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1.
Aust Vet J ; 95(11): 403-415, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29076219

RESUMO

OBJECTIVE: To investigate if administration of potential chemosterilants by transvaginal, ultrasound-guided intraovarian injection is an alternative to surgical sterilisation. DESIGN: Randomised control study. METHODS: Bos indicus heifers were treated with intraovarian injections of saline (n = 10), CaCl2 (n = 10), zinc gluconate (ZG; n = 10) or a combination of CaCl2 and ZG (CaCl2 + ZG; n = 10). Heifers were exposed to a bull from 82 to 84 days after treatment and slaughtered between 364 and 396 days after treatment. RESULTS: After treatment administration, the concentrations of haptoglobin and anti-Müllerian hormone and the total oocyte counts did not differ (P > 0.150) between treatments. Pain responses were observed in heifers treated with ZG and CaCl2 + ZG but not in heifers treated with saline or CaCl2 . Total ovarian mass at slaughter was less in heifers treated with CaCl2 compared with the other treatments (P < 0.05). Complete regression of one ovary was observed in 40% (4/10) of the heifers treated with CaCl2 . Pregnancies were recorded in ≥ 70% of heifers administered each treatment. CONCLUSION: Treatments used in this study were not able to sterilise most of the B. indicus heifers, but treatment with CaCl2 has the potential to cause complete ovarian atrophy without causing detectable pain.


Assuntos
Cloreto de Cálcio/administração & dosagem , Esterilizantes Químicos/administração & dosagem , Gluconatos/administração & dosagem , Ovário/efeitos dos fármacos , Animais , Hormônio Antimülleriano/sangue , Austrália , Comportamento Animal , Cloreto de Cálcio/farmacologia , Bovinos , Esterilizantes Químicos/farmacologia , Feminino , Gluconatos/farmacologia , Frequência Cardíaca , Injeções/métodos , Injeções/veterinária , Ovário/patologia , Análise de Sobrevida , Resultado do Tratamento
2.
Theriogenology ; 88: 73-83, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27865415

RESUMO

Chemosterilants have long been used in sterilization programs for managing pet, stray, and wild animals but adverse effects such as trauma, incomplete responses to treatment, and complete abolition of gonadal sources of testosterone often occurs. This study describes the biosterilant effects of administering three doses of Bacillus thuringiensis kurstaki HD-73 (Bt 5, 50, and 250 mg/kg; 20 rats/dose) extract in adult male Wistar albino rats on testicular parameters, function, histology, and a number of biochemical markers of overall health, free radical production, and cell proliferation. Intratesticular administration of Bt extract to rats induces testicular oxidative stress and damages and consequently, perturb spermatogenesis, degeneration of testis, reduction in testes size, and depletion of testosterone and antioxidant enzyme concentrations in a dose-dependent manner because of free radical-mediated lipid peroxidation. No morbidity or mortality adverse effects were observed in both the saline control and Bt extract-treated rats. Significant variation was noted in clinical manifestations, weight and volume of testes, and hormonal and biochemical profiles between Bt doses in comparison with the saline control. Aspermia/azoospermia (100%) resulted in Bt-treated rats without any adverse effects. Histopathological analysis showed degeneration, necrosis, vacuolation, fewer germ cells, formation of multinucleated giant cells, and a lack of elongated spermatids in atrophic seminiferous tubules in Bt extract-treated groups in the presence of low concentrations of testosterone, antioxidant enzymes, and suppression of germ cell proliferation. Dose-dependent effects were evident in most parameters that were measured. The vast array of tests that were undertaken also provides some important indicators of the physiological effects associated with the treatments that were applied. Intratesticular injection of Bt extract impairs spermatogenesis and induces permanent sterility in rats.


Assuntos
Bacillus thuringiensis/química , Esterilizantes Químicos/farmacologia , Animais , Asparaginase/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos
3.
Chimia (Aarau) ; 70(10): 715-720, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27779930

RESUMO

Both historically and at present, vector control is the most generally effective means of controlling malaria transmission. Insecticides are the predominant method of vector control, but the sterile insect technique (SIT) is a complementary strategy with a successful track record in both agricultural and public health sectors. Strategies of genetic and radiation-induced sterilization of Anopheles have to date been limited by logistical and/or regulatory hurdles. A safe and effective mosquito chemosterilant would therefore be of major utility to future deployment of SIT for malaria control. Here we review the prior and current use of chemosterilants in SIT, and assess the potential for future research. Recent genomic and proteomic studies reveal opportunities for specific targeting of seminal fluid proteins, and the capacity to interfere with sperm motility and storage in the female.


