Similarity in physiological and perceived exertion responses to exercise at continuous and intermittent critical power

The purpose of this study was to compare the physiological responses [oxygen uptake (VO₂), heart rate (HR) and blood lactate concentrations ([BLa])] and the rating of perceived exertion (RPE) response until exhaustion (TTE) at the continuous (CP_c) and intermittent (CP_i) critical power workloads. Ten moderately active men (25.5 ± 4.2 years, 74.1 ± 8.0 kg, 177.6 ± 4.9 cm) participated in this study. The incremental test was applied to determine the highest values of oxygen uptake (VO_2max), heart rate (HR_max), blood lactate concentrations ([BLa_max]), and maximal aerobic power (MAP). Continuous and intermittent exhaustive predictive trials were performed randomly. The hyperbolic relation between power and time was used to estimate CP_c and CP_i. CP_i was derived from predictive trial results at an effort and recovery ratio of 30:30 s. Exercise at CP_c and CP_i as well as the physiological and RPE responses were measured until exhaustion. The values of physiological variables during CP_c and CP_i did not differ in either TTE test and were lower than the VO_2max, HR_max and [BLa_max] values. RPE was maximal at the end of exercise at CP_c and CP_i. There was a high correlation between VO_2max (L min⁻¹) and CP_c and CP_i intensities (r ≥ 0.90) and between MAP, CP_c and CP_i (r ≥ 0.95). Similar physiological and RPE responses were found at CP_c and CP_i for the times analyzed.     

A cytogenetic analysis of 2 cases of phosphaturic mesenchymal tumor of mixed connective tissue type

Phosphaturic mesenchymal tumor of mixed connective tissue type is a rare, histologically distinctive mesenchymal neoplasm associated with tumor-induced osteomalacia resulting from production of the phosphaturic hormone fibroblast growth factor 23. Because of its rarity, specific genetic alterations that contribute to the pathogenesis of these tumors have yet to be elucidated. Herein, we report the abnormal karyotypes from 2 cases of confirmed phosphaturic mesenchymal tumor of mixed connective tissue type. G-banded analysis demonstrated the first tumor to have a karyotype of 46,Y,t(X;3;14)(q13;p25;q21)[15]/46XY[5], and the second tumor to have a karyotype of 46, XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,der(2)t(2;4)(q14.2;p14),der(4)t(2;4)(q14.2;p14),add(4)(q31.1)[10]/46,sdl,add(13)(q34)[4]/92,sdl2x2[1]. These represent what is, to our knowledge, the first examples of abnormal karyotypes obtained from phosphaturic mesenchymal tumor of mixed connective tissue type.     

Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor

The treatment of Alzheimer's disease and many other brain-related disorders is limited because of the presence of the blood-brain barrier, which highly regulate the crossing of drugs. Metal nanoparticles have unique features that could contribute to the development of new therapies for these diseases. Nanoparticles have the capacity to carry several molecules of a drug; furthermore, their unique physico-chemical properties allow, for example, photothermal therapy to produce molecular surgery to destroy tumor cells and toxic structures. Recently, we demonstrated that gold nanoparticles conjugated to the peptide CLPFFD are useful to destroy the toxic aggregates of β-amyloid, similar to the ones found in the brains of patients with Alzheimer's disease. However, nanoparticles, like many other compounds, have null or very low capacity to cross the blood-brain barrier. In order to devise a strategy to improve drug delivery to the brain, here we introduced the peptide sequence THRPPMWSPVWP into the gold nanoparticle-CLPFFD conjugate. This peptide sequence interacts with the transferrin receptor present in the microvascular endothelial cells of the blood-brain barrier, thus causing an increase in the permeability of the conjugate in brain, as shown by experiments in?vitro and in?vivo. Our results are highly relevant for the therapeutic applications of gold nanoparticles for molecular surgery in the treatment of neurodegenerative diseases such as Alzheimer's disease.     

Excretory/secretory antigens from Dirofilaria immitis adult worms interact with the host fibrinolytic system involving the vascular endothelium

Dirofilaria immitis is the causative agent of canine and feline heartworm disease. The parasite can survive for long periods of time (7 years or more) in the circulatory system of immunocompetent reservoirs, producing usually a chronic inflammatory vascular disease. In addition, the simultaneous death of groups of adult worms can trigger an acute disease characterized by the exacerbation of inflammatory reactions and the emergence of serious thromboembolic events. In the context of the D. immitis/host relationships, the aim of this study was to investigate the interaction between the excretory/secretory antigens from D. immitis adult worms (DiES) and the fibrinolytic system of the host. Using an enzyme-linked immunosorbent assay we showed that DiES extract is able to bind plasminogen and generate plasmin, although this fact requires the presence of the tissue plasminogen activator (t-PA). Moreover, we established that DiES extract enhances t-PA expression in cultured vascular endothelial cells. Additionally, 10 plasminogen-binding proteins from DiES extract were identified by mass spectrometry (HSP60, actin-1/3, actin, actin 4, transglutaminase, GAPDH, Ov87, LOAG_14743, galectin and P22U). The data suggest that DiES antigens interact with the environment of the parasite regulating the activation of the fibrinolytic system of the host with involvement of the vascular endothelium in the process.     

