DEFB1 5'UTR polymorphisms modulate the risk of HIV-1 infection in Mexican women.

Immunologic and genetic factors are involved in HIV-1/AIDS pathogenesis. Defensins are key molecules in innate immunity that participate in the control and/or development of infection and disease. Using PCR-RFLPs, we determined the association between HIV-1/AIDS and human ß-defensin 1 (DEFB1) 5'UTR -52 G/A (rs1799946), -44 C/G (rs1800972), and -20 G/A (rs11362) polymorphisms in three groups of women from the state of Sinaloa, located in the Northwest region of Mexico: i) healthy blood donors; ii) sex-workers; and iii) HIV-1 patients. The -52GG genotype was more frequent in blood donors than in patients (p= 0.023; Odds Ratio, OR= 0.49; 95% CI= 0.25-0.95), whereas the - 52GA genotype was significantly higher in patients (p= 0.013; OR= 2.03; 95% CI= 1.11-3.79, statistical power SP= 98.8%), as well as the frequencies of -20A allele (p= 0.017; OR= 1.60; 95% CI= 1.06-2.40), -20AA genotype (p= 0.047; OR = 2.02; 95% CI= 0.93-4.33) and the ACA haplotype with respect to healthy blood donors (p= 0.000012; OR= 5.82; 95% CI= 2.33-16.43, SP= 99.89%) and sex-workers (p= 0.019; OR= 2.18; 95% CI= 1.07-4.46). Conversely, the ACG haplotype was higher in healthy blood donors than in patients (p= 0.009; OR= 0.55; 95% CI= 0.34-0.89). In addition, the -44CC genotype was associated with a low plasma viral load (p= 0.015), whereas AGA, AGG and GGA haplotypes were more prevalent in individuals with high CD4 counts (p= 0.004, 0.046, and 0.029, respectively). These findings associate DEFB1 5'UTR polymorphisms with HIV-1/AIDS in Mexican women for the first time.

Mapping of neurokinin b in the cat brainstem.

We studied the distribution of neurokinin B-immunoreactive cell bodies and fibers in the cat brainstem using an indirect immunoperoxidase technique. The highest density of immunoreactive fibers was found in the motor trigeminal nucleus, the laminar and alaminar spinal trigeminal nuclei, the facial nucleus, the marginal nucleus of the brachium conjunctivum, the locus coeruleus, the cuneiform nucleus, the dorsal motor nucleus of the vagus, the postpyramidal nucleus of the raphe, the lateral tegmental field, the Kölliker-Fuse nucleus, the inferior central nucleus, the periaqueductal gray, the nucleus of the solitary tract, and in the inferior vestibular nucleus. Immunoreactive cell bodies containing neurokinin B were observed, for example, in the locus coeruleus, the dorsal motor nucleus of the vagus, the median division of the dorsal nucleus of the raphe, the lateral tegmental field, the pericentral nucleus of the inferior colliculus, the internal division of the lateral reticular nucleus, the inferior central nucleus, the periaqueductal gray, the postpyramidal nucleus of the raphe, and in the medial nucleus of the solitary tract. This widespread distribution of neurokinin B in the cat brainstem suggests that the neuropeptide could be involved in many different physiological functions. In comparison with previous studies carried out in the rat brainstem on the distribution of neurokinin B, our results point to a more widespread distribution of this neuropeptide in the cat brainstem.

Mapping of tachykinins in the cat spinal cord.

Using an indirect immunoperoxidase technique, the location of cell bodies and fibers containing substance P, neurokinin A and neurokinin B was studied in the cat spinal cord. The former two neuropeptides showed a widespread distribution throughout the whole spinal cord, whereas the distribution of neurokinin B was more restricted. Neurokinin A-immunoreactive structures showed a more widespread distribution and a higher density than the immunoreactive structures observed to contain substance P. In the cat spinal cord, we observed cell bodies containing neurokinin A, but no cell bodies containing neurokinin B or substance P were found. These cell bodies were located in laminae V (sacral 1 and 2 levels), VI (sacral 1 and 3), VII (lumbar 7, sacral 1 and 3, caudal 1) and X (sacral 1). Laminae I and II showed the highest density of immunoreactive fibers for each of the three tachykinins studied, being in general lamina IV who showed the lowest number of immunoreactive fibers containing substance P, neurokinin A or B. The anatomical distribution of the three tachykinins studied in the cat spinal cord indicates that the neuropeptides could be involved in the neurotransmission and/or in the neuromodulation of nociceptive information, as well as in autonomic and affective responses to pain. Moreover, the involvement of substance P, neurokinin A or B in other functions unrelated to the transmission of pain is also possible (autonomic and motor functions). The distribution of the neuropeptides studied in the cat is compared with the location of the same neuropeptides in the spinal cord of other species. The possible origin of the tachykinergic fibers in the cat spinal cord is also discussed.

