Anti-proliferative Effects of Organic Extracts from Root Bark of Juglans Regia L. (RBJR) on MDA-MB-231 Human Breast Cancer Cells: Role of Bcl-2/Bax, Caspases and Tp53

Asian Pacific Journal of Cancer Prevention : APJCP. 2011  |  Pubmed ID: 21545224

With increasing use of plant-based cancer chemotherapeutic agents, exploring the antiproliferative effects of phytochemicals has gained increasing momentum for anticancer drug design. The present study was undertaken to investigate the effect of root bark of Juglans regia (RBJR) organic extracts on cell proliferation, and to determine the molecular mechanism of RBJR-induced cell death by determining the expression of Bcl-2, Bax, caspases, Tp53, Mdm-2 and TNF-alpha in MDA-MB-231 human breast cancer cells. The results demonstrate that WNRB suppressed proliferation and induced apoptosis in a dose and time dependent manner by modulating expression of key genes. This involved characteristic changes in cytoplasmic and nuclear morphology, DNA fragmentation (TUNEL assay), levels of mRNA and expression of corresponding proteins. Real Time PCR and western blot analysis revealed that the expression of of Bax, caspases, tp53, and TNF-alpha was markedly increased in MBA-MB-231 cells treated with the RBJR extract. In contrast Bcl2 and mdm-2 expression was down regulated after exposure. In summary, our data suggest the presence of bioactive compound(s) in WNRB capable of killing breast carcinoma cells through induction of apoptosis, and therefore a candidate source of anticancer drugs.

Benchmarking the Environmental Performance of the Jatropha Biodiesel System Through a Generic Life Cycle Assessment

Environmental Science & Technology. Jun, 2011  |  Pubmed ID: 21591673

In addition to available country or site-specific life cycle studies on Jatropha biodiesel we present a generic, location-independent life cycle assessment and provide a general but in-depth analysis of the environmental performance of Jatropha biodiesel for transportation. Additionally, we assess the influence of changes in byproduct use and production chain. In our assessments, we went beyond the impact on energy requirement and global warming by including impacts on ozone layer and terrestrial acidification and eutrophication. The basic Jatropha biodiesel system consumes eight times less nonrenewable energy than conventional diesel and reduces greenhouse gas emissions by 51%. This result coincides with the lower limit of the range of reduction percentages available in literature for this system and for other liquid biofuels. The impact on the ozone layer is also lower than that provoked by fossil diesel, although eutrophication and acidification increase eight times. This study investigates the general impact trends of the Jatropha system, although not considering land-use change. The results are useful as a benchmark against which other biodiesel systems can be evaluated, to calculate repayment times for land-use change induced carbon loss or as guideline with default values for assessing the environmental performance of specific variants of the system.

Successful Embolization of a Suprascapular Artery Aneurysm

Annals of Vascular Surgery. May, 2011  |  Pubmed ID: 21620668

A 45-year-old woman was referred to our service because 9 months earlier she had developed a pulsating mass on the right supraclavicular fossa and torticollis. Ultrasounds and computed tomographic arteriography showed the presence of a subclavian collateral artery aneurysm with a diameter of 21 mm. On selective arteriography, an aneurysm of a suprascapular artery arising directly from the right subclavian artery was reported. The presence of thoracic outlet syndrome was excluded. The aneurysm was successfully treated with ethylene-vinyl alcohol polymer, a liquid embolic agent. The patient was discharged on postoperative day 1 in good general condition. After 12 months, control ultrasounds confirmed the complete thrombosis of the aneurysm sac.

A Rare Presentation of Pulmonary Lymphangitic Carcinomatosis in Cancer of Lip: Case Report

World Journal of Surgical Oncology. 2011  |  Pubmed ID: 21756338

Squamous cell carcinoma of lip is a common malignancy in Indian subcontinent. Metastatic spread is infrequent. Although advanced tumours spread to lymph nodes in the neck, it does not typically present with lung metastasis or with lymphangitic carcinomatosis. We describe a patient who developed cough and increasing dyspnoea while on treatment for carcinoma of lip. Chest x-ray and computed tomography were consistent with lymphangitic carcinomatosis. Lymphangitic carcinomatosis occurs with many different primary tumours and can rarely occur in oral cancers. This is the first report from carcinoma of lip.

