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1.
Int J Dev Neurosci ; 46: 115-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26315400

RESUMO

Thyrotropin-releasing hormone (TRH) synthesized in hypothalamic paraventricular nucleus directs hypothalamus-pituitary-thyroid (HPT) axis function, regulating thyrotropin release from adenohypophysis and thyroid hormones serum concentration. Pyroglutamyl aminopeptidase II (PPII), a Zn-dependent metallopeptidase located in adenohypophysis and medial-basal-hypothalamus degrades TRH released from the median eminence and participates in HPT axis function by regulating TRH-induced thyrotropin release from adenohypophysis. It is unknown whether dietary Zn deficiency down-regulates PPII. Our aim was to compare adenohypohyseal and medial-basal-hypothalamic PPII activity and expression of adult rats fed a Zn-deficient diet (2ppm) throughout their lifespan (DD), prenatally (DC) or after weaning (CD) vs. that of animals fed a control diet (20ppm:CC). Female rats consumed a Zn-deficient or control diet from two weeks before gestation and up to the end of lactation. We analyzed adenohypophyseal and medial-basal-hypothalamic PPII activity of dams and male offspring when adults; its relation to median eminence TRH, serum thyrotropin, leptin and thyroid hormones concentration. Offspring ate the same diet as their dams (CC, DD) or were switched from dietary regime after weaning (CD, DC) and until 2.5 months of age. DD males showed decreased adenohypophyseal and medial-basal-hypothalamic PPII activity, along with high thyrotropin serum concentration. Post-weaning Zn-deficiency (CD) decreased PPII activity only in adenohypophysis and increased thyrotropin circulating levels. Zn-replenishment (DC) normalized PPII activity in both regions and serum thyrotropin concentration. Adenohypophyseal PPII activity decreased and prolactin levels increased in Zn-deficient dams. We concluded that long-term changes in dietary Zn down-regulate PPII activity independently of T3, increasing thyrotropin serum concentration, overall resembling sub-clinical hypothyroidism.


Assuntos
Regulação para Baixo/fisiologia , Hipotálamo Médio/metabolismo , Zinco/deficiência , Fatores Etários , Aminopeptidases/deficiência , Aminopeptidases/genética , Análise de Variância , Animais , Regulação para Baixo/efeitos dos fármacos , Feminino , Lactação/efeitos dos fármacos , Masculino , Gravidez , Prolactina/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , RNA Mensageiro/metabolismo , Radioimunoensaio , Ratos , Ratos Wistar , Fatores Sexuais , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/metabolismo , Zinco/administração & dosagem , Zinco/sangue
2.
J Pharmacol Exp Ther ; 342(1): 222-31, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22532627

RESUMO

Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH(2)) has multiple, but transient, homeostatic functions in the brain. It is hydrolyzed in vitro by pyroglutamyl peptidase II (PPII), a narrow specificity ectoenzyme with a preferential localization in the brain, but evidence that PPII controls TRH communication in the brain in vivo is scarce. We therefore studied in male Wistar rats the distribution of PPII mRNA in the septum and the consequence of PPII inhibition on the analeptic effect of TRH injected into the medial septum. Twelve to 14% of cell profiles expressed PPII mRNA in the medial septum-diagonal band of Broca; in this region the specific activity of PPII was relatively high. Twenty to 35% of PPII mRNA-labeled profiles were positive for TRH-receptor 1 (TRH-R1) mRNA. The intramedial septum injection of TRH reduced, in a dose-dependent manner, the duration of ethanol-induced loss of righting reflex (LORR). Injection of the PPII inhibitor pGlu-Asn-Pro-7-amido-4-methylcoumarin into the medial septum enhanced the effect of TRH. The injection of a phosphinic TRH analog, a higher-affinity inhibitor of PPII, diminished the duration of LORR by itself. In contrast, the intraseptal injection of pGlu-Asp-Pro-NH(2), a peptide that did not inhibit PPII activity, or an inhibitor of prolyl oligopeptidase did not change the duration of LORR. We conclude that in the medial septum PPII activity may limit TRH action, presumably by reducing the concentration of TRH in the extracellular fluid around cells coexpressing PPII and TRH-R1.


