Automatically Controlled Dust Generation System Using Arduino.

A dust generator was developed to disperse and maintain a desired concentration of airborne dust in a controlled environment chamber to study poultry physiological response to sustained elevated levels of particulate matter. The goal was to maintain an indicated PM10 concentration of 50 µg/m3 of airborne dust in a 3.7 m × 4.3 m × 2.4 m (12 ft × 14 ft × 8 ft) controlled environment chamber. The chamber had a 1.5 m3/s (3200 cfm) filtered recirculation air handling system that regulated indoor temperature levels and a 0.06 m3/s (130 cfm) exhaust fan that exchanged indoor air for fresh outdoor air. Dry powdered red oak wood dust that passed through an 80-mesh screen cloth was used for the experiment. The dust generator metered dust from a rectangular feed hopper with a flat bottom belt to a 0.02 m3/s (46 cfm) centrifugal blower. A vibratory motor attached to the hopper ran only when the belt was operated to prevent bridging of powdered materials and to provide an even material feed rate. A laser particle counter was used to measure the concentration of airborne dust and provided feedback to an Arduino-based control system that operated the dust generator. The dust generator was operated using a duty cycle of one second on for every five seconds off to allow time for dispersed dust to mix with chamber air and reach the laser particle counter. The control system maintained an airborne PM10 dust concentration of 54.92 ± 6.42 µg/m3 in the controlled environment chamber during six weeks of continuous operation using red oak wood dust. An advantage of the automatically controlled dust generator was that it continued to operate to reach the setpoint concentration in response to changes in material flow due to humidity, partial blockages, and non-uniform composition of the material being dispersed. Challenges included dust being trapped by the recirculation filter and the exhaust fan removing airborne dust from the environmental chamber.

Ammonia Generation System for Poultry Health Research Using Arduino.

An ammonia gas (NH3) generator was developed to maintain a set concentration of ammonia gas in a controlled environment chamber to study poultry physiological responses to sustained elevated levels of ammonia gas. The goal was to maintain 50 parts per million (ppm) of ammonia gas in a 3.7 m × 4.3 m × 2.4 m (12 ft × 14 ft × 8 ft) controlled environment chamber. The chamber had a 1.5 m3/s (3000 cfm) recirculation system that regulated indoor temperature and humidity levels and a 0.06 m3/s (130 cfm) exhaust fan that exchanged indoor air for fresh outdoor air. The ammonia generator was fabricated by coupling ultrasonic humidifiers with an Arduino-based microcontroller and a metallic oxide MQ-137 ammonia gas sensor. Preliminary evaluation under steady conditions showed the average MQ-137 gas sensor accuracy was within 1.4% of the 65.4 ppm concentration measured using a highly accurate infrared gas analyzer. Further evaluation was performed for a setpoint concentration of 50 ppm where ammonia generator reservoirs were filled with 2% or 10% ammonia liquid. For the system tested, it was found that two generators operating at the same time filled with 3.8 L (1.0 gallon) of 2% ammonia cleaning liquid each (7.6 L or 2.0 gallons total) could maintain a gas level of 49.45 ± 0.79 ppm in the chamber air for a duration of 30 h before refilling was required. One generator filled with 3.8 L of 10% ammonia cleaning liquid could maintain 51.24 ± 1.53 ppm for 195 h. Two ammonia generators were deployed for a six-week animal health experiment in two separate controlled environment chambers. The two ammonia generators maintained an average ammonia concentration of 46.42 ± 3.81 ppm and 45.63 ± 4.95 ppm for the duration of the experiment.

Incidence of Bacterial Chondronecrosis with Osteomyelitis (Femoral Head Necrosis) Induced by a Model of Skeletal Stress and its Correlation with Subclinical Necrotic Enteritis.

