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1.
Neurol Sci ; 34(5): 741-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22661103

RESUMO

A number of experimental and clinical reports suggest the involvement of oxidative stress in pathophysiology of epilepsy. Topiramate, a new antiepileptic drug, induces antioxidant effect in epileptic animals. However, to date, no further studies appear to be carried out in order to demonstrate the ability of topiramate to act as antioxidant. Therefore, the objective of this work was to evaluate the in vitro superoxide (O2(·-)), hydroxyl radical (OH·), hypochlorous acid (HOCl), hydrogen peroxide (H2O2), singlet oxygen ((1)O2) and peroxynitrite (ONOO(-)) scavenging capacity of topiramate in comparison with reference compounds. In addition, we investigated the possible antitumour activity of this compound in some cancer cell lines. Topiramate displays a scavenging capacity compared to the reference compound, with the exception of ONOO(-), although it was less efficient than nordihydroguaiaretic acid, dimethylthiourea, ascorbic acid, sodium pyruvate and glutathione for O2(·-), OH·, HOCl, H2O2 and (1)O2(P < 0.0001), respectively, and not induced significant growth inhibition in cancer cell lines. The direct antioxidant properties of topiramate could explain the neuroprotective effects attributed to this compound and suggest its use as chemopreventive agent in a future.


Assuntos
Antioxidantes/farmacologia , Sequestradores de Radicais Livres/metabolismo , Frutose/análogos & derivados , Linhagem Celular Tumoral/classificação , Linhagem Celular Tumoral/patologia , Relação Dose-Resposta a Droga , Frutose/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Topiramato
2.
Bioorg Med Chem ; 18(1): 274-81, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19926293

RESUMO

A series of new analogues of trifluralin (TFL) were synthesized and characterized in view of changing the unfavorable properties that limits its use as antileishmanial agent. Some of the TFL analogues display more activity than a standard drug (miltefosine) against the promastigote forms of Leishmania infantum and Leishmania donovani and the intracellular form (THP-1 infected with L. infantum). All analogues showed a clear advantage over miltefosine, as they are not hemolytic. Some analogues can conjugate these characteristics with reduced cell toxicity and improved intracellular activity.


Assuntos
Antiprotozoários/química , Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Trifluralina/química , Trifluralina/farmacologia , Antiprotozoários/síntese química , Morte Celular/efeitos dos fármacos , Linhagem Celular , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Trifluralina/síntese química
3.
Int J Antimicrob Agents ; 31(1): 37-45, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18006283

RESUMO

Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The low permeation of antimycobacterial agents and their difficult access to infected macrophages necessitate long-term use of high drug doses. Liposomes preferentially accumulate in macrophages, increasing the efficacy of antibiotics against intracellular parasites. In the present work, several rifabutin (RFB) liposomal formulations were developed and characterised and their in vivo profile was compared with free RFB following intravenous administration. With the RFB liposomal formulations tested, higher concentrations of the antibiotic were achieved in liver, spleen and lungs 24h post administration compared with free RFB. The concentration of RFB in these organs was dependent on the rigidity of liposomal lipids. The liposomal RFB formulation prepared with dipalmitoyl phosphatidylcholine:dipalmitoyl phosphatidylglycerol (DPPC:DPPG) was the most effective and was selected for biological evaluation in a mouse model of disseminated TB. Compared with mice treated with free RFB, mice treated with the DPPC:DPPG RFB formulation exhibited lower bacterial loads in the spleen (5.53 log(10) vs. 5.18 log(10)) and liver (5.79 log(10) vs. 5.41 log(10)). In the lung, the level of pathology was lower in mice treated with encapsulated RFB. These results suggest that liposomal RFB is a promising approach for the treatment of extrapulmonary TB in human immunodeficiency virus co-infected patients.