Assuntos
Aminopeptidases/antagonistas & inibidores , Estimulantes do Sistema Nervoso Central/farmacologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Septo do Cérebro/efeitos dos fármacos , Septo do Cérebro/enzimologia , Hormônio Liberador de Tireotropina/farmacologia , Aminopeptidases/genética , Aminopeptidases/metabolismo , Animais , Masculino , Peptídeos/farmacologia , Prolil Oligopeptidases , Ácido Pirrolidonocarboxílico/antagonistas & inibidores , Ácido Pirrolidonocarboxílico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores do Hormônio Liberador da Tireotropina/genética , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Reflexo de Endireitamento/genética , Septo do Cérebro/metabolismo , Serina Endopeptidases/farmacologia
3.
Rev Alerg Mex ; 59(4): 214-7, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-24008032

RESUMO

Methotrexate (MTX) is a folic acid antagonist; its main effects are immunosuppressive and antineoplastic. It is used in the treatment of malignancies, lung and rheumatic diseases. There are few reports of immediate hypersensitivity and these include anaphylaxis, urticaria and angioedema. We present a 17 years old male, with a history of anaphylaxis to methotrexate during the induction therapy of ALL L2. It was decided that the drug was necessary for the patientís survival, thus diagnostic skin testing was performed, during which he presented anaphylaxis. The desensitization consisted of 5 days premedication and a 12-steps protocol of intravenous infusions of 8 hoursí duration, starting with a 1:1.000.000 dilution. The patient was successfully desensitized. He was maintained with IV MTX 50mg/m2 weekly for 1 year using the same protocol successfully. This protocol of 12 steps was successful and safe to desensitize a patient with anaphylaxis due to MTX. During such protocol intensive care supervision is critical, as all precautions should be taken to avoid endangering the life of the patient.


Assuntos
Dessensibilização Imunológica , Metotrexato , Anafilaxia , Hipersensibilidade a Drogas , Antagonistas do Ácido Fólico , Humanos , Urticária
4.
Int J Biochem Cell Biol ; 43(3): 363-71, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21093607

RESUMO

Dipeptidyl peptidase IV is an ectopeptidase with multiple physiological roles including the degradation of incretins, and a target of therapies for type 2 diabetes mellitus. Divalent cations can inhibit its activity, but there has been little effort to understand how they act. The intact membrane-bound form of porcine kidney dipeptidyl peptidase IV was purified by a simple and fast procedure. The purified enzyme hydrolyzed Gly-Pro-p-nitroanilide with an average V(max) of 1.397±0.003 µmol min(-1) mL(-1), k(cat) of 145.0±1.2 s(-1), K(M) of 0.138±0.005 mM and k(cat)/K(M) of 1050 mM(-1) s(-1). The enzyme was inhibited by bacitracin, tosyl-L-lysine chloromethyl ketone, and by the dipeptidyl peptidase IV family inhibitor L-threo-Ile-thiazolidide (K(i) 70 nM). The enzyme was inhibited by the divalent ions Ca(2+), Co(2+), Cd(2+), Hg(2+) and Zn(2+), following kinetic mechanisms of mixed inhibition, with K(i) values of 2.04×10(-1), 2.28×10(-2), 4.21×10(-4), 8.00×10(-5) and 2.95×10(-5) M, respectively. According to bioinformatic tools, Ca(2+) ions preferentially bound to the ß-propeller domain of the porcine enzyme, while Zn(2+) ions to the α-ß hydrolase domain; the binding sites were strikingly conserved in the human enzyme and other homologues. The functional characterization indicates that porcine and human homologues have very similar functional properties. Knowledge about the mechanisms of action of divalent cations may facilitate the design of new inhibitors.


Assuntos
Cátions Bivalentes/farmacologia , Dipeptidil Peptidase 4/metabolismo , Córtex Renal/enzimologia , Animais , Sítios de Ligação , Cálcio/metabolismo , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/isolamento & purificação , Inibidores da Dipeptidil Peptidase IV/farmacologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Íons , Cinética , Membranas/efeitos dos fármacos , Membranas/enzimologia , Ligação Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína , Sus scrofa , Temperatura , Zinco/metabolismo
5.
Brain Res ; 1367: 188-97, 2011 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-20940002

