25 research outputs found
L’Indice di Capacità di Lavoro in operatori sanitari.
The Work Ability Index was used as a complementary tool for the periodical health surveillance of health care workers in order to evaluate their functional working capacity and to plan more appropriate preventive and compensatory measures. 867 health care workers of both sexes (337 men, 530 women), aged between 23 to 65 years and with a work experience from 0.5 to 48 years ere examined. They were physicians, registered and assistant nurses, biologists, technicians and clerks, working in hospital departments, ambulatory health care services, laboratories and offices. WAI proved to be "excellent" in 27.0%, "good" in 49.7%, "moderate" in 20.1% and "poor" in 3.2%. Women showed significantly lower mean WAI than men in all age groups, particularly among registered and assistant nurses. Women shift workers showed a more pronounced decrease of WAI over the years as compared to their colleagues day workers by increasing the number of illnesses suffered, WAI similarly decreased in all age groups, but less among physicians and clerks
In vivo and in vitro inhibition of osteosarcoma growth by the pan Bcl-2 inhibitor AT-101
Osteosarcoma (OS) is the most common primary malignant bone tumor and mainly affects children and adolescents. The OS five-year survival rate remains very low. Thus, novel therapeutic protocols for the treatment of OS are needed. Several approaches targeting deregulated signaling pathways have been proposed. The antitumoral effects of polyphenols, which are naturally occurring compounds with potent antioxidant and anti-inflammatory activity, have been investigated in different tumors. Gossypol, which is a natural polyphenolic aldehyde isolated from the seeds of the cotton plant, has been shown to exert antitumoral activity in leukemia and lymphoma and in breast, head and neck, colon and prostate cancers. Therefore, in this study, we evaluated the effect of AT-101, which is the (-) enantiomer and more active form of gossypol, on the growth of human and murine OS cells in vitro and in vivo. Several clinical trials employing AT-101 have been performed, and some clinical trials are ongoing. Our results showed for the first time that AT-101 significantly inhibits OS cell growth in a dose- and time-dependent manner, inducing apoptosis and necrosis and partially activating autophagy. Our results demonstrated that AT-101 inhibits prosurvival signaling pathways depending on Akt, p38 MAPK and JNK. In addition, treatment with AT-101 increases the survival of OS-bearing mice. Overall, these results suggest that AT-101 is a candidate chemo-supportive molecule for the development of novel chemotherapeutic protocols for the treatment of OS
Polyphenols as immunomodulatory compounds in the tumor microenvironment: friends or foes?
Polyphenols are natural antioxidant compounds ubiquitously found in plants and, thus, ever present in human nutrition (tea, wine, chocolate, fruits and vegetables are typical examples of polyphenol-rich foods). Widespread evidence indicate that polyphenols exert strong antioxidant, anti-inflammatory, anti-microbial and anti-cancer activities, and thus, they are generally regarded to as all-purpose beneficial nutraceuticals or supplements whose use can only have a positive influence on the body. A closer look to the large body of results of years of investigations, however, present a more complex scenario where polyphenols exert different and, sometimes, paradoxical effects depending on dose, target system and cell type and the biological status of the target cell. Particularly, the immunomodulatory potential of polyphenols presents two opposite faces to researchers trying to evaluate their usability in future cancer therapies: on one hand, these compounds could be beneficial suppressors of peri-tumoral inflammation that fuels cancer growth. On the other hand, they might suppress immunotherapeutic approaches and give rise to immunosuppressive cell clones that, in turn, would aid tumor growth and dissemination. In this review, we summarize knowledge of the immunomodulatory effects of polyphenols with a particular focus on cancer microenvironment and immunotherapy, highlighting conceptual pitfalls and delicate cell-specific effects in order to aid the design of future therapies involving polyphenols as chemoadjuvants
Radiological, Histological and Chemical Analysis of Breast Microcalcifications: Diagnostic Value and Biological Significance
