Functional insights into nucleotide-metabolizing ectoenzymes expressed by bone marrow-resident cells in patients with multiple myeloma.

Human myeloma cells grow in a hypoxic acidic niche in the bone marrow. Cross talk among cellular components of this closed niche generates extracellular adenosine, which promotes tumor cell survival. This is achieved through the binding of adenosine to purinergic receptors into complexes that function as an autocrine/paracrine signal factor with immune regulatory activities that i) down-regulate the functions of most immune effector cells and ii) enhance the activity of cells that suppress anti-tumor immune responses, thus facilitating the escape of malignant myeloma cells from immune surveillance. Here we review recent findings confirming that the dominant phenotype for survival of tumor cells is that where the malignant cells have been metabolically reprogrammed for the generation of lactic acidosis in the bone marrow niche. Adenosine triphosphate and nicotinamide-adenine dinucleotide extruded from tumor cells, along with cyclic adenosine monophosphate, are the main intracellular energetic/messenger molecules that serve as leading substrates in the extracellular space for membrane-bound ectonucleotidases metabolizing purine nucleotides to signaling adenosine. Within this mechanistic framework, the adenosinergic substrate conversion can vary significantly according to the metabolic environment. Indeed, the neoplastic expansion of plasma cells exploits both enzymatic networks and hypoxic acidic conditions for migrating and homing to a protected niche and for evading the immune response. The expression of multiple specific adenosine receptors in the niche completes the profile of a complex regulatory framework whose signals modify multiple myeloma and host immune responses.

[Torture survivor asylum seekers in Italy: the experience of the humanitarian association "Doctors Against Torture"]. / Vittime di tortura richiedenti asilo in Italia: l'esperienza dell'associazione umanitaria "Medici Contro la Tortura".

In recent years, the arrival in Italy of people who suffered torture in their countries led a group of volunteer doctors to set up a humanitarian association, "Doctors Against Torture", to provide care and treatment for torture survivors present in Rome. The paper describes the characteristics of 354 persons having at least one access from 1-1-1999 to 31-12-2001. About 51% of the victims came from the Middle East, 43% from Africa. Mean age was 29.6 (SD 7.0). The victims have suffered beatings and other forms of blunt trauma (64%), suspension and other positional torture (14%), psychological violence (28%), inhuman conditions of detention (10%), burns/electric shock (21%), wet asphyxiation and water jets (11%), sexual violence (15%), amputation/penetrating injuries (22%), dental torture and traumatic removal of nails (6%) and 58% suffered more than one type of torture. The types of violence observed require a thorough analysis of our knowledge in the field, in order to help victims on their way to rehabilitation, which is long and uncertain; at the same time, it is fundamental that public health begins to make itself responsible for these persons.

Entrapment of dispersed pancreatic islet cells in CultiSpher-S macroporous gelatin microcarriers: Preparation, in vitro characterization, and microencapsulation.

Immunoprotection of pancreatic islets for successful allo- or xenotransplantation without chronic immunosuppression is an attractive, but still elusive, approach for curing type 1 diabetes. It was recently shown that, even in the absence of fibrotic overgrowth, other factors, mainly insufficient nutrition to the core of the islets, represent a major barrier for long-term survival of intraperitoneal microencapsulated islet grafts. The use of dispersed cells might contribute to solve this problem due to the conceivably easier nutritional support to the cells. In the present study, purified bovine islets, prepared by collagenase digestion and density gradient purification, and dispersed bovine islet cells, obtained by trypsin and DNAsi (viability > 90%), were entrapped into either 2% (w/v) sodium alginate (commonly used for encapsulation purposes) or (dispersed islet cells only) macroporous gelatin microcarriers (CulthiSpher-S, commonly used for the production of biologicals by animal cells). Insulin release studies in response to glucose were performed within 1 week and after 1 month from preparation of the varying systems and showed no capability of dispersed bovine islet cells within sodium alginate microcapsules to sense glucose concentration changes. On the contrary, bovine islet cells entrapped in CulthiSpher-S microcarriers showed maintained capacity of increasing insulin secretion upon enhanced glucose concentration challenge. In this case, insulin release was approximately 60% of that from intact bovine islets within sodium alginate microcapsules. MTT and hematoxylineosin staining of islet cell-containing microcarriers showed the presence of viable and metabolically active cells throughout the study period. This encouraging functional data prompted us to test whether the microcarriers could be immunoisolated for potential use in transplantation. The microcarriers were embedded within 3% sodium alginate, which was then covered with a poly-L-lysine layer and a final outer alginate layer. Maintained insulin secretion function of this system was observed, which raises the possibility of using microencapsulated CulthiSpher-S microcarriers, containing dispersed pancreatic islet cells, in experimental transplantation studies.