Bacterial chondronecrosis with osteomyelitis (BCO) is a septic necrosis of the skeletal system of unknown origin and an important cause of lameness in broiler chickens. Epithelial inflammation has been proposed as an avenue for bacterial translocation leading to BCO. We evaluated the effect of subclinical necrotic enteritis (SNE), an intestinal inflammatory event, with the development of BCO. In each of two experiments, chickens were divided into three treatments: 1) SNE challenge, including both dietary (wheat- and fish-based diet) and intestinal pathogenic challenges (Eimeria maxima and Clostridium perfringens), 2) dietary challenge only, and 3) control diet (corn- and soy-based diet). Floor ramps were introduced as part of an established method for increasing the frequency of BCO. The efficacy of the SNE challenge was corroborated by necropsy evaluation of a representative sample of the population. At the end of each experiment, all birds were evaluated for BCO. A high incidence of BCO was found, even in birds with no external signs of lameness. However, the incidence of BCO was not correlated with the intestinal challenge. Conclusions: under the conditions used in these studies, a treatment that is associated with severe damage to the intestinal mucosa does not change the incidence of BCO in broiler chickens.

Effect of Aspirin on the Intestinal Response to a Necrotic Enteritis Challenge.

The effect of aspirin on intestinal lesions was evaluated in birds undergoing an experimental challenge with Clostridium perfringens as part of a model for inducing subclinical necrotic enteritis (SNE). Broilers were raised on clean wood shavings and randomly assigned to three treatments: Uninfected (U), Infected (I), and Infected + Aspirin (I+A; 0.025% acetylsalicylic acid in drinking water during days 21-25). Birds in the I and I+A groups were gavaged with Eimeria maxima on day 18 and their feed was inoculated with C. perfringens (1 × 109 CFU/bird) during days 23-25. On day 26, birds were euthanatized, intestinal lesions were evaluated, and intestinal tissue was collected for qPCR assessment of genes thought to be involved in the immune response to SNE: IL-1ß, IL-10, MMP-2, and MMP-7. Birds in the I+A group had more-severe and numerous lesions compared to the I group. For all genes except MMP-2, expression was upregulated in the I group compared to the U group, but did not differ between the I and I+A groups. These results indicate that aspirin exacerbated the intestinal lesions associated with this disease. Aspirin could play a role in the development of a reliable and consistent model for the induction of necrotic enteritis under experimental settings.

Efecto de la aspirina en la respuesta intestinal a un desafío por enteritis necrótica. El efecto de la aspirina en las lesiones intestinales se evaluó en aves sometidas a un desafío experimental con Clostridium perfringens como parte de un modelo para inducir enteritis necrótica subclínica (SNE). Los pollos de engorde se criaron sobre viruta de madera limpia y se asignaron aleatoriamente a tres tratamientos: no infectado (U), infectado (I) e infectado + aspirina (I+A; ácido acetilsalicílico al 0.025% en el agua potable durante los días 21-25). A las aves de los grupos I e I+A se les administró por sonda gástrica Eimeria maxima en el día 18 y el alimento fue inoculado con C. perfringens (1×109 unidades formadoras de colonias/ ave) durante los días 23-25. En el día 26, las aves fueron sacrificadas, se evaluaron las lesiones intestinales y se recolectó tejido intestinal para la evaluación cuantitativa por PCR en tiempo real de los genes que se cree están involucrados en la respuesta inmune a la enteritis necrótica subclínica: IL-1ß, IL-10, MMP-2, y MMP-7. Las aves del grupo I+A tuvieron lesiones más graves y numerosas en comparación con el grupo I. Para todos los genes, excepto MMP-2, la expresión se regulaba positivamente en el grupo I en comparación con el grupo U pero no difería entre los grupos I e I+A. Estos resultados indican que la aspirina exacerbó las lesiones intestinales asociadas con esta enfermedad. La aspirina podría desempeñar un papel en el desarrollo de un modelo confiable y consistente para la inducción de enteritis necrótica bajo condiciones experimentales.

Anti-PSMA 124I-scFvD2B as a new immuno-PET tool for prostate cancer: preclinical proof of principle.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I. METHODS: The 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET. RESULTS: The uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75-91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30-40. CONCLUSIONS: Preclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed. These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA 124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.

Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ((90)Y) and a medium-energy beta/gamma emitter ([(177)Lu) in patients with metastatic NET refractory to conventional therapy. METHODS: A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [[(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [[(177)Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. RESULTS: Administration of tandem [(90)Y]DOTA-TATE and [[(177)Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment. CONCLUSION: The results of our study indicates that combined [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.

