Unraveling the diagnostic clues of depression and GAD: the primary care challenge

Anxiety and depression are commonly encountered in primary care, with a prevalence ranging from 5% to 10%. These disorders are associated with significant and persistent impairment in functioning, risk of suicide, and substantial economic cost. Comorbidity of depression and anxiety is frequent and intensifies the burden of illness. However, patients with anxiety and depression often present to primary care physicians (PCPs) with ill-defined somatic symptoms, and both disorders are under-recognized and under-treated. PCPs should be aware that the typical presentation of anxiety and depression may not be with classical psychological symptoms, but rather with vague somatic symptoms that are often hard to treat and result in frequent repeat visits. Once anxiety and depression are accurately recognized, most patients can successfully be managed in primary care. A wide range of effective drugs is available, allowing selection of an optimal treatment for each patient. Antidepressants are effective as monotherapy in comorbid patients, and newer agents such as selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors have been shown to be effective in the treatment of anxiety and depression. Adherence to medication can be improved if drug treatment is integrated into a package of patient education and support. PCPs have a vital role to play in identifying anxiety and depression amongst their patients, and building a therapeutic partnership to achieve successful treatment.     

14'-Hydroxymytoxin B and 16-hydroxyroridin E,two new cytotoxic trichothecenes from Myrothecium roridum

Two new trichothecenes, 14'-hydroxymytoxin B (1) and 16-hydroxyroridin E (3), were isolated from a fermentation extract of Myrothecium roridum. The structures of 1 and 3 were determined by spectral data interpretation. Both compounds showed potent cytotoxic activity against primary soft-tissue sarcoma cells.     

Fluorescent zinc indicators for neurobiology

Mounting evidence indicates that zinc has multiple roles in cell biology, viz. as a part of metalloenzyme catalytic sites, as a structural component of gene regulatory proteins, and (like calcium) as a free signal ion, particularly in the cortex of the brain. While most Zn(II) in the brain is tightly bound, such that free Zn(II) levels extracellularly and intracellularly are likely to be picomolar, a subset of glutamatergic neurons possess weakly bound zinc in presynaptic boutons which is released at micromolar levels in response to a variety of stimuli. Key to further progress in understanding the multiple roles of zinc will be the availability of fluorescent indicator systems that will permit quantitative determination and imaging of zinc fluxes and levels over a broad concentration range both intracellularly and extracellularly using fluorescence microscopy. Towards that end, we have compared a variety of fluorescent indicators for their sensitivity to Zn(II) and Cu(II), selectivity for Zn(II) in the presence of potential interferents such as Ca(II) or Mg(II), and potential for quantitative imaging. The commercially available probes Fura-2, Mag-Fura-5, Newport Green DCF, and FuraZin-1 were compared with the carbonic anhydrase-based indicator systems for selectivity and sensitivity. In addition, intracellular levels of Zn following excitotoxic insult were determined by single pixel fluorescence lifetime microscopy of Newport Green DCF, and extracellular levels of free zinc following stimulus of rat hippocampal slices were determined ratiometrically with a carbonic anhydrase-based indicator system. These results suggest that zinc ion at high nM to microM levels can be accurately quantitated by FuraZin-1 ratiometrically or by Newport Green DCF by fluorescence lifetime; and at levels down to pM by intensity ratio, lifetime, or polarization using carbonic anhydrase-based systems.     

Biodirected epitaxial nanodeposition of polymers on oriented macromolecular templates

Biodirected epitaxial nanodeposition of polymers was achieved on a template with an oriented molecular surface. Acetobacter xylinum synthesized a ribbon of cellulose I microfibrils onto a fixed, nematic ordered substrate of glucan chains with unique surface characteristics. The substrate directed the orientation of the motion due to the inverse force of the secretion during biosynthesis, and the microfibrils were aligned along the orientation of the molecular template. Using real-time video analysis, the patterns and rates of deposition were elucidated. Field emission scanning electron microscopy revealed that a strong molecular interaction allowed for the deposition of nascent biosynthesized 3.5-nm cellulose microfibrils with inter-microfibrillar spacings of 7-8 nm on the surface of the template. The cellulose was deposited parallel to the molecular orientation of the template. Directed cellulose synthesis and ordered movement of cells were observed only by using a nematic ordered substrate made from cellulose, and not from ordered crystalline cellulose substrates or ordered cellulose-related synthetic polymers such as polyvinyl alcohol. This unique relationship between directed biosynthesis and the ordered fabrication from the nano to the micro scales could lead to new methodologies for the design of functional materials with desired nanostructures.     

Identification of the glutathione conjugate of 4-nitroquinoline 1-oxide formed in the reaction catalyzed by murine glutathione transferases

The product of the enzyme-catalyzed conjugation of glutathioneand 4-nitroquinoline 1-oxide was isolated and its structuredetermined by MS and NMR. The results indicate that the cysteinesulfur of glutathione replaces the nitro group of 4-nitroquinoline1-oxide in the reaction with the formation of 4-(glutathion-S-yI)-quinoline1-oxide. No evidence was found for the binding of glutathioneto any other position of 4-nitroquinoline 1-oxide or throughany group other than the cysteine sulfur.