Breast Cancer Selective Disruption of Actin Cytoskeleton by Diallyl Trisulfide

Diallyl trisulfide (DATS) is an attractive anti-cancer phytochemical with in vitro and in vivo growth inhibitory effects against different solid tumors including breast cancer. We have shown previously that an immortalized mammary epithelial cell line (MCF-10A) is resistant to growth inhibition by DATS. In this study, we performed RNA-seq analysis using a breast cancer cell line (SK-BR-3) and MCF-10A cells to gain insights into cancer selective effects of DATS. The Gene Ontology analysis revealed upregulation of genes associated with actin cytoskeleton but downregulation of mitochondria-related genes in the SK-BR-3 human breast cancer cell line but not in the non-oncogenic MCF-10A cell line upon treatment with DATS. Quantitative real-time reverse transcription polymerase chain reaction confirmed DATS-mediated upregulation of several actin cytoskeleton-related genes in the SK-BR-3 cell line. The DATS treatment dose-dependently disrupted actin cytoskeleton in the SK-BR-3 cell line, whereas the MCF-10A cell line was more resistant to this effect. The DATS treatment caused a marked increase in phosphorylation of dynamin-1-like (DRP1) protein in the SK-BR-3 cell line. However, the DATS-mediated apoptosis was not affected by genetic deletion of DRP1 protein. The Reactome pathway analysis showed downregulation of genes associated with citric acid cycle in the SK-BR-3 cell line but not in the MCF-10A cells. However, expression of aconitase 2 or dihydrolipoamide S-succinyltransferase was not affected by DATS treatment. In conclusion, this study reveals that actin cytoskeleton is a novel target of DATS in the SK-BR-3 cell line, which may explain its inhibitory effect on breast cancer cell migration.

Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis

Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.

Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis

Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.

Dexmedetomidine improves surgical field in cochlear implant surgery: a randomized, double-blind, placebo-controlled trial

Objectives: Sympatholytic properties of dexmedetomidine have many advantages to use in general anesthesia especially in pediatric age group undergoing cochlear implant surgeries. This study is designed to compare the effects of bolus dose of dexmedetomidine followed by infusion with placebo in cochlear implant surgeries for quality of hypotensive anesthesia with hemodynamic stability and incidence of complications in pediatric age group particularly emergence delirium with sevoflurane

Methodology: 60 pediatric patient of ASA grade I or II with congenital or acquired deafness of age ranging from 2 to 8 years scheduled for cochlear implant surgery were included in this study. Group D were administered dexmedetomidine 0.5 micro g/kg in 100 ml 0.9% NaCI over 10 min followed by infusion of dexmedetomidine at 0.5 micro g/kghr[-1] and Group P was given placebo only i.e. 0.9% NaCl 100 ml over 10 min followed by infusion at 2 ml.hr[-1]. Heart rate [HR] and mean arterial pressure [MAP] at different time interval, intraoperative fentanyl and propofol consumption, surgeons' satisfaction score and complications, particularly incidences of emergence delirium were recorded

Statistical analysis: Mean with standard deviation of various parameters of both groups was compared using student's t test were analyzed

Result: statistical significant lowering of MAP, HR, opioid consumption and rate of complications were lower in dexmedetomidine group compared to placebo group

Conclusion: Intraoperative administration of dexmedetomidine provides better surgical field and subsequently higher surgeon's satisfaction score leading to reduced surgery time with better recovery profile

Symposium: “Oncology Leadership in Asia” / Journal of the Korean Cancer Association, 대한암학회지

