Nitric oxide sensing by cytochrome c bonded to a conducting polymer modified glassy carbon electrode

A nitric oxide biosensor based on cytochrome c (an heme protein) covalently immobilized to poly(5-amino-1-naphthol) by using cyanuric chloride as a bridge was developed. The immobilization was studied by cyclic voltammetry and quartz crystal microbalance. The nitric oxide detection as a function of poly(5-amino-1-naphthol) amount was recorded, and the best result was obtained with the electrode prepared by 70 cycles. The sensitivity and detection limit were 0.015 mu A cm(-2)/mu mol L(-1) and 2.85 mu mol L(-1), respectively. (C) 2009 Elsevier B.V. All rights reserved.

Beröringens betydelse i vården : en systematisk litteraturstudie

Den fysiska beröringen är en förutsättning för att vård överhuvudtaget skall kunna utföras. Varje dag sker inom hälso- och sjukvården ett oräkneligt antal beröringar i skiftande situationer. Beröringen finns där som en självklar del i den dagliga vården men kan också användas i olika fysiska behandlingsmetoder. Syftet med denna litteraturstudie var att beskriva vilken betydelse beröring hade i omvårdnaden för patienten. Vetenskapliga artiklar och litteratur i ämnet användes och var publicerade efter 1995. Fysisk beröring i omvårdnaden visade sig ha flera olika betydelser som gick att dela in i begreppen: symtomlindring och återhämtning, komfort, kommunikation, obehag samt samspel. Den fysiska beröringen gav både fysiska och psykiska förbättrade tillstånd. En del patienter minskade sin läkemedelsanvändning efter behandlingar med olika fysiska beröringsformer. Detta kunde vara en väg till ökad livskvalitet för människor, framförallt när det handlade om smärta, oro, och depression. Positiva känslor som trygghet, välbefinnande och komfort upplevdes av en del patienter i beröringsögonblicket och ibland som en följd av själva beröringen. Beröring visade sig vara ett sätt att kommunicera med patienter, framförallt var det viktigt när det verbala språket sviktade eller saknades. Även om många positiva betydelser för patienterna framkom i studierna fanns det också negativa upplevelser. Beröring av stressad och hårdhänt personal, smärta och att inte känna sig delaktig i skeendet var exempel på obehagliga upplevelser. I flera studier framkom att samspelet mellan patienter och vårdare kunde förbättras med stöd av den fysiska beröringen.

Depression Hos Tonåringar : Möjligheter för tidig upptäckt och behandling av tonåringar med depressioner

Denna litteraturstudie syftar till att undersöka hur tonåringar med depressioner tidigt kan upptäckas och få hjälp och vilken roll sjuksköterskan har i detta samt vad tonåringar själva tycker är viktigt i mötet med vården. Till resultatdelen har 17 vetenskapliga artiklar valts ut efter litteratursökning ifrån databaserna Cinahl, Elin och Pubmed. Depressioner hos tonåringar är ett allvarligt problem som innebär ett stort lidande och som i värsta fall kan leda till självmord. Förekomsten av depressioner hos tonåringar ökar och detta ställer allt högre krav på både skolhälsovård och primärvård. Resultatet visade att tonåringar i allmänhet hellre söker sig till skolhälsovården och ungdomsmottagningar än till primärvården och specialister. Genom att finnas nära tonåringarna har skolsköterskan och ungdomsmottagningar unika möjligheter att kunna upptäcka och hjälpa tonåringar som har depressioner eller nedstämdhet. För att öka möjligheterna till tidig upptäckt och behandling av tonåringar med depressioner är det viktigt att satsa resurser på skolhälsovård och ungdomsmottagningar. Det bör också spridas mer kunskap om systematisk screening som har visat sig vara ett värdefullt verktyg för att upptäcka depressioner.

