Iron-related markers of inflammation in horses with colic.

The aim of the study was to compare and correlate levels of ferritin, transferrin, iron and APPs in healthy horses and those surgically treated for strangulating colic. On admission, measurements of inflammatory markers related to iron and total protein, fibrinogen, albumin, haptoglobin and ceruloplasmin were made. The study comprised 22 horses, divided into a control group (CG) of healthy horses (n = 10) and horses with surgically treated acute abdomen (n = 12), obstruction group (OG). The OG was subdivided according to the affected intestinal segment (small vs. large) and according to outcome (survivors vs. non survivors). The OG had higher haptoglobin (34.8±14.2 mg/dL vs 20.8±7.21 mg/dL) and transferrin (487±161 mg/dL vs 369±71.4 mg/dL) values and lower iron (96.9±65 µg/dL vs 218±105 µg/dL) values than the CG. The OG horses with large intestine obstruction had lower values of transferrin (374.6±130 mg/dL) than horses with small intestinal obstruction (598.6±98.9 mg/dL). There was no difference in outcome between horses with large and small intestinal obstruction. Ferritin levels were moderately correlated with total protein (r = 0.594; P = 0.042) and albumin (r = 0.584; P = 0.046) in OG. In the multivariate exploratory analysis, fibrinogen levels were higher in animals that did not survive. In conclusion, haptoglobin, transferrin and iron were useful inflammatory markers for colic in horses. The correlation of ferritin with other APPs shows a possible role of ferritin as an APP in horses. Fibrinogen levels are higher in horses with greater risk of death from strangulating obstructions.

Control of the growth of Alicyclobacillus acidoterrestris in industrialized orange juice using rosemary essential oil and nisin.

The use of rosemary essential oil (RO) and its combination with nisin (RO+N) in preventing the multiplication of Alicyclobacillus acidoterrestris in orange juice was evaluated. The minimum inhibitory and bactericidal concentrations (MIC and MBC) for RO were both 125 µg ml-1 while RO+N displayed a synergistic effect. The use of RO and RO+N at concentrations of 1, 4 and 8× MIC in orange juice for 96 h was evaluated in terms of their sporicidal effectiveness. With regard to the action against A. acidoterrestris spores, RO at 8× MIC was sporostatic, whereas RO+N at 1× MIC was sporicidal. Morphological changes in the structure of the micro-organism after treatment were also observed by microscopy. Furthermore, flow cytometric analysis showed that most cells were damaged or killed after treatment. In general, the antioxidant activity after addition of RO+N decreased with time. The results demonstrate that using the combination of RO and nisin can prevent the A. acidoterrestris growth in orange juice.

Effect of an oral preparation containing hyaluronic acid, chondroitin sulfate, hydrolyzed collagen type II and hydrolyzed keratin on synovial fluid features and clinical indices in knee osteoarthritis. A pilot study.

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1ß, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.

Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects.

Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, because OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore, the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures. In order to determine the effect of PRP and HA, K4IM cells were maintained in culture with or without TNF-α stimulation. In the presence of PRP, unstimulated K4IM cells presented the same expression of IL1B, IL6, CXCL8, VEGF, TIMP1, and hyaluronic synthase isoform HAS3 as primary human synoviocytes, while HA addition did not change their expression pattern, which was similar to control cells. Stimulated cells expressed significantly higher values of IL1B, CXCL8, and VEGF compared with unstimulated ones. PRP did not show any modification, except for VEGF, while HA addition modulated IL1B expression. PRP did not modulate HA release of both stimulated and unstimulated cells. Our study showed the possibility to use K4IM synoviocytes as an in vitro model to test biological compounds useful for the treatment of early OA. Primary cells reflect the phenotype of cells in vivo, but limited recovery from biopsies and restricted lifespan makes experimental manipulation challenging. Therefore, despite cell lines present some limitations, they could be used as an alternative for preliminary experiments.

Photodynamic inactivation of foodborne bacteria by eosin Y.