Assuntos
Esterilizantes Químicos/farmacologia , Insetos Vetores , Malária/prevenção & controle , Controle de Mosquitos/métodos , Animais , Aziridinas/farmacologia , Quitinases/antagonistas & inibidores , Hormônios Juvenis/farmacologia
4.
Prev Vet Med ; 123: 106-120, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26657528

RESUMO

Population management of free-roaming domestic dogs (Canis lupus familiaris) is of interest due to the threat these animals pose to people, other animals and the environment. Current sterilization procedures for male dogs include surgical and chemical methods. However, little is known about how these procedures affect their behavior. The primary objective of this study was to investigate changes in selected behaviors following chemical and surgical sterilization in a male free-roaming dog (FRD) population in southern Chile. We also examined the association between serum testosterone levels and behaviors thought to be influenced by circulating androgens. A total of 174 dogs were randomly assigned to either a surgical or chemical sterilization group, or a control group. At the onset of the intervention period, 119 dogs remained and 102 dogs successfully completed the study. Each dog was monitored pre- and post-intervention using video recordings, GPS collars, and blood samples for the measurement of testosterone. Analysis of behavior revealed that surgically castrated dogs showed no reduction of sexual activity or aggression when compared to their pre-intervention behavior. Chemically sterilized dogs showed a statistically significant increase in dog-directed aggression, but no change in sexual activity. There was no change in home range size in any groups between the pre- and post-intervention measurement. We found no consistent association between levels of serum testosterone concentration and behavioral changes in any of the groups. This study presents the first detailed behavioral observations following surgical and chemical sterilization in male FRDs. The information generated is highly relevant to communities struggling with the control of FRDs. Complementary studies to further our understanding of the effects of male sterilization on the behavioral and reproductive dynamics of FRD populations are needed.


Assuntos
Agressão , Esterilizantes Químicos/farmacologia , Cães/fisiologia , Gluconatos/farmacologia , Comportamento Sexual Animal , Esterilização Reprodutiva/veterinária , Agressão/efeitos dos fármacos , Animais , Arginina/administração & dosagem , Arginina/farmacologia , Esterilizantes Químicos/administração & dosagem , Chile , Cães/cirurgia , Análise Fatorial , Gluconatos/administração & dosagem , Masculino , Orquiectomia/veterinária , Comportamento Sexual Animal/efeitos dos fármacos , Esterilização Reprodutiva/métodos , Testosterona/sangue
5.
J Neuroimmunol ; 284: 57-66, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26025059

RESUMO

Signaling mechanisms involved in regulating blood-brain barrier (BBB) integrity during central nervous system (CNS) inflammation remain unclear. We show that an imbalance between pro-/anti-inflammatory cytokines/chemokines alters claudin-5 expression. In vivo, gliotoxin-induced changes in glial populations and an imbalance between pro-/anti-inflammatory cytokine/chemokine expression occurred as BBB integrity was compromised. The balance was restored as BBB integrity was re-established. In vitro, TNF-α, IL-6, and MCP-1 induced paracellular claudin-5 expression loss. TNF-α- and IL-6- effects were mediated through the PI3K pathway and IL-10 attenuated TNF-α's effect. This study shows that pro-/anti-inflammatory modulators play a critical role in BBB integrity during CNS inflammation.


Assuntos
Claudina-5/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Colículos Inferiores/citologia , Neuroglia/metabolismo , Animais , Antígeno CD11b/metabolismo , Linhagem Celular Transformada , Esterilizantes Químicos/farmacologia , Cromonas/farmacologia , Citocinas/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Morfolinas/farmacologia , Neuroglia/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo , alfa-Cloridrina/farmacologia
6.
Theriogenology ; 83(6): 1021-7, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25557187

