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3.
Vet Comp Oncol ; 15(3): 890-909, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27229930

ABSTRACT

Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours.


Subject(s)
ErbB Receptors/drug effects , Neoplasms/veterinary , Receptor, ErbB-2/drug effects , Signal Transduction/drug effects , Animals , Antineoplastic Agents/therapeutic use , Cat Diseases/drug therapy , Cat Diseases/metabolism , Cat Diseases/pathology , Cats , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Cell Proliferation/physiology , Dog Diseases/drug therapy , Dog Diseases/metabolism , Dog Diseases/pathology , Dogs , Drug Synergism , ErbB Receptors/genetics , ErbB Receptors/physiology , In Vitro Techniques , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Protein-Tyrosine Kinases/antagonists & inhibitors , RNA, Small Interfering/therapeutic use , Real-Time Polymerase Chain Reaction , Receptor, ErbB-2/genetics , Receptor, ErbB-2/physiology , Signal Transduction/physiology
4.
J Neuroendocrinol ; 22(10): 1061-71, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20673300

ABSTRACT

In female rats, vaginal-cervical stimulation (VCS) received during mating induces bicircadian prolactin surges that are required for the maintenance of pregnancy or pseudopregnancy (PSP). The neural circuits that transmit VCS inputs to the brain have not been fully described, although mating stimulation is known to activate medullary noradrenergic cell groups that project to the forebrain. In response to VCS, these neurones release noradrenaline within the ventrolateral division of the ventromedial hypothalamus (VMHvl) and the posterodorsal medial amygdala (MePD), two forebrain sites that are implicated in the initiation of PSP. Noradrenaline receptor activation within the VMHvl is both necessary and sufficient for PSP induction, suggesting that noradrenaline acting within the VMHvl is particularly important in mediating the effects of VCS towards the establishment of PSP. We therefore investigated whether or not endogenous, VCS-induced noradrenaline release within the VMHvl is involved in PSP induction in the rat. Before the receipt of sufficient mating stimulation to induce PSP, a retrograde neurotoxin, dopamine-ß-hydroxylase-saporin (DBH-SAP), was infused bilaterally into the either the VMHvl or the MePD to selectively destroy afferent noradrenergic nuclei in the brainstem. DBH-SAP infusions into the VMHvl lesioned mating-responsive noradrenergic neurones in A1 and A2 medullary nuclei and reduced the incidence of PSP by 50%. Infusions of DBH-SAP into the MePD had no effect on the subsequent induction of PSP. These results suggest that VCS is conveyed to mating-responsive forebrain areas by brainstem noradrenergic neurones, and that the activity of noradrenergic cells projecting to the VMHvl is involved in the induction of PSP.


Subject(s)
Afferent Pathways , Norepinephrine/metabolism , Pseudopregnancy , Sexual Behavior, Animal/physiology , Ventromedial Hypothalamic Nucleus/anatomy & histology , Ventromedial Hypothalamic Nucleus/physiology , Afferent Pathways/anatomy & histology , Afferent Pathways/physiology , Amygdala/anatomy & histology , Amygdala/drug effects , Amygdala/physiology , Animals , Dopamine beta-Hydroxylase/metabolism , Dopamine beta-Hydroxylase/pharmacology , Female , Immunoglobulin G/pharmacology , Male , Pregnancy , Protein Synthesis Inhibitors/metabolism , Protein Synthesis Inhibitors/pharmacology , Rats , Rats, Long-Evans , Ribosome Inactivating Proteins, Type 1/metabolism , Ribosome Inactivating Proteins, Type 1/pharmacology , Saporins , Ventromedial Hypothalamic Nucleus/drug effects
5.
J Neuroendocrinol ; 21(1): 30-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19094091