Gestión y calidad en atención a personas mayores y/o discapacitadas / Management and quality of atention in elderly and disabled

El objetivo de este trabajo es transmitir la experienciaadquirida en la aplicación de un modelode gestión moderno, considerado excelente,como es el modelo EFQM, en una organizaciónsociosanitaria así como su contribución a la mejorade la calidad de vida de las personas mayoresy/o discapacitadas y sus familias. Se analizanlos elementos principales de la gestión y dela calidad así como la metodología establecidapara evaluar el sistema establecido y los resultadosobtenidos. Se presenta la experiencia de laFundación Matia en este sentido

The aim of this article is to transmit the acquiredexperience in application of modern managementmodel, considered excellent, like EFQMmodel, in a socio-sanitary organization just as itscontribution to the improvement of quality of lifeof elderly and/or disabled people and their family.We analyse the main aspects of managementand quality of care, just as the established methodsto evaluate the system and the obtained results.We present the experience of Matia Foundationin this sense

5-HT1A receptor activation before acute stress counteracted the induced long-term behavioral effects.

The long-term behavioral consequences of acute immobilization (IMMO) in rats and the effects of 5-HT(1A) receptor activation (8-OH-DPAT: 0.3 mg/kg, sc) were studied. Corticosterone levels after IMMO with previous 8-OH-DPAT treatment were also studied. Twenty-four hours after IMMO (3 h), rats performed conditioned (passive avoidance) and unconditioned (escape behavior) anxiety tests in the elevated T maze. Pre-exposure to IMMO induces long-term behavioral changes in contrast with control rats. These behavioral alterations include an increase of anxiogenic responses, such as exploratory behavior and passive avoidance response. This effect was counteracted by 8-OH-DPAT pretreatment and reversed by WAY-100635 when administered before 8-OH-DPAT. Serum corticosterone levels increased during the first hour of stress and after 8-OH-DPAT administration. Our results support the hypothesis that involvement of acute stress is crucial in the anxiety-like behaviors and in the potentiation of fear. The activation of 5-HT(1A) receptors counteracted the long-term effects induced by IMMO.

c-Fos expression in supramammillary and medial mammillary nuclei following spatial reference and working memory tasks.

To investigate brain substrates of spatial memory, neuronal expression of c-Fos protein was studied. Two groups of rats were trained in two spatial memory tasks in the Morris water maze, where the rats have to apply a reference memory rule or a working memory rule. In addition to the experimental groups, two control groups were used to study c-fos activation not specific to the memory processes studied. After immunohistochemical procedures, the number of c-Fos positive neuronal nuclei was quantified in the mammillary body (MB) region (medial mammillary nucleus [MMn] and supramammillary nucleus [SuM]). The results have shown that some MMn neurons expressed c-Fos nuclear immunoreactivity related to spatial working memory but not to spatial reference memory. The increased number of c-Fos immunoreactive neuronal nuclei in the SuM was related to spatial training but not to either working or reference memory demands of the tasks.

[Neuropeptides in the raphe nuclei: an immunocytochemical study]. / Neuropéptidos en los núcleos del rafe: estudio inmunocitoquímico.

