Segmental aplasia of the uterus associated with hydrometra in a goat.
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Animals↗
Biomedical subjects
A Espinosa
Publications and source records attributed to A Espinosa.
Concatenated retrieval of correlated stored information in neural networks.
We consider a coupled map lattice defined on a hypercube in M dimensions, taken here as the information space, to model memory retrieval and information association by a neural network. We assume that both neuronal activity and spike timing may carry information. In this model the state of the network at a given time t is completely determined by the intensity y(sigma,t) with which the information pattern represented by the integer sigma is being expressed by the network. Logistic maps, coupled in the information space, are used to describe the evolution of the intensity function y(sigma(upper arrow),t) with the intent to model memory retrieval in neural systems. We calculate the phase diagram of the system regarding the model ability to work as an associative memory. We show that this model is capable of retrieving simultaneously a correlated set of memories, after a relatively long transient that may be associated to the retrieving of concatenated memorized patterns that lead to a final attractor.
Action Potentials↗
A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer's disease.
OBJECTIVE: To determine the usefulness of an interactive multimedia internet-based system (IMIS) for the cognitive stimulation of Alzheimer's disease. METHODS: This is a 24-week, single-blind, randomised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer's disease receiving stable treatment with cholinesterase inhibitors (ChEIs). The patients were divided into three groups: (1) those who received 3 weekly, 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program (IPP); (2) those who received only IPP sessions; and (3) those who received only ChEI treatment. The primary outcome measure was the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Secondary outcome measures were: Mini-Mental State Examination (MMSE), Syndrom Kurztest, Boston Naming Test, Verbal Fluency, and the Rivermead Behavioral Memory Test story recall subtest. RESULTS: After 12 weeks, the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE, which was maintained through 24 weeks of follow-up. The patients treated with IPP alone had better outcome than those treated with ChEIs alone, but the effects were attenuated after 24 weeks. All patients had improved scores in all of the IMIS individual tasks, attaining higher levels of difficulty in all cases. CONCLUSION: Although both the IPP and IMIS improved cognition in patients with Alzheimer's disease, the IMIS program provided an improvement above and beyond that seen with IPP alone, which lasted for 24 weeks.
Aged↗
Suppression of ferromagnetic double exchange by vibronic phase segregation.
From Raman spectroscopy, magnetization, and thermal expansion on the system La(2/3)(Ca(1-x)Sr(x))(1/3)MnO3, we have been able to provide a quantitative basis for the heterogeneous electronic model for manganites exhibiting colossal magnetoresistance (CMR). We construct a mean-field model that accounts quantitatively for the measured deviation of T(C)(x) from the T(C) predicted by de Gennes double-exchange in the adiabatic approximation and predicts the occurrence of a first-order transition for a strong coupling regime, in accordance with the experiments. The existence of a temperature interval T(C) < T < T*, where CMR may be found, is discussed in connection with the occurrence of an idealized Griffiths phase.
Journal Article↗
(Q)SAR studies to design new human choline kinase inhibitors as antiproliferative drugs.
Most of the signal transduction pathways are mediated by protein kinases regulating every aspect of cell function. Mutations which deregulate their expression or their function or both result in cancers. Therefore, protein kinase inhibitors have become the focus of development of new therapies for cancer. A comprehensive review of Choline kinase (ChoK) was published by us in 2003. Since then, molecular information of ChoK inhibitors has been accumulated. In this review, we intend to summarize the new lines of evidence that will include the design of the most active antiproliferative agents so far described against ChoK. Studies have been aimed at the establishment of structure-activity relationships and the structural parameters that define ChoK inhibitory and antiproliferative activities of a set of twenty-five acyclic biscationic pyridophane and forty acyclic biscationic quinolinephane compounds. The corresponding QSAR equation was obtained for the whole set of bisquinolinium compounds for the antiproliferative activity, taking into consideration the electronic parameter sigma(R) of R(4), the molar refractivity (MR) of R(8), and the lipophilic parameters clog P and pi(linker). The most potent antiproliferative agent shows an IC(50) = 0.45 microM, predicted by the QSAR equation, whilst its experimental value is IC(50) = 0.20 microM. Finally, toxicity assays were performed for the most promising compounds because of their interesting antiproliferative activities [IC(50 HT-29) = 0.70, 0.80, 1.50 and 1.90 microM] and low toxicity [LD(50) = 16.7, 12.5, > 25 and > 20 mg/kg of mouse]. These biological activities justify further analysis for antitumoral assays under in vivo conditions.