Surgical Approach and Oncologic Outcomes Following Multidisciplinary Management of Retrorectal Sarcomas

Background

Retrorectal sarcomas are rare, and limited data are available on oncologic outcomes following surgery. Our aim was to evaluate outcomes in this patient population at our institution.

Materials and Methods

All patients who underwent surgical resection of a malignant retrorectal/presacral sarcoma between 1985 and 2005 were identified. Data analyzed included demographics, histopathologic diagnosis, surgical morbidity and mortality, use of adjuvant therapy, local and distant recurrence, and survival.

Results

A total of 37 patients were identified (20 males) with a median age of 49 years (range, 22–81 years). The most common histopathologic diagnosis was malignant peripheral nerve sheath tumor (n = 8). Also, 22 tumors were high grade and 15 were low grade. Surgical margin status was R0 in 31 patients and R1 in 6. Adjuvant therapy was given to 26 patients. Postoperative morbidity and mortality was 57% and 3%, respectively. Median length of follow-up in 16 patients alive at last contact was 4.7 years. The 5-year survival free of local (LDFS), distant (DDFS), and local or distant recurrence (DFS) was 51, 58, and 39%, respectively. Patient survival at 2, 5, and 10 years was 75, 55, and 47%, respectively. Disease-free survival was not significantly associated with gender (P = .16), primary vs secondary (P = .94), R0 vs R1 resection (P = .26), low vs high tumor grade (P = .17), or the use of surgery with or without adjuvant therapy (P = .33).

Conclusions

Retrorectal sarcomas are often high grade and locally advanced. Most tumors are resectable with free margins, and long-term survival may be possible in up to one-half of patients following an aggressive surgical approach.     

Method of targeted delivery of laser beam to isolated retinal rods by fiber optics

A method of controllable light delivery to retinal rod cells using an optical fiber is described. Photo-induced current of the living rod cells was measured with the suction electrode technique. The approach was tested with measurements relating the spatial distribution of the light intensity to photo-induced current. In addition, the ion current responses of rod cells to polarized light at two different orientation geometries of the cells were studied.     

The aerobic capacity and muscle strength are correlated in candidates for liver transplantation

Liver diseases are responsible for metabolic and cardiorespiratory alterations. The objective of this paper is to correlate the maximal oxygen uptake (VO(2max)) and respiratory muscle strength and evaluating the quality of life in liver transplant candidates. Cross-sectional study consisted of 26 patients with cirrhosis who underwent maximal exercise testing, respiratory muscle strength and SF-36. There was a correlation of VO(2max) with MIP (r = 0.61) and low scores of quality of life. A correlation of VO(2max) to muscle strength and decreased quality of life in patients with liver disease.     

Critical role for Syk in responses to vascular injury

Although current antiplatelet therapies provide potent antithrombotic effects, their efficacy is limited by a heightened risk of bleeding and failure to affect vascular remodeling after injury. New lines of research suggest that thrombosis and hemorrhage may be uncoupled at the interface of pathways controlling thrombosis and inflammation. Here, as one remarkable example, studies using a novel and highly selective pharmacologic inhibitor of the spleen tyrosine kinase Syk [PRT060318; 2-((1R,2S)-2-aminocyclohexylamino)-4-(m-tolylamino)pyrimidine-5-carboxamide] coupled with genetic experiments, demonstrate that Syk inhibition ameliorates both the acute and chronic responses to vascular injury without affecting hemostasis. Specifically, lack of Syk (murine radiation chimeras) attenuated shear-induced thrombus formation ex vivo, and PRT060318 strongly inhibited arterial thrombosis in vivo in multiple animal species while having minimal impact on bleeding. Furthermore, leukocyte-platelet-dependent responses to vascular injury, including inflammatory cell recruitment and neointima formation, were markedly inhibited by PRT060318. Thus, Syk controls acute and long-term responses to arterial vascular injury. The therapeutic potential of Syk may be exemplary of a new class of antiatherothrombotic agents that target the interface between thrombosis and inflammation.