admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

The heme oxygenase (HO) system consists of two forms identified to date: the oxidative stress-inducible protein HO-1 (HSP32) and the constitutive isozyme HO-2. These proteins, which are different gene products, have little in common in primary structure, regulation, or tissue distribution. Both, however, catalyze oxidation of heme to biologically active molecules: iron, a gene regulator; biliverdin, an antioxidant; and carbon monoxide, a heme ligand. Finding the impressive heme-degrading activity of brain led to the suggestion that "HO in brain has functions aside from heme degradation" and to subsequent exploration of carbon monoxide as a promising and potentially significant messenger molecule. There is much parallelism between the biological actions and functions of the CO- and NO-generating systems; and their regulation is intimately linked. This review highlights the current information on molecular and biochemical properties of HO-1 and HO-2 and addresses the possible mechanisms for mutual regulatory interactions between the CO- and NO-generating systems.

THE HEME OXYGENASE SYSTEM:A Regulator of Second Messenger Gases

The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO). In recent years, endogenously produced CO has been shown to possess intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. The era of gaseous molecules in biomedical research and human diseases initiated with the discovery that the endothelial cell-derived relaxing factor was identical to the gaseous molecule nitric oxide (NO). The discovery that endogenously produced gaseous molecules such as NO and now CO can impart potent physiological and biological effector functions truly represented a paradigm shift and unraveled new avenues of intense investigations. This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress. Furthermore, the current understanding of the functional significance of HO shall be discussed from the perspective of each of the metabolic by-products, with a special emphasis on CO. Finally, this presentation aspires to lay a foundation for potential future clinical applications of these systems.

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Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.

Natural products afford a window of opportunity to study important biology. If the natural product is used or abused by human beings, finding its biological target(s) is all the more significant. Hot pepper is eaten on a daily basis by an estimated one-quarter of the world’s population and

Vanilloid (Capsaicin) Receptors and Mechanisms

The role of antioxidants in the chemistry of oxidative stress: A review.

OBJECTIVES: Aspiration of oral secretions and their bacteria is increasingly being recognized as an important factor in pneumonia. We investigated whether oral care lowers the frequency of pneumonia in institutionalized older people. DESIGN: Survey. SETTING: Eleven nursing homes in Japan. PARTICIPANTS: Four hundred seventeen patients randomly assigned to an oral care group or a no oral care group. INTERVENTION: Nurses or caregivers cleaned the patients’ teeth by toothbrush after each meal. Swabbing with povidone iodine was additionally used in some cases. Dentists or dental hygienists provided professional care once a week. MEASUREMENTS: Pneumonia, febrile days, death from pneumonia, activities of daily living, and cognitive functions. RESULTS: During follow-up, pneumonia, febrile days, and death from pneumonia decreased significantly in patients with oral care. Oral care was beneficial in edentate and dentate patients. Activities of daily living and cognitive functions showed a tendency to improve with oral care. CONCLUSION: We suggest that oral care may be useful in preventing pneumonia in older patients in nursing homes. J Am Geriatr Soc 50:430‐433, 2002.

Oral care reduces pneumonia in older patients in nursing homes.

Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients receiving or not receiving inhaled corticosteroids and in nonsmoking and smoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids (5.6 ± 0.6 ppm, p < 0.001) and similar in asthmatic patients receiving inhaled corticosteroids (1.7 ± 0.1 ppm) compared with those in nonsmoking healthy control subjects (1.5 ± 0.1 ppm). Smoking healthy control subjects had the highest levels of exhaled CO concentration among the groups (21.6 ± 2.8 ppm, p < 0.001). To examine whether inhaling corticosteroids reduce exhaled CO concentration in a given asthmatic patient, 12 patients with symptomatic asthma who were being treated by inhaled β2-agonists alone underwent measurements of exhaled CO concentration before and 4 wk after the initiation of inhal...

Increased Carbon Monoxide in Exhaled Air of Asthmatic Patients

Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia.

Interventions to Prevent Pneumonia Among Older Adults

There is evidence that certain components of the renin-angiotensin system (RAS) may have a crucial role in learning and memory processes.1,2⇓ Angiotensin-converting enzyme (ACE) is overexpressed in the hippocampus, frontal cortex, and caudate nucleus of patients with Alzheimer disease (AD).1 In an animal model with AD, brain-distributing ACE inhibitors are reported to rescue neuronal damage and improve behavior.2 Furthermore, we have shown that brain-penetrating ACE inhibitors can reduce the incidence of AD in elderly hypertensive patients.3 In the present study, we tested the hypothesis that treatment with brain-penetrating ACE inhibitors3 would slow the rate of cognitive decline in mild-to-moderate AD patients with hypertension.

We performed a randomized, prospective, parallel group trial with 1-year exposure to study medications. Participants were recruited from three long-term care facilities in Sendai, Japan. Patients eligible for this study had a diagnosis of mild to moderate AD,4,5⇓ were aged 65 years and older, had Mini-Mental State Examination (MMSE) scores within the range of 13 to 23, showed no evidence of stroke; insulin-dependent diabetes mellitus, or other endocrine disorders, or asthma or obstructive pulmonary disease, and had a blood pressure of higher than 140 mm Hg systolic or 90 mm Hg diastolic. The diagnosis of probable AD was made according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria with no clinical or laboratory evidence of a cause other than AD for dementia.5 Brain MRI was obtained in all participants within 3 months prior to the study enrollment to exclude patients with possible or probable vascular dementia and other neurodegenerative dementias. Patients …

Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression.

Exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. To study the effects of rhinovirus infection on respiratory epithelium, a primary target for respirat...

Takashi Ohrui

Papers

Oral care reduces pneumonia in older patients in nursing homes.

Increased Carbon Monoxide in Exhaled Air of Asthmatic Patients

Interventions to Prevent Pneumonia Among Older Adults

Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression.

Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1β