RESUMO

Neurons of the paraventricular nuclei of the hypothalamus (PVN) that synthesize the peptide thyrotropin releasing hormone (TRH) control energy homeostasis. Identifying the circuits which regulate these neurons is critical to fully understand integration of metabolic information and the mechanisms that set thyroid hormone levels. We tested the hypothesis that nitric oxide (NO) acutely controls PVN TRH expression and thyrotropin (TSH) secretion by the anterior pituitary. The subcutaneous treatment of rats with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthases, enhanced PVN TRH mRNA and medio-basal hypothalamic TRH levels, and reduced serum TSH concentration. Analysis of the effect of a NO donor in primary cultures of hypothalamic or anterior pituitary cells suggested that the effect of NO includes a direct action on hypothalamic neurons. The cold stress-induced increase in TSH release was inhibited by sc L-NAME. Therefore, production of NO may control the activity of the hypothalamus-pituitary-thyroid axis.


Assuntos
Temperatura Baixa , Óxido Nítrico/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/metabolismo , Estresse Fisiológico/fisiologia , Hormônio Liberador de Tireotropina/genética , Tireotropina/sangue , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/farmacologia , Radioimunoensaio/métodos , Ratos , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Tri-Iodotironina/sangue
6.
J Biomed Biotechnol ; 2011: 469481, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20981147

RESUMO

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T(4) (FT(4)) and tissue FT(4) and FT(3) versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels.


Assuntos
Clofibrato/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Clofibrato/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Wistar , Cloreto de Sódio na Dieta , Sístole/efeitos dos fármacos , Hormônios Tireóideos/metabolismo
7.
Ther Drug Monit ; 32(4): 525-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20463633

RESUMO

Although the reported incidence of carboplatin hypersensitivity is low, it is important to describe it because of its potentially fatal consequences. A 1-year-old Mexican girl weighing 10 kg who had optic nerve glioma was initially scheduled to receive 12 cycles of 600 mg/m2 carboplatin (CBP) as two 300-mg/m2 intravenous infusions administered over 1 hour on 2 different days and a 1-hour intravenous infusion of 1.5 mg/m2 vincristine every 4 weeks. The patient had no history of drug allergies or any type of adverse drug reaction, but she developed itchiness, maculopapular rash, sweating, respiratory distress, and anxiety during the seventh cycle of CBP. According to the algorithm developed by Naranjo et al, the adverse drug reaction was classified as definite secondary to CBP and confirmed by positive skin tests indicating hypersensitivity to the drug. After evaluating the clinical course of the adverse drug reaction and considering the need to continue cancer treatment, a decision was made to desensitize the patient to CBP. The desensitization procedure took 8 hours and was performed during each new chemotherapy cycle until the 12 cycles of chemotherapy were successfully completed. In summary, a case of CBP hypersensitivity in a 1-year-old girl who was successfully desensitized to CBP is reported.


Assuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/terapia , Anafilaxia/sangue , Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Carboplatina/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Monitoramento de Medicamentos , Quimioterapia Combinada , Exantema/induzido quimicamente , Feminino , Humanos , Imunoglobulina E/imunologia , Lactente , Glioma do Nervo Óptico/complicações , Glioma do Nervo Óptico/tratamento farmacológico , Neoplasias do Nervo Óptico/complicações , Neoplasias do Nervo Óptico/tratamento farmacológico , Encaminhamento e Consulta , Testes Cutâneos , Vincristina/uso terapêutico
8.
Endocrinology ; 150(5): 2283-91, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19179432

RESUMO

Pyroglutamyl peptidase II (PPII), a highly specific membrane-bound metallopeptidase that inactivates TRH in the extracellular space, is tightly regulated by thyroid hormone in cells of the anterior pituitary. Whether PPII has any role in the region where axons containing hypophysiotropic TRH terminate, the median eminence, is unknown. For this purpose, we analyzed the cellular localization and regulation of PPII mRNA in the mediobasal hypothalamus in adult, male rats. PPII mRNA was localized in cells lining the floor and infralateral walls of the third ventricle and coexpressed with vimentin, establishing these cells as tanycytes. PPII mRNA extended in a linear fashion from the tanycyte cell bodies in the base of the third ventricle to its cytoplasmic and end-feet processes in the external zone of the median eminence in close apposition to pro-TRH-containing axon terminals. Compared with vehicle-treated, euthyroid controls, animals made thyrotoxic by the i.p. administration of 10 microg L-T(4) daily for 1-3 d, showed dramatically increased accumulation of silver grains in the mediobasal hypothalamus and an approximately 80% increase in enzymatic activity. PPII inhibition in mediobasal hypothalamic explants increased TRH secretion, whereas i.p. injection of a specific PPII inhibitor increased cold stress- and TRH-induced TSH levels in plasma. We propose that an increase in circulating thyroid hormone up-regulates PPII activity in tanycytes and enhances degradation of extracellular TRH in the median eminence through glial-axonal associations, contributing to the feedback regulation of thyroid hormone on anterior pituitary TSH secretion.