RESUMO

There is a growing interest in chemical sterilization as an alternative to surgical castration in large-scale sterilization campaigns to control canine populations. An important step toward understanding the short-term and long-term effects of chemical sterilants is to determine their impact on blood testosterone concentrations, particularly as these could influence dog behavior after treatment. A field trial was conducted with 118 free-roaming male dogs in the Chilean Patagonia, where 36 dogs were chemically sterilized using EsterilSol, 39 dogs were surgically castrated, and 43 dogs remained intact as controls. Blood testosterone levels were determined at four time periods: on enrollment 6 months before treatment (t-6m), at the time of treatment (t0, within one hour after surgical castration or chemical sterilization and during a concurrent 2-week period for the control group), four (t+4m), and six (t+6m) months after treatment. Intrinsic and temporal factors were evaluated; age was significantly associated with testosterone, where dogs 2- to 4-year-old had the highest testosterone concentrations (P = 0.036), whereas body weight and body condition scores were not associated with testosterone; testosterone concentration was not influenced by time of day, month, or season. After treatment (t+4m and t+6m), all of the surgically castrated dogs had testosterone concentrations below 1.0 ng/mL. On the basis of this cut point (<1 ng/mL), testosterone remained unchanged in 66% of the chemically sterilized dogs at both t+4m and t+6m; it remained low for 22% of dogs at both t+4m and t+6m; it was unchanged at t+4m but low at t+6m in 9% of dogs; and, it was low at t+4m but reverted back to unchanged at t+6m in one dog (3%). Incidentally, testosterone in chemically sterilized dogs increased dramatically within 1 hour of treatment (t0), more than doubling (131%) the concentration of control dogs at the time of treatment (t0), likely because of severe necrosis of interstitial cells. The use of EsterilSol as a method of sterilizing dogs had a variable effect on blood testosterone concentrations. Approximately, 30% of chemically sterilized dogs had a reduced testosterone concentration (actual maximum, 1 ng/mL) after 6 months, similar to that of surgically castrated dogs. Most chemically sterilized dogs, however, showed no long-term changes in blood testosterone concentrations.


Assuntos
Esterilizantes Químicos/farmacologia , Cães , Gluconatos/farmacologia , Orquiectomia/veterinária , Esterilização Reprodutiva/veterinária , Testosterona/sangue , Animais , Gluconatos/administração & dosagem , Masculino , Orquiectomia/métodos , Esterilização Reprodutiva/métodos
7.
Malar J ; 13: 210, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24888439

RESUMO

BACKGROUND: Current vector-based malaria control strategies are threatened by the rise of biochemical and behavioural resistance in mosquitoes. Researching mosquito traits of immunity and fertility is required to find potential targets for new vector control strategies. The seminal transglutaminase AgTG3 coagulates male Anopheles gambiae seminal fluids, forming a 'mating plug' that is required for male reproductive success. Inhibitors of AgTG3 can be useful both as chemical probes of A. gambiae reproductive biology and may further the development of new chemosterilants for mosquito population control. METHODS: A targeted library of 3-bromo-4,5-dihydroxoisoxazole inhibitors were synthesized and screened for inhibition of AgTG3 in a fluorescent, plate-based assay. Positive hits were tested for in vitro activity using cross-linking and mass spectrometry, and in vivo efficacy in laboratory mating assays. RESULTS: A targeted chemical library was screened for inhibition of AgTG3 in a fluorescent plate-based assay using its native substrate, plugin. Several inhibitors were identified with IC50 < 10 µM. Preliminary structure-activity relationships within the library support the stereo-specificity and preference for aromatic substituents in the chemical scaffold. Both inhibition of plugin cross-linking and covalent modification of the active site cysteine of AgTG3 were verified. Administration of an AgTG3 inhibitor to A. gambiae males by intrathoracic injection led to a 15% reduction in mating plug transfer in laboratory mating assays. CONCLUSIONS: A targeted screen has identified chemical inhibitors of A. gambiae transglutaminase 3 (AgTG3). The most potent inhibitors are known inhibitors of human transglutaminase 2, suggesting a common binding pose may exist within the active site of both enzymes. Future efforts to develop additional inhibitors will provide chemical tools to address important biological questions regarding the role of the A. gambiae mating plug. A second use for transglutaminase inhibitors exists for the study of haemolymph coagulation and immune responses to wound healing in insects.


Assuntos
Anopheles/enzimologia , Esterilizantes Químicos/farmacologia , Proteínas de Insetos/antagonistas & inibidores , Isoxazóis/farmacologia , Controle de Mosquitos/métodos , Sêmen/enzimologia , Transglutaminases/antagonistas & inibidores , Animais , Domínio Catalítico , Esterilizantes Químicos/síntese química , Esterilizantes Químicos/química , Reagentes para Ligações Cruzadas/química , Reagentes para Ligações Cruzadas/farmacologia , Inibidores de Cisteína Proteinase/farmacologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Concentração Inibidora 50 , Isoxazóis/síntese química , Isoxazóis/química , Masculino , Modelos Moleculares , Estrutura Molecular , Conformação Proteica , Proteínas Recombinantes/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas , Especificidade da Espécie , Relação Estrutura-Atividade , Especificidade por Substrato
8.
J Econ Entomol ; 106(6): 2541-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24498756

