Can we modulate asthma maintenance treatment level with disease seasonal variations?

Asthma can have clinical seasonal fluctuations due to different exposure factors. The analysis of our data and literature confirm a seasonal trend of asthma severity. In this brief review, authors discuss the possibility to adapt maintenance therapy level to clinical seasonal fluctuations, by increasing treatment in some seasons to prevent exacerbations and by decreasing it in others, when symptoms are low, in order to minimize costs and maximize safety. Literature and our data (concerning studies carried out in areas with a temperate climate) indicate that asthma severity is reduced in summer while it tends to increase in the other seasons. Authors conclude that a preventive increasing maintenance treatment level during the season when we know that patients worsen (starting some weeks before symptom worsening) may reduce asthma exacerbation risks. On the contrary, a summer treatment reduction, in patients that improve during this period, may be considered only in asthma phenotypes with a benign disease course in time.

PIXE analysis of some medicinal plants used in cleaning teeth in southwestern Nigeria.

Sixteen medicinal plants used for cleaning teeth in southwestern Nigeria were analyzed using the particle-induced X-ray emission (PIXE) technique. These medicinal plants have other therapeutic uses, but the emphasis and main focus were on their beneficial effects on human teeth. PIXE measurements were carried out using 1.8 MeV collimated proton beam from the 2.5 MV AN 2000 Van de Graaff accelerator at the Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro, Padova Italy. The results showed the presence of 18 different elements at different concentrations, 2 plants had traces of gold, and none of the plants contained any toxic heavy metals. The metabolic roles of the detected elements were discussed especially as they affected the formation, growth, development, and protection of human teeth. The results of this study are presented and discussed.

Measuring the imaged-object distance with a stationary high-spatial-resolution scintillation camera.

A method to measure the detector-to-object distance from the images obtained with stationary high-spatial-resolution gamma-ray cameras for in vivo studies has been developed. It exploits the shift of the imaged object in the image plane, obtained at a certain tilt of the parallel-hole collimator. A linear dependence of the image displacement on the distance to the object has been measured using a high-spatial-resolution scintillation camera employing an yttrium-aluminium perovskite (YAP) scintillator. It is shown that the modified YAP camera can be used to obtain three-dimensional information without moving the camera or the object. The method could be applied in scintimammography and radioguided surgery, in lymphoscintigraphy, as well as in the analysis of the biodistribution of radiopharmaceuticals.

Evaluation of Nigerian animal feeds by particle-induced X-ray emission.

There is need to evaluate the locally available animal feeds in Nigeria so as to be able to combine them in acceptable proportions to the animals to achieve the desired growth rate. The technique of particle-induced X-ray emission (PIXE) was employed for the evaluation of these locally available animal feeds, which include Panicum maximum (Guinea grass), Cynodon plectostachyum (grass), Leucaena leucephala (legume), Calopogonium mucunoides (legume), Gliricidia sepium (legume), Euphorbia polychrome (legume), Pueraria phaseloides (legume), and Centrosema pubescens (legume). The proton beam delivered by the 2.5-MV AN 2,000 Van de Graaff accelerator at the International Centre for Theoretical Physics Laboratori Nazionali di Legnaro (LNL), Padova, Italy was used for the PIXE measurements. Twenty-one different elements were detected at various concentrations and their nutritional effects on different animals are discussed.

Performance measurements of a high-spatial-resolution YAP camera.

Physical properties of a position-sensitive camera for the analysis of biodistributions of gamma- and beta-emitting radiopharmaceuticals in small animals have been studied, in order to achieve optimal operating conditions. The camera consisted of a highly segmented yttrium-aluminate perovskite (YAP) scintillator, coupled to a position-sensitive photomultiplier. The energy resolution, the detection efficiency, the spatial resolution, the spatial linearity and the count-rate linearity of the YAP camera have been determined. Images related to initial activity levels and successive biodistribution evolution in mice organs are presented as an illustration of the camera performance.