The symposium on “Oncology Leadership in Asia” was held as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association with International Cancer Conference. Given the increasing incidence of cancer in all countries and regions of Asia, regardless of developmental stage, and also in light of the recognized need for Asian countries to enhance collaboration in cancer prevention, research, treatment and follow-up, the symposium was held with the aim of bringing together oncology specialists from eight countries and regions in Asia to present the status in their own national context and discuss the key challenges and requirements in order to establish a greater Asian presence in the area of cancer control and research. The task of bringing together diverse countries and regions is made all the more urgent in that while Asia now accounts for more than half of all new cancer cases globally, clinical guidelines are based predominantly on practices adopted in Western countries, which may not be optimized for unique ethnic, pharmacogenomic and cultural characteristics in Asia. Recognizing the need for Asia to better gather information and data for the compilation of Asia-specific clinical guidelines, the participants discussed the current status in Asia in the national and regional contexts and identified future steps towards integrated and collaborative initiatives in Asia. A key outcome of the symposium was a proposal to combine and integrate the activities of existing pan-Asian societies, including the Asian Pacific Federation of Organizations for Cancer Research and Control (APFOCC) and Asian Clinical Oncology Society (ACOS). Further proposals included the expansion of pan-Asian society membership to include individuals and the essential need to encourage the participation of young researchers in order to ensure self-sustainability of cancer control efforts in the future.

Outcome of bone marrow instillation at fracture site in intracapsular fracture of femoral neck treated by head preserving surgery / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>The aim of present study is to evaluate the outcome of bone marrow instillation at the fracture site in fracture of intracapsular neck femur treated by head preserving surgery.</p><p><b>METHODS</b>This study included 32 patients of age group 18-50 years with closed fracture of intracapsular neck femur. Patients were randomized into two groups as per the plan generated via www.randomization.com. The two groups were Group A (control), in which the fracture of intracapsular neck femur was treated by closed reduction and cannulated cancellous screw fixation, and Group B (intervention), in which additional percutaneous autologous bone marrow aspirate instillation at fracture site was done along with cannulated cancellous screw fixation. Postoperatively the union at fracture site and avascular necrosis of the femoral head were assessed on serial plain radiographs at final follow-up. Functional outcome was evaluated by Harris hip score.</p><p><b>RESULTS</b>The average follow-up was 19.6 months. Twelve patients in each group had union and 4 patients had signs of nonunion. One patient from each group had avascular necrosis of the femoral head. The average Harris hip score at final follow-up in Group A was 80.50 and in Group B was 75.73, which was found to be not significant.</p><p><b>CONCLUSION</b>There is no significant role of adding on bone marrow aspirate instillation at the fracture site in cases of fresh fracture of intracapsular neck femur treated by head preserving surgery in terms of accelerating the bone healing and reducing the incidence of femoral head necrosis.</p>

Failure to decolonize mupirocin and linezolid resistant MRSA from a patient with necrotizing soft tissue infection

Colonization with methicillin resistant Staphylococcus aureus [MRSA] is considered to be a major risk factor for skin and soft tissue infections. We present a case of a patient suffering from necrotizing soft tissue infection and exposed to multiple antibiotics and developed colonization with linezolid resistant MRSA [LRMRSA]. He could not be decolonized despite prolonged conventional or modified MRSA decolonization protocols

Chronic Nonmodulated Microwave Radiations in Mice Produce Anxiety-like and Depression-like Behaviours and Calcium- and NO-related Biochemical Changes in the Brain

The present study was aimed to investigate behavioural and biochemical effects of chronic exposure of amplitude modulated and non-modulated microwave radiation on laboratory mice. Chronic microwave exposures were executed with 2.45 GHz of either modulated (power density, 0.029 mW/cm²; specific absorption rate, 0.019 W/Kg with sinusoidal modulation of 400 Hz) or nonmodulated continuous sinusoidal wave (power density, 0.033 mW/cm²; specific absorption rate, 0.023 W/Kg) for 2 hrs daily for 1 month. Mice subjected to non-modulated microwave exposure had significantly increased acetylcholinesterase activity and increased intracellular calcium and nitric oxide levels in the cerebral cortex and hippocampus, and also had increased glucose and corticosterone levels in blood compared to control mice. These non-modulated microwave-exposed mice exhibited anxiety-like and depression-like behaviours. In contrast, mice exposed to modulated microwave for the same period did not show such changes in concomitant biochemical and behavioural analyses. These results suggest that chronic non-modulated microwave, but not modulated microwave, radiation may cause anxiety-like and depression-like behaviours and calcium- and NO-related biochemical changes in the brain.