ABSTRACT

Pseudopregnancy (PSP) is a neuroendocrine reflex triggered by vaginocervical stimulation similar to the neuroendocrine response of early pregnancy and is characterised by short-term neural activity, resulting in long-term neuroendocrine responses that cause repeated release of pituitary prolactin (PRL) over many days. PSP is a useful model to study how somatosensory input is transduced in the brain into neuroendocrine responses, and has been extensively characterised in rats. With increasing use of mice as an experimental model, however, and to allow use of transgenic mice to investigate mechanisms of this sensory response, it is important to characterise the principal neuroendocrine response of pseudopregnancy in this species. The present study aimed to examine the induction and neuroendocrine responses of PSP in mice using vasectomised stud males, to investigate mating-induced changes in vaginal cytology, uterine growth, and PRL secretion, and to map certain aspects of somatosensory transduction by assessing the neural activity marker FOS. Unlike the induction of pseudopregnancy in rats, which can be induced simply by multiple intromissions from a male or artificial mechanical stimulation of the cervix, PSP induction in mice required the receipt of an ejaculation from a male. In mice that received PSP-inducible mating stimuli, FOS expression was observed in a slightly different range of brain regions than has been observed in rats, with increases in the bed nucleus of the stria terminalis, medial preoptic area, and ventromedial hypothalamus, but not in limbic areas examined. Moreover, PSP mice expressed a single diurnal PRL surge on day 6 of PSP. Thus, the data demonstrate important species differences in the neuroendocrine mechanisms activated in response to a mating stimulus in mice compared with rats. A clear understanding of the species-specific response will be required in interpreting research into the reproductive biology of this species.


Subject(s)
Copulation/physiology , Neurosecretory Systems/metabolism , Pseudopregnancy , Sexual Behavior, Animal/physiology , Animals , Brain/anatomy & histology , Brain/metabolism , Ejaculation , Female , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Pregnancy , Prolactin/blood , Proto-Oncogene Proteins c-fos/metabolism , Pseudopregnancy/metabolism , Rats , Uterus/cytology , Uterus/metabolism
6.
Neuroscience ; 153(3): 581-93, 2008 May 15.
Article in English | MEDLINE | ID: mdl-18407423

ABSTRACT

Female rats require a sufficient amount and pattern of vaginal-cervical stimulation to initiate neuroendocrine changes required for the successful implantation of a fertilized ovum in the uterus. These changes are characterized by twice daily prolactin surges that last 10-12 days. Following a sterile mating, the endocrine changes are still observed, and are termed pseudopregnancy (PSP). The mating stimulation required to initiate these changes prior to pregnancy or PSP has a neural representation, which we have termed the intromission mnemonic. We sought to examine if the formation of the intromission mnemonic is accompanied by alterations in the number or density of synapses in limbic areas by immuno-labeling a pre-synaptic protein, synapsin. Groups of cycling female rats on proestrus day received either 15 or 5 intromissions or mounts-without intromissions from a vasectomized male; an additional time-matched control group was left in the home cage. All females were perfused after 90 min or 8 h. The brains were removed and sliced, and the amygdala and hippocampus immunostained for synapsin, then imaged by confocal microscopy. We found that 90 min after mating sufficient for PSP, the number of synapsin puncta (points of immunoreactivity equivalent to a synapse) was decreased and the intensity of the synapsin staining was increased in the posterodorsal medial amygdala (MePD). A similar reduction of puncta was observed in the CA1 region of the hippocampus, and an increase of intensity occurred in the basolateral amygdala. Spaced intromissions had no effect on synapsin expression anywhere examined. Intensity reductions unrelated to receipt of vaginal-cervical stimulation were observed in the hippocampus. None of these effects were observed after 8 h. Together, these results raise the possibility that synapses in the MePD may be pruned after mating stimulation, resulting in pathway-specific stabilization that contributes to the intromission mnemonic associated with the establishment of PSP.


Subject(s)
Amygdala/metabolism , Pseudopregnancy/metabolism , Sexual Behavior, Animal/physiology , Synapsins/metabolism , Animals , Cervix Uteri , Female , Male , Microscopy, Confocal , Rats , Rats, Long-Evans , Vagina
7.
J Neuroendocrinol ; 18(8): 577-83, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16867178

ABSTRACT

The ventromedial hypothalamus (VMH) is an oestrogen-responsive area known to facilitate female sexual behaviour in the rat. The VMH is innervated by noradrenergic neurones projecting from the brain stem, and it has been demonstrated that noradrenaline receptor activation in the VMH plays a role in the expression of the lordosis reflex. Noradrenaline has been shown to be released within the VMH after a female receives vaginocervical stimulation (VCS) from the male during mating. VCS also is required to induce twice-daily surges of prolactin (PRL) characteristic of early pregnancy or pseudopregnancy (PSP). To determine whether noradrenaline within the ventrolateral ventromedial hypothalamus (VMHvl) plays a facilitatory role in initiation of PSP, we administered the alpha(1)-noradrenergic receptor agonist, phenylephrine, and the alpha(2)-autoreceptor antagonist, yohimbine, unilaterally into the VMHvl. Phenylephrine stimulated PSP in 85.7% of females given an amount of VCS known to be subthreshold for the induction of PSP, whereas saline infusion (0%) or cannula misplacement (7.7%) were ineffective. Yohimbine had a similar effect, inducing PSP in 85.7% of females, whereas 7.6% of both control groups together showed PSP. Finally, bilateral blockade of alpha(1)-receptors using prazosin blocked PSP in 100% of females given sufficient VCS to induce PSP, whereas saline infusion or misplaced intracerebral cannulae failed to prevent PSP in any animal. In all experiments, vaginal dioestrous was indicative of PSP, in that animals showed a mean number of days between oestrus of 12.8 +/- 0.9. The results of the study demonstrate an important role for the VMHvl in initiation of PSP and suggest that the release of noradrenaline in the VMHvl at the time of mating contributes to neuroendocrine mechanisms responsible for establishing PSP in the female rat.