RESUMO

The success of sterile males in area-wide sterile insect technique (aw-SIT) programs against Ceratitis capitata (Wiedemann) is currently measured by using indirect methods as the wild:sterile male ratio captured in monitoring traps. In the past decade, molecular techniques have been used to improve these methods. The development of a polymerase chain reaction-restriction fragment-length polymorphism-based method to identify the transfer of sterile sperm to wild females, the target of SIT, was considered a significant step in this direction. This method relies on identification of sperm by detecting the presence of Y chromosomes in spermathecae DNA extract complemented by the identification of the genetic origin of this sperm: Vienna-8 males or wild haplotype. However, the application of this protocol to aw-SIT programs is limited by handling time and personnel cost. The objective of this work was to obtain a high-throughput protocol to facilitate the routine measurement in a pest population of sterile sperm presence in wild females. The polymerase chain reaction-restriction fragment-length polymorphism markers previously developed were validated in Mediterranean fruit fly samples collected from various locations worldwide. A laboratory protocol previously published was modified to allow for the analysis of more samples at the same time. Preservation methods and preservation times commonly used for Mediterranean fruit fly female samples were assessed for their influence on the correct molecular detection of sterile sperm. This high-throughput methodology, as well as the results of sample management presented here, provide a robust, efficient, fast, and economical sterile sperm identification method ready to be used in all Mediterranean fruit fly SIT programs.


Assuntos
Ceratitis capitata/fisiologia , Controle Biológico de Vetores/métodos , Reação em Cadeia da Polimerase/métodos , Espermatozoides/efeitos dos fármacos , Animais , Ceratitis capitata/efeitos dos fármacos , Ceratitis capitata/genética , Esterilizantes Químicos/farmacologia , Feminino , Masculino , Polimorfismo de Fragmento de Restrição , Espermatozoides/fisiologia
9.
Micron ; 44: 125-32, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22739123

RESUMO

The effects of ingested neem oil, a botanical insecticide obtained from the seeds of the neem tree, Azadirachta indica, on the midgut cells of predatory larvae Ceraeochrysa claveri were analyzed. C. claveri were fed on eggs of Diatraea saccharalis treated with neem oil at a concentration of 0.5%, 1% and 2% during throughout the larval period. Light and electron microscopy showed severe damages in columnar cells, which had many cytoplasmic protrusions, clustering and ruptured of the microvilli, swollen cells, ruptured cells, dilatation and vesiculation of rough endoplasmic reticulum, development of smooth endoplasmic reticulum, enlargement of extracellular spaces of the basal labyrinth, intercellular spaces and necrosis. The indirect ingestion of neem oil with prey can result in severe alterations showing direct cytotoxic effects of neem oil on midgut cells of C. claveri larvae. Therefore, the safety of neem oil to non-target species as larvae of C. claveri was refuted, thus the notion that plants derived are safer to non-target species must be questioned in future ecotoxicological studies.


Assuntos
Glicerídeos/farmacologia , Insetos/efeitos dos fármacos , Larva/efeitos dos fármacos , Terpenos/farmacologia , Animais , Esterilizantes Químicos/farmacologia , Repelentes de Insetos/farmacologia , Inseticidas/farmacologia , Extratos Vegetais/farmacologia
10.
Theriogenology ; 77(6): 1223-31, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22284225

RESUMO

Quinestrol, a synthetic estrogen with marked estrogenic effects and prolonged activity, has potential as a contraceptive for Mongolian gerbils. The objective of this study was to describe the effects of quinestrol on reproductive hormone expression, secretion, and receptor levels in female Mongolian gerbils. Serum and pituitary concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were decreased, whereas serum concentrations of estradiol (E2) and progesterone (P4) were increased after quinestrol treatment; the effects were both time- and dose-dependent. Furthermore, quinestrol downregulated expression of FSHß and LHß mRNA in the pituitary gland, as well as FSH receptor (FSHR) and estrogen receptor (ER) ß in the ovary. However, it up-regulated mRNA expression levels of ERα and progesterone receptor (PR) in the pituitary gland and uterus, as well as mRNA for LH receptor (LHR) and PR in the ovary (these effects were time- and dose-dependent). In contrast, quinestrol had no significant effects on the mRNA expression levels of ERα in the ovary, or the gonadotropin α (GtHα) subunit in the pituitary gland. We inferred that quinestrol impaired synthesis and secretion of FSH and LH and that the predominant ER subtype in the pituitary gland of Mongolian gerbils may be ERα. Overall, quinestrol disrupted reproductive hormone receptor expression at the mRNA level in the pituitary-gonadal axis of the Mongolian gerbil.