Animals↗
Medical ethnobotany of the Teribes of Bocas del Toro, Panama.
Ethnomedical uses of 108 medicinal plant species, belonging to 52 families, 89 genera, used by the Teribe Amerindians of Bocas del Toro Province in Panama, along with their socio-cultural practices are reported here. The methods of administration of the herbal remedies, the plant parts used, their families and local names are also documented. The recorded medicinal plants were used mainly for fever, various type of pain and inflammation. The potential value of 26 plants and their traditional uses was elucidated through literature search.
Ethnobotany↗
Structural elucidation of a new delta2-pyrazoline derivatives using 1H and 13C NMR spectroscopy.
This paper describes the unequivocal structural elucidation of a new kind of Delta2-pyrazoline derivatives carried out by means of monodimensional 1H and 13C NMR spectroscopies, bidimensional ones such as HMBC and HMQC experiments, and NOEDIFF effects. Conformational analysis of this molecule agrees very well with the experimentally NOEDIFF effects found.
Carbohydrates↗
Capacitative calcium entry in testosterone-induced intracellular calcium oscillations in myotubes.
Ca2+ oscillations are one of the most important signals within the cell. The mechanism for generation of Ca2+ oscillations is still not yet fully elucidated. We studied the role of capacitative Ca2+ entry (CCE) on intracellular Ca2+ oscillations induced by testosterone at the single-cell level in primary myotubes. Testosterone (100 nM) rapidly induced an intracellular Ca2+ rise, accompanied by Ca2+ oscillations in a majority of myotubes. Spectral analysis of the Ca2+ oscillations revealed a periodicity of 20.3 +/- 1.8 s (frequency of 49.3 +/- 4.4 mHz). In Ca(2+)-free medium, an increase in intracellular Ca2+ was still observed, but no oscillations. Neither nifedipine nor ryanodine affected the testosterone-induced Ca2+ response. This intracellular Ca2+ release was previously shown in myotubes to be dependent on inositol-1,4,5-trisphosphate (IP3). Intracellular Ca2+ store depletion in Ca(2+)-free medium, using a sarcoplasmic/endoplasmic reticulum calcium ATPase-pump inhibitor, followed by re-addition of extracellular Ca2+, gave a fast rise in intracellular Ca2+, indicating that CCE was present in these myotubes. Application of either testosterone or albumin-bound testosterone induced Ca2+ release and led to CCE after re-addition of Ca2+ to Ca(2+)-free extracellular medium. The CCE blockers 2-aminoethyl diphenylborate and La3+, as well as perturbation of the cytoskeleton by cytochalasin D, inhibited testosterone-induced Ca2+ oscillations and CCE. The steady increase in Ca2+ induced by testosterone was not, however, affected by either La3+ or cytochalasin D. These results demonstrate testosterone-induced Ca2+ oscillations in myotubes, mediated by the interplay of IP3-sensitive Ca2+ stores and Ca2+ influx through CCE.
Animals↗
Primary trochlear headache: a new cephalgia generated and modulated on the trochlear region.
