Current Drugs News Results

SnapShot: Bioreactors systems in tissue engineering (TE) & regenerative medicine (RM).

Biomaterials. 2010 Apr; 31(11): 3114-5
Martin I, Riboldi SA, Jakob M, Wendt D

Diabetic kidney disease: act now or pay later.

Am J Nephrol. 2010; 31(2): I-III
Atkins RC, Zimmet P

Electrocution-related mortality: a survey of 295 deaths in Tehran, Iran between 2002 and 2006.

Am J Forensic Med Pathol. 2010 Mar; 31(1): 42-5
Sheikhazadi A, Kiani M, Ghadyani MH

BACKGROUND AND AIM: Electrical burns are associated with significant morbidity and mortality, which are usually preventable with simple safety measures. METHODS: We conducted a retrospective study of non-lightening electrocution deaths in Tehran, Iran, between 2002 and 2006. RESULTS: Of 295 deaths, 285 investigated were accidental. The remnants were suicidal. The age range was 11 months to 75 years with a mean age of 28.99 + or - 12.58 years. Two hundred seventy-nine victims (96.6%) were males. The upper extremity was the most frequently involved contact site in 185 deaths (66.3%). No electrical burn marks were present in 16 (5.4%) cases. Workrelated accidents were responsible for 188 cases deaths (63.9%) and home accident for 85 cases deaths (28.8%). Deaths were caused most frequently by touching an electrical cable (95 cases, 32.2%). There was an increase in electrocution deaths in the summer (119 cases, 40.3%). One hundred seventy-nine cases (60.7%) were dead on the scene of death and 94 cases (31.9%) were dead on arrival at hospital. The unique findings of our study include 10 cases (3.4%) of suicidal electrocution and a high rate of workrelated accidental electrocution among Afghan workers. CONCLUSION: Death rates from electrocution among all medico-legal deaths were found to be lower in our study than in previous reports, most of them were work-related and preventable. Workers and their employers should be educated to avoid such accidents with safety measures.

The fourth incision: a cosmetic autopsy incision technique.

Am J Forensic Med Pathol. 2010 Mar; 31(1): 37-41
Patowary A

Autopsy procedure includes thorough external examination as well as internal examination including opening of all the body cavities for proper visualization of all the visceral organs. As such, there remains incision marks with stitches which harts the sentiment of the already traumatized relatives of the deceased. Moreover, it looks odd especially in cases of otherwise healthy dead bodies. So, autopsy incisions should be such that, we can get maximum possible visualization of the body cavities, particularly the thorax and abdomen, and at the same time the incision as well as the stitch marks are also hidden. This article is aimed to describe few modifications in the autopsy incisions for opening the thorax and abdomen and also proper visualization of the neck structures during autopsy where the incisions and the stitches are kept hidden.

Age estimation from the rib by components method analysis in white males.

Am J Forensic Med Pathol. 2010 Mar; 31(1): 27-33
Verzeletti A, Cassina M, Micheli L, Lorenzo A, De Ferrari F

Changes at the sternal extremity of the fourth rib have already been established as reliable indicators of age at death. Still now, the Iscan "phase method," based on the morphologic changes at the sternal extremity of the fourth rib, is one of the best effective for age estimation at death. The present study was carried out to develop an alternative method considering the morphologic characteristics of articular surface (A), anterior/posterior walls (B), and superior/inferior edges (C) of the sternal extremity of the fourth rib. For each parameter a numerical score was assigned and some regression formulae was elaborated. The best correlation between morphologic characteristics and age was obtained through the formula Age = 10.43 (AB)(0.53). The sample consisted of sternal extremities of the fourth rib obtained at autopsy from 49 white males of known age.

A histone code for DNA repair.

Nat Rev Mol Cell Biol. 2010 Mar; 11(3): 164
Scully R

Optimization of magnetosonoporation for stem cell labeling.

