Erythropoietin neuroprotection is enhanced by direct cortical application following subdural blood evacuation in a rat model of acute subdural hematoma

Recombinant human erythropoietin (EPO) has been successfully tested as neuroprotectant in brain injury models. The first large clinical trial with stroke patients, however, revealed negative results. Reasons are manifold and may include side-effects such as thrombotic complications or interactions with other medication, EPO concentration, penetration of the blood-brain-barrier and/or route of application. The latter is restricted to systemic application. Here we hypothesize that EPO is neuroprotective in a rat model of acute subdural hemorrhage (ASDH) and that direct cortical application is a feasible route of application in this injury type. The subdural hematoma was surgically evacuated and EPO was applied directly onto the surface of the brain. We injected NaCl, 200, 2000 or 20,000IU EPO per rat i.v. at 15min post-ASDH (400μl autologous venous blood) or NaCl, 0.02, 0.2 or 2IU per rat onto the cortical surface after removal of the subdurally infused blood t at 70min post-ASDH. Arterial blood pressure (MAP), blood chemistry, intracranial pressure (ICP), cerebral blood flow (CBF) and brain tissue oxygen (ptiO2) were assessed during the first hour and lesion volume at 2days after ASDH. EPO 20,000IU/rat (i.v.) elevated ICP significantly. EPO at 200 and 2000IU reduced lesion volume from 38.2±0.6mm(3) (NaCl-treated group) to 28.5±0.9 and 22.2±1.3mm(3) (all p<0.05 vs. NaCl). Cortical application of 0.02IU EPO after ASDH evacuation reduced injury from 36.0±5.2 to 11.2±2.1mm(3) (p=0.007), whereas 0.2IU had no effect (38.0±9.0mm(3)). The highest dose of both application routes (i.v. 20,000IU; cortical 2IU) enlarged the ASDH-induced damage significantly to 46.5±1.7 and 67.9±10.4mm(3) (all p<0.05 vs. NaCl). In order to test whether Tween-20, a solvent of EPO formulation 'NeoRecomon®' was responsible for adverse effects two groups were treated with NaCl or Tween-20 after the evacuation of ASDH, but no difference in lesion volume was detected. In conclusion, EPO is neuroprotective in a model of ASDH in rats and was most efficacious at a very low dose in combination with subdural blood removal. High systemic and topically applied concentrations caused adverse effects on lesion size which were partially due to increased ICP. Thus, patients with traumatic ASDH could be treated with cortically applied EPO but with caution concerning concentration.

Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent – preliminary results in a rabbit model

Hypothesis and Objectives PEGylated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Secondly, visualization of the (real-time) therapeutic effects of tissue-Plasminogen Activator (t-PA) on pulmonary embolism (PE) was attempted. Materials and Methods Six rabbits (approximate 4 kg weight) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml, GE HealthCare, Princeton, NJ) at a dose of 1400 mgI per animal and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mgI/animal). Subsequently, five animals were injected with 2mg t-PA and imaging continued for up to 4 ½ hours. Results Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited non uniform opacification and rapid clearance post injection. Three out of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, Pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10–57%, mean 42%). One animal showed no response to t-PA. Conclusions Liposomal blood pool agents effectively identified acute PE without need for re-injection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections

Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent: preliminary results in a rabbit model.

RATIONALE AND OBJECTIVES: Polyethylene glycol-coated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Also, visualization of the (real-time) therapeutic effects of tissue plasminogen activator (t-PA) on pulmonary embolism (PE) was attempted. MATERIALS AND METHODS: Six rabbits (weight approximately 4 kg) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml; GE HealthCare, Princeton, NJ) at a dose of 1400 mg I per animal, and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mg I/animal). Subsequently, five animals were injected with 2 mg of t-PA and imaging continued for up to 4(1/2) hours. RESULTS: Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited nonuniform opacification and rapid clearance postinjection. Three of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10-57%, mean 42%). One animal showed no response to t-PA. CONCLUSIONS: Liposomal blood pool agents effectively identified acute PE without need for reinjection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections.