BACKGROUND: The authors have observed a group of patients complaining of periorbital pain, emanating from the trochlear area, in absence of trochleitis or other orbital or systemic disease. All were previously diagnosed and treated as different types of headaches, but pain was not controlled until local treatment on the sore trochlea was performed. The authors have investigated the role of the trochlear area in causing and modulating headache. METHODS: Observational case series. Trochlear pain was defined as pain on this area, exacerbated upon examination and looking in supraduction. Pain was studied after trochlear injections of lidocaine, corticosteroids, and placebo. Secondary orbital pain was ruled out. RESULTS: Seventeen women and one man were evaluated (mean age: 44 years). All presented unilateral pain in the trochlear area (60% reported more extended headache), for more than 1 year in 70%. Neither ocular autonomic signs nor motility restrictions were observed. Imaging examinations were normal in 100%. The temporal pattern was either chronic or remitting, with acute exacerbations. Pain increased at night in 55%. A total of 62% presented concurrent headaches. Locally injected corticosteroids relieved the pain within 48 hours in 95% and also improved concurrent headaches, by decreasing attack frequency and analgesics intake. Placebo was not helpful. Relapses were observed in 45% (average 8 months). CONCLUSIONS: The trochlear region is the origin of a specific and unrecognized headache, which we have named primary trochlear headache. Local treatment on the trochlear area is also useful for other concurrent primary headaches with inadequate response to oral therapy.
Adrenal Cortex Hormones↗
IGF-I and insulin induce different intracellular calcium signals in skeletal muscle cells.
We studied the effect of IGF-I and insulin on intracellular Ca(2+) in primary cultured myotubes. IGF-I induced a fast and transient Ca(2+) increase, measured as fluo-3 fluorescence. This response was blocked by both genistein and AG538. IGF-I induced a fast inositol-1,4,5-trisphosphate (IP(3)) increase, kinetically similar to the Ca(2+) rise. The Ca(2+) signal was blocked by inhibitors of the IP(3) pathway. On the other hand, insulin produced a fast (<1 s) and transient Ca(2+) increase. Insulin-induced Ca(2+) increase was blocked in Ca(2+)-free medium and by either nifedipine or ryanodine. In the normal muscle NLT cell line, the Ca(2+ )signals induced by both hormones resemble those of primary myotubes. GLT cells, lacking the alpha1-subunit of dihydropyridine receptor (DHPR), responded to IGF-I but not to insulin, while GLT cells transfected with the alpha1-subunit of DHPR reacted to both hormones. Moreover, dyspedic muscle cells, lacking ryanodine receptors, responded to IGF-I as NLT cells, however they show no insulin-induced calcium increase. Moreover, G-protein inhibitors, pertussis toxin (PTX) and GDPbetaS, blocked the insulin-induced Ca(2+) increase without major modification of the response to IGF-I. The different intracellular Ca(2+) patterns produced by IGF-I and insulin may improve our understanding of the early action mechanisms for these hormones in skeletal muscle cells.
Animals↗
Gas-bubble lesions in stranded cetaceans.
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Animals↗
Aberrant expression of the CD8 antigen in B cell chronic lymphocytic leukaemia.
We report a case of aberrant expression of the T cell antigen CD8 in a patient with B cell chronic lymphocytic leukaemia (B-CLL). A 62-year-old Caucasian female with several enlarged lymph nodes and suspected to have B-CLL was referred to our laboratory for routine immunophenotyping. Peripheral blood cell count showed moderate leucocytosis without other abnormalities. The dual-colour flow cytometric analysis showed a typical B-CLL phenotype (CD45+, CD19+, kappa+, lambda-, CD20+, CD23+, IgM+, HLA-DR+, CD5/CD19+, CD3-). In addition, aberrant expression of the T cell marker CD8 was found, present on approximately 64% of the leukemic cells. This is a rare even, the significance and nature of this aberration has not yet been fully determined. In this case, our patient had a rapid response to treatment with a remarkable reduction in the number of leukemic cells only two weeks after beginning treatment.
Antigens, CD↗
QSAR-derived choline kinase inhibitors: how rational can antiproliferative drug design be?
