Blue integumentary structural colours in dragonflies (Odonata) are not produced by incoherent Tyndall scattering.
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For nearly 80 years, the non-iridescent, blue, integumentary structural colours of dragonflies and damselflies (Odonata) have been attributed to incoherent Tyndall or Rayleigh scattering. We investigated the production of the integumentary structural colours of a damselfly--the familiar bluet, Enallagma civile (Coenagrionidae)--and a dragonfly--the common green darner, Anax junius (Aeshnidae)--using fibre optic spectrophotometry and transmission electron microscopy (TEM). The reflectance spectra of both species showed discrete reflectance peaks of approximately 30% reflectance at 475 and 460 nm, respectively. These structural colours are produced by light scattering from closely packed arrays of spheres in the endoplasmic reticulum of box-shaped epidermal pigment cells underlying the cuticle. The observed reflectance spectra do not conform to the inverse fourth power relationship predicted for Tyndall/Rayleigh scattering. Two-dimensional (2-D) Fourier analysis of the TEM images of the colour-producing arrays reveals ring-shaped distributions of Fourier power at intermediate spatial frequencies, documenting a quasiordered nanostructure. The nanostructured Fourier power spectra falsify the assumption of spatial independence of scatterers that is required for incoherent scattering. Radial averages of the Fourier power spectrum indicate that the spheres are substantially nanostructured at the appropriate spatial scale to produce visible colours by coherent scattering. However, the spatial periodicity of the arrays is apparently too large to produce the observed colour by coherent scattering. The nanospheres could have expanded substantially (approximately 50%) during preparation for TEM. Alternatively, coherent light scattering could be occurring both from the surfaces and from structures at the centre of the spheres. These arrays of colour-producing spheres within pigment cells have convergently evolved at least 11-14 times independently within the Odonata. Structural colouration from arrays in living cells has also fostered the convergent evolution of temperature-dependent colour change in numerous odonate lineages. (+info)
Cloud point extraction and preconcentration for the gas chromatography of phenothiazine tranquilizers in spiked human serum.
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Cloud point extraction was successfully applied to the preconcentration of phenothiazine derivatives, such as pericyazine (PC), chlorpromazine (CP) and fluphenazine (FUL), for gas chromatography (GC). Phenothiazine derivatives were separated from surfactants by passing the surfactant-rich phase through a cation exchange column after cloud point extraction, permitting the determination of the phenothiazine derivatives extracted in the surfactant-rich phase by GC. The optimal condition for the cloud point extraction of phenothiazine derivatives was also investigated using Triton X-100, Triton X-114, and PONPE10. Triton X-114 provided the most efficient recovery of phenothiazine derivatives among the surfactants used. The addition of sodium chloride and excess ammonia to the sample solution resulted in a decrement of the recovery of the phenothiazine derivatives. The proposed method was applied to the determination of phenothiazine derivatives in spiked human serum by GC. The recoveries of PC, CP, and FUL in spiked human serum were 95.1%, 87.1%, and 84.7%, respectively. (+info)
Interaction between cardiac calsequestrin and drugs with known cardiotoxicity.
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Ca(2+) regulation is coupled to critical signals in eucaryotic cells, and calsequestrin is one of the crucial components for this calcium regulation. Our previous observations of calsequestrins revealed the existence of three thioredoxin-like folds, a basic motif that often provides the platform for small molecule binding. Therefore, we have examined the previously reported trifluoperazine and other pharmaceuticals that have similar heart-related side effects (such as tachycardia; bradycardia; palpitation; changing PR, QRS, QTc intervals in electrocardiogram; heart failure) for their binding affinity to cardiac calsequestrin (cCSQ) using isothermal titration calorimetry. Our results showed that several antipsychotic phenothiazine derivatives, tricyclic antidepressants, and anthracycline derivatives bind cCSQ with K(d) in the micromolar range. For these compounds that have a significantly low K(d), their effect on Ca(2+) binding capacity of cCSQ was checked using equilibrium dialysis and atomic absorption spectroscopy, which clearly showed a significant reduction in Ca(2+) binding capacity of cCSQ as a result of this interaction. Furthermore, 8-anilino-1-naphthalene sulfonate (ANS) binding to cCSQ closely resembles ANS binding to flavine or nucleotide binding sites. The combination of this information with the high abundance of CSQ in SR and the high membrane permeability of those drugs led us to the specific hypothesis that there are undesirable and damaging interactions between cCSQ and tricyclic antidepressants, phenothiazine derivatives, anthracyclines, and many other pharmaceutical compounds and to the corollary hypothesis that better understanding of the molecular details of cCSQ-drug interactions could lead to modified drug molecules with reduced heart-related side effects. (+info)
Weight gain and new onset diabetes associated with olanzapine and risperidone.
