Neutrophil Elastase Increases Airway Epithelial Nonheme Iron Levels

Alpha-1-antitrypsin (A1AT) deficiency is characterized by increased neutrophil elastase (NE) activity and oxidative stress in the lung. We hypothesized that NE exposure generates reactive oxygen species by increasing lung nonheme iron. To test this hypothesis, we measured bronchoalveolar lavage (BAL) iron and ferritin levels, using inductively coupled plasma (ICP) optical emission spectroscopy and an ELISA, respectively, in A1AT-deficient patients and healthy subjects. To confirm the role of NE in regulating lung iron homeostasis, we administered intratracheally NE or control buffer to rats and measured BAL and lung iron and ferritin. Our results demonstrated that A1AT-deficient patients and rats postelastase exposure have elevated levels of iron and ferritin in the BAL. To investigate the mechanism of NE-induced increased iron levels, we exposed normal human airway epithelial cells to either NE or control vehicle in the presence or absence of ferritin, and quantified intracellular iron uptake using calcein fluorescence and ICP mass spectroscopy. We also tested whether NE degraded ferritin in vitro using ELISA and western analysis. We demonstrated in vitro that NE increased intracellular nonheme iron levels and degraded ferritin. Our results suggest that NE digests ferritin increasing the extracellular iron pool available for cellular uptake.

In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm

Isoflavones are plant compounds, proposed to have health benefits in a variety of human diseases, including coronary heart disease and endocrine-responsive cancers. Their physiological effects include possible antioxidant activity, therefore suggesting a role for isoflavones in the prevention of male infertility. The aim of this study was to test the antioxidant effects of the isoflavones genistein and equol on sperm DNA integrity, assessed in vitro after hydrogen peroxide-mediated damage, using the cornet assay. Pre-treatment with genistein or equol at doses of 0.01-100 mumol/l significantly protected sperm DNA against oxidative damage. Both ascorbic acid (10-600 mumol/l) and alpha-tocopherol (1-100 mumol/l) also protected. Compared with ascorbic acid and alpha-tocopherol, added at physiological concentrations, genistein was the most potent antioxidant, followed by equol, ascorbic acid, and alpha-tocopherol. Genistein and equol added in combination were more protective than when added singly. Based on these preliminary data, which are similar to those observed previously in lymphocytes, these compounds may have a role to play in antioxidant protection against male infertility.

Coronary heart disease: health knowledge and behaviour

Objective To determine the current level of knowledge and understanding of CHD in the general public in Northern Ireland and to identify factors that are associated with higher knowledge levels. Setting Six provincial centres in Northern Ireland. Methods The data in the present study were collected using an interview administered questionnaire. 1,000 members of the general public were interviewed face-to-face. CHD knowledge was computed as a continuous variable, i.e. higher score represents better CHD knowledge. Main outcome measure CHD knowledge in the general public in Northern Ireland. Results Study respondents displayed limited knowledge and understanding of CHD. Study respondents who achieved higher CHD knowledge scores were more likely to report: exercising for 30 min three times or more per week, paying attention to their diet, being overweight, having a family history of CHD, living in a higher socioeconomic area (according to postcode) and having attended tertiary education. Respondents in the present study while recognising the role that community pharmacists had to play in helping patients manage their prescribed medicines, did not recognise the community pharmacists' role in other aspects of CHD detection or management. Conclusion The deficit in CHD knowledge could translate into inadequate preventative behaviour patterns and suboptimal clinical outcomes. If community pharmacists wish to become increasingly involved in public health delivery relating to CHD they need to develop effective and accessible services and promote these to the public who at present do not recognise this role of the community pharmacist.

Extent and nature of unlicensed and off-label medicine use in hospitalised children in Palestine

Objective of the study: To determine the extent and nature of unlicensed/off-label prescribing patterns in hospitalised children in Palestine. Setting: Four paediatric wards in two public health system hospitals in Palestine [Caritas children’s hospital (Medical and neonatal intensive care units) and Rafidia general hospital (Medical and surgical units)]. Method: A prospective survey of drugs administered to infants and children <18 years old was carried out over a five-week period in the four paediatric wards. Main outcome measure: Drug-licensing status of all prescriptions was determined according to the Palestinian Registered Product List and the Physician’s Desk Reference. Results: Overall, 917 drug prescriptions were administered to 387 children. Of all drug prescriptions, 528 (57.5%) were licensed for use in children; 65 (7.1%) were unlicensed; and 324 (35.3%) were used off-label. Of all children, 49.6% received off-label prescriptions, 10.1% received unlicensed medications and 8.2% received both. Seventy-two percent of off-label drugs and 66% of unlicensed drugs were prescribed for children <2 years. Multivariate analysis showed that patients who were admitted to the neonatal intensive care unit and infants aged 0–1 years were most likely to receive a greater number of off-label or unlicensed medications (OR 1.80; 95% CI 1.03–3.59 and OR 1.99; 95% CI 0.88–3.73, respectively). Conclusion: The present findings confirmed the elevated prevalence of unlicensed and off-label paediatric drugs use in Palestine and strongly support the need to perform well designed clinical studies in children.

Job strain and adverse health behaviors: The Finnish public sector study

Objective: The objective of this study was to explore the association between job strain and the co-occurrence of adverse health behaviors, smoking; heavy drinking; obesity, and physical inactivity. Methods. The authors studied cross-sectional data of 34,058 female and 8154 male public sector employees. Results: Multinomial logistic regression models adjusted for sex, age, basic education, marital status, and type of job contract showed that high job strain and passive jobs were associated with 1.3 to 1.4 times higher odds of having >= 3 (vs 0) adverse health behaviors. Among men, low job control was associated with a 1.3 fold likelihood and amon women active jobs were associated with a 1.2 fold likelihood of having >= 3 (vs 0) adverse behaviors. High demands were associated with a higher likelihood of co-occurrence of one to two (vs 0) adverse behav irs among women. Conclusions. b strain conditions may be associated with the co-occurrence of adverse health behaviors that contribute to preventable chronic diseases. Clinical Significance. Adversejob conditions may increase the likelihood of co-occurring health risk behaviors. Reducing work stress by increasingl ob control and decreasing psychologic demands might help efforts to promote healthy 1 festyles.

