Probing the mystery of Chinese medicine meridian channels with special emphasis on the connective tissue interstitial fluid system, mechanotransduction, cells durotaxis and mast cell degranulation

This article hypothesizes that the Chinese medicine meridian system is a special channel network comprising of skin with abundant nerves and nociceptive receptors of various types, and deeper connective tissues inside the body with the flowing interstitial fluid system. These meridian channels provide efficient migratory tracks mainly due to durotaxis (also including chemotaxis) for mast cells, fibroblasts and other cells to migrate and carry out a number of physiological functions. Acupuncture acting on meridian channel causes cytoskeletal remodeling through mechanotransduction, leading to regulation of gene expression and the subsequent production of related proteins. Also, stimulation on cell surface can trigger Ca²⁺ activities, resulting in a cascade of intra- and inter-cellular signaling. Moreover, nerve endings in the meridian channels interact with mast cells and induce the degranulation of these cells, leading to the release of many specific biomolecules needed for homeostasis, immune surveillance, wound healing and tissue repair. Acupoint along a meridian channel is a functional site to trigger the above functions with specificity and high efficiency.     

Prenatal depiction of cystic hygroma using three-dimensional ultrasound

Prenatal diagnosis of fetal cystic hygroma is very important in clinical medicine. In this series, we report our work of detecting cystic hygroma using three-dimensional (3-D) ultrasound (US). We reviewed our computer database of prenatal diagnosis on cystic hygroma in National Cheng Kung University Hospital from May 1995 to June 2000. All the fetuses were initially scanned by a high-resolution, real-time, 2-D US scanner and subsequently by a 3-D US scanner. In total, 23 cases of fetal cystic hygroma were diagnosed in utero. The range of gestational age at prenatal diagnosis by US was between 11 and 24 weeks, and 91% were diagnosed before 21 weeks. Among them, 8 cases (35%) were Turner syndrome (45,X), and 10 cases (43%) were complicated with hydrops fetalis. Although the diagnostic rates by 2-D US and 3-D US were both 100% (23 of 23), notably, 3-D US can provide additional vivid illustrations in 3-D after various modes of reconstruction, but 2-D US cannot. In conclusion, 3-D US may add novel visual depiction of the lesion in 3-D after reconstruction and, thus, assists substantially in prenatal consultation.     

CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells

Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent.     

Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C

Background

Regulatory T cells (Tregs) play a pivotal role in the persistence of hepatitis C virus infection. The aim of this study was to evaluate the frequency and function of Tregs in patients with chronic hepatitis C (CHC).

Methods

We enrolled 44 CHC patients with elevated alanine aminotransferase (ALT) levels (CH group), 13 CHC patients with persistent normal ALT levels (PNALT group), and 14 age-matched healthy subjects (HS group; controls). Tregs were identified as CD4+, CD25+, and forkhead box P3 (Foxp3)+ T lymphocytes, using three-color fluorescence-activated cell sorting (FACS). The frequency of Tregs was determined by calculating the percentage of CD4+CD25^high T cells among CD4 T cells. CD127 and CD45RA were also analyzed for subsets of Tregs. The levels of serum transforming growth factor (TGF)-β and interleukin (IL)-10 in immunosuppressive assays were detected by enzyme-linked immunosorbent assay (ELISA). The immunosuppressive abilities of Tregs were evaluated by measuring their ability to inhibit the proliferation of effector cells.

Results

Higher proportions of Tregs were found in the CH and PNALT groups compared with the HS group. The populations of CD127 low/negative and CD45RA negative cells were higher in the CH group than in the PNALT group. The expressions of IL-10 and TGF-β in the CH and PNALT groups were significantly higher than those in the HS group. In addition, the immunosuppressive ability of Tregs from the CH group was increased relative to that in the PNALT and the HS group.

Conclusions

CHC patients, irrespective of liver function, had higher frequencies of Tregs than healthy subjects; however, only CHC patients with inflammation showed enhanced immunosuppressive function of Tregs.     