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OBJECTIVE: To assess whether newer antipsychotic medications are associated with weight gain and development of diabetes. DESIGN: Retrospective cohort study. SETTING: Data from a comprehensive electronic medical record serving an urban public hospital and a citywide network of mental health clinics. PATIENTS/PARTICIPANTS: Three thousand one hundred fifteen patients at least 18 years old who were prescribed a single antipsychotic drug for at least 1 year. METHODS: We identified independent predictors of significant weight gain (> or =7%) and new onset of diabetes mellitus in the first year of antipsychotic drug treatment, using logistic regression adjusted for demographic characteristics, obesity, preexisting psychiatric diagnoses, alcohol and drug abuse, number of primary care, psychiatric clinic, and emergency department visits, and pretreatment weight. MEASUREMENTS AND MAIN RESULTS: Twenty-five percent of patients taking older phenothiazines developed significant weight gain in the first year of treatment compared to 40% of the patients taking olanzapine (adjusted odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7 to 4.6; P <.0001) and 37% of patients taking risperidone (adjusted OR, 2.3; 95% CI, 1.5 to 3.4; P <.0001). New diabetes developed in 3% of patients taking older phenothiazines was new onset diabetes compared to 8.0% of patients taking olanzapine (adjusted OR, 1.9; 95% CI, 1.1 to 3.3; P=.03) and 3.5% of patients taking risperidone (adjusted OR, 0.7; 95% CI, 0.4 to 1.4; P=.3). No association was found between significant weight gain and developing diabetes (adjusted OR, 0.7; 95% CI, 0.4 to 1.4; P=.4). CONCLUSIONS: Olanzapine and risperidone use was associated with gaining weight in the first year, but only olanzapine was associated with developing diabetes mellitus. (+info)
Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins.
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Tau protein is the major component of the intraneuronal filamentous inclusions that constitute defining neuropathological characteristics of Alzheimer's disease and other tauopathies. The discovery of tau gene mutations in familial forms of frontotemporal dementia has established that dysfunction of the tau protein is sufficient to cause neurodegeneration and dementia. Here we have tested 42 compounds belonging to nine different chemical classes for their ability to inhibit heparin-induced assembly of tau into filaments in vitro. Several phenothiazines (methylene blue, azure A, azure B, and quinacrine mustard), polyphenols (myricetin, epicatechin 5-gallate, gossypetin, and 2,3,4,2',4'-pentahydroxybenzophenone), and the porphyrin ferric dehydroporphyrin IX inhibited tau filament formation with IC(50) values in the low micromolar range as assessed by thioflavin S fluorescence, electron microscopy, and Sarkosyl insolubility. Disassembly of tau filaments was observed in the presence of the porphyrin phthalocyanine. Compounds that inhibited tau filament assembly were also found to inhibit the formation of Abeta fibrils. Biochemical analysis revealed the formation of soluble oligomeric tau in the presence of the inhibitory compounds, suggesting that this may be the mechanism by which tau filament formation is inhibited. The compounds investigated did not affect the ability of tau to interact with microtubules. Identification of small molecule inhibitors of heparin-induced assembly of tau will form a starting point for the development of mechanism-based therapies for the tauopathies. (+info)
Antimicrobial activity of phenothiazines.
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Multidrug-resistant Mycobacterium tuberculosis (MDRTB) and antibiotic-resistant Plasmodium falciparum are the major global lethal infections accounting for over 4 million deaths per year. Methicillin-resistant Staphylococcus aureus (MRSA) is the major global nosocomial infection and resistance to vancomycin is evident and may become common. This review provides the scientific and medical basis that support the use of one particular group of compounds, the phenothiazines, and in particular thioridazine, for the management of the above antibiotic-resistant infections. Because thioridazine, a relatively mild neuroleptic as compared to its parental compound chlorpromazine, kills intracellular MDRTB and MRSA at clinical concentrations, its use for the management of these infections may be considered. The review also discusses the activity of phenothiazines against protozoa and parasites, the mechanisms by which phenothiazines promote their antimicrobial effects, their potential for regulating efflux pumps that are a cause for mono or multidrug resistance, as well as their potential for the therapy of problematic infections caused by bacteria that have acquired plasmid-antibiotic-resistant genes. (+info)
Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs.
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Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. Analysis of the Mtb genome predicts the existence of a branched aerobic respiratory chain terminating in a cytochrome bd system and a cytochrome aa(3) system. Both chains can be initiated with type II NADH:menaquinone oxidoreductase. We present a detailed biochemical characterization of the aerobic respiratory chains from Mtb and show that phenothiazine analogs specifically inhibit NADH:menaquinone oxidoreductase activity. The emergence of drug-resistant strains of Mtb has prompted a search for antimycobacterial agents. Several phenothiazines analogs are highly tuberculocidal in vitro, suppress Mtb growth in a mouse model of acute infection, and represent lead compounds that may give rise to a class of selective antibiotics. (+info)
The in vitro activity of phenothiazines against Mycobacterium avium: potential of thioridazine for therapy of the co-infected AIDS patient.
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Patients presenting with Acquired Immune Deficiency Syndrome (AIDS) are predisposed to co-infection with Mycobacterium avium. The management of such patients is problematic due to underlying immuno-incompetence and the high resistance of M. avium to most non-toxic compounds. Therefore, the need for effective agents is obvious. Because phenothiazines, especially the relatively mild thioridazine, have significant activity against Mycobacterium tuberculosis, we investigated the in vitro activity of chlorpromazine, thioridazine, promazine, promethazine and desipramine against a reference and clinical strains of M. avium. The results obtained show that whereas all of the phenothiazines employed in this study had an minimum inhibitory concentration (MIC) against the strains studied that ranged from ca. 10 to > 50 mg/L, as was previously shown for M. tuberculosis, thioridazine was the most active of the group against M. avium. (+info)