A patient-specific study of type-B aortic dissection: evaluation of true-false lumen blood exchange

BACKGROUND Aortic dissection is a severe pathological condition in which blood penetrates between layers of the aortic wall and creates a duplicate channel - the false lumen. This considerable change on the aortic morphology alters hemodynamic features dramatically and, in the case of rupture, induces markedly high rates of morbidity and mortality. METHODS In this study, we establish a patient-specific computational model and simulate the pulsatile blood flow within the dissected aorta. The k-ω SST turbulence model is employed to represent the flow and finite volume method is applied for numerical solutions. Our emphasis is on flow exchange between true and false lumen during the cardiac cycle and on quantifying the flow across specific passages. Loading distributions including pressure and wall shear stress have also been investigated and results of direct simulations are compared with solutions employing appropriate turbulence models. RESULTS Our results indicate that (i) high velocities occur at the periphery of the entries; (ii) for the case studied, approximately 40% of the blood flow passes the false lumen during a heartbeat cycle; (iii) higher pressures are found at the outer wall of the dissection, which may induce further dilation of the pseudo-lumen; (iv) highest wall shear stresses occur around the entries, perhaps indicating the vulnerability of this region to further splitting; and (v) laminar simulations with adequately fine mesh resolutions, especially refined near the walls, can capture similar flow patterns to the (coarser mesh) turbulent results, although the absolute magnitudes computed are in general smaller. CONCLUSIONS The patient-specific model of aortic dissection provides detailed flow information of blood transport within the true and false lumen and quantifies the loading distributions over the aorta and dissection walls. This contributes to evaluating potential thrombotic behavior in the false lumen and is pivotal in guiding endovascular intervention. Moreover, as a computational study, mesh requirements to successfully evaluate the hemodynamic parameters have been proposed.

The impact of pelvic venous pressure on blood loss during open radical cystectomy and urinary diversion: Results from a secondary analysis of a randomized clinical trial

PURPOSE Blood loss and blood substitution are associated with higher morbidity after major abdominal surgery. During major liver resection, low local venous pressure, has been shown to reduce blood loss. Ambiguity persists concerning the impact of local venous pressure on blood loss during open radical cystectomy. We aimed to determine the association between intraoperative blood loss and pelvic venous pressure (PVP) and determine factors affecting PVP. MATERIAL AND METHODS In the frame of a single-center, double-blind, randomized trial, PVP was measured in 82 patients from a norepinephrine/low-volume group and in 81 from a control group with liberal hydration. For this secondary analysis, patients from each arm were stratified into subgroups with PVP <5 mmHg or ≥5 mmHg measured after cystectomy (optimal cut-off value for discrimination of patients with relevant blood loss according to the Youden's index). RESULTS Median blood loss was 800 ml [range: 300-1600] in 55/163 patients (34%) with PVP <5 mmHg and 1200 ml [400-3000] in 108/163 patients (66%) with PVP ≥5 mmHg; (P<0.0001). A PVP <5 mmHg was measured in 42/82 patients (51%) in the norepinephrine/low-volume group and 13/81 (16%) in the control group (P<0.0001). PVP dropped significantly after removal of abdominal packing and abdominal lifting in both groups at all time points (at begin and end of pelvic lymph node dissection, end of cystectomy) (P<0.0001). No correlation between PVP and central venous pressure could be detected. CONCLUSIONS Blood loss was significantly reduced in patients with low PVP. Factors affecting PVP were fluid management and abdominal packing.

Christian-Muslim Relations. A Bibliographical History Volume 6: Western Europe (1500-1600)

Christian-Muslim Relations. A Bibliographical History, volume 6 (CMR 6), covering the years 1500-1600, is a continuing volume in a history of relations between followers of the two faiths as it is recorded in their written works. Together with introductory essays, it comprises detailed entries on all the works known from this century. This volume traces the attitudes of Western Europeans to Islam, particularly in light of continuing Ottoman expansion, and early despatches sent from Portuguese colonies around the Indian Ocean. The result of collaboration between numerous leading scholars, CMR 6, along with the other volumes in this series, is intended as a fundamental tool for research in Christian-Muslim relations.

Bone loss after ridge expansion with or without reflection of the periosteum.

