Biomedical subjects

S E Brien

Publications and source records attributed to S E Brien.

6 recordsLinked to original sources

PubMed2002

Development of a rat model of sexual performance anxiety: effect of behavioural and pharmacological hyperadrenergic stimulation on APO-induced erections.

As part of the multifactorial nature of erectile dysfunction, anxiety associated with sexual performance (SPA) remains a major contributing factor to its progression. In fact, the heightened sympathetic activity associated with sexual performance anxiety may be a key early component of this disruption of normal erectile responses. We are not aware that any animal models have been developed to assess this phenomenon. Using apomorphine (APO, 80 microg/kg s.c.)-induced erections in rats we characterised the effects of behavioural or pharmacological hyperadrenergic stimulation (that is, anxiety) on erections and hemodynamics. We developed an experimental SPA paradigm by exposing male rats to the stress of being observed by a larger, older male rat placed in close proximity to test rats during APO testing. In a separate group, adrenergic stress was simulated using a sympathomimetic, methoxamine (MXA) given prior to APO testing. In a third group, the changes in circulatory parameters (mean arterial pressure, heart rate) were determined following instrumentation with radiotelemetric transducers for each scenario. APO-induced erections were significantly lower in both the behavioural (1.25+/-0.8) and pharmacological (0.33+/-0.5) stressor paradigms compared to controls (2.81+/-0.9). Further, erections in MXA-treated rats were significantly lower than in the observed scenario. Despite the differences in erections hemodynamic assessments showed no differences in MAP or HR changes between the different experimental conditions. Thus, both the behavioural and pharmacological paradigms of SPA decreased erections, but did not affect the circulation. This suggests that the level of hyperadrenergic input required to induce erectile dysfunction can be subtle, and target only erectogenic pathways.

Animals↗

PubMed2000

The conditioned response erection (CRE)--a new approach to modelling erectile responses in the rat.

Several animal models are currently used in erectile (dys)function research; these models fail to account for the conditions involving the more spontaneous erections in humans. Recently, we observed an increase in the number of 'spontaneously' occurring erections in rats with previous exposure to apomorphine (APO), a centrally acting drug that initiates penile erections and yawns. Based on this observation, we designed a series of experiments to characterize the development of enhanced, non-apomorphine-induced erections or 'spontaneous' erectile responses to vehicle administration in rats with previous exposure to APO. We further examined the effects of castration on these conditioned erections. Naive (ie never received APO) rats were administered vehicle (1 ml/kg saline) to determine the frequency of baseline erections and yawns. An alternating series of APO (80 microg/kg s.c.) and vehicle administrations were performed over several days and subsequent erectile and yawning responses were recorded. Following 3 sets of 3 APO administrations (with vehicle administered between sets), and the 3rd vehicle administration, these rats were then surgically castrated and allowed 30 days to recover. Following this, APO was administered 3 times to determine erectile and yawning responses post-castration, followed by vehicle administration to determine the effects of castration on conditioned APO responses. The major findings were: (1) that although naive rats had a basal spontaneous erectile response (0.75 +/- 0.88; 4 of 8 rats with at least one erection), repetitive administration (up to 22 treatments) of the central initiator apomorphine significantly increased the number of erections (1.8 +/- 0.7; 7 of 8 rats with at least one erection) and yawning (2.5 +/- 2.47) responses to vehicle administration; and (2) both spontaneous yawning and erectile responses were found to be androgen dependent since castration dramatically lowered the number of erections (0.13 +/- 0.35; 1 of 8 rats with at least one erection) and yawns (0). Therefore, this method of producing erections without a pharmacological manipulation provides an additional animal model which can be used in conjunction with the APO-induced erections in characterizing the physiology and pathophysiology of erectile function in conscious rats.

Androgens↗

PubMed2000

Effects of an environmental anti-androgen on erectile function in an animal penile erection model.