Subject(s)
Copulation/physiology , Neural Pathways/metabolism , Norepinephrine/metabolism , Pseudopregnancy/metabolism , Ventromedial Hypothalamic Nucleus/metabolism , Adrenergic Agents/administration & dosage , Animals , Female , Microinjections , Nerve Fibers/drug effects , Nerve Fibers/metabolism , Neural Pathways/cytology , Neural Pathways/drug effects , Rats , Receptors, Adrenergic, alpha/drug effects , Receptors, Adrenergic, alpha/metabolism , Ventromedial Hypothalamic Nucleus/cytology , Ventromedial Hypothalamic Nucleus/drug effects
8.
Rev. chil. ortop. traumatol ; 47(1): 8-14, 2006. ilus, tab, graf
Article in Spanish | LILACS | ID: lil-459240

ABSTRACT

Se estudiaron retrospectivamente 11 pacientes de sexo femenino con hallux valgus moderado a severo, 7 bilaterales (18 pies en total), con un promedio de edad de 46,5 años. En todos los casos se realizó el mismo procedimiento quirúrgico, que consistió en liberación de partes blandas y resección de exostosis medial por abordaje amplio intermetatarsiano, agregando luego osteotomía proximal transversa del primer metatarsiano abierta medial, con adicción de injerto de la exostosis resecada. No se requirió método de fijación para la osteotomía. Durante el postoperatorio la deambulación fue inmediata y se mantuvo el vendaje por 21 días. El seguimiento promedio fue de 16,3 meses. Según la escala de la OAFAS de obtuvo una score promedio de 89,1 puntos. No se observaron complicaciones al mediano plazo como metatarsalgia por transferencia o hallux varus y sólo 2 pies presentaron infección precoz de herida operatoria que fue tratada con antibióticos. Todos los casos consolidaron entre la 6ª y 8ª semana postoperatoria. La técnica quirúrgica utilizada mostró ser sencilla, reproducible y con buenos resultados al corto y mediano plazo.


Subject(s)
Female , Adult , Humans , Hallux Valgus/surgery , Metatarsus , Osteotomy/methods , Follow-Up Studies , Retrospective Studies
9.
Neuroscience ; 136(1): 55-64, 2005.
Article in English | MEDLINE | ID: mdl-16183203

ABSTRACT

Neurons within the posterodorsal medial amygdala of female rats are known to process vaginocervical stimulation received during mating through N-methyl-D-aspartate channel activation, conveying information to downstream hypothalamic cell groups that modulate neuroendocrine function. Stimulation of these neurons with an excitatory amino acid cocktail of glutamate, aspartate and glycine initiates 10-12 days of prolactin surge secretion that normally are observed only after the receipt of vaginocervical stimulation. Posterodorsal medial amygdala neurons responsive to vaginocervical stimulation also contain estrogen and progesterone receptors. The present experiment examined which downstream sites involved in prolactin secretion show c-fos expression following glutamate receptor activation within the posterodorsal medial amygdala and whether ovarian steroids influence cellular activation in these areas. Ovariectomized female rats implanted with unilateral cannulas directed at the posterodorsal medial amygdala received injections of estradiol benzoate and progesterone or oil before infusion treatment with either excitatory amino acid or control PBS. An additional group of estradiol benzoate+progesterone-treated females was infused with 1.0 microM glycine alone in PBS. Infusions were administered three times at 30 min intervals. FOS induction 90 min after infusion was determined immunohistochemically on the sides ipsilateral and contralateral to the infusion. Of the examined regions, excitatory amino acid treatment and hormone treatment induced three patterns of c-fos expression: 1) responses to both excitatory amino acid and hormone treatment [posterodorsal medial amygdala, medial preoptic area, ventrolateral ventromedial hypothalamic nucleus, bed nucleus of the stria terminalis]; 2) responses to estradiol benzoate+progesterone treatment only [anteroventral periventricular nucleus and dorsomedial nucleus]; and 3) responses to excitatory amino acid only [arcuate nucleus, suprachiasmatic nucleus, and paraventricular nucleus]. These data identify possible circuits by which vaginocervical stimulation, via activation of posterodorsal medial amygdala glutamate-type receptors, initiates and coordinates a series of events within a larger neuroendocrine circuit important for pregnancy.


