Confocal Laser Scanning Microscopic Studies on Alveolar Bone Remodeling with Orthodontic Tooth Movement and Retention

Alveolar bone reconstruction in growing dog during the retention period following orthodontic tooth movement was studied. Three beagle dogs (8-10 kg body weight, about one-year-old) were used and two of the animals were subjected to histological observation. The upper 2nd and lower 3rd premolars on both sides were extracted prior to the orthodontic treatments. After a healing period of one month, the upper 3rd premolar and the lower 4th premolar on the right side were moved mesially with a conventional orthodontic force for 8 weeks, and then retained in their new position for 4 weeks. The contralateral corresponding premolars were used as control. The alveolar bone was double-labeled with tetracycline (TC) during the movement and calcein (Cal) during the retention period. Alveolar bone structure and labeling patterns were examined by contact microradiography, conventional fluorescence microscopy, and confocal laser scanning microscopy (CLSM). Optimizing the separation of TC and Cal labelings in the alveolar bone was attained by the simultaneous use of ultraviolet (364 nm) and argon (488 nm) laser sources for excitation of TC and Cal, respectively. Cal labeling, indicative of new bone deposition showed two distinct patterns: lamination at the periodontal surface and rings circumscribing the vascular canal. The cementum surface also exhibited active deposition during the experimental period. Bone formation was affected by slight changes in magnitude and direction of orthodontic or occlusal forces. CLSM is valuable in deciphering the process of alveolar bone remodeling

Photoelectron angular distribution studies for two spin\u2013orbit-split components of Xe 3d subshell: a critical comparison between theory and experiment

The photoelectron angular distribution asymmetry parameters \u3b2 of the Xe 3d subshell were investigated using an x-ray free-electron laser (XFEL) at photon energies of 750 and 800 eV. Owing to the perfect polarization of the XFEL and two-dimensional momentum imaging capability of our velocity map imaging spectrometer, we determined the \u3b2 values with high accuracy. The \u3b2 values were also investigated based on relativistic time-dependent density functional theory calculations of up to 900 eV of photon energies. By comparing all the available experimental results including our data with the most reliable theories on the photon energy dependence of the \u3b2 parameters, serious differences are noted between the experiments and theories. Further studies on resolving this difference will provide new insight into the photoionization processes of the deep inner shells

Towards a new tuberculosis drug: pyridomycin - nature's isoniazid

Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an important source of antibiotics including potent anti-tuberculosis agents. Here, we describe pyridomycin, a compound produced by Dactylosporangium fulvum with specific cidal activity against mycobacteria. By selecting pyridomycin-resistant mutants of Mycobacterium tuberculosis, whole-genome sequencing and genetic validation, we identified the NADH-dependent enoyl(Acyl-Carrier-Protein) reductase InhA as the principal target and demonstrate that pyridomycin inhibits mycolic acid synthesis in M. tuberculosis. Furthermore, biochemical and structural studies show that pyridomycin inhibits InhA directly as a competitive inhibitor of the NADH-binding site, thereby identifying a new, druggable pocket in InhA. Importantly, the most frequently encountered isoniazid-resistant clinical isolates remain fully susceptible to pyridomycin, thus opening new avenues for drug development

Broccoli or Sulforaphane:Is It the Source or Dose That Matters?

There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population