Cancer mortality among chemical workers in an Italian plant.

Objective of this study was to assess the mortality experience of a cohort of chemical workers at a plant located in central Italy. Subjects employed for any time between 1954 and 1970 at the chemical plant were included in the cohort and followed up to June 1991. The workers were classified as having ever/never worked in one of the following work processes: organic chemicals, acid mixtures, cleansing agents and insecticides. Mortality experience of the cohort was compared with that of the regional population by computing SMRs (standardized mortality ratios) and 90% CI (confidence intervals). Vital status was ascertained for 96% of the 505 cohort members. All causes of mortality for the entire cohort were lower than expected (Obs: 176; SMR: 0.90; 90% CI: 0.79-1.03). Analysis by work process revealed an increased mortality for lymphatic and hematopoietic tissue neoplasm in the cleansing agents department (Obs: 3; SMR: 5.00; 90% CI: 1.36-12.9); peritoneum and retropertioneum neoplasm in the organic compounds production (Obs: 2; SMR: 13.33; 90% CI: 2.37-42.0), and bladder cancer in the insecticides process (Obs: 3; SMR: 3.53; 90% CI: 0.96-9.12). Although the study had a low statistical power, the increased cancer risks detected are consistent with previous observations and may be of etiologic interest.

[D.lgsl. 625/1994--Protection against carcinogenic agents: the obligation to educate]. / D.lgsl. 626/1994--Protezione da agenti cancerogeni: dovere di formazione.

According to act 626/1994, employers have the duty to inform and train workers and their representatives. The implementation of training activities requires the following points: planning the training program according to the needs of the target population, use of the methods aimed at promoting learning and the adoption of safe behaviour, setting-up of evaluation tools. The disciplines of risk perception and communication and adult training may provide useful contribution in this frame. At the light of the preliminary experiences in this field, the importance of the following items for workers, workers representatives and employers is emphasized: probabilistic causality models, role of cognitive and emotional factors in the learning process, definition of carcinogenic according to national and international organisation, meaning of TLV with respect to carcinogenic exposure, interaction between carcinogens in the case of multiple exposition, risk evaluation, preventive measures, transfer of carcinogen risk from workplace to domestic environment, due to lack of compliance with basic hygienic rules such proper use of work clothes.

[Safety assurance for occupational tumors in agriculture]. / La tutela assicurativa dei tumori professionali in agricoltura.

Cancer risk in farming is characterized by:-multiple exposure varying in time, space and between crops;-poor knowledge of agrochemical used by workers;-interset of both sellers and users mainly or acute toxicity of pesticides;-availibility of sufficient evidence of carcinogenicity in humans only for arsenical insecticides and for benzene used as solvent. The frequency of both claims for compensation and recognized cased is extremely low. Referral to exper agronomists operations in the area of interest can turn out to be of great value in assessing exposures. In case of exposure to carcinogenic agents defined as possible or probable, the following criteria may be adopted:-duration of exposure and latency time in agreement with findings from scientific literature;-biological plausibility of the association of interest;-evaluation of the interaction in the frame of multiple exposure, with special reference to the role of brief and/or low exposures. The above mentioned items are discussed by examining practical cases.

[Insurance coverage in repetitive strain injury of the upper limbs as provided by the National Insurance Institute for Occupational Diseases]. / Aspetti assicurativi nelle patologie da movimenti ripetitivi degli arti superiori in ambiente INAIL.

A brief outline is given of the current status of the insurance "coverage" provided by INAIL for WMSDs. In breach of a specific European Union recommendation, in Italy various WMSDs can be recognised as occupational only based upon sentence No 179/88 of the Constitutional Court, since such disorders are not included in the list attached to DPR law 336/94. At present, during the period 1990-95, INAIL awarded indemnities in only a handful of cases. Details are provided concerning the evidence that must be submitted in the specific case of claims pertaining to suspected occupational diseases. The authors discuss the problems associated with quantifying injuries for the purposes of claiming indemnities for work-related musculo-skeletal disorders.

[Medico-legal aspects of the 89/931 act of the EEC]. / Gli aspetti medico legali della direttiva quadro 89/931 della CEE.

The act 391/89 which introduces some substantial news regarding the protection of public welfare and the safety of workers, will be taken in account in a next future. The A.A. examine these innovations and underline the way they will reassert the importance of a concrete application of the principles of primary prevention. Moreover, this act will have a large impact on forensic medicine as it will allow the acquisition of objective elements to asses the casual nexus between occupational exposure and injury, while evaluating the occupational etiology of the damage.