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1.  Adenosine Kinase Inhibition Protects The Kidney Against Streptozotocin-Induced Diabetes Through Anti-inflammatory and Anti-oxidant Mechanisms 
Adenosine provides anti-inflammatory effects in cardiovascular disease via the activation of adenosine A2A receptors; however, the physiological effect of adenosine could be limited due to its phosphorylation by adenosine kinase. We hypothesized that inhibition of adenosine kinase exacerbates extracellular adenosine levels to reduce renal inflammation and injury in streptozotocin-induced diabetes. Diabetes was induced in male C57BL/6 mice by daily injection of streptozotocin (50 mg/kg/day, i.p. for 5 days). Control and diabetic mice were then treated with the adenosine kinase inhibitor ABT702 (1.5 mg/kg, i.p two times a week for 8 weeks, n = 7–8/group) or the vehicle (5% DMSO). ABT702 treatment reduced blood glucose level in diabetic mice (~ 20%; p<0.05). ABT702 also reduced albuminuria and markers of glomerular injury, nephrinuria and podocalyxin excretion levels, in diabetic mice. Renal NADPH oxidase activity and urinary thiobarbituric acid reactive substances (TBARS) excretion, indices of oxidative stress, were also elevated in diabetic mice and ABT702 significantly reduced these changes. ABT702 increased renal endothelial nitric oxide synthase expression (eNOS) and nitrate/nitrite excretion levels in diabetic mice. In addition, the diabetic mice displayed an increase in renal macrophage infiltration, in association with increased renal NFB activation. Importantly, treatment with ABT702 significantly reduced all these inflammatory parameters (P< 0.05). Furthermore, ABT702 decreased glomerular permeability and inflammation and restored the decrease in glomerular occludin expression in vitro in high glucose treated human glomerular endothelial cells. Collectively, the results suggest that the reno-protective effects of ABT702 could be attributed to the reduction in renal inflammation and oxidative stress in diabetic mice.
PMCID: PMC4302753  PMID: 24841126
Diabetes; adenosine kinase inhibition; albuminuria; renal injury; oxidative stress; nitric oxide; macrophage infiltration
2.  Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess 
Annals of Thoracic Medicine  2015;10(1):69-72.
Cystic fibrosis (CF) and apparent mineralocorticoid excess (AME) syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR) gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2), which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR) resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11βHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.
PMCID: PMC4286850  PMID: 25593612
Apparent mineralocorticoid excess; autosomal recessive; Arab; cystic fibrosis; Qatar
3.  Reporting ureteroscopy complications using the modified clavien classification system 
Urology Annals  2015;7(1):53-57.
Perioperative complications are one of the surrogate indicators of surgical outcomes. However, reporting these complications need a precise grading system. Our aim is to report and grade the complications of semirigid ureteroscopy in ureteral stone management according to the modified Clavien classification system.
Materials and Methods:
This is a prospective study conducted From January 2012 to June 2013. All patients with ureteral stones who were indicated for semirigid URS were evaluated. All procedures were performed by the same surgeon. The data recorded including patient demographics, clinical indication, stone size and location, operative time and complications were classified according to the modified Clavien classification system. The patients were followed for 8 weeks postoperatively.
148 patients included, Stone distribution was: 89 (60.1%) lower ureteral, 26 (17.6%) mid ureteral, and 33 (22.3%) upper ureteral. the mean stone size was 8.6 mm. Urgent URS done in 23% of patient. The overall stone free rate was 88.5%, the individual stone free rate for the upper, middle and lower ureter were 87.9%, 84.6%, and 89.9%, respectively. The mean operative time was 31.9 min (20-50 min.). Complications occurred in 26.35% of patients. Grade I complications occurred in 32 patients (26.1%), grade II in 9 (6.1%), grade IIIa in 7 (4.7%), grade IIIb in 8 (5.4%), grade IVa in two patient (1.35%), and grade IVb in one patient (0.7%). No grade V complication was encountered.
Ureteroscopy becomes the vanguard interventional therapy for ureteral stones with well-established efficacy and safety. It is of paramount importance to adopt a precise structured classification system for reporting surgical complications, that should be flexible and comprehensive in order to accommodate the various and rapidly expanding surgical fields.