This review presents an overview of Choline Kinase (ChoK) inhibitors with antiproliferative activity. The consideration of ChoK as a novel target for the development of new anticancer drugs is justified. The synthesis of several derivatives based on structural modifications of hemicholinium-3 (HC-3) is not accompanied by potentiation of the neurological toxicity of HC-3. The increment of both ChoK inhibitory and antiproliferative activities was successfully obtained by the two following changes: a) substitution of the oxazonium moiety of HC-3 by several aromatic heterocycles, and b) using the 1,2-ethylene(bisbenzyl) moiety instead of the 4,4'-biphenyl fragment. In an attempt to understand the ChoK inhibitory activity, a quantitative structure-activity relationship was developed. The QSAR equations have described the forces involved in quantitative terms. The electron characteristic of the substituent at position 4 of the heterocycle and the lipophilic character of the whole molecule were found to significantly affect the antitumour activity in compounds 17-95. Trispyridinium compounds 91-95 are more potent than the bispyridinium ones 87-89 as ChoK inhibitors. Nevertheless, 91-95 are less active than 87-89 as antiproliferative agents because the latter show better lipophilicities to cross the cytosolic membranes. Inhibition of the growth of human tumours in nude mice has been demonstrated: Antitumour activity of compound 64 against human HT-29 produced a decrease of up to 70% in the size of the tumour in nude mice. These results indicate that ChoK can be used as a general target for anticancer drug design against Ras-dependent tumourigenesis.
Animals↗
Assessing clinical probability of organic disease in patients with involuntary weight loss: a simple score.
BACKGROUND: Involuntary weight loss (IWL) is a frequent complaint with a difficult diagnosis. Any one of a number of different diseases may be the source of the symptom. However, there is no universal clinical protocol that can help physicians study this complex syndrome. METHODS: In March 1998, we defined a diagnostic protocol for the study of IWL. IWL was defined as an involuntary and documented weight loss of at least 5% of the usual body weight in the previous 3 months. We analyzed 78 consecutive patients with IWL who came to our clinic between March 1998 and December 2000. RESULTS: An organic disease was found in 56% of cases; cancer, metabolic and digestive diseases were the most common entities. Psychiatric problems were found in 33% of cases. After extensive study, an idiopathic group of 11% was identified. The variables that were independently predictive of a final diagnosis of organic disease were: age>50 years (OR: 8.6, CI 95%: 1.7-43.6), psychiatric symptoms (OR: 0.2, CI 95%: 0.1-0.8), smoking (OR: 14.3, CI 95% 2.3-74), the presence of guide symptoms (OR: 8.0, CI 95%: 1.8-34.4), and anemia (OR: 3.1, CI 95%: 2.5-387). Sixteen percent of the patients died, more often those suffering from organic diseases. Based on multivariate regression coefficients, a clinical risk score was established. CONCLUSIONS: IWL is a complex and frequent syndrome with a 16% rate of mortality during the first year. A protocol based on clinical data can help in the management of IWL. Our clinical prediction rule may help physicians to identify those patients with IWL who are likely to have an underlying organic disease.
Journal Article↗
Quantitative structure-activity relationships for a series of symmetrical bisquaternary anticancer compounds.
56 biscationic dibromides with distinct polar heads [bis(4-substituted)pyridinium, bis(4-aminoquinolinium), bisquinolinium, and bisisoquinolinium moieties] and several spacers between the two charged nitrogen atoms were synthesised. This oriented synthesis produced 45 inhibitors of choline kinase with antitumour activity against the HT-29 cell line. In an attempt to understand the antiproliferative activity, a quantitative structure-activity relationship was developed. The unknown sigma(R) and sigma(R)(+) descriptors for the diallylamino, pyrrolidino, piperidino and perhydroazepino groups and sigma(R) for the N-methylanilino moiety, were estimated by (13)C NMR spectroscopy in a simple, fast and reproducible manner. The electron characteristic of the substituent at position 4 of the heterocycle and the theoretical lipophilic character of the whole molecule were found to significantly affect the antitumour activity. 1,1'-[Ethylenebis(benzene-1,4-diylmethylene)]bis[4-(N-methylanilino)pyridinium] dibromide is the most active compound of the series so far described and shows a reasonable agreement between predicted and observed antiproliferative data (predicted pIC(50)=6.50, experimental pIC(50)=6.46).
Antineoplastic Agents↗
Effect of levels of starch, fiber, and lactose on digestion and growth performance of early-weaned rabbits.
