Alterations in nitric oxide synthase isoforms in acute lower limb ischemia and reperfusion

Alterations in nitric oxide synthase (NOS) are implicated in ischemia and ischemia-reperfusion injury. Changes in the 3 NOS isoforms in human skeletal muscle subjected to acute ischemia and reperfusion were studied. Muscle biopsies were taken from patients undergoing total knee replacement. Distribution of the specific NOS isoforms within muscle sections was studied using immunohistochemistry. NOS mRNA levels were measured using real-time reverse transcription-polymerase chain reaction and protein levels studied using Western blotting. NOS activity was also assessed using the citrulline assay. All 3 NOS isoforms were found in muscle sections associated with muscle fibers and microvessels. In muscle subjected to acute ischemia and reperfusion, NOS I/neuronal NOS mRNA and protein were elevated during reperfusion. NOS III/endothelial NOS was also upregulated at the protein level during reperfusion. No changes in NOS II/inducible NOS expression or NOS activity occurred. In conclusion, alterations in NOS I and III (neuronal NOS and endothelial NOS) at different levels occurred after acute ischemia and reperfusion in human skeletal muscle; however, this did not result in increased NOS activity. In the development of therapeutic agents based on manipulation of the NO pathway, targeting the appropriate NOS isoenzymes may be important.

The Dynamics of Secondary Forest Landscapes in the Lower Mekong Basin: A Regional-Scale Analysis

Secondary forests in the Lower Mekong Basin (LMB) are increasingly recognized as a valuable component of land cover, providing ecosystem services and benefits for local users. A large proportion of secondary forests in the LMB, especially in the uplands, are maintained by swidden cultivation. In order to assess the regional-scale status and dynamic trends of secondary forests in the LMB, an analysis of existing regional land cover data for 1993 and 1997 was carried out and forms the basis of this paper. To gain insight into the full range of dynamics affecting secondary forests beyond net-change rates, cross-tabulation matrix analyses were performed. The investigations revealed that secondary forests make up the largest share of forest cover in the LMB, with over 80% located in Laos and Cambodia. The deforestation rates for secondary forests are 3 times higher than the rates for other forest categories and account for two-thirds of the total deforestation. These dynamics are particularly pronounced in the less advanced countries of the LMB, especially in Laos, where national policies and the opening up of national economies seem to be the main drivers of further degradation and loss of secondary forests.

Provenance discrimination of Lower Cretaceous synrift sandstones (eastern Iberian Chain Spain) Constraints from detrital modes heavy minerals and geochemistry

Petrography, geochemical whole-rock composition, and chemical analyses of tourmaline were performed in order to determine the source areas of Lower Cretaceous Mora, El Castellar, and uppermost Camarillas Formation sandstones from the Iberian Chain, Spain. Sandstones were deposited in intraplate subbasins, which are bound by plutonic and volcanic rocks of Permian, Triassic, and Jurassic age, Paleozoic metamorphic rocks, and Triassic sedimentary rocks. Modal analyses together with petrographic and cathodoluminescence observations allowed us to define three quartz-feldspathic petrofacies and recognize diagenetic processes that modified the original framework composition. Results from average restored petrofacies are: Mora petrofacies = P/F >1 and Q(r)70 F(r)22 R(r)9; El Castellar petrofacies = P/F >1 and Q(r)57 F(r)25 R(r)18; and Camarillas petrofacies = P/F ∼ zero and Q(r)64 F(r)28 R(r)7 (P—plagioclase; F—feldspar; Q—quartz; R—rock fragments; r—restored composition). Trace-element and rare earth element abundances of whole-rock analyses discriminate well between the three petrofacies based on: (1) the Rb concentration, which is indicative of the K content and reflects the amount of K-feldspar modal abundance, and (2) the relative modal abundance of heavy minerals (tourmaline, zircon, titanite, and apatite), which is reproduced by the elements hosted in the observed heavy mineral assemblage (i.e., B and Li for tourmaline; Zr, Hf, and Ta for zircon; Ti, Ta, Nb, and their rare earth elements for titanite; and P, Y, and their rare earth elements for apatite). Tourmaline chemical composition for the three petrofacies ranges from Fe-tourmaline of granitic to Mg-tourmaline of metamorphic origin. The three defined petrofacies suggest a mixed provenance from plutonic and metamorphic source rocks. However, a progressively major influence of granitic source rocks was detected from the lowermost Mora petrofacies toward the uppermost Camarillas petrofacies. This provenance trend is consistent with the uplift and erosion of the Iberian Massif, which coincided with the development of the latest Berriasian synrift regional unconformity and affected all of the Iberian intraplate basins. The uplifting stage of Iberian Massif pluton caused a significant dilution of Paleozoic metamorphic source areas, which were dominant during the sedimentation of the lowermost Mora and El Castellar petrofacies. The association of petrographic data with whole-rock geochemical compositions and tourmaline chemical analysis has proved to be useful for determining source area characteristics, their predominance, and the evolution of source rock types during the deposition of quartz-feldspathic sandstones in intraplate basins. This approach ensures that provenance interpretation is consistent with the geological context.