PMCID: PMC4310118  PMID: 25657545
Complications; clavien classification; lithotripsy; ureteroscopy; ureteral stone
4.  Pattern of Blood Stream Infections within Neonatal Intensive Care Unit, Suez Canal University Hospital, Ismailia, Egypt 
Introduction. Blood stream infection (BSI) is a common problem of newborn in neonatal intensive care units (NICUs). Monitoring neonatal infections is increasingly regarded as an important contributor to safe and high-quality healthcare. It results in high mortality rate and serious complications. So, our aim was to determine the incidence and the pattern of BSIs in the NICU of Suez Canal University Hospital, Egypt, and to determine its impact on hospitalization, mortality, and morbidity. Methods. This study was a prospective one in which all neonates admitted to the NICUs in Suez Canal University hospital between January, 2013 and June 2013 were enrolled. Blood stream infections were monitored prospectively. The health care associated infection rate, mortality rate, causative organism, and risk factors were studied. Results. A total of 317 neonates were admitted to the NICU with a mortality rate of 36.0%. During this study period, 115/317 (36.3%) developed clinical signs of sepsis and were confirmed as BSIs by blood culture in only 90 neonates with 97 isolates. The total mean length of stay was significantly longer among infected than noninfected neonates (34.5 ± 18.3 and 10.8 ± 9.9 days, resp., P value < 0.001). The overall mortality rates among infected and noninfected neonates were 38.9% and 34.8%, respectively, with a significant difference. Klebsiella spp. were the most common pathogen (27.8%) followed by Pseudomonas (21.6%) and Staphylococcus aureus (15.4%). Conclusion. The rate of BSIs in NICU at Suez Canal University Hospital was relatively high with high mortality rate (36.0%).
PMCID: PMC4217241  PMID: 25389439
5.  Rationale and design of the Pan African Pulmonary hypertension Cohort (PAPUCO) study: implementing a contemporary registry on pulmonary hypertension in Africa 
BMJ Open  2014;4(10):e005950.
Pulmonary hypertension (PH) is a devastating, progressive disease with increasingly debilitating symptoms and usually shortened overall life expectancy due to a narrowing of the pulmonary vasculature and consecutive right heart failure. Little is known about PH in Africa, but limited reports suggest that PH is more prevalent in Africa compared with developed countries due to the high prevalence of risk factors in the region.
Methods and analysis
A multinational multicentre registry-type cohort study was established and tailored to resource-constraint settings to describe disease presentation, disease severity and aetiologies of PH, comorbidities, diagnostic and therapeutic management, and the natural course of PH in Africa. PH will be diagnosed by specialist cardiologists using echocardiography (right ventricular systolic pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure), usually accompanied by shortness of breath, fatigue, peripheral oedema and other cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per guidelines (European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines). Additional investigations such as a CT scan, a ventilation/perfusion scan or right heart catheterisation will be performed at the discretion of the treating physician. Functional tests include a 6 min walk test and the Karnofsky Performance Score. The WHO classification system for PH will be applied to describe the different aetiologies of PH. Several substudies have been implemented within the registry to investigate specific types of PH and their outcome at up to 24 months. Data will be analysed by an independent institution following a data analyse plan.
Ethics and dissemination
All local ethics committees of the participating centres approved the protocol. The data will be disseminated through peer-reviewed journals at national and international conferences and public events at local care providers.
PMCID: PMC4202005
pulmonary hypertension; Africa; HIV/AIDS
6.  Behavioral impact of sickle cell disease in young children with repeated hospitalization 
Saudi Journal of Anaesthesia  2014;8(4):504-509.
Sickle cell disease (SCD) in children with a history of repeated hospitalization is distressing for children as well as their parents leading to anxiety and has negative effects on the psychological state of children and their families. Objective: The aim of the study was to determine the overall effect of SCD on the behavior of young children age 1½ to 5 years old who had repeated history of hospitalization, compared to a control group of healthy children attended a vaccination clinic.
Patients and Methods:
Thirty-five children of age 1½ to 5 years who have SCD and repeated history of hospitalization were recruited from pediatric clinic as the study group and matched with same number of healthy children who attended vaccination clinic, as a control group. Both groups were administered the child behavior checklist (CBCL) 1½ to 5 years and diagnostic and statistical (DSM)-oriented scale. Behavior data were collected through a semi-structured questionnaire.