DNA fragmentation in V79 cells irradiated with light ions as measured by pulsed-field gel electrophoresis. I. Experimental results.

PURPOSE: To compare the results on DNA fragmentation induced in Chinese hamster V79 cells by various doses of gamma-rays and low-energy protons and helium-4 ions. MATERIALS AND METHODS: V79 cells were irradiated as monolayers with monoenergetic protons and helium-4 ions; gamma-rays were used as the reference radiation. DNA double-strand breaks were evaluated by calibrated pulsed-field gel electrophoresis using conditions covering the range 5.7 Mbp-23.1 kbp. RESULTS: The fragment-counting method gave double-strand breaks yields and the relative biological effectiveness higher than those obtained by the fraction of activity released method. The frequency distribution of fragments showed that protons and helium ions induced more fragments below the Mbp region than did gamma-rays at the same dose. The distributions for both the irradiated and non-irradiated samples clearly appeared to be non-random. CONCLUSION: Differences were observed in the yield and spatial correlation, at a molecular size scale characteristic of loop dimensions, of the double-strand breaks induced by gamma-rays and by light ions. These effects may have a role in the observed different cell response to these radiations.

PIXE micro-beam mapping of metals in human peri-implant tissues.

Previous investigations did not agree about the possible presence of titanium and other metals in the tissues around endosteal dental implants and joint prostheses. Indeed, while some authors reported diffusion of metals into the tissues, some others did not find evidence of this phenomenon. In the present study, four dental titanium implants, removed with the surrounding tissues from patients at various time intervals after the insertion, were studied by means of the micro-beam proton-induced X-ray emission (PIXE micro-beam) technique, which draws maps showing the tissue distribution of elements with a detection limit of about 1 ppm. One implant was built in commercially pure titanium, two others in titanium coated with titanium plasma spray, and the fourth in Ti-Al-V alloy. Their composition was confirmed by the PIXE micro-beam analyses. The removed samples were embedded in epoxy and processed with a cutting-grinding appliance, mounted on plastic holders, and ground up to a thickness of about 35 microm. Optical microscope examinations were also carried out, to compare the optical findings with the elemental maps obtained with the PIXE micro-beam. One implant, removed after 70 days because the patient had developed peri-implantitis, had some inflammatory soft tissue attached, with no evidence of metal leakage. The other three implants had been removed after 6, 7 and 9 years of valid clinical service, because of the fracture of the prosthetic abutment or the implant stem. At the optical microscope, all these fixtures were embedded in mature bone. The elemental maps indicated small titanium deposits in about 5% of the bone bordering the implants, while aluminum, when present in the fixture, leaked diffusely into the surrounding bone and vanadium was not found in the tissues. These results suggest that titanium may be found occasionally in peri-implantar tissues, but has very little tendency to spread, while the presence of aluminum in the implant alloy may cause an important leakage of this metal.

DNA fragmentation in mammalian cells exposed to various light ions.

Elucidation of how effects of densely ionizing radiation at cellular level are linked to DNA damage is fundamental for a better understanding of the mechanisms leading to genomic damage (especially chromosome aberrations) and developing biophysical models to predict space radiation effects. We have investigated the DNA fragmentation patterns induced in Chinese hamster V79 cells by 31 keV/micrometer protons, 123 keV/micrometer helium-4 ions and gamma rays in the size range 0.023-5.7 Mbp, using calibrated Pulsed Field Gel Electrophoresis (PFGE). The frequency distributions of fragments induced by the charged particles were shifted towards smaller sizes with respect to that induced by comparable doses of gamma rays. The DSB yields, evaluated from the fragments induced in the size range studied, were higher for protons and helium ions than for gamma rays by a factor of about 1.9 and 1.2, respectively. However, these ratios do not adequately reflect the RBE observed on the same cells for inactivation and mutation induced by these beams. This is a further indication for the lack of correlation between the effects exerted at cellular level and the initial yield of DSB. The dependence on radiation quality of the fragmentation pattern suggests that it may have a role in damage repairability. We have analyzed these patterns with a "random breakage" model generalized in order to consider the initial non-random distribution of the DNA molecules. Our results suggest that a random breakage mechanism can describe with a reasonable approximation the DNA fragmentation induced by gamma rays, while the approximation is not so good for light ions, likely due to the interplay between ion tracks and chromatin organization at the loop level.

