[Sidaxue, a traditional Guizhou Miao herbal medicine formula, reduces necroptosis and synovial vascular proliferation in rats with collagen-induced arthritis by inhibiting the RIPK1/RIPK3/MLKL pathway].

OBJECTIVE: To explore the inhibitory effect of Sidaxue (SX), a traditional Guizhou Miao herbal medicine formula, on necrotic apoptosis and synovial angiogenesis in rats with collagen-induced arthritis (CIA) and the role of the RIPK1/RIPK3/MLKL pathway in mediating this effect. METHODS: Forty-two SD rats were randomized into 6 groups (n=7), including a normal control group, a CIA model group, 3 SX treatment groups at low (10 g/kg), moderate (20 g/kg) and high (40 g/kg) doses, and a GTW treatment group. CIA rat models were established by subcutaneous injections of bovine type II collagen, and the treatments were administered daily by gavage for 21 days. The rats were observed for swelling of the hind limb joints, which was rated using the arthritis index (AI) score on a weekly basis. Serum levels of TNF-α, IL-1ß and IL-17 in the rats were detected using ELISA, and the pathological changes in the synovium were observed with HE staining. Real-time PCR was performed to detect the mRNA expression levels of VEGF, MMP-9, Ang-1, RIPK1, RIPK3, and caspase-8 in the synovial tissues, and the protein expressions of VEGF, MMP9, Ang-1, Stat-3, RIPK1, RIPK3, MLKLl, p-MLKL and caspase-8 were detected using Western blotting. RESULTS: Compared with those in CIA model group, the rats receiving treatment with GTW and SX showed milder swelling of the hind limb joints with significantly lower AI scores (P < 0.05). In CIA model group, a large number of inflammatory cells were observed in the synovium with obvious damages of the tissue structure. In the drug treatment groups, inflammatory cell infiltration, synovial angiogenesis and synovial hyperplasia were alleviated, and the therapeutic effects were obviously enhanced as SX dose increased. Compared with those in the model group, the rats treated with GTW and high-dose SX showed significantly decreased serum levels of IL-1ß, IL-17 and TNF-α (P < 0.05), lower mRNA and protein expressions of RIPK1, RIPK3, VEGF, Ang-1, and MMP9 (P < 0.05), higher expressions of caspase-8 (P < 0.01), and obviously lowered expression of Stat-3 protein and phosphorylation level of MLKL (P < 0.05). CONCLUSION: SX can improve synovial angiogenesis in CIA rats possibly by inhibiting the activation of RIP1/RIP3/MLKL signaling pathway and down-regulating the expression of the vascular growth factors VEGF, Ang-1, MMP9, and Stat-3.

Fish oil- and soy oil-based lipid emulsions in neonatal parenteral nutrition: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The precise role of fish oil-based lipid emulsions (FBL=any lipid emulsion containing any amount of fish oil) and soy oil-based lipid emulsions (SBL=any lipid emulsion not containing fish oil or containing at least 50% soy oil) in neonatal parenteral nutrition (PN) needs to be explored. SUBJECTS/METHODS: The PubMed, MedLine and Google Scholar databases were searched for randomised control trials in which PN with FBL and SBL was the only difference between intervention and control groups. Methodological quality was assessed based on the Cochrane handbook for systemic reviews and Jadad's score. Revman 5.2 software was used for meta-analysis. RESULTS: Of 420 trials, 25 met the inclusion criteria. The aggregate results showed that both FBLs and SBLs are beneficial. FBLs were associated with significantly lower incidences of cholestasis (relative risk (RR)=0.50; 95% confidence interval (CI)=0.27-0.92, P=0.03) compared with SBLs. FBLs also had a tendency to improve the rates of weight gain, increase in head circumference and the time to regain birth weight (mean difference (MD)=0.24; 95% CI=-0.63-0.15). SBLs were associated with reduced duration of respiratory support (MD=2.22, 95% CI=0.35-4.09, P=0.02) and mortality rate in the first 28 days (RR=1.24, 95% CI=-0.72-2.13). CONCLUSIONS: Both FBLs and SBLs are beneficial for neonatal PN. FBLs reduce cholestasis, and SBLs reduce the duration of respiratory support.

Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest.

