Phyllodes tumors of the breast: the role of pathologic parameters

We aimed to establish whether morphologic parameters were prognostically important in a large series of breast phyllodes tumors in Asian women. Of 335 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital, Singapore, between January 1992 and December 2002, 250 (74.6%) were benign, 54 (16.1%) borderline, and 31 (9.3%) malignant, based on histologic review of archival slides. Of the women, 43 (12.8%) experienced recurrences during the follow-up period. Recurrent disease was correlated with grade or classification (P = .028), stromal atypia (P = .016), stromal hypercellularity (P = .046), and permeative microscopic borders (P = .021). Multivariate analysis revealed that independent predictors of recurrence were pseudoangiomatous stromal hyperplasia (PASH) and margin status, whereby the presence of PASH and complete or negative margins reduced recurrence hazards by 51.3% and 51.7% respectively. The 7 women who died of disease during follow-up had malignant phyllodes tumor at the outset and experienced recurrences, and death was preceded by distant metastases.     

Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model.

1,2-Dimethylhydrazine (DMH) is a toxic environmental pollutant which was reported also to be a colon-specific carcinogen. This study was performed to study the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxycurcumin analog (BDMC-A) on DMH-induced colon carcinogenesis in male Wistar rats and effects were compared with that of the reference drug, curcumin. Rats were given a weekly subcutaneous injection of DMH (20mg/kg body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization) tumor incidence was 100% in DMH-treated rats. Tumor was identified histologically as adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in DMH-treated rats. However, there was no colonic tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total bile acids and cholesterol in 24h fecal samples were significantly lower in DMH administered rats when compared to control rats, while, the excretion of bile acids and cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In DMH-induced tumor bearing rats the levels of colonic and intestinal cholesterol was significantly increased whereas, the levels of phospholipid was decreased with a concomitant increase in the activities of phospholipase A (PLA) and phospholipase C (PLC), compared to untreated control rats. Intragastric administration of BDMC-A and curcumin to DMH administered rats significantly lowered the cholesterol content and raised the phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of BDMC-A during DMH-induced colon carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii). bile acids, (iii). cholesterol, and (iv). phospholipid metabolism in the target organ. Absence of histological changes in the colon of rats treated with BDMC-A, shows that long term administration of BDMC-A is nontoxic to experimental animals. Our study suggest that BDMC-A may emerge as a potent anticarcinogenic agent against colon cancer. As both BDMC-A and curcumin are equipotent in inhibiting the DMH-induced colon tumor incidence and normalizing histological changes, it could be concluded that the terminal phenolic group and the conjugated double bonds in the central seven carbon change may be responsible for the beneficial effects.     

Ameliorating effect of vitamin E on in vitro development of preimplantation buffalo embryos

Purpose  Oxidative stress has been implicated in the etiology of defective embryo development. Vitamin E is an effective lipid-soluble antioxidant, protecting cell membranes from peroxidative damage. In this context, this study was undertaken to find if supplementation of vitamin E in culture medium could ameliorate the developmental competence of preimplantation buffalo embryos. Methods  Vitamin E was supplemented in maturation/embryo culture medium at concentrations of 0, 50, 100, 200 and 400 μM. The developmental competence of buffalo embryos was assessed by observing the cleavage, morulae, blastocyst rate, total cell count and comet assay. Results  Vitamin E had no significant effect in maturation medium. Vitamin E in embryo culture medium under 5% O₂ significantly reduced blastocyst formation in the 400 μM supplemented group. Culture under 20% O₂ enhanced the frequency of blastocyst formation, total cell count and significantly reduced comet tail in the 100 μM supplemented group (P < 0.001) when compared with the control. Vitamin E in ECM for the first 72 h of culture period enhanced blastocyst rate and total cell number in the 100 μM group (P < 0.001) when compared with the control. Conclusion  Our results demonstrate that the addition of Vitamin E may enhance the developmental competence of buffalo embryos in vitro by protecting them from oxidative stress. Capsule Buffalo embryos are prone to oxidative stress due to high lipid content; supplementation of vitaminE enhanced their developmental competence by protecting them from oxidative stress.     

