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Biomedical subjects

E Font

Publications and source records attributed to E Font.

18 recordsLinked to original sources

Chemosensory assessment of sperm competition levels and the evolution of internal spermatophore guarding.

Males of many species adjust their reproductive behaviour according to the perceived risk of sperm competition. Although this phenomenon is widespread in insects and other animals, the mechanisms that allow mates to assess sperm competition levels remain largely unexplored. In this study, we analysed the mating behaviour of pairs of Tenebrio molitor beetles under three odour treatments representing increasing levels of sperm competition risk (SCR) and sperm competition intensity (SCI). Copula duration and male and female post-copulatory behaviour varied significantly with odour treatment. Both copula duration and post-copulatory associations (PCAs) increased significantly in odour treatments reflecting high male density. To our knowledge, this is the first study to report that insects may assess the actual density of potential competitors at the time of mating, a cue to SCR and SCI, on the basis of chemical cues. In T. molitor, males inhibit sperm release from the spermatophore of a rival male when remating takes place at short intervals. We show that, when sperm competition levels are high, PCAs increase female remating interval just above that necessary to prevent spermatophore inhibition by rival males. This finding strongly suggests that strategic male behaviour plays a 'spermatophore guarding' role in this species. Although common in insects with external spermatophore transfer, spermatophore guarding is not expected in species with rapid ejaculate transfer and internal spermatophore delivery. Our results reveal that spermatophore guarding may evolve, even under these circumstances, as an evolutionary response to short-term spermatophore inhibition or displacement mechanisms.

Analysis of Variance↗

A double-blind randomized comparative trial: eberconazole 1% cream versus clotrimazole 1% cream twice daily in Candida and dermatophyte skin infections.

In a double-blind phase III study the efficacy and tolerance of eberconazole 1% cream was compared with clotrimazole 1% cream, applied twice daily for four consecutive weeks in 157 patients, with mycologically proven cutaneous candidosis (24 patients, 25 infected sites) and in 133 patients with dermatophyte skin infections (141 treated sites). The analysis was carried out by number of infected and treated sites. The four groups of sites and the distribution of target lesions were similar. The distribution of the sum of clinical scores and infecting organisms were also similar. There were no differences between the groups in terms of the range and mean duration of infection. At the end of therapy and on follow-up in skin candidosis the proportion of patients with effective treatment was 73 and 50% for clotrimazole and eberconazole, respectively. Premature termination due to adverse effects was 26.7% for clotrimazole and 20% for eberconazole. At the end of treatment of dermatophyte infections the proportion of patients with effective treatment was 46% for clotrimazole and 61% for eberconazole. At the overall assessment (6 weeks after the end of treatment) eberconazole was judged effective in 72% of treated sites, whereas clotrimazole was effective in 61%, this difference was not statistically significant (P = 0.15). There were three relapses (4%) in the clotrimazole-treated group and one relapse (1%) in the eberconazole group. One patient treated with eberconazole cream (1%) had a premature termination due to adverse events attributable to the medication.

Administration, Topical↗

Neurogenesis and neuronal regeneration in the adult reptilian brain.

Evidence accumulated over the last few decades demonstrates that all reptiles examined thus far continue to add neurons at a high rate and in many regions of the adult brain. This so-called adult neurogenesis has been described in the olfactory bulbs, rostral forebrain, all cortical areas, anterior dorsal ventricular ridge, septum, striatum, nucleus sphericus, and cerebellum. The rate of neuronal production varies greatly among these brain areas. Moreover, striking differences in the rate and distribution of adult neurogenesis have been noted among species. In addition to producing new neurons in the adult brain, lizards, and possibly other reptiles as well, are capable of regenerating large portions of their telencephalon damaged as a result of experimentally-induced injuries, thus exhibiting an enormous potential for neuronal regeneration. Adult neurogenesis and neuronal regeneration take advantage of the same mechanisms that are present during embryonic neurogenesis. New neurons are born in the ependyma lining the ventricles and migrate radially through the brain parenchyma along processes of radial glial cells. Several lines of evidence suggest that radial glial cells also act as stem cells for adult neurogenesis. Once they reach their final destination, the young neurons extend axons that reach appropriate target areas. Tangential migration of neurons alongside the ventricular ependyma has also been reported. Most of these tangentially migrating neurons seem to be destined for the olfactory bulbs and are, thus, part of a system similar to the mammalian rostral migratory stream. The proliferation and recruitment of new neurons appear to result in continuous growth of most areas showing adult neurogenesis. The functional consequences of this continuous generation and integration of new neurons into existing circuits is largely conjectural, but involvement of these phenomena in learning and memory is one likely possibility.

Aging↗

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review.

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV-infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.

Adult↗

[Anorexia nervosa: a multidisciplinary approach].