PURPOSE: Erectile function is testosterone dependent. For example, interference with either the levels or receptor binding of this steroid hormone may induce erectile dysfunction. Several environmental contaminants can interfere with the actions of endogenous hormones and have been termed 'endocrine disrupters.' p,p-DDE, a prominent and persistent metabolite of the insecticide DDT, has been shown to be an androgen receptor antagonist. The objective was to determine whether endocrine disrupters, as exemplified by p,p-DDE, are factors in the etiology of erectile dysfunction. MATERIALS AND METHODS: Using the established rat model of apomorphine-induced (80 microg./kg, s.c.) erections we assessed the dose-response effects of p,p-DDE in comparison to the known androgen receptor antagonist flutamide in acute (0.5 to 12 hours) and short-term (up to 8 weeks) experiments in both intact (Study 1) and castrated (Study 2) rats. As a follow up (Study 3), castrated rats treated with p,p-DDE were given increasing doses of testosterone (0.48 to 2.4 mg./kg., i.p.), eight weeks after p,p-DDE administration, to assess reversibility of p,p-DDE effect. RESULTS: A single dose of flutamide (50 mg./kg., i.p.) was found to significantly decrease apomorphine-induced erections to less than 50% over 12 hours following flutamide administration with recovery of erectile response within 48 hours. In comparison, a single dose of p,p-DDE (500 mg./kg., i.p.) decreased apomorphine-induced erections for at least two weeks (1.15+/-0.3 versus 2.5+/-1.1). Castration significantly decreased apomorphine-induced erections to approximately 0.5 erections/30 minutes. Flutamide (50 mg./kg.; i.p.) or p,p-DDE (50 mg./kg.; i.p.) did not further suppress the apomorphine erections in castrated rats. Testosterone supplementation (480 microg./kg; s.c.) in vehicle treated castrated rats recovered erectile response to pre-castrated levels, whereas p,p-DDE treated castrated rats required 4 times the dose of testosterone (2 mg./kg.; s.c.) given to vehicle treated rats to recover erections. CONCLUSIONS: The endocrine disrupter p,p-DDE can markedly interfere with erectile function and demonstrates persistence after a single dose. This supports our novel concept that environmental hormones may cause erectile dysfunction.

Androgen Antagonists↗

PubMed1990

Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor.

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain.

Animals↗

PubMed1989

Rapid in situ cellular kinetics of intracerebral tumor angiogenesis using a monoclonal antibody to bromodeoxyuridine.

The application of a monoclonal antibody to bromodeoxyuridine (BUdR) provides a rapid, reproducible, nontoxic, immunohistochemical method to measure cellular kinetics of intracerebral tumor angiogenesis. The rabbit brain tumor model of angiogenesis consists of tumor and endothelial cell populations with high proliferative rates that demonstrate the close interdependence between microvascular and neoplastic growths as well as topographic gradients, heterogeneity, and regional microdomains of cell proliferation. The labeling index (LI) of endothelial cells was 25.8% at the tumor periphery, compared to 1.7% in the tumor center (P less than 0.001). Concomitant with an increased turnover of neoplastic cells at the tumor periphery. LI was 26.6% with a LI of 7.7% in the center (P less than 0.01). Furthermore, labeled tumor cells tended to be organized around proliferating capillaries, with less DNA synthesis farther from the nearest blood vessel. The established normal microvessels of the brain, e.g., in the opposite tumor-free hemisphere, were mitotically inactive with a LI of less than 0.001%. Quantitation of vascular cytokinetics should be useful in further studies of the pathophysiology of brain tumor angiogenesis and the development of pharmacological approaches directed toward the microvasculature.

Animals↗

PubMed1984

Musicogenic epilepsy.

A case of musicogenic epilepsy is reported in which the seizures were precipitated by singing voices. It was found that some singers' voices were particularly epileptogenic and that some of their songs, but not others, would precipitate a seizure. A study of the "offending" songs and singers did not reveal a common key, chord, harmonic interval, pitch or rhythm, and the emotional feeling or intensity of the music did not seem to be relevant. However, the voices that caused the seizures had a throaty, "metallic" quality. Such a singing voice results from incorrect positioning of the larynx such that it is not allowed to descend fully during singing; consequently, the vowel sounds produced must be manipulated by the lips or jaw to be distinguished. This trait is most common in singers with a low voice range who sing softly and use a microphone. It is not seen in trained operatic or musical theatre singers. The results of repeated testing showed that the seizures in this patient were caused by listening to singers who positioned the larynx incorrectly.

Electroencephalography↗