Comportamento ingestivo de novilhas de corte em pastagem de sorgo forrageiro implantada com diferentes arranjos populacionais / Ingestive behavior of heifers in sorghum implanted with different population arrangements

O objetivo do presente estudo foi avaliar os efeitos da implantação de pastagem de sorgo forrageiro com diferentes arranjos populacionais no comportamento animal e na estrutura do pasto e de suas relações. Os tratamentos foram a combinação de dois espaçamentos entrelinhas e duas densidades de sementes ha-1, sendo 22 ou 44cm entrelinhas e 12 ou 24kg de sementes ha-1. Foram utilizadas 36 novilhas, com idade e peso corporal inicial de 15 meses e 262kg, respectivamente. Os tratamentos E44D24 e E22D12 apresentaram maior tempo de pastejo (469,33 e 467,78 minutos, respectivamente). Os animais do tratamento E44D24 apresentaram menor taxa de bocado (23,99 bocados minuto-1) em relação ao tratamento E22D24 (32,45 bocados minuto-1). Os animais do tratamento E44D12 apresentaram maior número de estações alimentares minuto-1 (9,21) e maior taxa de deslocamento (11,76 passos minuto-1). O espaçamento entrelinhas de plantio de 22cm aumenta o número de bocados estação-1. O aumento na densidade de sementes (24kg ha-1) e a utilização de maiores espaçamentos entrelinhas de plantio aumentam a densidade de folhas nos estratos inferior (0-30cm) e superior (acima de 60cm) do pasto. Os tratamentos E44D12 e E22D24 apresentaram maiores quantidades de colmos no estrato superior do pasto.(AU)

The objective of the study was to evaluate the effects of sorghum pasture implantation with different population arrangements in animal behavior and pasture structure and their relationships. The treatments were the combination of two row lines and two seeds per hectare densities, 22 or 44cm between rows and 12 or 24kg ha -1 of seed. 36 heifers at 15 months of age and 262kg body weight were used. The E44D24 and E22D12 treatments showed higher time of grazing (469.33 and 467.78 minutes, respectively). The animals in E44D24 treatment had lower bit rate (23.99 bites minute -1 ) compared to treatment with E22D24, a higher bit rate (32.45 bits min -1 ). The animals in E44D12 treatment presented the largest number of stations minute -1 (9.21) and higher displacement rate (11.76 steps min -1 ). The row spacing of 22cm increases the number of bits station -1 . The increase in seed density and the use of larger planting row spacing's increase the leaf density of the lower (0-30cm) and higher stratum (above 60cm) of pasture. The E44D12 and E22D24 treatment have higher amounts of stems in the upper stratum of the pasture.(AU)

TM9SF4 is a novel V-ATPase-interacting protein that modulates tumor pH alterations associated with drug resistance and invasiveness of colon cancer cells.

An inverted pH gradient across the cell membranes is a typical feature of malignant cancer cells that are characterized by extracellular acidosis and cytosol alkalization. These dysregulations are able to create a unique milieu that favors tumor progression, metastasis and chemo/immune-resistance traits of solid tumors. A key event mediating tumor cell pH alterations is an aberrant activation of ion channels and proton pumps such as (H+)-vacuolar-ATPase (V-ATPase). TM9SF4 is a poorly characterized transmembrane protein that we have recently shown to be related to cannibal behavior of metastatic melanoma cells. Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity. Such effects are associated with a significant inhibition of the invasive behavior of colon cancer cells and with an increased sensitivity to the cytotoxic effects of 5-fluorouracil. Our study shows for the first time the important role of TM9SF4 in the aberrant constitutive activation of the V-ATPase, and the development of a malignant phenotype, supporting the potential use of TM9SF4 as a target for future anticancer therapies.

A practical tool to evaluate dose distributions using radiochromic film in radiation oncology.

