Experiences of mental health discrimination in New Zealand

Discrimination against people with experience of mental illness is a recognised problem, and there is a lack of information in New Zealand regarding the nature of this discrimination. The Like Minds, Like Mine project is a New Zealand initiative to combat the stigma and discrimination associated with mental illness. This paper reports on a study undertaken as part of this initiative, and describes the nature of discrimination that people with experience of mental illness face in New Zealand. A written survey was undertaken with people with experience of mental illness from throughout New Zealand, using a mixture of qualitative and quantitative questions. This questionnaire was distributed throughout the country in 2003, using a variety of distribution methods, and 785 responses were received and analysed from people self-identifying as having experienced mental illness. Respondents reported discrimination in all areas of their lives. The most commonly reported areas were discrimination by friends and family (59%), a fear of being discriminated against (46%), and discrimination in looking for employment (34%) and mental health services (34%). Discrimination can limit the participation of people with experience of mental illness in our society. We all need to examine our own attitudes and behaviours and take responsibility for discrimination.     

Naturally appearing N-feruloylserotonin isomers suppress oxidative burst of human neutrophils at the protein kinase C level

N-feruloylserotonin (N-f-5HT) isomers, isolated from seeds of Leuzea carthamoides (Wild) DC, inhibited dose-dependent oxidative burst in human whole blood and isolated neutrophils in vitro, which were measured by luminol- and/or isoluminol-enhanced chemiluminescence in the following rank order of stimuli: PMA > OpZ > calcium ionophore A23187. In isolated neutrophils that were stimulated with PMA, N-f-5HT isomers were effective against extracellular and intracellular reactive oxygen species. Liberation of ATP, analysis of apoptosis, and recombinant caspase-3 activity revealed that N-f-5HT isomers, used in concentrations up to 100 μM, did not alter the viability and integrity of isolated neutrophils. Western blot analysis documented that in concentrations of 10 and 100 μM, N-f-5HT isomers significantly decreased PMA-induced phosphorylation of PKC α/β II. The results suggest that N-f-5HT isomers are an effective, naturally occurring substance with a potent pharmacological effect on the oxidative burst of human neutrophils. It should be further investigated for its pharmacological activity against oxidative stress in ischemia-reperfusion, inflammation and other pathological conditions.     

Cardiovascular diseases and the nitric oxide pathway

Fifteen years after its discovery, NO has fully reached an established position in physiology, medicine and therapeutics. It is difficult to find a biological function or a pathological condition where NO does not play a relevant role. Discoveries in the NO field have historically evolved from cardiovascular research, although its influences have already covered nearly all the medical specialties. This review analyzes, step by step, the pathway through which NO is synthesized in the cells of the cardiovascular system and the main physiological and pathological routes it undergoes once it is released. We focus on various diseases affecting the cardiovascular system (atherosclerosis, hypertension, diabetes mellitus and septic shock). We describe in detail those steps of the NO pathway in which anomalies have been detected and may account for the pathophysiology of these diseases. In atherosclerosis, hypertension and diabetes mellitus, the endothelial form of NOS is upregulated, but is very sensitive to environmental conditions, such as substrate or cofactor deficiencies or increases in LDL or glucose. In this situation NOS synthesizes superoxide anion instead of NO leading to oxidative and nitrosative stress. In diabetes mellitus and, very importantly, in septic shock, the inducible form of NOS is highly upregulated. Overproduction of NO appears to underlie the hypotension and tissue damage of septicemia and the destruction of beta-cells in diabetes mellitus. New knowledge of the role of NO in these diseases has started to influence therapeutic design. We also review the current status of research on NO-based therapies.     

Abuse liability of flunitrazepam among methadone-maintained patients

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential. Received: 13 February 1998/Final version: 1 May 1998     