Amplification of multiple copies of mitochondrial Cytochrome b gene fragments in the Australian freshwater crayfish, Cherax destructor Clark (Parastacidae: Decapoda)

Non-coding copies of fragments of the mitochondrial genome translocated to the nucleus or pseudogenes are being found with increasing frequency in a diversity of organisms. As part of a study to evaluate the utility of a range of mitochondrial gene regions for population genetic and systematic studies of the Australian freshwater crayfish, Cherax destructor (the yabby), we report the first detection of Cytochrome b (Cyt b) pseudogenes in crustaceans. We amplified and sequenced fragments of the mitochondrial Cyt b gene from 14 individuals of C. destructor using polymerase chain reaction (PCR) with primers designed from conserved regions of Penaeus monodon and Drosophila melanogaster mitochondrial genomes. The phylogenetic tree produced from the amplified fragments using these primers showed a very different topology to the trees obtained from sequences from three other mitochondrial genes, suggesting one or more nuclear pseudogenes have been amplified. Supporting this conclusion, two highly divergent sequences were isolated from each of two single individuals, and a 2 base pair (bp) deletion in one sequence was observed. There was no evidence to support inadvertent amplification of parasite DNA or contamination of samples from other sources. These results add to other recent observations of pseudogenes suggesting the frequent transfer of mitochondrial DNA (mtDNA) genes to the nucleus and reinforces the necessity of great care in interpreting PCR-generated Cyt b sequences used in population or evolutionary studies in freshwater crayfish and crustaceans more generally.

Depression and expression: life begins on the other side of despair

This paper has two parts. In Part I, it consists of a letter written by the subject of the ‘case study’ that forms the basis of Part II. Part I demonstrates how the writer Aliki Pavlou discovered that, in attempting to help a friend face uncomfortable truths in relation to his perception of his mother, she inadvertently was able to voice her own dilemma in relation to her mother that hitherto had been elusive.
This paper forms a part of a larger project being researched by Aliki Pavlou, Justin Clemens and me. The study, to be entitled, "In the Heart of Hell: Depression and its Expression," is one that contends that Literature expresses the ineffable nature of depression in its symbolic mode; that, indeed, literary texts reveal in their concealment. The work therefore argues that ‘depression’ is expressible.
Part II of this paper analyses the response of a depressive to Jean-Paul Sartre’s novel Nausea (1964). Beginning with a brief discussion of the role of the ‘mother’ as psychologically pivotal in some depressives’ struggle towards well-being, this section analyses a reading of Nausea by a depressive. The objective of this study was to ascertain the extent to which the condition of nausea, as represented in Sartre’s novel, expresses the experience of depression.

Treatment of depression in low-level residential care facilities for the elderly

Background: The rate of recognition and treatment of depressed older people in nursing homes is low. Data from the low-level residential care population have not been reported. This study aimed to collect information about the treatment of depression among older persons living in low-level residential care (hostels).

Method: The participants comprised 300 elderly residents from ten low-level residential care facilities from various suburbs in metropolitan Melbourne. The participants were interviewed by a trained clinical psychologist to determine the presence or absence of major or minor depressive disorder using the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). Each participant was also administered the Standardized Mini-mental State Examination (SMMSE) to determine level of cognitive function. The clinical psychologist then reviewed all cases in consultation with a geropsychiatrist experienced in the diagnosis of depression among older people, prior to assigning a diagnosis of depression.

Results: An important finding in this study was the low treatment for currently depressed residents, with less than half of those in the sample who were depressed receiving treatment. However, 61 of the 96 residents out of the sample of 300 who were on antidepressants were not currently depressed.

Conclusion: There is an under recognition and under treatment of currently depressed older people in low-level residential care facilities (hostels) just as has been reported in studies in nursing homes. However, there are high numbers receiving antidepressants who are not currently depressed.

Omega 3 fatty acids and the brain : review of studies in depression

The brain is a lipid-rich organ containing mostly complex polar  phospholipids, sphingolipids, gangliosides and cholesterol. These lipids are involved in the structure and function of cell membranes in the brain. The glycerophospholipids in the brain contain a high proportion of  polyunsaturated fatty acids (PUFA) derived from the essential fatty acids, linoleic acid and alpha-linolenic acid. The main PUFA in the brain are docosahexaenoic acid (DHA, all cis 4,7,10,13,16,19-22:6) derived from the omega 3 fatty acid, alpha-linolenic acid, and arachidonic acid (AA, all cis 5,8,11,14-20:4) and docosatetraenoic acid (all cis 7,10,13,16-22:4), both derived from the omega 6 fatty acid, linoleic acid. Experimental studies in animals have shown that diets lacking omega 3 PUFA lead to substantial disturbances in neural function, which in most circumstances can be restored by the inclusion of omega 3 PUFA in the diet. In the past 10 years there has been an emerging interest in treating neuropsychological  disorders (depression and schizophrenia) with omega 3 PUFA. This paper discusses the clinical studies conducted in the area of depression and omega 3 PUFA and the possible mechanisms of action of these PUFA. It is clear from the literature that DHA is involved in a variety of processes in neural cells and that its role is far more complex than simply influencing cell membrane properties.