Assuntos
Esterilizantes Químicos/farmacologia , Gerbillinae/fisiologia , Hormônios Hipofisários/metabolismo , Quinestrol/farmacologia , Receptores do Hormônio Hipofisário/metabolismo , Animais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Expressão Gênica/efeitos dos fármacos , Gerbillinae/metabolismo , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hormônios Hipofisários/sangue , Progesterona/sangue , RNA Mensageiro/metabolismo
11.
J Environ Pathol Toxicol Oncol ; 30(2): 93-102, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21967454

RESUMO

To examine the effects of α-chlorohydrin on testis and cauda epididymis in the male house rat (Rattus rattus), 24 adult male rats were segregated into two groups. Group I rats were force-fed daily by intragastric intubation with α-chlorohydrin at a single dose of 1.0 mg/100 g body weight/d for 5, 15, and 45 days. Another group was fed with distilled water, which served as the control. The treated male rats were paired with 24 adult proestrus female rats for 5 days after the last oral treatment and fertility was tested. At the end of the experiments, all of the male rats were weighed and killed by cervical dislocation. The right testes were removed, weighed, and processed for ultrastructural changes of spermatozoa from the cauda epididymis and testis under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The seminiferous tubular area, nuclear diameter of the Sertoli and Leydig cells, percentage of spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids, spermatozoa, and Sertoli cells in each group were compared morphometrically. Our results showed that the percentages of primary spermatocytes steadily increased from 5 to 15 days, but primary and secondary spermatocytes decreased significantly at 45 days. There was a steady decline in the percentages of spermatozoa and spermatids at all fixation intervals in the treated animals, but the percentages of spermatogonia and Sertoli cells increased significantly at 15 and 45 days. Seminiferous tubular areas, nuclear diameter of Leydig and Sertoli cells, and fertility rates were reduced after 45 days of treatment. SEM and TEM studies revealed severe morphological abnormalities in the spermatozoa, including deglutination of the acrosomal part, loss of head capsules, and fragmentation of tail fibrils. There was an enhanced anti-fertility effect and a lower number of implantation sites in the rats treated for 5 days. Our results validate α-chlorohydrin as a successful anti-fertility agent that prevents spermatogenesis.


Assuntos
Esterilizantes Químicos/farmacologia , Fertilidade/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , alfa-Cloridrina/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Ratos , Contagem de Espermatozoides , Espermatogênese/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/ultraestrutura , Testículo/ultraestrutura , Fatores de Tempo
12.
Pest Manag Sci ; 66(6): 657-63, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20157929

RESUMO

BACKGROUND: Chemosterilisation with lufenuron bait stations is a recently developed technique that is being implemented for Ceratitis capitata Wiedemann control. The aim of this work was to evaluate the chemosterilising effect of lufenuron against four economically important Latin American fruit flies species: Anastrepha ludens (Loew.), A. obliqua Macquart, A. serpentina Wiedemann and A. striata Schiner (Diptera: Tephritidae) in order to design a similar strategy for their control. RESULTS: Sexually mature adults were treated by ingestion with concentrations ranging from 0.1 to 30.0 mg g(-1) of lufenuron in the diet. In addition, conspecific crosses with only one of the sexes being treated (30.0 mg g(-1)) were performed in order to appraise the contribution of each sex to the sterilising effect. In all cases, fecundity was not affected by the treatments, as opposed to fertility where all Anastrepha species studied were significantly affected, although to different extents. The conspecific crosses showed that treated males of A. ludens, A. obliqua and A. serpentina were not able to transmit the sterility to their respective untreated females. Only in the case of A. striata did crossing treated males with untreated females significantly reduced egg hatch. CONCLUSION: Although further investigations are required, the present results demonstrate that the use of lufenuron for controlling A. striata could be potentially viable.


Assuntos
Benzamidas/farmacologia , Esterilizantes Químicos/farmacologia , Tephritidae/efeitos dos fármacos , Tephritidae/fisiologia , Animais , Feminino , Fertilidade/efeitos dos fármacos , Masculino
13.
Biol Reprod ; 79(2): 367-75, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18480469

RESUMO

Whether the main energy source for sperm motility is from oxidative phosphorylation or glycolysis has been long-debated in the field of reproductive biology. Using the rhesus monkey as a model, we examined the role of glycolysis and oxidative phosphorylation in sperm function by using alpha-chlorohydrin (ACH), a glycolysis inhibitor, and pentachlorophenol (PCP), an oxidative phosphorylation uncoupler. Sperm treated with ACH showed no change in percentage of motile sperm, although sperm motion was impaired. The ACH-treated sperm did not display either hyperactivity- or hyperactivation-associated changes in protein tyrosine phosphorylation. When treated with PCP, sperm motion parameters were affected by the highest level of PCP (200 microM); however, PCP did not cause motility impairments even after chemical activation. Sperm treated with PCP were able to display hyperactivity and tyrosine phosphorylation after chemical activation. In contrast with motility measurements, treatment with either the glycolytic inhibitor or the oxidative phosphorylation inhibitor did not affect sperm-zona binding and zona-induced acrosome reaction. The results suggest glycolysis is essential to support sperm motility, hyperactivity, and protein tyrosine phosphorylation, while energy from oxidative phosphorylation is not necessary for hyperactivated sperm motility, tyrosine phosphorylation, sperm-zona binding, and acrosome reaction in the rhesus macaque.