Pregnancy-associated asymptomatic bacteriuria and drug resistance

In developing countries, bacteriuria is associated with significant maternal and foetal risks. Rapid emergence of antibiotic resistance warrants continuous monitoring of the susceptibility patterns of bacterial isolates. In this study, we report our findings regarding the drug resistance patterns of bacteria isolates from pregnant women with urinary tract infections [UTI]. This study included 1358 pregnant women attending the antenatal clinic at the Department of Obstetrics and Gynecology between July 2013 and August 2014. Urine specimens were processed for isolation and identification of bacterial species following standard microbiological methods. The disc diffusion test was used to determine the antimicrobial resistance patterns of the recovered isolates at the Central Laboratory of Microbiology of Nepalgunj Medical College, Nepal. Three hundred and seventeen isolates were positive for significant bacteriuria. E. coli, K. pneumonia, P. aeruginosa, E. faecalis, S. aureus, P. mirabilis, CoNS, and P. vulgaris accounted for 61.5%, 17%, 7.5%, 5.3%, 2.8%, 2.5%, 1.8%, and 1.2% of bacterial isolates, respectively. Resistance to erythromycin [58.6%], co-trimoxazole [57.4%] and ciprofloxacin [50.1%] was observed. Among the 317 positive isolates, 203 [64%] were from women in the 21-30-year-old age group, and the rate of bacteriuria in this group was statistically significantly more than those for the other age groups [P < 0.05]. Bacteriuria is frequent among pregnant women, which generates a need for routine urine culture screening. In this study, E. coli was the most predominant bacterial species identified followed by K. pneumonia. Furthermore, women in the 21-30-year-old group were at a higher risk of UTI. Erythromycin, co-trimoxazole and ciprofloxacin should not be empirically used as first-line drugs in the treatment of UTIs. Continuous local monitoring of resistance patterns is necessary to determine the appropriate empirical antimicrobial therapy

Simulation and comparison of radiology X-ray spectra by MCNP and GEANT4 codes

Monte Carlo method is a very accurate method to optimize medical diagnostic radiology spectra and simulation of radiation transportation. Using MCNP code, radiology and mammography attenuated x-rayspectraweresimulated.The IPEM report number 78 was used as a reference to compare with the GEANT4 and MCNP simulations because of its popularity and wide availability. The results of GEANT4 in 40keV showed a good homogeneity with IPEM report in terms of intensity, whilst the MCNP code in tube voltage 150kVp showed a very good agreement. Whereas theGEANT4outputintensityinallcases was less than the IPEM report, MCNP code showed higher characteristic peak intensity. The MCNP results were obtained with a less error percentage in comparison with IPEM reportexceptatlowenergies. The comparison shows a good agreement between these two codes. MCNP shows a very goodagreement in high tube voltage whereas GEANT4 showsvery goodagreement in low tube voltage

Optimization of process variables for enhanced lactic acid production utilizing paneer whey as substrate in submerged fermentation process

In the present study lactic acid production was enhanced by optimizing the three process variables viz; inoculum size, temperature and pH using three factor five level CCRD [central composite rotatable design] by Lactobacillus delbruckii under SMF [submerged fermentation process]. Paneer [dairy byproduct] whey was used as sole substrate for lactic acid production. Design Expert 8.0.2.0 software depicted that an optimum concentration of 8% [v/v] size of inoculum, 5.50 pH and 36.53°C temperature gave lactic acid and biomass yield of 5.61 g/L[-1] and 4.27 g/L[-1], respectively. Lactic acid production was scale up in 7.5 L bioreactor under optimized conditions and it gave lactic acid and biomass yield of 39.2 +/- 1.4 and 47.6 +/- 0.8 g/L[-1], respectively. micro[g], Y[P/S], Y[P/X] and productivity were found to be 0.14 h[-1], 0.66 g/g, 0.7 g/g and 1.98 g/L[-1] h, respectively. Leudking Piret equation deduced that lactic acid production was growth associated which varies from earlier reports. Lactic acid was characterized by FTIR [Fourier transform infrared spectroscopy] and HPLC

Isolation and molecular identification of Mycoplasma equigenitalium from equine genital tracts in northern India

