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Biomedical subjects

B Morales

Publications and source records attributed to B Morales.

At least 19 recordsLinked to original sources
PubMed2006

Plasma aminopeptidase activities in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by a progressive motor disorder, but frequently is accompanied by autonomic symptoms such as hypotension. Together with the decrease of dopamine, significant decreases in aminopeptidase activities have been reported in PD brains. However, up to date there are no studies about changes of aminopeptidase activities in plasma of PD patients. We studied plasma activities of alanyl-, aspartyl-(AspAP), cystinyl-(CysAP) and glutamyl-aminopeptidase (GluAP) in two groups of subjects: control (n=41) and PD (n=48). Plasma activities of AspAP, CysAP, and GluAP showed significant decreases of 24.9% (p<0.05), 39.4% (p<0.01) and 33.3% (p<0.01), respectively, in PD group. These aminopeptidases are involved in the metabolism of circulating peptides such as the ones of the renin-angiotensin system. The importance of aminopeptidases in striatal dopamine content and in neuroendocrine system in PD is discussed.

Aged↗
PubMed2005

Dopaminergic function in a family with the PARK6 form of autosomal recessive Parkinson's syndrome.

A G309D mutation in the PINK1 gene in a consanguineous Spanish kindred with seven siblings, three of whom are clinically affected, has recently been shown to be a cause of the PARK6 form of autosomal-recessive Parkinson's syndrome. In this family, we studied pre- and postsynaptic dopaminergic function using 123I-FP-CIT- and 123I-iodobenzamide-SPECT to determine binding to the presynaptic dopamine transporter (DAT) and postsynaptic D2 receptors respectively. All three PARK6 patients showed reduced striatal DAT binding with posterior preponderance similar to sporadic idiopathic PD, but only one patient showed significant striatal asymmetry. In two of the siblings, DAT binding was markedly increased. IBZM-SPECT was normal in both patients and sibs. Our findings indicate that 123I-FP-CIT-SPECT shows similar DAT binding in PARK6 patients compared to idiopathic Parkinson's disease. The increased DAT binding in heterozygous PARK6 carriers may be a new very early preclinical finding, but its significance is still unclear.

Adult↗
PubMed2005

Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1).

Depression is a common symptom in Parkinson's disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT)n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet (AAT)n of the gene that encodes CB1 (CNR1) receptor in 89 subjects (48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression (Fisher's exact test: P=0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.

Aged↗
PubMed2004

Detection of circulating antigens in experimental anisakiasis by two-site enzyme-linked immunosorbent assay.

A two-site enzyme-linked immunosorbent assay (ELISA) based on the avidin-biotin system was developed to study circulating antigens in the sera of rats orally or intraperitoneally infected with L3 larvae of Anisakis simplex s.l. Somatic and excretory-secretory antigens were detected from 24 h post-infection in all infected rats. A direct relationship between the number of larvae inoculated and the concentration of antigens in the sera was demonstrated; however, the amount of antigen decreased with the course of the infection. Comparative analysis revealed that intraperitoneal inoculation is most appropriate for detecting excretory-secretory antigens in serum. The minimum concentrations of A. simplex antigen detectable were approximately 2.5 microg/ml for somatic and excretory-secretory antigens. This antigen detection assay may have application in the diagnosis of anisakiasis.

Animals↗
PubMed2002

Apolipoprotein E genotype and schizophrenia: further negative evidence.

OBJECTIVE: To investigate the association between apolipoprotein E (ApoE) genotype and schizophrenia. METHOD: We genotyped 106 schizophrenic out-patients [Diagnostic Statistic Manual IV (DSM-IV) criteria] and 250 healthy volunteers (hospital staff and blood donors) from Asturias (Northern Spain). The ApoE genotypes (epsilon2, epsilon3, epsilon4-alleles) were determined after polymerase chain reaction (PCR) amplification, followed by digestion with the restriction enzyme Cfol and electrophoresis on a 4% agarose gel. RESULTS: No significant differences in ApoE-allele frequencies between patients and controls was found, although an increased 64-frequency was recorded in patients compared with controls [9.0% vs. 6.2%, P = 0.124; odds ratio (OR) = 1.49; 95% confidence interval (CI) = 0.82-2.70]. ApoE-genotype frequencies did not differ between both groups. The mean age of onset for schizophrenic patients that carried the epsilon4-allele was not significantly different from that of patients without this allele. CONCLUSION: Variation in the ApoE gene was not associated with the development of schizophrenia in our population. ApoE-genotypes did not modify the age of onset of the disease.

Adult↗
PubMed2001

Developmental inhibitory gate controls the relay of activity to the superficial layers of the visual cortex.