Classification of mammary microcalcifications is based on radiological and histological characteristics that are routinely evaluated during the diagnostic path for the identification of breast cancer, or in patients at risk of developing breast cancer. The main aim of this study was to explore the relationship between the imaging parameters most commonly used for the study of mammary microcalcifications and the corresponding histological and chemical properties. To this end, we matched the radiographic characteristics of microcalcifications to breast lesion type, histology of microcalcifications and elemental composition of microcalcifications as obtained by energy dispersive x ray (EDX)-microanalysis. In addition, we investigated the properties of breast cancer microenvironment, under the hypothesis that microcalcification formation could result from a mineralization process similar to that occurring during bone osteogenesis. In this context, breast lesions with and without microcalcifications were compared in terms of the expression of the main molecules detected during bone mineralization (BMP-2, BMP-4, PTX3, RANKL OPN and RUNX2). Our data indicate that microcalcifications classified by mammography as "casting type" are prevalently made of hydroxyapatite magnesium substituted and are associated with breast cancer types with the poorest prognosis. Moreover, breast cancer cells close to microcalcifications expressed higher levels of bone mineralization markers as compared to cells found in breast lesions without microcalcifications. Notably, breast lesions with microcalcifications were characterized by the presence of breast-osteoblast-like cells. In depth studies of microcalcifications characteristics could support a new interpretation about the genesis of ectopic calcification in mammary tissue. Candidating this phenomenon as an integral part of the tumorigenic process therefore has the potential to improve the clinical management of patients early during their diagnostic path
Polyphenol-mediated autophagy in cancer: Evidence of in vitro and in vivo studies
One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants
Pathophysiological adaptations to walking and cycling in primary pulmonary hypertension
Exercise tolerance inversely correlates with the severity of the disease in patients with idiopathic pulmonary arterial hypertension (IPAH). Cycling and walking protocols are commonly utilized in the evaluation of exercise intolerance in IPAH, but little information exists on possible differences in ventilatory and gas exchange adaptations to these exercise modalities. In a group of patients with moderate to severe IPAH (n = 13), we studied the ventilatory, cardiovascular and gas exchange adaptations to maximal incremental walking (W) and maximal incremental cycling (C). During W, compared to C, the ventilatory equivalents for CO2 Output (V'(E)/V'CO2) were significantly higher either expressed as the rate of increment (56 5 vs. 45 +/- 3; P < 0.0001) or as the absolute values at anaerobic threshold (AT) and at peak exercise. At AT, the increase in V'(E)/V'CO2 during W was associated with a significant lower value of end-tidal carbon dioxide. At peak W, compared to peak C, dyspnea sensation was higher and arterial oxygen saturation (SPO2) was lower (87 +/- 2 vs. 91 +/- 2, P < 0.001). In patients with IPAH the physiologic information obtained with W are different from those obtained with C. Tolerance to W exercise is limited by high ventilatory response and dyspnea sensation. W should be used to assess the degree of lung gas exchange inefficiency and arterial O-2 desaturation during exercise
Mapping specificity, cleavage entropy, allosteric changes and substrates of blood proteases in a high-throughput screen
Proteases are among the largest protein families and critical regulators of biochemical processes like apoptosis and blood coagulation. Knowledge of proteases has been expanded by the development of proteomic approaches, however, technology for multiplexed screening of proteases within native environments is currently lacking behind. Here we introduce a simple method to profile protease activity based on isolation of protease products from native lysates using a 96FASP filter, their analysis in a mass spectrometer and a custom data analysis pipeline. The method is significantly faster, cheaper, technically less demanding, easy to multiplex and produces accurate protease fingerprints. Using the blood cascade proteases as a case study, we obtain protease substrate profiles that can be used to map specificity, cleavage entropy and allosteric effects and to design protease probes. The data further show that protease substrate predictions enable the selection of potential physiological substrates for targeted validation in biochemical assays
A comparison of skinfold anthropometry and dual-energy X-ray absorptiometry for the evaluation of body fat in cirrhotic patients
Skinfold anthropometry has been used to evaluate the nutritional status in cirrhosis. Such estimates are based on the calculations which derive from healthy subjects and may not apply to cirrhotic patients. We aimed to calculate the limits of agreement between Skinfold anthropometry (SA) and dual-energy X-ray absorptiometry (DXA) in estimating body fat in cirrhotics