Although Mycoplasma equigenitalium has been implicated in equine reproductive problems, its prevalence is largely unexplored due to the lack of specific diagnostic tests. To address this limitation, the authors developed and optimized species-specific primer pairs that target M. eguigenitalium rpoB [RNA polymerase B subunit] gene sequences. The specificity of the PCR assay developed in this study was determined using 12 field isolates including the type strain of M. equigenitalium and other Mycoplasma species. In the field study, a total of 122 mare and stallion samples comprising of 50 clinical and 72 random samples were subjected to speciesspecific PCR assay to detect M. equigenitalium in equine genital tracts. Mycoplasma equigenitalium [MEG] species-specific PCR detected 22.13% positive samples; however, only 9.01% of the samples were found to be positive using the conventional culture technique. The PCR established in this study could be used for rapid, specific and accurate diagnosis of M. equigenitalium strains. To the authors' knowledge, this is the first report addressing the development and evaluation of species-specific PCR to detect M. equigenitalium

Malunion in displaced intracapsular fracture of femoral neck: A rare case / 中华创伤杂志(英文版)

Intracapsular fracture of femoral neck is treated by anatomical reduction (preferably closed) and cannulated cancellous lag screw fixation. Malunion of these fractures have been described in the coronal plane (coxa valga or coxa vara). We reported a case of young adult patient with displaced intracapsular fracture of femoral neck that had malunited in sagittal plane with callus formation with excellent functional outcome. The radiographs revealed intracapsular fracture of femoral neck right side (Garden type 4 and Pauwel type 3). The patient was operated and closed reduction and internal fixation with three cannulated cancellous screws was performed. The postoperative radiograph revealed a loss of reduction in the lateral view. Due to this technical error, the patient was counselled for revision fixation for which he refused. At 9 months we observed union of the fracture in the displaced position by callus formation. Harris hip score at 2 years was 96 that indicate excellent functional outcome and the radiographs did not reveal any evidence of avascular necrosis of femoral head. We advised revision surgery to our patient as he had increased chances of implant failure and nonunion. However he refused the revision surgery and was continued with the suboptimal reduction. However, the fracture united and that too with callus formation, which is not a described phenomenon in neck of femur fracture.

Japanese encephalitis

We present a case of Japanese encephalopathy, which posed serious problems during diagnosis as well management. Our patient had to be nursed in ICU and mechanically ventilated for a prolonged period [more than 50 days] and was successfully weaned, but with difficulty and with sustained and careful monitoring and flexible planning. A multispecialty approach made all the difference between life and death

Immediate implants in dentistry: a review

Presently dental implants are one of the most exciting and rapidly developing aspects of dental practice. Implant dentistry has come a long way from skepticism to being accepted as the best modality to treat complete or partial edentulism. In the last two decades a great deal of activity in the field has occurred with the development of better materials and newer techniques that have resulted in improved clinical performance of implants. Placement of dental implants into fresh extraction sites offers a number of significant advantages to both the patients and the clinicians. Although some of the early implant practitioners assume that long term implant survival depended on placement on healed alveolar ridge, the growing body of evidence confirms that immediate implant placement yields excellent and predictable results. Considering the important role of a Periodontist in the insertion and maintenance of implant, the available literature has been reviewed

Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models

OBJECTIVE@#To evaluate the hepatoprotective potential of ethanolic (50%) extract of Ziziphus oenoplia (L.) Mill (Z. oenoplia) root against isoniazid (INH) and rifampicin (RIF) induced liver damage in animal models.@*METHODS@#Five groups of six rats each were selected for the study. Ethanolic extract at a dose of 150 and 300 mg/kg as well as silymarin (100 mg/kg) were administered orally once daily for 21 d in INH + RIF treated groups. The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), and bilirubin were estimated along with activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione peroxidase, and hepatic melondialdehyde formation. Histopathological analysis was carried out to assess injury to the liver.@*RESULTS@#The considerably elevated serum enzymatic activities of glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin due to INH + RIF treatment were restored towards normal in a dose dependent manner after the treatment with ethanolic extract of Z. oenoplia roots. Meanwhile, the decreased activities of superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were also restored towards normal dose dependently. In addition, ethanolic extract also significantly prevented the elevation of hepatic melondialdehyde formation in the liver of INH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections.@*CONCLUSIONS@#The results of this study strongly indicate that ethanolic extract of Z. oenoplia has a potent hepatoprotective action against INH + RIF induced hepatic damage in rats.