Assuntos
Aminopeptidases/fisiologia , Axônios/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Eminência Mediana/inervação , Neuroglia/fisiologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Glândula Tireoide/fisiologia , Aminopeptidases/genética , Aminopeptidases/metabolismo , Animais , Axônios/metabolismo , Comunicação Celular/fisiologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Eminência Mediana/citologia , Eminência Mediana/enzimologia , Modelos Biológicos , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Precursores de Proteínas/metabolismo , Ácido Pirrolidonocarboxílico/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Glândula Tireoide/metabolismo , Tireotropina/sangue , Hormônio Liberador de Tireotropina/metabolismo , Tiroxina/farmacologia , Distribuição Tecidual
9.
Neurosci Lett ; 449(3): 211-4, 2009 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-19013213

RESUMO

Ecto-peptidases hydrolyze peptides in the extracellular fluid of the brain. This process is critical for defining the strength of peptidergic communication. A few studies suggest that brain ecto-peptidase activities are regulated by brain function but the extracellular messengers involved are generally unknown. Pyroglutamyl peptidase II (PPII) is specific for thyrotropin releasing hormone (TRH), a tripeptide with multiple homeostatic functions in brain. The purpose of this study was to identify regulators of brain PPII activity. Electrical stimulation (multiple tetani) did not change PPII activity in cortical or hippocampal slices. However, in hippocampal slices, blockade of calcium channels with high magnesium, or of L-type calcium channels (LTCC) or NMDA receptors, decreased PPII activity, while blockade of AMPA or GABA(A) receptors did not. Blockade of NMDA receptors did not change PPII mRNA levels but decreased PPII levels. The activity of another ecto-peptidase, aminopeptidase N, was also down regulated by a magnesium blockade, not regulated by NMDA receptor blockade and increased by LTCC blockade. The data show a differential regulation of the activity of ecto-peptidases by that of Ca(2+) channel and that synaptic activity, through the NMDA receptor, specifically regulates that of pyroglutamyl peptidase II.


Assuntos
Aminopeptidases/metabolismo , Hipocampo/enzimologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Receptores de N-Metil-D-Aspartato/fisiologia , Regulação para Cima/fisiologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Agonistas dos Canais de Cálcio/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Magnésio/farmacologia , Masculino , Ácido Pirrolidonocarboxílico/metabolismo , Ratos , Ratos Wistar , Regulação para Cima/efeitos dos fármacos
10.
Peptides ; 29(11): 1953-64, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18703099

RESUMO

Ecto-peptidases modulate the action of peptides in the extracellular space. The relationship between peptide receptor and ecto-peptidase localization, and the physiological role of peptidases is poorly understood. Current evidence suggests that pyroglutamyl peptidase II (PPII) inactivates neuronally released thyrotropin-releasing hormone (TRH). The impact of PPII localization in the anterior pituitary on the endocrine activities of TRH is unknown. We have studied whether PPII influences TRH signaling in anterior pituitary cells in primary culture. In situ hybridization (ISH) experiments showed that PPII mRNA was expressed only in 5-6% of cells. ISH for PPII mRNA combined with immunocytochemistry for prolactin, beta-thyrotropin, or growth hormone, showed that 66% of PPII mRNA expressing cells are lactotrophs, 34% somatotrophs while none are thyrotrophs. PPII activity was reduced using a specific phosphorothioate antisense oligodeoxynucleotide or inhibitors. Compared with mock or scrambled oligodeoxynucleotide-treated controls, knock-down of PPII expression by antisense targeting increased TRH-induced release of prolactin, but not of thyrotropin. Similar data were obtained with either a transition-state or a tight binding inhibitor. These results demonstrate that PPII expression in lactotrophs coincides with its ability to control prolactin release. It may play a specialized role in TRH signaling in the anterior pituitary. Anterior pituitary ecto-peptidases may fulfill unique functions associated with their restricted cell-specific expression.