INTRODUCTION: The raphe nuclei are involved in numerous mechanisms, included the antinociceptives. In the raphe nuclei of the cat, the distribution of neuropeptides is not very studied. Aim. To know the distribution of peptidergic fibers and cell bodies in the raphe nuclei of the cat. We studied a total of fifteen neuropeptides. MATERIAL AND METHODS: We used four control cats (without colchicine) and six with colchicine (administered into the Sylvian aqueduct). We used an indirect immunocytochemical technique. The histologic controls carried out confirm the specificity of the primary and secondary antibodies used. RESULTS: We observed in the fibers and/or the cell bodies located in the dorsal raphe nucleus a total of 14 neuropeptides, 12 in the raphe pallidus, 11 in the medial raphe, 10 in the raphe magnus, 8 in the raphe pontis and 7 in the raphe obscurus. We observed immunoreactive cell bodies in the raphe pallidus (with neurokinin A/leucine enkephalin), in the medial raphe (beta endorphin/alpha neo endorphin), in the raphe magnus (leucine enkephalin) and in the dorsal raphe (beta endorphin/alpha neo endorphin/methionine enkephalin Arg6 Gly7 Leu8/leucine enkephalin/neurokinin A/neurotensin). CONCLUSIONS: 1. There are differences on the distribution of the peptidergic fibers/cell bodies observed in the raphe nuclei of the rat, the cat and the man; 2. The raphe nuclei could receive peptidergic afferences containing dynorphin A, galanin, neuropeptide Y, somatostatin ; 3. The cell bodies located in the medial raphe and containing beta endorphin or alpha neo endorphin could be projecting neurons; 4. There is a great functional complexity in the raphe nuclei due to the great number of neuropeptides observed in them; 5. The neuropeptides could interact between them, and 6. The neuropeptides located in the raphe nuclei could be involved in the control of the nociceptive information.

Group I mGluR antagonist AIDA protects nigral DA cells from MPTP-induced injury.

The effects of i.c.v. injection of AIDA, a group I mGluR antagonist, were studied on the nigral DA cells after MPTP-induced injury in the black mouse, using TH immunocytochemistry and unbiased stereology. MPTP reduced the total number of TH-IR neurons by 55.2% and non-TH-IR neurons by 27.5%. A 15 min AIDA pre-treatment (10 nmol) selectively counteracted the loss of TH-IR cells caused by MPTP as evaluated 10 days after the insult without changing the total number of non-neuronal cell nuclei. The results suggest that group I mGluR antagonists may have a neuroprotective role against MPTP-induced degeneration of DA neurons and thus probably also against neurodegenerative processes occurring in Parkinson's disease.

Effects of thyroid hormone on the renal dopaminergic system.

This study determined the effects of thyroid hormone on the renal dopaminergic system. Surgical thyroidectomy (Tx) and treatment with 2-thiouracil (Thio) decreased renal cortex Na+/K+ ATPase activity and urinary volume. Tx also decreased urinary Na+ and urinary L-DOPA without changing urinary excretion of Dopamine (DA). Thio treatment decreased slightly urinary L-DOPA and Na+, but increased urinary excretion of DA. In both models of thyroid hormone deficiency, the ratio urinary DA/DOPA increased. Changes after Thio treatment were reversed after one month of drug withdrawal. Treatment with T3 via osmotic minipump increased Na+/K+ ATPase activity and urinary L-DOPA, did not change urinary DA, and increased the ratio DA/DOPA. To further analyze the effects of thyroid hormone deficiency, we administered selective DA1 (SCH-23390), DA2 (Sulpiride), and a non selective (Haloperidol) DA receptor antagonists to Thio treated and control animals. The DA1 antagonist decreased diuresis, natriuresis and urinary L-DOPA in control, but had no effect in Thio treated rats. Sulpiride had no effect in either group. The combination of SCH-23390 plus Sulpiride decreased urinary L-DOPA and urinary volume only in Thio treated animals. Haloperidol decreased urinary volume in Thio treated animals, but had no effect in controls. Our findings suggest that renal DA synthesis is to some extent dependent on thyroid hormone levels, and that the response of DA receptors is altered by thyroid hormone deficiency, indicating a role of this hormone in the regulation of the renal dopaminergic system.

The galanin receptor antagonist M40 blocks the central cardiovascular actions of the galanin N-terminal fragment (1-15).