Does interpersonal psychotherapy improve clinical care for adolescents with depression attending a rural child and adolescent mental health service? Study protocol for a cluster randomised feasibility trial

Background: Depression amongst adolescents is a costly societal problem. Little research documents the effectiveness of public mental health services in mapping this problem. Further, it is not clear whether usual care in such services can be improved via clinician training in a relevant evidence based intervention. One such intervention, found to be effective and easily learned amongst novice clinicians, is Interpersonal Psychotherapy (IPT). The study described in the current paper has two main objectives. First, it aims to investigate the impact on clinical care of implementing Interpersonal Psychotherapy for Adolescents for the treatment of adolescent depression within a rural mental health service compared with Treatment as Usual (TAU). The second objective is to record the process and challenges (i.e. feasibility, acceptability, sustainability) associated with implementing and evaluating an evidence-based intervention within a community service. This paper outlines the study rationale and design for this community based research trial.

Methods/design: The study involves a cluster randomisation trial to be conducted within a Child and Adolescent Mental Health Service in rural Australia. All clinicians in the service will be invited to participate.  Participating clinicians will be randomised via block design at each of four sites to (a) training and delivery of IPT, or (b) TAU. The primary measure of impact on care will be a clinically significant change in depressive  symptomatology, with secondary outcomes involving treatment satisfaction and changes in other symptomatology. Participating adolescents with significant depressive symptomatology, aged 12 to 18 years, will complete assessment measures at Weeks 0, 12 and 24 of treatment. They will also complete a depression inventory once a month during that period. This study aims to recruit 60 adolescent participants and their parent/guardian/s. A power analysis is not indicated as an intra-class correlation coefficient will be calculated and used to inform sample size calculations for subsequent large-scale trials. Qualitative data regarding process implementation will be collected quarterly from focus groups with participating clinicians over 18 months, plus phone interviews with participating adolescents and parent/guardians at 12 weeks and 24 weeks of treatment. The focus group qualitative data will be analysed using a Fourth Generation Evaluation methodology that includes a constant comparative cyclic analysis method.

Discussion: This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting cluster randomised trials within community practice such as mental health services.

Cytochrome bc1 regulates the mitochondrial permeability transition by two distinct pathways

The mitochondrial permeability transition (MPT) pore is a calcium-sensitive channel in the mitochondrial inner membrane that plays a crucial role in cell death. Here we show that cytochrome bc₁ regulates the MPT in isolated rat liver mitochondria and in CEM and HL60 cells by two independent pathways. Glutathione depletion activated the MPT via increased production of reactive oxygen species (ROS) generated by cytochrome bc₁. The ROS producing mechanism in cytochrome bc₁ involves movement of the "Rieske" iron-sulfur protein subunit of the enzyme complex, because inhibition of cytochrome bc₁ by pharmacologically blocking iron-sulfur protein movement completely abolished ROS production, MPT activation, and cell death. The classical inhibitor of the MPT, cyclosporine A, had no protective effect against MPT activation. In contrast, the calcium-activated, cyclosporine A-regulated MPT in rat liver mitochondria was also blocked with inhibitors of cytochrome bc₁. These results indicate that electron flux through cytochrome bc1 regulates two distinct pathways to the MPT, one unregulated and involving mitochondrial ROS and the other regulated and activated by calcium.

Genetic polymorphisms of cytochrome P450 2B6 gene in Han Chinese

Cytochrome P450 (CYP2B6) is an important enzyme that metabolizes more than eight compounds and about 3.0% of therapeutic drugs. The genetic polymorphisms of CYP2B6 have earlier been studied in Caucasian, Japanese and Korean, but the data are lacking for Han Chinese. The aim of this study was to investigate the frequencies of allelic variants of CYP2B6 in healthy Han Chinese and compare with those in other ethnic groups reported in the literature. Polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) method was used to test the five common non-synonymous single nucleotide polymorphisms (SNPs) of CYP2B6 gene, namely, 64C > T, 516G > T, 777C > A, 785A > G and 1459C > T in unrelated healthy Han Chinese (n = 193). The study demonstrated that the frequencies of 64C > T, 516G > T, 777C > A, 785A > G and 1459C > T SNPs in Han Chinese were 0.03, 0.21, 0, 0.28 and 0.003, respectively. The frequencies of all five SNPs tested in female were higher than those in male, but the statistical difference was insignificant (P > 0.05). Compared to the data reported in the literature, the frequencies of common CYP2B6 allelic variants in Chinese are similar to those of other Asian populations including Japanese and Korean, but markedly different from those in Caucasians. These results indicate the presence of marked ethnic difference in CYP2B6 SNP frequencies between Chinese and Caucasian. Further studies are required to explore the impact of these SNPs of CYP2B6 gene on the clinical response (efficacy and toxicity) to drugs that are substrates for CYP2B6 in patients.

