Raman spectroscopy as a detection and analysis tool for in vitro specific targeting of pancreatic cancer cells by EGF-conjugated, single-walled carbon nanotubes

Single-walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC-1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme-linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT-EGF conjugates, at a concentration of 85 μg ml(-1), to the PANC-1 cell surfaces was significant in the first 30 min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNT-EGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone.     

Role of oxidative stress in diabetes-mediated vascular dysfunction: Unifying hypothesis of diabetes revisited

Oxidative stress is recognized as a key participant in the development of diabetic complications in the vasculature. One of the seminal studies advancing the role of oxidative stress in vascular endothelial cells proposed that oxidative stress-mediated diversion of glycolytic intermediates into pathological pathways was a key underlying element in the development of diabetic complications. It is widely recognized that flux through glycolysis slows during diabetes. However, several bottlenecks develop in the glycolytic pathway, including glucose transport, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase. Of these limiting steps in glycolysis, glyceraldehyde-3-phosphate dehydrogenase is most sensitive to oxidative stress, leading to the hypothesis that glyceraldehyde-3-phosphate inactivation by ribosylation underlies the diversion of glycolytic intermediates into pathological pathways. However, recent studies question the mechanism underlying the effect of reactive oxygen species on key enzymes of the glycolytic pathway. The present review critiques the major premises of the hypothesis and concludes that further study of the role of oxidative stress in the development of diabetes-mediated vasculature dysfunction is warranted.     

Characterization of Drug Release and Diffusion Mechanism Through Hydroxyethylmethacrylate/Methacrylic Acid pH-Sensitive Hydrogel

Hydroxyethylmethacrylate/methacrylic acid copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk free radical polymerization method. The permeability studies of this pH-sensitive hydrogel to drugs with different water solubilities showed a water-content dependent diffusion or pore mechanism for ephedrine HCl (water-soluble model drug), whereas, a partition or solute-diffusion mechanism for indomethacin (a water-insoluble drug) was seen. Data analysis of release tests, according to the swelling interface number and Peppas equation for ephedrine HCl in pH 7.4, showed a biexponential model kinetic, whereas in pH 1.2 a swelling-controlled mechanism was seen. Indomethacin was released by an anomalous or non-Fickian release kinetics.     

Management of epistaxis in the oral and maxillofacial surgery setting: An update on current practice

Epistaxis is a common and, in most cases, benign event. Although most nosebleeds resolve spontaneously, some may be profuse and life-threatening. Severe or recurrent epistaxis can be a challenging management problem. In otolaryngologic practice, it is the most commonly seen emergency. Oral and maxillofacial surgeons will also encounter this clinical problem in varied settings. It is our aim to present an update on the contemporary management of epistaxis in maxillofacial practice. The etiology and relevant surgical anatomy are discussed. This is followed by an update on current treatment regimens in different scenarios. A stepwise algorithm for the management of epistaxis is presented.     

Rose Angina Questionnaire: Validation with cardiologists' diagnoses to detect coronary heart disease in Bangladesh

Aim/objectivesThe study aimed to validate the Rose Angina Questionnaire (RAQ) to detect coronary heart disease (CHD) by comparing with cardiologists' diagnoses in Bangladesh.MethodsPatients aged 40–75 years attending to two cardiac hospitals were diagnosed as either CHD positive or CHD negative by cardiologists. The RAQ was used to reclassify them into CHD positive [RAQ] and CHD negative [RAQ].FindingsThere were 302 CHD positive [cardiologists] and 302 CHD negative [cardiologists] individuals. The RAQ reclassified 194 individuals as CHD positive [RAQ] and 409 individuals as CHD negative [RAQ]. Therefore, the RAQ had 53% sensitivity and 89% specificity. There was no difference in sensitivity and specificity during subgroup analyzes by age and gender; the sensitivity was higher among people from lower socio-economic status.ConclusionThe RAQ, having moderate sensitivity but high specificity to detect CHD, can be used to screen individuals at risk of CHD in large-scale epidemiological surveys.     

Expression Patterns of Carcinogen Detoxifying Genes (CYP1A1, GSTP1 & GSTT1) in HNC Patients

Carcinogen detoxifying genes may be involved in pathogenesis of head and neck cancer (HNC). CYP1A1 is phase I enzyme that converts carcinogens into water soluble compounds which are easily excreted from body. GSTs constitute phase II detoxification enzymes that recognize these highly electrophilic compounds and detoxify them. Abnormal expression of these genes can potentially lead to cancer initiation. In present study, we analyzed protein expression of these genes in a total of 192 HNC patients and noncancerous healthy control serum samples screened for GSTs specific activity by ELISA. Furthermore, expression of these molecules was also determined in 49 HNC tissues/ adjacent control tissue by immunohistochemistry with specific antibodies. Mean serum GSTs specific activity was found to be 7.7 (+11.5)U/L in HNC patients and 11.4 (+7.5)U/L in controls. Significant decrease (P?<?0.05) in GSTs specific activity was observed in HNC patients compared with controls (P?<?0.001). Data for immunohistochemistry showed that CYP1A1 and GSTT1 was down expressed whereas GSTP1 was over expressed in HNC tissues compared with adjacent normal control tissues. Results of immunohistochemistry revealed 63 % HNC tissues had weak, 27 % moderate and 10 % strong staining for CYP1A1. For GSTT1, 27 % HNC tissues had no staining, 49 % weak staining, 16 % moderate and 8 % strong staining. Similarly for GSTP1, percentages for weak, moderate and strong staining were 6 %, 12 % and 82 % respectively. These reduced proteins observed in cancer patients highlight a potential breach on DNA repair mechanism when compared with control. Thus altered expression of these detoxifying molecules may collectively contribute to HNC development in Pakistani population.     

Aortic Runoff as a Sign of Intracranial Arteriovenous Malformation: Report of Two Cases

Background

Intracranial arteriovenous malformation rarely causes pulmonary hypertension and congestive heart failure in the newborn. Its diagnosis is challenging because cardiomegaly may suggest an intra-cardiac structural lesion.

Case Presentation

We present two newborns, one 2-day-old male and the other 11-day-old female, with intracranial arteriovenous malformation and misdiagnosis of congenital heart disease.

Conclusion

Precise echocardiography revealed the secondary signs of cranial arteriovenous malformation and had the major role in early diagnosis.     

Do adventitial mast cells contribute to the pathogenesis of ascending thoracic aorta aneurysm?

The precise pathogenesis of the ascending aortic aneurysm (AscAA) remains to be determined. Mast cells in the adventitia of human AscAA lesions may play a role in this pathogenesis. Adventitial mast cell density per 10 high-power fields (0.25 mm(2)) was assessed in multiple biopsy samples, from aneurysmal aortic sections (n = 41) and control (nondilated) aortic specimens (n = 50), stained by orcein-Giemsa method, an inexpensive (<$1) method. In a multivariable adjusted logistic regression model, using AscAA as the dependent variable, mast cell density was found to be an independent predictor of AscAA occurrence (odds ratio = 2.21; 95% confidence interval = 1.58-3.08; P < .001). Receiver operating characteristic curve analysis showed that the proposed cutoff value of ≥3 mast cells per 10 high-power fields was very sensitive to detect AscAA occurrence, yielding a sensitivity of 90% with a specificity of 80%. In conclusion, a significant increase in the number of mast cells in the adventitia of human ascending aortic lesions proposes a role for these cells in the pathogenesis of AscAA.