It has been shown that galanin plays a role in central cardiovascular regulation. Galanin administered centrally induces an increase of heart rate and a weak vasodepressor response, whereas the N-terminal galanin fragment (1-15) elicits vasopressor effects and tachycardia. Furthermore, it has been shown that galanin-(1-15), but not galanin-(1-29), decreases the baroreceptor reflex sensitivity. Since these data demonstrate that both galanin and its N-terminal fragment (1-15) exert a different modulation on central cardiovascular control, the aim of this work has been to study if the specific galanin receptor antagonist Galanin-(1-12)-Pro-(Ala-Leu)(2)-Ala]-amide (M40) could modulate their cardiovascular actions. Urethane anaesthetized rats were injected intracisternally and the changes in mean arterial pressure and heart rate were monitored. Two doses of M40 alone have been tested for their cardiovascular effects. With the dose of 1.0 nmol, a significant tachycardia was observed (P<0.001), but 0.1 nmol was ineffective. This suggests a possible agonistic effect for the higher doses of M40. The galanin receptor antagonist M40 at the dose of 0.1 nmol failed to modify the weak vasodepressor effects and tachycardia induced by 3.0 nmol of galanin-(1-29). However, the same dose completely blocked the vasopressor and tachycardic responses elicited by 3.0 nmol of galanin-(1-15). These data show that M40 differentially counteracts the central cardiovascular responses of the galanin fragment and give a functional support for the existence of galanin receptor subtypes within the brainstem. Therefore, the present findings can be explained on the basis that the cardiovascular actions of galanin-(1-29) could be mediated by one type of galanin receptor, whereas a galanin receptor subtype that recognizes N-terminal fragments of galanin may mediate the actions of galanin-(1-15).

Mapping of alpha-melanocyte-stimulating hormone-like immunoreactivity in the cat brainstem.

The distribution of alpha-melanocyte-stimulating hormone-like immunoreactive structures was studied in the brainstem of the cat using an indirect immunoperoxidase technique. Immunoreactivity was observed in several brainstem nuclei of the cat in which no immunoreactivity had been previously reported. Immunoreactive fibres were observed in the following; the inferior central nucleus; the pontine gray nuclei; the Kölliker-Fuse nucleus; the motor trigeminal nucleus, the anteroventral cochlear nucleus; the abducens nucleus; the retrofacial nucleus; the superior, lateral, inferior, and medial vestibular nuclei; the lateral nucleus of the superior olive; the external cuneate nucleus; the nucleus of the trapezoid body; the postpyramidal nucleus of the raphe; the medial accessory inferior olive; the dorsal accessory nucleus of the inferior olive; the nucleus ambiguus; the principal nucleus of the inferior olive; the preolivary nucleus; the nucleus ruber; the substantia nigra; and in the area postrema. Our results point to a more widespread distribution of alpha-melanocyte-stimulating hormone-like immunoreactive structures in the cat brainstem than that reported in previous studies carried out in the same region of the cat, rat and humans.

Distribution of luteinizing hormone-releasing hormone in the upper brainstem and diencephalon of the cat: an immunocytochemical study.

The distribution of luteinizing hormone-releasing hormone (LH-RH)-immunostained cell bodies and fibres was studied in the brainstem and diencephalon of the cat using an indirect immunoperoxidase technique. The brainstem and the thalamus were devoid of immunostained cell bodies, whereas in the hypothalamus immunopositive perikarya were observed in the supraoptic nucleus, the anterior hypothalamus, the preoptic region and in the arcuate nucleus. Our findings also showed that the hypothalamus is richer in immunostained fibres, and that in this region such fibres are more widely distributed than in the thalamus and upper brainstem. No immunopositive fibres were observed in the lower brainstem. Our results point to a more widespread distribution of LH-RH-immunostained perikarya in the cat hypothalamus than that previously reported in the cat; a similar distribution to that found in the rat, and a more restricted distribution than in primates. Additionally, our study shows a more widespread distribution of immunostained fibres in the cat brainstem and diencephalon than that previously described for other mammals. In this context, our results describe for the first time in the mammals central nervous system fibres containing LH-RH located in the stria medullaris of the thalamus, the supramammillary decussation, the laterodorsal and lateroposterior thalamic nuclei, the nucleus reuniens, the supraoptic nucleus, and the optic chiasm. Thus, our findings reveal that LH-RH-immunostained structures are widely distributed in the upper brainstem and in the diencephalon of the cat, suggesting that the peptide may be involved in several physiological functions.

