Protective effects of curcumin against gamma radiation-induced ileal mucosal damage

The major objective of this study was to test curcumin as a potential radioprotectant for the ileum goblet cells of the rat. Wistar albino rats were used in the study. Group A was the control group and group B was the single dose radiation group. Group C was the two dose radiation group (4 days interval). The rats in groups D and E were given a daily dose of 100 mg/kg of curcumin for 14 and 18 days, respectively. During the curcumin administration period, the rats in group D were exposed to abdominal area gamma (γ)-ray dose of 5 Gy on the 10th day and group E was exposed to same dose radiation on the 10th and 14th day. Irradiation and treatment groups were decapitated on the 4th day after exposure to single or two-dose irradiation and ileum tissues were removed for light and electron microscopic investigation. Single or two dose 5 Gy γ-irradiation caused a marked intestinal mucosal injury in rats on the 4th day. Radiation produced increases in the number of goblet cells. Curcumin appears to have protective effects against radiation-induced damage, suggesting that clinical transfer is feasible

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Emergency department spirometric volume and base deficit delineate risk for torso injury in stable patients

BACKGROUND: We sought to determine torso injury rates and sensitivities associated with fluid-positive abdominal ultrasound, metabolic acidosis (increased base deficit and lactate), and impaired pulmonary physiology (decreased spirometric volume and PaO(2)/FiO(2)). METHODS: Level I trauma center prospective pilot and post-pilot study (2000–2001) of stable patients. Increased base deficit was < 0.0 in ethanol-negative and ≤ -3.0 in ethanol-positive patients. Increased lactate was > 2.5 mmol/L in ethanol-negative and ≥ 3.0 mmol/L in ethanol-positive patients. Decreased PaO(2)/FiO(2 )was < 350 and decreased spirometric volume was < 1.8 L. RESULTS: Of 215 patients, 66 (30.7%) had a torso injury (abdominal/pelvic injury n = 35 and/or thoracic injury n = 43). Glasgow Coma Scale score was 14.8 ± 0.5 (13–15). Torso injury rates and sensitivities were: abdominal ultrasound negative and normal base deficit, lactate, PaO(2)/FiO(2), and spirometric volume – 0.0% & 0.0%; normal base deficit and normal spirometric volume – 4.2% & 4.5%; chest/abdominal soft tissue injury – 37.8% & 47.0%; increased lactate – 39.7% & 47.0%; increased base deficit – 41.3% & 75.8%; increased base deficit and/or decreased spirometric volume – 43.8% & 95.5%; decreased PaO(2)/FiO(2 )– 48.9% & 33.3%; positive abdominal ultrasound – 62.5% & 7.6%; decreased spirometric volume – 73.4% & 71.2%; increased base deficit and decreased spirometric volume – 82.9% & 51.5%. CONCLUSIONS: Trauma patients with normal base deficit and spirometric volume are unlikely to have a torso injury. Patients with increased base deficit or lactate, decreased spirometric volume, decreased PaO(2)/FiO(2), or positive FAST have substantial risk for torso injury. Increased base deficit and/or decreased spirometric volume are highly sensitive for torso injury. Base deficit and spirometric volume values are readily available and increase or decrease the suspicion for torso injury

Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: A prospective study in 716 patients over 8 years

<p>Abstract</p> <p>Background</p> <p>To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.</p> <p>Methods</p> <p>We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.</p> <p>Results</p> <p>During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.</p> <p>Conclusion</p> <p>By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.</p

Local control by radiotherapy: is that all there is?

Radiotherapy is a local treatment modality employed in breast cancer to reduce local recurrence following surgery. The observed association of optimal local control with improved survival was not expected in a disease characterized by early systemic spread. The underlying mechanisms whereby the application of ionizing radiation to the primary tumor site can have systemic effects remain unclear and are the subject of much debate. In the present article we discuss the hypothesis that radiotherapy has unique biological effects and that, in addition to killing residual neoplastic cells after surgery is performed, it might favorably alter the microenvironment at the primary tumor site during the process of wound healing and the development of antitumor immune responses

Mitochondrionopathy Phenotype in Doxorubicin-Treated Wistar Rats Depends on Treatment Protocol and Is Cardiac-Specific