AIMS: The aim of this study was evaluate the effect of photodynamic inactivation mediated by eosin Y in Salmonella enterica serotype Typhimurium ATCC 14028, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778. METHODS AND RESULTS: Bacteria (107 CFU per ml) were incubated with eosin Y at concentrations ranging from 0·1 to 10 µmol l-1 , irradiated by green LED (λmax 490-570 nm) for 5, 10 and 15 min and the cellular viability was determined. Pseudomonas aeruginosa was completely inactivated when treated with 10 µmol l-1 eosin Y for 10 min. Treatments reduced B. cereus and Salm. Typhimurium counts to 2·7 log CFU per ml and 1·7 log CFU per ml, respectively. Escherichia coli counts were slightly reduced. Staphylococcus aureus presented the highest sensitivity, being completely inactivated by eosin Y at 5 µmol l-1 and 5 min of illumination. The reduction of cellular viability of photoinactivated Staph. aureus was also demonstrated by flow cytometry and morphological changes were observed by scanning electron microscopy. CONCLUSIONS: Eosin Y in combination with LED produced bacterial inactivation, being a potential candidate for photodynamic inactivation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study evidenced the efficacy of photodynamic inactivation as a novel and promising alternative to bacterial control.

Inflammation and oxidative stress in heart failure: effects of exercise intensity and duration.

Although acute exercise is apparently pro-inflammatory and increases oxidative stress, it can promote the necessary stress stimulus to train chronic adaptations in patients with chronic heart failure (CHF). This study aimed to compare the effects of exercise intensity and duration on the inflammatory markers soluble tumor necrosis factor receptor (sTNFR1) and interleukin-6 (IL-6), and on oxidative stress [malondialdehyde (MDA) and antioxidant enzymes: catalase (CAT) and superoxide dismutase (SOD)] in individuals with CHF. Eighteen patients performed three exercise sessions: 30 min of moderate-intensity (M30) exercise, 30 min of low-intensity (L30) exercise, and 45 min of low-intensity (L45) exercise. Blood analysis was performed before exercise (baseline), immediately after each session (after), and 1 h after the end of each session (1h after). Thirty min of M30 exercise promoted a larger stressor stimulus, both pro-inflammatory and pro-oxidative, than that promoted by exercises L30 and L45. This was evidenced by increased sTNFR1 and MDA levels after exercise M30. In response to this stressor stimulus, 1 h after exercise, there was an increase in IL-6 and CAT levels, and a return of sTNFR1 to baseline levels. These findings suggest that compared with the duration of exercise, the exercise intensity was an important factor of physiologic adjustments.

Biomarkers, imaging and disease activity indices in patients with early axial spondyloarthritis: the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) Study.

The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.

Inflammation and oxidative stress in heart failure: effects of exercise intensity and duration

Although acute exercise is apparently pro-inflammatory and increases oxidative stress, it can promote the necessary stress stimulus to train chronic adaptations in patients with chronic heart failure (CHF). This study aimed to compare the effects of exercise intensity and duration on the inflammatory markers soluble tumor necrosis factor receptor (sTNFR1) and interleukin-6 (IL-6), and on oxidative stress [malondialdehyde (MDA) and antioxidant enzymes: catalase (CAT) and superoxide dismutase (SOD)] in individuals with CHF. Eighteen patients performed three exercise sessions: 30 min of moderate-intensity (M30) exercise, 30 min of low-intensity (L30) exercise, and 45 min of low-intensity (L45) exercise. Blood analysis was performed before exercise (baseline), immediately after each session (after), and 1 h after the end of each session (1h after). Thirty min of M30 exercise promoted a larger stressor stimulus, both pro-inflammatory and pro-oxidative, than that promoted by exercises L30 and L45. This was evidenced by increased sTNFR1 and MDA levels after exercise M30. In response to this stressor stimulus, 1 h after exercise, there was an increase in IL-6 and CAT levels, and a return of sTNFR1 to baseline levels. These findings suggest that compared with the duration of exercise, the exercise intensity was an important factor of physiologic adjustments.