The effect of source of carbohydrate on gut histology, digestion efficiency, and growth performance in early-weaned (25 d) rabbits at the starter period (25 to 39 d) was investigated. Six diets were factorially arranged to study the effect of partial substitution of starch (0, 25, or 50%) by lactose at two levels of fiber (30 or 36% NDF). Diets were formulated to meet or exceed essential nutrient requirements of growing rabbits. A feeding trial was conducted to measure the effect of treatments on growth performance in 252 rabbits that were fed the experimental diets in the starter period and thereafter received a common feed until 60 d of age. Fecal apparent digestibility was determined at 35 d of age in nine animals per diet. The four diets with extreme lactose content were used to determine ileal apparent digestibility of starch and lactose (nine replicates per diet), weights of stomach and cecum, stomach pH, cecal fermentation traits, amylase and disaccharidase activities (10 animals per diet), and jejunal morphology (six animals per diet). Weaning increased (P < 0.001) amylase activity by 59% but decreased (P < 0.001) maltase, sucrase, and lactase activities by 30, 48, and 72%, in parallel with a reduction of villus height by 19%. Dietary NDF level did not affect either jejunal morphology or sucrase and lactase activities but increased amylase (P = 0.05) and maltase (P < 0.001) activities by 22 and 92%, respectively. Substitution of starch by lactose had no effect on jejunal morphology or enzymatic activity. Ileal lactose and starch digestibility were not affected by dietary NDF or lactose level and averaged 73.8 and 90.8%, respectively. Substitution of starch by fiber and lactose affected ileal flux of starch plus lactose (by -0.5 and +1.7 g/d) and cecal pH (by +2.1 and -2.8%, respectively). Fecal NDF digestibility was relatively low (23.1% on average) and was not affected by treatments, whereas that of lactose and starch was almost complete. An increase of dietary NDF level led to an impairment of ADG and feed efficiency in the starter (P < 0.002) and in the overall (P < 0.03) fattening period. Substitution of starch by lactose linearly decreased (P < 0.001) feed efficiency in the starter period and linearly increased (P < 0.001) diarrhea incidence in the fattening period. The results indicate that digestive capability of early-weaned rabbits is limited and should be taken into account to establish optimal levels and sources of carbohydrates in the starter diet.
Animal Feed↗
The bifunctional Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) protein is necessary for amebic growth and survival and requires an intact C-terminal domain for both alcohol dahydrogenase and acetaldehyde dehydrogenase activity.
The intestinal protozoan pathogen Entamoeba histolytica lacks mitochondria and derives energy from the fermentation of glucose to ethanol with pyruvate, acetyl enzyme Co-A, and acetaldehyde as intermediates. A key enzyme in this pathway may be the 97-kDa bifunctional E. histolytica alcohol dehydrogenase 2 (EhADH2), which possesses both alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase activity (ALDH). EhADH2 appears to be a fusion protein, with separate N-terminal ALDH and C-terminal ADH domains. Here, we demonstrate that EhADH2 expression is required for E. histolytica growth and survival. We find that a mutant EhADH2 enzyme containing the C-terminal 453 amino acids of EhADH2 has ADH activity but lacks ALDH activity. However, a mutant consisting of the N-terminal half of EhADH2 possessed no ADH or ALDH activity. Alteration of a single histidine to arginine in the putative active site of the ADH domain eliminates both ADH and ALDH activity, and this mutant EhADH2 can serve as a dominant negative, eliminating both ADH and ALDH activity when co-expressed with wild-type EhADH2 in Escherichia coli. These data indicate that EhADH2 enzyme is required for E. histolytica growth and survival and that the C-terminal ADH domain of the enzyme functions as a separate entity. However, ALDH activity requires residues in both the N- and C-terminal halves of the molecule.
Alcohol Dehydrogenase↗
LUMO energy of model compounds of bispyridinium compounds as an index for the inhibition of choline kinase.
Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include electron-releasing, neutral or electron-withdrawing groups. A one-parameter regression equation has been derived which satisfactorily describes the ex vivo inhibitory potency of ChoK of the title compounds. The electronic effect plays a critical function in the ex vivo inhibition of ChoK although the role of electrostatic interactions could be altered due to a solvation process of both ChoK and ligands.
Choline Kinase↗