Children who have SCD had statistically significant behavioral changes on CBCL compared to the control group: Anxiety/depression (65.2 vs. 55.1; P < 0.001), somatic complaint (66.7 vs. 54.4; P < 0.001) withdrawn (63.4 vs. 53.2; P < 0.001), aggressive behavior (60.4 vs. 56; P=0.04), and internalizing symptoms (64.7 vs. 51.5; P < 0.001), respectively. The DSM scale showed that children with SCD scored significantly higher in pervasive developmental disorder compared to the control group (60.9 vs. 53.9; P < 0.001) respectively.
Children with SCD who had history of repeated hospitalization are at an increased risk of developing behavioral problems. Psychological counseling, social support, and proper pain management could minimize these behavioral consequences.
PMCID: PMC4236938  PMID: 25422609
Behavioral; CBCL 1½-5; hospitalization; pediatric; SCD
7.  Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage 
Biomedical Optics Express  2014;5(11):3748-3764.
Oxygen plays an important role in wound healing, as it is essential to biological functions such as cell proliferation, immune responses and collagen synthesis. Poor oxygenation is directly associated with the development of chronic ischemic wounds, which affect more than 6 million people each year in the United States alone at an estimated cost of $25 billion. Knowledge of oxygenation status is also important in the management of burns and skin grafts, as well as in a wide range of skin conditions. Despite the importance of the clinical determination of tissue oxygenation, there is a lack of rapid, user-friendly and quantitative diagnostic tools that allow for non-disruptive, continuous monitoring of oxygen content across large areas of skin and wounds to guide care and therapeutic decisions. In this work, we describe a sensitive, colorimetric, oxygen-sensing paint-on bandage for two-dimensional mapping of tissue oxygenation in skin, burns, and skin grafts. By embedding both an oxygen-sensing porphyrin-dendrimer phosphor and a reference dye in a liquid bandage matrix, we have created a liquid bandage that can be painted onto the skin surface and dries into a thin film that adheres tightly to the skin or wound topology. When captured by a camera-based imaging device, the oxygen-dependent phosphorescence emission of the bandage can be used to quantify and map both the pO2 and oxygen consumption of the underlying tissue. In this proof-of-principle study, we first demonstrate our system on a rat ischemic limb model to show its capabilities in sensing tissue ischemia. It is then tested on both ex vivo and in vivo porcine burn models to monitor the progression of burn injuries. Lastly, the bandage is applied to an in vivo porcine graft model for monitoring the integration of full- and partial-thickness skin grafts.
PMCID: PMC4242015  PMID: 25426308
(170.2655) Functional monitoring and imaging; (160.2540) Fluorescent and luminescent materials; (170.3880) Medical and biological imaging; (170.6510) Spectroscopy, tissue diagnostics
8.  The Utility of Outcome Studies in Plastic Surgery 
Outcome studies help provide the evidence-based science rationalizing treatment end results that factor the experience of patients and the impact on society. They improve the recognition of the shortcoming in clinical practice and provide the foundation for the development of gold standard care. With such evidence, health care practitioners can develop evidence-based justification for treatments and offer patients with superior informed consent for their treatment options. Furthermore, health care and insurance agencies can recognize improved cost-benefit options in the purpose of disease prevention and alleviation of its impact on the patient and society. Health care outcomes are ultimately measured by the treatment of disease, the reduction of symptoms, the normalization of laboratory results and physical measures, saving a life, and patient satisfaction. In this review, we outline the tools available to measure outcomes in plastic surgery and subsequently allow the objective measurements of plastic surgical conditions. Six major outcome categories are discussed: (1) functional measures; (2) preference-based measures and utility outcome scores; (3) patient satisfaction; (4) health outcomes and time; (5) other tools: patient-reported outcome measurement information system, BREAST-Q, and Tracking Operations and Outcomes for Plastic Surgeons; and (6) cost-effectiveness analysis. We use breast hypertrophy requiring breast reduction as an example throughout this review as a representative plastic surgical condition with multiple treatments available.
PMCID: PMC4229293  PMID: 25426372
9.  Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction 
EMBO Molecular Medicine  2014;6(6):760-777.
Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium.
PMCID: PMC4203354  PMID: 24797668
cardiac stem cells; cardioblasts; cardiomyocyte progenitor cells; cardiosphere-derived cells; heart regeneration
10.  Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay 
BioMed Research International  2014;2014:898670.