Synthesis of non-toxic,biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity. However, their poor long-term stability in different environments, namely, pH, ionic strength, and temperature, and cytotoxicity toward mammalian cells has restricted their more extensive applications. Hence, there is urgent need to develop highly biocompatible, non-toxic, and stable silver nanoparticles for wide-ranging environments and applications. In the present study, a simple, sustainable, cost-effective and green method has been developed to prepare highly stable aqueous colloidal silver nanoparticles (AgNPs-EW) using the ovalbumin, ovotransferrin, and ovomucoid of egg-white as reducing and capping agents accomplished under the irradiation of direct sunlight. Then, we evaluated the effects of freezing–drying (lyophilization) and freeze–thaw cycles on the stability of AgNPs-EW in aqueous solution under visual inspection, transmission electron microscopy, and absorbance spectroscopy. In addition, we studied the antibacterial activity against Salmonella typhimurium and Escherichia coli, carried out biocompatibility studies on chicken blood, and tested acute, chronic toxicity in Drosophila melanogaster. The results suggest that AgNPs-EW did not aggregate upon freeze-thawing and lyophilization, thus exhibiting remarkable stability. The antibacterial activity results showed that the AgNPs-EW had the highest antibacterial activity, and the minimum inhibitory concentration (MIC) of AgNPs-EW for E. Coli and S. typhimurium were 4 and 6 μg ml⁻¹, respectively. The biocompatibility study revealed that the AgNPs-EW did not induce any hemolytic effect or structural damage to the cell membranes of chicken erythrocytes up to a concentration of 12 μg ml⁻¹. Similarly, no acute and chronic toxicity was observed on melanization, fecundity, hatchability, viability, and the duration of development in the 1^st generation of Drosophila melanogaster at the concentration range of 10 mg L⁻¹ to 100 mg L⁻¹ of AgNPs-EW, and all the flies completed their full developmental cycle. Therefore, the present study successfully demonstrated the green and sustainable preparation of non-toxic AgNPs-EW having good biocompatibility, enhanced colloidal stability, and antibacterial activity. Hence, the synthesized AgNPs-EW could be used for the development of an antimicrobial formulation for controlling microbial infection.

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity.     

Ovicidal, repellent, adulticidal and field evaluations of plant extract against dengue, malaria and filarial vectors

Mosquitoes are insect vectors responsible for the transmission of parasitic and viral infections to millions of people worldwide, with substantial morbidity and mortality. Infections transmitted by mosquitoes include malaria, yellow fever, chikungunya, filariasis and other arboviruses. Insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. The adulticidal activities of crude hexane, benzene, ethyl acetate, acetone and methanol leaf extracts of Acalypha alnifolia were assayed for their toxicity against three important vector mosquitoes, viz., Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. The adult mortality was observed after 24 h of exposure. All extracts showed moderate adulticide effects; however, the highest adult mortality was found in methanol extract were observed. The LC₅₀ values of A. alnifolia leaf extracts against adulticidal activity of (hexane, benzene, ethyl acetate, acetone and methanol) A. aegypti, A. stephensi and C. quinquefasciatus were the following: A. aegypti values were 371.87, 342.97, 320.17, 300.86 and 279.75 ppm; A. stephensi values were 358.35, 336.64, 306.10, 293.01 and 274.76 ppm; C. quinquefasciatus values were 383.59, 354.13, 327.74, 314.33 and 291.71 ppm. The results of the repellent activity of hexane, benzene, ethyl acetate, acetone and methanol extract of A. alnifolia plant at three different concentrations of 1.0, 3.0, and 5.0 mg/cm² were applied on skin of forearm in man and exposed against adult female mosquitoes. In this observation, this plant crude extracts gave protection against mosquito bites without any allergic reaction to the test person, and also, the repellent activity is dependent on the strength of the plant extracts. Mean percent hatchability of the ovicidal activity was observed 48 h post-treatment. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. Mortality of 100 % with methanol extract of A. alnifolia was exerted at 125 and 300 ppm. The larval density was decreased after the treatment of plant extracts at the breeding sites (water bodies system) of vector mosquitoes, and hence, these plant extracts are suitable alternatives of synthetic insecticides for mosquito vector management.These results suggest that the leaf solvent plant extracts have the potential to be used as an ideal eco-friendly approach for the control of mosquitoes. This study provides first report on the mosquito ovicidal, repellent and adulticidal activities of these plant extracts against mosquito vector species from India.     

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Venous blood gas in adult patients with diabetic ketoacidosis

Report by Ziauddin Hassan, Devasena M Subramonyam, Registrars
Checked by Shobhan Thakore, Specialist Registrar