Nitric oxide protects against mitochondrial permeabilizastion induced by gluthathione depletion: role of S-nitrosylation?

Nitric oxide (NO) is known to mediate a multitude of biological effects including inhibition of respiration at cytochrome c oxidase (COX), formation of peroxynitrite (ONOO⁻) by reaction with mitochondrial superoxide (O2^{• −}), and S-nitrosylation of proteins. In this study, we investigated pathways of NO metabolism in lymphoblastic leukemic CEM cells in response to glutathione (GSH) depletion. We found that NO blocked mitochondrial protein thiol oxidation, membrane permeabilization, and cell death. The effects of NO were: (1) independent of respiratory chain inhibition since protection was also observed in CEM cells lacking mitochondrial DNA (ρ⁰) which do not possess a functional respiratory chain and (2) independent of ONOO⁻ formation since nitrotyrosine (a marker for ONOO⁻ formation) was not detected in extracts from cells treated with NO after GSH depletion. However, NO increased the level of mitochondrial protein S-nitrosylation (SNO) determined by the Biotin Switch assay and by the release of NO from mitochondrial fractions treated with mercuric chloride (which cleaves SNO bonds to release NO). In conclusion, these results indicate that NO blocks cell death after GSH depletion by preserving the redox status of mitochondrial protein thiols probably by a mechanism that involves S-nitrosylation of mitochondrial protein thiols.

Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs

Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of CYP3A4 is characterised by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYP isoenzymes to reactive metabolites capable of irreversibly binding covalently to CYP3A4. Approaches using in vitro, in silico and in vivo models can be used to study CYP3A4 inactivation by drugs. Human liver microsomes are always used to estimate inactivation kinetic parameters including the concentration required for half-maximal inactivation (K(I)) and the maximal rate of inactivation at saturation (k(inact)).Clinically important mechanism-based CYP3A4 inhibitors include antibacterials (e.g. clarithromycin, erythromycin and isoniazid), anticancer agents (e.g. tamoxifen and irinotecan), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine, verapamil and diltiazem), sex steroids and their receptor modulators (e.g. gestodene and raloxifene), and several herbal constituents (e.g. bergamottin and glabridin). Drugs inactivating CYP3A4 often possess several common moieties such as a tertiary amine function, furan ring, and acetylene function. It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs.Compared with reversible inhibition of CYP3A4, mechanism-based inhibition of CYP3A4 more frequently cause pharmacokinetic-pharmacodynamic drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesised CYP3A4 protein. The resultant drug interactions may lead to adverse drug effects, including some fatal events. For example, when aforementioned CYP3A4 inhibitors are coadministered with terfenadine, cisapride or astemizole (all CYP3A4 substrates), torsades de pointes (a life-threatening ventricular arrhythmia associated with QT prolongation) may occur.However, predicting drug-drug interactions involving CYP3A4 inactivation is difficult, since the clinical outcomes depend on a number of factors that are associated with drugs and patients. The apparent pharmacokinetic effect of a mechanism-based inhibitor of CYP3A4 would be a function of its K(I), k(inact) and partition ratio and the zero-order synthesis rate of new or replacement enzyme. The inactivators for CYP3A4 can be inducers and P-gp substrates/inhibitors, confounding in vitro-in vivo extrapolation. The clinical significance of CYP3A inhibition for drug safety and efficacy warrants closer understanding of the mechanisms for each inhibitor. Furthermore, such inactivation may be exploited for therapeutic gain in certain circumstances.

