Showing papers by "Manipal University published in 2008"

Quantitative proteomics using stable isotope labeling with amino acids in cell culture

Abstract: Stable isotope labeling with amino acids in cell culture (SILAC) is a simple in vivo labeling strategy for mass spectrometry-based quantitative proteomics. It relies on the metabolic incorporation of nonradioactive heavy isotopic forms of amino acids into cellular proteins, which can be readily distinguished in a mass spectrometer. As the samples are mixed before processing in the SILAC methodology, the sample handling errors are also minimized. Here we present protocols for using SILAC in the following types of experiments: (i) studying inducible protein complexes, (ii) identification of Tyr kinase substrates, (iii) differential membrane proteomics and (iv) studying temporal dynamics using SILAC 5-plexing. Although the overall time is largely dependent on the rate of cell growth and various sample processing steps employed, a typical SILAC experiment from start to finish, including data analysis, should take anywhere between 20 and 25 d.

Mass and lifetime measurements of exotic nuclei in storage rings

Abstract: Mass and lifetime measurements lead to the discovery and understanding of basic properties of matter. The isotopic nature of the chemical elements, nuclear binding, and the location and strength of nuclear shells are the most outstanding examples leading to the development of the first nuclear models. More recent are the discoveries of new structures of nuclides far from the valley of stability. A new generation of direct mass measurements which allows the exploration of extended areas of the nuclear mass surface with high accuracy has been opened up with the combination of the Experimental Storage Ring ESR and the FRragment Separator FRS at GSI Darmstadt. In-flight separated nuclei are stored in the ring. Their masses are directly determined from the revolution frequency. Dependent on the half-life two complementary methods are applied. Schottky Mass Spectrometry SMS relies on the measurement of the revolution frequency of electron cooled stored ions. The cooling time determines the lower half-life limit to the order of seconds. For Isochronous Mass Spectrometry IMS the ring is operated in an isochronous ion-optical mode. The revolution frequency of the individual ions coasting in the ring is measured using a time-of-flight method. Nuclides with lifetimes down to microseconds become accessible. With SMS masses of several hundreds nuclides have been measured simultaneously with an accuracy in the 2 x 10(-7)-range. This high accuracy and the ability to study large areas of the mass surface are ideal tools to discover new nuclear structure properties and to guide improvements for theoretical mass models. In addition, nuclear half-lives of stored bare and highly charged ions have been measured. This new experimental development is a significant progress since nuclear decay characteristics are mostly known for neutral atoms. For bare and highly charged ions new nuclear decay modes become possible, such as bound-state beta decay. Dramatic changes in the nuclear lifetime have been observed in highly charged ions compared to neutral atoms due to blocking of nuclear decay channels caused by the modified atomic interaction. High ionization degrees prevail in hot stellar matter and thus these experiments have great relevance for the understanding of the synthesis of elements in the universe and astrophysical scenarios in general.

Students' perceptions of learning environment in an Indian medical school

Abstract: Background Learning environment in any medical school is found to be important in determining students' academic success. This study was undertaken to compare the perceptions of first year and clinical phase students regarding the learning environment at Melaka Manipal Medical College (MMMC) (Manipal Campus) and also to identify the gender wise differences in their perceptions.

A study of rivastigmine liposomes for delivery into the brain through intranasal route

Abstract: The present study is mainly aimed at delivering a drug into the brain via the intranasal route using a liposomal formulation. For this purpose, rivastigmine, which is used in the management of Alzheimer's disease, was selected as a model drug. Conventional liposomes were formulated by the lipid layer hydration method using cholesterol and soya lecithin as lipid components. The concentration of rivastigmine in brain and plasma after intranasal liposomes, free drug and per oral administration was studied in rat models. A significantly higher level of drug was found in the brain with intranasal liposomes of rivastigmine compared to the intranasal free drug and the oral route. Intranasal liposomes had a longer half-life in the brain than intranasally or orally administered free drug. Delivering rivastigmine liposomes through the intranasal route for the treatment of Alzheimer's disease might be a new approach to the management of this condition.

Herbal excipients in novel drug delivery systems

Abstract: The use of natural excipients to deliver the bioactive agents has been hampered by the synthetic materials. However advantages offered by these natural excipients are their being non-toxic, less expensive and freely available. The performance of the excipients partly determines the quality of the medicines. The traditional concept of the excipients as any component other than the active substance has undergone a substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation. Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form. This article gives an overview of herbal excipients which are used in conventional dosage forms as well as novel drug delivery systems.