Fetal brain function in response to maternal alcohol consumption: Early evidence of damage

Background: Studies of the adverse neurobehavioral effects of maternal alcohol consumption on the fetus have been largely confined to the postnatal period, after exposure to alcohol has finished. This study explored the brain function of the fetus, at the time of exposure to alcohol, to examine its effect on information processing and stability of performance. Methods: Five groups of fetuses, defined by maternal alcohol consumption patterns, were examined: control (no alcohol); moderate (5 to 10 units/wk either drunk evenly across the week or as a binge, in 2 to 3 days); heavy (20+ units/wk drunk evenly or as a binge). Fetal habituation performance was examined on 3 occasions, separated by 7 days, beginning at 35 weeks of gestation. The number of trials required to habituate on each test session and the difference in performance across test sessions were recorded. Results: Fetuses exposed to heavy binge drinking required significantly more trials to habituate and exhibited a greater variability in performance across all test sessions than the other groups. Maternal drinking, either heavily but evenly or moderately as a binge, resulted in poorer habituation, and moderate binge drinking resulted in greater variability compared with no, or even, drinking. Conclusions: Decreased information processing, reflected by poorer habituation, and increased variability in performance may reflect the initial manifestations of structural damage caused by alcohol to the brain. These results will lead to a greater understanding of the effects of alcohol on the fetus's brain, enable the antenatal identification of fetal alcohol spectrum disorders, and lead to the early implementation of better management strategies. © 2012 by the Research Society on Alcoholism.


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Perceptions and attitudes of Jordanian paediatricians towards off-label paediatric prescribing

Objective To assess current experiences and attitudes of hospital based paediatricians towards off-label medicine prescribing. Setting Paediatric hospital wards and out-patient clinics. Design A prospective, questionnaire based study. Results A 30 item questionnaire was sent to 300 hospital based paediatricians and 250 (83%) were returned completed. Over 69% of responders were familiar with the term off-label medicines. However, only 28% were knowingly prescribing off-label medicines to children. The majority of respondents (90%) expressed concerns about the safety and efficacy of off-label medicines. Only 15% had observed Adverse Drug Reactions, and 31% a treatment failure. The vast majority of respondents (83%) did not obtain informed consent or tell parents they were prescribing off label medicines to their children. Conclusions Off-label prescribing of medicines to children is a familiar concept to the majority of paediatricians in Jordan although only a smaller number are aware that it is common in their practice. Respondents showed concern about off label prescribing, although the majority do not consider it necessary to inform parents. More comprehensive research is needed in this area in Jordan and other Middle Eastern countries.

Societal perceptions of community pharmaceutical services in Malta

Objective: To assess the views of the Maltese general public on services provided by community pharmacies in Malta and their opinions on the proposed extended role for pharmacies.

Buccal absorption of enalapril and lisinopril

Objective: The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects.

Pharmaceutical care of patients with congestive heart failure: Interventions and outcomes

We evaluated a structured pharmaceutical care program for elderly patients (> 65 yrs) with congestive heart failure (CHF) based on objective measures of disease control, quality of life, and use of health care facilities in a randomized, controlled, longitudinal, prospective clinical trial. The 42 patients in group A received education from a pharmacist on the disease and its treatment, and lifestyle changes that could help control symptoms. Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy. If necessary, dosage regimens were simplified in liaison with hospital physicians. The 41 control patients (group B) received standard care. The following outcome measures were assessed in all patients at baseline (before the start of the trial) and at 3, 6, 9, and 12 months: 2-minute walk test, blood pressure, body weight, pulse, forced vital capacity, quality of life [disease-specific (Minnesota Living with Heart Failure questionnaire) and generic (SF-36)], knowledge of symptoms and drugs, compliance with therapy, and use of health care facilities (hospital admissions, visits to emergency room, emergency calls). Patients in group A showed improved compliance with drug therapy, which in turn improved their exercise capacity compared with those in group B; education on management of symptoms, lifestyle changes, and dietary recommendations were also of benefit. Group A patients significantly improved knowledge of their drug therapy over the 12-month study and had fewer hospital admissions compared with group B patients. They also had improved outcomes compared with group B, despite the small samples. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF.

Local DNA damage by proton microbeam irradiation induces poly(ADP-ribose) synthesis in mammalian cells

Cellular recovery from ionizing radiation (IR)-induced damage involves poly(ADP-ribose) polymerase (PARP-1 and PARP-2) activity, resulting in the induction of a signalling network responsible for the maintenance of genomic integrity. In the present work, a charged particle microbeam delivering 3.2 MeV protons from a Van de Graaff accelerator has been used to locally irradiate mammalian cells. We show the immediate response of PARPs to local irradiation, concomitant with the recruitment of ATM and Rad51 at sites of DNA damage, both proteins being involved in DNA strand break repair. We found a co-localization but no connection between two DNA damage-dependent post-translational modifications, namely poly(ADP-ribosyl)ation of nuclear proteins and phosphorylation of histone H2AX. Both of them, however, should be considered and used as bona fide immediate sensitive markers of IR damage in living cells. This technique thus provides a powerful approach aimed at understanding the interactions between the signals originating from sites of DNA damage and the subsequent activation of DNA strand break repair mechanisms.