Italian Society for Rheumatology recommendations for the management of hand osteoarthritis.

Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations' review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.

Italian Society of Rheumatology recommendations for the management of gout.

OBJECTIVE: Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout. METHODS: The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales. RESULTS: The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout. CONCLUSIONS: The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.

The timing of impulse activity shapes the process of synaptic competition at the neuromuscular junction.

The development of neuromuscular junctions exhibits profound remodeling that brings from an immature state characterized by multiple motoneuronal inputs per muscle fiber, to a mature mononeuronal innervation. This striking elimination process occurs both perinatally and during adult reinnervation, and is also widely present in the developing CNS. The accelerating influence of the amount of impulse activity on this process, has been shown by various studies, but a more subtle role of the time correlation of action potential firing in the competing inputs, has also been suggested. Here we explore the latter influence using a rat adult model of neuromuscular junction formation, that is reinnervation following a motor nerve crush. This shares all important features with perinatal development, especially the strict juxtaposition of the competing inputs. In fact the regenerating axons converge on a single cluster of postsynaptic receptors, that is the original endplate of each muscle fiber. This focus on the spatial aspect of competition between nerve endings was missing in our previous experiments employing a similar paradigm. We impose a chronic synchronous firing to the competing terminals, by in vivo electrical stimulation of their axons distal to a sciatic nerve conduction block. Control preparations, with similar post-crush reinnervation, are left with their natural impulse activity unperturbed. We find that the experimental muscles display a prolonged duration of polyneuronal innervation with respect to controls, indicating that hebbian mechanisms participate in the synapse elimination process. Another aspect dealt with in our study is the genuine nature of the polyneuronal innervation occurring during adult muscle reinnervation, because it is supported by both confocal microscopy and by appropriate electrophysiological tests that exclude electrical coupling of myofibers by gap junctions.

Inactivation of animal and human prions by hydrogen peroxide gas plasma sterilization.

Prions cause various transmissible spongiform encephalopathies. They are highly resistant to the chemical and physical decontamination and sterilization procedures routinely used in healthcare facilities. The decontamination procedures recommended for the inactivation of prions are often incompatible with the materials used in medical devices. In this study, we evaluated the use of low-temperature hydrogen peroxide gas plasma sterilization systems and other instrument-processing procedures for inactivating human and animal prions. We provide new data concerning the efficacy of hydrogen peroxide against prions from in vitro or in vivo tests, focusing on the following: the efficiency of hydrogen peroxide sterilization and possible interactions with enzymatic or alkaline detergents, differences in the efficiency of this treatment against different prion strains, and the influence of contaminating lipids. We found that gaseous hydrogen peroxide decreased the infectivity of prions and/or the level of the protease-resistant form of the prion protein on different surface materials. However, the efficiency of this treatment depended strongly on the concentration of hydrogen peroxide and the delivery system used in medical devices, because these effects were more pronounced for the new generation of Sterrad technology. The Sterrad NX sterilizer is 100% efficient (0% transmission and no protease-resistant form of the prion protein signal detected on the surface of the material for the mouse-adapted bovine spongiform encephalopathy 6PB1 strain and a variant Creutzfeldt-Jakob disease strain). Thus, gaseous or vaporized hydrogen peroxide efficiently inactivates prions on the surfaces of medical devices.

On the mechanism of action of muscle fibre activity in synapse competition and elimination at the mammalian neuromuscular junction.