A developmental reduction in the radial transmission of synaptic activity has been proposed to underlie the end of the critical period for experience-dependent modification in layers II/III of the visual cortex. Using paired-pulse stimulation, we investigated in visual cortical slices how the propagation of synaptic activity to the superficial layers changes during development and how this process is affected by sensory experience. The results can be summarized as follows. (1) Layers II/III responses to repetitive stimulation of the white matter become increasingly depressed between the third and sixth week of postnatal development, a time course that parallels the end of the critical period. (2) Paired-pulse depression is reduced after dark rearing and also by blocking inhibitory synaptic transmission. (3) Paired-pulse depression and its regulation by age and sensory experience is more pronounced when stimulation is applied to the white matter than when applied to layer IV. Together, these results are consistent with the idea that the maturation of intracortical inhibition reduces the capability of the cortex to relay incoming high-frequency patterns of activity to the supragranular layers.

Aging↗
PubMed2001

Platelet activating factor increases ciliary activity in the hamster oviduct through epithelial production of prostaglandin E2.

We investigated the signal transduction mechanisms associated with an increase in ciliary beat frequency (CBF) produced by platelet activating factor (PAF) in oviductal ciliated cell cultures. In the range of concentrations similar to that produced by preimplantation embryos, PAF increased the CBF in a dose-dependent manner. The addition of PAF and prostaglandin E2 (PGE2) to the cultures produced a synergic increase of ciliary beating, suggesting that PAF and PGE2 signal transduction pathways may be associated. To demonstrate this hypothesis, cyclooxygenase-2 (COX-2) was selectively blocked by a specific inhibitor, NS-398, and the PAF-induced CBF increase was abolished. Moreover, a phospholipase A2 (PLA2) inhibitor, AACOCF3, blocks the PAF-induced CBF increase. PGE2 production by oviductal epithelial cells is stimulated by PAF, and WEB-2086, a PAF-receptor blocker, specifically blocks the PAF-induced PGE2 production. Using the fluorescent indicator fura-2, we measured the effect of PAF on intracellular Ca2+ concentration ([Ca2+]i) in individual ciliated cells. PAF induced a transient increase of [Ca2+]i that was blocked by WEB-2086 or by removal of extracellular Ca2+. We propose a mechanism for PAF-mediated signal transduction in the ciliated cells of the oviductal epithelium. Minimal doses of PAF trigger Ca2+ mobilization in tandem with increased PLA2 activity and a COX-2-mediated increase in PGE2. Local PGE2 production by the oviductal mucosa suggests the presence of an autocrine loop controlling ciliary activity.

Animals↗
PubMed2001

[Radioguided surgery of hyperparathyroidism. A case report].

Primary hyperparathyroidism is the main cause of hypercalcemia in ambulatory patients. Classic surgical resolution of this disease includes bilateral cervical exploration with exhibition of the four parathyroid glands and evaluation of the suspicious gland with a rapid biopsy. We report a 79 years old female with a primary hyperparathyroidism in whom the adenoma causing the disease was located with the help of an intraoperative gamma-probe that detected the zone of higher radiation counting of Tc99m Sestamibi, that was injected preoperatively. The patient was discharged with normal serum calcium and phosphate levels.

Adenoma↗
PubMed2000

Zinc and copper modulate differentially the P2X4 receptor.

The rat ATP P2X4 receptor was expressed in Xenopus laevis oocytes to assess the effect of zinc and copper as possible regulators of purinergic mechanisms. ATP applied for 20 s evoked an inward cationic current with a median effective concentration (EC50) of 21.4+/-2.8 microM and a Hill coefficient (nH) of 1.5+/-0.1. Coapplication of ATP plus 10 microM zinc displaced leftward, in a parallel fashion, the ATP concentration-response curve, reducing the EC50 to 8.4+/-1.8 microM (p < 0.01) without altering the receptor nH. The zinc potentiation was fast in onset, easily reversible, and voltage-independent and did not require metal preexposure. The zinc EC50 was 2-5 microM, with a bell-shaped curve. At concentrations of 100-300 microM, zinc produced less potentiation, and at 1 mM, it inhibited 50% the ATP current. The effect of zinc was mimicked by cadmium. In contrast, copper inhibited the ATP-evoked currents in a time- and concentration-dependent fashion, reducing the maximal current (Imax) without altering the EC50. The copper-induced inhibition was slow in onset, slowly reversible, and voltage-independent. Whereas coapplication of 300 microM copper plus ATP reduced Imax to 36.2+/-5%, the coapplication of, or 60-s preexposure by, 10 microM copper reduced Imax to 79+/-9.2% (p < 0.05) and 39.6+/-8.7% (p < 0.01), respectively. The inhibition was noncompetitive in nature and mimicked by mercury. Cobalt, barium, and manganese did not modify significantly the ATP-evoked current, demonstrating metal specificity. The simultaneous 1-min preapplication of both metals revealed that the 10 microM zinc-induced potentiation was obliterated by 10 microM copper, whereas 30 microM copper not only reduced the potentiation, but inhibited the ATP response. Following coapplication of both metals for 20 s with ATP, at least 100 microM copper was required to counteract the 10 microM zinc-induced potentiation. The simultaneous preincubation with both metals provided evidence for a noncompetitive interaction. We hypothesize the existence of metal binding site(s), which are most likely localized in the extracellular domain of the P2X4 receptor structure. These sites are selective and accessible to extracellular metal applications and bind micromolar concentrations of metals. The present results are compatible with the working hypothesis that trace metals, such as copper and zinc, are physiological modulators of the P2X4 receptor. The modulation of brain purinergic transmission by physiologically and toxicologically relevant trace metal cations is highlighted.