Balancing Rational Care with Consumer Beliefs: Tightrope Walking

The National Medical Journal of India. May-Jun, 2011  |  Pubmed ID: 21786855

Affinity of Estrogens for Human Progesterone Receptor A and B Monomers and Risk of Breast Cancer: a Comparative Molecular Modeling Study

Advances and Applications in Bioinformatics and Chemistry : AABC. 2011  |  Pubmed ID: 21918635

The human progesterone receptor (hPR) belongs to the steroid receptor family. It may be found as monomers (A and B) and or as a dimer (AB). hPR is regarded as the prognostic biomarker for breast cancer. In a cellular dimer system, AB is the dominant species in most cases. However, when a cell coexpresses all three isoforms of hPR, the complexity of the action of this receptor increases. For example, hPR A suppresses the activity of hPR B, and the ratio of hPR A to hPR B may determine the physiology of a breast tumor. Also, persistent exposure of hPRs to nonendogenous ligands is a common risk factor for breast cancer. Hence we aimed to study progesterone and some nonendogenous ligand interactions with hPRs and their molecular docking.

Path to Facilitate the Prediction of Functional Amino Acid Substitutions in Red Blood Cell Disorders--a Computational Approach

PloS One. 2011  |  Pubmed ID: 21931771

A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs) are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs) that affect protein functions and relate to disease is an important task.

Associations of Lifestyle-related Factors, Hsa-miR-149 and Hsa-miR-605 Gene Polymorphisms with Gastrointestinal Cancer Risk

Molecular Carcinogenesis. Oct, 2011  |  Pubmed ID: 21976437

To explore the associations of SNPs within hsa-miR-605 (rs2043556) and hsa-miR-149 (rs2292832) and lifestyle-related factors with gastrointestinal cancer, a case-control study including 762 cases and 757 controls was conducted. Marginally significant associations were found both for hsa-miR-149 rs2292832 with gastric cancer risk (TC + CC vs. TT, OR = 0.68, 95% CI: 0.44-1.04) and for hsa-miR-605 rs2043556 with colorectal cancer risk (AG + GG vs. AA, OR = 0.70, 95% CI: 0.48-1.02) in males. Tea drinking showed a protective effect on gastric cancer risk (OR = 0.28, 95% CI: 0.13-0.60), while smoke inhalation increased the risk of gastric cancer (OR = 1.94, 95% CI: 1.08-3.47). Irritability was found to be a risk factor for both colorectal cancer (OR = 1.61, 95% CI: 1.02-2.53) and gastric cancer (OR = 1.96, 95% CI: 1.17-3.29). Among those that engaged in smoke inhalation, miR-149 CT/CC and miR-605 AG/GG genotype carriers had increased susceptibilities to colorectal cancer (OR = 1.90, 95% CI: 1.11-3.25) and gastric cancer (OR = 1.87, 95% CI: 1.03-3.42), respectively. Among the tea drinkers, there exists a marginally protective effect of miR-605 AG/GG genotypes on colorectal cancer incidence (OR = 0.71, 95% CI: 0.47-1.06) and a significantly protective effect of miR-149 CT/CC on gastric cancer incidence (OR = 0.47, 95% CI: 0.29-0.77). The SNPs of rs2292832 and rs2043556 might be able to modify the susceptibility to male gastric and colorectal cancers, respectively. Tea drinking is a protective factor, while smoke inhalation is a risk factor for gastric cancer, and they might have the potential to modify the associations between miR-149 and miR-605 polymorphisms with gastrointestinal cancer risk. In addition, irritability was shown to be a risk factor for both gastric and colorectal cancers. © 2011 Wiley Periodicals, Inc.