The childhood-adolescent psychiatrics field has, for various years, been confronted by a very significant increase in cases of nervous anorexia, a serious eating disorder characterized by a noticeable loss of weight. At the bottom of this situation lie complex biological, psychological and social-cultural problems, which demand an interdisciplinary approach to solve them. This article presents the predisposing factors, the initial factors, the factors which maintain this disorder...; what behaviors are considered to be normal; what the physical and psychological manifestations are; as well as what the medical evaluation carried out is ... to finalize with an explanation of the different functions to be performed by each member of a multidisciplinary team.

Adolescent↗

Determination of zidovudine triphosphate intracellular concentrations in peripheral blood mononuclear cells from human immunodeficiency virus-infected individuals by tandem mass spectrometry.

Nucleoside reverse transcriptase inhibitors (NRTIs) used against the human immunodeficiency virus (HIV) need to be activated intracellularly to their triphosphate moiety to inhibit HIV replication. Intracellular concentrations of these NRTI triphosphates, especially zidovudine triphosphate (ZDV-TP), are relatively low (low numbers of femtomoles per 10(6) cells) in HIV-infected patient peripheral blood mononuclear cells. Recently, several methods have used either high-performance liquid chromatography (HPLC) or solid-phase extraction (SPE) coupled with radioimmunoassay to obtain in vivo measurements of ZDV-TP. The limit of detection (LOD) by these methods ranged from 20 to 200 fmol/10(6) cells. In this report, we describe the development of a method to determine intracellular ZDV-TP concentrations in HIV-infected patients using SPE and HPLC with tandem mass spectrometry for analysis. The LOD by this method is 4.0 fmol/10(6) cells with a linear concentration range of at least 4 orders of magnitude from 4. 0 to 10,000 fmol/10(6) cells. In hispanic HIV-infected patients, ZDV-TP was detectable even when the sampling time after drug administration was 15 h. Intracellular ZDV-TP concentrations in these patients ranged from 41 to 193 fmol/10(6) cells. The low LOD obtained with this method will provide the opportunity for further in vivo pharmacokinetic studies of intracellular ZDV-TP in different HIV-infected populations. Furthermore, this methodology could be used to perform simultaneous detection of two or more NRTIs, such as ZDV-TP and lamivudine triphosphate.

Adult↗

Analysis of antiretroviral nucleosides by electrospray ionization mass spectrometry and collision induced dissociation.

Antiretroviral nucleoside drugs used against the human immunodeficiency virus (HIV) infection have been analyzed using negative ion electrospray ionization (ESI) mass spectrometry and collision-induced dissociation (CID-MS/MS). Mass fragmentation of azidothymidine (AZT), didanosine (ddI), dideoxycytidine (ddC) and dideoxythiacytidine (3TC) were obtained at different cone voltages and collision energies. Fragmentation of purines and pyrimidines occurred by different pathways. For purines (ddI), the fragmentation was similar to those found in endogenous nucleosides; mainly the pseudo molecular ion is present (M-H)- and a cleavage through the glycosidic bond forming (B)- was observed. For pyrimidines (AZT, ddC, 3TC), the fragmentation pathways were different from endogenous nucleosides; for AZT, the fragmentation occurred primarily through the elimination of the azido group in the 3'-position (M-H2-N3)-, whereas ddC and 3TC presented more complex fragmentation patterns. For ddC, fragmentation appeared to be dominated by a retro Diels-Alder mechanism (M-CONH)-. For 3TC, the sulfur atom in the sugar moiety provided greater stability to the charge, producing fragments where the charge resided initially in the dideoxyribose (M-C2O2H6)-.

Anti-HIV Agents↗

Trigeminal projections to the dorsal thalamus in a lacertid lizard, Podarcis hispanica.

Trigeminothalamic projections in the lizard Podarcis hispanica were investigated by means of biotinylated dextranamine (BDA) injections into different nuclei of the dorsal thalamus. Previous studies of lizards found a projection from the sensory trigeminal nuclei in the brainstem to the nuclei ventromedialis and ventrolateralis of the ventral thalamus. The present results show that, in addition to these projections to ventral thalamic nuclei, neurons of the nucleus of the descending tract and the principal sensory nucleus project contralaterally to the pretectal nucleus lentiformis thalami and bilaterally to the nucleus dorsolateralis anterior thalami of the dorsal thalamus. The contralateral projection to the nucleus dorsolateralis anterior is more developed than its ipsilateral counterpart and appears to be topographically organized. Since the nucleus dorsolateralis thalami has ascending projections to the cortex telencephali, this nucleus may be the thalamic relay of trigeminal sensory information to the telencephalon.