Adenosine Triphosphate↗
PubMed2000

Functional cross talk after activation of P2 and P1 receptors in oviductal ciliated cells.

The presence of ATP and adenosine receptors and their role in controlling ciliary activity in oviductal ciliated cells was studied by measuring the ciliary beat frequency (CBF) in oviductal tissue cultures. ATP, adenosine, and related compounds increased the CBF in a dose-dependent manner. We established that P2 receptors of subtype 2Y(2) and P1 receptors of subtype A(2a) mediated the responses to ATP and adenosine, respectively. We found evidence to suggest that stimulation of ciliary activity by ATP requires D-myo-inositol 1,4, 5-trisphosphate [Ins(1,4,5)P(3)] metabolism, intracellular Ca(2+) mobilization, and protein kinase C activation. On the other hand, the adenosine effect is mediated by activation of a G(s) protein-dependent pathway that enhances cAMP intracellular levels. To study the interaction between P2 and P1 receptors, cells were stimulated simultaneously with both agonists. We observed a synergistic increase of the CBF even at agonist concentrations (100 nM) that did not produce a significant response when added separately to the culture. Furthermore, a blocker of the cAMP pathway produced a reduction of the ATP response, whereas a blocker of the Ins(1,4,5)P(3) pathway also produced an inhibition of the adenosine response. Our evidence demonstrates that both ATP and adenosine receptors are present in a single ciliated cell and that a mechanism of cross talk could operate in the transduction pathways to control ciliary activity.

Adenosine↗
PubMed1999

BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex.

Maturation of the visual cortex is influenced by visual experience during an early postnatal period. The factors that regulate such a critical period remain unclear. We examined the maturation and plasticity of the visual cortex in transgenic mice in which the postnatal rise of brain-derived neurotrophic factor (BDNF) was accelerated. In these mice, the maturation of GABAergic innervation and inhibition was accelerated. Furthermore, the age-dependent decline of cortical long-term potentiation induced by white matter stimulation, a form of synaptic plasticity sensitive to cortical inhibition, occurred earlier. Finally, transgenic mice showed a precocious development of visual acuity and an earlier termination of the critical period for ocular dominance plasticity. We propose that BDNF promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity.

Age Factors↗
PubMed1999

Cold-hot mismatch between Tc-99m HMPAO-labeled leukocytes and Tc-99m ciprofloxacin in axial skeleton infections: a report of three cases.

Radiolabeled leukocyte scintigraphy is a well-established technique for the diagnosis of inflammation and infection with a typical presentation of a hot spot within the abnormal areas. However, in some cases of osteomyelitis of the axial skeleton, a cold defect pattern has been described. Tc-99m ciprofloxacin is a new agent claimed to be specific for imaging sites containing viable bacteria. In this report, we present three cases of proved bacterial infection of the axial skeleton with a mismatch pattern between Tc-99m ciprofloxin and tagged leukocytes. Although Tc-99m-labeled leukocyte scanning showed a cold defect, probably caused by bone marrow replacement, the Tc-99m ciprofloxacin consecutively revealed a hot spot at the site of infection. These data suggest that Tc-99m ciprofloxacin should be a better agent than radiolabeled leukocytes for detecting osteomyelitis of the axial skeleton.

Adult↗
PubMed1998

Multiple kinship in two Spanish regions: new model relating multiple and simple consanguinity.