NMR Biomed. 2010 Mar 8;
Xie D, Qiu B, Walczak P, Li X, Ruiz-Cabello J, Minoshima S, Bulte JW, Yang X

Recent advances in magnetic cell labeling have taken place with the development of a magnetosonoporation (MSP) technique. The aim of this study was to optimize the MSP protocol in order to achieve high cell viability and intracellular uptake of MR contrast agents. First, we determined the sub-optimal MSP parameters by evaluating the viabilities of C17.2 neural stem cells without Feridex using various MSP intensities ranging from 0.1 to 1 w/cm(2), duty cycles at 20%, 50% or 100%, and exposure times from 1-15 min. The sub-optimized MSP parameters with cell viabilities greater than 90% were further optimized by evaluating both cell viability and intracellular iron uptake when Feridex was used. We then used the optimized MSP parameters to determinate the optimal concentration of Feridex for magnetic cell labeling. Subsequently, we validated the feasibility of using MRI to track the migration of neural stem cells from the transplanted sites to glioma masses in four mouse brains when the cells had been labeled with Feridex using the optimized MSP protocol. The MRI findings were confirmed by histological correlations. In vitro experiments demonstrated that the optimal MSP protocol was achieved at 20% duty cycle, 0.3 w/cm(2) ultrasound intensity, 5-min exposure time and 1mg/mL Feridex. This study demonstrated that the optimized MSP cell labeling technique can achieve both high cell viability and intracellular uptake of MR contrast agents, and has the potential to be a useful cell labeling technique to facilitate future clinical translation of MRI-integrated cell therapy. Copyright (c) 2010 John Wiley & Sons, Ltd.

An interesting partnership: Undergraduate (college) and medical education.

Anat Sci Educ. 2010 Mar 8;
Drake RL, Pawlina W

An outsider's perspective on a provocative proposal: What would Flexner think?

Anat Sci Educ. 2010 Mar 8;
Anderson MB

This viewpoint commentary focuses on a proposal for integrated anatomy education in undergraduate college from Dr. Darda published in the Anatomical Sciences Education. Although the proposal is for college level education, the proposal echoes some ideas proposed a century ago by Abraham Flexner when he wrote his report titled "Medical Education in the United States and Canada." It begins with an acknowledgement of the author's status as an outsider. There have been numerous calls for change in basic science education, particularly in medical education. Interestingly, however, the monumental reforms of the "Flexner Report" were impelled largely from outside the specific discipline of medical education. The commentary discussion then moves to observations about the proposal for Integrative Anatomy and support for the proposal from both the Flexner Report and the 2009 report from the Association of American Medical Colleges and the Howard Hughes Medical Institute, "Scientific Foundations for Future Physicians." The essay considers the benefits of the research on the learning sciences that now inform our work in education; the influence of competency-based education that frees education from a lock-step approach of course completion to a student-focused integrative approach to learning; and the availability of online resources for anatomy education through repositories, such as MedEdPORTAL. The final observation is that the changes underway in education and in the sciences basic to medicine, in particular, are substantial and will require the dialogue that Dr. Darda is promoting with his provocative proposal. Anat Sci Educ, 2010. (c) 2010 American Association of Anatomists.

Comparative efficacy of group and individual feedback in gross anatomy for promoting medical student professionalism.

Anat Sci Educ. 2010 Mar 8;
Camp CL, Gregory JK, Lachman N, Chen LP, Juskewitch JE, Pawlina W

Professionalism is a core competency of medical training that requires students to develop the skills of providing and receiving feedback. Our study evaluated the effectiveness of delivering feedback in a group setting compared with an individual setting. The first-year class of Mayo medical students (n = 49) enrolled in gross anatomy (in dissection teams), completed weekly anonymous evaluations of themselves and their teammates regarding seven aspects of professionalism (altruism, compassion, respect, honesty/integrity, responsibility, commitment to excellence, and self-reflection). Professionalism scores from these surveys were calculated using a six-point Likert scale. Students were also asked to comment on strengths and possible areas for improvement on each peer. At the midpoint of the course, peer comments and professionalism scores were shared with students in debriefing sessions either individually or with their team. Analysis of preintervention and postintervention professionalism scores indicated that the students receiving feedback in a one-on-one setting (student and instructor) were more likely to demonstrate higher scores on subsequent evaluations as compared with those students receiving feedback in a group setting (all team members and one instructor). Our findings suggest that providing feedback to first-year medical students on an individual basis is the best way to improve professional attitudes and behaviors. Anat Sci Educ, 2010. (c) 2010 American Association of Anatomists.

A prospective evaluation of the prevalence of symptomatic von Willebrand disease (VWD) in a pediatric primary care population.

