健康管理模式下药学服务的实践

通过论述与比较药学服务和健康管理的理念,分析两者在提出背景、实施过程中的内在联系,探讨如何结合健康管理模式,拓宽药学服务的内容,加强药学服务的实践。     

Bifurcated intraarticular long head of biceps tendon

Though rare, many anomalous origins of long head of the biceps tendon (LHBT) have been reported in the literature. Anatomic variations commonly explained are a third humeral head, anomalous insertion, congenital absence and adherence to the rotator cuff. We report a rare case who underwent shoulder arthroscopy with impingement symptoms where in LHBT was found to be bifurcated with a part attached to superior labrum and the other part to the posterior capsule of joint. Furthermore, intraarticular portion of LHBT was adherent to the undersurface of the supraspinatus tendon. Awareness of such an anatomical aberration during the shoulder arthroscopy is of great importance as it can potentially avoid unnecessary confusion and surgery.     

多模态超声检查技术及超声评分方法在类风湿性关节炎中的应用

类风湿性关节炎(rheumatoid arthritis,RA)是一种自身免疫性疾病,以慢性、进展性关节损伤为主要表现,主要的病理基础是滑膜炎症与滑膜血管翳形成[1].RA引起进行性和不可逆的关节疾病,最终可导致关节畸形和功能丧失,严重影响患者生存质量.在临床的诊疗过程中,临床医师对RA的诊疗主要根据患者的体格检查、实...     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).     

Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.Actin is critically involved in the regulation of neuronal polarization, differentiation, and growth of neuronal processes, cargo trafficking, and plasticity of synapses (1–3). Spectrin is an actin-binding protein that is important for the development and stabilization of axons and maintenance of neuronal polarization (4–6). In Caenorhabditis elegans, spectrin is important for the stability and integrity of axons under mechanical stress (4, 6) and for mechanosensation (6), and spectrin depletion results in axon breakage during animal locomotion (4). In Drosophila, spectrin has been shown to be involved in axonal path finding (7) and stabilization of presynaptic terminals (8). In mice, spectrin null mutations are embryonically lethal, and neurons with spectrin knockdown display defects in axonal initial segment assembly (5, 9, 10).Actin and spectrin form a 2D polygonal lattice structure underneath the membrane of erythrocytes (11). Recently, a novel form of actin–spectrin-based submembrane skeleton structure was discovered in neuronal axons (12) using superresolution STORM imaging (13, 14). This membrane-associated periodic skeleton (MPS) has been observed in both fixed and live cultured neurons (12, 15, 16) and in brain tissue sections (12). In this structure, short actin filaments are organized into repetitive, ring-like structures that wrap around the circumference of the axon with a periodicity of ∼190 nm; adjacent actin rings are connected by spectrin tetramers, and actin short filaments in the rings are capped by adducin (12). This structure also appears to organize other associated molecules, such as ankyrin and sodium channels, into a periodic distribution in axons (12, 16). During neuronal development, MPS originates from the axonal region proximal to the soma and propagates to distal axonal terminals (16). At a relatively late stage during development, specific isoforms of ankyrin and spectrin molecules, ankyrin-G and βIV spectrin, are recruited to the axon initial segment (AIS) (17, 18), and these molecules are also assembled into the MPS structure, adopting a similar periodic distribution (16, 19). As in the AIS, this periodic structure is also present in the nodes of Ranvier (20). This periodic skeletal structure has been shown to preferentially form in axons compared with dendrites in primary neuronal cultures: actin and spectrin typically form a long-range, periodic lattice structure throughout the entire axonal shaft, except for the very distal region near the growth cone, in essentially all observed axons. In contrast, such a periodic structure was observed in only a small fraction (∼10–30%) of dendrites and typically appeared as short, isolated patches in portions of these dendrites (16, 20). The local concentration of spectrin is a key determinant for the preferential formation of MPS in axons: in wild-type neurons, βII spectrin is enriched in axons, and artificially increasing the concentration of βII spectrin through overexpression is sufficient to induce the formation of MPS in all dendrites (16). Ankyrin-B appears to be an important regulator of this structure: in ankyrin-B knockout mice, βII spectrin becomes evenly distributed between axons and dendrites, leading to the formation of the long-range MPS structure in all dendrites (16) without perturbing the MPS structure in axons (16, 21).The ubiquitous expression of spectrin in the nervous systems of nearly all animal species (22) raises the questions of how widespread the MPS structure is in different nervous system cell types and distinct subcellular compartments and of how conserved this structure is across different animal species. A recent paper reports the presence of periodic actin structures in several nervous system cell types from rodents (23). Here we investigated these questions regarding the prevalence and conservation of the MPS structure by examining the distribution of spectrin in many different types of rodent neurons and glial cells and across a variety of organisms ranging from C. elegans to Homo sapiens. Furthermore, we examined the distribution of spectrin in presynaptic and postsynaptic compartments of axons and dendrites, respectively, to shed light on the relation between the MPS structure and synapses.     