Subject(s)
Amygdala/drug effects , Copulation/physiology , Excitatory Amino Acids/pharmacology , Prosencephalon/physiology , Proto-Oncogene Proteins c-fos/metabolism , Steroids/pharmacology , Animals , Aspartic Acid/pharmacology , Drug Combinations , Estradiol/pharmacology , Female , Glutamic Acid/pharmacology , Glycine/pharmacology , Immunohistochemistry , Ovariectomy , Progesterone/pharmacology , Prosencephalon/metabolism , Rats , Rats, Long-Evans , Receptors, Glutamate/metabolism
10.
Can J Neurol Sci ; 32(2): 205-12, 2005 May.
Article in English | MEDLINE | ID: mdl-16018156

ABSTRACT

BACKGROUND: Changes in brain lesion loads assessed with magnetic resonance imaging obtained at 1.5 Telsa (T) are used as a measure of disease evolution in natural history studies and treatment trials of multiple sclerosis. METHODS: A comparison was made between the total lesion volume and individual lesions observed on 1.5 T images and on high-resolution 4 T images. Lesions were quantified using a computer-assisted segmentation tool. RESULTS: There was a 46% increase in the total number of lesions detected with 4 T versus 1.5 T imaging (p < 0.005). The 4 T also showed a 60% increase in total lesion volume when compared with the 1.5 T (p < 0.005). In several instances, the 1.5 T scans showed individual lesions that coalesced into larger areas of abnormality in the 4 T scans. The relationship between individual lesion volumes was linear (slope 1.231) showing that the lesion volume observed at 4 T increased with the size of the lesion detected at 1.5 T. The 4 T voxels were less than one quarter the size of those used at 1.5 T and there were no consistent differences between their signal-to-noise ratios. CONCLUSIONS: The increase in signal strength that accompanied the increase in field strength compensated for the loss in signal amplitude produced by the use of smaller voxels. This enabled the acquisition of images with improved resolution, resulting in increased lesion detection at 4 T and larger lesion volumes.


Subject(s)
Brain/pathology , Image Processing, Computer-Assisted/methods , Image Processing, Computer-Assisted/standards , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/standards , Multiple Sclerosis/diagnosis , Adult , Brain/physiopathology , Disease Progression , Humans , Multiple Sclerosis/physiopathology , Nerve Fibers, Myelinated/pathology , Predictive Value of Tests , Reproducibility of Results
11.
Vet Microbiol ; 108(1-2): 101-12, 2005 Jun 15.
Article in English | MEDLINE | ID: mdl-15917138

ABSTRACT

Mycobacteria other than the Mycobacterium tuberculosis complex (MOTT), isolated from Northern Ireland cattle, were identified by PCR amplification of the 16S rRNA gene, and subsequent reverse cross blot hybridisation and sequence analyses. Elucidation of the MOTT species was to facilitate specificity testing of new and existing diagnostic test reagents for bovine tuberculosis. The presence of the genes for potential diagnostic antigens: MPB70, MPB64, ESAT-6 and CFP-10 in the isolated MOTT species was investigated. Molecular analyses of cultured isolates from bovine lymph node specimens of 48 cattle identified a wide variety of mycobacterial species including Mycobacterium nonchromogenicum, Mycobacterium malmoense, Mycobacterium bohemicum, Mycobacterium paratuberculosis, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium holsaticum, Mycobacterium palustre, Mycobacterium sp. IWGMT 90210, Mycobacterium sp. LIV-2129, a potentially novel mycobacterial species (EMBL/GenBank/DDBJ Accession Number AJ617495) and Rhodococcus equi. Apart from M. kansasii, the results of traditional (standard phenotypic and biochemical) and molecular identification methods did not correlate well, with traditional methods identifying fewer species. Most of the species identified were either recognised pathogenic or potential pathogenic species. The genes for ESAT-6, CFP-10 and, unusually, MPB64 were detected in M. kansasii only. The MPB70 gene was not detected in any of the species. This study supported restricted species distribution of these genes as well as identifying a different range of MOTT species that could be included in specificity testing of new diagnostic reagents for bovine tuberculosis.