Iodine-131 metaiodobenzylguanidine (I-131 MIBG) diagnosis and therapy of pheochromocytoma and paraganglioma: current problems, critical issues and presentation of a sample case.

Iodine-131 metaiodobenzylguanidine (I-131 MIBG) has been used for the diagnosis and treatment of malignant pheochromocytomas (PHEO) and paragangliomas (PGL) since 1980's. Despite increasing amount of experience with iodine-131 (I-131) MIBG therapy, many important questions still exist. In this article, we will discuss the current problems learned from clinical experience in diagnosis and therapy of PHEO/PGL with I-131 MIBG, and present a sample case to emphasize the critical aspects for an optimal treatment strategy.

Dosimetry in 131I-mIBG therapy: moving toward personalized medicine.

Internal dosimetry was developed as a basis for 131I-mIBG treatment at an early stage and has continued to develop for over the last 20 years. Whole-body dosimetry was introduced to prevent hematological toxicity. It will be the basis for a forthcoming European multicentre trial, in which the activity of a second administration is determined according to the results calculated from the first. Lesion dosimetry has also been performed in a small number of centres. The major goal of dosimetry now is to establish dose-effect correlation studies, which will be the basis for individualized treatment planning. The aim of this paper is to analyse previously published studies and to consider the potential for improvement in order to obtain a stronger predictive power of dosimetry. The intrinsic radiobiological limits of dosimetry are also illustrated. Due to the development and dissemination of methods of internal dosimetry and radiobiology over the last two decades, and to the increasing availability of quantitative 124I PET imaging, dosimetry could provide in the near future a more systematic basis for standardization and individualization of mIBG therapy. This will however require a number of multicentre trials which are performed under good instrumental and scientific methodology.

Radionuclide therapy and integrated protocols for bone metastases.

Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing encouraging results as to potential anti-tumor efficacy are also reviewed.

Virulence of Mexican isolates of entomopathogenic fungi (Hypocreales: Clavicipitaceae) upon Rhipicephalus=Boophilus microplus (Acari: Ixodidae) larvae and the efficacy of conidia formulations to reduce larval tick density under field conditions.

The first objective was laboratory evaluation of the virulence of 53 Mexican isolates of fungi against larvae of Rhipicephalus (Boophilus) microplus. Thirty-three isolates of Metarhizium anisopliae var. anisopliae (Metschnickoff) Sorokin (Hypocreales: Clavicipitaceae) and 20 isolates of Isaria (Paecilomyces) fumosorosea (fumosoroseus) (Wize) (Eurotiales: Trichomaceae) were tested on 7-day-old larvae under laboratory conditions. Larvae were immersed in a suspension containing 10(8)conidia/mL and the CL(50) values were estimated. Then, field tests were conducted to determine the efficacy of formulations of the isolate with the highest virulence. M. anisopliae (Ma 14 isolate) was formulated with four carriers: Tween, Celite, wheat bran, and Citroline (mineral oil) and applied on pasture beds of Cynodon plectostachyus (L.), at a dose of 2 x 10(9)CFU/m(2). In the first trial, M. anisopliae was applied on plots naturally infested with larvae; in the second trial, tick populations in the experimental plots were eliminated and then re-infested with 20,000 7-day-old larvae. In the laboratory, all M. anisopliae isolates infected larvae with a mortality range between 2 and 100%; also, 13 of 20 I. fumosorosea isolates caused mortality rates between 7 and 94%. In the first field trial, 14 days post-application, conidial formulations in Celite and wheat bran caused 67.8 and 94.2% population reduction, respectively. In the second trial, the Tween formulation caused the highest larval reduction, reaching up to 61% (28 days post-application). Wheat bran formulation caused 58.3% larval reduction (21 days post-application) and was one of the most effective. The carriers and emulsifiers have a large impact on the effectiveness of conidial formulations.

Cellular component of lavage fluid from broilers with normal versus aerosol-primed airways.