Evaluation of leukocyte arylsulphatase a, serum interleukin-6 and urinary heparan sulphate following tamoxifen therapy in breast cancer.

Leukocyte arylsulphatase A (AS-A) was shown to be significantly high in newly-diagnosed breast cancer patients. Previous reports imply a connection between serum interleukin-6 (IL-6) and breast cancer, possibly through a modulation of enzymes involved in estrogen synthesis. Abnormal distribution of heparan sulphate proteoglycans (HSPGs) in malignant breast epithelial cells suggests that they play a key role in the regulation of cell growth. Estradiol is believed to be effective in modulating glycosaminoglycans (GAGs) and their depolymerizing enzymes. Therefore, in this study, attempts were made to evaluate the activity of leukocyte arylsulphatase A, serum interleukin-6, urinary GAGs and heparan sulphate (HS) in response to tamoxifen (TAM) therapy in mastectomised breast cancer patients. Thirty-four patients (aged 30-82 years) were administered TAM (20 mg twice daily). Blood and urine samples of each patient were collected three times (at the beginning, and in third and sixth month of TAM therapy), and biochemical parameters were measured. There was no difference between baseline leukocyte AS-A activity and that measured after three months. At the end of six months, enzyme activity was significantly higher than the former values (p=0.022), but within the reference intervals reported in the literature. Although this increase might imply a normalization, the duration of TAM therapy is not long enough to make a decision about either regression or aggravation of the disease. TAM did not have any effect on serum IL-6, urinary HS and GAG levels which may be due to insensitivity of these variables to TAM during the short period of therapy. Both urinary GAG and HS levels measured at sixth month exhibited a positive correlation with the baseline level of leukocyte AS-A (p=0.005 and 0.009, respectively), suggesting that positive responses to the drug might be seen in patients with low AS-A activity.     

Cutaneous anthrax of the hand and its reconstruction with a reverse-flow radial forearm flap

Bacillus anthracis infection can lead to necrosis in tissues and may manifest as a fatal disease in human beings. The authors present a patient with a large area of skin necrosis on the dorsum of the hand that was reconstructed with a reverse flow-through radial forearm flap, and they discuss the relevant literature. To the authors' knowledge, this is the first published report of such extensive necrosis resulting from anthrax limited to the extensor retinaculum of the hand.     

The mechanisms of peroxynitrite-induced relaxations in isolated rat anococcygeus muscle

We have previously reported that peroxynitrite (ONOO(-)) caused relaxations on isolated rat anococcygeus muscle and in the present study the possible mechanisms of the relaxant effect were investigated. ONOO(-) (0.03- 1.0 mmol/l)-induced relaxations were reduced significantly by the presence of an ATP-sensitive potassium channel (K(+)(ATP) channel) blocker, glibenclamide (0.3 micromol/l), or 1H-(1,2,4)oxadiazolo(4,3-alpha)quinoxalin-1-one (ODQ) (30.0 micromol/l), a guanylyl cyclase inhibitor. However, 3-aminobenzamide (3.0 mmol/l), an inhibitor of poly(ADP- ribose)synthase, did not influence the relaxant effect of ONOO(-) (1.0 mmol/l). Results of the present study implicate that activation of K(+)(ATP) channels and/or cGMP/K(+)(ATP) channel interaction might play a role in the relaxant responses to ONOO(-) in isolated rat anococcygeus muscle.     

Embolization of uterine artery in terminal stage cervical cancers

Ligation of the hypogastric artery has been a standard and effective procedure in controlling massive bleeding in advanced cervical carcinoma. The authors wanted to demonstrate the selective use of embolization of hypogastric or uterine artery to achieve the same end result--the stoppage of vaginal bleeding. In a number of cases, surgical approach may not be appropriate either because of the critically ill patient or because of the highly deformed pelvic anatomy due to radiotherapy or to the recurrence of cancerous tissue. As an alternative therapy, we used selective embolization of the uterine artery in eight patients. In all the patients, embolization served to control bleeding. As the bleeding was brought under control, a gradual recovery of the patient was generally observed. The most common side-effect was temporary severe pain related to ischemia of tumoral tissue. Embolization may be regarded as an effective procedure, which can be used to control massive bleeding in selected cervical cancer patients.