Low-energy Electron-induced Single Strand Breaks in 2'-deoxycytidine-3'-monophosphate Using the Local Complex Potential Based Time-dependent Wave Packet Approach

The Journal of Physical Chemistry. A. Dec, 2011  |  Pubmed ID: 21999881

Recent experimental and theoretical investigations on resonant electron scattering off DNA and DNA fragments using low-energy electrons (LEEs), to propose the mechanism for single strand breaks (SSBs) and double strand breaks (DSBs), have received considerable attention. It is our purpose here to understand theoretically the comprehensive route to SSB in a selected DNA fragment, namely, 2'-deoxycytidine-3'-monophosphate (3'-dCMPH), induced by LEE (0-3 eV) scattering using the local complex potential based time-dependent wave packet (LCP-TDWP) approach. To the best of our knowledge, there is no time-dependent quantum mechanical study that has been reported in the literature for this DNA fragment to date. Initial results obtained from our calculation in the gas phase provide a good agreement with experimental observation and show the plausibility of SSB at 0.75 eV, which is very close to the highest SSB yield reported from the experimental measurement (0.8 eV) on plasmid DNA in the condensed phase.

The Prevalence of Hyperuricemia in China: a Meta-analysis

BMC Public Health. 2011  |  Pubmed ID: 22032610

The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China.

A Systems-based Medication Reconciliation Process: with Implications for Home Healthcare

Home Healthcare Nurse. Nov-Dec, 2011  |  Pubmed ID: 22067504

This article describes the medication reconciliation process applied on hospital discharge of patients to home with home care services within Seton Health System, an integrated health delivery network located in Troy, New York. The project, which was not research based, was characterized by an intensive pharmacotherapeutic medication reconciliation at hospital discharge by the hospital-based pharmacist with continued pharmacist support available to home healthcare nurses collaboratively at the time of start of care and resumption of care. The goal of this process was to identify and resolve medication-related problems and reduce hospital readmissions.

[The Immunocompromised Patient: Can You Vaccinate Him? You Even Must!]

MMW Fortschritte Der Medizin. Oct, 2011  |  Pubmed ID: 22097623

Pharmacokinetic Drug Interaction Between Gemfibrozil and Sitagliptin in Healthy Indian Male Volunteers

European Journal of Clinical Pharmacology. Dec, 2011  |  Pubmed ID: 22173280

PURPOSE: To study the impact of gemfibrozil co-administration on the pharmacokinetics of sitagliptin in healthy Indian male volunteers. METHODS: A randomized open label two-period crossover study involving 12 healthy Indian male volunteers was conducted at a single center. In each phase, the volunteers were administered sitagliptin as 100 mg tablets, either alone or co-administered with gemfibrozil as 600 mg tablets twice daily for 3 days. There was a 2-week washout period between phases. The venous blood samples were serially collected at 0-12 h post-dose, and plasma concentrations of the study drugs were estimated by a validated high-performance liquid chromatography-ultraviolet method. RESULTS: Relative to the administration of sitagliptin alone, co-administration with gemfibrozil increased the AUC(0-12) (2,167 ± 82.9 vs. 2,970 ± 76.4 ng h/ml; p < 0.0001), AUC(0-∞) (3,621 ± 222.5 vs. 5,574 ± 249.6 ng h/ml; p < 0.0002), C(max) (282.9 ± 7.7 vs. 344.1 ± 5.9 ng/ml; p < 0.0001), and t(½) (7.4 ± 0.6 vs. 10 ± 0.6 h; p = 0.0076) to statistically significant levels. The interindividual differences in the pharmacokinetic parameters of sitagliptin were found to be within acceptable limits (coefficient of variation <20%). No adverse drug events associated with sitagliptin occurred in the subjects during the study period. CONCLUSION: Although the bioavailability of sitagliptin was increased by 54% when co-administered with gemfibrozil, this interaction may not have any clinical significance as sitagliptin has a wide therapeutic index. Hence, in clinical practice, sitagliptin as 100 mg tablets and gemfibrozil as 600 mg tablets may be co-prescribed without much threat of sitagliptin toxicity. However, these results may not hold if the dose of sitagliptin is increased or if is co-prescribed with other antidiabetic drugs and/or cytochrome P450 2C8/human organic anion transporter-3 inhibitors. Further studies are needed to confirm these results in patients.

