Journal of Experimental & Clinical Medicine

Modes of Action of Taurine and Granulocyte Colony-stimulating Factor in Neuroprotection

Chandana Buddhala, Howard Prentice, Jang-Yen Wu — 2011-12-19

New therapeutic targets are becoming increasingly popular for the treatment of a wide array of neurodegenerative diseases, the preferred targets being those that prevent neuronal apoptosis at multiple levels or those that can cross the blood-brain barrier in order to replace degenerated cells and promote neuronal regeneration. One such rapidly emerging neuroprotective agents is taurine. Taurine is a ubiquitous amino acid that satisfies most criteria to be classified as a neurotransmitter. Because of a wide spectrum of effects that taurine can induce on intrinsic apoptosis pathways, such as modulating mitochondrial pore permeability, attenuating endoplasmic reticulum stress, maintaining calcium homeostasis, and downregulating the activities of a range of pro-apoptotic proteins, including calpain and caspases, while upregulating a variety of anti-apoptotic proteins involved in glutamate and hypoxia-induced toxicity, taurine is being extensively studied and successfully applied for the treatment of neurodegenerative diseases. Another potential molecule being researched for combating neurodegenerative diseases is granulocyte colony-stimulating factor (G-CSF), which originates from the cytokine family of growth factors. G-CSF has gained widespread attention because of its ability to cross the blood-brain barrier, the presence of its receptors in the central nervous system, anti-apoptotic functions, and its proliferative role in the restoration of tissue survival via neurogenesis. In this review from the available current literature, the modes of action of taurine and G-CSF are discussed. Further mechanistic studies are warranted in order to fully realize the potential of these two molecules.

Antimicrobial Resistance Surveillance among Nosocomial Pathogens in South Africa: Systematic Review of Published Literature

P. Nyasulu, J. Murray, O. Perovic, H. Koornhof — 2011-12-29

There has been a significant increase in the prevalence of antimicrobial drug resistance in sub-Saharan Africa. This may increase health-care costs due to patients' needs for more diagnostic tests, longer hospitalization, and poor outcome. Therefore, monitoring systems for resistance patterns are needed to effectively minimize poor outcome. A systematic review was conducted to find out the prevalence of antimicrobial drugs' resistance among Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and to understand whether or not such data were part of an ongoing surveillance system for nosocomial infections in South Africa. An online search of main databases, including Cochrane Library, PUBMED, and MEDLINE, was done using the following search terms: “antimicrobial resistance” and “surveillance”; “antimicrobial susceptibility” and “surveillance”; Staphylococcus aureus or Klebsiella pneumoniae or Pseudomonas aeruginosa; “nosocomial” or “hospital acquired”; or South Africa or Africa. We also performed manual search of local conferences, theses, and dissertations to identify relevant articles. In total, 41 manuscripts were identified of which eight were analyzed. There is no evidence of any ongoing antimicrobial resistance surveillance for nosocomial pathogens in South Africa. Data reported in this review seem to have been analyzed on an ad hoc basis and do not show a particular resistance pattern; however, data show evidence of resistance to commonly used antimicrobial drugs in this population: for S aureus, resistance to cloxacillin was 29% and to erythromycin 38%; for K pneumoniae, resistance to ciprofloxacillin was 35% and to ampicillin 99%; and for P aeruginosa, the mean resistance to ciprofloxacillin was 43% and to amikacin 35%. Surveillance of antimicrobial resistance is essential to better understand the complexity of antimicrobial resistance development. Such evidence would be used in developing an effective surveillance program to monitor patterns and trends of resistance over time.

New Insights into the Pathogenesis and Treatment of Patients with Immunoglobulin A Nephropathy

Yasuhiko Tomino — 2011-12-14

Immunoglobulin A (IgA) nephropathy (also called Berger’s disease) is the most common primary chronic glomerulonephritis worldwide, and was first described by J. Berger et al in 1968. Histopathologically, IgA nephropathy is characterized by expansion of glomerular mesangial matrix with mesangial cell proliferation and/or mononuclear cell infiltration. Glomeruli typically contain generalized-diffuse granular mesangial deposits of IgA (mainly IgA1), IgG and C3. Electron-dense deposits are observed in the glomerular mesangial areas and partially in the glomerular basement membrane. Thus, this disease is considered to be an immune-complex-mediated glomerulonephritis. Clinically, patients with IgA nephropathy show microscopic and macroscopic hematuria and/or proteinuria. Advanced patients (almost 40% of patients) progress to end-stage kidney disease during 20 years of observation. However, the pathogenesis and radical treatment of IgA nephropathy have still not been established.