Human hepatocellular carcinoma (HCC) has an elevated requirement for arginine in vitro, and pegylated recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors. While supplementation of the culture medium with ornithine failed to rescue Hep3B cells from growth inhibition induced by rhArg-PEG, citrulline successfully restored cell growth. The data support the roles previously proposed for ornithine transcarbamylase (OTC) in the arginine auxotrophy and rhArg-PEG sensitivity of HCC cells. Expression profiling of argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL) and OTC in 40 HCC tumor biopsy specimens predicted that 16 of the patients would be rhArg-sensitive, compared with 5 who would be sensitive to arginine deiminase (ADI), another arginine-depleting enzyme with anti-tumor activity. Furthermore, rhArg-PEG-mediated deprivation of arginine from the culture medium of different HCC cell lines produced cell cycle arrests at the G(2)/M or S phase, possibly mediated by transcriptional modulation of cyclins and/or cyclin dependent kinases (CDKs). Based on these results, together with further validation of the in vivo efficacy of rhArg-PEG against HCC, we propose that the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against HCC.

An integrated healthcare enterprise information portal and healthcare information system framework.

The paper presents an integrated, distributed Healthcare Enterprise Information Portal (HEIP) and Hospital Information Systems (HIS) framework over wireless/wired infrastructure at National Taiwan University Hospital (NTUH). A single sign-on solution for the hospital customer relationship management (CRM) in HEIP has been established. The outcomes of the newly developed Outpatient Information Systems (OIS) in HIS are discussed. The future HEIP blueprints with CRM oriented features: e-Learning, Remote Consultation and Diagnosis (RCD), as well as on-Line Vaccination Services are addressed. Finally, the integrated HEIP and HIS architectures based on the middleware technologies are proposed along with the feasible approaches. The preliminary performance of multi-media, time-based data exchanges over the wireless HEIP side is collected to evaluate the efficiency of the architecture.

Remission of hepatocellular carcinoma with arginine depletion induced by systemic release of endogenous hepatic arginase due to transhepatic arterial embolisation, augmented by high-dose insulin: arginase as a potential drug candidate for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is auxotrophic for the semi-essential amino acid arginine, depletion of which leads to tumor death. In humans, arginine is not an essential amino acid since many adult somatic cells can re-synthesize it from other sources, such as citrulline. Enzymes capable of depleting arginine in vitro include the urea cycle enzyme arginase, which is found in abundance in human liver. For over three decades, arginase has not been considered as a potential drug candidate because of its low substrate affinity, short circulatory half-life and sub-optimal enzymatic activity at physiological pH, though its in vitro anti-tumor activities in certain tumors have been amply reported. Arginine deiminase, a bacterial enzyme from Mycoplasma hominus has been shown to induce HCC remission through the mechanism of arginine depletion. We report here an innovative treatment approach for the treatment of locally advanced and metastatic HCC with transhepatic arterial embolisation (TAE) of the liver tumor with lipiodol and gel foam as a means of inducing a leakage of hepatic arginase from the liver into the circulation. Hepatic arginase released into the systemic circulation rapidly depleted plasma arginine. High-dose insulin was included to induce a state of hypoaminoacidaemia to augment arginine depletion. With this protocol, we have treated seven patients with locally advanced and/or metastatic HCC. Five patients achieved arginine depletion, ranging from 0 to 20 microM (normal plasma level 100-120 microM); all had varying degrees of tumor remission in their primary tumors and extra-hepatic sites in the lymph nodes, lungs and bones, suggesting systemic anti-cancer effect of arginine depletion. The two non-responders did not show significant reduction in plasma arginine. Based on our findings, we propose that the urea cycle enzyme, arginase, is a good drug candidate for the treatment of HCC.

BMS-201620: a selective beta 3 agonist.

A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.

Before the paradigm shift: concepts and communication between doctors and nurses in a burns team.

The evolution of care delivered by a multidisciplinary burns team is a function of the effectiveness of the professional communication between team members. In this exercise, we have explored concepts and communication between nurses and doctors in a burns team. Loosely structured weekly meetings were held over a 4-month period. The explicit objective was to determine and define the current model of burns care in a regional burn centre. The implicit objective, however, was to develop a mutual appreciation of actual and potential problems in communication. Consensus task identification was achieved at the end of each meeting with full compliance in completing the tasks before the next meeting. Although there was a unanimous commitment to the team concept, traditional, professional, paradigms persist. For nurses, the concept of holistic modelling predominated, whilst the disease centred paradigm remained the focus of medical modelling. Linguistic, cultural and professional barriers to effective communication were identified but did not readily conform to prior expectations. Experience in burns care can transcend these barriers more effectively than a common culture or profession. In conclusion, team work and team building is a complex process that can benefit from an ongoing process of re-evaluation. An obvious yet common error is to assume a level of mutual understanding that does not in fact exist. Stepping aside to re-explore fundamental principles on which team members base their personal and professional practice can help in elucidating and determining new paradigms of care, which can be evaluated and appropriately implemented. The consensus conclusion was that this approach was a very valuable investment in time in pursuing excellence in the field of burns care.