PURPOSE: Triple channel algorithm and specific procedures make more reliable radiochromic dosimetry for treatment planning verification and quality assurance in radiation therapy. A tool to obtain radiochromic dose distributions and compare them with the ones resulting from a treatment planning system was developed and applied. METHODS: The tool was developed as Microsoft Excel macro; it builds dose calibration curves against net optical density of Gafchromic EBT3 film, produces axial, coronal and sagittal dose maps and allows to evaluate them against dose distributions calculated by the Varian treatment planning system Eclipse using gamma index and gamma angle. RESULTS: The net optical density standard errors of estimate of calibration curves at 6 MV Varian DBX600 linac energy were 0.2%, 0.4% and 0.2% for the red, green and blue channels. Tests of these curves by means of three independent eight dose points measurement series, at 15 MV and 6 MV Varian 2100C linac and at 6 MV DBX600 linac energies, showed less than 2% of dose errors for the red channel and less than 3% for the green channel in the range 100-450 cGy. The comparisons between dose distributions from Gafchromic EBT3 triple channel algorithm and the ones from Eclipse analytic anisotropic algorithm (AAA) showed values of gamma index 95th percentile between 0.6 and 1.0. CONCLUSION: The obtained results encourage the application of this tool in radiation therapy quality assurance.

Adaptations to changing speed, load, and gradient in human walking: cost of transport, optimal speed, and pendulum.

It has been observed that the optimal speed (OPT) of human walking is independent of load on level surfaces because of the unaltered trajectory of the center of mass and consequent conservation of the pendular mechanism. However, the role of the inverted pendulum mechanism that combines speed, load, and gradient during walking remains unknown. In the present study, 10 subjects walked on a treadmill, with and without loading (25% of the body mass), at different speeds and slopes (0%, +7%, and +15%). The three-dimensional motion and VO2 were simultaneously registered. The mechanical external and internal work and the cost of transport (C) changed with the speed and gradient, but the load only affected C. OPT decreased with increasing gradient, and the pendular mechanics (R) was modified mainly as a result of changes in speed and gradient. OPT and R were independent of the load in these gradients. Remarkably, R increased with increasing speed and decreased (to 30%) with an increasing gradient; moreover, R was independent of load. Therefore, the energy-saving strategy by the pendular mechanism persists, although at a diminished level, in loaded walking on gradients and partially explains the OPT in this condition.

[Ranolazine in the treatment of chronic stable angina]. / La Ranolazina nella terapia della angina cronica stabile.

Coronary artery disease is the leading cause of death in Europe and in the US and angina is the most common symptom associated with stable coronary artery disease. Despite receiving optimal antianginal therapy, based on agents such as beta-blockers, calcium channel antagonists and nitrates, many patients continue to experience angina. Furthermore, the administration of these drugs is limited by adverse effects such as bradycardia or hypotension. Ranolazine is a new antianginal agent, recently approved as add-on therapy in patients with stable angina. This review will focus on its mechanism of action, tolerability, highlighting the clinical benefit coming from its use.

Anti-inflammatory treatment of acute coronary syndromes.

The past decade has seen a steady growth in the treatment options available for Acute Coronary Syndromes (ACS), as a consequence of our better understanding of ACS pathophysiology. Administration of fibrinolytics in ST-elevation myocardial infarction, and of potent antiplatelet and anticoagulant drugs in all ACS, has allowed us to considerably improve their outcome. Yet, the rate of adverse cardiac events at early follow-up ranges from 15% to 20%. Thus, to further improve the outcome of ACS or to prevent their occurrence, it is important to identify new therapeutic target. A number of experimental and clinical studies have highlighted the key role of inflammation in all phases of atherosclerosis, from fatty streaks to disrupted plaques and raised levels of inflammatory markers have been associated to a poor outcome despite optimal treatment, including myocardial revascularization. In this review, we will focus on inflammation as a possible new therapeutic target of ACS, discussing the anti-inflammatory treatments in four sections: 1) non specific anti-inflammatory drugs; 2) specific antagonists of key cytokines; 3) immunomodulatory therapies; 4) immunization as promising therapeutic modality against atherosclerosis.

[High-sensitivity troponin assay: biochemistry and clinical application]. / Troponine ad alta sensibilita: dalla biochimica alle applicazioni cliniche.

