP (sterol carrier protein) during a 24-h dark-light cycle are due to alterations in the relative synthetic rate of SCP. However, functional SCP mRNA, measured by a cell-free translational assay, does not fluctuate in the dark-light cycle. Since cell-free translational assays do not always reflect the actual abundance of an mRNA molecule, a specific cDNA hybridization assay was used to directly quantitate SCP mRNA sequences. The cDNA probe was selected from a rat liver library by hybridization to a mixture of synthetic oligonucleotides containing a portion of the sequence of SCP mRNA. The relative amount and size distribution of the SCP mRNA species (approximately 700-800 nucleotides) does not change during the diurnal cycle. To explore possible mechanisms of this translational control, the polysomal distribution of SCP mRNA was compared at the maximum and minimum points of SCP synthesis. No significant amounts of SCP mRNA were present in nonpolysomal ribonucleoprotein particles. Furthermore, no alteration in the relative level of SCP mRNA associated with polysomes or in polysome size occurs at the maximum and minimum points of SCP synthesis. Thus, changes in total SCP mRNA levels or its polysomal distribution cannot account for the diurnal variation in SCP synthesis.

Animals↗
PubMed1984

Rapid eye movement (REM)-sleep during and after continuous infusion of the oxazoline derivate S3341: a comparison with clonidine.

The frequency and duration of rapid eye movement (REM)-sleep episodes were examined in normotensive rats during and after cessation of continuous infusion of either clonidine (10 micrograms/kg/h) or the oxazoline derivative S3341 (50 micrograms/kg/h) for 10 days. Both compounds abolished REM-sleep during the infusion. On cessation of the clonidine infusion there was a rebound increase in the frequency and duration of REM-sleep episodes. These episodes were associated with markedly exaggerated blood pressure fluctuations. On cessation of the S3341 infusion, the frequency and duration of REM-sleep episodes returned to control levels. Blood pressure responses were not different from controls. These post-infusion differences may be related to the greater degree of selectivity of S3341 for the alpha 2-adrenoceptor rather than the alpha 1-adrenoceptor subtype.

Animals↗