Assuntos
Antituberculosos/administração & dosagem , Rifabutina/administração & dosagem , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/farmacocinética , Antituberculosos/uso terapêutico , Química Farmacêutica , Lipossomos , Fígado/química , Fígado/microbiologia , Pulmão/química , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Rifabutina/farmacocinética , Rifabutina/uso terapêutico , Baço/química , Baço/microbiologia , Fatores de Tempo
4.
Vet J ; 178(1): 133-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17855131

RESUMO

Liposomes are used as carriers to deliver drugs and to treat diseases where infection is localised in the mononuclear phagocyte system cells, as is the case of leishmaniosis. Trifluralin is a dinitroaniline with proved anti-Leishmania activity in vitro. The efficacy of liposomal trifluralin (LIP/TFL) was studied in the treatment of experimental canine leishmaniosis through quantification of parasite burden using the limiting dilution assay, follow-up of anti-Leishmania antibodies by indirect fluorescent immunoassay and cytokine expression by Reverse Transcriptase-PCR, in the bone marrow, lymph nodes, skin and peripheral blood mononuclear cells in 5 female beagle dogs. After treatment, dogs showed a general remission of clinical signs related to parasite burden reduction and Th1 cytokine mRNA expression, but there was no significant decrease in antibody levels. Alternative treatment schemes with LIP/TFL are necessary to achieve optimal results.


Assuntos
Doenças do Cão/tratamento farmacológico , Leishmaniose Cutânea/veterinária , Trifluralina/uso terapêutico , Animais , Anticorpos Antiprotozoários/sangue , Citocinas/metabolismo , Doenças do Cão/patologia , Cães , Regulação da Expressão Gênica/fisiologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Th1/metabolismo
5.
Biochim Biophys Acta ; 640(1): 43-54, 1981 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-7194113

RESUMO

A brush border membrane fraction isolated from hog kidney cortex was solubilized with 0.5% Triton X-100 and subjected to affinity chromatography on a phlorizin polymer. As demonstrated by transport studies with reconstituted proteoliposomes, the polymer adsorbs the sodium-dependent D-glucose transport system. The latter can be eluted from the polymer by 0.5 M D-glucose. The purified fraction contains 0.4% of the membrane protein extract and exhibits a 20--30-fold higher transport activity than the crude membrane extract. Other brush border membrane proteins such as alkaline phosphatase and aminopeptidase M are markedly reduced in the purified fraction. Thus, affinity chromatography on a phlorizin polymer is a suitable tool for the isolation of the sodium-glucose transport system present in brush border membranes.


Assuntos
Glucose/metabolismo , Córtex Renal/metabolismo , Sódio/metabolismo , Animais , Transporte Biológico , Proteínas de Transporte/metabolismo , Cromatografia de Afinidade , Cinética , Lipossomos , Microvilosidades/metabolismo , Peso Molecular , Proteínas de Transporte de Monossacarídeos , Monossacarídeos/metabolismo , Florizina , Suínos
6.
Biochim Biophys Acta ; 732(3): 691-8, 1983 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-6871221

RESUMO

Sodium-dependent D-glucose uptake into proteoliposomes reconstituted from dimyristoylphosphatidylcholine (DMPC) and hog kidney brush border membrane extract is strongly affected by temperature and the physical state of the membranes. This dependence is defined by a nonlinear Arrhenius plot with a break point at 23 degrees C, a temperature not significantly different from the phase transition temperature of the pure lipid (24 degrees C). The transport process is characterized by different activation energies: 35.1 kcal/mol below and 5.5 kcal/mol above the transition temperature. The shift in the break point for the D-glucose transport activity from 15 degrees C, in the brush border membranes, to 23 degrees C in the reconstituted system leads us to conclude that the lipids surrounding the sodium/D-glucose cotransport system can exchange readily with the bulk lipid used for reconstitution. The results thus provide no evidence for the presence of an annulus of specific lipids surrounding the transport system.


Assuntos
Membrana Celular/metabolismo , Glucose/metabolismo , Rim/metabolismo , Lipossomos , Microvilosidades/metabolismo , Fosfatidilcolinas/metabolismo , Proteolipídeos/metabolismo , Animais , Transporte Biológico Ativo , Dimiristoilfosfatidilcolina , Cinética , Suínos , Temperatura
7.
Biochim Biophys Acta ; 1609(2): 211-7, 2003 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-12543383

