Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.     

The effect of ABCG1 deficiency on atherosclerotic lesion development in LDL receptor knockout mice depends on the stage of atherogenesis

ObjectiveAs ABCG1 plays a role in cholesterol efflux, macrophage ABCG1 expression has been suggested to protect against atherosclerosis. However, we and others observed varying effects of ABCG1 deficiency on atherosclerotic lesion size. The objective of this study was to define the effect of ABCG1 deficiency during atherosclerotic lesion progression in LDL receptor knockout (LDLr^?/?) mice.Methods and resultsABCG1^?/?/LDLr^?/? and ABCG1^+/+/LDLr^?/? littermates were fed a Western-type diet for 10 and 12 weeks in order to study the effect of ABCG1 deficiency in the exponential phase of atherosclerotic lesion formation. At 10 weeks of diet feeding, a significant 1.5-fold increase in early atherosclerotic lesion size (130 ± 12 × 10³ μm²) was observed in ABCG1^?/?/LDLr^?/? mice compared to ABCG1^+/+/LDLr^?/? mice (88 ± 11 × 10³ μm²; p < 0.05). Interestingly, in more advanced lesions, induced by 12 weeks of WTD feeding, ABCG1^?/?/LDLr^?/? mice showed a significant 1.7-fold decrease in atherosclerotic lesion size (160 ± 20 × 10³ μm² vs 273 ± 19 × 10³ μm² in control mice; p < 0.01), indicating that in the ABCG1^?/?/LDLr^?/? mice progression of lesion formation is retarded as compared to ABCG1^+/+/LDLr^?/? mice. In addition, correlation analysis performed on 7 independent published studies and the current study confirmed that ABCG1 is atheroprotective in early lesions, while the development of advanced lesions is stimulated.ConclusionsIt appears that the effect of ABCG1 deficiency on lesion development in LDLr^?/? mice depends on the stage of atherogenesis, whereby the absence of ABCG1 leads to increased lesions at sizes < 167 × 10³ μm² while in more advanced stages of atherosclerosis enhanced apoptosis and/or compensatory mechanisms lead to retarded lesion progression.     

Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2

We assessed somatic alleles of six receptor tyrosine kinase genes mutated in lung adenocarcinoma for oncogenic activity. Five of these genes failed to score in transformation assays; however, novel recurring extracellular domain mutations of the receptor tyrosine kinase gene ERBB2 were potently oncogenic. These ERBB2 extracellular domain mutants were activated by two distinct mechanisms, characterized by elevated C-terminal tail phosphorylation or by covalent dimerization mediated by intermolecular disulfide bond formation. These distinct mechanisms of receptor activation converged upon tyrosine phosphorylation of cellular proteins, impacting cell motility. Survival of Ba/F3 cells transformed to IL-3 independence by the ERBB2 extracellular domain mutants was abrogated by treatment with small-molecule inhibitors of ERBB2, raising the possibility that patients harboring such mutations could benefit from ERBB2-directed therapy.     

The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment

Background

Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology.

Methods

A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010.

Results

The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest.

Conclusions

The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event.

     

Surface Modifications of Titanium Aluminium Vanadium Improve Biocompatibility and Osteogenic Differentiation Potential

Osteogenic cells are strongly influenced in their behaviour by the surface properties of orthopaedic implant materials. Mesenchymal stem and progenitor cells (MSPCs) migrate to the bone–implant interface, adhere to the material surface, proliferate and subsequently differentiate into osteoblasts, which are responsible for the formation of the bone matrix. Five surface topographies on titanium aluminium vanadium (TiAl₆V₄) were engineered to investigate biocompatibility and adhesion potential of human osteoblasts and the changes in osteogenic differentiation of MSPCs. Elemental analysis of TiAl₆V₄ discs coated with titanium nitride (TiN), silver (Ag), roughened surface, and pure titanium (cpTi) surface was analysed using energy-dispersive X-ray spectroscopy and scanning electron microscopy. In vitro cell viability, cytotoxicity, adhesion behaviour, and osteogenic differentiation potential were measured via CellTiter-Glo, CytoTox, ELISA, Luminex^® technology, and RT-PCR respectively. The Ag coating reduced the growth of osteoblasts, whereas the viability of MSPCs increased significantly. The roughened and the cpTi surface improved the viability of all cell types. The additive coatings of the TiAl₆V₄ alloy improved the adhesion of osteoblasts and MSPCs. With regard to the osteogenic differentiation potential, an enhanced effect has been demonstrated, especially in the case of roughened and cpTi coatings.     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.     

Management of cervical thoracic duct cyst with cyst-venous anastomosis

INTRODUCTION

Cervical thoracic duct cyst (CTDC) is a rare cause of lateral neck mass. Surgical excision with ligation of the cervical thoracic duct is the current standard for definitive management with symptomatic patients. We report the first case of an alternative method of management performing a cyst venous anastomosis for decompression.

PRESENTATION OF CASE

A 77 year old female presented with a six month history of left arm pain, swelling and a left-sided cystic neck mass. She was treated with cyst-venous anastomosis between the cyst wall and the left internal jugular vein. At two year follow-up, she has had resolution of pain and no recurrence of the mass.

DISCUSSION

Many potential etiologies have been proposed for CTDC, though surgical management of this rare problem has consistently required cyst excision and thoracic duct ligation. Few innovative modes of therapy have been developed to address this problem in a less invasive manor. Maintaining a more natural thoracic duct anatomy decreases the likely of complications associated with duct ligation.

CONCLUSION

Cyst-venous anastomosis for the management of CTDC provides an effective, novel form of treatment which maintains the integrity of the thoracic duct and avoids potential complications associated with duct ligation.