Assuntos
Aminopeptidases/fisiologia , Adeno-Hipófise/enzimologia , Prolactina/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , Hormônio Liberador de Tireotropina/fisiologia , Animais , Células Cultivadas , Feminino , Hibridização In Situ , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
11.
Cell Biol Int ; 32(8): 984-1000, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18501645

RESUMO

In Entamoeba histolytica little is known about the microfilament rearrangements formed by actin and ABPs. Fibronectin regulates many aspects of cell behavior involving the actin cytoskeleton and members of the Rho family of small GTPases. Using trophozoites interacted with fibronectin and glass, we present evidence related with the formation and regulation of different microfilament rearrangements and their cellular distribution, the effect of actin affecting drugs on these arrangements, and on trophozoites adhesion; we also demonstrate that actin isoforms are induced after adhesion, and also the selective participation of specific actin binding proteins such as ABP-120 and phospho-paxillin, regarding their location in the different actin structures. In addition, we show results that confirm the participation of EhRho, ROCK-2, and GAP activities. We propose that fibronectin induced signaling in E. histolytica trophozoites have important consequences in the actin cytoskeleton that may affect its behavior during the invasive process in the host.


Assuntos
Citoesqueleto de Actina/metabolismo , Fibronectinas/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Trofozoítos/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Citoesqueleto de Actina/ultraestrutura , Actinas/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Citocalasina D/farmacologia , Citoesqueleto/metabolismo , Depsipeptídeos/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/metabolismo , Entamoeba histolytica/ultraestrutura , Humanos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Isoformas de Proteínas/metabolismo , Transdução de Sinais , Tiazolidinas/farmacologia , Trofozoítos/citologia , Trofozoítos/efeitos dos fármacos
12.
J Mol Neurosci ; 33(3): 252-61, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17952634

RESUMO

Aminopeptidase N (APN) and neprilysin (NEP) inactivate neuropeptides released into the brain extracellular fluid. We previously showed that the expression of pyroglutamyl peptidase II (PPII), the TRH degrading ecto-enzyme, is regulated in rat brain by amygdaline kindling, a paradigm that activates neuronal pathways in the limbic system increasing the expression of several neuropeptides including TRH and opioids. To understand the specificity of this phenomenon, we studied APN and NEP expression in brains of partially or fully kindled rats (stage II and V), sacrificed 6 h after last stimulus, compared with sham-operated animals. In situ hybridization analysis of NEP mRNA levels showed decreased expression at stage II in CA1, CA2, olfactory tubercle and medial mammillary nucleus, and increased at stage V in CA1 and CA2 cells. These changes were specific for the ipsilateral side. APN mRNA levels, semi-quantified by RT-PCR, were decreased at stage II and increased at stage V, in frontal cortex-olfactory tubercle, and hippocampus. NEP and APN enzymatic activities, determined by fluorometric assays, followed similar variations to their respective mRNA levels. The coordinated changes (in some regions) of NEP and APN expression were opposite to those previously observed for PPII mRNA and activity levels in limbic regions. These results demonstrate that expression of ectopeptidases can be regulated when peptide neurons are activated and, that regulation is enzyme-, region-, and stage-specific.


Assuntos
Antígenos CD13/metabolismo , Excitação Neurológica/fisiologia , Sistema Límbico/fisiologia , Neprilisina/metabolismo , Animais , Antígenos CD13/genética , Estimulação Elétrica , Hibridização In Situ , Masculino , Neprilisina/genética , Ratos , Ratos Wistar
13.
Rev Alerg Mex ; 54(3): 96-103, 2007.
Artigo em Espanhol | MEDLINE | ID: mdl-17849795

RESUMO

Atopic dermatitis is an inflammatory process characterized by a series of cutaneous alterations of typical morphology and distribution, with intense pruritus of nocturnal predominance, of chronic evolution, stational appearance, and with personal and family history of atopy. On genetically predisposed skin, dry and hypersensitive, the immune factors and other types are implicated in determining the abnormal reactions to multiple endogenous and environmental factors. The diagnosis is clinical, generally obtained by a group of signs and symptoms known as the Hanifin and Rajka criteria. The patients with atopic dermatitis can present with clinical typical manifestations, or minimized and localized variations as well, considered a stigma of atopic constituent. In some patients there can be observed clinical and morphological variations with special localizations denominated atypical variations of atopic dermatitis. The identification of these atypical presentations of atopic dermatitis leads to the differential diagnosis, with an early establishment of the disease's diagnosis and the appropriate and early treatment.