Assuntos
Reação Acrossômica/fisiologia , Macaca mulatta/fisiologia , Mitocôndrias/fisiologia , Motilidade Espermática/fisiologia , Interações Espermatozoide-Óvulo/fisiologia , Zona Pelúcida/metabolismo , Reação Acrossômica/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Esterilizantes Químicos/farmacologia , Feminino , Glicólise/efeitos dos fármacos , Glicólise/fisiologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Pentaclorofenol/farmacologia , Capacitação Espermática/efeitos dos fármacos , Capacitação Espermática/fisiologia , Motilidade Espermática/efeitos dos fármacos , Interações Espermatozoide-Óvulo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Desacopladores/farmacologia , alfa-Cloridrina/farmacologia
14.
Brain Res ; 1173: 126-36, 2007 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-17803981

RESUMO

The multidrug transporter, P-glycoprotein, expressed at the blood-brain barrier is thought to be important for limiting access of toxic agents to the brain, but its relationship to astrocyte expression is unclear. We have studied P-glycoprotein expression in the inferior colliculus after a temporary loss of blood-brain barrier integrity following chemically induced astrocyte loss and at the fenestrated vascular endothelium of the area postrema. Male Fisher F344 rats given 3-chloropropanediol showed astrocyte loss from 12 to 24 h until the lesion was repopulated 8-28 days later. In non-dosed tissue, P-glycoprotein expression was seen the entire length of platelet endothelial cell adhesion molecule immunoreactive vessels. Within 6 h of dosing, a significant (p<0.05) reduction in the total length of P-glycoprotein immunoreactive vasculature was evident. By 48 h, P-glycoprotein immunoreactivity was heavily fragmented. The total length of P-glycoprotein immunoreactive vessels became minimal at 4 days (p<0.001) but was still present in many vessels. From 6 to 28 days, P-glycoprotein immunoreactivity returned across the inferior colliculus, in parallel with astrocytic repopulation of the lesion, and by 28 days resembled that seen in control tissue. The area postrema showed GFAP immunoreactive astrocytes but which made limited contact with the vasculature, while the platelet endothelial cell adhesion molecule immunoreactive vasculature showed no expression of P-glycoprotein. These findings provide evidence supporting a link between GFAP-astrocyte and P-glycoprotein expression in the mature brain vasculature in vivo.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Astrócitos/fisiologia , Barreira Hematoencefálica/metabolismo , Endotélio Vascular/fisiologia , Regulação da Expressão Gênica/fisiologia , Análise de Variância , Animais , Área Postrema/anatomia & histologia , Área Postrema/metabolismo , Astrócitos/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Esterilizantes Químicos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/lesões , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Laminina/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo , alfa-Cloridrina/farmacologia
15.
Contraception ; 73(3): 289-300, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16472573

RESUMO

OBJECTIVE: To investigate a method of chemical sterilization and its efficacy in adult albino rats. METHOD: Evaluation was conducted 3 weeks after a single bilateral intratesticular injection of calcium chloride (CaCl2) at the dose of 5, 10, 15 or 20 mg per testis per 100 g body weight. RESULTS: The significant graded diminution in relative sex organ weights, testicular androgenic enzymes like Delta5,3beta-hydroxysteroid dehydrogenase (Delta5,3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and superoxide dismutase (SOD) activities, testicular content of reduced glutathione (GSH), plasma and intratesticular concentrations of testosterone, epididymal sperm count as well as significant elevation in plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testicular content of malondialdehyde (MDA) were noted in all the treated groups with respect to vehicle control. There was no chronic general stress in experimental animals as indicated by insignificant changes in plasma concentrations of corticosterone, prolactin, total protein, blood urea nitrogen and fasting blood sugar level. Dose-dependent responses on testicular histopathology were recorded by noting multinucleated giant cells in seminiferous tubules, derangement of tubular architecture along with infiltration of leucocytes and appearance of fibrous tissue throughout the testicular sections. The fertility efficacy of the 10, 15 or 20 mg CaCl2-treated males was nil, proven after mating with fertile, virgin healthy females, as there were no implantation sites in each uterine horns noted by laparotomy. CONCLUSION: Intratesticular CaCl2 injection at a specific dose might serve as a way of sterilization and may be considered as an alternative to surgical castration in male animals.


