Bệnh loãng xương là gì? Các công bố khoa học về Bệnh loãng xương

We describe the case of a 55-year-old woman initially diagnosed with locally advanced rectal cancer and one synchronous hepatic metastasis in 1998 who was treated by neoadjuvant chemotherapy and chemoradiotherapy followed by resection of the rectum and simultaneous atypical liver resection. After complete remission for about 4 years, the patient metachronously developed two local relapses and a liver metastasis, which were curatively treated by means of either radical resection or local ablative therapies and chemotherapy. Since the patient has refused radical resection of pulmonary metastases in November 2010, she is under palliative chemotherapy and is still alive. This case illustrates that a multimodality treatment can provide long-term survival in patients with metastasized colorectal cancer.

A minimal filling of a finite metric space is a weighted graph of a minimal possible weight spanning this space so that the weight of any path in it is not less than the distance between its ends. Bifurcation diagrams of types and the weight of minimal fillings for four points of the Euclidean plane are built in the present work.

“Phages” include viruses of eubacteria and archaea. At least 5568 phages have been examined in the electron microscope since the introduction of negative staining in 1959. Most virions (96%) are tailed. Only 208 phages (3.7%) are polyhedral, filamentous, or pleomorphic. Phages belong to one order, 17 families, and three “floating” groups. Phages are found in 11 eubacterial and archaeal phyla and infect 154 host genera, mostly of the phyla Actinobacteria, Firmicutes, and Proteobacteria. Of the tailed phages, 61% have long, noncontractile tails and belong to the family Siphoviridae. Convergent evolution is visible in the morphology of certain phage groups.

Purpose. The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. Methods. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in bio-relevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. Results. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0, and 7.4 relative to marketed dose strengths in 250 ml. The pK a values for the acidic NSAIDs studied were between 3.5 and 5.1, and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen, and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs (high solubility-high permeability) relative to solubility at pH 7.4. The use of bio-relevant media simulating gastric and intestinal milieu for solubility measurements or increasing the dose volume to 500 ml did not provide for a better boundary for solubility classification. Conclusions. Based on the current definition of solubility, 15 of the 18 acidic NSAIDs in this study will be classified as Class II compounds as the solubility criteria applies to the entire pH range of 1.2 to 7.4, although the low solubility criteria does not hold true over the entire pH range. Whence, of the 18 acidic drugs, 15 can be classified as Class I based on the pH 7.4 solubility alone. This finding is intriguing because these drugs exhibit Class I behavior as their absorption does not seem to be dissolution or solubility limited. It could then be argued that for acidic drugs, the boundaries for solubility are too restrictive. Solubility at pH > 5 (pH in duodenum) may be more appropriate because most compounds are mainly absorbed in the intestinal region. Consideration for an intermediate solubility classification for highly permeable ionizable compounds that reflects physiological conditions seems warranted.

One typically disturbs a system from equilibrium and studies its behavior to understand its stability. This procedure gives insight into the dynamics at play. It is one of the few techniques used in all areas of physics, be it Newtonian mechanics, quantum mechanics, or general relativity. We have continued this effort by disturbing black holes. We will see that a black hole chimes like a bell when it is disturbed. We will study this chiming mathematically in Schwarzschild black holes.