A new class of antituberculosis agents

Long-chain lipid envelopes are characteristic of mycobacteria such as those that cause tuberculosis and leprosy. Inhibition of fatty acid synthesis or elongation is a strategy demonstrated to be clinically effective against M. tuberculosis. A new class of compounds designed to inhibit the beta-ketoacyl synthase reaction of fatty acid synthesis has been developed. Of >30 compounds described, the most active were acetamides containing alkylsulfonyl substituents. Inhibitory activities were acutely sensitive to net charge, chain length, and degree of unsaturation. The most active compound 5 (alkyl = C(10)) contained a single methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75-1.5 microg/mL, comparable to first-line antituberculosis drugs. These compounds are species-specific, exhibiting no significant activity against bacterial species other than M. tuberculosis and closely related strains. The synthesis, biological activity, and specificity of these compounds are described.     

Metal chelators as antiviral agents

Processes involving the creation and modification of oligomeric nucleotide substrates are key events in the replication cycles of many viruses, and have been successful targets for much pharmaceutical research. Because of high levels of intracellular divalent magnesium, and the high affinity of oxyanions for this hard Lewis acid, enzymes responsible for these transformations have evolved to use the divalent magnesium cation in their catalytic function. The interruption of enzyme function via active-site metal coordination has recently emerged as a viable approach to viral inhibition, and the most advanced programs in this field have now entered late-stage clinical trials, thus validating the approach. This review summarizes such programs that were initiated from alpha,gamma-diketo acid leads and that resulted in optimized candidates. Key relationships between structure and activity for successful high-affinity magnesium binding in the active site of these enzymes have been identified.     

Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD)

BACKGROUND: Brain activation differences between 12 control and 12 attention deficit hyperactivity disorder (ADHD) children (9- to 12-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). METHOD: Visual selective attention was measured with the visual search of a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go/no-go task. RESULTS: There were limited group differences in the selective attention task, with control children showing significantly greater intensity of activation in a small area of the superior parietal lobule region of interest. There were large group differences in the response inhibition task, with control children showing significantly greater intensity of activation in fronto-striatal regions of interest including the inferior, middle, superior and medial frontal gyri as well as the caudate nucleus and globus pallidus. CONCLUSION: The widespread hypoactivity for the ADHD children on the go/no-go task is consistent with the hypothesis that response inhibition is a specific deficit in attention deficit hyperactivity disorder.     

Priming effects in the fusiform gyrus: changes in neural activity beyond the second presentation

Repetition priming typically leads to a decrease in the activation of sensory cortical areas upon a second exposure to the same visual stimulus. This effect is thought to reflect more efficient or fluent re-processing of previously seen stimuli so that less neural activity is required. Fluent re-processing has been hypothesized to be a potential link from repetition priming to neural changes associated with visual expertise. To examine this potential connection, the neural correlates of priming were examined across eight stimulus repetitions using functional magnetic resonance imaging. Sizeable regions of bilateral ventral occipito-temporal cortex (including the fusiform gyrus) exhibited reduced responses to the second presentation of a stimulus. Most of these areas displayed no further reduction in response to subsequent repetitions of the same stimuli. Because expertise accrues over many exposures, these areas, while clearly involved in priming, do not exhibit an activity pattern consistent with the development of expertise. In contrast, an area in the right posterior fusiform gyrus exhibited reductions in evoked response that grew in magnitude for stimulus repetitions from the second to the eighth presentations. This region exhibits a pattern of activity consistent with a gradual and cumulative enhancement of the fluency effect across trials, suggesting that it may mediate the link between priming and the development of visual expertise.     

Pulmonary cystic hydatid disease in Ireland

Background Hydatid disease is rare in Ireland and its incidence and prevalence are unknown. Most cases are diagnosed by a combination of clinical findings, morphological features on imaging and by serological testing. Aims We describe an Irish case of pulmonary hydatid disease detected at bronchoscopy by bronchoalveolar lavage, and discuss the diagnosis and treatment of the disorder.     

BACTEC MGIT 960培养结合INNO-LIPA~(TM) RIF.TBDNA探针新技术快速诊断结核病

目的通过MGIT960培养系统结合国外最新的INNO -LIPATM RIF.TB(LIPA)DNA探针技术的应用 ,探讨其快速诊断结核病的可行性。方法应用BACTECMGIT960系统进行临床疑似结核病例标本的培养 ,筛选了70例结核分枝杆菌 ,35例非结核分枝杆菌 ,用LIPA探针技术诊断是否为结核分枝杆菌。结果用LIPADNA方法在70例结核分枝杆菌中获得阳性69例 ,占98.6 % ;35例非结核分枝杆菌均为阴性。与单纯消化纯化后涂片的82.9 % (58/70)的阳性率相比增加了15.7个百分点 ,两者在统计学上差异有显著性(P<0.05)。BactecMGIT960培养结合LIPADNA探针与传统诊断方法4～8周相比 ,整个过程只需6～37天 ,平均15天 (2周 )。结论LIPADNA探针是一种具有高度敏感性和特异性、能够简便、快速、准确地诊断结核病的新技术。同时还能鉴定rpoβ 基因位点的突变 ,诊断耐利福平 (RMP)性结核 ,有望适用于结核分枝杆菌耐RMP性结核的快速检测 ,进一步为结核病快速准确的治疗提供理论依据。     

Anxiety-control strategies: Is there room for neutralization in successful exposure treatment?

Cognitive-behavioral theory suggests that anxiety-control strategies such as neutralization, distraction and various forms of safety behavior have the potential to diminish the effectiveness of and/or interfere with exposure treatment. Yet, it is common practice when treating individuals with anxiety disorders to employ various anxiety-control strategies as a means of assisting clients/patients with difficult exposure situations. Questions surrounding the issue of which anxiety-control strategies help vs. hinder exposure-based treatments (and under which circumstances) have been a topic of much investigation and continue to be a focus of theoretical debate. The present article reviews several key studies which collectively shed some light on this debate. The evidence suggests that clients' anxiety-control strategies may be less likely to become counter-productive when: (i) they promote increases in self-efficacy, (ii) they do not demand excessive attentional resources, (iii) they enable greater approach behavior and integration of corrective information (via 'disconfirmatory experiences'), and (iv) they do not promote misattributions of safety. Theoretical and clinical implications of these findings are discussed, and future directions for research in this area are suggested.