Induction immunosuppression strategies and long-term outcomes after heart transplantation

Although the use of induction therapy has reduced the risk of acute rejection after heart transplantation, its use may be associated with other adverse outcomes. We aimed to examine the effect of no induction (NoInd), induction with basiliximab (BAS), or induction with antithymocyte globulin (ATG) on outcome after heart transplantation. We analyzed data from the International Society for Heart and Lung Transplantation (ISHLT) registry for adult heart transplants performed between 2000 and 2013. The primary outcome was cumulative all-cause mortality, and the secondary outcome was cause-specific death. We identified 27 369 transplants whose recipients received NoInd (n = 15 688), ATG (n = 6830), or BAS (n = 4851). Over a median follow-up of 1497 days, overall 30-day mortality was 5% and 1-year mortality was 11%. Survival after transplant was similar in patients treated with NoInd compared with ATG. The survival was improved using NoInd compared with BAS (log-rank P = .040), adjustment HR = 1.11 (95% CI, 1.04-1.19). Compared to NoInd, BAS was associated with higher risk of graft failure-related deaths, HR = 1.27 (95% CI, 1.02-1.58), and ATG was associated with higher risk of malignancy-related deaths, HR = 1.18 (95% CI, 1.01-1.39). Survival of patients who received NoInd was similar to ATG and better compared with BAS. Further, the use of ATG may be associated with increased malignancy-related mortality, compared with NoInd.     

Meta-analysis of retrojugular versus antejugular approach for carotid endarterectomy

Introduction

The retrojugular approach for carotid endarterectomy (CEA) has been reported to have the advantages of shorter operative time and ease of dissection, especially in high carotid lesions. Controversial opinion exists with regard to its safety and benefits over the conventional antejugular approach.

Methods

A systematic review of electronic information sources was conducted to identify studies comparing outcomes of CEA performed with the retrojugular and antejugular approach. Synthesis of summary statistics was undertaken and fixed or random effects models were applied to combine outcome data.

Findings

A total of 6 studies reporting on a total of 740 CEAs (retrojugular approach: 333 patients; antejugular approach: 407 patients) entered our meta-analysis models. The retrojugular approach was found to be associated with a higher incidence of laryngeal nerve damage (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 1.46–7.07). No significant differences in the incidence of hypoglossal or accessory nerve damage were identified between the retrojugular and antejugular approach groups (OR: 1.09 and 11.51, 95% CI: 0.31–3.80 and 0.59–225.43). Cranial nerve damage persisting during the follow-up period was similar between the groups (OR: 2.96, 95% CI: 0.79–11.13). Perioperative stroke and mortality rates did not differ in patients treated with the retrojugular or antejugular approach (OR: 1.26 and 1.28, 95% CI: 0.31–5.21 and 0.25–6.50).

Conclusions

Currently, there is no conclusive evidence to favour one approach over the other. Proof from a well designed randomised trial would help determine the role and benefits of the retrojugular approach in CEA.     

Electrodegradation of 2,4-dichlorophenoxyacetic acid herbicide from aqueous solution using three-dimensional electrode reactor with G/β-PbO2 anode: Taguchi optimization and degradation mechanism determination

This study aimed to investigate the electro-degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous solution using two and three-dimensional electrode (2D and 3D) reactors with graphite(G)/β-PbO₂ anode. To increase the degradation efficiency, affecting parameters on the electro-degradation process were investigated and optimized by adopting the Taguchi design of experiments approach. The structure, morphology and electrochemical properties of the electrodes were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), linear sweep voltammetry and cyclic voltammograms. The controllable factors, i.e., electrolysis time, 2,4-D initial concentration, solution pH and current density (j) were optimized. Under optimum conditions, the 2,4-D degradation efficiency was 75.6% using 2D and 93.5% using 3D electrode processes. The percentage contribution of each controllable factor was also determined. The pH of the solution was identified as the most influential factor, and its percentage contribution value was up to 39.9% and 40.4% for 2D and 3D electrode processes, respectively. Considering the parameters of the kinetics, it was found that the degradation of 2,4-D and removal of COD using the G/β-PbO₂ electrode obey the pseudo-first order kinetics. In addition, the mineralization pathway of 2,4-D at G/β-PbO₂ electrode was proposed. The results also demonstrated that the 3D electrode process with G/β-PbO₂ anode can be considered as a useful method for degradation and mineralization of 2,4-D herbicides from aqueous solution.

Optimization of process parameters using the Taguchi method, electrochemical degradation and electrochemical degradation mechanism of 2,4-D herbicide using 2D and 3D reactors with G/β-PbO₂ anode were investigated.     

Assessment of Circulating Biochemical Markers in Mice Receiving Cinnamon and Glycyrrhizin Under Carbon Tetrachloride Induced Hepatic Injury

The study evaluated the hepatoprotective activity of plant extracts of cinnamon and glycyrrhizin in distinct dosage ways to minimize the oxidative stress induced by carbon tetrachloride (CCl₄) in BALB/cJ inbred albino mice. Fifteen albino mice were divided into five groups, each group containing three mice. Group A was referred as positive control while group B, C, D and E were injected intraperitoneally with 1 mL/kg body weight of CCl₄ twice a week for 1 month. Group C and D were treated orally with isolated extracts of cinnamon @50 mg/kg and glycyrrhizin @50 mg/kg respectively on daily basis for 1 month. However, group E was treated orally with combination dose of cinnamon @50 mg/kg + glycyrrhizin @50 mg/kg body weight. The increase in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), triglyceride (TG), malondialdehyde (MDA) and glucose were recorded in CCl₄ induced liver injury in mice while there is decrease in the levels of total protein (TP), reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (CAT) in CCL₄ intoxicated mice. Isolated therapy of plant extracts of cinnamon and glycyrrhizin decreased the levels of ALT, AST, ALP, MDA, TG and glucose whereas increase in TP, GSH, SOD and CAT was observed in plant extracts treated mice. The best restoration of all the above said parameters near to control was observed in group of mice treated with combination dose of cinnamon and glycyrrhizin @50 mg/kg. Therefore, the present study declared the antioxidative, anti-inflammatory and hepatoprotective activity of standardized extracts of cinnamon and glycyrrhizin and their potent defensive property.

     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

Influence of chitosan coating on the oral bioavailability of gold nanoparticles in rats

Gold nanoparticles are one of the most extensively investigated metallic nanoparticles for several applications. It is less toxic than other metallic nanolattices. The exceptional electrical and thermal conductivity of gold make it possible to be administered as non-invasive radiofrequency irradiation therapy that produces sufficient heat to kill tumor cells. Nanoparticles are generally administered intravenously instead of orally due to negligible oral absorption and cellular uptake. This study evaluated the oral bioavailability of gold nanoparticles coated with chitosan (C-AuNPs), a natural mucoadhesive polymer. We employed traditional method of evaluating bioavailability that involve estimation of maximum concentrations and area under the curve of 3?nm chitosan coated gold nanoparticles (C-AuNPs) in the rat plasma following intravenous and oral administrations (0.8?mg and 8?mg/kg body weight respectively). The oral bioavailability of C-AuNPs was found to be 2.46% (approximately 25 folds higher than polyethylene glycol (PEG) coated gold nanoparticles, reported earlier). These findings suggest that chitosan coating could be better than PEG coating for the enhancement of oral bioavailability of nanoparticles.