RESUMO

Superoxide dismutase (SOD) was chemically modified by covalent linkage of fatty acid chains to the accessible epsilon-amino groups of the enzyme. This acylation method gave rise to a different enzyme entity (Ac-SOD) as evidenced by different physicochemical properties such as octanol/water partition coefficient and isoelectric point (pI) as compared to SOD. Ac-SOD was incorporated in conventional and long-circulating liposomes (LCL) and characterized in terms of incorporation efficiency, protein to lipid ratio (Prot/Lip), enzymatic activity retention and zeta potential. The observation that Ac-SOD liposomes present enzymatic activity on their external surface indicates that these formulations can act independent of rate and extent of enzyme release as required in case of SOD liposomes. The decrease of superficial charge of liposomal formulations containing Ac-SOD, as compared to SOD liposomes, may be related to the negatively charged enzyme molecules localized on the liposome surface. The comparative characterization of Ac-SOD and SOD liposomal formulations evidenced that the two enzyme forms differ substantially regarding their intraliposomal location: SOD tends to be localized in the internal aqueous spaces, whereas Ac-SOD is expected to be localized in the lipid bilayers of the liposomes, partially buried into the outer surface and exposed to the external medium. These liposomal structures with surface-exposed SOD were designated as Ac-SOD enzymosomes. The properties of these enzymosomes may influence the therapeutic effect, as the release of the enzyme from extravasated vesicles is no longer a necessary requirement for achieving dismutating activity within the inflamed target site.


Assuntos
Lipossomos/química , Superóxido Dismutase/química , Acilação , Aminas , Dimiristoilfosfatidilcolina , Desenho de Fármacos , Ponto Isoelétrico , Bicamadas Lipídicas/química , Peso Molecular , Tamanho da Partícula , Polietilenoglicóis , Temperatura
8.
Biochim Biophys Acta ; 1419(2): 325-34, 1999 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10407083

RESUMO

Rheumatoid arthritis (RA) is a prevalent and debilitating autoimmune disease that affects the joints. RA is characterized by an infiltration of the affected joint by blood-derived cells. In response to activation, these cells generate reactive oxygen species, resulting in an oxidative stress situation. One approach to counteract this oxidative stress situation is the use of antioxidants as therapeutic agents. The free radical scavenger enzyme superoxide dismutase (SOD) may be used as a therapeutic agent in rheumatoid arthritis, but its rapid elimination from the circulation is a major limitation. Targeted delivery of SOD may overcome this limitation. In this study, the utility of PEGylated liposomes (PEG-liposomes) for targeting SOD to arthritic sites was explored. The targeting of SOD to arthritic sites following intravenous administration of both PEG-liposomes and positively charged liposomes lacking PEG but containing stearylamine (SA-liposomes) in rats with adjuvant arthritis was studied. At 24 h post injection, the blood levels of long circulating liposomes with a mean size of 0.11 micrometer and 0.20 micrometer were 8- and 3-fold higher, respectively, as compared to the SA-liposomes. The majority of SOD administered in liposomal form remains within the liposomes when they circulate in the bloodstream. The highest target uptake was observed with PEG-liposomes with a mean size of 0.11 micrometer and the lowest uptake with the SA-liposomes. These results demonstrate that SOD can be targeted to inflamed sites most efficiently via small-sized PEG-liposomes. Small-sized PEG-coated liposomes are to be preferred if prolonged circulation and enhanced localization of SOD at arthritic sites are desired.


Assuntos
Artrite Experimental/tratamento farmacológico , Superóxido Dismutase/administração & dosagem , Animais , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/etiologia , Modelos Animais de Doenças , Portadores de Fármacos , Pé/diagnóstico por imagem , Coração/diagnóstico por imagem , Radioisótopos de Índio , Injeções Intravenosas , Radioisótopos do Iodo , Lipossomos/farmacocinética , Masculino , Mycobacterium , Tamanho da Partícula , Ácido Pentético , Fosfatidiletanolaminas , Polietilenoglicóis , Cintilografia , Ratos , Ratos Wistar , Superóxido Dismutase/farmacocinética , Fatores de Tempo , Distribuição Tecidual
9.
J Control Release ; 103(2): 419-34, 2005 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-15763624