Assuntos
Cloreto de Cálcio/farmacologia , Esterilizantes Químicos/farmacologia , Esterilização Reprodutiva/veterinária , Testículo/efeitos dos fármacos , Animais , Glicemia/análise , Cloreto de Cálcio/administração & dosagem , Esterilizantes Químicos/administração & dosagem , Corticosterona/sangue , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante/sangue , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Histocitoquímica/veterinária , Hidroxiesteroide Desidrogenases/metabolismo , Injeções , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Contagem de Espermatozoides/veterinária , Esterilização Reprodutiva/métodos , Superóxido Dismutase/metabolismo , Testículo/química , Testículo/patologia , Testosterona/sangue
16.
Toxicol Sci ; 90(1): 49-60, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16322075

RESUMO

The environmentally prevalent arsenate (AsV) is reduced in the body to the much more toxic arsenite (AsIII). Recently, we have demonstrated that the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the reduction of AsV in the presence of glutathione, yet the role of GAPDH in AsV reduction in vivo is unknown. Therefore, we examined the effect of (S)-alpha-cholorhydrin (ACH), which forms a GAPDH-inhibitory metabolite, on the reduction of AsV in rats. These studies confirmed the in vitro role of GAPDH as an AsV reductase, inasmuch as 3 h after administration of ACH (100 or 200 mg/kg, ip) to rats both the cytosolic GAPDH activity and the AsV-reducing activity dramatically fell in the liver, moderately decreased in the kidneys, and remained unchanged in the muscle. Moreover, the AsV-reducing activity closely correlated with the GAPDH activity in the hepatic cytosols of control and ACH-treated rats. Two confounding effects of ACH (i.e., a slight fall in hepatic glutathione levels and a rise in urinary AsV excretion) prompted us to examine its influence on the disposition of injected AsV (50 micromol/kg, iv) in rats with ligated bile duct as well as in rats with ligated bile duct and renal pedicles. These experiments demonstrated that the hepatic retention of AsV significantly increased, and the combined levels of AsV metabolites (i.e., AsIII plus methylated arsenicals) in the liver decreased in response to ACH; however, ACH failed to delay the disappearance of AsV from the blood of rats with blocked excretory routes. Thus, the GAPDH inactivator ACH inhibits AsV reduction by the liver, but not by the whole body, probably because the impaired hepatic reduction is compensated for by hepatic and extrahepatic AsV-reducing mechanisms spared by ACH. It is most likely that ACH inhibits hepatic AsV reduction predominantly by inactivating GAPDH in the liver; however, a slight ACH-induced glutathione depletion may also contribute. While this study seems to support the conclusion that GAPDH in the liver is involved in AsV reduction in rats, confirmation of the in vivo role of GAPDH as an AsV reductase is desirable.


Assuntos
Arseniatos/farmacocinética , Poluentes Ambientais/farmacocinética , Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Herbicidas/farmacocinética , Bombas de Íon/antagonistas & inibidores , Complexos Multienzimáticos/antagonistas & inibidores , Animais , Arsênico/análise , ATPases Transportadoras de Arsenito , Esterilizantes Químicos/farmacologia , Citosol/química , Citosol/efeitos dos fármacos , Citosol/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Bombas de Íon/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Complexos Multienzimáticos/metabolismo , Ratos , Ratos Wistar , alfa-Cloridrina/farmacologia
18.
J Androl ; 23(2): 250-8, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11868819

RESUMO

Sperm from the caudal epididymis of 2 inbred strains of Sprague-Dawley (SD) rats, selected on the basis of their high- or low-shuttlebox avoidance responses, were analyzed for motion characteristics by a computer-assisted sperm motion analysis (CASA) system. Sperm motion in high-avoidance animals (HAA) was characterized by high velocities, high amplitude of lateral head displacement (ALH), and low beat cross frequency (BCF). Conversely, sperm from low-avoidance animals (LAA) displayed low velocities, low ALH, and high BCF. These characteristics in sperm motion were not changed by washing. Furthermore, after treatment with alpha-chlorohydrin (aCH) as a male antifertility agent affecting rat epididymal sperm motion, sperm velocities in HAA rats were significantly reduced to levels similar to those in untreated LAA rats. However, ALH and BCF in HAA rats treated with aCH were different from those in untreated LAA rats. Sperm adenosine triphosphate (ATP) content was higher in HAA than in LAA rats, correlating with values of their sperm velocities. These data suggest there are apparent strain differences in sperm motion between HAA and LAA rats and that these differences are dependent on factors, including sperm energy production.