A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse.

The effect of an acute administration of the vigilance-promoting drug modafinil ((+/-)(diphenyl-methyl)-sulfinyl-2 acetamide; Modiodal) on the nigrostriatal dopamine system was studied after damage induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by means of immunohistochemistry for tyrosine hydroxylase (TH) and a stereological method. MPTP (40 mg/kg) reduced from 24,380 +/- 902 to 13,501 +/- 522 and from 37,868 +/- 3300 to 20,568 +/- 1270, respectively, the number of TH immunoreactive (IR) and non-TH IR nigral neurons. Co-administration of Modafinil restored to normal the number of these neuronal populations. MPTP treatment induced also a reduction in the volume of TH IR neurons, which was counteracted by Modafinil administration. The data provide morphological evidence, based on unbiased stereological analysis, for a potential neuroprotective role of Modafinil, not only in dopaminergic neurons, but also with a similar magnitude in the non-DA nerve cell population of the substantia nigra after MPTP lesion. These results suggest that Modafinil has a neuroprotective role in the substantia nigra via a still undefined mechanism in which a crucial role of DA uptake blockade should be excluded. Modafinil may therefore have a therapeutic potential in neurodegenerative processes such as those occurring in Parkinson's disease.

Comparative bioavailability evaluation of two cyclosporine oral formulations in healthy Mexican volunteers.

BACKGROUND: The use of conventional cyclosporine (Sandimmune) requires great care, as this drug exhibits a narrow therapeutic index and wide interindividual variability in its pharmacokinetics. Recently, a new microemulsion formulation (Neoral) was developed. With this formulation, cyclosporine is absorbed at the small intestine without the presence of bile. Therefore, the objective of this study was to compare the bioavailability of cyclosporine after the administration of conventional and microemulsion formulations in healthy Mexican volunteers in order to approach the optimal dosage regimen of microemulsion in the Mexican population. METHODS: The trial was conducted using 23 healthy volunteers according to a randomized crossover design. Volunteers received one 7.5-mg/kg dose as each formulation, with a 1-week washout period between treatments. Blood samples of 0.5 mL were obtained according to the following schedule: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 h after medication. RESULTS: These indicated that Cmax and AUC0-24 values were higher with the microemulsion than with the conventional formulation. CONCLUSIONS: The microemulsion had a better absorption profile than the conventional formulation, because plasma levels with the conventional formulation demonstrated oscillations rather than reflecting an erratic absorption. Lower doses of the microemulsion are required to obtain Cmax values similar to those obtained with conventional cyclosporine.

Subchronic toluene exposure in low concentrations produces signs of reduced dysfunction in the 6-hydroxydopamine lesioned nigrostriatal dopaminergic system of the rat.

The effect of a subchronic (4-week) exposure to low concentrations of toluene (40 or 80 parts per million, ppm) on the brain dopaminergic system has been examined in a rat model of Parkinson's disease. A unilateral lesion of the substantia nigra (SN) dopamine (DA) nerve cells was performed by injection of a low dose of 6-hydroxydopamine (6-OH DA). The peak activity of contralateral rotational behavior induced by apomorphine was significantly decreased after exposure to 80 ppm toluene. Analysis of the neostriatum and SN ipsilateral to the lesion revealed that toluene (80 ppm, but not 40 ppm) counteracted the 6-OH DA-induced reductions of DA tissue levels both within the SN and the neostriatum. Also the lesion-induced reduction of immunoreactivity for tyrosine hydroxylase (TH IR) in the neostriatum was partly counteracted by the toluene exposure (80 ppm). In conclusion, a subchronic exposure to low doses of toluene (80 ppm) leads to signs of reduced dysfunction of the nigrostriatal dopaminergic system after the neurotoxic treatment.

Immunohistochemical mapping of enkephalins, NPY, CGRP, and GRP in the cat amygdala.

This immunohistochemical study shows a wide distribution of neuropeptides in the cat amygdala. Neuropeptide Y is present along the whole amygdaloid complex, and fibers and cell bodies containing neuropeptide Y are observed in all the nuclei studied. Leucine-enkephalin-, gastrin-releasing peptide/bombesin-, and calcitonin gene-related peptide-immunoreactive fibers and perikarya are observed only in discrete nuclei of the amygdaloid complex, whereas only fibers -but no cell bodies- containing methionine-enkephalin-Arg6-Gly7-Leu8 have been observed. No immunoreactivity has been found for gamma-melanocyte-stimulating hormone, dynorphin A (1-17), or galanin. These data are compared with those reported in the amygdala of other mammals.