Delays in Service for Non-Emergent Patients Due to Arrival of Emergent Patients in the Emergency Department: A Case Study in Hong Kong

Background

In Hong Kong Emergency Departments (EDs), the timeliness of providing high-quality services has been compromised by the increasing attendance of non-emergent patients in addition to the unpredictable arrival of emergency patients.

Objectives

We sought to quantify the impact of the presence of emergent patients and other related factors on the delay in service for non-emergent patients.

Methods

We conducted a retrospective study in patients who visited the ED of a large hospital in Hong Kong from July 1, 2009 to June 30, 2010. We estimated waiting and length of stay (LOS) for individual non-emergent patients registered during day and evening shifts. Using multiple linear regression, we estimated waiting time and LOS as a function of the presence of emergent patients and other related factors such as patient demographics and clinical factors. In particular, we evaluated the influence of the arrival or presence of emergent patients on the odds of violating the 120-min waiting time target for semi-urgent patients.

Results

The arrival of a new emergent patient prolonged the waiting time and LOS of a non-emergent patient by 14.9% (95% confidence interval [CI] 14.2–15.5) and 10.8% (95% CI 10.6–11.0), respectively. An additional patient-hour needed for an emergent patient increased the probability of violating the waiting time target for non-emergent patients (odds ratio 2.3, 95% CI 2.2–2.4).

Conclusions

The arrival of an emergent patient significantly prolonged the waiting time and LOS for non-emergent patients. Discouraging non-urgent ED utilization and building a real-time decision-support system are critical methods needed to relieve staff pressure and guide contingent resource reallocation when emergent patients arrive.     

Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia

PURPOSE: To examine the efficacy and safety of colesevelam hydrochloride, a novel, nonsystemic, lipid-lowering agent, when coadministered with starting doses of simvastatin in a multicenter, randomized, double-blind, placebo-controlled trial. PATIENTS AND METHODS: Subjects with hypercholesterolemia (plasma low density lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level < or = 300 mg/dL) were randomly assigned to receive daily doses of placebo (n = 33), colesevelam 3.8 g (recommended dose, n = 37), simvastatin 10 mg (n = 35), colesevelam 3.8 g with simvastatin 10 mg (n = 34), colesevelam 2.3 g (low dose, n = 36), simvastatin 20 mg (n = 39), or colesevelam 2.3 g with simvastatin 20 mg (n = 37), for 6 weeks. RESULTS: Mean LDL cholesterol levels decreased relative to baseline in the placebo group (P < 0.05) and in all active treatment groups (P < 0.0001). For groups treated with combination therapy, the mean reduction in LDL cholesterol level was 42% (-80 mg/dL; P < 0.0001 compared with baseline), which exceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-34%, -61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (-16%, -31 mg/dL) alone (P < 0.001). The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone. Side effects were similar among treatment groups, and there were no clinically important changes in laboratory parameters. CONCLUSION: Coadministration of colesevelam and simvastatin was effective and well tolerated, providing additive reductions in LDL cholesterol levels compared with either agent alone.     

Cerebrospinal fluid hepatocyte growth factor level in meningitis

BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis. METHODS: In a retrospective study, the levels of HGF in the cerebrospinal fluid of 65 patients were measured prior to treatment. The association of HGF with non-infectious diseases and clinically or microbiologically proven bacterial, tuberculous, viral, fungal and parasitic meningitis was observed, along with its relation to other parameters of the cerebrospinal fluid. RESULTS: Forty six of the 65 patients (71%) were diagnosed as having meningitis. Cerebospinal fluid HGF level was significantly elevated in patients with meningitis compared with patients with non-infectious diseases (1501 vs 578 pg/mL; Mann-Whitney U test, p=0.001). The highest HGF level was found in bacterial meningitis (2699 pg/mL), followed by tuberculous meningitis (1540 pg/mL), viral meningitis (1431 pg/mL), fungal meningitis (714 pg/mL) and parasitic meningitis (174 pg/mL). There was no association between HGF level and other parameters of the cerebrospinal fluid (Pearson's correlation test). CONCLUSION: Cerebrospinal fluid HGF may offer additional information in the classification of meningitis. This may assist in patient management when no pathogen is cultured from the cerebrospinal fluid and when other parameters of the cerebrospinal fluid demonstrate equivocal results.