Evaluation of Antiviral Activities of Four Local Malaysian Phyllanthus Species against Herpes Simplex Viruses and Possible Antiviral Target

Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug.     

Isoproterenol induced rat endomyocardial damage in relationship to local capillary geometry

Summary Isoproterenol (2 mg/kg) injected subcutaneously into male Sprague-Dawley rats elicited morphological damage in the endomyocardium which was analyzed 16h following injection. Our aim was to study the relationship between damaged individual myocytes asnd their capillary supply. Myocardial tissue sections were differentially stained in order to distinguish arteriolar (AC) and venular (VC) capillary portions. Tissue areas surrounding individual capillaries and the position of the capillaries with respect to the damaged individual myocytes were established by using the method of capillary domains. In multicellular necrotic lesions 84 % of the capillaries located within the necrotic foci and 77 % of the capillaries in the surrounding tissue area were identified as the distal, venular portion with presumably low OZ content. The proportion of VCs related to necrotic lesions was significantly higher than in surviving endomyocardial regions. In the case of individual necrotic myocytes, we found 88 % to be supplied by VCs, while the adjacent normal myocytes were supplied by 61 % VCs. Both values were significantly higher when compared to control hearts (42 %). These results strongly support the crucial role of a lack of oxygen delivery in the pathogenesis of isoproterenol-induced necrosis.     

Cosmetic arm lengthening with monorail fixator

Upper limb length discrepancy is a rare occurrence. Humerus shortening may need specialized treatment to restore the functional and cosmetic status of upper limb. We report a case of humerus lengthening of 9 cm with a monorail external fixator and the result was observed during a 2-year follow-up. Humerus lengthening needs specialized focus as it is not only a cosmetic issue but also a functional demand. The monorail unilateral fixator is more functional and cosmetically acceptable, and thus becomes an effective treatment option.     

Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury

Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin‐fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non‐AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p‐value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.     

Development of a Specimen-Sparing Multichannel Bead Assay to Detect Antiparasite IgG4 for the Diagnosis of Schistosoma and Wuchereria Infections on the Coast of Kenya

To better delineate the impact of parasitic coinfection in coastal Kenya, we developed a novel specimen-sparing bead assay using multiplex flow immunoassay (MFI) technology to simultaneously measure serum or plasma immunoglobulin G4 (IgG4) against Brugia malayi antigen (BMA) and Schistosoma haematobium soluble worm antigen (SWAP). Properties of the bead assay were estimated by latent class analysis using data from S. haematobium egg counts/filarial rapid diagnostic cards (RDTs), parasite-specific enzyme-linked immunosorbent assays (ELISAs), and the multichannel IgG4 assay. For schistosomiasis, the bead assay had an estimated sensitivity of 81% and a specificity of 45%, and it was more sensitive than ELISA or urine egg counts for diagnosing infection. For filariasis, it had a sensitivity of 86% and a specificity of 39%, and it was more sensitive than ELISA or RDT. Measuring antibody by MFI is feasible and may provide more accurate epidemiological information than current parasitological tests, especially in the setting of low-intensity infections.     

GSTT1 and GSTM1 Gene Polymorphisms as Major Risk Factors for Asthma in a North Indian Population

Background

According to the National Family Health Survey, asthma is one of the leading diseases in India. In order to understand the complexity of asthma, the susceptibility genes need to be targeted for their association. Glutathione S-transferases play a major role in the detoxification of metabolites of oxidative stress resulting in inflammation and asthma. In the present study, the hypothesis that GSTT1 and GSTM1 gene polymorphisms are associated with asthma was examined.

Methods

This is the first study to investigate the role of GSTT1 and GSTM1 gene polymorphisms in asthma pathogenesis in a North Indian population. A total of 824 subjects were recruited, of which 410 were asthma patients, including 323 patients suffering from allergic rhinitis. The other 414 recruits were healthy controls from regions of North India. Multiplex PCR was used for genotyping the GSTT1 and GSTM1 gene polymorphisms.