Influence of age on stress responses to metabolic cage housing in rats.

1. We studied the effect of isolation stress in 3- and 12-month-old rats individually housed in metabolic cages for 7 days. Urine (24 hr) was collected daily from one group of animals of each age. The other group was tested in an open field and on a hot plate on days 1 and 7. 2. Total deambulation in the open-field test was lower in young than in older rats both on day 1 (54.7 +/- 9.9 vs 80 +/- 8.9 crossings/session; P < 0.04) and on day 7 (21 +/- 9 vs 48 +/- 7 crossings per session; P < 0.04) and decreased significantly in the two groups when tested on day 7 (P < 0.03). Latency to paw-licking in the hot-plate test was longer in young than in older animals on day 1 (14 +/- 2 vs 8 +/- 4 sec; P < 0.05) but was similar in the two groups on day 7. 3. Urinary excretions of norepinephrine (NE) and epinephrine (E) were determined by HPLC with electrochemical detection. Urinary NE in day 1 was similar in young and older animals (2627 +/- 828 vs 3069 +/- 598 ng/24 hr). In young animals NE excretion decreased along the study and was significantly (P < 0.02) lower than on day 1 during the last 3 days of the study. Conversely, in older animals urinary excretion of NE remained similar throughout the study. On day 7 urinary excretion of NE in older animals was about two fold that in young rats. Urinary E was similar in young and older rats (341 +/- 127 vs 532 +/- 256 ng/24 hr) on day 1 and showed a tendency to increase throughout the study. 4. Urinary monoamine oxidase inhibitory (IMAO) activity was determined by testing the ability of urine extracts to inhibit rat liver MAO activity in vitro and was higher in young than in older animals throughout the study (day 1, 54.8 +/- 4.2 vs 25.1 +/- 5.1%; P < 0.02). In young rats excretion of IMAO was significantly higher during the last 3 days of the study than on day 1 (P < 0.05). In older animals urinary IMAO showed a tendency to increase at the end of the study. 5. Isolation stress caused by housing rats in metabolic cages results in different behavioral and metabolic responses in young and older animals. Young animals exhibit a lower locomotor and analgesic response and excrete lower amounts of NE and higher IMAO activity in the urine than older rats. The metabolic and behavioral responses to isolation stress are highly dependent on the age of the animals tested. These results should be taken into consideration when designing experiments requiring the use of metabolic cages.

Effect of glucocorticoids on renal dopamine production.

This study assess the effects of glucocorticoids on dopamine excretion and evaluates the participation of renal dopamine in the effects of glucocorticoids on renal function and Na+ excretion. Dexamethasone (i.m.; 0.5 mg/kg) was administered to male Wistar rats on day 2 or on days 2 and 5. Daily urinary excretions of Na+, dihydroxyphenylalanine (DOPA), dopamine and dihydroxyphenylacetic acid were determined from day 1 to day 7. Renal function was evaluated 8 h after dexamethasone administration in a separate group. The first dose of dexamethasone increased about 100% diuresis and natriuresis, increased urinary DOPA and renal plasma flow, and did not affect urinary dopamine or the other parameters evaluated. These effects were not affected by previous administration of haloperidol. The second dexamethasone dose increased about 200% diuresis and natriuresis, increased urinary dopamine, DOPA, dihydroxyphenylacetic acid, Uosm x V and both glomerular filtration rate and renal plasma flow. Carbidopa administered before the second dexamethasone dose blunted both the diuretic and the natriuretic response whereas haloperidol abolished or blunted all the effects of the second dexamethasone dose. These results show that modifications in renal dopamine production produced by corticoids may contribute to the effects of these hormones on Na+ balance and diuresis and suggest that regardless the factor that promotes an increase in renal perfusion and glomerular filtration rate during long term administration of glucocorticoids, a dopaminergic mechanism is actively involved in the maintenance of these hemodynamic changes.