OBJECTIVE To evaluate the role of the periosteum in preserving the buccal bone after ridge splitting and expansion with simultaneous implant placement. MATERIAL AND METHODS In 12 miniature pigs, the mandibular premolars and first molars were removed together with the interdental bone septa and the buccal bone. Three months later, ridge splitting and expansion of the buccal plate was performed with simultaneous placement of two titanium implants per quadrant. Access by a mucosal flap (MF) was prepared on test sides, while a mucoperiosteal flap (MPF) with complete denudation of the buccal bone was increased on control sides. After healing periods of six and 12 weeks, the animals were sacrificed for histologic and histometric evaluation. RESULTS In the MF group, all 16 implants were osseointegrated, while in the MPF group, four of 16 implants were lost. Noticeable differences of bone levels on the implant surface and of the bone crest (BC) were found between the MF and the MPF group. Buccally after 6 weeks, the median distance between the implant shoulder (IS) and the coronal-most bone on the implant (cBIC) was for the MF group -1.42 ± 0.42 mm and for the MPF group -4.80 ± 2.72 mm (P = 0.15). The median distance between the IS and the buccal BC was -1.24 ± 0.51 mm and -2.78 ± 1.98 mm (P = 0.12) for the MF and MPF group, respectively. After 12 weeks, median IS-cBIC was -2.12 ± 0.84 mm for MF and -7.19 mm for MPF, while IS-BC was -2.08 ± 0.79 mm for MF and -5.96 mm for MPF. After 6 weeks, the median buccal bone thickness for MF and MPF was 0.01 and 0 mm (P < 0.001) at IS, 1.48 ± 0.97 mm and 0 ± 0.77 mm (P = 0.07) at 2 mm apical to IS, and 2.12 ± 1.19 mm and 1.72 ± 01.50 mm (P = 0.86) at 4 mm apical to IS, respectively. After 12 weeks, buccal bone thickness in the MF group was 0 mm at IS, 0.21 mm at 2 mm apical to IS, and 2.56 mm at 4 mm apical to IS, whereas complete loss of buccal bone was measured from IS to 4 mm apical to IS for the MPF group. CONCLUSIONS In this ridge expansion model in miniature pigs, buccal bone volume was significantly better preserved when the periosteum remained attached to the bone.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator.

OBJECTIVES Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. METHODS The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. RESULTS Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. CONCLUSIONS We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator

Gebiet: Chirurgie Biomedizintechnik Biophysik Transplantationsmedizin Kardiologie Abstract: OBJECTIVES: – Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. – – METHODS: – The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. – – RESULTS: – Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. – – CONCLUSIONS: – We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion. – – © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications

OBJECTIVES The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.

Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.

Blood-oxygen-level-dependent (BOLD) signal changes in total cortex and subcortex, pain, reward, and vigilance regions during mechanical pressure pain after morphine administration

Morphine is the most common clinical choice in the management of severe pain. Although the molecular mechanisms of morphine have already been characterized, the cerebral circuits by which it attenuates the sensation of pain have not yet been studied in humans. The objective of this two-arm (morphine versus placebo), between-subjects study was to examine whether morphine affects pain via pain-related cortical circuits, but also via reward regions that relate to the motivational state, as well as prefrontal regions that relate to vigilance as a result of morphine's sedative effects. Cortical activity was measured by the blood-oxygen-level-dependent (BOLD) signal changes using functional magnetic resonance imaging (fMRI). ^ The novelty of this study is at three levels: (i) to develop a methodology that will assess the average BOLD signal across subjects for the pain, reward, and vigilance cortical systems; (ii) to examine whether the reward and/or sedative effects of morphine are contributing factors to cortical regions associated with the motivational state and vigilance; and (iii) to propose a neuroanatomical model related to the opioid-sensitive effects of reward and sedation as a function of cortical activity related to pain in an effort to assess future analgesics. ^ Consistent with our hypotheses, our findings showed that the decrease in total pain-related volume activated between the post- and the pre-treatment morphine group was about 78%, while the post-treatment placebo group displayed only a 5% decrease when compared to pre-treatment levels of activation. The volume increase in reward regions was 451% in the post-treatment compared to the pre-treatment morphine condition. Finally, the volumetric decrease in vigilance regions was 63% in the posttreatment compared to the pre-treatment morphine condition. ^ These findings imply that changes in the blood flow of the reward and vigilance regions may be contributing factors in producing the analgesic effect under morphine administration. Future studies need to replicate this study in a higher resolution fMRI environment and to assess the proposed neuroanatomical model in patient populations. The necessity of pain research is apparent, since pain cuts across different diseases especially chronic ones, and thus, is recognized as a vital public health developing area. ^

Proteomic identification and functional characterization of prohibitin 1 and 2 in T cell activation, expansion, survival and disease

