The oral education clinic: A pharmacist- and nurse-led clinic to support patients starting oral systemic anti-cancer treatments.

With the increased number of oral systemic anti-cancer treatments available, patients need to be managed safely and effectively in line with national guidance. In response to guidance in 2011, Oxford University Hospitals NHS Foundation Trust implemented an 'Oral Education Clinic'. This nurse- and pharmacist-led clinic facilitates the delivery of patient education, highlighting key safety aspects of drug administration and management, and ensures follow-up is arranged as per protocol. Patients have found this service to be effective and it has had a positive impact on the running of outpatient units, the volume of triage calls, emergency admissions and workload associated with consenting patients to an oral systemic anti-cancer treatments.

Endocrinology of sex steroid hormones and cell dynamics in the periodontium.

Numerous scientific studies assert the existence of hormone-sensitive periodontal tissues. Tissue specificity of hormone localization, identification of hormone receptors and the metabolism of hormones are evidence that periodontal tissues are targets for sex steroid hormones. Although the etiologies of periodontal endocrinopathies are diverse, periodontal pathologies are primarily the consequence of the actions and interactions of sex steroid hormones on specific cells found in the periodontium. This review provides a broad overview of steroid hormone physiology, evidence for the periodontium being a target tissue for sex steroid hormones and theories regarding the roles of sex steroid hormones in periodontal pathogenesis. Using this information, a teleological argument for the actions of steroid hormones in the periodontium is assessed.

Physiology, pathology and pharmacology of the male reproductive system.

The male reproductive system consists of the testes, a ductal system and sex accessory organs. Production of sperm by the testes combined with fluids formed by the sex accessory organs (e.g. seminal vesicles, prostate and bulbourethral glands) produce a secretion that supports the survival of spermatozoa and provides a medium through which they can move through the reproductive ducts (e.g. epididymis, vas deferens, ejaculatory duct and urethra) for ejaculation of viable sperm into the female reproductive tract. Summarized herein are the essentials of normal male reproductive physiology, disorders of male sexual differentiation, pharmacological therapy of common diseases of the male genitourinary tract and the impact of drugs of abuse on the male reproductive system.

Down-regulation of neutral sphingomyelinase in androgen-dependent smooth muscle.

BACKGROUND: During puberty, proliferation of guinea pig seminal vesicle smooth muscle (SVM) is mediated by androgen-induced basal release of norepinephrine (NE), signaling through the post-junctional alpha1-adrenoceptor. In the adult, the SVM is terminally differentiated, such that cell number is androgen resistant. Sphingomyelinase activation generates second messenger ceramides, which in vascular smooth muscle have been reported to counter the alpha1-adrenoceptor-mediated contractile response and activate apoptosis. Accordingly, we hypothesized that SVM sphingomyelinase down-regulation by androgen may facilitate NE-induced proliferation and subsequent transition to the terminally differentiated state of the adult. MATERIALS AND METHODS: Pre-pubertal and adult guinea pigs were orchiectomized and treated+/-dihydrotestosterone (DHT). SVM was harvested free of epithelium, frozen, and stored for enzymatic analyses. Using radioactive sphingomyelin substrate, optimized reaction conditions for both neutral and acidic sphingomyelinase were established and used to assay the enzymes. RESULTS: Although acidic sphingomyelinase was stimulated by androgen in both the proliferative and amitotic phases of smooth muscle development, neutral sphingomyelinase was irreversibly reduced 35% at the time of DHT-induced proliferation. CONCLUSIONS: Decreased concentrations of a second messenger ceramide attenuate apoptosis and increase sensitivity to alpha(1)-adrenoceptor-mediated mitogenic signaling. Therefore, DHT-dependent suppression of neutral sphingomyelinase activity may reduce ceramide concentrations and facilitate NE-dependent smooth muscle growth.

Androgen-induced norepinephrine release mediating guinea pig seminal vesicle smooth muscle proliferation: potential role of pre-synaptic alpha2-adrenoceptors.