A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, HMBC, and UV spectroscopy) and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3-TBA manifested the best protective effect against DNA damage induced by bleomycin.
PMCID: PMC4034439  PMID: 24900997
11.  Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy 
Stem Cell Reports  2014;2(5):606-619.
The CADUCEUS trial of cardiosphere-derived cells (CDCs) has shown that it may be possible to regenerate injured heart muscle previously thought to be permanently scarred. The mechanisms of benefit are known to be indirect, but the mediators have yet to be identified. Here we pinpoint exosomes secreted by human CDCs as critical agents of regeneration and cardioprotection. CDC exosomes inhibit apoptosis and promote proliferation of cardiomyocytes, while enhancing angiogenesis. Injection of exosomes into injured mouse hearts recapitulates the regenerative and functional effects produced by CDC transplantation, whereas inhibition of exosome production by CDCs blocks those benefits. CDC exosomes contain a distinctive complement of microRNAs, with particular enrichment of miR-146a. Selective administration of a miR-146a mimic reproduces some (but not all) of the benefits of CDC exosomes. The findings identify exosomes as key mediators of CDC-induced regeneration, while highlighting the potential utility of exosomes as cell-free therapeutic candidates.
•Cardiosphere-derived cells (CDCs) regenerate the heart by unclear indirect mechanisms•Exosomes from CDCs promote angiogenesis, cardiomyocyte survival and proliferation•CDC exosomes are necessary and sufficient to explain the therapeutic effects of CDCs•MicroRNAs transferred by CDC exosomes at least partially mediate the benefits of CDCs
Marbán and colleagues pinpoint exosomes as critical mediators of myocardial regeneration triggered by cardiosphere-derived cells (CDCs). CDC exosomes inhibit apoptosis, promote proliferation of cardiomyocytes, and enhance angiogenesis. Injection of exosomes into injured mouse hearts recapitulates the CDC effect. CDC exosomes contain a distinctive complement of microRNAs, including miR-146a, that reproduces some of the benefits of CDC exosomes. Our findings highlight the utility of exosomes as therapeutic candidates.
PMCID: PMC4050492  PMID: 24936449
12.  Free-B-Ring flavonoids as potential lead compounds for colon cancer therapy 
Molecular and Clinical Oncology  2014;2(4):581-585.
Although flavonoids have been identified as a versatile source of anticancer agents, to the best of our knowledge, no study has yet investigated their anticolon cancer activity in depth. Therefore, the aim of this study was to investigate the association between the structural characteristics of flavonoids and their anticolon cancer activity in the Caco-2 human colon cancer cell line. Our findings demonstrated that the hydroxylation of C5 and C7 in ring A significantly enhanced the anticolon cancer activity of flavonoids over that of 5-fluorouracil, the classic reference cytotoxic agent. By contrast, the glycosylation or the presence of hydroxyl groups in ring B significantly decreased flavonoid anticancer activity. Collectively, these findings suggest a novel, rational design of flavonoid-related compounds that may improve the treatment of colorectal cancer.
PMCID: PMC4051550  PMID: 24940499
colorectal cancer; flavonoids; free-B-Ring flavonoids
13.  Determination of Suitable Microspore Stage and Callus Induction from Anthers of Kenaf (Hibiscus cannabinus L.) 
The Scientific World Journal  2014;2014:284342.
Kenaf (Hibiscus cannabinus L.) is one of the important species of Hibiscus cultivated for fiber. Availability of homozygous parent lines is prerequisite to the use of the heterosis effect reproducible in hybrid breeding. The production of haploid plants by anther culture followed by chromosome doubling can be achieved in short period compared with inbred lines by conventional method that requires self pollination of parent material. In this research, the effects of the microspore developmental stage, time of flower collection, various pretreatments, different combinations of hormones, and culture condition on anther culture of KB6 variety of Kenaf were studied. Young flower buds with immature anthers at the appropriate stage of microspore development were sterilized and the anthers were carefully dissected from the flower buds and subjected to various pretreatments and different combinations of hormones like NAA, 2,4-D, Kinetin, BAP, and TDZ to induce callus. The best microspore development stage of the flower buds was about 6–8 mm long collected 1-2 weeks after flower initiation. At that stage, the microspores were at the uninucleate stage which was suitable for culture. The best callus induction frequency was 90% in the optimized semisolid MS medium fortified with 3.0 mg/L BAP + 3.0 mg/L NAA.