Chromium Alleviates Glucose Intolerance, Insulin Resistance, and Hepatic ER Stress in Obese Mice

Abstract: objective: Chromium has gained popularity as a nutritional supplement for diabetic patients. This study evaluated the effect of chronic administration of a chromium complex of d-phenylalanine (Cr(d-phe) 3 ) on glucose and insulin tolerance in obese mice. The study tested the hypothesis that Cr(d-phe) 3 suppresses endoplasmic reticulum (ER) stress and insulin resistance in these animals. Methods and Procedures: C57BL lean and ob/ob obese mice were randomly divided to orally receive vehicle or Cr(d-phe) 3 (3.8 µg of elemental chromium/kg/day) for 6 months. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Protein levels of phosphorylated pancreatic ER kinase (PERK), α subunit of translation initiation factor 2 (eIF2α) and inositol-requiring enzyme-1 (IRE-1), p-c-Jun, and insulin receptor substrate-1 (IRS-1) phosphoserine-307 were assessed by western blotting. In vitro ER stress was induced by treating cultured muscle cells with thapsigargin in the presence or absence of Cr(d-phe) 3 . Results: ob/ob mice showed poor glucose and insulin tolerance compared to the lean controls, which was attenuated by Cr(d-phe) 3 . Markers of insulin resistance (phospho-c-Jun and IRS-1 phosphoserine) and ER stress (p-PERK, p-IRE-1, p-eIF2α), which were elevated in ob/ob mice, were attenuated following Cr(d-phe) 3 treatment. Chromium treatment was also associated with a reduction in liver triglyceride levels and lipid accumulation. In cultured myotubes, Cr(d-phe) 3 attenuated ER stress induced by thapsigargin. Discussion: Oral Cr(d-phe) 3 treatment reduces glucose intolerance, insulin resistance, and hepatic ER stress in obese, insulin-resistant mice.

Effect of holding time, temperature and different parenteral solutions on viability and functionality of adult bone marrow-derived mesenchymal stem cells before transplantation.

Abstract: Mesenchymal stem cells (MSCs) have the ability to proliferate and differentiate into various lineages, given the appropriate microenvironment, thus making MSCs promising candidates for cell transplantation. For clinical applications, MSCs need to be stored in optimal conditions so that they may be transported and made available as an off-the-shelf product for companies to market. Freshly harvested and cultured or frozen-thawed bone marrow-derived MSCs were prepared for cell transplantation. Both freshly cultured or frozen-thawed MSCs were washed and resuspended in parenteral solutions, either 0.9% saline, Dulbecco's phosphate-buffered saline (DPBS), plasmalyte A or 5%dextrose and held for 2, 4, 6 and 8 h at 4 degrees C, 37 degrees C and RT (22 degrees C). The viability of the cells, differentiation capability and expression of cell surface markers were analysed. MSCs harvested from fresh cultures, resuspended in the parenteral solutions and maintained at 4 degrees C for 6 h showed more than 90% viability, and the viability was appreciably better when suspended in 5% dextrose at 4 degrees C for 8 h. In contrast, frozen-thawed cells can be held for a maximum of 2 h after thawing before losing their viability significantly below permissible limits for transplantation. We are reporting for the first time the effect of various parenteral solutions, holding times and temperatures on the viability and functionality of bone marrow-derived freshly cultured or frozen-thawed MSCs for transplantation. Our results suggested that freshly harvested MSCs can be held for 8 h at 4 degrees C in 5% dextrose or for up to 6 h at 4 degrees C in saline, DPBS or plasmalyte A. Freeze-thawed MSCs can be held for a maximum of 2 h in plasmalyte A before transplantation without affecting their viability and ability to differentiate.

Effectiveness of reproductive health education among rural adolescent girls: a school based intervention study in Udupi Taluk, Karnataka.

Abstract: BACKGROUND: Adolescence is the most important and sensitive period of one's life [1] . According to the World Health Organization (WHO) Expert Committee, adolescence is defined as the period between 10 and 19 years, the second decade of life. OBJECTIVE: To determine the effectiveness of an educational intervention program on knowledge of reproductive health among adolescent girls. SETTINGS AND DESIGN: This educational intervention study was carried out over a period of one year. A total of 791 rural girls in the age group 16-19 years were randomly selected from coastal villages in Udupi District, Karnataka. MATERIALS AND METHODS: Adolescent girls were educated regarding reproductive health and their awareness levels were evaluated immediately following intervention. STATISTICAL ANALYSIS: Data was tabulated and analyzed using SPSS version 11.0 for Windows. Findings were described in terms of proportions and percentages. Chi square test was used to test the effect of the intervention. RESULTS: A significant increase in overall knowledge after the intervention (from 14.4 to 68%, P < 0.01) was observed regarding contraception. Knowledge regarding ovulation, first sign of pregnancy and fertilization improved by 37.2% (95% CI = (35.2, 39.2), P < 0.001). Knowledge regarding the importance of diet during pregnancy improved from 66 to 95% following the intervention. CONCLUSION: This study clearly showed that an educational intervention program can bring about a desirable change in knowledge among adolescent girls regarding reproductive health.