Infectious Diseases after the 2011 Great East Japan Earthquake

Takashi Takahashi, Mieko Goto, Haruno Yoshida, Hiroyuki Sumino, Hidenori Matsui — 2011-12-21

A catastrophic earthquake occurred off the Pacific coast of Japan on 11 March 2011, striking the northeastern part of the country. The earthquake was followed by huge tsunamis, which destroyed many coastal cities and towns. Many displaced people moved into shelters or temporary homes supplied by the government, not only because of disruptions to community utility services but also because of health risks associated with nuclear power plant malfunctions in Fukushima. In this review, we summarize the characteristics of illnesses that occurred in the aftermath of this earthquake, including respiratory tract infection (tsunami-related aspiration pneumonia, legionellosis and influenza), wound infection (tetanus) and other infections (food poisoning, tsutsugamushi disease and measles). Our review also outlines several activities concerning the management of illnesses and infection control.

Effects of Arginine Supplementation on Exogenous Advanced Glycation End Product-induced Renal Inflammatory Mediator Expression in Rats

Ya-Mei Hu, Chiu-Li Yeh, Man-Hui Pai, Cheng-Chung Li, Jun-Jen Liu, Sung-Ling Yeh — 2011-12-16

Background: This study investigated the effects of dietary Arg supplementation on renal inflammatory mediator expression and oxidative damage in rats with exogenous advanced glycation end product (AGE) administration.Methods: There were two groups of rats: the CA group was fed a common diet and given a tail vein injection of AGE–bovine serum albumin (BSA); and the AA group was fed the Arg-supplemented diet and injected with AGE–BSA. Arg provided 2% of the total energy. The tail vein injection and diets for the respective groups were given for 10 days. After that, all rats were sacrificed, and blood and kidneys were harvested for further analysis.Results: Blood adhesion molecule expression and NO levels were higher in the AA group. Also, the kidney nitrotyrosine concentration, phospho-nuclear factor-κB p65 and inducible NO synthase protein expression was higher in the AA group than in the CA group. The finding of immunohistochemical staining was consistent with the results that the AA group had higher receptor of AGE expression in the kidneys.Conclusion: Supplemental dietary Arg may have adverse effect in AGE-induced kidney inflammatory response and oxidative damage in rats.

Induction of Mitochondrion-mediated Apoptosis by Semecarpus anacardium in the BCR–ABL+ 12B1 Leukemia Cell Line: Possible Mechanism of Therapeutic Action In Vivo

2011-12-16

Background/Purpose: Chronic myeloid leukemia (CML) is a clonal disorder leading to massive proliferation of hematopoietic cells. It is characterized by the BCR–ABL gene, resulting in production of a 210-kD chimeric tyrosine kinase that plays a major role in its etiopathogenesis. There is an increasing interest in identifying potent preventive and therapeutic agents for leukemia. Semecarpus anacardium Linn. nut milk extract (SA) has antileukemic activity in murine BCR–ABL+ leukemia in vivo. The present study aimed to elucidate the mechanism of action of SA by assessing its antiproliferative and apoptotic effects in the BCR–ABL+ 12B1 murine leukemic cell line.Methods: Cell viability and apoptosis assay using MTT analysis, propidium iodide staining, DNA fragmentation, intracellular reactive oxygen species/calcium, mitochondrial membrane potential, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting were determined in 12B1 cells.Results: Cell viability of SA-treated 12B1 cells was dose and time dependent. SA-induced cell death was considered to be apoptotic by observing the typical apoptotic morphological changes seen on propidium iodide staining and DNA ladder formation on electrophoresis. A reduction in the BCR–ABL + mRNA levels, induced by SA, was observed by RT-PCR. This may have been the result of a reduction in the transcription of the BCR–ABL fusion gene, with concomitant activation of apoptosis. SA induced a rapid increase in intracellular Ca2+ ions, which led to increased levels of reactive oxygen species. Concomitantly, we observed a significant loss of mitochondrial membrane potential and release of cytochrome c into the cytosol in 12B1 cells. These effects of SA are accompanied by downregulation of Bcl-2, upregulation of Bax, and activation of the caspase-3 and caspase-9 genes.Conclusion: These results provide unprecedented evidence that SA triggers mitochondrial receptor pathways to induce apoptotic signals in 12B1 cells. This study highlights the beneficial effect of SA in inducing apoptosis in cancer cells and thereby revealing a possible mechanism of therapeutic action in vivo.