Animals↗

Postnatal neurogenesis in the telencephalon of turtles: evidence for nonradial migration of new neurons from distant proliferative ventricular zones to the olfactory bulbs.

Postnatal neurogenesis in the the turtle telencephalon was investigated by using bromodeoxyuridine immunocytochemistry and [3H]thymidine autoradiography. Red-eared slider turtles Trachemys scripta elegans (Cryptodira, Emydidae) 2-3 months old were injected with the thymidine analogue 5'-bromodeoxyuridine (BrdU) and allowed to survive for 7, 30, 90, and 180 days. Results indicate that cells in the walls of the lateral ventricles continue to proliferate postnatally. Shortly after BrdU treatment (seven days) most labelled cells were found in the walls of the lateral ventricles (ventricular zone: VZ). Labelled cells were particularly abundant in and around the ventricular sulci. The same pattern of labelling was found in the telencephalon of juvenile turtles (> two years old) injected with BrdU and killed seven day later, suggesting that the proliferative activity continues in the telencephalic VZ of turtles during juvenile stages of life and possibly into adulthood. With longer survival periods after BrdU administration (30, 90, and 180 days), the VZ of the telencephalon showed a similar pattern of labelling to that found at seven days. Furthermore, with survival periods of 90 and 180 days labelled cells resembling neurons were found in most telencephalic regions. The largest numbers of these putative neurons were found in the olfactory bulbs. By using [3H]thymidine autoradiography combined with electron microscopy these postnatally generated cells were confirmed as neurons. We conclude that postnatal neurogenesis occurs in the turtle telencephalon. This process is most prominent in the olfactory bulbs. From the pattern of proliferation of neuronal precursors in the VZ we infer that neurons recruited postnatally into the olfactory bulbs come from distant proliferative VZs in the walls of the lateral ventricles.

Animals↗

3-Acetylpyridine-induced degeneration and regeneration in the adult lizard brain: a qualitative and quantitative analysis.

The neurotoxin 3-acetylpyridine (3AP) produces highly selective neuronal damage in specific areas of the lizard brain. Following 3AP intoxication, proliferation and migration of replacement neurons born in the ventricular walls lead to regeneration of the lesioned areas. Earlier studies established the time course of 3AP-induced degeneration and subsequent regeneration in the medial cerebral cortex of adult lizards (Font, E., García-Verdugo, J.M., Alcántara, S. and Lopez-García, C., Neuron regeneration reverses 3-acetylpyridine-induced cell loss in the cerebral cortex of adult lizards, Brain Res., 551 (1991) 230-235 [13]). Complementary to our previous studies, we now provide a qualitative and quantitative account of the extent and distribution of neurotoxic damage in the brain as a whole of lizards treated with 3AP using Nissl and Golgi stains, a degeneration-sensitive reduced-silver method, and electron microscopy. Additionally, [3H]thymidine autoradiography was used to assess changes in the rate of neurogenesis caused by the 3AP treatment. Single doses of 3AP caused degenerative changes in all the cortical areas, anterior dorsal ventricular ridge, deep layers of the lateral cortex, lateral amygdaloid nucleus, and nucleus sphericus, while sparing other brain areas. The most frequent neuropathic change after 3AP treatment was clumping of the nuclear chromatin with formation of pyknotic nuclei. Occasionally, a second type of injury was observed in neurons of the cell layer of the dorsomedial cortex (DMC). 3AP also caused a conspicuous loss of dendritic spines in bipyramidal neurons of the dorsomedial and dorsal cortices possibly representing transneuronal degeneration. Numbers of [3H]thymidine-labeled cells were higher in lizards previously treated with 3AP than in controls. These results demonstrate that the neurotoxic lesion is capable of inducing an increase in the normal rate of adult neurogenesis. Whereas regeneration in the remaining areas was morphologically and histologically complete, in some animals, cell proliferation in the DMC resulted in formation of an abnormal cell plate.

Animals↗

Localization of brainstem motoneurons involved in dewlap extension in the lizard, Anolis equestris.

Dewlap extension is a characteristic component of inter- and intraspecific displays of Anolis lizards. Dewlap extension is accomplished by the contraction of ceratohyoid muscles associated with the hyoid apparatus. Retrograde transport of horseradish peroxidase (HRP) was used to investigate the brainstem origins of efferent fibers to the ceratohyoid muscles in Anolis equestris. Following application of HRP to the ceratohyoid muscle or to its nerve supply on one side of the throat, large polygonal motoneurons were found ipsilaterally in the vagal (Amb X) and glossopharyngeal (Amb IX) parts of nucleus ambiguus. Labelled neurons were more abundant and more heavily labelled in Amb X than in Amb IX. In addition, small spindle-shaped cells were labelled ipsilaterally in three parasympathetic nuclei that innervate glandular structures in the pharyngeal floor. HRP injections of the larynx labelled cells in many of the same locations, including Amb X and Amb IX. Thus, the nucleus ambiguus in Anolis contains motoneurons for supply of striated muscles in the hyoid (i.e. ceratohyoid muscles) and the larynx.