Results

The GSTT1 null allele was more prevalent in asthma patients (40?%) than in the control subjects (13.3?%), which yielded a nearly fourfold risk towards asthma with odds ratio (OR) (95?% CI)?=?4.35 (3.04–6.24), χ²?=?75.34, and p?=?0.000. The GSTM1 polymorphism also revealed a greater prevalence of the GSTM1 null allele in asthma patients (46.6?%) than in controls (39.4?%). Statistical analysis yielded a marginal risk toward asthma with OR (95?% CI)?=?1.34 (1.01–1.79), χ²?=?4.37, and p?=?0.036.

Conclusions

Polymorphisms as a result of deletions in the GSTT1 and GSTM1 genes confer an increased risk towards asthma thereby suggesting the protective role of these functional genes in the development of the disease.     

Transcatheter Retrieval of Embolized AMPLATZER Septal Occluder

In selected patients, transcatheter closure of atrial septal defects with the AMPLATZER Septal Occluder has yielded excellent results. However, there is a slight risk of device embolization after deployment. We report the case of a 26-year-old woman in whom an embolized AMPLATZER device was retrieved percutaneously from the right pulmonary artery. We also discuss important technical principles for managing this uncommon but potentially severe complication.Key words: Device removal/methods, embolization, therapeutic/instrumentation, heart catheterization/instrumentation, heart septal defects, atrial/ultrasonography, patient selection, prosthesis implantation/adverse effects, prostheses and implants, septal occluder device/adverse effects, treatment outcomeTranscatheter closure of atrial septal defects (ASDs) with use of the AMPLATZER® Septal Occluder (St. Jude Medical, Inc.; St. Paul, Minn) has yielded excellent results in properly selected patients.^1,2 The major advantage of the AMPLATZER occluder is its easy retrieval at all stages of deployment before its final release from the delivery cable. Although embolization of AMPLATZER ASD occluders is rare, it can occur even when interventional cardiologists are experienced. Despite an earlier belief that the transcatheter retrieval of embolized AMPLATZER devices would be difficult, success rates from 50% to 75% have been reported.^3,4 We describe the retrieval of an embolized AMPLATZER device in a young woman. In addition, we present some technical principles with which operators practicing device closure should be familiar.     

Scoring accuracy of automated sleep staging from a bipolar electroocular recording compared to manual scoring by multiple raters

Objectives

Electroencephalography (EEG) assessment in research and clinical studies is limited by the patient burden of multiple electrodes and the time needed to manually score records. The objective of our study was to investigate the accuracy of an automated sleep-staging algorithm which is based on a single bipolar EEG signal.

Methods

Three raters each manually scored the polysomnographic (PSG) records from 44 patients referred for sleep evaluation. Twenty-one PSG records were scored by Rechtschaffen and Kales (R&K) criteria (group 1) and 23 PSGs were scored by American Academy of Sleep Medicine (AASM) 2007 criteria (group 2). Majority agreement was present in 98.4% of epochs and was used for comparison to automated scoring from a single EEG lead derived from the left and right electrooculogram.

Results

The κ coefficients for interrater manual scoring ranged from 0.46 to 0.89. The κ coefficient for the auto algorithm vs manual scoring by rater ranged from 0.42 to 0.63 and was 0.61 (group 1, κ = 0.61 and group 2, κ = 0.62) for majority agreement for all studies. The mean positive percent agreement across subjects and stages was 72.6%, approximately 80% for stages wake (78.3%), stage 2 sleep (N2) (80.9%), and stage 3 sleep (N3) (78.1%); the percentage slightly decreased to 73.2% for rapid eye movement (REM) sleep and dropped to 31.9% for stage 1 sleep (N1). Differences in agreement were observed based on raters, obstructive sleep apnea (OSA) severity, medications, and signal quality.

Conclusions

Our study demonstrated that automated scoring of sleep obtained from a single-channel of forehead EEG results in agreement to majority manual scoring are similar to results obtained from studies of manual interrater agreement. The benefit in assessing auto-staging accuracy with consensus agreement across multiple raters is most apparent in patients with OSA; additionally, assessing auto-staging accuracy limited disagreements in patients on medications and in those with compromised signal quality.