PMCID: PMC3976891  PMID: 24757416
14.  Urinary Bladder Stone Complicating Ventriculovesical Shunt 
The standard treatment for hydrocephalus is either a ventriculoperitoneal or a ventriculo-atrial shunt. However, these conventional shunts may be associated with considerable complications and high revision rates which make these familiar shunts inappropriate for a certain subset of patients. A rare complication is reported associated with an unusual procedure in a 42-year-old woman who had had a ventriculovesical shunt for four years. She presented with recurrent urinary tract infections, haematuria and urge incontinence, and was discovered to have a large vesical stone over the vesical end of the shunt. She was treated with open suprapubic cystolithotomy and the redirection of the shunt to the peritoneal cavity. The patient was followed up for 12 months postoperatively and remained free of any urinary tract symptoms.
PMCID: PMC3916271  PMID: 24516748
Urinary Bladder Calculi; Ventriculoperitoneal Shunt, Surgical; Urinary Incontinence; Hematuria; Surgical Procedures, Operative; Case Report; Iraq
15.  Bone Flap Perfusion Assessment using Near-Infrared Fluorescence Imaging 
The Journal of surgical research  2012;178(2):e43-e50.
Microsurgical vascularized bone flaps are a versatile technique for reconstructing large bone defects. However, assessment of perfusion is challenging, as clinical examination is difficult intra-operatively and often not possible post-operatively. Therefore, it is important to develop techniques to assess perfusion of vascularized bone flaps, and potentially improve surgical outcomes. Near-infrared (NIR) fluorescence imaging has been previously shown to provide real-time, intra-operative evaluation of vascular perfusion. This pilot study investigates the ability of NIR imaging to assess perfusion of vascularized bone flaps.
Materials and Methods
Vascularized bone flaps were created on female Yorkshire pigs using well-established models for porcine forelimb osteomyocutaneous flap allotransplantation (N = 8) and hindlimb fibula flaps (N = 8). Imaging of the bone flaps was performed during harvest using the FLARE™ intraoperative fluorescence imaging system following systemic injection of indocyanine green (ICG). Perfusion was also assessed using standard of care by clinical observation and Doppler. NIR fluorescence perfusion assessment was confirmed by intermittent clamping of the vascular pedicle.
NIR fluorescence imaging can identify bone perfusion at the cut end of the osteotomy site. When the vascular pedicle is clamped or ligated, NIR imaging demonstrates no fluorescence when injected with ICG. With clamp removal, the osteotomy site emits fluorescence indicating bone perfusion. Results using fluorescence imaging show 100% agreement with clinical observation and Doppler.
Vascularized bone transfers have become an important tool in reconstructive surgery; however, no established techniques adequately assess perfusion. Our pilot study indicates that NIR imaging can provide real-time, intra-operative assessment of bone perfusion.
PMCID: PMC3435470  PMID: 22664132
Near-infrared imaging; vascularized bone flaps; bone perfusion; microsurgery; free flap; composite tissue allotransplantation
16.  Trends of adult primary malignant renal tumors over 6 years 
Pakistan Journal of Medical Sciences  2013;29(6):1385-1388.
Objective: To assess the demographic and clinico-pathological trends, as well as the management options of adult patients with primary malignant renal tumors over 6 years.
Methods: From July 2003 – July 2009, 55 adult patients with primary malignant renal tumors were treated in two teaching hospitals (Jordan University Hospital in Amman – Jordan and Al-Jumhory Teaching Hospital in Mosul – Iraq). Their data were reviewed retrospectively.
Results: Of the 55 patients, 44 had renal cell carcinoma (RCC), eight patients had Transitional cell carcinoma (TCC) of the renal pelvis, two had Sarcoma and one Patient had primary renal lymphoma. Among patients with RCC: the mean age was 56 years, male to female ratio was 3:1. The most common presenting symptom was hematuria. Most of the patients were treated with radical nephrectomy, the clear cell subtype was predominant and most of the patients were diagnosed at stage T2. Regarding patients with TCC: mean age was 57 years, all were treated with radical nephro-ureterectomy and removal of bladder cuff, however (50%) of them developed TCC of urinary bladder within 12 months of radical nephro-ureterectomy.