Two-step postmortem angiography with a modified heart-lung machine: preliminary results

OBJECTIVE: The purpose of this study was to adapt and improve a minimally invasive two-step postmortem angiographic technique for use on human cadavers. Detailed mapping of the entire vascular system is almost impossible with conventional autopsy tools. The technique described should be valuable in the diagnosis of vascular abnormalities. MATERIALS AND METHODS: Postmortem perfusion with an oily liquid is established with a circulation machine. An oily contrast agent is introduced as a bolus injection, and radiographic imaging is performed. In this pilot study, the upper or lower extremities of four human cadavers were perfused. In two cases, the vascular system of a lower extremity was visualized with anterograde perfusion of the arteries. In the other two cases, in which the suspected cause of death was drug intoxication, the veins of an upper extremity were visualized with retrograde perfusion of the venous system. RESULTS: In each case, the vascular system was visualized up to the level of the small supplying and draining vessels. In three of the four cases, vascular abnormalities were found. In one instance, a venous injection mark engendered by the self-administration of drugs was rendered visible by exudation of the contrast agent. In the other two cases, occlusion of the arteries and veins was apparent. CONCLUSION: The method described is readily applicable to human cadavers. After establishment of postmortem perfusion with paraffin oil and injection of the oily contrast agent, the vascular system can be investigated in detail and vascular abnormalities rendered visible.

Haptics in forensics: the possibilities and advantages in using the haptic device for reconstruction approaches in forensic science

Non-invasive documentation methods such as surface scanning and radiological imaging are gaining in importance in the forensic field. These three-dimensional technologies provide digital 3D data, which are processed and handled in the computer. However, the sense of touch gets lost using the virtual approach. The haptic device enables the use of the sense of touch to handle and feel digital 3D data. The multifunctional application of a haptic device for forensic approaches is evaluated and illustrated in three different cases: the representation of bone fractures of the lower extremities, by traffic accidents, in a non-invasive manner; the comparison of bone injuries with the presumed injury-inflicting instrument; and in a gunshot case, the identification of the gun by the muzzle imprint, and the reconstruction of the holding position of the gun. The 3D models of the bones are generated from the Computed Tomography (CT) images. The 3D models of the exterior injuries, the injury-inflicting tools and the bone injuries, where a higher resolution is necessary, are created by the optical surface scan. The haptic device is used in combination with the software FreeForm Modelling Plus for touching the surface of the 3D models to feel the minute injuries and the surface of tools, to reposition displaced bone parts and to compare an injury-causing instrument with an injury. The repositioning of 3D models in a reconstruction is easier, faster and more precisely executed by means of using the sense of touch and with the user-friendly movement in the 3D space. For representation purposes, the fracture lines of bones are coloured. This work demonstrates that the haptic device is a suitable and efficient application in forensic science. The haptic device offers a new way in the handling of digital data in the virtual 3D space.

Successful lower extremity angioplasty improves brachial artery flow-mediated dilation in patients with peripheral arterial disease