Subject(s)
Cattle Diseases/microbiology , Mycobacterium Infections/veterinary , Mycobacterium/isolation & purification , Animals , Base Sequence , Cattle , Cattle Diseases/epidemiology , Genes, Bacterial , Molecular Sequence Data , Mycobacterium/classification , Mycobacterium Infections/microbiology , Northern Ireland/epidemiology
12.
J Neuroendocrinol ; 16(9): 750-7, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15344913

ABSTRACT

In the female rat, the integrity of the ventral noradrenergic bundle (VNAB) is necessary to carry stimuli from the uterine cervix and vagina to brain areas involved in mating-induced pseudopregnancy. Because adrenal hormones are known to alter noradrenergic function, we examined whether adrenalectomy altered mating-induced Fos expression in the A1 and A2 noradrenergic cell groups that project through the VNAB. Ovariectomized females were adrenalectomized (ADX) or sham-operated (Sham) and, 2 weeks after surgery, were given oestrogen and progesterone and mated. They received 15 intromissions, five intromissions or 15 mounts-without-intromission (mounts-only) from a male. Two hours after mating, rats were perfused and brains were collected; controls were perfused after being taken directly from their home cage. After immunocytochemical staining, Fos-immunoreactive (Fos-IR) and dopamine-beta-hydroxylase-immunoreactive (DBH-IR) cells and the percentage of DBH cells that were labelled with Fos (% DBH/Fos) were counted. In the A1 area, Fos-IR and percentage DBH/Fos were not affected by adrenalectomy. Although an overall effect of mating treatment was found for both measures, no specific mating treatment increased labelled cells above home cage levels. In the caudal, middle and rostral A2, 15 intromissions induced a significant increase in Fos-IR in Sham females above all other groups and a higher percentage of DBH/Fos in the middle and rostral A2 areas. ADX females showed no rise in either Fos-IR or percentage DBH/Fos after 15 intromissions. However, in the middle and rostral A2, ADX females showed significantly increased Fos-IR and percentage DBH/Fos after mounts-only treatment above Sham mounts-only females and all other ADX groups. These results demonstrate that adrenal hormones suppress activation of A2 cells to mounts-only stimuli but contribute to A2 activation in response to intromissions from males. The latter effect may result from stress associated with receipt of vaginocervical stimulation during mating.


Subject(s)
Adrenal Glands/physiology , Copulation/physiology , Medulla Oblongata/metabolism , Norepinephrine/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Animals , Corticosterone/blood , Dopamine beta-Hydroxylase/metabolism , Estradiol/physiology , Female , Immunohistochemistry , Medulla Oblongata/cytology , Neurons/cytology , Neurons/metabolism , Ovariectomy , Progesterone/physiology , Pseudopregnancy/metabolism , Rats , Rats, Long-Evans , Tissue Distribution
14.
J Neurosci ; 21(11): 4104-10, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11356898

ABSTRACT

In female rats, genitosensory stimulation received during mating initiates twice-daily prolactin (PRL) surges, a neuroendocrine response that is the hallmark of early pregnancy or pseudopregnancy (P/PSP). Nocturnal and diurnal PRL surges are expressed repeatedly for up to 2 weeks after copulation, suggesting that a neuroendocrine memory for vaginocervical stimulation (VCS) is established at the time of mating. These studies investigated whether the processing and retention of VCS involves acute glutamatergic activation or de novo protein synthesis within the medial nucleus of the amygdala (MEA), a VCS-responsive brain site that is implicated in P/PSP initiation. Pharmacological activation of the MEA with the glutamate agonist, NMDA, initiated nocturnal PRL surges, causing a PSP state in females that had not received VCS. P/PSP initiation by mating was prevented by intra-amygdalar infusion of the NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP-5), provided that it was administered before mating. AP-5 treatment also disrupted mating-induced c-fos expression in the principle bed nucleus of the stria terminalis and the ventrolateral division of the ventromedial hypothalamic nucleus, but not in the medial or anteroventral periventricular preoptic nuclei. Neither P/PSP nor downstream cellular activation was prevented when a protein synthesis inhibitor, anisomycin, was administered to the MEA. The results indicate that MEA cells are critical to the early processing of VCS through NMDA channel activation, rapidly conveying information to downstream hypothalamic cell groups that modulate neuroendocrine function.