Conclusion: In our series of patients with RCC: there is a trend toward younger age at Diagnosis. We still encountered locally advanced and metastatic disease with a lower rate of incidentally Diagnosed tumors.With regard to patients with renal pelvis TCC: there are trends toward younger age affection, localized disease and early development of bladder TCC which indicate the importance of strict surveillance protocol.
PMCID: PMC3905374  PMID: 24550959
Renal tumors; Hematuria; Renal cell carcinoma; Transitional cell carcinoma; Radical nephrectomy
17.  In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines 
Brain metastasis from breast cancer poses a major clinical challenge. Integrins play a role in regulating adhesion, growth, motility, and survival, and have been shown to be critical for metastatic growth in the brain in preclinical models. Cilengitide, an αvβ3/αvβ5 integrin inhibitor, has previously been studied as an anti-cancer drug in various tumor types. Previous studies have shown additive effects of cilengitide and radiation in lung cancer and glioblastoma cell lines. The ability of cilengitide to enhance the effects of radiation was examined preclinically in the setting of breast cancer to assess its possible efficacy in the setting of brain metastasis from breast cancer.
Our panel of breast cells was composed of four cell lines: T-47D (ER/PR+, Her2-, luminal A), MCF-7 (ER/PR+, Her2-, luminal A), MDA-MB-231 (TNBC, basal B), MDA-MB-468 (TNBC, basal A). The presence of cilengitide targets, β3 and β5 integrin, was first determined. Cell detachment was determined by cell counting, cell proliferation was determined by MTS proliferation assay, and apoptosis was measured by Annexin V staining and flow cytometry. The efficacy of cilengitide treatment alone was analyzed, followed by assessment of combined cilengitide and radiation treatment. Integrin β3 knockdown was performed, followed by cilengitide and radiation treatment to test for incomplete target inhibition by cilengitide, in high β3 expressing cells.
We observed that all cell lines examined expressed both β3 and β5 integrin and that cilengitide was able to induce cell detachment and reduced proliferation in our panel. Annexin V assays revealed that a portion of these effects was due to cilengitide-induced apoptosis. Combined treatment with cilengitide and radiation served to further reduce proliferation compared to either treatment alone. Following β3 integrin knockdown, radiosensitization in combination with cilengitide was observed in a previously non-responsive cell line (MDA-MB-231). Clonogenic assays suggested little radiosensitization effects of cilengitide.
Cilengitide appears to enhance radiation response in preclinical models of breast cancer. These data suggest that the combination of radiation therapy and cilengitide may prove to be effective where radiation is utilized for the treatment of gross disease in breast cancer, such as in the setting of brain metastasis.
PMCID: PMC3816586  PMID: 24153102
Cilengitide; Breast cancer; Brain metastasis; Radiation
18.  Face Transplant Perfusion Assessment using Near-Infrared Fluorescence Imaging 
The Journal of surgical research  2012;177(2):e83-e88.
Composite tissue allografts (CTAs) including partial face transplantation have been achieved clinically. However, risks of complications including tissue ischemia, rejection, and transplant failure are significant. Safe and effective techniques to assess perfusion are needed to decrease complications in composite tissue flaps. Near-infrared (NIR) fluorescence imaging has been previously shown to provide a real-time, intraoperative evaluation of perfusion. This study investigates the use of NIR imaging in partial face CTA harvest.
Materials and Methods
Hemifacial CTAs (N = 8) were created using an established porcine model. This included ear cartilage, nerve, lymphoid tissue, muscle, and skin with perfusion by the carotid artery and external jugular vein. Animals were injected systemically with indocyanine green (ICG), and NIR fluorescence images were obtained simultaneously with color video. In addition, the elevated hemifacial flaps were assessed using standard of care, i.e. clinical examination and Doppler.
Flap design was facilitated by NIR imaging with localization of perforators to the hemifacial CTA flap. In particular, an arterial and venous phase could be clearly identified. Perfusion of the flap was assessed by NIR fluorescence intensity following injection of ICG. Sequential clamping of the artery and vein confirmed correlation of perfusion deficits with NIR imaging as well as with clinical examination and Doppler.
Evaluation and assessment of perfusion is important in facial transplantation. The results from our pilot study indicate that NIR imaging has the capability to assess perfusion of partial facial CTAs. This emergent technology shows promise in assessing tissue perfusion in a composite flap.