Airways Dysfunction and Inflammation in Pool and Non-Pool Based Elite Athletes

Medicine and Science in Sports and Exercise. Jan, 2012  |  Pubmed ID: 22297809

PURPOSE: This study sought to determine and compare the levels of airway dysfunction and inflammation in a large cohort of symptomatic international athletes from pool and non-pool based sporting backgrounds. In total 118 athletes were recruited. METHODS: All subjects had symptoms of exercise asthma and were steroid naïve. They completed baseline spirometry, a symptom score, exhaled nitric oxide (FENO), an eucapnic voluntary hyperventilation (EVH) test and a post challenge induced sputum and urine test. RESULTS: Pool based athletes had better lung function (FEV1 110 vs 102% predicted; mean difference 8.200 ± 2.339; p=0.0006 and FVC 5.64 vs 4.75 l; mean difference 0.8855 ± 0.1951; p<0.0001) and more marked AHR (% drop in FEV1 post EVH18.14 vs 11.47; mean difference 6.67; 95% CI: 2.89 to 10.53; p=0.0009). More pool based athletes had a positive EVH test (72% pool v 39% non-pool), but there was no difference between groups with respect to eosinophilic inflammation (sputum eos % pool=2.07, non-pool=2.28, p=0.77; FENO, pool = 32.54, non-pool= 35.77, p=0.60). Athletes with a positive EVH test had less neutrophilic inflammation (p=0.01) and more epithelial cells (p=0.03) in their sputum. CONCLUSION: Pool based endurance athletes have greater evidence of AHR than non-pool based athletes but no evidence of greater eosinophilic airways inflammation. Athletes who test positive on EVH are more likely to be eosinophilic and have higher levels of epithelial cells in their sputum.

Benefits and Harms of Screening Mammography Frequency by Age and Comorbidity Score

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337538

BACKGROUND: There is uncertainty about the appropriate use of screening mammography in older women. We compared the benefits and harms of screening mammography frequency according to age and comorbidity scores. METHODS: We conducted analyses within a prospective cohort study of four mammography registries in the Breast Cancer Surveillance Consortium that had mammography data linked to Medicare claims information. Participants included 137,949 women aged 66-89 years without breast cancer and 2,993 women with breast cancer. We estimated odds of advanced (IIb, III, IV) stage, large tumor size (>20 millimeters), and estrogen receptor (ER) negative tumors and cumulative probability of false-positive mammography after 10 years of screening by mammography frequency, age and comorbidity score as determined by the Charlson Comorbidity Index. RESULTS: Mammography biennially vs. annually for women aged 66-89 years does not increase risk of tumors with unfavorable characteristics regardless of women's comorbidity score. Cumulative probability of a false-positive result for annual and biennial screening of women aged 66-89 years with a comorbidity score of ≥1 was 48 (46.1, 49.9) and 29 (28.1, 29.9) respectively. False-positives were more common among annual screeners than among those screened biennially irrespective of women's comorbidity score. CONCLUSION: Mammography annually vs. biennially does not have added benefit for women aged 66-89 years, even among those in good overall health as reflected by the lack of comorbidity. Risk of false-positive mammography is much higher with annual mammography.