Assuntos
Dermatite Atópica/patologia , Adulto , Criança , Pré-Escolar , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Progressão da Doença , Feminino , Humanos , Lactente , Erupções Liquenoides/etiologia , Erupções Liquenoides/patologia , Masculino , Transtornos de Fotossensibilidade/patologia , Prurigo/etiologia , Prurigo/patologia
14.
Rev Alerg Mex ; 54(2): 41-53, 2007.
Artigo em Espanhol | MEDLINE | ID: mdl-17542245

RESUMO

Allergic conjunctivitis is a group of diseases that are frequent in childhood, associated to several allergic diseases affecting the ocular surface. It is related to type 1 hypersensitivity reactions. Two acute disorders: seasonal allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do three chronic diseases: vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. The ocular surface inflammation causes itching, tearing, lid and conjunctival edema-redness, and photophobia during the acute phase and can lead to a classic late-phase response (associated to eosinophilia and neutrophilia) in a subset of individuals. As in the case of several chronic allergic diseases, it can remodel the ocular surface tissue. This allergic disease is very frequent. Vernal keratoconjunctivitis could produce corneal lesions and visual illness; however, atopic keratoconjunctivitis does not permanently affect the vision. The aim of this review is to provide a current overview for a better understanding of the symptoms associated to this disease, to describe its classification, recent advances in its physiopathology and its treatment.


Assuntos
Conjuntivite Alérgica , Corticosteroides/uso terapêutico , Algoritmos , Alérgenos/efeitos adversos , Antialérgicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/etiologia , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/fisiopatologia , Conjuntivite Alérgica/terapia , Citocinas/fisiologia , Dessensibilização Imunológica , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Lactente , Ceratoconjuntivite/complicações , Mastócitos/imunologia , Rinite Alérgica Perene/complicações , Rinite Alérgica Sazonal/complicações , Vasoconstritores/uso terapêutico
15.
Allergy Asthma Proc ; 27(4): 334-40, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16948346

RESUMO

Reports of previous studies done without following the international guidelines in different cities of Mexico showed a decrease in asthma prevalence. The aim of this study was to determine the prevalence and severity of asthma symptoms in children and teenagers living in north Mexico City and compare them with those of other Latin American cities and world regions. The cross-sectional survey followed the protocol of the International Study of Asthma and Allergies in Childhood IIIb phase survey. The study population included children 6-7 years old and teenagers 13-14 years old from randomly selected primary and secondary schools. There were 1629 boys and 1582 girls in the group of 6- to 7-year-old children and 2039 boys and 1860 girls in the 13- to 14-year-old group. "Wheezing or whistling in the chest at any time in the past" was present in 19.2% (95% confidence interval [CI], 17.9, 20.6) of the children and in 17.0% (95% CI, 15.8, 18.1) of the teenagers; "wheezing or whistling in the chest in the last 12 months" was reported in 6.8% (95% CI, 5.9, 7.6) of the children and 9.9% (95% CI, 9.0, 10.8) of the teenagers; "asthma ever" was claimed in 4.5% (95% CI, 3.8, 5.2) of the children and 8.0% (95% CI, 7.1, 8.8) of the teenagers. These prevalences were low compared with other ISAAC Latin American surveys and intermediate in comparison with worldwide regional prevalences reported by ISAAC surveys. The prevalence of asthma is low in Mexico City in comparison with other surveyed locations, but the number of patients with asthma makes it an important issue for Mexican public health programs.