RESUMO

The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (Tfs), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that 1 mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Superóxido Dismutase/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Artrite Experimental/sangue , Artrite Experimental/diagnóstico por imagem , Ácido Ascórbico/sangue , Portadores de Fármacos/química , Extremidades/diagnóstico por imagem , Contagem de Leucócitos , Lipossomos , Masculino , Tamanho da Partícula , Radiografia , Ratos , Ratos Wistar , Compostos de Sulfidrila/sangue , Superóxido Dismutase/administração & dosagem , Superóxido Dismutase/química , Resultado do Tratamento
10.
Eur J Pharm Sci ; 26(3-4): 307-17, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16129587

RESUMO

To understand better the wide-spread pharmaceutical use of non-ionic surfactant Tween 80 (TW), the colloidal properties of the surfactant alone and in combinations with the common phospholipid, phosphatidylcholine (PC), were studied. Static and dynamic light scattering revealed that TW solubilises PC at TW/PC approximately 2.75/1 mol/mol and that TW micelle disintegration occurs on time-scale of 2.5 min, independent of amphipath concentration. This is up to nearly 300-times faster than the TW caused dissolution of PC containing unilamellar vesicles. The apparent dissolution time of TW/PC mixed aggregates, in contrast, decelerates from >700 min to <5 min upon increasing starting total amphipath concentration, with thermal activation energy > or =24 (< or =80) kJ mol(-1). The aggregate dissolution rate in highly concentrated TW/PC suspensions reflects the dissolved polysorbate-aggregate exchange rate (approximately 6.7 x 10(-3)s(-1)) rather than TW flip-flop rate across a bilayer (>0.2 min(-1)). PC solubilisation proceeds linearly with the square-root of time, and is kinetically governed by the speed of surfactant diffusion through the bulk (D approximately 2.8 x 10(-11)m2 s(-1)). Creation of small Tween-phosphatidylcholine mixed micelles is typically preceded by pre-solubilisation structures, first in the form of deformable, strongly fluctuating, bilayer vesicles and then of elongated, presumably thread-like, mixed micelles. TW/PC mixed micelles become smaller with growing surfactant/lipid molar ratio, whereas TW/PC mixed vesicles become more and more leaky with increasing surfactant concentration. Our results highlight the molecular and kinetic aspects of polysorbate-membrane interactions and provide a rationale for the popularity of Tween surfactants in pharmaceutical products: such surfactants can solubilise fatty molecules and bilayer membranes but need quite a long time for this, which is available in pharmaceutical preparations but normally not in vivo; this makes Tweens relatively efficient and safe. Furthermore, our data could help design better ultra-deformable mixed lipid-surfactant vesicles for the non-invasive transdermal drug delivery across the skin.


Assuntos
Glycine max , Fosfatidilcolinas/administração & dosagem , Polissorbatos/administração & dosagem , Bicamadas Lipídicas , Micelas , Permeabilidade , Solubilidade , Temperatura
11.
Med Trop (Mars) ; 65(4): 343-5, 2005 Sep.
Artigo em Francês | MEDLINE | ID: mdl-16548486

RESUMO

Mini mental state tests (MMS) were administered to 227 adults over the age of 40 years living in an Ecuadorian urban Andean community known to be an endemic zone for Taenia solium taeniasis and cysticercosis. The overall prevalence of cognitive impairment was 8.4% (19/227). The prevalence of cognitive impairment was 23.5% (8 cases) in adults over 75 years (n=34). The Hachinski ischemic score for vascular dementia was abnormal in 4 of the 19 adults (21%) exhibiting cognitive impairment. This survey highlighted a high prevalence of dementia in comparison with industrialised countries. Parasitic encephalopathy that was present in one out of five persons in this Andean community could play a part in early damage of cognitive function.


Assuntos
Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/parasitologia , Doenças Endêmicas , Neurocisticercose/complicações , Neurocisticercose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Equador/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Urbana
12.
Endocrine ; 49(3): 809-19, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25586874