Microwave-induced synthesis of schiff bases of aminothiazolyl bromocoumarins as antibacterials

Abstract: A fast and highly efficient method for the synthesis of some of the schiff bases of aminothiazolylbromocoumarin (4a-m) has been performed by microwave irradiation of 2'-amino-4'-(6-bromo-3-coumarinyl) thiazole (3) and substituted aromatic aldehydes (a-m). Microwave assisted reactions have resulted in better yields of the desired products than when prepared under conventional conditions. The resulting products were evaluated for their qualitative and quantitative antibacterial activity.

Synthesis, Structure, Electrochemistry, and Spectral Characterization of Bis-Isatin Thiocarbohydrazone Metal Complexes and Their Antitumor Activity Against Ehrlich Ascites Carcinoma in Swiss Albino Mice

Abstract: The synthesis, structure, electrochemistry, and biological studies of Co(II), Ni(II), Cu(II), and Zn(II) complexes of thiocarbohydrazone ligand are described. The ligand is synthesized starting from thiocarbohydrazide and isatin. It is evident from the IR data that in all the complexes, only one part of the ligand is coordinated to the metal ion resulting mononuclear complexes. The ligand coordinates essentially through the carbonyl oxygen of the isatin fragment, the nitrogen atom of the azomethine group, and sulfur atom after deprotonation to give five membered rings. H1 NMR spectrum of the ligand shows only one set of signals for the aromatic protons, while the NH of isatin and NH of hydrazone give rise to two different singlets in the 11–14 ppm range. The formulations, [Cu(L)Cl]·2H2O, [Cu(L)(CH3COO)]·2H2O, [Ni(L)Cl], [Ni(L)(CH3COO)], [Co(L2)], and [Zn(L2)]·2H2O are in accordance with elemental analyses, physical, and spectroscopic measurements. The complexes are soluble in organic solvents. Molar conductance values in DMF indicate the nonelectrolytic nature of the complexes. Copper complex displays quasireversible cyclic voltametric responses with Ep near −0.659 v and 0.504 v Vs Ag/AgCl at the scan rate of 0.1 V/s. Copper(II) complexes show a single line EPR signals. For the observed magnetic moment and electronic spectral data possible explanation has been discussed. From all the available data, the probable structures for the complexes have been proposed. The compounds synthesized in present study have shown promising cytotoxic activity when screened using the in vitro method and at the same time were shown to have good activity when tested using the Ehrlich ascites carcinoma (EAC) model. The antimicrobial screening showed that the cobalt complex possesses enhanced antimicrobial activity towards fungi.

Prediction of radiotherapy response in cervix cancer by Raman spectroscopy: a pilot study.

Abstract: Radiotherapy is the choice of treatment for locally advanced stages of the cervical cancers, one of the leading female cancers. Because of intrinsic factors, tumors of same clinical stage and histological type often exhibit differential radioresponse. Radiotherapy regimen, from first fraction of treatment to clinical evaluation of response, spans more than 4 months. Clinical assessment by degree of tumor shrinkage is the only routinely practiced method to evaluate the tumor response. Hence, a need is created for development new methodologies that can predict the tumor response to radiotherapy at an early stage of the treatment which can lead to tailor-made protocols. To explore the feasibility of prediction of tumor radioresponse, Raman spectra of cervix cancer tissues that were collected before (malignant) and 24 h after patient was treated with 2nd fraction of radiotherapy (RT) were recorded. Data were analyzed by Principal Components Analysis (PCA) and results were correlated with clinical evaluation of radioresponse. Mean Raman spectra of RT tissues corresponding to different levels of tumor response, complete, partial, and no response, showed minute but significant variations. The unsupervised PCA of malignant tissues failed to provide any classification whereas RT spectra gave clear classification between responding (complete and partial response) and nonresponding conditions as well as a tendency of separation among responding conditions. These results were corroborated by supervised classification, by means of discrimination parameters: Mahalanobis distance and spectral residuals. Thus, findings of the study suggest the feasibility of Raman spectroscopic prediction of tumor radioresponse in cervical cancers.