Risk of Non-Hodgkin Lymphoma in Relation to Tricyclic Antidepressant Use

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337549

PURPOSE: We investigated the relationship between prior use of tricyclic antidepressants (TCA) and risk of non-Hodgkin lymphomas (NHL), both overall and for common subtypes of NHL; previous studies provided some evidence of an association with NHL, but did not assess the risk of specific subtypes of NHL, which have been shown to be etiologically diverse.METHODS: We conducted a population-based matched case-control study among members of Group Health (GH), an integrated healthcare delivery system. Cases included GH members diagnosed with NHL between 1980-2011 at age ≥25 with no record of a prior cancer or of certain autoimmune conditions, who had been enrolled for ≥2 years at the reference date (date of diagnosis). Eight controls were matched to each case on age, sex, enrollment on the reference date, and length of prior enrollment at GH. Information on prior TCA use, including dose, duration, recency, and type, was ascertained from automated pharmacy data. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for NHL (and common subtypes) in relation to various patterns of TCA exposure using conditional logistic regression adjusted for confounders.RESULTS: We identified 2,768 cases and 22,127 matched controls. We did not observe an appreciably increased risk of NHL among persons who had filled ≥2 TCA prescriptions prior to the reference date compared to those who had filled none (OR: 1.1; 95% CI: 1.0-1.2). Overall risk of NHL was associated to at most a small degree with longer-term use (OR: 1.2; 95% CI: 1.0-1.4 for ≥10 prescriptions), high-dose use (OR: 1.1; 95% CI: 0.8-1.5 for ≥50 mg or equivalent), or use that began more than 5 years prior to reference date (OR: 1.0; 95% CI: 0.9-1.2). TCA use was generally not associated with most major NHL subtypes, though longer-term TCA use was associated with increased risk of chronic lymphocytic leukemia/small lymphocytic lymphoma (OR: 1.5; 95% CI: 1.1-2.0).CONCLUSIONS: We found little evidence that TCA use increases risk of NHL, overall or for specific common subtypes of NHL. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Catheter Lock Technique: in Vitro Efficacy of Ethanol for Eradication of Methicillin-resistant Staphylococcal Biofilm Compared with Other Agents

FEMS Immunology and Medical Microbiology. Mar, 2012  |  Pubmed ID: 22380476

Biofilm formation in central venous catheters (CVC) is a prerequisite for catheter-related bloodstream infection (CRBSI). The catheter lock technique has been used to treat biofilm infection, but the ideal agent, concentration and the minimum exposure time necessary to eradicate the biofilms are not clearly known. In this study, biofilm-producing strains of staphylococci were used to find out the minimum biofilm eradication concentration of ethanol compared with three other conventional antibacterial agents. Eight representative methicillin-resistant staphylococci, from colonized CVCs, were studied. The biofilms were exposed to 1, 5 and 10 mg mL(-1) of gentamicin, ciprofloxacin and vancomycin. The ethanol concentrations used were 20%, 40% and 80%. Biofilms were examined for the presence of live organisms after exposure to these agents from 30 min to 24 h. The three antibiotics were unable to eradicate the biofilms even after 24 h, while ethanol at 40% concentration could do so for all the isolates in 1 h. Our study highlights the efficacy and rationale of using 40% ethanol for a short period as catheter lock solution to eradicate biofilms and thus to prevent CRBSI, instead of using high concentrations of antibiotics for extended periods.

Homocysteine Slovakia Study: Study Design and Occurrence of Hyperhomocysteinaemia and Other Risk Factors