Beta 3 agonists. Part 1: evolution from inception to BMS-194449.

Screening of the BMS collection identified 4-hydroxy-3-methylsulfonanilidoethanolamines as full beta 3 agonists. Substitution of the ethanolamine nitrogen with a benzyl group bearing a para hydrogen bond acceptor promoted beta(3) selectivity. SAR elucidation established that highly selective beta(3) agonists were generated upon substitution of C(alpha) with either benzyl to form (R)-1,2-diarylethylamines or with aryl to generate 1,1-diarylmethylamines. This latter subset yielded a clinical candidate, BMS-194449 (35).(1)

The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens.

The CD19/CD21 complex is an essential B cell coreceptor that functions synergistically to enhance signaling through the B cell Ag receptor in response to T cell-dependent, complement-tagged Ags. In this study, we use a recombinant protein containing three tandemly arranged copies of C3d and the Ag hen egg lysozyme, shown to be a highly effective immunogen in vivo, to evaluate the role of the CD19/CD21 complex in Ag processing in B cells. Evidence is provided that coengagement of the CD19/CD21 complex results in more rapid and efficient production of antigenic peptide/class II complexes as compared with B cell Ag receptor-mediated processing alone. The CD19/CD21 complex does not itself target complement-tagged Ags for processing, but rather appears to influence B cell Ag processing through its signaling function. The ability of the CD19/CD21 complex to augment processing may be an important element of the mechanism by which the CD19/CD21 complex functions to promote B cell responses to T cell-dependent complement-tagged Ags in vivo.

The effects of plateau time on vestibular-evoked myogenic potentials triggered by tone bursts.

Vestibular-evoked myogenic potentials (VEMPs) can be triggered by acoustic, vibratory or galvanic stimuli. However, each method has drawbacks for studying if the vestibulocollic reflex is intact in the patients tested. We used air-conducted VEMPs as a screening test to examine the integrity of the sacculocollic reflex. In a previous study, we defined the optimal rise/fall time of short tone bursts (STBs) to evoke VEMPs. In this paper, we studied the optimal plateau time of tone bursts to evoke VEMPs. Four different plateau times (1, 2, 5 and 10 ms) were used in a random order to test 26 normal ears. VEMP responses (p13/n23) triggered by the tone bursts were clearly observed in all ears. When the plateau time was increased in order from 1 to 10 ms, the latencies (p13, n23) and interval (p13-n23) were also increased in parallel, although significant differences were not observed between some plateau times. Considering the latencies and interval together for the four plateau times, the variances were smallest for the 2 ms plateau time, meaning that it caused the smallest interaural VEMP differences. The amplitude or relative amplitude in individual ears was lowest for the 1 ms plateau time, while it was comparable for the other three plateau times. In conclusion, we recommend that the ideal stimulation pattern for evoking STB VEMPs is as follows: frequency 500 Hz; stimulation repetition rate 5 Hz; rise, fall time 1 ms; and plateau time 2 ms. The waveform morphology of the VEMP responses observed with this stimulation pattern was simultaneously the most constant and marked.

Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate.

Epidemiological, in vitro cell culture, and in vivo animal studies have shown that green tea or its constituent polyphenols, particularly its major polyphenol epigallocatechin-3-gallate (EGCG) may protect against many cancer types. In earlier studies, we showed that green tea polyphenol EGCG causes a G0/G1-phase cell cycle arrest and apoptosis of human epidermoid carcinoma (A431) cells. We also demonstrated that these effects of EGCG may be mediated through the inhibition of nuclear factor kappa B that has been associated with cell cycle regulation and cancer. In this study, employing A431 cells, we provide evidence for the involvement of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery during cell cycle deregulation by EGCG. As shown by immunoblot analysis, EGCG treatment of the cells resulted in significant dose- and time-dependent (i) upregulation of the protein expression of WAF1/p21, KIP1/p27, p16 and p18, (ii) downmodulation of the protein expression of cyclin D1, cdk4 and cdk6, but not of cyclin E and cdk2, (iii) inhibition of the kinase activities associated with cyclin E, cyclin D1, cdk2, cdk4 and cdk6. Taken together, our study suggests that EGCG causes an induction of G1-phase ckis, which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle thereby causing a G0/G1-phase arrest of the cell cycle, which is an irreversible process ultimately resulting in an apoptotic cell death. We suggest that the naturally occurring agents such as green tea polyphenols which may inhibit cell cycle progression could be developed as potent anticancer agents for the management of cancer.