Factors affecting dental anxiety and beliefs in an Indian population.

Abstract: The purpose of this study was to describe the possible factors that may affect dental anxiety and beliefs and to validate and test the psychometric properties of the Modified Dental Anxiety Scale (MDAS) and a Modified Dental Beliefs Scale (MDBS) among the patients attending a university dental clinic in India. A cross-sectional study design was used. A total of 482 general dental patients attending a university dental clinic returned completed forms of the Indian translations of the MDAS and MDBS. General information about the age, sex, occupation and educational qualifications of the respondents as well as information about past dental experiences was also collected. All the statistical analysis was carried out by the spss (version 10) statistical software package. The Indian translations of the MDAS and the MDBS were found to be internally reliable with a Cronbach's alpha of 0.78 and 0.85, respectively. Validity was demonstrated by a statistically significant correlation between the MDAS and the MDBS scores with the correlation coefficient of 0.47. Age was also inversely related to dental anxiety. Anxiety scores were higher among the less educated patients. Those who had a prior unpleasant dental experience showed higher dental anxiety and more negative dental beliefs. The data obtained in this study provided strong evidence for the psychometric properties of the Indian version of the MDAS and the MDBS.

Chromium (D-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice.

Abstract: Chromium has gained popularity as a nutritional supplement for diabetic and insulin-resistant subjects. This study was designed to evaluate the effect of chronic administration of a novel chromium complex of d-phenylalanine [Cr(D-phe)(3)] in insulin-resistant, sucrose-fed mice. Whole-body insulin resistance was generated in FVB mice by 9 wk of sucrose feeding, following which they were randomly assigned to be unsupplemented (S group) or to receive oral Cr(D-phe)(3) in drinking water (SCr group) at a dose of 45 mug.kg(-1).d(-1) ( approximately 3.8 mug of elemental chromium.kg(-1).d(-1)). A control group (C) did not consume sucrose and was not supplemented. Sucrose-fed mice had an elevated serum insulin concentration compared with controls and this was significantly lower in sucrose-fed mice that received Cr(D-phe)(3), which did not differ from controls. Impaired glucose tolerance in sucrose-fed mice, evidenced by the poor glucose disposal rate following an intraperitoneal glucose tolerance test, was significantly improved in mice receiving Cr(D-phe)(3). Chromium supplementation significantly enhanced insulin-stimulated Akt phosphorylation and membrane-associated glucose transporter-4 in skeletal muscles of sucrose-fed mice. In cultured adipocytes rendered insulin resistant by chronic exposure to high concentrations of glucose and insulin, Cr(D-phe)(3) augmented Akt phosphorylation and glucose uptake. These results indicate that dietary supplementation with Cr(D-phe)(3) may have potential beneficial effects in insulin-resistant, prediabetic conditions.

Simultaneous determination of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage form by RP-HPLC method.

Abstract: A simple, fast, and precise reverse phase, isocratic HPLC method was developed for the separation and quantification of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage form. The quantification was carried out using Inertsil ODS (250 +/- 4.6 mm, 5 micro) column and mobile phase comprised of acetonitrile and ammonium acetate (pH 4.5; 20mM) in proportion of 60:40 (v/v). The flow rate was 1.0 ml/min and the effluent was monitored at 230 nm. The retention time of pioglitazone and glimepiride were 7.0+/-0.1 and 10.2+/-0.1 min respectively. The method was validated in terms of linearity, precision, accuracy, and specificity, limit of detection and limit of quantitation. Linearity of pioglitazone and glimepiride were in the range of 2.0 to 200.0 microg/ ml and 0.5-50microg/ ml respectively. The percentage recoveries of both the drugs were 99.85% and 102.06% for pioglitazone and glimepiride respectively from the tablet formulation. The proposed method is suitable for simultaneous determination of pioglitazone and glimepiride in pharmaceutical dosage form and bulk drug.