PMCID: PMC3434268  PMID: 22572616
Near-infrared imaging; face transplantation; composite tissue allotransplantation; microsurgery; free flap
20.  Case Report Evidence of Relationships between Hepatocellular Carcinoma and Ochratoxicosis 
PLoS ONE  2013;8(8):e71423.
The incidence of Hepatocellular carcinoma (HCC) is on the rise, but what is causing that trend has remained a mystery. Mycotoxins are almost entirely ignored health problems, and sometimes actually naively belittled in advanced medical care. Ochratoxin A (OTA) is one of the most abundant food contaminating mycotoxins worldwide that is carcinogenic, but no studies have evaluated its levels in HCC patients. Therefore, this study was designed to monitor the presence of OTA in the serum of HCC patients and to quantify the strength of the association between OTA and HCC.
We conducted a case control-based study on 61 participants. Thirty-nine were HCC cases identified between 2010 and 2012 and individually matched by age, sex, residence and date of recruitment to 22 healthy controls. Serum OTA and alpha-fetoprotein levels were measured by using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay, respectively.
HPLC analysis of 61 serum samples indicated that the highest incidence of elevated OTA was found in the HCC group and was 5-fold higher than in the control group. The concentration of OTA in the HCC group ranged between 0.129 and 10.93 ng/mL with a mean value±SD of 1.1±0.3 ng/mL, while in the normal group it ranged between 0.005 and 0.50 ng/mL with a mean value±SD of 0.201±0.02 ng/mL. The odds ratio for HCC patients presenting OTA levels above the cut-off of 0.207 (calculated by the receiver operating characteristic curve) was 9.78 (95% confidence interval = 2.9095–32.9816, P = 0.0002) with respect to normal controls, suggesting that HCC is 9.8 times as frequent in the exposed group to OTA.
Our results reveal a strong association between the presence of OTA and HCC, which may offer a coherent explanation for much of the descriptive epidemiology of HCC and suggest new avenues for analytical research.
PMCID: PMC3748048  PMID: 23977041
21.  Impact of reconstruction methods and pathological factors on survival after pancreaticoduodenectomy 
South Asian Journal of Cancer  2013;2(3):160-168.
Surgery remains the mainstay of therapy for pancreatic head (PH) and periampullary carcinoma (PC) and provides the only chance of cure. Improvements of surgical technique, increased surgical experience and advances in anesthesia, intensive care and parenteral nutrition have substantially decreased surgical complications and increased survival. We evaluate the effects of reconstruction type, complications and pathological factors on survival and quality of life.
Materials and Methods:
This is a prospective study to evaluate the impact of various reconstruction methods of the pancreatic remnant after pancreaticoduodenectomy and the pathological characteristics of PC patients over 3.5 years. Patient characteristics and descriptive analysis in the three variable methods either with or without stent were compared with Chi-square test. Multivariate analysis was performed with the logistic regression analysis test and multinomial logistic regression analysis test. Survival rate was analyzed by use Kaplan-Meier test.
Forty-one consecutive patients with PC were enrolled. There were 23 men (56.1%) and 18 women (43.9%), with a median age of 56 years (16 to 70 years). There were 24 cases of PH cancer, eight cases of PC, four cases of distal CBD cancer and five cases of duodenal carcinoma. Nine patients underwent duct-to-mucosa pancreatico jejunostomy (PJ), 17 patients underwent telescoping pancreatico jejunostomy (PJ) and 15 patients pancreaticogastrostomy (PG). The pancreatic duct was stented in 30 patients while in 11 patients, the duct was not stented. The PJ duct-to-mucosa caused significantly less leakage, but longer operative and reconstructive times. Telescoping PJ was associated with the shortest hospital stay. There were 5 postoperative mortalities, while postoperative morbidities included pancreatic fistula-6 patients, delayed gastric emptying in-11, GI fistula-3, wound infection-12, burst abdomen-6 and pulmonary infection-2. Factors that predisposed to development of pancreatic leakage included male gender, preoperative albumin < 30g/dl, pre-operative hemoglobin < 10g/dl and non PJ-duct to mucosa type of reconstruction. The ampullary cancers presented at an earlier stage and had a better prognosis than pancreatic cancer and cholangiocarcinoma. Early stage (I and II), negative surgical margin, well and moderate differentiation and absence of lymph node involvement significantly predicted for longer survival.