RESUMO

We analyzed the effects of chemically blocking type 1 muscarinic receptors (M1R) on either the left or right ovary on ovulation rate, number of ova shed and steroid hormones levels. M1R were unilaterally blocked in ovary with the M1R selective antagonist pirenzepine (PZP). PZP was delivered into the bursa ovarica of the left or right ovary of adult rats at 13:00 h on proestrus day. PZP treatment in the left but not in the right ovary blocked ovulation. PZP did not modify the number of ova shed, nor progesterone or 17ß-estradiol serum levels. The surge of luteinizing hormone levels was diminished while that of follicle-stimulating hormone did not change in animals treated with PZP in the left ovary. Interestingly, treatment with either synthetic luteinizing hormone-releasing hormone or human chorionic gonadotropin 1 h after PZP administration in the left ovary restored ovulation in both ovaries. The presence of M1R protein in the theca cells of the ovarian follicles as well as in cells of the corpus luteum was detected on proestrus day. These results suggest that M1R activation in the left ovary is required for pre-ovulatory gonadotropin-releasing hormone (GnRH) secretion and ovulation. Furthermore, these results also suggest that M1R in the left ovary might be regulating ovulation asymmetrically through a stimulatory neural signal relayed to the hypothalamus via the vagus nerve to induce the GnRH secretion which then triggers ovulation.


Assuntos
Ovário/metabolismo , Ovulação/fisiologia , Proestro/fisiologia , Receptor Muscarínico M1/metabolismo , Animais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/farmacologia , Hipotálamo/metabolismo , Hormônio Luteinizante/sangue , Antagonistas Muscarínicos/farmacologia , Folículo Ovariano/metabolismo , Ovulação/efeitos dos fármacos , Pirenzepina/farmacologia , Proestro/efeitos dos fármacos , Progesterona/sangue , Ratos , Receptor Muscarínico M1/efeitos dos fármacos , Células Tecais , Vagotomia
13.
Stem Cells Int ; 2015: 583984, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064137

RESUMO

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1ß, IL-8, LIF and TGFß2.

14.
Biochimie ; 72(9): 671-5, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2126208

RESUMO

Acylation of L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) with complete retention of catalytic activity was achieved. Several parameters of the acylation method, based on the binding of palmitoyl residues to epsilon-NH2 groups of protein, were optimized. The correlation between the acylation degree of L-asparaginase and the retention of catalytic activity was established. For a palmitoyl chloride/protein molar ratio ranging from 50 to 900, a degree of modification of 10 to 30% and a retention of catalytic activity of 98 to 60% respectively, was observed. Hydrophobicity of 30% acylated protein was correlated with turbidity in water and octanol and was compared with the native protein. Acylated protein incorporated into liposomes, showed an increase in catalytic activity in intact form as compared to the native enzyme. By the introduction of a sequential acylation cycle, an improvement of the degree of modification with a maximal value at 50% was obtained. Total retention of catalytic activity was achieved by acylation in the presence of 8 mM L-asparagine in a reactional medium.


Assuntos
Acilação , Asparaginase/metabolismo , Lipossomos/metabolismo , Octanóis , Palmitatos/metabolismo , Solubilidade , Especificidade por Substrato , Água
15.
J Endocrinol ; 113(3): 397-401, 1987 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3625097

RESUMO

The possible existence of peripheral asymmetry in the neuroendocrine mechanisms participating in the response of the ovary to gonadotrophins, and the participation of the vagus nerve, was investigated. At oestrus, the ovulation rate (number of ovulating/number of treated rats) of the left ovary in right unilaterally ovariectomized rats was lower than that in the right ovary in left unilaterally ovariectomized rats (42 vs 84%). No differences in the number of ova shed per ovulating animal nor in compensatory ovarian hypertrophy (COH) were observed. Bilateral section of the vagus nerve resulted in reduced COH only in those animals with the left ovary in situ (right unilaterally ovariectomized). Section of the left vagus nerve induced different effects depending upon which ovary was left in situ. When the left ovary was in situ an increase in ovulation rate, COH and number of ova shed was observed; however, when the right ovary was left in place the above three parameters decreased. Section of the right vagus nerve produced a decrease only in COH in both right and left unilaterally ovariectomized animals. It is concluded that in the unilaterally ovariectomized rat the right ovary seems more able to react to compensatory regulatory systems than does the left. The character of the information carried by the left and right vagus nerve is different.


