Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation

The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with pathologic, psychological, and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, among others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models have allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation.     

A novel method for culturing sweat gland epithelia: comparison of normal and cystic fibrosis tissues.

A new method is described to produce epithelial sheets by direct explantation of human sweat glands onto matrigel-coated millipore filters. The method is applicable to whole glands, separated coils or ducts and to normal and CF tissues. Electrogenic transport studies show that epithelia develop sodium transporting capability, even when explants are derived from secretory coils.     

Differences in SLE disease activity between patients of Caucasian and South‐East Asian/Chinese background in an Australian hospital

Aim: We performed a semiprospective and retrospective review of all admissions to a single institution of systemic lupus erythematosus (SLE) patients, admitted due to active disease. The aim was to describe differences in disease activity as a cause of hospital admissions between patients originating from South‐East Asia/China (SAC) and Caucasians. Method: There were 210 patients admitted for active disease, with a total of 567 admissions for active SLE over a 16‐year period. Allowing for patients who had left our database, there was a total of 3415 patient years of observation. Results: Patients from SAC with a flare requiring admission presented earlier in their disease course and with more active disease than did Caucasians (median SLE Disease Activity Index 13 vs. 8, P= 0.002). They had longer inpatient stays (7 vs. 5 days P = 0.03). There was a trend to higher rates of re‐presentation to hospital for flare (59% in SAC patients vs. 41% in Caucasians, P = 0.09) with more subsequent admissions (3 vs. 2 P = 0.06) despite a shorter period of observation. Conclusions: South‐East Asian/Chinese were more likely to be diagnosed with class III/IV glomerulonephritis and require cyclophosphamide both at presentation and subsequent admissions. More patients from SAC were readmitted to hospital for severe central nervous system disease after their first hospital admission. In this population, lupus patients had more severe flares and more frequently required admission for these than Caucasians.     

Challenges and opportunities of nursing care in special-needs shelters.

Hurricanes Katrina and Rita forced many individuals along the coast of Texas and Louisiana to seek shelter inland. Among the evacuees were residents with special needs and residents of nursing homes and group homes caring for mentally retarded and physically disabled persons. Many nurses volunteered to provide health care for those in need. This article discusses challenges and opportunities that were encountered by nurses volunteering in special-needs shelters. Issues related to human and physical resources, patient care, and confidentiality are discussed including lessons learned. As nurses who cared for evacuees in the shelter, it is hoped some of the lessons learned can be utilized in future disasters.     

The effects of neuropeptide Y and its fragments upon basal and electrically stimulated ion secretion in rat jejunum mucosa.

1. The effects of acute or chronic morphine treatment on the changes in blood pressure and pulse rate in response to ganglionic stimulation or blockade and to vagal stimulation, and of isolated atria to field stimulation or noradrenaline, were studied. 2. In pithed rats, intravenously injected hexamethonium significantly depressed the blood pressure responses to sympathetic nerve stimulation. The ganglionic blocking effects of hexamethonium were significantly greater in chronically morphine-treated rats, but were not significantly affected by acute morphine administration in naive animals. 3. Intravenous administration of nicotine dose-dependently increased blood pressure and pulse rate. The magnitudes of these changes were not significantly affected by acute or chronic morphine pretreatment. 4. Studies with rat isolated atrial preparations revealed that the changes in atrial contractile rate and force in response to noradrenaline or field stimulation were not influenced by either acute or chronic morphine treatment. 5. Cervical vagal stimulation produced voltage- or frequency-dependent decreases in pulse rate and blood pressure. The responses were not significantly affected by chronic morphine treatment. 6. These findings suggest that the site of the changes in sympathetic function following prolonged exposure to the opiate appears to be on the preganglionic nerve fibres.     

Evidence for two leukotriene receptor types in the guinea-pig isolated ileum

Leukotriene (LT) receptors in the guinea-pig ileum were characterized using LTB4, LTC4, LTD4 and LTE4 and the LT antagonists FPL 55712, ICI 198615 and (+/-)SKF 104353. LTB4 was inactive but the other LTs induced concentration-related contractions. LTC4 responses differed to those induced by LTD4 or LTE4. Inhibitors of LT metabolism had no significant effects on any LT responses. LTD4 contractions were inhibited by all three antagonists but a resistant response was apparent at concentrations of ICI 198615 greater than 10(-8) M. All three antagonists were weak/inactive against LTC4. LTE4 was a partial agonist which antagonized LTD4 responses but had little or no activity against LTC4 or histamine. These results suggest that two distinct LT receptor types exist on guinea-pig ileum. One type is predominantly activated by LTD4 and is antagonized by three structurally distinct LT antagonists and the partial agonist LTE4. The second type is predominantly activated by LTC4 and is insensitive to the LT antagonists.     

Advances in the treatment of depression in older adults

Depressive symptoms in older adults are common, but the minority of elderly meet criteria for major depressive disorder. This has led to confusion regarding the recognition of diagnosis, approach to treatment, and monitoring of outcomes in this needy population. Few depressed older adults are willing to seek treatment from psychiatrists or mental health specialists. Treatment approaches to the depressive spectrum of disorders in late life, which encompasses major and minor depressive disorder, dysthymic disorder, and mood disorders related to medical conditions, must include evidence-based algorithms that can be delivered in a variety of health care settings. Several recent multisite trials have advanced the use of collaborative care models and the systematic stepwise approach to the treatment of depression and anxiety states in older adults. This offers the ability to provide effective treatment of depression for older adults, consistent with current guidelines, in primary care and specialized health care settings.     

Sham in CAM

Several unique methodological challenges exist concerning the choice of the most appropriate comparator or control group for clinical research in complementary and alternative medicine (CAM). This article reviews the four major types of control groups (active control, placebo or sham, no intervention control, and different protocols of the experimental intervention), noting the different questions they answer and the different contexts in which they may be used, and discusses how this framework may be applied to CAM research in an effort to avoid methodologically flawed study designs. The choice of comparator depends on complex factors such as the research question being asked, the most plausible competing rival hypotheses, and logistical considerations related to ethics, methodology and feasibility. For example, for sham to be an effective comparator it must capture the ‘nonspecific’ elements of the treatment without containing those that are ‘specific’ to the research question at hand. However, as demonstrated by the examples of acupuncture and energy medicine, designing such sham intervention is not always easy. Controlling for social interaction between practitioners and subjects, addressing issues around ethics, having good-quality measurement of treatment integrity and intensity, and selecting practitioners of sufficient competence when doing a sham process are other important parts of correct design choices. In the light of these complexities, clinicians and researchers alike need a better match between the research questions and the design employed in order for their research to be both scientifically valid and clinically meaningful.     

Apoptosis: understanding the new molecular pathway.

Advances in science have increased the knowledge of how cells die in the body (apoptosis). A basic understanding of this process can improve nurses' ability to review new scientific literature and enable them to provide safer bedside care.