Previously, we reported that intratracheal administration of lipopolysaccharide elicited pulmonary hypertension (PH) in broilers reared under commercial conditions and in broilers reared in environmental chambers and pretreated with aerosolized red food colorant # 3 and propylene glycol (Red#3+PG), but not in control broilers reared in environmental chambers. The objective of the present experiment was to determine possible changes in the number or proportion of airway leukocytes that could contribute to the magnitude of the PH responses elicited in broilers. Birds were aerosolized for 40 min with a saturated mixture of Red#3+PG. After 24 h, a blood sample was taken, the broilers were killed, and a pulmonary lavage process was conducted in each bird. Leukocyte concentration (white blood cells/microL) and differential leukocyte counts (%) were measured in blood and lavage fluid. Leukocyte concentration in blood did not differ between groups, but the percentage of blood lymphocytes was lower in broilers from the Red#3+PG group compared with birds from the control group (52.4+/-2.9 and 56.9+/-2.9%, respectively). Cells recovered from the lavage fluid from both groups were primarily heterophils. The concentration of leukocytes was greater in the lavage fluid of broilers from the Red#3+PG group compared with broilers from the control group (763.2+/-158.7 and 402.9+/-62.6 white blood cells/microL, respectively), but the proportions among leukocytes were not different between the 2 groups. We propose that the increased concentration of leukocytes present within the airways was one of the components that enabled broilers pre-treated with aerosolized Red#3+PG to exhibit PH responses to intratracheal lipopolysaccharide.

Anaplastic thyroid cancer: prevalence, diagnosis and treatment.

UNLABELLED: Anaplastic thyroid cancer (ATC) is a rare aggressive tumor arising from the follicular cells of the thyroid gland (as does well differentiated thyroid cancer, WDTC), but ATC cells do not retain any of the biological features of the original follicular cells, such as uptake of iodine and synthesis of thyroglobulin. Prognosis is almost invariably fatal. In this article the Authors review the pathology, epidemiology, clinical presentation, diagnosis and treatment options of ATC. ATC incidence typically peaks at the 6-7th decade of life (mean age at diagnosis 55-65 years), women representing 55-77% of all patients. ATC represents 2-5% of all thyroid tumors, with a decreasing trend with respect to the incidence of WDTC. The histologic patterns of ATC include giant-cell, spindle-cell and squamoid-cell tumors; these subtypes frequently coexist and are not predictive of patients' outcome. Immuno-cyto-chemistry for thyroglobulin is usually negative or weakly positive and some cases are also negative for keratin, particularly in the spindle-cell areas. ATC may arise de novo, but in most cases it develops from a pre-existing WDTC, especially the follicular subtype. Most ATC patients complain of local compressive symptoms, such as dysphagia, dysphonia, stridor and dyspnea in addition to neck pain and tenderness; in over 70% of the patients the tumor infiltrates surrounding tissues, such as fat, trachea, muscle, esophagus, and larynx. The clinical course of a rapidly enlarging mass that is firm and fixed to surrounding structures in an elderly patient is quite suggestive for ATC. Diagnosis can be confirmed by fine needle aspiration cytology or, in doubtful cases, by histology on core biopsy. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are useful for defining the local extent of disease and for identifying distant metastases, as is also positron-emission tomography (PET) with [(18)F]FDG. Tracheoscopy and esophagoscopy should be performed every two months, or whenever patients refer the appearance or worsening of local symptoms. Bone scintigraphy may be included in the follow-up of patients with a longer survival and relatively good health. Because of its aggressive behavior, the latest American Joint Committee on Cancer Staging Manual classifies all ATCs as T4 and Stage IV tumors, regardless of their actual overall tumor burden. Treatment of ATC has not been standardized because it is not clear whether or not therapy is effective in prolonging survival; most patients die within six momths from diagnosis, primarily because of asphyxiation caused by local tumor invasion. When employed alone, surgery, radiotherapy, or chemotherapy are seldom adequate to achieve overall control of the disease, but a combination of these treatments may improve local control. Surgical treatment of local disease offers the best opportunity for prolonged survival if the tumor is intrathyroidal. When the tumor is extrathyroidal, the surgical approach to ATC is controversial. Some favourable results have recently been reported with newly developed chemotherapy agents and hyper-fractioned radiation therapy. Tracheostomy should be performed in patients with impending airway obstruction when death is not imminent from other sites of disease, and if patients are not candidates for local resection or chemoradiation. Interventional bronchoscopy, including Nd-YAG laser and airways stenting are alternatives to surgery in inoperable ATC-induced tracheal obstruction. Gene therapy is under investigation. Although very rare, ATC is a highly aggressive tumor that belongs to the group of killer tumors with median survival time not longer than 6-8 months. Surgery, chemotherapy and radiotherapy are the conventional therapeutic strategies performed in the attempt to improve survival. Unfortunately, very often they do not succeed any clinical benefit but only palliative RESULTS: New therapeutic strategies based on molecular approaches are desirable.