Assuntos
Aprendizagem da Esquiva/fisiologia , Motilidade Espermática/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Esterilizantes Químicos/farmacologia , Masculino , Ratos , Ratos Endogâmicos , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Irrigação Terapêutica , alfa-Cloridrina/farmacologia
19.
Vet Res Commun ; 26(8): 651-73, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12507039

RESUMO

This study concerned the minimum and optimum effective doses of calcium chloride needed for induction of chemosterilization in male albino rats, 30 days after a single intratesticular injection of calcium chloride (CaCl2.2H2O) solution at 2.5, 5, 10 or 20 mg per 100 g body weight per testis. There was a significant diminution in the relative wet weight of the sex organs (p<0.01), epididymal sperm count (p<0.001), plasma concentration of testosterone (p<0.01), testicular activities of delta5,3beta-hydroxy steroid dehydrogenase (delta5,3beta-HSD), 17beta-hydroxy steroid dehydrogenase (17beta-HSD) (p<0.01), glutathione S-transferase (GST) (p<0.01), superoxide dismutase (SOD) (p<0.01), and peroxidase (p<0.01), significant elevations in testicular content of malondialdehyde (MDA) and conjugated dienes (p<0.01), along with derangement of seminiferous tubular architecture and degeneration of the Leydig cells in the testis and elevations in the concentrations in the plasma of LH and FSH (p<0.01), commencing at a dose of 5 mg, with the greatest effects at a dose of 20 mg. No significant alterations in these factors occurred at the dose of 2.5 mg in comparison to the control that received only the vehicle. There was no significant alteration in the plasma concentrations of prolactin (p>0.05), corticosterone (p>0.05) or fasting blood glucose or in the rectal temperature (p>0.05) at any of the doses relative to the control group, suggesting that this chemosterilizing procedure did not exert any chronic stress on the experimental animals. From these observations, it may be suggested that 5 mg should be considered as the minimum dose, and 10 mg or 20 mg as the optimum dose, whereas 2.5 mg was ineffective for induction of chemosterilization. There would seem to be little point in using more than 20 mg of calcium chloride for this purpose. Intratesticular injection of calcium chloride at an effective dose may be considered as an alternative to surgical castration.


Assuntos
Cloreto de Cálcio/farmacologia , Esterilizantes Químicos/farmacologia , Orquiectomia/veterinária , Testículo/efeitos dos fármacos , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Glicemia/análise , Temperatura Corporal , Cloreto de Cálcio/administração & dosagem , Esterilizantes Químicos/administração & dosagem , Corticosterona/sangue , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante/sangue , Glutationa Transferase/metabolismo , Histocitoquímica/veterinária , Peroxidação de Lipídeos/fisiologia , Hormônio Luteinizante/sangue , Masculino , Orquiectomia/métodos , Tamanho do Órgão , Peroxidase/metabolismo , Prolactina/sangue , Ratos , Ratos Wistar , Contagem de Espermatozoides/veterinária , Superóxido Dismutase/metabolismo , Testosterona/sangue
20.
RBCF, Rev. bras. ciênc. farm. (Impr.) ; 37(2): 203-209, maio-ago. 2001. tab, graf
Artigo em Português | LILACS | ID: lil-314046

RESUMO

A esterilização por óxido de etileno consiste no principal método esterilizante aplicado à esterilização de materiais termossensíveis. O óxido de etileno pode ser usado puro ou em misturas com gases inertes, a fim de diminuir suas características de inflamabilidade e explosividade. O presente trabalho objetivou o estudo da influência da concentração gasosa sobre a efetividade esterilizante da mistura de óxido de etileno com HCFCs 22 e 124 (Oxyfume 2002R), sob distintas temperaturas (45, 55 e 65ºC). Procedeu-se a desafios sub-letais (3, 6, 9, 12 e 15 minutos), empregando indicadores biológicos Attest 1264R da 3M, contendo Bacilus subtilus var. niger ATCC 9372. A eficácia esterilizante da mistura...


Assuntos
Bacillus subtilis , Esterilização/métodos , Esterilizantes Químicos/farmacologia , Gases , Técnicas In Vitro , Óxido de Etileno/análise , Óxido de Etileno/farmacologia , Análise de Variância , Indicadores e Reagentes , Fluxo Laminar , Esporos
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