Cardiac troponin is the marker of choice for the diagnosis of acute coronary syndrome. Its introduction in clinical practice consistently improved both sensibility and specificity as compared with other biomarkers, as creatin-chinase MB. However traditional troponin assays show some limits: the relatively long time elapsing between the onset of ischemia and the increase in serum concentration, and the difficulty in distinguishing ischemic from non ischemic damage. An earlier diagnosis could be obtained by adopting new high sensitivity troponin assays, with a coefficient of variation ≤10% at the 99° percentile of a reference healthy population, and capable of detecting circulating troponin in the most healty subjects. The difficulty in distinguishing ischemic from non ischemic harm can be overcome considering that only a rising and falling pattern can be attributed to ischemic harm. Further studies are needed to evaluate the prognostic role of low circulating troponin levels in healthy subjects and for properly fixing cut off values. Indeed biomarker increase has always to be considered in the specific clinical context.

Strong CD8+ T cell antigenicity and immunogenicity of large foreign proteins incorporated in HIV-1 VLPs able to induce a Nef-dependent activation/maturation of dendritic cells.

Virus-like particles (VLPs) are excellent tools for vaccines against pathogens and tumors. They can accommodate foreign polypeptides whose incorporation efficiency and immunogenicity however decrease strongly with the increase of their size. We recently described the CD8(+) T cell immune response against a small foreign antigen (i.e., the 98 amino acid long human papilloma virus E7 protein) incorporated in human immunodeficiency virus (HIV)-1 based VLPs as product of fusion with an HIV-1 Nef mutant (Nef(mut)). Here, we extended our previous investigations by testing the antigenic/immunogenic properties of Nef(mut)-based VLPs incorporating much larger heterologous products, i.e., human hepatitis C virus (HCV) NS3 and influenza virus NP proteins, which are composed of 630 and 498 amino acids, respectively. We observed a remarkable cross-presentation of HCV NS3 in dendritic cells challenged with Nef(mut)-NS3 VLPs, as detected using a NS3 specific CD8(+) T cell clone as well as PBMCs from HCV infected patients. On the other hand, when injected in mice, Nef(mut)-NP VLPs elicited strong anti-NP CD8(+) T cell and CTL immune responses. In addition, we revealed the ability of Nef(mut) incorporated in VLPs to activate and mature primary human immature dendritic cells (iDCs). This phenomenon correlated with the activation of Src tyrosine kinase-related intracellular signaling, and can be transmitted from VLP-challenged to bystander iDCs. Overall, these results prove that Nef(mut)-based VLPs represent a rather flexible platform for the design of innovative CD8(+) T cell vaccines.

[Radiation protection issues in brachytherapic treatment of prostatic cancer]. / Problematiche radioprotezionistiche nel trattamento brachiterapico del cancro della prostata.

Brachytherapy is an effective radiotherapeutic treatment for localized prostatic cancer. The permanent brachytherapy is a particular kind of radiotherapy which, US guided, uses permanently implanted seeds containing radioactive sources (Pd103 or I 125). The procedure is minimally invasive and allows to obtain high percentage of success which is comparable to surgery. The possibility to confine permanent radioactive implants in a well delimitated area doesn't exclude the exposition of both the medical staff and family's members of implanted patients. The radiation exposure involves the medical physicists, the radiotherapists, the Medical Radiology Technician, the anaesthetists, the surgeons, the professional nurses but also, after the brachytherapy treatment, public and family members, comforters and cares. It's necessary to consider radiation safety aspects of brachytherapy in order to reduce the risks of exposition. At the end, several studies showed that cremation of bodies could be a possible radiation source that remains in the patient's ashes, potentially inhaled by crematorium staff or members of the public.

Efficacy of clarithromycin in preventing viridans streptococcal bacteremia following autologous stem cell transplantation.

BACKGROUND: In a study involving 200 patients, we previously found that 17.5% of patients developed viridans streptococcal (VS) bacteremia following autologous peripheral blood stem cell transplantation (aPBSCT) when ciprofloxacin or ciprofloxacin plus ampicillin was used for prophylaxis. PATIENTS AND METHODS: A retrospective evaluation of 100 consecutive recipients of aPBSCT was conducted to ascertain the incidence and outcome of VS bacteremia when a combination of ciprofLoxacin and clarithromycin was utilized for antimicrobiaL prophylaxis following transplantation. The 200 patients from our previous study, in which ciprofloxacin alone or ciprofloxacin with ampicillin was used for prophylaxis, were combined with the current group for the purpose of statistical analysis. RESULTS: Streptococcus mitis was isolated from the blood of five individuals at a median of 5 days following stem cell infusion. Each of these patients was neutropenic and presented with fever. Three isolates demonstrated intermediate resistance to macrolides in vitro. However, all episodes of bacteremia were treated successfully with systemic antibiotic therapy. CONCLUSION: Age, duration of neutropenia, type of underlying malignancy and type of conditioning chemotherapy regimen failed to have a significant impact on subsequent VS bacteremia. Only female sex and use of ciprofloxacin without clarithromycin as antimicrobiaL prophyLaxis predicted a significantly increased risk of VS bacteremia in both univariate and Logistic regression analyses.