Pattern of computer and internet use among medical students in Coastal South India

Abstract: Background: The use of computers is increasing among medical students, therefore we carried out a cross sectional study in Mangalore, India, with the objective of assessing the pattern of computer and Internet use among both undergraduate and postgraduate medical students. Methods: A total of 500 medical students from 4 different medical colleges in Mangalore participated in the study. 400 were undergraduates and 100 were postgraduates / interns. A pre-tested semi-structured questionnaire was used to collect data and data analysis was done using SPSS Version 11. Results: The majority of students who participated in the study were from the age group 19-21years constituting 34.6%. The computer was used for entertainment mainly by the 1 st and 2 nd year medical students (69.5%) whereas 40% PG / Interns use it for general information and 31% for research activities. Majority of the PG/Interns (77%) were satisfied with computer assisted teaching while 20% 1 st and 2 nd year students were not. Majority of 1 st and 2 nd year medical students (50.5%) use Internet most often to communicate socially while 21% Pre final and final year students use Internet most often to engage in work for classes. The use of E-mail was the most popular of Internet services used by 87% PG/Interns. Conclusion: A significant relationship was demonstrated between the year of study and the purpose of computer/Internet use. As the students progress through their curriculum the use of computer for entertainment is declining and use for general information and thesis / research work is rising.

Differential Membrane Proteomics Using 18O-Labeling To Identify Biomarkers for Cholangiocarcinoma

Abstract: Quantitative proteomic methodologies allow profiling of hundreds to thousands of proteins in a high-throughput fashion. This approach is increasingly applied to cancer biomarker discovery to identify proteins that are differentially regulated in cancers. Fractionation of protein samples based on enrichment of cellular subproteomes prior to mass spectrometric analysis can provide increased coverage of certain classes of molecules. We used a membrane protein enrichment strategy coupled with 18O labeling based quantitative proteomics to identify proteins that are highly expressed in cholangiocarcinomas. In addition to identifying several proteins previously known to be overexpressed in cholangiocarcinoma, we discovered a number of molecules that were previously not associated with cholangiocarcinoma. Using immunoblotting and immunohistochemical labeling of tissue microarrays, we validated Golgi membrane protein 1, Annexin IV and Epidermal growth factor receptor pathway substrate 8 (EPS8) as candidate biomark...

Raman spectroscopy of breast tissues.

Abstract: Breast cancer is one of the leading female cancers. The major drawback of the gold standard of screening, mammography, is the high rate of false reports, aside from the risk from repeated exposure to harmful ionizing radiations. Histopathology, the gold standard of diagnosis, is time consuming and often prone to subjective interpretations. Molecular level diagnosis 'omics' is becoming increasingly popular; among these is metabolomics, diagnosis based on 'metabolic fingerprinting'. In the present article we review a Raman spectroscopic approach to metabolic fingerprinting in breast cancer detection. This review opens with a brief background on anatomical and etiological aspects of breast cancers. We present an overview of conventional detection approaches in breast cancer screening and diagnosis methods, followed by a concise note on the basics of optical spectroscopy and its applications in the screening/diagnosis of breast malignancy. We present the recent developments in Raman spectroscopic diagnosis of breast cancers and also share our experience in Raman spectroscopic classification of normal, benign and malignant breast tissues. Perspectives and current status of Raman spectroscopic screening/diagnosis of breast cancers are also discussed.

Enhancement of hippocampal CA3 neuronal dendritic arborization by Centella asiatica (Linn) fresh leaf extract treatment in adult rats.

Abstract: Background: Centella asiatica (CeA) is a creeper, growing in moist places in India and other Asian countries. Leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternate system of medicine in India. In the present study, we investigated the role of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions concerned with learning and memory, in adult rats. Methods: In the present study, adult rats (2.5 months old) were fed with 2, 4 and 6 mL/kg body weight of fresh leaf extract of CeA for 2, 4 and 6 weeks, respectively. After the treatment period, the rats were killed, brains were removed and hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with those of age-matched control rats. Results: The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 6 mL/kg body weight/day of CeA for 6 weeks. However, the rats treated with 2 and 4 mL/kg body weight/day for 2 and 4 weeks did not show any significant change in hippocampal CA3 neuronal dendritic arborization. Conclusion: We conclude that constituents present in Centella asiatica fresh leaf extract has neuronal dendritic growth- stimulating properties. (J Chin Med Assoc 2008;71(1):6-13)

Primary gastrointestinal mucormycosis in an immunocompetent person.

Abstract: In the past decade, mucormycosis has emerged as an important lethal infection in diabetics and other immunocompromised hosts. Rhinosinusitis, pansinusitis, rhino-orbital and rhinocerebral are the common classical manifestations of mucormycosis. However, primary gastrointestinal (GI) mucormycosis is an uncommon disease associated with a high mortality rate. Stomach is the most common site involved in GI mucormycosis. Reported cases of GI mucormycosis in an immunocompetent host are very few in the literature. Here we present a case of a young male with fungal sepsis secondary to GI mucormycosis in an immunocompetent person.