Subject(s)
Amygdala/metabolism , Memory/physiology , N-Methylaspartate/metabolism , Neurosecretory Systems/metabolism , Pseudopregnancy/metabolism , Amygdala/drug effects , Animals , Cervix Uteri/innervation , Cervix Uteri/physiology , Drug Implants , Excitatory Amino Acid Agonists/administration & dosage , Excitatory Amino Acid Antagonists/administration & dosage , Female , Memory/drug effects , Microinjections , N-Methylaspartate/administration & dosage , Neurosecretory Systems/drug effects , Preoptic Area/drug effects , Preoptic Area/metabolism , Prolactin/blood , Protein Synthesis Inhibitors/administration & dosage , Proto-Oncogene Proteins c-fos/biosynthesis , Pseudopregnancy/chemically induced , Rats , Rats, Long-Evans , Receptors, Glutamate/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Septal Nuclei/drug effects , Septal Nuclei/metabolism , Vagina/innervation , Vagina/physiology , Ventromedial Hypothalamic Nucleus/drug effects , Ventromedial Hypothalamic Nucleus/metabolism
15.
J Neuroendocrinol ; 13(1): 13-21, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11123511

ABSTRACT

This study examined the role of the posterodorsal medial amygdala (MePD) in the control of prolactin secretion in gonadally intact female rats 20 min after mating, during the oestrous cycle, and during early pregnancy/pseudopregnancy (P/PSP). Cycling females received bilateral infusions of an excitotoxic dose of N-methyl-D-aspartate (NMDA) or vehicle into the MePD. Two to 4 weeks later, they were surgically implanted with intra-atrial catheters for repeated blood sampling and were mated on the evening of proestrus until receiving 5, 10, 15 or 20 intromissions or 15 mounts-without-intromission (MO) from males. The percentages of rats becoming P/PSP increased as a function of numbers of intromissions received. All groups receiving intromissions showed similar approximately four-fold increases in plasma prolactin concentrations 20 min after mating, while MO rats showed no increase at this time. There was no effect of NMDA lesion on this acute secretory response. Among rats that continued cycling, bilateral MePD lesion completely abolished the diurnal preovulatory prolactin surge, while incomplete and sham lesions did not. In rats that subsequently became P/PSP, bilateral lesion of the MePD resulted in dampening of prolactin concentrations at all sampling times 6-7 days after mating, while incomplete or sham lesions did not alter prolactin secretion at these times. These results demonstrate that the MePD is selectively important for the secretion of prolactin on the afternoon of proestrus and that this structure may also modulate prolactin release in P/PSP rats. Activity within MePD neurones does not appear to be required for the acute prolactin response to vaginocervical stimulation which occurs within minutes after mating.


Subject(s)
Amygdala/metabolism , Amygdala/pathology , Copulation/physiology , Estrus/metabolism , Prolactin/metabolism , Animals , Excitatory Amino Acid Agonists/toxicity , Female , Follicular Phase/metabolism , N-Methylaspartate/toxicity , Nerve Degeneration/chemically induced , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Neurotoxins , Posture/physiology , Progesterone/blood , Prolactin/blood , Radioimmunoassay , Rats , Rats, Long-Evans
16.
Brain Res ; 861(1): 26-36, 2000 Apr 07.
Article in English | MEDLINE | ID: mdl-10751562

ABSTRACT

Vaginocervical stimulation (VCS) received during mating is known to induce analgesia and to suppress FOS-immunoreactivity (FOS-IR) in lumbar spinal cord. However, it is not known whether this suppression of FOS-IR reflects inhibition of afferent nociceptive input. The present studies examined whether two immediate-early gene (IEG) products, FOS and Egr-1, covary with nociception by comparing both responses in estrous females that received mating stimulation known to induce varying amounts of FOS-IR in brain. Ovariectomized steroid-treated rats were mated under conditions in which they paced or did not pace sexual contacts with males until receiving 5 or 15 intromissions. Control groups received mounts-without-intromission only from males or remained in their homecages. In experiment I, paced mating resulted in a significant overall suppression of FOS-IR in the lumbar 6 (L6) spinal segment compared to nonpaced and mounts only stimulation. This reduction occurred specifically among paced females receiving five intromissions. In contrast, significant elevations above homecage levels were seen in paced females given 15 intromissions, all nonpaced females, and mounts only animals. The numbers of Egr-1-immunoreactive (Egr-1-IR) cells increased equally above homecage levels in all male-exposed females. In experiment II, females that received five intromissions (paced or nonpaced) showed significant increases in tail-flick latency (TFL) within 5 s (time 0) after mating, while females receiving 15 intromissions showed hyperalgesia (15 nonpaced) or no change (15 paced) in TFL throughout 90 s postmating. Additional females tested immediately after receiving two ejaculations showed analgesia. Paced mating, though more effective than nonpaced mating in suppressing FOS-IR, did not influence the appearance of VCS-induced analgesia. We conclude that the suppression of FOS-IR by paced mating is not related to mating-induced analgesia.