Several immune pathologies are the result of aberrant regulation of T lymphocytes. Pronounced T cell proliferation can result in autoimmunity or hematologic malignancy, whereas loss of T cell activity can manifest as immunodeficiency. Thus, there is a critical need to characterize the signal transduction pathways that mediate T cell activation so that novel and rational strategies to detect and effectively control T cell mediated disease can be achieved. ^ The first objective of this dissertation was to identify and characterize novel T cell regulatory proteins that are differentially expressed upon antigen induced activation. Using a functional proteomics approach, two members of the prohibitin (Phb) family of proteins, Phb1 and Phb2, were determined to be upregulated upon activation of primary human T cells. Furthermore, their regulated expression was dependent upon CD3 and CD28 signaling pathways which synergistically increased their expression. In contrast to previous reports of Phb nuclear localization, both proteins were determined to localize to the mitochondrial inner membrane of human T cells. Additionally, novel Phb phosphorylation sites were identified and characterized using mass spectrometry, phosphospecific antibodies and site directed mutagenesis. ^ Prohibitins have been proposed to play important roles in cancer development however the mechanism of action has not been elucidated. The second objective of this dissertation was to define the functional role of Phbs in T cell activity, survival and disease. Compared to levels in normal human T cells, Phb expression was higher in the human tumor T cell line Kit225 and subcellularly localized to the mitochondrion. Ablation of Phb expression by siRNA treatment of Kit225 cells resulted in disruption of mitochondrial membrane potential and significantly enhanced their sensitivity to cell death, suggesting they serve a protective function in T cells. Furthermore, Q-RT-PCR analysis of human oncology cDNA expression libraries indicated the Phbs may represent hematological cancer biomarkers. Indeed, Phb1 and Phb2 protein levels were 6-10 fold higher in peripheral blood mononuclear cells isolated from malignant lymphoma and multiple myeloma patients compared to healthy individuals. ^ Taken together, Phb1 and Phb2 are novel phosphoproteins upregulated during T cell activation and transformation to function in the maintenance of mitochondrial integrity and perhaps energy metabolism, thus representing previously unrecognized intracellular biomarkers and therapeutic targets for regulating T cell activation and hematologic malignancies. ^

Expansion of Asparagus Production and Exports in Peru

Peru is the one of the most important exporters of asparagus in the world. Its export volume of fresh asparagus is ranked number one, and its export volume of preserved asparagus number two, globally. The objective of this paper is to provide an overview of the recent trends in asparagus production and exports around the world and to analyze factors in the development of the Peruvian asparagus industry. The production of asparagus has spread geographically. The center of its production used to be in the principal consuming countries, such as France, Germany and the United States. Afterward, it spread to neighboring countries such as Spain and Mexico where production factors such as climate and labor costs are favorable. After the rise and fall of Taiwan as a major preserved white asparagus exporter, China and Peru replaced its position. Finally, in recent years, Peru expanded its fresh green asparagus exports to the U.S. market by taking advantage of the increasing demand for fresh vegetables and supplying produce in seasons when neither U.S. nor Mexican producers can harvest. In addition to the changing factors in the international market, there are several factors in the development of the industry: high yields of produce due to favorable climatic and soil conditions; the introduction of the drip irrigation system, which enabled desert cultivation; the integration of production and exports, which is indispensable for fresh produce exports; and the collective efforts of the industry with help from the public sector.

The degree of nonlinearity and anisotropy of blood vessel elasticity

Blood vessel elasticity is important to physiology and clinical problems involving surgery, angioplasty, tissue remodeling, and tissue engineering. Nonlinearity in blood vessel elasticity in vivo is important to the formation of solitons in arterial pulse waves. It is well known that the stress–strain relationship of the blood vessel is nonlinear in general, but a controversy exists on how nonlinear it is in the physiological range. Another controversy is whether the vessel wall is biaxially isotropic. New data on canine aorta were obtained from a biaxial testing machine over a large range of finite strains referred to the zero-stress state. A new pseudo strain energy function is used to examine these questions critically. The stress–strain relationship derived from this function represents the sum of a linear stress–strain relationship and a definitely nonlinear relationship. This relationship fits the experimental data very well. With this strain energy function, we can define a parameter called the degree of nonlinearity, which represents the fraction of the nonlinear strain energy in the total strain energy per unit volume. We found that for the canine aorta, the degree of nonlinearity varies from 5% to 30%, depending on the magnitude of the strains in the physiological range. In the case of canine pulmonary artery in the arch region, Debes and Fung [Debes, J. C. & Fung, Y. C.(1995) Am. J. Physiol. 269, H433–H442] have shown that the linear regime of the stress–strain relationship extends from the zero-stress state to the homeostatic state and beyond. Both vessels, however, are anisotropic in both the linear and nonlinear regimes.