The Role of High Sensitivity C-Reactive Protein and Coronary Artery Calcium as Predictors of the Long-term Prognosis in Men with Coronary Artery Disease

2012-01-03

Purpose: Measurements of coronary artery calcium (CAC) and of high sensitivity C-reactive protein (hsCRP) are used to predict the risk of cardiovascular events in patients with coronary artery disease (CAD). The aim of our study was to investigate the hypothesis that combining the hsCRP level and CAC score can increase the predictive value of these parameters for future cardiovascular events in male patients with suspected CAD.Methods: We included 90 male patients with stable angina. We measured their serum hsCRP and CAC scores by using electron-beam computerized tomography. These baseline parameters were correlated to the clinical cardiovascular events within the follow-up period.Results: During the follow-up period of up to 50 months (median 27 months), 13 major cardiovascular events were recorded. In multivariate regression analysis, after being adjusted for conventional risk factors, hsCRP and CAC score, hsCRP level was the only independent predictor of cardiovascular events. Further analysis was performed among the four groups classified by CAC score (CAC score ≥100 or < 100) and hsCRP (hsCRP ≥ 1 or < 1 mg/l). The relative risk for the hsCRP ≥ 1 mg/l and CAC score ≥ 100 group, when compared with that for the hsCRP < 1 mg/l and CAC score < 100 group, showed a marked increase to 7.50 (95% confidence interval: 1.42–39.61, p = 0.018) for the cardiovascular events.Conclusion: We concluded that risk stratification on the basis of both hsCRP level and CAC score might be of benefit to male patients with suspected CAD, as the combined use of these two markers allowed significantly more accurate prediction of cardiovascular events.

Parallel Pin Guide in Femoral Neck Fractures: Comparing the Effect of the Guide between Two Surgeons with Different Levels of Experience

I-Ju Tsai, Wei-Pin Ho — 2011-12-28

Purpose: Proper fixation of femoral neck fractures requires the parallel insertion of cannulated screws. Using a parallel pin guide has been definitively shown to improve the accuracy of pin insertion. However, no studies have addressed whether or not the surgeon's experience has any influence on the benefits of using a parallel pin guide.Methods: The accuracy of parallel pin insertion was investigated in the laboratory to determine if the surgeon’s experience has an effect on the usefulness of the guide. The experiment was carried out using a self-designed parallel pin guide, 24 Sawbones femurs and 48 pins. Two surgeons with different levels of experience performed the procedures with and without the parallel guide. After three pins had been inserted, fluorescent images were taken in anteroposterior (AP) and lateral (Lat) views. Then, two observers measured the divergent angles twice, using computers equipped with Agfa PAS systems. The data were analyzed with the Student t test and the Mann–Whitney U test.Results: When the parallel pin guide was not used, the accuracy of parallel insertion of pins was not affected by the surgeon’s experience (p=0.088, 0.075). Although the difference was not statistically significant, the attending surgeon inserted the pins with a greater degree of parallelism. In contrast, when the parallel pin guide was used, the resident doctor was significantly more accurate than the attending surgeon (p=0.015, 0.037).Conclusion: Use of a parallel pin guide tended to improve the accuracy of parallel pin insertion in both surgeons. However, the effect of the guide was more obvious in the less experienced resident surgeon.

The Correlations of the Six-minute Walk Test and Respiratory Functions in Chronic Obstructive Pulmonary Disease Patients with Chronic Hypercapnia

2011-12-26

Background: Dyspnea and related disabling symptoms are common in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnia. Unfortunately, the indicators during the six-minute walk test (6MWT) for prediction of respiratory functions or exercise intolerance in severe COPD has been little investigated. The relationship between parameters during the 6MWT and respiratory functions was therefore assessed in COPD patients with chronic hypercapnia.Methods: In 2002 and 2003, 37 COPD outpatients with chronic hypercapnia performed the 6MWT, and their respiratory function was measured. Twenty-eight males and nine females with COPD (mean forced expiratory volume in the first second of 26.1% of the predicted value, SD 7.7%) and hypercapnia (mean PaCO2 of 55.5 mmHg, SD 6.4 mmHg) were recruited. All patients were tested to measure pulmonary function, respiratory drive (airway occlusion pressure at 100 ms, P0.1), and respiratory muscle strength on the first day. On the second day, arterial blood gas analysis and the 6MWT were performed. Pearson’s correlation coefficient and regression analysis were used for data analysis.Results: The study showed that the six-minute walk distance (6MWD) was weakly correlated with the resting arterial oxygen partial pressure (PaO2) (r = 0.349, p = 0.034), expiratory muscle strength (Pemax) (r = 0.358, p = 0.030), and changes of dyspnea sensation (∆Borg) (r = 0.385, p = 0.019); furthermore, ∆Borg was weakly correlated with Pemax (r = 0.377, p = 0.021). The oxygen saturation measured at the end of the 6MWT (ExSpO2) was significantly correlated with FEV1/FVC (r = −0.443, p = 0.006), pH (r = 0.375, p = 0.022), arterial carbon dioxide partial pressure (PaCO2) (r = −0.470, p = 0.003), PaO2 (r = 0.664, p = 0.000) and P0.1 (r = −0.344, p = 0.037). The results of the multiple linear regression with the 6MWD as the dependent variable revealed that PaO2, Pemax, and ∆Borg were significant determinants of the 6MWD (p = 0.018, adjusted R2 = 0.259).Conclusion: Measurement of the 6MWT demonstrated that a stronger association of exercise limitation is the value of ∆Borg in COPD patients with chronic hypercapnia. Ventilation constraints, hypoxemia, hypercapnia, and respiratory drive might be associated with oxygen desaturation during the 6MWT in COPD patients with chronic hypercapnia.