Subject(s)
DNA-Binding Proteins/metabolism , Genes, fos/physiology , Immediate-Early Proteins , Pain Threshold/physiology , Posterior Horn Cells/metabolism , Sexual Behavior, Animal/physiology , Transcription Factors/metabolism , Animals , Early Growth Response Protein 1 , Female , Genes, Immediate-Early/physiology , Lumbosacral Region , Male , Rats , Rats, Long-Evans , Spinal Cord/metabolism
17.
J Comp Neurol ; 418(4): 484-503, 2000 Mar 20.
Article in English | MEDLINE | ID: mdl-10713575

ABSTRACT

The transneuronal tracer, pseudorabies virus (PRV), was used to identify pathways from the uterine cervix which may be involved in induction of analgesia and abbreviation of estrus by vaginocervical stimulation. In Experiment I, PRV immunoreactivity (PRV-IR) in brain and spinal cord was examined 3-5 days after injection into the cervix of ovariectomized (OVX) female rats given estrogen (E) or control treatments. No differences in viral labeling were observed between OVX and OVX+E females at any time. PRV-infected cells were observed to increase as a function of time and at progressively higher CNS levels. PRV-IR neurons were first observed on day 3 post-infection at L6 in the SPN. Increased labeling was observed at day 4 in the SPN and the DGC at L6 and S1 spinal segments. Dorsal horn neurons showed PRV-IR by 4.5 days. Five days post-infection, labeling was seen in the IML and lamina X in T12-L1 segments, and in medullary raphe, A5, nPGi, nGi, DMV, lateral reticular, Barrington's nuclei, and in the midbrain PAG. In Experiment II, the effects of bilateral L6 dorsal root rhizotomy (RH) combined with unilateral (UPx) or bilateral (BPx) pelvic nerve transection on PRV infectivity were examined 5 days after infection. Despite reductions in substance P labeling in the dorsal horn following RH, PRV-IR neurons persisted in this area. In RH+UPx females, labeling persisted bilaterally in the SPN and DGC at L6. RH+BPx almost completely eliminated the PRV labeling in L6 and S1. Horizontal sections showed distinct patterns of infectivity within the IML of thoracolumbar and SPN of lumbosacral segments consistent with infection in the hypogastric and pelvic nerves, respectively. Our data indicate that retrograde transport of PRV occurs via the hypogastric and pelvic nerves after injection of the virus into the uterine cervix. Furthermore, significant intraspinal processing is likely to occur between thoracolumbar and lumbosacral levels in the modulation of reproductive tract function.


Subject(s)
Central Nervous System/cytology , Cervix Uteri/innervation , Estrogens/pharmacology , Herpesvirus 1, Suid/metabolism , Hypogastric Plexus/surgery , Neural Pathways/cytology , Animals , Brain/cytology , Brain/physiology , Brain/virology , Central Nervous System/physiology , Central Nervous System/virology , Cervix Uteri/physiology , Cervix Uteri/virology , Female , Hypogastric Plexus/cytology , Hypogastric Plexus/physiology , Immunohistochemistry , Lumbar Vertebrae/surgery , Neural Pathways/physiology , Neural Pathways/virology , Neurons, Afferent/cytology , Neurons, Afferent/physiology , Neurons, Afferent/virology , Rats , Rats, Long-Evans , Spinal Cord/cytology , Spinal Cord/physiology , Spinal Cord/virology , Spinal Nerve Roots/cytology , Spinal Nerve Roots/physiology , Spinal Nerve Roots/surgery , Time Factors
18.
J Obstet Gynaecol ; 20(2): 180-2, 2000 Mar.
Article in English | MEDLINE | ID: mdl-15512513

ABSTRACT

We carried out a retrospective analysis of the continuation rates of 142 Norplant acceptors. Follow-up data was available on 110. We assessed the relative impact of side effects on discontinuation. No serious complications (immediate or late) were observed during the 3-year study period and no pregnancies occurred. The 3-year continuation rate was 88%. The commonest reported side effect was cycle disruption (64% of users). However this only accounted for 31% of discontinuations. This we attribute to thorough counselling about menstrual disruption. On the other hand androgenic side effects accounted for 12% of discontinuations but were experienced by 10% of users-perhaps because some users did not expect them. We conclude that Norplant is highly acceptable when offered with specialist counselling and support. Non-bleeding side effects accounted for relatively higher discontinuations and may need to be emphasised in counselling. A dedicated service enhanced acceptability.