BACKGROUND: Recent studies from our laboratory have demonstrated that androgen-induced basal norepinephrine (NE) release is responsible for the onset of proliferation in seminal vesicle smooth muscle (SVM) cells during early puberty. With subsequent sexual maturation, SVM was irreversibly differentiated to an androgen-resistant-amitotic state in which basal NE release remained elevated and resistant to androgen withdrawal or repletion. Based on these findings, we hypothesized that this irreversible elevation of basal NE release during pubertal development is caused, at least in part, by the down-regulation of pre-synaptic NE feedback inhibition, secondary to irreversible reduction in the expression of neuronal (pre-synaptic) alpha(2)-adrenoceptors. Functional alpha(2)-adrenoceptors are selectively localized to pre-synaptic sites in SVM. METHODS: To test this hypothesis, we employed ligand binding techniques with [(3)H]RX821002, an antagonist which labeled all alpha(2)-adrenoceptor sub-types. Initial experiments focused on analysis of competitor specificity to identify the predominant alpha(2)-adrenoceptor sub-type in SVM. Subsequently, we quantified the changes in the receptor concentration (B(max)) for [(3)H]RX821002 at the point of maximal dihydrotestosterone (DHT)-induced change in basal NE release. RESULTS: Based on competitor specificity for [(3)H]RX821002, the alpha(2D)-adrenoceptor sub-type predominated in SVM. We treated pre-pubertal castrate animals with DHT for 7 days, which was previously demonstrated to maximally induce basal NE release. This treatment reduced the pre-synaptic alpha(2)-adrenoceptor B(max) 4-fold. In animals which had been castrated as adults, the B(max) for [(3)H]RX821002 remained irreversibly suppressed. CONCLUSIONS: The DHT-dependent reduction in the alpha(2)-adrenoceptor concentration is consistent with the developmental pattern of increased basal NE release. These findings support the hypothesis that the down-regulation of pre-synaptic NE feedback is mechanistically involved in the irreversible elevation of basal NE release. NE mediates proliferation in SVM in early pubertal development. Thus, the androgen-dependent pubertal growth of smooth muscle cells may be indirectly controlled at the level of neurotransmission.

Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues.

Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea-pigs resulted in an average delivery of 1.185 mg selegiline/cm(2) patch/24 h. STS dose-response curves were generated by altering patch size (cm(2)). A transdermal dose range was identified which inhibited guinea-pig brain monoamine oxidase-B (MAO-B) by greater than 95% yet provided for a dose-dependent inhibition of monoamine oxidase-A (MAO-A) activity. The ID50 for inhibition of MAO-A activity in response to a 21-day daily regimen with transdermal selegiline was approximately 7.5-fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO-A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO-A to the same extent, and generated a shallower dose-inhibition curve for brain MAO-A inhibition. In addition, transdermal delivery was approximately 6-8-times more potent than oral selegiline for the inhibition of brain MAO-A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose-dependent inhibition of brain vs peripheral MAO-A activity.

Androgen induced norepinephrine release from postganglionic neurons mediates accessory sex organ smooth muscle proliferation.

PURPOSE: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle. MATERIALS AND METHODS: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium. Norepinephrine release from postganglionic adrenergic nerve terminals in seminal vesicle smooth muscle was measured using several techniques. Prazosin sensitive electrical field stimulation of contractile responses qualitatively assessed norepinephrine release. Norepinephrine release was quantified directly in vitro from incubated seminal vesicle smooth muscle minces and indirectly ex vivo from intact tissue using the endogenous seminal vesicle smooth muscle concentration ratio of 3,4-dihydroxyphenylglycol-to-norepinephrine (Sigma Chemical Co., St. Louis, Missouri). Norepinephrine mediated seminal vesicle smooth muscle proliferation was assessed by the time course relationships of androgen induced norepinephrine release, protein kinase C activation-depletion and increases in total DNA, the impact of in vivo reserpine induced norepinephrine depletion on protein kinase C activation-depletion and the mitogenic response, and the alpha1-adrenoceptor mediated mitogenic response in cultured seminal vesicle smooth muscle cells. RESULTS: In prepubertal smooth muscle androgen induced norepinephrine release from postganglionic neurons. The effect was independent of preganglionic innervation. Increased norepinephrine release was concurrent with the onset of androgen induced protein kinase C activation-depletion and cellular proliferation. In vivo norepinephrine depletion to 1% or less of control values by chronic reserpine treatment selectively antagonized the androgen induced increases in smooth muscle DNA and protein kinase C down-regulation. Norepinephrine depletion by reserpine neither induced apoptosis nor altered cell number. Cell culture experiments demonstrated that alpha1-adrenoceptors mediated the proliferative response to norepinephrine. Together these findings indicate that increased norepinephrine release has an obligatory role in androgen dependent muscle cell proliferation during puberty. Terminally differentiated smooth muscle in adults was characterized by androgen resistance to elevated norepinephrine release and protein kinase C activation. CONCLUSIONS: Androgen induced norepinephrine release from postganglionic neurons in seminal vesicle smooth muscle mediated the proliferative response that occurs in early pubertal development. Normal uncoupling of elevated norepinephrine release and protein kinase C activation-depletion may represent a key event in the normal terminal differentiation of accessory sex organ smooth muscle in adults.