Anterior Chamber Paracentesis Facilitates Laser Peripheral Iridotomy and Restores Vision in Mild-to-moderate Acute Primary Angle-closure Glaucoma

2011-12-22

Purpose: Acute primary angle-closure glaucoma (PACG) is an ocular emergency that commonly presents in Asian populations. For patients with contraindications for mannitol infusion, it is imperative to perform an alternative therapy in order to rapidly decrease intraocular pressure (IOP) and prevent further visual complications. The purpose of this study is to evaluate the therapeutic efficiency of anterior chamber paracentesis (ACP) and mannitol infusion in patients with PACG.Methods: Patients who suffered from their first attack of acute PACG when receiving ACP or mannitol infusion (20%, 300 mL) were included. They were divided into three subgroups: mild, moderate, or severe acute PACG, according to each patient’s initial IOP upon presentation (mild group, 45–50 mmHg; moderate group, 50–60 mmHg; severe group, >60 mmHg). IOP at multiple time points, best-corrected visual acuity (BCVA), severity of corneal edema, and waiting time for laser peripheral iridotomy (LPI) were recorded.Results: Compared with mannitol infusion (n = 29), ACP treatment (n = 30) achieved more rapid and effective IOP control within 2 hours, resulted in faster regression of corneal edema (grade: 0.98 ± 0.729 [ACP] vs. 1.50 ± 0.720 [mannitol], p = 0.011), and patients were able to undergo LPI within a reasonable amount of time (1.4 ± 0.93 days [ACP] vs. 2.5 ± 1.17 days [mannitol], p = 0.0002). All patients who received ACP or mannitol demonstrated improved BCVA within 2 weeks. Intriguingly, ACP restored visual acuity more effectively than mannitol infusion in patients with an initial IOP lower than 60 mmHg.Conclusion: ACP effectively treats acute PACG by rapidly stabilizing the anterior chamber. When the initial IOP is above 60 mmHg, ACP should only be considered when mannitol is contraindicated.

Using Appraisal of Guidelines Research and Evaluation to Appraise Nursing Clinical Practice Guidelines in Taiwan and to Compare Them to International Studies

2011-12-19

Background: Implementation of clinical practice guidelines (CPGs) can reduce medical practice variations and enhance effectiveness. In 2008, the Taiwan Department of Health delegated the development of CPGs on six health topics. By February 2010, these CPGs had been completed.Methods: The Appraisal of Guidelines Research and Evaluation (AGREE) instrument was used to assess the quality of the guidelines. We organized groups to develop CPGs and called on 131 experts with various specialties.Results: The average AGREE scores for the six major domains were 86% (scope and purpose), 63% (stakeholder involvement), 77% (rigor of development), 72% (clarity and presentation), 53% (applicability), and 69% (editorial independence).Conclusion: We recommend the following: (1) opinions from all stakeholders, especially patients, should be considered to improve the content of the guidelines; and (2) health education resources, audit forms, and other tools should be emphasized more in the development of CPGs.