19.
Rev. Hosp. Clin. Univ. Chile ; 11(2): 137-42, 2000. ilus, tab
Article in Spanish | LILACS | ID: lil-286893

ABSTRACT

La cirugía astroscópica ha despertado gran interés desde la década de los 60. Es una técnica útil en el diagnóstico y tratamiento de la patología articular, en especial en la rodilla. Con el objetivo de evaluar la experiencia existente en este tipo de cirugía, fueron revisados en forma retrospectiva 350 pacientes consecutivos, sometidos a artroscopía de rodilla, entre los años 1995 y 1998, en el Hospital Clínico de la Universidad de Chile. La mayoría de los pacientes de la serie eran hombres (67, 2 por ciento) y el rango de edad fluctuaba entre los 7 y los 77 años, con un promedio de 37 años. La manifestación clínica preoperatoria más frecuente fue el dolor (96 por ciento), seguido por la disminución de rangos articulares (68 por ciento). El estudio imagenológico más utilizado, sin considerar la radiografía simple, fue la neumoartrografía. La mayoría de los pacientes (46,5 por ciento), presentaban lesión meniscal aislada como diagnóstico postoperatorio principal. No se consignaban complicaciones intraoperatorias. El tiempo promedio de estadía hospitalaria fue de 1,7 días. Hubo 3 casos de complicaciones mayores, un paciente desarrolló una artritis séptica y los otros 2 presentaron una trombosis venosa profunda, todos con buena respuesta al manejo habitual. La cirugía artroscópica de rodilla es una técnica poco invasiva, con buen rendimiento en el diagnóstico y tratamiento de la patología articular, requiriendo una estadía hospitalaria mínima, con escasa morbilidad y con buenos resultados funcionales


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Arthroscopy , Knee Injuries/surgery , Arthroscopes/statistics & numerical data , Arthroscopy/adverse effects , Length of Stay , Menisci, Tibial/surgery , Postoperative Complications , Retrospective Studies , Signs and Symptoms
20.
Rev. Hosp. Clin. Univ. Chile ; 10(1): 5-10, 1999. tab, graf
Article in Spanish | LILACS | ID: lil-274700

ABSTRACT

El manejo terapéutico de la artritis séptica se basa en la identificación del germen, la administración de antibióticos adecuados y el drenaje articular, la mayoría de las veces. En relación a este último, en la actualidad se han planteado las ventajas del uso de la artroscopía. Con el objeto principal de evaluar la experiencia existente en el Hospital Clínico de la Universidad de Chile en el tratamiento artroscópico de la artritis séptica, y comparar los resultados de éste, con los obtenidos con artromía, se revisaron retrospectivamente los casos de 21 pacientes tratados en forma consecutiva en los últimos 5 años en el Servicio de Traumatología. La mayoría de los pacientes de la serie eran hombres (71 por ciento) y el promedio de edad fue de 48 años. La articulación afectada con mayor frecuencia fue la rodilla (71 por ciento) y en un 33 por ciento de los casos se pudo identificar una vía de infección. Los cultivos fueron positivos en un 43 por ciento, siendo el germen más frecuente el estafílococo coagulasa positivo (56 por ciento). En 12 pacientes se realizó artrotomía, en 6 artroscopía y en el resto no fue realizado drenaje articular. Al comparar la evolución entre ambas técnicas de aseo articular, en grupos homogéneos (misma articulación y edad), se encontró un promedio de estadía hospitalaría menor (7 días), asociadas a mejores resultados funcionales en aquellos pacientes tratados con artroscopía. Los resultados obtenidos coinciden con lo publicado en la literatura con respecto a las ventajas del drenaje articular artroscópico en el manejo de la artritis séptica, tanto en la evolución clínica del paciente, como en la eficacia del método, basado en la visión directa que se obtiene de la articulación


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Arthritis, Infectious/surgery , Arthroscopy , Knee Joint/microbiology , Arthritis, Infectious/etiology , Knee Joint/surgery , Clinical Evolution , Drainage , Staphylococcal Infections/therapy , Length of Stay , Retrospective Studies
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