Intratracheal administration of bacterial lipopolysaccharide elicits pulmonary hypertension in broilers with primed airways.

Broilers reared under commercial conditions inhale irritant gases and aerosolized particulates contaminated with gram-negative bacteria and bacterial lipopolysaccharide (LPS). Previous studies demonstrated that i.v. injections of LPS can trigger an increase in the pulmonary arterial pressure (PAP); however, the pulmonary hemodynamic response to aerosolized LPS entering via the most common route, the respiratory tract, had not been evaluated in broilers. In experiment 1, broilers reared on new wood shavings litter in clean environmental chambers either were not pretreated (control group) or were pretreated via aerosol inhalation of substances (food color dyes and propylene glycol) known to sensitize the airways. One day later, the broilers were anesthetized, catheterized to record the PAP, and an intratracheal aerosol spray of LPS (1 mL of 2 mg/mL of LPS) was administered. Broilers in the control group as well as broilers pretreated with aerosolized distilled water or yellow and blue food color dyes did not develop pulmonary hypertension (PH; an increase in PAP) after the intratracheal spray of LPS, whereas broilers that had been pretreated with red food color did develop PH in response to intratracheal LPS. In experiment 2, birds raised under commercial conditions on used wood shavings litter developed PH in response to intratracheal LPS regardless of whether they had been pretreated with aerosolized red food color dye. In experiment 3, broilers reared in clean environmental chambers on new wood shavings litter were used to demonstrate that Red Dye #3 and propylene glycol are capable of priming the responsiveness of the airways to a subsequent intratracheal LPS challenge. Common air contaminants such as LPS can result in PH leading to pulmonary hypertension syndrome (ascites) in broilers with appropriately primed airways.

Transpulmonary pressure gradient verifies pulmonary hypertension is initiated by increased arterial resistance in broilers.

Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance.

Inhaling one hundred percent oxygen eliminates the systemic arterial hypoxemic response of broilers to intravenous microparticle injections.

The pathogenesis of pulmonary hypertension syndrome (PHS, ascites) includes the development of systemic arterial hypoxemia (reduction in the saturation of hemoglobin with O(2), HbO(2)), which can be mimicked in clinically healthy broilers by i.v. injections of microparticles (MP). In experiment 1, arterial blood samples were collected from clinically healthy broilers before and after i.v. MP injections, and during a subsequent 100% O(2) inhalation period. The arterial samples were analyzed for HbO(2), partial pressure of O(2) and CO(2), and pH using a blood gas analyzer. In experiment 2, broilers that initially averaged > or =75% HbO(2) were assigned to a "high O(2)" group, whereas those that initially averaged < 75% HbO(2) were assigned to a "low O(2)" group. The HbO(2) and heart rate (HR) were measured using a pulse oximeter before, during, and after broilers in both groups inhaled 100% O(2). In experiment 3, HbO(2) and HR were measured using a pulse oximeter before, during, and after broilers inhaled 100% O(2), after i.v. MP injections, and during a second period of 100% O(2) inhalation. The HbO(2) rapidly decreased after i.v. MP injections, and subsequently providing 100% O(2) to breathe increased the HbO(2) above preinjection control levels in experiments 1 and 3. In experiment 2, inhaling 100% oxygen eliminated the initial spontaneous differences in HbO(2) between the high O(2) and low O(2) groups, whereas the return to breathing ambient air restored the initial group differences in HbO(2). These experiments indicate that MP-induced and spontaneous hypoxemia can be attributed to a diffusion limitation rather than to arterial-venous shunts, because the hypoxemia resulting from arterial-venous shunts cannot be wholly eliminated by providing 100% O(2) to inhale.