Assuntos
Ovário/fisiologia , Ovulação , Nervo Vago/fisiologia , Animais , Feminino , Hipertrofia , Ovariectomia , Ovário/patologia , Ratos , Vagotomia
16.
J Endocrinol ; 133(2): 205-10, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1613423

RESUMO

The effects were analysed of a unilateral implant of atropine on ovulation in intact and hemiovariectomized adult rats, together with the response of the atropine-implanted rats to hormone replacement. An outer cannula directed to the left or right preoptic (POA)-anterior-hypothalamic area (AHA) was implanted into cyclic adult rats. A group of animals in oestrus was hemiovariectomized and some were also implanted with a cannula. After two consecutive 4-day cycles, the hemiovariectomized animals were implanted with atropine (23 +/- 4 micrograms) or cholesterol (25 +/- 2 micrograms) on the day of oestrus. Atropine implanted into the left side of the POA-AHA blocked ovulation and compensatory ovarian hypertrophy, whilst implants in the right side had no effects. Administration of gonadotrophin-releasing hormone (GnRH; 3.7 micrograms/kg) at 13.00 h on the expected day of pro-oestrus induced ovulation in six out of seven treated animals. Of 19 rats with an implant of atropine in the left side of the POA-AHA, one ovulated after treatment with pregnant mare serum gonadotrophin (PMSG) on oestrus, or oestradiol benzoate or human chorionic gonadotrophin (hCG) on day 2 of dioestrus. The effects on ovulation of a unilateral implant of atropine into the POA-AHA of cyclic adult rats and the responses of such rats to GnRH, PMSG, hCG and oestradiol benzoate replacement were also studied. Ovulation was induced in rats with a unilateral implant of atropine and which had been treated with GnRH or hCG at 13.00 h on the expected day of pro-oestrus after the implant.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Atropina/farmacologia , Hipotálamo Anterior/fisiologia , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Animais , Feminino , Hormônio Liberador de Gonadotropina/fisiologia , Gonadotropinas/fisiologia , Hipotálamo Anterior/anatomia & histologia , Ovariectomia , Área Pré-Óptica/fisiologia , Ratos , Ratos Endogâmicos
17.
J Endocrinol ; 123(3): 437-9, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2607252

RESUMO

The effects were analysed, on ovulation at the next oestrus, of unilaterally implanting atropine in the anterior hypothalamus of rats on each day of the oestrous cycle. Implantation on day 1 of dioestrus on either side of the anterior hypothalamus blocked ovulation. Implantation on the left side of the hypothalamus on day 2 of dioestrus blocked ovulation in all animals, whereas implantation on the right side allowed 71% of the animals to ovulate (0/4 vs 5/7; P less than 0.05). Implantation at pro-oestrus on either side of the hypothalamus did not modify the rate of ovulation. When implantation was carried out on the day of oestrus on the right, none of the animals ovulated, but all ovulated when the implant was on the left (0/8 vs 8/8; P less than 0.01). The results suggest the existence of a cholinergic hypothalamic lateralization in the mechanism regulating ovulation which depends on the day of the oestrous cycle.


Assuntos
Atropina/farmacologia , Estro/fisiologia , Hipotálamo Anterior/fisiologia , Ovulação/efeitos dos fármacos , Animais , Atropina/administração & dosagem , Implantes de Medicamento , Feminino , Ratos
18.
J Endocrinol ; 124(1): 37-41, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2299276

RESUMO

The effects were analysed of a unilateral lesion in the anterior or medial hypothalamus made on the day of oestrus on right or left hemicastrated rats. On the day of oestrus after two consecutive oestrous cycles of the same length, the ovulation rate in rats with lesions in the anterior left hypothalamus was lower than in control hemicastrated animals (5/16 vs 18/20; P less than 0.01), and normal in those rats with lesions in the right side (14/18). None of the animals with lesions in the left side of the anterior hypothalamus and with the left ovary in situ ovulated (0/7), but 5/9 with the right ovary in situ did ovulate (P less than 0.05). Lesions on either side of the medial hypothalamus did not modify ovulation rate. Compensatory ovulation was reduced in those animals with lesions in the right anterior hypothalamus and with the right ovary in situ. Lesions in either side of the medial hypothalamus reduced compensatory ovulation. Lesions in the right side of the anterior and medial hypothalamus increased compensatory ovarian hypertrophy in the left ovary and decreased it in the right ovary. Lesions in the left side of the anterior hypothalamus increased compensatory ovarian hypertrophy in the left ovary only, whereas lesions in the left side of the medial hypothalamus reduced compensatory ovarian hypertrophy in the right ovary. The results suggest that the information arising in each side of the anterior and medial hypothalamus plays different roles in the ipsi-and contralateral ovary, when either the left or the right ovary is absent.