INTRODUCTION: Peripheral arterial disease (PAD) is associated with systemic impaired flow-mediated dilation (FMD) and increased risk for cardiovascular events. Decreased FMD may be caused by a decrease in arterial shear stress due to claudication and inflammation due to muscle ischemia and reperfusion. We assumed that endovascular revascularization of lower limb arterial obstructions ameliorates FMD and lowers inflammation through improvement of peripheral perfusion. METHODS: The study was a prospective, open, randomized, controlled, single-center follow-up evaluation assessing the effect of endovascular revascularization on brachial artery reactivity (FMD) measured by ultrasound, white blood cell (WBC) count, high-sensitive C-reactive protein (hs-CRP), and fibrinogen. We investigated 33 patients (23 men) with chronic and stable PAD (Rutherford 2 to 3) due to femoropopliteal obstruction. Variables were assessed at baseline and after 4 weeks in 17 patients (group A) who underwent endovascular revascularization and best medical treatment, and in 16 patients (group B) who received best medical treatment only. RESULTS: FMD did not differ between group A and B (4.96% +/- 1.86% vs 4.60% +/- 2.95%; P = .87) at baseline. It significantly improved after revascularization in group A (6.44% +/- 2.88%; P = .02) compared with group B at 4 weeks of follow-up (4.53% +/- 3.17%; P = .92), where it remained unchanged. The baseline ankle-brachial index (ABI) was similar for group A and B (0.63 +/- 0.15 vs 0.66 +/- 0.10; P = .36). At 4 weeks of follow-up, ABI was significantly increased in group A (1.05 +/- 0.15; P = .0004) but remained unchanged in group B (0.62 +/- 0.1). WBC counts of the two groups were comparable at baseline (group A: 7.6 +/- 2.26 x 10(6)/mL and group B: 7.8 +/- 2.02 x 10(6)/mL, P = .81). In group A, the leukocyte count significantly decreased after angioplasty from 7.6 +/- 2.26 to 6.89 +/- 1.35 x 10(6)/mL (P = .03). For group B, WBC count did not differ significantly compared with baseline (7.76 +/- 2.64 x 10(6)/mL; P = .94). No effects were observed on hs-CRP or fibrinogen from endovascular therapy. CONCLUSION: Endovascular revascularization with reestablishment of peripheral arterial perfusion improves FMD and reduces WBC count in patients with claudication. Revascularization may therefore have clinical implications beyond relief of symptoms, for example, reducing oxidative stress caused by repeated muscle ischemia or increased shear stress due to improved ambulatory activity.

Single center experience with provisional abciximab therapy in complex lower limb interventions

BACKGROUND: Abciximab, a glycoprotein IIb/IIIa antagonist has been shown to improve patency and clinical outcome in patients undergoing endovascular recanalization of femoro-popliteal occlusions. However, data on abciximab therapy in complex peripheral catheter interventions of lower limbs are quite limited. The objective of this retrospective study was to evaluate the clinical and hemodynamic outcomes of patients treated with provisional abciximab during complex peripheral catheter interventions. PATIENTS AND METHODS: Analysis of a consecutive series of 44 patients with provisional abciximab therapy in complex peripheral catheter interventions with imminent risk of early rethrombosis defined as revascularization of arterial occlusions associated with one or more of the following additional circumstances named as time-consuming intervention > 3 hours, compromised contrast flow not solved by stenting, distal embolization not solved by mechanical thromboembolectomy, and peri-interventional notice of thrombus evolution despite adequate heparin adjustment of lower limbs. Adjunctive abciximab therapy was started in accordance to percutaneous coronary bailout situations. The decision to add abciximab was based on the decision of the operator and went along with the judgement that there is a rising risk of reocclusion due to the progressive complexity of an individual intervention. A bolus of 0.25 mg per kilogram of body weight, followed by a maintenance infusion of 0.125 microg/kg/min (up to a maximum dosage of 10 microg/min) for 12 hours was administered. Clinical and hemodynamic outcome was prospectively assessed at discharge, three and six months after the index procedure. RESULTS: The occluded artery of 44 limbs was in the iliac (2%), in the femoro-popliteal (73%) or below the knee segment (25%). Overall, occlusion length was 11.5 +/- 6.5 cm. Technical success rate was 95%. Mean ABI increased from 0.5 +/- 0.16 to 0.88 +/- 0.19 (p < 0.001) with immediate hemodynamic improvement of 91%. Overall, sustained clinical improvement was 84% and 66% at three and six months follow-up, with best results in iliac (100%), followed by below the knee (73%) and by femoro-popliteal segment (63%) at six months, respectively. Overall, secondary clinical improvement was 86% at six months. Minor and major bleeding complications were 16% and 9%, respectively. CONCLUSION: Abciximab should be noticed as medical adjunct in the interventional armamentarium to prevent imminent rethrombosis in complex peripheral catheter interventions.