Assuntos
Asma/epidemiologia , Saúde da População Urbana , Adolescente , Asma/complicações , Criança , Estudos Transversais , Feminino , Saúde Global , Inquéritos Epidemiológicos , Humanos , América Latina , Masculino , México , Prevalência , Sons Respiratórios/etiologia , Índice de Gravidade de Doença
16.
Pediatr Allergy Immunol ; 16(7): 609-14, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16238587

RESUMO

This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double-blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 microl/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 microg/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 microg/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 mul/kg plus fluticasone at an accumulated dose of 1500 microg produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Androstadienos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Administração por Inalação , Agonistas Adrenérgicos beta/administração & dosagem , Albuterol/administração & dosagem , Androstadienos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/sangue , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fluticasona , Humanos , Masculino , Nebulizadores e Vaporizadores , Oxigênio/sangue , Pico do Fluxo Expiratório , Fatores de Tempo
17.
J Neurochem ; 92(4): 807-17, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15686482

RESUMO

Thyrotropin-releasing hormone is inactivated in the extracellular space by a membrane-bound peptidase, pyroglutamyl aminopeptidase II (PPII), a member of the M1 family of zinc metallopeptidases. The functional significance of multiple PPII RNA species expression is unknown. We detected, in rat tissues, a RNA species derived from an alternative processing at the exon 14-intron 14 boundary. The alternatively processed RNA encoded a shorter version of PPII (PPII*), lacking part of the C-terminal domain. PPII* was expressed in COS-7 (or C6 glioma) cells but it did not exhibit any PPII activity. Co-transfection of PPII and increasing amounts of PPII* expression vectors resulted in a dose-dependent reduction in PPII activity and the formation of covalent PPII-PPII* heterodimers. PPII* is therefore a powerful dominant-negative isoform of PPII, and heterodimerization may be its mechanism of action. Natural expression of shortened versions of M1 aminopeptidases may constitute a new mode of regulation of their activity.


Assuntos
Aminopeptidases/biossíntese , Aminopeptidases/genética , Éxons/genética , Ácido Pirrolidonocarboxílico/análogos & derivados , Processamento Alternativo , Sequência de Aminoácidos , Aminopeptidases/antagonistas & inibidores , Animais , Sequência de Bases , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Ativação Enzimática/genética , Humanos , Isoenzimas/biossíntese , Isoenzimas/genética , Masculino , Camundongos , Dados de Sequência Molecular , Ácido Pirrolidonocarboxílico/antagonistas & inibidores , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar
18.
Biochem J ; 380(Pt 3): 881-8, 2004 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-14992683

RESUMO

Enzymes of the M13 family of zinc-containing endopeptidases are recognized as important regulators of neuropeptide and peptide hormone activity. Peptidases of this family are type II integral-membrane proteins characterized by short cytosolic domains and large extracellular domains containing the active site. The M13 family has, at present, seven members, including ECEL1 (endothelin-converting enzyme-like 1), one of the newest members. ECEL1 is expressed predominantly in the central nervous system. It has been proposed that the enzyme has a role in the nervous regulation of the respiratory system. No physiological substrate has been identified yet. To better understand the function(s) of this enzyme, we have expressed human ECEL1 in cultured cells and monitored its biosynthesis and subcellular localization. Immunoblot and cell-surface biotinylation analysis of transfected cells expressing ECEL1 showed that only a fraction of the protein travelled to the cell surface, while most of the enzyme was present in an intracellular compartment identified by confocal immunofluorescence microscopy and cell fractionation as the ER (endoplasmic reticulum). Pulse-chase experiments showed that ER-localized ECEL1 was stable, with a half-life of more than 3 h. Endogenous ECEL1 from mouse pituitary gland had a similar distribution between the cell surface and the ER. Finally, using domain-swapping experiments with neprilysin, another member of the M13 family, we showed that localization of ECEL1 to the ER requires both the transmembrane and cytoplasmic domains. It thus appears that ECEL1 may have functions both at the cell surface and in the ER.