Pediatr Blood Cancer. 2010 Mar 8;
Bowman M, Hopman WM, Rapson D, Lillicrap D, Silva M, James P

The prevalence of von Willebrand disease (VWD) is reported as approximately 1%; however, these estimates were not based on individuals with significant symptoms. Four thousand five hundred ninety-two unselected parents/children were asked: "Does your child have a problem with bleeding/bruising?"; 223 (5%) answered yes, 41 of whom were administered the validated Pediatric Bleeding Questionnaire and had VWF testing. Five were diagnosed with VWD (three type 1, one type 2A, one type 2B). The prevalence of bleeding/bruising in a general pediatric population is 5%; the prevalence of symptomatic VWD at the level of pediatric primary care is at least 1 in 1,000. Pediatr Blood Cancer. (c) 2010 Wiley-Liss, Inc.

Terminology challenges: Defining modified release dosage forms in veterinary medicine.

J Pharm Sci. 2010 Mar 8;
Martinez MN, Lindquist D, Modric S

Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as "immediate release," "modified release," "extended release," and "delayed release" are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this confusion is attributable to differences between human and veterinary dosage forms (such as the preponderance of parenteral vs. oral extended release products for use in animals vs. the focus on oral extended release formulations for human use) which reflect interspecies differences in physiology and conditions of use. It also simply reflects a lack of attention to existing definitions. In an effort to remedy this problem, this manuscript reflects an initial effort to suggest definitions that may be appropriate for describing formulation effects in veterinary medicine. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

Successful endoscopic treatment of biliary cast syndrome in an orthotopic liver transplant patient with a Roux-en-Y anastomosis via balloon enteroscopy.

Liver Transpl. 2010 Jan 15;
Saleem A, Baron TH

Effects of chronic subthalamic stimulation on intractable akathisia in Parkinson's disease.

Mov Disord. 2010 Mar 8;
Shin HW, Chang JW, Kang SY, Sohn YH

Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: From fabrication to preclinical validation.

J Biomed Mater Res A. 2010 Mar 8;
Mondalek FG, Ashley RA, Roth CC, Kibar Y, Shakir N, Ihnat MA, Fung KM, Grady BP, Kropp BP, Lin HK

Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane angiogenesis model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging.

J Biomed Mater Res A. 2010 Mar 8;
Ren PG, Huang Z, Ma T, Biswal S, Smith RL, Goodman SB

Macrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra-high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2-day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 +/- 0.09-, 2.36 +/- 0.92-, and 10.32 +/- 7.61-fold, respectively. The values at same time points for saline-injected control group were 1.08 +/- 0.07-, 1.14 +/- 0.27-, and 1.14 +/- 0.35-fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation.

J Biomed Mater Res A. 2010 Mar 8;
Carpenedo RL, Seaman SA, McDevitt TC

Differentiation of pluripotent embryonic stem cells (ESCs) in vitro via multicellular spheroids called embryoid bodies (EBs) is commonly performed to model aspects of early mammalian development and initiate differentiation of cells for regenerative medicine technologies. However, the three-dimensional nature of EBs poses unique challenges for directed ESC differentiation, including limited diffusion into EBs of morphogenic molecules capable of specifying cell fate. Degradable polymer microspheres incorporated within EBs can present morphogenic molecules to ESCs in a spatiotemporally controlled manner to more efficiently direct differentiation. In this study, the effect of microsphere size on incorporation into EBs and ESC differentiation in response to microsphere- mediated morphogen delivery were assessed. PLGA microspheres with mean diameters of 1, 3, or 11 mum were fabricated and mixed with ESCs during EB formation. Smaller microspheres were incorporated more efficiently throughout EBs than larger microspheres, and regardless of size, retained for at least 10 days of differentiation. Retinoic acid release from incorporated microspheres induced EB cavitation in a size-dependent manner, with smaller microspheres triggering accelerated and more complete cavitation than larger particles. These results demonstrate that engineering the size of microsphere delivery vehicles incorporated within stem cell environments can be used to modulate the course of differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Normal nailfold end row loops are associated with a shorter duration of untreated disease in children with juvenile dermatomyositis.

Arthritis Rheum. 2010 Mar 8;
Ostrowski RA, Sullivan CL, Seshadri R, Morgan GA, Pachman LM