Novel 2-pyrazoline derivatives as potential antibacterial and antifungal agents

Abstract: The 1,3,5-trisubstituted-2-pyrazolines were synthesized by refluxing isoniazid with various substituted diarylchalcones in N,N-dimethylformamide at 120-140°. The physical and spectral data such as M.P., R f , elemental analysis, IR, NMR and Mass was obtained for the synthesized compounds and the structures were confirmed. The screening of the synthesized compounds for antimicrobial activity was performed against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Aspergillus niger .

Simultaneous UV Spectrophotometric Estimation of Ambroxol Hydrochloride and Levocetirizine Dihydrochloride.

Abstract: A novel, simple, sensitive and rapid spectrophotometric method has been developed for simultaneous estimation of ambroxol hydrochloride and levocetirizine dihydrochloride. The method involved solving simultaneous equations based on measurement of absorbance at two wavelengths 242 nm and 231 nm, the gamma max of ambroxol hydrochloride and levocetirizine dihydrochloride, respectively. Beer's law was obeyed in the concentration range 10-50 mug/ml and 8-24 mug/ml for ambroxol hydrochloride and levocetirizine dihydrochloride respectively. Results of the method were validated statistically and by recovery studies.

Simultaneous Estimation of Esomeprazole and Domperidone by UV Spectrophotometric Method.

Abstract: A novel, simple, sensitive and rapid spectrophotometric method has been developed for simultaneous estimation of esomeprazole and domperidone. The method involved solving simultaneous equations based on measurement of absorbance at two wavelengths, 301 nm and 284 nm, lambda max of esomeprazole and domperidone respectively. Beer's law was obeyed in the concentration range of 5-20 mug/ml and 8-30 mug/ml for esomeprazole and domperidone respectively. The method was found to be precise, accurate, and specific. The proposed method was successfully applied to estimation of esomeprazole and domperidone in combined solid dosage form.

Activated epidermal growth factor receptor as a novel target in pancreatic cancer therapy.

Abstract: Pancreatic cancer is one of the most fatal among all solid malignancies. Targeted therapeutic approaches have the potential to transform cancer therapy as exemplified by the success of several tyrosine kinase inhibitors. Prompted by this, comprehensive profiling of tyrosine kinases and their substrates was carried out using a panel of low passage pancreatic cancer cell lines. One of the pancreatic cancer cell lines, P196, which showed dramatic upregulation of tyrosine kinase activity as compared to non-neoplastic cells, was systematically studied using a quantitative proteomic approach called stable isotope labeling with amino acids in cell culture (SILAC). A careful analysis of activated tyrosine kinase pathways revealed aberrant activation of epidermal growth factor receptor pathway in this cell line. Mouse xenograft based studies using EGFR inhibitor erlotinib confirmed EGFR pathway to be responsible for proliferation in these tumors. By a systematic study across low passage pancreatic cancer cell line...

Lamellar lubrication in vivo and vitro: friction testing of hexagonal boron nitride.

Abstract: Phospholipid molecules (PLs) in vivo and graphite, molybdenum disulfide, tungsten disulfide and hexagonal boron nitride (h-BN) in vitro are good examples of frictionless lubricants. PLs and solid materials have the ability to form multi-bilayer or layered structures similar to lamellate solid. It has been confirmed experimentally that PLs as lamellar lubricants protect the surface of joints against wear while acting as frictionless lubricant. An experimental study has been conducted on the friction properties of h-boron nitride on porous non-full journal bearings. The porous non-full journal bearings were a mixture of 97.5 wt.% Fe and 2.5 wt.% Cu powder, and compressed to a density of 5.9 g/cm(3). The porosity of non-full journal bearings were 15.5 and 27.8 wt.% and were impregnated with vaseline and vaseline+5 wt.% h-BN. Additionally, the two additives SFR NLGI #2 (or SFR 2522) grease and graphite grease were used for comparison to h-BN. The tribological tests were performed on a four-ball machine under load of 49 daN, and a friction tribotester. The above experiment strongly suggested that h-BN has the ability to lubricate under load with very low friction coefficient comparable to phospholipids. Relatively low surface energy and low adhesion between the crystallites are giving the additives low friction coefficient. The results of the experimental studies showed that h-BN as an additive in vaseline possesses friction reducing properties, and excellent anti-wear properties.