The structure of the different categories of multiple consanguineous marriages (MCMs) and their historical variation patterns are analyzed in the Spanish dioceses of Alava (Basque Country) and Sigüenza-Guadalajara (Castile). Consanguineous marriages, up to third cousins, were taken from ecclesiastical dispensations, and the periods studied were 1831-1980 for Alava and 1861-1980 for Sigüenza-Guadalajara. Significant differences exist in the MCM rates in the two Spanish areas. In this study a model is proposed to prove that in a general population there may be dependence between MCM rates for specific relationships and the frequencies of those types of relationships in the form of simple consanguineous marriages (SCMs). The effects of avoidance and preferentiality and of underreporting are discussed to explain the deviations between observed and expected consanguineous marriage frequencies. A limit to the weight of remote consanguinity on the population inbreeding coefficient F is determined. The relationship between FT/FS and ms values from our two Spanish populations are fitted to curvilinear regressions. FT is the total population inbreeding coefficient, FS is the contribution to FT from SCMs, and ms is the relative observed frequency of SCMs in the general population.

Cohort Studies↗
PubMed1997

Calcium mediates the activation of the inhibitory current induced by odorants in toad olfactory receptor neurons.

In toad olfactory neurons, a putrid odorant mixture inducing inhibitory responses increases Ca2+-activated K+ conductance, developing a hyperpolarizing receptor potential. Removal of extracellular Ca2+ or exposure to nifedipine reversibly reduced the inhibitory response, suggesting that odorants induce a Ca2+ influx. We show evidence for an odorant-induced Ca2+ current. Using confocal microscopy, it is shown that odorants induce a nifedipine-sensitive elevation of Ca2+ in the apical end of the cell. These results suggest an inhibitory mechanism in which an apical Ca2+ influx causes an increase in internal Ca2+, opening Ca2+-activated K2+ channels that lead to membrane hyperpolarization.

Animals↗
PubMed1997

Postpartum bilateral subdural hematomas following spinal anesthesia: case report.

BACKGROUND: Intracranial subdural hematoma is an exceptionally rare complication of spinal anesthesia. We report a case of this infrequent event and consider the influence of cerebral atrophy as a predisposing factor. METHODS AND RESULTS: This 18-year-old woman with severe headaches was admitted to the hospital 42 days after delivery. She had a history of normal pregnancy and uneventful labor and delivery. The epidural anesthesia was satisfactory. Computed tomography showed bilateral chronic subdural hematomas that were surgically removed. An early follow-up scan showed marked resolution of the hematomas and a small sized brain with large subarachnoid space. A late follow-up scan confirmed the diagnosis of brain atrophy. CONCLUSIONS: Persistence of headache and gradual progression despite treatment must be regarded as a sign of intracranial complication following spinal anesthesia. In this case, cerebral atrophy is considered to be a contributory factor for the development of subdural hematoma following dural puncture.

Adolescent↗
PubMed1997

Senile chorea: a multicenter prospective study.

Senile chorea (SC) is characterized by the presence of late onset, generalized chorea with no family history and no dementia. It is unclear whether it is a distinct clinical entity or represents late onset Huntington's disease (HD) with an undetected family history. In order to clarify this issue, we carried out a prospective, multicenter study of suspected cases of SC. Since 1994 we identified six cases that met clinical criteria for SC. Their study included routine lab tests, cerebral MRI, neuropsychological assessment, and lastly gene IT15 analysis. An abnormal expansion of the (CAG)n repeat was found in three patients. Although there were no criteria for dementia, most neuropsychological tests revealed mild to moderate deficits, particularly in visuospatial and prefrontal tasks, m all six patients, those that were finally diagnosed as having late onset "sporadic" HD, but also in patients that finally had SC. This study provides further evidence on the existence of SC; however, the distinction from late onset "sporadic" HD seems not to be possible on clinical grounds unless a genetic study is carried out. Some cases of suspected "SC" have late onset "sporadic" HD.

Age of Onset↗
PubMed1997

New method for comparing levels of microdifferentiation: application to migration matrices of two populations from the Basque Country (Spain).

Population microdifferentiation rates can be obtained by various coefficients. Despite differences in the formulations of these coefficients, the obtained values lead to convergent empirical interpretations. One of the most widely used coefficients is Wright's FST. Insofar as all these statistics depend on the number of subpopulations r and their effective size Ne, they are far from easy to compare and interpret. Here, we propose a new method for comparing microdifferentiation rates: a measurement referred to as -log(p), inferred from the relationship between the statistics FST and chi 2. The most interesting quality of -log(p) is that it is independent of r and Ne so that its use facilitates comparisons between populations with different characteristics. Using parent-offspring migration matrices, we estimated the values of -log(p) for two populations in the Basque Country: Lanciego and Orozco. The obtained values were compared with the -log(p) for other world populations whose microdifferentiation rates had already been calculated by other researchers using different data sources. Both Basque populations showed low -log(p) values, as did most of the considered continental populations, whereas island and nonmodern populations showed higher values. This implies microdifferentiation only in island and nonmodern populations, although the secular trend of this process in some populations, such as the Aland Islanders and the Papago, leads to isolation breakdowns.

Censuses↗