Resistive inspiratory muscle training: its effectiveness in patients with acute complete cervical cord injury.

OBJECTIVE: To evaluate if resistive inspiratory muscle training (RIMT) can improve lung function in patients with complete tetraplegia within half a year after trauma. DESIGN: A prospective study. The experimental patients received training with a Diemolding Healthcare Division inspiratory muscle trainer for 15 to 20 minutes per session, twice per day, 7 days a week for 6 weeks. SETTING: Hospital-based rehabilitation units. PATIENTS: Twenty patients who were in their first 6 months of complete cervical cord injury were randomly enrolled into RIMT (10 patients) and control (10 patients) groups. MAIN OUTCOME MEASURE: Spirometry, lung volume test, maximal inspiratory pressure, maximal expiratory pressure, and modified Borg scale measurements at rest were performed before training and at the end of 6 weeks of training. RESULTS: Most of the pulmonary parameters showed statistically significant improvements within the RIMT and control groups, but the improvements were greater in the RIMT group. In addition, the improvements in total lung capacity, total lung capacity predicted percentage, vital capacity, minute ventilation, forced expiratory volume in 1 second predicted percentage, and the resting Borg scale in the RIMT group showed significantly greater improvement. CONCLUSION: RIMT can improve ventilatory function, respiratory endurance, and the perceived difficulty of breathing in patients with complete cervical spinal cord injury within half a year after trauma.

[Exploration on containers for medicinal measurement].

Containers for measuring medicines, including Qian bi (coin dagger) . dao gui (knife dagger), san fen bi (3 - fen dagger) . wu fen bi (5 - fen dagger) and fang cun bi (square - ital dagger) are discussed on the basis of ancient literature records and unearthed relics. It is claimed that besides applied as a 5 - zhu coin, coin dagger can also be interpreted as the weight of 1 coin dagger. Knife dagger is a measuring container with a volume of 0.5 ml. Based on the fact that "1 - fen copper volume" measures 1.2 mil, it is suggested that a 3 - fen dagger equals 3.6 ml; while 5 - fen dagger, 6 ml. Being a flattened spoon, concave at its center, a square - cun dagger measures approximately 10 or approximately 18 ml.

Clinical trial of electrical acupuncture on hemiplegic stroke patients.

To assess the efficacy of electrical acupuncture in the rehabilitation of patients with hemiplegia in stroke, we randomized 128 patients within 2 wk of stroke onset to receive either comprehensive rehabilitation plus electrical acupuncture (n = 59) or comprehensive rehabilitation only (n = 59). Electrical acupuncture was administered by electrical stimulation of acupuncture points through adhesive surface electrodes five times per week. Neurological status (Brunnstrom's stage) and the Chinese version of the Functional Independence Measure were assessed before treatment and at discharge. Patients treated with electrical acupuncture had a shorter duration of hospital stay for rehabilitation and better neurological and functional outcomes than the control group had, with a significant difference in scores for self-care and locomotion (P = 0.02). This result did not postulate the previous study that acupuncture therapy for stroke patients should depend on needle manual and "de qi" response. We suggest that electrical acupuncture through adhesive surface electrodes in conjunction with current optimal rehabilitation programs is a convenient and effective therapy for stroke patients.

A therapeutic trial of acupuncture in neurogenic bladder of spinal cord injured patients--a preliminary report.