Cytoreduction and stem cell mobilization with a regimen of paclitaxel, etoposide and cyclophosphamide followed by autologous transplantation using a preparative regimen of busulfan, etoposide and cyclophosphamide for patients with advanced lymphoma.

Forty-one patients with advanced Hodgkin's disease or intermediate or high-grade lymphoma, after having received standard salvage chemotherapy, were treated with a nonablative high-dose regimen of paclitaxel, etoposide and cyclophosphamide (D-TEC) to optimally cytoreduce their disease and simultaneously mobilize peripheral blood stem cells. This regimen produced a response rate of 78% (35% complete and 43.2% partial response) and mobilized sufficient peripheral blood stem cells in 94% of the patients. Thirty-two of these patients then underwent autologous progenitor cell transplantation after ablative conditioning with busulfan, etoposide and cyclophosphamide. Actuarial overall survival at 61 months was 71.9% with an event-free survival (EFS) of 65.6%. Median EFS was 24.4 months. EFS of patients responsive to salvage chemotherapy was 75% at 61 months, compared to 33.3% at 51.4 months in patients resistant to salvage chemotherapy. EFS of patients with disease sensitive to D-TEC was 75% at 61 months compared to 0% at 13.1 months in patients resistant to D-TEC. In a multivariate analysis, the only significant parameter for transplant outcome was sensitivity to D-TEC (p = 0.016), but not sensitivity to standard salvage chemotherapy. Aggressive cytoreduction may permit even those patients who are resistant to standard salvage chemotherapy to become successful transplant candidates.

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma.

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.

AIDS and thrombosis: retrospective study of 131 HIV-infected patients.

The recent literature contains reports of thrombotic episodes occurring in patients with human immunodeficiency virus (HIV) infection and various abnormalities predisposing to a hypercoagulable state have also been reported in such patients. To study the incidence of thrombosis in patients infected with HIV, and to assess the correlation of thrombosis with the degree of immunosuppression as well as the association with active illnesses and neoplasms, we reviewed the charts of 131 patients, which include all the patients with the diagnosis of HIV admitted or seen in the clinic between January 1, 1993, and January 1, 1998. The diagnosis of thrombosis was based on documented reports of venous plethysmography or venography for deep venous thrombosis and ventilation-perfusion scan or pulmonary angiography for pulmonary embolus. Risk factors for thrombotic disease were evaluated including general risk factors such as family history, ambulatory status, medications, and data were also collected regarding CD4 cell counts and the presence of concurrent or remote opportunistic infections, acquired immune deficiency syndrome (AIDS)-related malignancy or other AIDS-related diseases at the time of diagnosis of the thrombotic event. We also reviewed the medical literature via MEDLINE and found 45 cases of patients with HIV who developed thromboembolic complications. We found thrombotic complications in 9 of 37 patients with a CD4 count less than 200 cells/mm3 and in 1 of the remaining 94 patients with a CD4 count more than 200 cells/mm3. The difference was significant, with p = 0.00004, and the estimated odds of an event given CD4 cell counts less than 200/mm3 is 29.89 (95% confidence interval). Three patients had abnormalities of anticoagulation proteins. There was a history of opportunistic infections in 5 patients and malignancy in 3 patients. Two patients with autoimmune hemolytic anemia (AIHA) secondary to HIV-infection developed PE upon transfusion of packed red blood cells. The results of this study suggests that AIDS appears to predispose to thrombosis. It also revealed a significant correlation between thrombotic disease and CD4 counts (<200/mm3) as well as the presence of opportunistic infections, AIDS-related neoplasms, or autoimmune disorders associated with HIV such as AIHA. Therefore, clinicians caring for these patients should be aware of thromboembolic disease as a possible complication of AIDS. Further studies to elucidate the mechanisms underlying this abnormal hemostatic profile, the epidemiology, and to answer several questions such as should patients with risk factors for HIV infection who develop thromboembolic complications be further evaluated including tests for HIV are warranted.

Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation.

OBJECTIVE: To report the outcome as well as the clinical, radiographic, and pathologic features of idiopathic pneumonia syndrome (IPS) following autologous peripheral blood stem cell transplantation (aPBSCT). CLINICAL FINDINGS: A total of 271 patients with a variety of underlying malignancies received busulfan-containing myeloablative chemotherapy prior to aPBSCT; none of these patients received total body irradiation. Ten individuals developed IPS, with a median time of onset of 102 days after stem cell infusion. The major clinical and radiographic findings included an acute or subacute onset of dyspnea, cough, hypoxemia, and bilateral or unilateral infiltrates with or without pleural effusion. Pathologic findings consisted mainly of diffuse interstitial pneumonitis, organizing alveolitis, and cellular atypia. Nine patients diagnosed with IPS were treated with high doses of glucocorticoids parenterally. Despite heroic measures, eight patients died of IPS. The two remaining individuals recovered without experiencing significant long-term pulmonary sequelae. DISCUSSION: Chronic low-dose busulfan therapy results in lung injury in 4-6% of patients after several years of treatment and once the cumulative dosage begins to approach 3g. High-dose, short-course busulfan (16 mg/kg)-containing conditioning chemotherapy prior to aPBSCT can also be complicated by IPS. IPS differs from lung damage due to chronic busulfan therapy by its earlier onset, an acute or subacute rather than indolent presentation, characteristic clinical and radiographic features, and lack of multinucleated giant cells on pathologic review. The pathophysiology of IPS secondary to high-dose busulfan-containing myeloablative regimens is not known, but cell-mediated immune reactions and release of cytokines may contribute to the lung injury. Mortality is high (80%) despite the use of heroic measures, including mechanical ventilation. Some patients, however, can respond to high doses of parenteral corticosteroid therapy. CONCLUSIONS: IPS following high-dose, short-course busulfan-containing regimens exhibits unique clinical, radiographic, and pathologic features that differ from lung damage characteristic of chronic, low-dose busulfan therapy. Mortality from this complication is 80%, but some patients survive without long-term pulmonary sequelae following early treatment with glucocorticoids.

Severe steroid-unresponsive ulcerative colitis: outcomes of restorative proctocolectomy in patients undergoing cyclosporin treatment.

PURPOSE: The recent introduction of the immune suppressor cyclosporin for treatment of steroid-refractory ulcerative colitis has required surgeons to perform a colectomy in those patients who eventually fail this rescue treatment, thus raising questions as to the safety of surgery as performed in patients with a heavily manipulated immune system. To assess the rates of mortality and morbidity in this setting, we studied a cohort of consecutive patients who had surgery after failing cyclosporin for refractory ulcerative colitis at our center. METHODS: Between January 1991 and December 1996, 25 patients with ulcerative colitis underwent restorative proctocolectomy performed in three steps (21 patients) and in two steps (4 patients). Seventeen of the 25 patients (68 percent) were initial nonresponders to a dose of 2 mg/kg/day of intravenous cyclosporin and underwent surgery immediately, the remaining 8 (32 percent) relapsed as outpatients on oral cyclosporin and were readmitted for surgery. RESULTS: There was no operative mortality. Nine patients of the 25 developed postoperative (early) complications (36 percent). The three-step operation subset had a 28 percent complication rate, the two-step 75 percent. Three patients needed reoperation. A total of 11 patients (44 percent) reported with late complications: two patients required surgical treatment, one for obstruction and one for pouch-perianal fistula. Three cases of pouchitis were recorded. No patient required pouch removal. CONCLUSION: Given the absence of postoperative mortality and a low overall complication rate, restorative proctocolectomy can safely be performed in patients who fail rescue treatment with a dose of 2 mg/kg of cyclosporin for steroid-refractory ulcerative colitis. Corollary evidence in this article hints but does not prove that the three-step procedure is safer than the two-step operation.

Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer.

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 x 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123-130.