Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43-kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems.
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PMID:Paracoccidioidomycosis: an update. 847 49

Patients with immune depression are at increased vulnerability to a variety of mycotic infections. These range from mucosal and disseminated candidiasis to invasive aspergillosis to regional mycoses, such as histoplasmosis and Penicillium morneffei, and the emerging mycoses including zygomycetes, phaeohyphomycetes, Fusarium sp, Trichosporon sp, and others. An increasing variety of antifungal drugs, among which are fluconazole and itraconazole, are used for the treatment of these opportunistic infections. Fluconazole has excellent absorption, linear renal excretion of largely active drug, and limited spectrum, primarily against yeast pathogens such as Candida sp. In its capsule formulation, itraconazole has broader activity, including mycelial pathogens, but suffers from irregular absorption, lack of intravenous formulation, and complex hepatic excretion. Itraconazole has recently undergone reformulation as a solution, which gives significant added advantages in bioavailability and increases the practical applications. It is at present unclear whether voriconazole, SCH56592, or itraconazole solution will be equally potent and have a similar range of applications.
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PMID:Itraconazole: managing mycotic complications in immunocompromised patients. 967 33

In this study, the binding and enzyme activity inhibitory effect of nano-TiO(2) on pepsin was explored compared with micro-TiO(2). Nano-TiO(2) was about 60 nm and micro-TiO(2) was about 200 nm, both round in shape. The activity of pepsin was depressed significantly by nano-TiO(2) comparing to micro-ones. The results of UV spectrometry, HPLC, SDS-PAGE and CD assay proved that micro-TiO(2) has only physical absorption effect on pepsin, but no impairment on primary sequences or secondary structure. However, nano-TiO(2) had coordination interaction with pepsin besides physical binding effect. The secondary structure of pepsin was unfolded with the treatment of nano-TiO(2) at pH 6.5 and pH 3.53, which might consequently affect the beta-hairpin loop that protects the active center of pepsin, and then reduce the enzyme activity. Furthermore, the thermodynamic mechanisms of interaction between nano-TiO(2) and pepsin were explored by fluorescence spectrum and ITC analysis. According to the results of thermodynamic analysis, the K value was 3.64x10(6), stoichiometry (N(pepsin:nano-TiO2)) was 3.04x10(3), the total DeltaH was -2277 cal/mol, DeltaS was 22.7 cal/(K mol), therefore the nano-TiO(2)-pepsin interaction is spontaneous. The depression of activity and the unfolding of secondary structure of pepsin were resulted from non-covalent reactions, including electrostatic force and hydrophobic binding. This work studied the different inhibitory effects and revealed mechanisms of the interaction between micro/nano-TiO(2) and pepsin, and provided a useful approach for evaluating the health risk of nano-materials on level of proteins.
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PMID:Enzyme activity inhibition and secondary structure disruption of nano-TiO2 on pepsin. 2054

A 3 yr old intact female Hellenic shepherd dog was referred due to depression, partial anorexia, fever, and a mild productive cough of 2 mo duration. Thoracic radiographs showed increased opacity of all of the left lung lobes. Upon bronchoscopy, a sanguineous, purulent discharge was detected in the tracheal lumen with hyperplastic tissue narrowing the left main stem bronchus. Cultures were positive for bacteria (Bacillus spp. and Clostridium spp.) but negative for fungi. Due to the severity of the lesions, a complete left lung pneumonectomy was performed. Histopathological examination of the excised lung tissues revealed a severe granulomatous bronchopneumonia with numerous alveolar macrophages laden with structures stained positively by periodic acid-Schiff and Grocott stain that had morphology consistent with fungi. PCR and sequencing of internal transcribed spacer regions 1 and 2 from genetic material extracted from paraffin-embedded pulmonary tissue confirmed the presence of Aspergillus fumigatus. Itraconazole was administrated for 5.5 mo and the dog was clinically normal 26 mo after surgery.
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PMID:Aspergillus fumigatus Bronchopneumonia in a Hellenic Shepherd Dog. 2135 14

GABAergic intercalated neurons of amygdala (ITCs) have recently been shown to be important in the suppression of fear-like behavior. Effects of ECa233 (a standardized extract of Centella asiatica), previously demonstrated anxiolytic activity, were then investigated on ITCs. Cluster of GABAergic neurons expressing fluorescence of GFP was identified in GAD67-GFP knock-in mice. We found that neurons of medial paracapsular ITC were GABAergic neurons exhibiting certain intrinsic electrophysiological properties similar to those demonstrated by ITC neurons at the same location in C57BL/6J mice. Therefore, we conducted experiments in both C57BL/6J mice and GAD67-GFP knock-in mice. Excitatory postsynaptic currents (EPSCs) were evoked by stimulation of the external capsule during the whole cell patch-clamp recordings from ITC neurons in brain slices. ECa233 was found to increase the EPSC peak amplitude in the ITC neurons by about 120%. The EPSCs in ITC neurons were completely abolished by the application of an AMPA receptor antagonist. Morphological assessment of the ITC neurons with biocytin demonstrated that most axons of the recorded neurons innervated the central nucleus of the amygdala (CeA). Therefore, it is highly likely that anxiolytic activity of ECa233 was mediated by increasing activation, via AMPA receptors, of excitatory synaptic input to the GABAergic ITC leading to depression of CeA neurons.
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PMID:Modulation of Neuronal Activity on Intercalated Neurons of Amygdala Might Underlie Anxiolytic Activity of a Standardized Extract of Centella asiatica ECa233. 2984 6

Human brain derived neurotrophic factor (BDNF) encodes a protein product consisting of a C-terminal mature domain (mature BDNF) and an N-terminal prodomain, which is an intrinsically disordered protein. A common single nucleotide polymorphism in humans results in a methionine substitution for valine at position 66 of the prodomain, and is associated with memory deficits, depression and anxiety disorders. The BDNF Met66 prodomain, but not the Val66 prodomain, promotes rapid structural remodeling of hippocampal neurons' growth cones and dendritic spines by interacting directly with the SorCS2 receptor. While it has been reported that the Met66 and Val66 prodomains exhibit only modest differences in structural propensities in the apo state, here we show that Val66 and Met66 prodomains differentially bind zinc (Zn). Zn2+ binds with higher affinity and more broadly impacts residues on the Met66 prodomain compared to the Val66 prodomain as shown by NMR and ITC. Zn2+ binding to the Met66 and Val66 prodomains results in distinct conformational and macroscopic differences observed by NMR, light scattering and cryoEM. To determine if Zn2+ mediated conformational change in the Met66 prodomain is required for biological effect, we mutated His40, a Zn2+ binding site, and observed a loss of Met66 prodomain bioactivity. As the His40 site is distant from the known region of the prodomain involved in receptor binding, we suggest that Met66 prodomain bioactivity involves His40 mediated stabilization of the multimeric structure. Our results point to the necessity of a Zn2+-mediated higher order molecular assembly of the Met66 prodomain to mediate neuronal remodeling.
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PMID:Zinc induced structural changes in the intrinsically disordered BDNF Met prodomain confer synaptic elimination. 3274 73