Bratislavské Lekárske Listy. 2012  |  Pubmed ID: 22394036

Background: Slovakia belong to the European Union countries with the high incidence and prevalence of cardiovascular diseases in general and IHD in particular. Method: Homocystein-Slovakia is crossectional population study realised in subjects in high risk age 35-75 years in two groups. The first consists of patients with verified stable ischemic heart disease (IHD) (M= 152; F = 167) aged 60.8±9.37 yrs (males) res. 63.1±7.56 years (females) (NS) who were randomly selected from two cardiological registrars. Second population was formed by general population who were dichotomised according their medical records into IHD patients (M= 31, F= 53) and apparently healthy controls (M= 47; F = 55), the later in significantly younger age as patients, but in same age for intergender comparison 49.6±10.3 vs 46.6±9.2 yrs (NS). Results: We found very high prevalence of classic as well as newer risk factors and risk markers both in IHD patients and in controls. Increased homocysteinen (Hcy >15 µmo/l for males and Hcy >13 µmo/l for females) was found even in 32.9 % of patients and 13.6 % of controls (p<0.001). Comparison of regulating vitamins levels between IHD patients and controls demonstrated similar prevalence. Conclusion: Homocystein Slovakia study found very high prevalence of hyperhomocysteinemia in patients with stable ischemic heart disease. Even the prevalence in healthy controls correspond to data resported for MI patients in Western countries. Vitamins regulating metabolism of homocysteine also shown high prevalence, however, without differences between IHD pacients and controls (Tab. 5, Fig. 1, Ref. 27). Keywords: homocystein Slovakia, epidemiology, risk factors, vitamins B6, B12 and folic acid.

Reliability of the Novel 7-joint Ultrasound Score (US7): Results from an Inter- and Intra-observer Study Performed by Rheumatologists

Arthritis Care & Research. Mar, 2012  |  Pubmed ID: 22438306

OBJECTIVE: To assess the inter- and intra-observer reliability of 26 rheumatologists when performing the US7 score. METHODS: Six RA patients were examined by 26 sonographers in 12 rater groups who performed the US7 score. The US7 score includes the clinically dominant wrist, MCP and PIP II and III, MTP II, and V joints which are evaluated for synovitis, tenosynovitis/paratenonitis and erosions from the dorsal and palmar/plantar aspects by grey scale and power Doppler (PD) ultrasound. Additional lateral scans were performed at MCP II and MTP V. All groups repeated the examination in four patients for calculating the intra-observer reliability. The results of one group that included two expert sonographers were considered as the reference standard. ?appa (κ) values, median agreement rates (inter-observer) and p-values (intra-observer evaluation) were calculated. RESULTS: The median overall κ-value for detecting synovitis was κ=0.51, for tenosynovitis/paratenonitis κ=0.57, and for erosions κ=0.45. In detail, best inter-observer results were found for the detection of erosions in MTP II from plantar (κ=1; median agreement rate 89.4%) and for PD signals' detection in the palmar wrist region (κ=0.79; median agreement rate 78.8%). A good agreement was found for detecting erosions in the MCP joint II from radial (κ=0.67; median agreement rate 77.3%). CONCLUSION: The inter- and intra-observer reliability of the US7 score shows moderate to substantial kappa values and good agreements. This ultrasound score, therefore, has the potential as an important imaging tool including also multicenter analysis to assess structural changes. © 2012 by the American College of Rheumatology.

Exploring the Binding Mechanism of Ondansetron Hydrochloride to Serum Albumins: Spectroscopic Approach

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Feb, 2012  |  Pubmed ID: 22112579

The mechanism of interaction of ondansetron hydrochloride (OND) to serum albumins [bovine serum albumin (BSA) and human serum albumin (HSA)] was studied for the first time employing fluorimetric, circular dichroism, FTIR and UV-vis absorption techniques under the simulated physiological conditions. Fluorimetric results were utilized to investigate the binding and conformational characteristics of protein upon interaction with varying concentrations of the drug. Higher binding constant values revealed the strong interaction between the drug and protein while the number of binding sites close to unity indicated single class of binding site for OND in protein. Thermodynamic results revealed that both hydrogen bond and hydrophobic interactions played a major role in stabilizing drug-protein complex. Site marker competitive experiments indicated that the OND bound to albumins at subdomin II A (Sudlow's site I). Further, the binding distance between OND and serum albumin was calculated based on the Förster's theory of non-radioactive energy transfer and found to be 2.30 and 3.41 nm, respectively for OND-BSA and OND-HSA. The circular dichroism data revealed that the presence of OND decreased the α-helix content of serum albumins. 3D-fluorescence results also indicated the conformational changes in protein upon interaction with OND. Further, the effects of some cations have been investigated in the interaction of drug to protein.