Activity-dependent competition plays a crucial role in the refinement of synaptic connections in the peripheral and central nervous system. The reduction in number of axons innervating each neuromuscular junction during development, i.e. synapse elimination, appears to be one such competitive activity-driven event. Recently, we showed that asynchronous firing of competing presynaptic terminals is a key player in synapse elimination. Although some previous studies suggested that activity of the postsynaptic cell may be an intermediary in the disposal of redundant presynaptic inputs, the mechanism involved remains unknown. In the present study, in order to assess the role of evoked muscle activity in this process, we inhibited the generation of postsynaptic action potentials in muscle fibers in vivo, through the overexpression of inwardly rectifying Kir2.1 and Kir2.2 channels, via electroporation of the soleus muscle in the mouse hindlimb. Electrophysiological and morphological data show that overexpression of potassium channels in the endplate region of neonatal muscle fibres induces membrane hyperpolarization and an increase in conductance, inhibition of the action potential mechanism and prolonged persistence of polyneuronal innervation. These changes are not seen in muscle fibres with overexpression of a non-conducting Kir2.1 mutant. Our results are compatible with the interpretation that the block of action potential generation, even in single endplates, can inhibit synapse elimination through local signalling.

Rheumatoid arthritis is the major risk factor for septic arthritis in rheumatological settings.

Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible functional loss. The reported incidence varies from 2-5 cases/100,000 person-years in the general population to 70 cases/100,000 person-years among patients with rheumatoid arthritis. In fact, individuals with rheumatoid arthritis are at particular risk for developing SA. This may be due to several reasons: joint disease predisposes to bacterial joint colonization and RA itself and its treatment with corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and biological therapies may decrease the immune function required for protection from pathogens. Steroids and DMARDs seem to affect the leukocyte synovial count; indeed, RA patients with SA have a leukocyte count in synovial fluid (SF) lower than patients with SA without underlying rheumatic diseases. The diagnosis of SA in RA patients can be difficult because the development of a hot painful joint is often confused with a relapse of the underlying joint disease leading to delay in diagnosis. For this reason the microscopic analysis and culture of synovial fluid are crucial to exclude septic arthritis.

[Septic arthritis: what is the role for the rheumatologist?]. / Artrite settica: il ruolo del reumatologo.

Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA). Predisposing factors are immunosuppressive and corticosteroids therapy and RA "itself". The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor alpha (TNF alpha) antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti-TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficult-to-access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.

[Septic arthritis: a 12 years retrospective study in a rheumatological university clinic]. / Artriti settiche: studio retrospettivo di 12 anni in un unico centro reumatologico.

BACKGROUND: Septic arthritis is a disabling and potentially life-threatening condition that requires prompt diagnosis and treatment. The most important risk factors are joint prosthesis, pre-existing joint disease and immunosuppressive drugs. The aim of our study therefore was to revaluate all septic arthritis cases discharged from our Rheumatologic Unit in the last 12 years, to assess the risk factors, the clinical and laboratory characteristics, the causative microorganisms and its possible increase in frequency. METHODS: The medical records of 42 consecutive patients with septic arthritis discharged from our Rheumatology Unit between January 1995 and December 2006 were reviewed. The patients ranged in age from 23 to 90 and there isn't gender predominance. Septic arthritis was diagnosed based on the finding of purulent material in the joint space and/or the isolation of a bacterial pathogen from joint fluid. Demographic data, risk factors, co-morbidity, clinical manifestations, time interval between symptoms onset and diagnosis, treatment and laboratory data including serum white blood cell count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), synovial white blood cells and culture results were analysed. We considered these parameters in the whole population and in two different age groups (< or =60, >60) and tried to determine if there was a change of microorganisms involved in septic arthritis during the years. RESULTS: Of 42 patients, 47% were aged 60 and younger. Only 10 patients were admitted to our unit before 2001. A predisposing factor was recorded in 90,5% of cases: 15 patients had rheumatoid arthritis, 8 were diabetic, 6 had seronegative arthritis, 4 had a connective tissue disease, 8 patients had a prosthetic infection and 3 were subjected recently to arthrocentesis. We found that patients aged 60 and younger were more frequently affected by joint disease and had a synovial white blood cell count lower than patients older than 60. Staphylococcus aureus caused septic arthritis in 70% of cases before 2001, and only in 35,8 % after 2001. Also, after 2001, some infections were caused by more unusual pathogens, prevalently in patients treated with TNFa inhibitors. Instead Streptococcus infections were found only in patients aged 70 and older. CONCLUSION: The incidence of bacterial arthritis has increased in the last six years and there was a modification of microorganisms involved, possibly related to a greater therapeutic aggressiveness. The increased frequency of joint disease and the use of immunosuppressive drugs in patients under the age of 60 could be responsible for a lower synovial white blood cell count in these patients.