Although doxorubicin (DOX) is a very effective antineoplastic agent, its clinical use is limited by a dose-dependent, persistent and cumulative cardiotoxicity, whose mechanism remains to be elucidated. Previous works in animal models have failed to use a multi-organ approach to demonstrate that DOX-associated toxicity is selective to the cardiac tissue. In this context, the present work aims to investigate in vivo DOX cardiac, hepatic and renal toxicity in the same animal model, with special relevance on alterations of mitochondrial bioenergetics. To this end, male Wistar rats were sub-chronically (7 wks, 2 mg/Kg) or acutely (20 mg/Kg) treated with DOX and sacrificed one week or 24 hours after the last injection, respectively. Alterations of mitochondrial bioenergetics showed treatment-dependent differences between tissues. No alterations were observed for cardiac mitochondria in the acute model but decreased ADP-stimulated respiration was detected in the sub-chronic treatment. In the acute treatment model, ADP-stimulated respiration was increased in liver and decreased in kidney mitochondria. Aconitase activity, a marker of oxidative stress, was decreased in renal mitochondria in the acute and in heart in the sub-chronic model. Interestingly, alterations of cardiac mitochondrial bioenergetics co-existed with an absence of echocardiograph, histopathological or ultra-structural alterations. Besides, no plasma markers of cardiac injury were found in any of the time points studied. The results confirm that alterations of mitochondrial function, which are more evident in the heart, are an early marker of DOX-induced toxicity, existing even in the absence of cardiac functional alterations

Use of outpatient care in VA and Medicare among disability-eligible and age-eligible veteran patients

<p>Abstract</p> <p>Background</p> <p>More than half of veterans who use Veterans Health Administration (VA) care are also eligible for Medicare via disability or age, but no prior studies have examined variation in use of outpatient services by Medicare-eligible veterans across health system, type of care or time.</p> <p>Objectives</p> <p>To examine differences in use of VA and Medicare outpatient services by disability-eligible or age-eligible veterans among veterans who used VA primary care services and were also eligible for Medicare.</p> <p>Methods</p> <p>A retrospective cohort study of 4,704 disability- and 10,816 age-eligible veterans who used VA primary care services in fiscal year (FY) 2000. We tracked their outpatient utilization from FY2001 to FY2004 using VA administrative and Medicare claims data. We examined utilization differences for primary care, specialty care, and mental health outpatient visits using generalized estimating equations.</p> <p>Results</p> <p>Among Medicare-eligible veterans who used VA primary care, disability-eligible veterans had more VA primary care visits (<it>p </it>< 0.001) and more VA specialty care visits (<it>p </it>< 0.001) than age-eligible veterans. They were more likely to have mental health visits in VA (<it>p </it>< 0.01) and Medicare-reimbursed visits (<it>p </it>< 0.01). Disability-eligible veterans also had more total (VA+Medicare) visits for primary care (<it>p </it>< 0.01) and specialty care (<it>p </it>< 0.01), controlling for patient characteristics.</p> <p>Conclusions</p> <p>Greater use of primary care and specialty care visits by disability-eligible veterans is most likely related to greater health needs not captured by the patient characteristics we employed and eligibility for VA care at no cost. Outpatient care patterns of disability-eligible veterans may foreshadow care patterns of veterans returning from Afghanistan and Iraq wars, who are entering the system in growing numbers. This study provides an important baseline for future research assessing utilizations among returning veterans who use both VA and Medicare systems. Establishing effective care coordination protocols between VA and Medicare providers can help ensure efficient use of taxpayer resources and high quality care for disabled veterans.</p

Neuropathological Similarities and Differences between Schizophrenia and Bipolar Disorder: A Flow Cytometric Postmortem Brain Study

Recent studies suggest that schizophrenia (SCH) and bipolar disorder (BPD) may share a similar etiopathology. However, their precise neuropathological natures have rarely been characterized in a comprehensive and quantitative fashion. We have recently developed a rapid, quantitative cell-counting method for frozen unfixed postmortem brains using a flow cytometer. In the present study, we not only counted stained nuclei, but also measured their sizes in the gray matter of frontopolar cortices (FPCs) and inferior temporal cortices (ITCs) from patients with SCH or BPD, as well as in that from normal controls. In terms of NeuN(+) neuronal nuclei size, particularly in the reduced densities of small NeuN(+) nuclei, we found abnormal distributions present in the ITC gray matter of both patient groups. These same abnormalities were also found in the FPCs of SCH patients, whereas in the FPCs of BPD patients, a reduction in oligodendrocyte lineage (olig2(+)) cells was much more common. Surprisingly, in the SCH FPC, normal left-greater-than-right asymmetry in neural nuclei densities was almost completely reversed. In the BPD FPC, this asymmetry, though not obvious, differed significantly from that in the SCH FPC. These findings indicate that while similar neuropathological abnormalities are shared by patients with SCH or BPD, differences also exist, mainly in the FPC, which may at least partially explain the differences observed in many aspects in these disorders

Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

Background:Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.Methods: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg-1 verteporfin. After 60-90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.Results:In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm 3 at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy.Conclusions:Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds. © 2014 Cancer Research UK