OBJECTIVE:: To determine the association of normal end row loops (ERL) at diagnosis of juvenile dermatomyositis (JDM) with clinical findings in untreated children and identify predictors of the development of decreased ERL. METHODS:: Clinical and laboratory data of 80 untreated children with JDM were collected. ERL scores were recorded at time of diagnosis, and at 24 months and 36 months thereafter. Twelve children with normal ERL at diagnosis were compared with the remaining 68 children. Outcomes included: duration of untreated disease, time on immunosuppresive medications, family medical history, disease activity score (DAS), and levels of creatine phosphokinase (CPK), aldolase, absolute CD3(-)CD56(+)/16(+) NK cells, and von Willebrand factor antigen (vWF:Ag). Cross-sectional and longitudinal analyses were performed. RESULTS:: At diagnosis, children with normal ERL had a shorter duration of untreated disease (p=0.03) and a lower skin DAS (p=0.045). Over time, an increased likelihood for having abnormal ERL was associated with a longer duration of untreated disease and with higher skin DAS. CONCLUSIONS:: The presence of a normal number of ERL in JDM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERL is also associated with lower skin DAS. The lack of association between normal ERL and other variables indicates that normal NFC should not be used as a justification to delay immunosuppressive therapy in children with typical JDM symptoms.

Adipocytokines, insulin resistance and coronary atherosclerosis in rheumatoid arthritis.

Arthritis Rheum. 2010 Mar 8;
Rho YH, Chung CP, Solus JF, Raggi P, Oeser A, Gebretsadik T, Shintani A, Stein CM

OBJECTIVES:: Subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA) and is associated with insulin resistance. Adipocytokines are associated with obesity, insulin resistance, inflammation and coronary heart disease in the general population. We examined the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA. METHODS:: Coronary calcium, insulin resistance (HOMA) and serum adipocytokine concentrations (leptin, adiponectin, resistin and visfatin) were measured in 169 patients with RA. The independent effect of each adipocytokine on HOMA and coronary artery calcification determined by electron beam CT was assessed adjusting for age, race, sex, BMI, traditional cardiovascular risk factors and inflammatory mediators. We also examined whether the effect of HOMA on coronary calcium is moderated by adipocytokines through an interaction analysis. RESULTS:: Leptin was associated with higher HOMA, even after adjusting for age, race, sex, BMI, traditional cardiovascular risk factors and inflammatory mediators (p<0.001), but visfatin (p=0.06), adiponectin (p=0.55) and resistin (p=0.98) were not. None of the adipocytokines were independently associated with coronary calcium (all p>0.05). Serum leptin concentrations interacted with HOMA (multivariate p interaction=0.02). Increasing leptin concentrations attenuated the increased risk of coronary calcification related to HOMA. The other adipocytokines and HOMA did not interact significantly (p>0.05). CONCLUSION:: Leptin is associated with insulin resistance in patients with RA but paradoxically attenuated the effects of insulin resistance on coronary calcification.

Multiparameter comparison of injection laryngoplasty, medialization laryngoplasty, and arytenoid adduction in an excised larynx model.

Laryngoscope. 2010 Jan 26;
Hoffman MR, Witt RE, Chapin WJ, McCulloch TM, Jiang JJ

OBJECTIVES/HYPOTHESIS:: Evaluate the effect of injection laryngoplasty (IL), medialization laryngoplasty (ML), and ML combined with arytenoid adduction (ML-AA) on acoustic, aerodynamic, and mucosal wave measurements in an excised larynx setup. STUDY DESIGN:: Comparative case study using ex vivo canine larynges. METHODS:: Measurements were recorded for eight excised canine larynges with simulated unilateral vocal fold paralysis before and after vocal fold injection with Cymetra. A second set of eight larynges was used to evaluate medialization laryngoplasty using a Silastic implant without and with arytenoid adduction. RESULTS:: IL and ML led to comparable decreases in phonation threshold flow (PTF), phonation threshold pressure (PTP), and phonation threshold power (PTW). ML-AA led to significant decreases in PTF (P = .008), PTP (P = .008), and PTW (P = .008). IL and ML led to approximately equal decreases in percent jitter and percent shimmer. ML-AA caused the greatest increase in signal-to-noise ratio. ML-AA discernibly decreased frequency (P = 0.059); a clear trend was not observed for IL or ML. IL significantly reduced mucosal wave amplitude (P = 0.002), whereas both ML and ML-AA increased it. All procedures significantly decreased glottal gap, with the most dramatic effects observed after ML-AA (P = 0.004). CONCLUSIONS:: ML-AA led to the greatest improvements in phonatory parameters. IL was comparable to ML aerodynamically and acoustically, but caused detrimental changes to the mucosal wave. Incremental improvements in parameters recorded from the same larynx were observed after ML and ML-AA. To ensure optimal acoustic outcome, the arytenoid must be correctly rotated. This study provides objective support for the combined ML-AA procedure in tolerant patients. Laryngoscope, 2010.