Animals↗

Neuron regeneration reverses 3-acetylpyridine-induced cell loss in the cerebral cortex of adult lizards.

Systemic administration of the neurotoxin 3-acetylpyridine to adult lizards results in extensive loss of neurons in the medial cerebral cortex, other brain areas remaining largely unaffected. After the neurotoxic trauma, new cells are produced by mitotic division of cells in the ventricular wall. The new cells migrate along radial glial fibers and replace lost neurons in the medial cortex. Electron microscopic examination of cells labeled with [3H]thymidine confirms that the newly generated cells are neurons. Thus, neuron regeneration can occur in the cerebral cortex of adult lizards.

Animals↗

Functional morphology of dewlap extension in the lizard Anolis equestris (Iguanidae).

The dewlap is an extendible flap of skin ordinarily folded under the throat. Lizards, particularly those in the genus Anolis, extend their dewlaps during interactions with conspecifics, other lizards, and potential predators. Dewlap extension is effected by movements of elements of the hyoid apparatus. This paper describes the anatomy of the hyoid and associated musculature in Anolis equestris, a large arboreal lizard with a prominent dewlap. A mechanism for dewlap extension is proposed based on results of morphological and experimental techniques. Specializations of the hyoid skeleton for dewlap extension include elongated second ceratobranchials and highly movable joints between the ceratohyals and the hypohyals and between the first ceratobranchials and the body of the hyoid. A well developed M. ceratohyoideus extends between the ceratohyals and the first ceratobranchials of the hyoid apparatus. During dewlap extension, the hyoid apparatus acts as a first order lever. Contraction of M. ceratohyoideus pulls the ceratohyals posteriorly causing the hypohyals and the body of the hyoid to rotate dorsally around the first ceratobranchial/body joints. This movement results in the second ceratobranchials swinging forward and down, unfolding the dewlap. The relative immobility of the first ceratobranchials provides stability to the hyoid apparatus during dewlap extension. A comparison is made of dewlap extension and other hyoid displays.

Animals↗

Dissimilar effects in acute toxicity studies of CDP-choline and choline.

The LD50 and LD0 of choline HCl and cytidine diphosphate choline (CDP-choline, citicoline, Somazina) by oral and intravenous route at equivalent doses of choline for both compounds were determined. The qualitative and quantitative analysis of the results obtained lead to the conclusion that choline shows a remarkable cholinergic action, while CDP-choline both orally and intravenously does not cause any cholinergic intoxication in the treated groups, like those recorded for choline administration. It should be emphasized that when the quantity of choline contained in CDP-choline administered was identical to that of choline with which the animal group was treated showing signs of cholinergic crisis, the animals corresponding to CDP-choline did not show any of these symptoms. Objective evaluation showed that CDP-choline by oral and intravenous route does not behave like a choline groups donator, at least not with an intensity which would make us believe that its only action was due to the increased levels of choline; this proves that CDP-choline administration yields clearly differentiated metabolic consequences from those yielded by choline administration.

Administration, Oral↗

Effect of oral CDP-choline on acrylamide-induced lesion.

Administration of low doses of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) (50 mg/kg) to mice and rats has proved to be effective in preventing acrylamide-induced neurological syndrome. Likewise, the simultaneous dosing of both drugs, which causes an evident loss of weight in the animals, has demonstrated that an activation on the dopaminergic system is produced.

Acrylamide↗

Bioavailability of methyl-14C CDP-choline by oral route.

In this work, the bioavailability of the 14C-methyl-labelled cytidine diphosphate choline (CDP-Choline, citicoline, Somazina), has been studied by oral route, leading to the result that it is slowly and completely absorbed, with a very low urinary and fecal elimination, thus producing maintained blood levels. The bioavailability related to oral route compared with intravenous route is practically the same.

Administration, Oral↗

Radioactivity incorporation into different cerebral phospholipids after oral administration of 14C methyl CDP-choline.

Oral administration of 14C methyl CDP-choline in Sprague-Dawley rats provided the following data: --Radioactivity from cytidine diphosphate choline (CDP-choline, citicoline, Somazina) is found in the brain at a high rate. --62.8% of total radioactivity measured in the brain is found as a part of phospholipids. --This radioactivity is detected by the labelling of phosphatidyl-choline and endogenous sphingomyelin from CDP-choline. This suggests that CDP-choline by oral administration has effects on the synthesis of basic phospholipids being essential for the structure and function of the cellular membrane.

Administration, Oral↗