Antihyperglycemic activity, antihyperlipedemic activity, haematological effects and histopathological analysis of Sapindus mukorossi Gaerten fruits in streptozotocin induced diabetic rats

OBJECTIVE@#To investigate the antihyperglycemic and antihyperlipidemic properties of hydroalcoholic extract of fruits of Sapindus mukorossi Gaerten and its beneficial effect on haematological parameters with histopathological analysis in streptozotocin induced diabetic rats.@*METHODS@#Sapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and standard drug glybenclamide (0.5 mg/kg body weight) were administered to diabetic rats. Effect of extract on hyperglycemia, hyperlipidemia and hematological parameters was studied in diabetic rats. Histopathological changes in diabetic rat pancreas were also observed after extract and glybenclamide treatment.@*RESULTS@#Daily oral administration of Sapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and glybenclamide for 20 days showed beneficial effects on blood glucose level (P<0.01) and lipid level. The extract has a favorable effect on the histopathological changes of the pancreas in streptozotocin induced diabetes.@*CONCLUSION@#These findings reveal that the hydroalcoholic extract of Sapindus mukorossi fruits extract possesses antihyperglycemic and antihyperlipidemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters.

Screening of C-kit gene mutation in acute myeloid leukaemia in northern India

Acute Myeloid Leukaemia [AML] is a cancer of blood-forming cells in bone marrow. C-kit gene is a Receptor Tyrosine Kinase class III [RTK] that is expressed by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. It is known that c-kit is a proto-oncogene and the activating c-kit mutations are likely to contribute in the development of leukaemia in humans. Exon 11 of c-Kit gene is the frequent site for mutations in different kinds of tumours. In order to determine the frequency and prevalence of exon 11 mutations in 51 AML cases, we have done polymerase chain reaction-single-strand conformational polymorphism followed by direct DNA sequencing. The c-kit mutations in exon 11 were detected in 15.68% [8/51] in AML cases. We have detected totally ten missense mutations in eight AML cases those include Lys550Asn, Tyr568Ser, Ile571Leu, Tyr578Pro, Trp582Ser and Arg588Met and novel missense mutations at codons Ile563Lys and Val569Leu. Mutations at codons Ile571Leu and Trp582Ser was found in two independent cases. The presence of c-kit mutations in our study adds to investigative spectrum of AML cases. Since the c-kit mutations are seen in other malignancies, mutations in exon 11 of the c-kit gene might be involve in pathogenesis and represent useful predictive genetic marker in AML. Further studies in larger group of cases possibly will be required to determine the prognostic implications and to investigate how these mutations are co-related to the progression and pathogenesis of AML

Urinary tract endometriosis: review of 19 cases

The aim of our study was to evaluate the treatment outcomes of medical and surgical management of urinary tract endometriosis. Urinary tract endometriosis patients enrolled between Jan 2006 and May 2010 were retrospectively reviewed. Preoperative datas [mode of presentation, diagnosis, imaging], intraoperative findings [location and size of lesion], postoperative histopathology and follow-up were recorded and results were analyzed and the success rate of different modalities of treatment was calculated. In our study, of nineteen patients, nine had vesical involvement and ten had ureteric involvement. Among the vesical group, the success rate of transurethral resection followed by injection leuproide was 60% [3/5], while among the partial cystectomy group, the success rate was 100%. Among patients with ureteric involvement, success rate of distal ureterectomy and reimplantation was 100%, laparoscopic ureterolysis with Double J stenting followed by injection leuprolide was 75% while that of Gonadotropin- releasing hormone [GnRh] analogue alone was 67%. One should have a high index of suspicion with irritative voiding symptoms with or without hematuria, with negative urine culture, in all premenopausal women to diagnose urinary tract endometriosis. Partial cystectomy is a better alternative to transurethral resection followed by GnRh analogue in vesical endometriosis. Approach to the ureter must be individualised depending upon the severity of disease and dilatation of the upper tract to maximise the preservation of renal function