Wegener's granulomatosis confined to nervous system.

Wegener's granulomatosis (WG) is a multisystemic necrotising granulomatous vasculitis of small and medium sized vessels, that primarily involves the upper and lower respiratory tracts, lung tissues and kidneys. Serum antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker of WG. Whereas the peripheral nervous system is often involved in WG, central nervous system manifestations are reported only in 2-8%, and are rarely present at onset. We report on a patient with atypical neurological presentation of ANCA negative WG in whom the diagnosis was made only after a meningeal biopsy.

Protein-energy malnutrition alters histological and ultrastructural characteristics of the bone marrow and decreases haematopoiesis in adult mice.

Protein-energy malnutrition (PEM) decreases resistance to infection by impairing a number of physiological processes, including haematopoiesis. The aim of this study was to evaluate the microanatomical aspects of bone marrow (BM) in mice that were subjected to PEM, in particular, with respect to the components of the local extracellular matrix and the proliferative activity of haematopoietic cells. For this, histological, histochemical, immunohistochemical and ultrastructural techniques were used. Two-month old male Swiss mice were fed with a low-protein diet containing 4% protein and control mice fed a 20% protein diet. When the experimental group had attained a 25% loss of their original body weight, we collected the different biological samples. Malnourished mice had presented severe BM atrophy as well as a reduction in proliferating cell nuclear antigen and gelatinous degeneration. The malnourished mice had more fibronectin accretion in paratrabecular and endosteal regions and more laminin deposition in perisinusal sites than controls. Endosteal cell activation and hyperplasia were found, suggesting their participation in the process. Additionally, we have observed a decrease in the capacity of malnourished haematopoietic stroma to support the growth of haematopoietic stem cells (CD34+) in vitro. These findings point to a structural impairment of the haematopoietic microenvironments in mice with PEM, possibly hampering the interactions between cells and cellular signalling.

Non-malignant consequences of decreasing asbestos exposure in the Brazil chrysotile mines and mills.

AIMS: To investigate the consequences of improvement in the workplace environment over six decades (1940-96) in asbestos miners and millers from a developing country (Brazil). METHODS: A total of 3634 Brazilian workers with at least one year of exposure completed a respiratory symptoms questionnaire, chest radiography, and a spirometric evaluation. The study population was separated into three groups whose working conditions improved over time: group I (1940-66, n = 180), group II (1967-76, n = 1317), and group III (1977-96, n = 2137). RESULTS: Respiratory symptoms were significantly related to spirometric abnormalities, smoking, and latency time. Breathlessness, in particular, was also associated with age, pleural abnormality and increased cumulative exposure to asbestos fibres. The odds ratios (OR) for parenchymal and/or non-malignant pleural disease were significantly lower in groups II and III compared to group I subjects (0.29 (0.12-0.69) and 0.19 (0.08-0.45), respectively), independent of age and smoking status. Similar results were found when groups were compared at equivalent latency times (groups I v II: 30-45 years; groups II v III: 20-25 years). Ageing, dyspnoea, past and current smoking, and radiographic abnormalities were associated with ventilatory impairment. Lower spirometric values were found in groups I and II compared to group III: lung function values were also lower in higher quartiles of latency and of cumulative exposure in these subjects. CONCLUSIONS: Progressive improvement in occupational hygiene in a developing country is likely to reduce the risk of non-malignant consequences of dust inhalation in asbestos miners and millers.