Influence of P. vivax malaria on erythrocyte aggregation and deformability

Malaria due to Plasmodium vivax affects blood flow in cardiovascular system. The present work is aimed to determine the variability of erythrocyte deformability and aggregation in malaria patients in comparison with that of normal subjects. Blood samples of malaria patients (n=16), selected based on occurrence of parasitaemia, are categorized into low (LP), medium (MP) and high parasitaemia (HP), which represent increasing levels of the disease severity. For measurement of aggregation and deformability, by laser aggregometer and optical hemorheometer, the erythrocyte suspensions are prepared in plasma and physiological saline at hematocrit 5%. The results show that the erythrocyte deformability is significantly reduced (p<0.001) with the increasing level of parasitaemia. Despite this decrease in deformability, the aggregation parameters are significantly increased, indicating the occurrence of hyper-aggregation, particularly in MP and HP, due to involvement of various factors. These changes may partly be contributing in the observed changes in blood flow in the microcirculation.     

Growth hormone directly stimulates testosterone and oestradiol secretion by rat Leydig cells in vitro and modulates the effects of LH and T3

The modulatory effect of GH on basal, LH and T3 mediated secretion of testosterone and oestradiol by purified rat (60 day old) Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 10(3)) were cultured for 48 hours at 34 degrees C in a medium containing different concentrations of rat GH (5-400 ng/mL), after an initial culture for 24 hours at 37 degrees C. GH increased testosterone and oestradiol secretions in a dose dependent manner. While testosterone secretion reached the saturation point with 50 ng GH, oestradiol secretion reached the saturation point with 150 ng GH, followed by diminished secretions. Co-administration of minimum (10 ng) effective does of GH with minimum (25 ng) or maximum (100 ng) effective doses of oLH significantly decreased the testosterone secretion. However, an increased secretion of testosterone was observed when maximum effective doses of rGH (50 ng) and oLH (100 ng) were co-administered. Minimum effective (25 ng) or maximum effective (50 ng) doses of T3 inhibited GH mediated secretion of testosterone in vitro. Oestradiol concentration in the culture medium increased when either dose of rGH was co-administered with the minimum or maximum effective doses of oLH. T3 50 ng augmented the secretion of oestradiol by Leydig cells in the presence of GH. These results indicate that GH acts as a gonadotrophin to stimulate testosterone and oestradiol secretions by Leydig cells, and that it modulates LH or T3 induced secretion of these steroids, depending on the intensity of their stimulation.     

Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection

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Anti-cancer activity of quercetin in neuroblastoma: an in vitro approach

Neuroblastoma is a neuroendocrine tumour derived from neural crest cells and it remains a major therapeutic challenge in pediatric oncology. As response rates to chemotherapy are low, surgery remains the only effective treatment but since many tumors have metastasized at the time of diagnosis, curative surgery is rarely achieved. Consequently, a substantial need for new therapeutic options emerges. Quercetin a flavonoid, has been reported to lower the risk of several cancers. This study was designed to investigate its effects on apoptosis induction in the N2a, a mouse neuroblastoma cell line. The cell viability was determined by dimethyl thiazolyl tetrazolium bromide assay and diamidino-2-phenylindole staining was performed to confirm the apoptosis. The gene expression of bcl-w, p53, p27 and protein expression of caspases (3 and 9), bax, cytochrome-c were studied. This in vitro outcome suggests that quercetin can be used as a potent anti-cancer drug in future.     

Pilot Study to Evaluate Feasibility of Image-Guided Breast-Conserving Therapy in the Advanced Multimodal Image-Guided Operating (AMIGO) Suite

Background

The rate of reexcision in breast-conserving surgery remains high, leading to delay in initiation of adjuvant therapy, increased cost, increased complications, and negative psychological impact to the patient.1 ^– 3 We initiated a phase 1 clinical trial to determine the feasibility of the use of intraoperative magnetic resonance imaging (MRI) to assess margins in the advanced multimodal image-guided operating (AMIGO) suite.

Methods

All patients received contrast-enhanced three-dimensional MRI while under general anesthesia in the supine position, followed by standard BCT with or without wire guidance and sentinel node biopsy. Additional margin reexcision was performed of suspicious margins and correlated to final pathology (Fig. 1). Feasibility was assessed via two components: demonstration of safety and sterility and acceptable duration of the operation and imaging; and adequacy of intraoperative MRI imaging for interpretation and its comparison to final pathology. Fig. 1

Schema of AMIGO trial     

Combinatorial approach for screening and assessment of multiple therapeutic enzymes from marine isolate Pseudomonas aeruginosa AR01

Industrialization and modernization have led to humans being more susceptible to diseases. Therapeutic enzymes from traditional earthbound bacterial origin result have less therapeutic value. Hence, the hunt for a novel source of enzymes is indispensable. Twenty different marine bacterial strains were isolated from mangrove soil around S. P. Pattinum, Tamilnadu, India. From repeated qualitative and quantitative experiments, the study results were that, out of twenty bacterial isolates, only one Gram-negative bacterium was positive for multiple therapeutic enzymes such as asparaginase, glutaminase, uricase and collagenase. Based on its 99% 16S rRNA sequence similarity with Pseudomonas aeruginosa, the isolate was designated as Pseudomonas aeruginosa AR01. Modified minimal medium amended with asparagine results in a simple and cost-effective, one-pot production medium for enhanced production and easy purification of all therapeutic enzymes. The biochemical studies imply that the therapeutic enzymes from P. aeruginosa AR01 may find a significant role in medical applications. The in vitro cytotoxic study reveals that the anticancer enzyme from P. aeruginosa is considerably effective with an IC₅₀ value of 12 μg mL⁻¹ against K-562 cell line. Colony PCR was performed for the detection of specific therapeutic enzyme-coding genes in the genome of P. aeruginosa AR01. PCR results confirm that P. aeruginosa AR01 possesses nucleotide regions for corresponding therapeutic enzymes in its gene cluster. BLASTN and BLASTX analyses of the partial nucleotide sequences of therapeutic enzymes were deposited in GenBank. The results appear so promising that Pseudomonas aeruginosa AR01 may be a potent candidate for medical biotechnology.

A simple and rapid screening of therapeutic enzymes from bacteria was conducted using functional- and sequence-based approach.     

Topical negative pressure for the treatment of neonatal post-sternotomy wound dehiscence

The use of topical negative pressure (TNP) dressings for sternal wound dehiscence or mediastinitis in the neonatal population is rare. The majority of case reports have focused on wound healing as an endpoint and have not discussed the physiological advantage that TNP dressings may impart with regard to sternal stabilisation, improved respiratory function and early weaning from mechanical ventilation. We present a case of the use of TNP in neonatal post-sternotomy wound dehiscence and mediastinitis, from a UK perspective, with an emphasis on wound healing and physiological optimisation. As well as an improvement in sternal wound healing due to the local effects of the TNP system, serial arterial blood gas analysis revealed a significant improvement in systemic physiological parameters, including a reduction in pCO(2) in the period (days 20-31) after application of TNP (p<0.0001) compared to the period before where simple occlusive dressings were applied. Hydrogen ion concentration also significantly reduced in this period (p=0.0058). The use of the TNP system in association with systemic antibiotics successfully treated the mediastinitis. A sealed, controlled wound environment also allowed ease of nursing and an expedited return to care by the parents. We would recommend the consideration of TNP dressings in similar cases of neonatal and paediatric sternal wound dehiscence. Not only do we observe the local effects of improved wound healing, the systemic effects of improved lung function are also valuable in the early management of such complex cases.