Elucidation of bucephalid parasite life-cycles using mutation scanning analysis

Nucleotide variation in a portion of the mitochondrial cytochrome c oxidase subunit1 (cox1) gene from asexual stages of bucephalids of southern Australian scallops (Chlamys asperrima, Chlamys bifrons and Pecten fumatus) was investigated using a mutation scanning–sequencing approach. Single-strand conformation polymorphism (SSCP) analysis revealed three main profile types (A, B and C) for parasites isolated from scallops. Sequence analysis revealed that samples represented by profiles B and C had a high degree (97.3%) of sequence similarity, whereas they were ~21% different in sequence from those represented by profile A. These findings suggested that at least two types or species (represented by profile A, or profile B or C) of bucephalid infect scallops, of which both were detected in South Australia, while only one was found in Victoria. The prevalence of bucephalids (and their SSCP haplotypes) appeared to differ among the three species of scallop in South Australia as well as between the two scallop species in Victoria, indicating a degree of host specificity. Adult bucephalids were collected from Eastern Australian Salmon (Arripis trutta), in an attempt to match them with the asexual stages from the scallop hosts. Neither of the two taxa of adult bucephalid (Telorhynchus arripidis and an un-named Telorhynchus species) shared SSCP profiles with the bucephalids from scallops, but were genetically similar, suggesting that the asexual stages from scallops may represent the genus Telorhynchus. This study, which assessed nucleotide sequence variation in a portion of the mitochondrial cox1 gene for bucephalids found in scallops and arripid fish, illustrates the usefulness of the mutation scanning approach to elucidate complex life-cycles of marine parasites.

Yoga as a preventative and treatment for depression, anxiety and stress

With the dual aims of better understanding the contribution of Yoga to positive mental health and exploring links between yogic philosophy and psychological theory, researchers at Deakin University in Melbourne, Australia, conducted a study on Yoga as a preventative and treatment for symptoms of mental illness. The Yoga classes were designed as a six-week program incorporating breathing techniques (prânâyâma), exercises for strength, vitality, and flexibility (âsanas), guided relaxation (yoga-nidrâ), and meditation. The aim of this process was to enhance self-awareness, encourage the perspective that emotional states are somewhat transient, and encourage a self-accepting and calm attitude through concentrating on synchronizing gentle movements and breathing. By developing calmness, selfacceptance, a balanced perspective, and enhanced concentration it was hypothesized that participants in the six-week Yoga program would strengthen their resistance to emotional distress. Psychometric testing was carried out to assess symptoms of stress, anxiety, and depression across three groups: regular Yoga practitioners, beginners entering the program, and people who did not practice Yoga, and these tests were re-administered after six weeks. In addition, a strong sense of intrinsic spiritual experience has been cited as a possible buffer to stress, anxiety, and depression and has been associated with decreased frequency of medical symptoms. All participants were therefore also assessed on their sense of intrinsic spirituality, but not on religious beliefs. At the end of six weeks, the Yoga beginners group showed lower average levels of symptoms of depression, anxiety, and stress than at commencement, but levels were stable for regular Yoga practitioners and people who did not practice Yoga. In addition, beginners showed growth in their self-reported level of intrinsic spiritual experience.

Subjective well-being as an indicator for clinical depression

The Theory of Homeostasis posits that Subjective Well-being (SWB) is regulated by a dynamic biological mechanism, assisting to maintain a positive view of life. Further, the theory suggests that clinical depression is the loss of SWB due to the defeat of this homeostatic defence system. To test this hypothesis it was predicted that people who were diagnosed as clinically depressed with the Semi-structured Clinical Interview (SCID-1/NP) based on the DSM-IV-TR Axis 1 would have a Personal Well-being Index-Adult (PWI-A) score below the normative range (70–80% of scale maximum). Following ethical approval a sample of 146 men was obtained and each was assessed on the SCID-1/NP and on the PWI-A. Subjects diagnosed as having one of several pathologies such as post traumatic stress disorder, panic disorder, social phobia and specific phobia were found to score significantly lower on the PWI-A compared to participants who received no diagnosis. However, as the data did not discriminate between currently depressed and persons with other non-depressive psychopathologies, a Receiver Operating Characteristics (ROC) curve analysis was used to explore this data further. Results indicated that the PWI-A was significantly better than guessing in discriminating clinically depressed cases, but only just so. Therefore, while this research found support for the proposition that the loss of SWB indicated clinical depression, the PWI-A is not sufficiently specific for diagnosis, nor can it be concluded that all instances of depression is the failure of SWB.