Assuntos
Membrana Celular/química , Retículo Endoplasmático/química , Metaloendopeptidases/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos , Linhagem Celular , Citoplasma/química , Feminino , Glicosilação , Humanos , Rim/química , Rim/citologia , Rim/embriologia , Rim/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Metaloendopeptidases/química , Metaloendopeptidases/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Hipófise/química , Hipófise/citologia , Isoformas de Proteínas/química , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transfecção/métodos
19.
Cochabamba; UMSS - Fac. Agronomía - TESIS; 2004. 115 ; 28 cm p. map.
Tese em Espanhol | LIBOCS, LIBOSP | ID: biblio-1334497

RESUMO

Elaborar participativamente un Plan de Ordenamiento Predial en la comunidad de Kirusillani, con la finalidad de identificar acciones orientadas al manejo sostenible de los Recursos Naturales existentes (agua, tierra y vegetación). La metodología se divide en tres fases que son: 1. Preparación y establecimiento de bases 2. Recopilación y análisis de la información y digitalización de mapas. 3. Validación-evaluación y entrega del POP. Los resultados obtenidos son: una memoria técnica descriptiva del POP que incluye información de unidades de tierra, uso actual de la tierra, uso potencial concertado o POP y priorización de acciones a corto, mediano y largo plazo. El POP al ser un instrumento de fácil manejo y comprensión para la comunidad, se constituye en un instrumento de planificación participativa adecuado para normar e implementar acciones orientadas al manejo y aprovechamiento sostenible de los recursos naturales y debe ser actualizado periódicamente


Assuntos
Recursos Naturais
20.
Rev Alerg Mex ; 50(5): 170-5, 2003.
Artigo em Espanhol | MEDLINE | ID: mdl-14631587

RESUMO

BACKGROUND: Rhinitis is the most frequent allergic disease in children. Symptoms may affect importantly life quality. Measures to avoid allergens when possible and the use of drugs are an important part of the treatment; however, specific immunotherapy is the only treatment altering the natural course of the disease. OBJECTIVE: To assess if specific immunotherapy improves life quality in children with allergic rhinitis. MATERIAL AND METHODS: Patients who attended to the allergy department during August and September 2002, and who fulfilled the inclusion criteria, were included. Two groups of treatment were formed: group A received specific immunotherapy with standardized allergenic extracts, from IPI ASAC Mexico. They started with a concentration of 0.07 bioequivalent units (BEU), with twice-a-week-application with increases of 10 (0.7, 7 and 80 BEU) each seven weeks up to maintenance dose of 700 BEU at six months. Group B only was given pharmacological treatment. Paediatric Rhinoconjunctivitis Quality of Life Questionnaires, specific to children with allergic rhinoconjunctivitis, validated for its use in Spanish in Mexican children by the department of Clinical Epidemiology and Biostatistics of Mc Master University, were applied to all patients. RESULTS: Twenty-seven patients were included in each group, 14 males, adjusted for age with a correlation coefficient (r2) = 0.9799. In both groups, mean age was of 11 years 6 months (group A: 7 to 16 years, group B: 7 to 17 years). Eighteen (44.4%) and fifteen patients (33.3%), of groups A and B respectively, had persistent mild rhinitis, and 9 (55.6%) and 12 cases (66.7%) of groups A and B, respectively, had moderate persistent rhinitis. All of them were sensitized to domiciliary allergens. As to life quality a high odds ratio (OR) was found when assessing patients six months after treatment, especially in nasal symptoms such as pruritus (OR = 6.8) and obstruction (OR = 5.9). Also for practical symptoms the OR was high: carving eyes and nose (OR = 7), blowing the nose (OR = 4.8) and carrying disposable tissues (OR = 4.7). OR for other symptoms was as follows: thirst and throatitch, OR = 4; irritability, OR = 6.2, and ocular pruritus, OR = 3.1. Patients without immunotherapy were likely to use more drugs (OR = 6.4) than those receiving immunotherapy. CONCLUSION: We did not find controlled studies on life quality with the use of immunotherapy in children. In this study, specific immunotherapy was found to improve life quality in children with allergic rhinoconjunctivitis, especially in nasal symptoms, such as pruritus and obstruction, as well as in practical symptoms. These results are similar to those by Fell, who found that 92% patients referred an improvement of nasal symptoms, a better labor performance and a lesser use of drugs after four months of using immunotherapy.


Assuntos
Dessensibilização Imunológica , Qualidade de Vida , Rinite Alérgica Perene/terapia , Adolescente , Alérgenos/uso terapêutico , Animais , Gatos , Criança , Baratas , Conjuntivite Alérgica/psicologia , Conjuntivite Alérgica/terapia , Feminino , Humanos , Masculino , Ácaros , Rinite Alérgica Perene/psicologia , Resultado do Tratamento
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