Effects of Bupivacaine on the Isolated Rat Tracheal Smooth Muscle

Ying-Nan Chang, Chih-Hung Wang, Chi-Chung Wu, Hsing-Won Wang — 2011-12-19

Background: Bupivacaine is an amide-linked local anesthetic that has been used in subcutaneous infiltration, epidural and peripheral nerve block for surgery over three decades. Several studies have suggested that inhaled local anesthetics can reduce respiratory reflexes. To assess the direct actions of bupivacaine on airway smooth muscle we used our preparation to examine the effectiveness of bupivacaine on isolated rat trachea.Methods: A 5-mm-long portion of rat trachea was mounted in Krebs solution at 37 °C. Changes in tracheal contractility in response to a parasympathetic mimetic agent and electrical stimulation were measured using a transducer connected to a Pentium III computer equipped with polygraphy software. The following assessments were done: (1) effect of bupivacaine on the resting tension of tracheal smooth muscle; (2) effect of bupivacaine on contraction caused by exposure to 10−6 M methacholine as a parasympathetic mimetic; (3) effect of bupivacaine on electrically induced contraction of tracheal smooth muscle.Results: Bupivacaine had a negligible effect on the basal tracheal tension as the concentration increased. Bupivacaine inhibited the tracheal smooth muscle contraction in response to methacholine and electrical stimulation in a concentration-dependent manner.Conclusion: The study indicates that bupivacaine might inhibit cholinergic neurotransmission and have an anti-spasmic effect on the trachea, in that it inhibited the contractions elicited by electrical field stimulation and a depolarizing agent.

Hepatoprotective and Antioxidant Properties of Rhizophora mucronata Mangrove Plant in CCl4 Intoxicated Rats

Sundaram Ravikumar, Murugesan Gnanadesigan — 2011-12-26

Purpose: To identify the hepatoprotective effect of bark, collar, hypocotyl and stilt root extracts of Rhizophora mucronata mangrove plant.Methods: Rats were divided into four groups of six animals. Group 1 was the control; Group 2 was treated with the CCl4 hepatotoxin Group 3 was treated with silymarin (positive control) group; and Group 4 was the treatment group. The phytochemcial components of the extracts were analyzed. Moreover, in vitro antioxidant properties such as, DPPH, HR, NO, FRAP, LPO and SOD were measured for the stilt root extract, which was the most potent.Results: Of the selected extracts, stilt root showed better hepatoprotective activity. The hepatoprotective activity of the R. mucronata stilt root extract was dose-dependent (75–300 mg/kg body weight) showed that the level of SGOT, SGPT, ALP, bilurubin, cholesterol, sugar and lactate dehydrogenase were significantly (p < 0.05) reduced by all the doses when compared with the levels in the hepatotoxin group rats. The maximum reduction of SGOT (191.36 ± 24.32 IU/L), SGPT (81.54 ± 5.73 IU/L), ALP (228.63 ± 18.56 IU/L), bilurubin (2.52 ± 0.83 mg/dL), cholesterol (129.87 ± 6.42 mg/dL), sugar (121.63 ± 7.38 mg/dL) and lactate dehydrogenase (1601.00 ± 305.65 IU/L) and no histopathological alteration other than mild fatty changes was observed with the high dose (300 mg/kg) of stilt root extract. Phytochemcial analysis of the extracts showed the presence of various chemical constituents, including flavonoids, alkaloids, coumarins and polyphenols. Further, the IC50 values were 58.33 ± 2.87 μg/mL, 64.78 ± 1.32 μg/mL, 72.14 ± 0.94 μg/mL, 25.79 ± 0.93 μg/mL, 163.38 ± 0.81 μg/mL and 22.80 ± 0.93 μg/mL for the DPPH, HR, NO, FRAP, LPO and SOD radical scavenging activity, respectively.Conclusion: We conclude that the R. mucronata stilt root extract could be used as an alternative herbal medicine for the treatment of liver damage following the successful completion of clinical trials.

Presence of the Eye-of-the-tiger Sign on Magnetic Resonance Imaging in a Subject with Atypical Hallervorden-Spatz Syndrome Lacking Pantothenate Kinase 2 Mutation

Szu-Kuan Yang, Chaur-Jongh Hu, Rey-Yue Yuan, Hung-Jung Wang, Jau-Jiuan Sheu — 2011-12-15

Hallervorden-Spatz syndrome (HSS) is generally considered to be a rare neurodegenerative disorder associated with autosomal recessive pantothenate kinase-associated neurodegeneration or neurodegeneration with brain iron accumulation. The most well-known hallmark of the syndrome is the eye-of-the-tiger sign on the brain magnetic resonance imaging (MRI) scan. Previous studies have highlighted a one-to-one correlation between the MRI findings of the eye-of-the-tiger sign and the presence of a pantothenate kinase 2 (PANK2) mutation, postulating that the MRI appearance is a good diagnostic tool for identifying PANK2 mutation-positive cases. We report an atypical HSS patient without a PANK2 mutation, who had an eye-of-the-tiger sign on MRI, therefore strengthening the notion of genetic and radiological heterogeneity in HSS.