An inadequate pulmonary vascular capacity and susceptibility to pulmonary arterial hypertension in broilers.

Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary vascular capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary vascular capacity have been demonstrated experimentally and include elevated pulmonary vascular resistance (PVR) attributable to noncompliant, fully engorged vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary vascular capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary vascular capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by i.v. microparticle injections, whereas microparticle-induced increases in PVR can be attributed principally to 5-HT. Our observations support the hypothesis that susceptibility to PHS is a consequence of anatomically inadequate pulmonary vascular capacity combined with the functional predominance of the vasoconstrictor 5-HT over the vasodilator NO. The contribution of TxA(2) remains to be determined. Selecting broiler lines for resistance to PHS depends upon improving both anatomical and functional components of pulmonary vascular capacity.

Effects of vitamin E and L-arginine on cardiopulmonary function and ascites parameters in broiler chickens reared under subnormal temperatures.

Two experiments were conducted to evaluate the effects of arginine (Arg) and vitamin E (VE) on ascites (pulmonary hypertension syndrome) parameters, nitric oxide synthase (NOS) activity, and cardiopulmonary performance after an acute challenge with epinephrine (Epi). One-day-old male broilers (n = 100) were fed a commercial corn-soybean meal-based diet meeting NRC (1994) requirements, including 1.2% Arg and 40 IU of VE/kg. In experiment 1, birds were provided tap water (control), water with 0.3% Arg (HArg), water with 400 IU of VE/L (HVE), or a combination of both compounds (Arg-VE). In experiment 2, the treatment groups were similar but the VE was incorporated in the diet (400 IU/ kg of feed). At d 18, temperature was reduced to amplify the incidence of pulmonary hypertension. Body weight and hematocrit were recorded weekly. From d 28 to 42, cardiopulmonary performance was evaluated in clinically healthy, anesthetized birds (n = 7 to 8/treatment). A pulmonary artery and a systemic artery were cannulated, the birds were allowed to stabilize for 10 min (basal), an i.v. injection of Epi was applied (1 or 0.5 mg/kg of BW, experiment 1 and 2, respectively), and a second dose was applied 20 min later. Pulmonary arterial pressure (PAP), mean arterial pressure (MAP), and heart rate (HR) were recorded continuously and data were analyzed by repeated measures ANOVA. The NOS activity was estimated through the conversion of 14C-Arginine to 14C-citrulline in isolated pulmonary arteries. Right/total ventricular weight ratio (RV/TV) was recorded at the end of the experiment. Body weight, RV/TV, and hematocrit values were not significantly affected by the dietary treatments. The PAP increased (P < 0.01) within 30 s after Epi in all treatments, except the HArg treatment in experiment 2. Overall, the time taken for PAP to return to basal levels was longer in the Arg-VE birds and shorter in the HArg birds, particularly after the second challenge. However, although NOS activity was highly variable, birds fed HArg tended to have the lowest NOS activity of all groups. The levels of VE supplementation used in these experiments did not improve cardiopulmonary performance or NOS activity in isolated pulmonary arteries.

[The impact of echo-guided percutaneous biopsy in the diagnosis of focal hepatic lesions]. / L'impatto della biopsia percutanea ecoguidata nella diagnosi delle lesioni epatiche focali.

In order to assess the clinical efficacy of percutaneous echo-guided biopsy (PBE), the authors evaluated its contribution to the diagnostic work-up and therapy selection in 165 cases of confirmed focal hepatic lesions. The cases were studied prospectively using a survey form. PBE yielded a significant contribution to the diagnosis in 79.4% of the cases. It was of substantial or conclusive value to therapeutic selection in 65% of the cases. Moreover, PBE allowed a high number of diagnoses which were unsuspected considering the previous standard clinical and instrumental work-ups. The clinical usefulness of PBE in focal hepatic lesion diagnoses is stressed. Its use saves time in the diagnostic management with considerable cost saving.