Clozapine and resistant schizophrenia

Clozapine is an atypical antipsychotic drug, with distinguishing features from neuroleptics which are believed to exert their therapeutic effect by blocking dopamine receptors in the limbic system. Clozapine is both chemically and pharmacologically distinct from neuroleptics such as chlorpromazine and haloperidol. This tricyclic dibenzodiazepine derivative is moderately active on the dopaminergic pathways, blocking D1 and D2 receptors to the same extent; and chronic treatment with clozapine does not lead to a compensatory increase in the number of striatal D2 receptors in rats. Pharmacological studies showed that clozapine produces psychomotor inhibition but without catalepsy and other typical effects of dopamine receptor blockade. The drug also has adrenergic (alpha 1), histamine (H1), and serotonin (5-HT2) blocking activity and is a potent muscarinic antagonist. The efficacy and side-effect profile of clozapine are unique. Treatment-resistant patients are much more likely to respond to clozapine than to haloperidol or chlorpromazine. In double-blind trials, clozapine has improved both positive and negative psychotic symptoms in schizophrenic patients who were refractory to conventional neuroleptics. Extrapyramidal side-effects are exceptional during therapy and tardive dyskinesia never demonstrated in relationship to clozapine. There is an increased risk of agranulocytosis with clozapine use estimated to be up to 20 cases of agranulocytosis per thousand patients treated during one year. Accordingly, a careful patient selection and regular blood monitoring are mandatory over the treatment period (blood testing to be performed weekly and immediately at the first sign of infection). Generally, this agranulocytosis is reversible with early detection and prompt drug discontinuation.     

Prevalencia y características de la enfermedad pulmonar obstructiva crónica en no fumadores

ObjectiveThe objective of the study was to know the profile of patients diagnosed with chronic obstructive pulmonary disease (COPD) and who have never been smokers.DesignA transversal study.LocationPrimary Care Centre of Pla d’Urgell (Primary care setting in Lleida, Spain).Participants512 patients older than 40 years with COPD from Primary Care Centre of Pla d’Urgell with a compatible spirometry [forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) ratio < 0.7) to the beginning of the study.Main measurementsThe dependent variable was de COPD in non-smokers and the independents were variables collected from the information on the respiratory clinical history, the risk factors of the patients and on quality of life. We designed a predictor model of COPD in non-smokers compared to smokers.Results33.2% of COPD patients had never been smokers, 59.4% of whom were women. The average FEV₁ for non-smokers was 70.5 (SD = 17.1), higher than 62.6 (SD = 18.5) for smokers/former smokers (p < 0.001). The coverage of pneumococcal vaccination 23V was better in non-smokers (75.3%), p < 0.001. COPD in non-smokers (compared to smokers/former smokers) were: mostly women (OR = 16.46), older (OR = 1.1), with better FEV₁ (OR = 1.1), better perception of quality, EuroQoL-5D (OR = 0.8), with lower prevalence of diabetes (OR = 0.5), lower level of studies (OR = 0.2), and with fewer previous hospitalizations (OR = 0.3).ConclusionsThe study evidences a high proportion of non-smokers in COPD patients. Our study aims that older women with less severity would be associated with an increased risk of COPD in non-smokers. It seems to indicate that COPD in non-smokers would appear at later ages and would be milder than smoking-related COPD.     

Assessment of the potential irritation and photoirritation of novel amino acid-based surfactants by in vitro methods as alternative to the animal tests

The ultraviolet-A radiation damage effects on skin and eyes will be increased by phototoxic compounds which could be present in pharmaceutical or cosmetic formulations. Great efforts have been made in the last years to find surfactants to replace those with phototoxic potential in commercial use. Series of different in vitro models for phototoxicity, included to validated neutral red uptake (NRU) 3T3 phototoxicity assay are useful screening tools. The phototoxic effects of a novel family of glycerol amino acid-based surfactant compounds were examined via these assays. Human red blood cells and two immortalised cell lines, murine fibroblast cell line 3T3, and one human keratinocyte cell line, HaCaT, were the in vitro models employed to predict potential photoirritation. The phototoxic end-points assessed were hemolysis (human red blood cell test) and resazurin transformation to resorufin and NRU in cell culture methods. The results suggest that no phototoxic effects by any new amino acid derived-surfactants, could be identified.     

Comparative evaluation of cytotoxicity and phototoxicity of mono and diacylglycerol amino acid-based surfactants

Extensive efforts have been made, recently, to find surfactants with lower irritancy potential than those presently commercially employed in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of novel mono and diacylglycerol amino acid-based surfactants (glutamic acid, or arginine) were evaluated.All tested surfactants showed a clear concentration–response relationship to two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, demonstrated by and decrease of NR uptake. Concentrations resulting in 50% inhibition of NR uptake (IC₅₀) range from 30 to 300 μg mL⁻¹.The potential phototoxicity which could result in irritant products, was determined by modulated cytotoxicity via the resazurin reduction to resorufin and neutral red uptake (NRU) endpoints. Surfactants with two chains showed, in general, less cytotoxic but higher phototoxic effect than surfactants with only one chain.