Eighty patients with spinal cord injury (SCI) and neurogenic bladder were studied. Among them, 28 (70%) cases in the control group and 32 (80%) cases in the electroacupuncture group achieved ultimately balanced voiding and were selected for further analysis. The acupuncture group received electroacupuncture at four acupoints: Chung Chi (Conception Vessel CV3), Kuan Yuan (CV4), and bilateral Tzu Liao (Urinary Bladder UB32), in addition to conventional intermittent catheterization program (ICP). Whereas the control group underwent conventional bladder training program with ICP only. The results revealed that the time of achieving balanced voiding was statistically significantly shorter with electroacupuncture than in the control group: 57.1 +/- 22.6 vs 85.2 +/- 27.4 days (P < 0.005) for upper motor neuron lesions, and 55.4 +/- 22.6 vs 83.4 +/- 26.1 days (P < 0.01) for lower motor neuron lesions. However, there was almost no difference between upper motor neuron lesions and lower motor neuron lesions. When acupuncture commenced was alos a factor to influence the results. Those who received acupuncture within 3 weeks after injury had significantly shortened the total days to achieve a balanced bladder, as compared to those who received acupuncture 3 weeks after injury (46.6 +/- 13.2 vs 65.8 +/- 15.4 days, P < 0.005). Our study implied that acupuncture might be beneficial in the management of neurogenic bladder of SCI, and the earlier the patient received electro-acupuncture therapy, the sooner the bladder balanced. On the other hand, we also found that complete spinal cord injury, either with pronounced detrusor-sphincter dyssynergia in upper motor neuron lesion or with persistent areflexic bladder in lower motor neuron-lesion, was not affected by acupuncture.

The immediate effectiveness of electrical nerve stimulation and electrical muscle stimulation on myofascial trigger points.

This study is designed to investigate the immediate effectiveness of electrotherapy on myofascial trigger points of upper trapezius muscle. Sixty patients (25 males and 35 females) who had myofascial trigger points in one side of the upper trapezius muscles were studied. The involved upper trapezius muscles were treated with three different methods according to a random assignment: group A muscles (n = 18) were given placebo treatment (control group); group B muscles (n = 20) were treated with electrical nerve stimulation (ENS) therapy; and group C muscles (n = 22) were given electrical muscle stimulation (EMS) therapy. The effectiveness of treatment was assessed by conducting three measurements on each muscle before and immediately after treatment: subjective pain intensity [(PI) with a visual analog scale], pressure pain threshold [(PT) with algometry], and range of motion [(ROM) with a goniometer] of upper trapezius muscle (lateral bending of cervical spine to the opposite side). When the effectiveness of treatment was compared with that of the placebo group (group A), there was significant improvement in PI and PT in group B (P < 0.01) but not in group C (P > 0.05). The improvement of ROM was significantly more in group C (P < 0.01) as compared with that in group A or group B. When each group was divided into two additional subgroups based on the initial PI, it was found that ENS could reduce PI and increase PT significantly (P < 0.05), but did not significantly (P > 0.05) improve ROM, as compared with the placebo group for both subgroups. EMS could significantly (P < 0.05) improve ROM, but not PT, better than the placebo groups, for either subgroup. It could reduce PI significantly more (P < 0.05) than placebo controls only for the subgroup with mild to moderate pain, but not with severe pain. For pain relief, ENS was significantly better (P < 0.05) than EMS; but for the improvement of ROM, EMS was significantly better (P < 0.05) than ENS. It is concluded that ENS is more effective for immediate relief of myofascial trigger point pain than EMS, and EMS has a better effect on immediate release of muscle tightness than ENS.

Visualization and interactive exploration of multidimensional confocal images.

A confocal image analysis system is developed for automatic extraction of surface representation of biological structures. A visualization system is also developed to manipulate these surface representations and to obtain morphometrical parameters and provides a powerful tool for biomedical research such as microstructural characterization, morphogenesis, cell differentiation, tissue organization, and embryo development.

Comparison of the efficacy of cilofungin, fluconazole and amphotericin B in the treatment of systemic Candida albicans infection in the neutropenic mouse.

The relative efficacies of cilofungin, amphotericin B and fluconazole were compared in the treatment of systemic Candida albicans infection in neutropenic mice. Thirty-one day survival rates were lowest for cilofungin (14.6%), intermediate for amphotericin B (37.6%) and highest for fluconazole (50.5%). Residual tissue infection in surviving animals was observed with all agents, but was heaviest with fluconazole, especially in the kidneys.

[Chemical constituents of Isodon albopilosus (C.Y. Wu et H.W. Li) Hara].

Five compounds have been isolated from the stems and leaves of Isodon albopilosus. On the basis of spectroscopic and chemical data, they were identified as macrocalyxin C, stearic acid, beta-sitosterol, ursolic acid and beta-sitosterol-beta-D-glucoside, respectively.