PJ duct-to-mucosa anastomosis was safe, caused least pancreatic leakage and least blood loss compared with the other methods of reconstruction and was associated with early return back to home and prolonged disease free and overall survival.
PMCID: PMC3889193  PMID: 24455609
Complication; mortality and survival; pancreaticojujenostomy duct to mucosa; periampullary cancer; postoperative pancreatic fistula; reconstruction
22.  Inhibitory effect of a mixture containing vitamin C, lysine, proline, epigallocatechin gallate, zinc and alpha-1-antitrypsin on lung carcinogenesis induced by benzo(a) pyrene in mice 
This study was aimed to evaluate protective and therapeutic effects of a specific mixture, containing vitamin C, lysine, proline, epigallocatechin gallate and zinc, as well as alpha-1-antitrypsin protein on lung tumorigenesis induced by benzo(a) pyrene [B(a)P] in mice.
Materials and Methods:
Swiss albino mice were divided into two main experiments, experiment (1) the mice were injected with 100 mg/kg B(a)P and lasted for 28 weeks, while experiment (2) the mice were injected with 8 doses each of 50 mg/kg B(a)P and lasted for 16 weeks. Each experiment (1 and 2) divided into five groups, group (I) received vehicle, group (II) received the protector mixture, group (III) received the carcinogen B(a)P, group (IV) received the protector together with the carcinogen (simultaneously) and group (V) received the carcinogen then the protector (consecutively).
Total sialic acid, thiobarbituric acid reactive substances, vascular epithelial growth factor, hydroxyproline levels, as well as elastase and gelatinase activities showed significant elevation in group (III) in the two experiments comparing to control group (P < 0.001). These biochemical alterations were associated with histopathological changes. Administration of the protector in group IV and group V causes significant decrease in such parameters with improvement in histopathological alterations with improvement in histopathological alterations when compared with group III in the two experiments (P < 0.001).
The present protector mixture has the ability to suppress neoplastic alteration and restore the biochemical and histopathological parameters towards normal on lung carcinogenesis induced by benzo(a) pyrene in mice. Furthermore, the present mixture have more protective rather than therapeutic action.
PMCID: PMC3810580  PMID: 24174951
Alpha-1-antitrypsin; benzo(a) pyrene; epigallocatechin gallate; lung tumorigenesis; lysine; proline; protector; vitamin C; zinc
23.  Role of adenosine in diabetic retinopathy 
In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. Adenosine and its receptors have been shown to possess anti-inflammatory properties that have only recently been studied in DR. Here, we review recent studies that determined the roles of adenosine and its associated proteins, including equilibrative nucleoside transporters, adenosine receptors, and underlying signaling pathways in retinal complications associated with diabetes.
PMCID: PMC3342407  PMID: 23308298
Diabetic retinopathy; Adenosine; Microglia; Cannabinoids; Adenosine receptors
24.  Iodized Salt Consumption in Sudan: Present Status and Future Directions 
Iodine Deficiency Disorders (IDD) Control Programme in Sudan adopted salt iodization as the long-term strategy in 1994. In 2000, it was found that less than 1% of households were using adequately-iodized salt. The objectives of this study were to: (i) study the coverage and variation of different geographical regions of Sudan regarding access to and use of iodized salt, (ii) explore the possible factors which influence the use of iodized salt, (iii) develop recommendations to help in the implementation of the Universal Salt Iodization (USI) strategy in Sudan. This paper is based on the Sudan Household Health Survey (SHHS) dataset. A total sample of 24,507 households was surveyed, and 18,786 cooking salt samples were tested for iodine levels with rapid salt-testing kits. Nationally, the percentage of households using adequately-iodized salt increased from less than 1% in 2000 to 14.4%, with wide variations between states. Access to iodized salt ranged from 96.9% in Central Equatoria to 0.4% in Gezira state. Population coverage with iodized salt in Sudan remains very low. The awareness and political support for USI programme is very weak. National legislation banning the sale of non-iodized salt does not exist. Utilization of the already-existing laws, like the National Standardization and Metrology Law (2008), to develop a compulsory national salt specification, will accelerate the USI in Sudan.
PMCID: PMC3763614  PMID: 23304909
Iodine deficiency disorders; Salt legislations; Universal Salt Iodization; Sudan

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