Assuntos
Hipotálamo/fisiologia , Ovário/fisiologia , Ovulação/fisiologia , Animais , Feminino , Hipertrofia , Ovariectomia , Ovário/patologia , Ratos , Ratos Endogâmicos
19.
Am J Med Genet ; 35(1): 85-90, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2301474

RESUMO

The clinical manifestations of various degrees of mental retardation, spastic diplegia, and deaf mutism are known as the neurologic type of endemic cretinism (EC), occurring in countries with high goiter endemicity. Maternal iodine deficiency has been established as the major cause in EC, whereas a genetic predisposition has not been well-documented. Genetic data on 70 families with EC from Highland Ecuador are reported. A segregation analysis of 49 fully classified families yielded an estimate of P = 0.245 (var [P] = 0.00167). Half-sibs were all unaffected and no significant birth order effect was observed among 101 probands. The data indicate an autosomal recessive predisposition as a major etiological factor. Because the neurologic type of EC represents a defined section of the spectrum of iodine deficiency disorders (IDD), the term fetal iodine deficiency disorder (FIDD) rather than cretinism is suggested. The clinical findings in 70 patients were used to delineate the minimal diagnostic criteria of FIDD.


Assuntos
Hipotireoidismo Congênito/genética , Surdez/genética , Doenças Fetais/etiologia , Iodo/deficiência , Anormalidades Múltiplas/etiologia , Antropometria , Hipotireoidismo Congênito/metabolismo , Dermatoglifia , Equador , Feminino , Genes Recessivos , Humanos , Masculino , Linhagem , Gravidez
20.
Int J Epidemiol ; 28(4): 799-803, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10480714

RESUMO

BACKGROUND: Taenia solium neurocysticercosis (NCC) has been documented as one of the major causes of epilepsy in developing countries. However, methodological limitations have hindered the evaluation of the epidemiological relationship between cysticercosis and epilepsy at the community level. METHODS: We used the WHO protocol for epidemiological evaluation of neurological disorders to conduct a door-to-door survey among 2723 residents of San Pablo del Lago, an Ecuadorean rural community in which T. solium taeniasis/cysticercosis was known to be endemic. The WHO protocol was complemented by neuroimaging and immunological tests to confirm the diagnosis of this infection. RESULTS: In all 31 people suffering from active epilepsy were detected (prevalence 11.4 per 1000, 95% CI:7.7-15.4); 26 agreed to undergo a computer tomography (CT) examination, and 28 agreed to have blood drawn for serodiagnosis. Fourteen of the 26 (53.8%) had CT changes compatible with NCC and six of the 28 (21.4%) tested positive in the enzyme-linked immunoelectro-transfer blot (EITB) assay. In a seizure-free random sample of this population, 17 of 118 (144 per 1000) subjects examined by CT and 10 out of 96 (104 per 1000) examined by EITB had evidence of this infection. The differences between the epilepsy group and the random sample of the population were statistically significant (OR = 6.93, 95% CI: 2.7-17.5, P < 0.001) for CT diagnosis, but not for EITB results (OR = 2.75, 95% CI: 0.8-7.1, P > 0.12, NS). CONCLUSIONS: These findings confirm that T. solium NCC is a significant cause of epilepsy at the community level in Andean villages of Ecuador. It is important to initiate effective public health interventions to eliminate this infection, which may be responsible for at least half of the cases of reported epilepsy in Ecuador.


Assuntos
Epilepsia/epidemiologia , Neurocisticercose/epidemiologia , Adolescente , Adulto , Animais , Anticorpos Anti-Helmínticos/análise , Criança , Pré-Escolar , Cysticercus/imunologia , Cysticercus/isolamento & purificação , Equador/epidemiologia , Ensaio de Imunoadsorção Enzimática , Epilepsia/diagnóstico por imagem , Epilepsia/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neurocisticercose/complicações , Neurocisticercose/diagnóstico por imagem , Vigilância da População , Prevalência , População Rural , Tomografia Computadorizada por Raios X
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