DNA DSB induction and rejoining in V79 cells irradiated with light ions: a constant field gel electrophoresis study.

PURPOSE: To study the induction and the time-course of rejoining of DNA double strand breaks (DSB) in V79 cells irradiated with light ions with different linear energy transfer (LET). MATERIALS AND METHODS: V79 cells were irradiated in monolayer with monoenergetic proton, deuteron, helium-3 or helium-4 ion beams, each at two different energy values. Gamma rays were used as reference radiation. DSB have been measured by constant field gel electrophoresis (CFGE). RESULTS: The initial yield depended little on the particle type and LET. The amount of DSB left unrejoined for up to 2 h incubation time could be roughly described by a decreasing exponential function with a final plateau, although more complex functions cannot be excluded. Radiation quality had little effect on the rejoining rate but affected the plateau. The amount of residual DSB after 2 h was higher for densely than for sparsely ionizing radiation, and for the same particle was dependent on LET. The corresponding RBE ranged from 1.8 to 6.0. CONCLUSIONS: The results support the hypothesis that complex, less reparable DSB are induced in higher proportion by light ions with respect to gamma-rays and that, for the same ion, increasing LET leads to an increase in this proportion.

Inactivation of human normal and tumour cells irradiated with low energy protons.

PURPOSE: To analyse the cell inactivation frequencies induced by low energy protons in human cells with different sensitivity to photon radiation. MATERIALS AND METHODS: Four human cell lines with various sensitivities to photon irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours of the tongue and larynx, respectively, and the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were irradiated with y-rays and proton beams with linear energy transfer (LET) from 7 to 33 keV/microm. Clonogenic survival was assessed. RESULTS: Survival curves are reported for each cell line following irradiation with gamma-rays and with various proton LETs. The surviving fraction after 2 Gy of gamma-rays was 0.72 for SQ20B cells, and 0.28-0.35 for the other cell lines. The maximum LET proton effectiveness was generally greater than that of gamma-rays. In particular there was a marked increase in beam effectiveness with increasing LET for the most resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with gamma-radiation down to 0.37 with 30 keV/microm protons. The relative biological effectiveness (RBE(2 Gy gamma)) with the 30 keV/microm beam, evaluated as the ratio of 2 Gy to the proton dose producing the same inactivation level as that given by 2 Gy of gamma-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively. CONCLUSIONS: RBE for inactivation with high-LET protons increased with the cellular radioresistance to gamma-rays. The cell line with the greatest resistance to gamma-rays was the most responsive to the highest LET proton beam. A similar trend has also been found in studies reported in the literature with He, C, N ions with LET in the range 20-125 keV/microm on human tumour cell lines.

Use of ultrasonography in the diagnosis of osteomalacia: preliminary results on experimental osteomalacia in the rat.

This study was performed to investigate the ability of ultrasonographic technique to distinguish osteomalacia from normal bone with the same mineral content. Ten rats with experimentally induced osteomalacia (group A) and 12 control rats having similar body size and weight (group B) were studied. Histomorphometric analysis confirmed the presence of osteomalacia in two rats from group A and showed normally mineralized bone in two rats from group B. Whole body bone mineral density, measured by dual-energy x-ray absorptiometry, was similar in the two groups (86 +/- 6 mg/cm2 in group A and 89 +/- 4 mg/cm2 in group B). The velocity of the ultrasound beam in bone was measured by densitometer at the first caudal vertebra of each rat. The velocity was measured when the first peak of the waveform reached a predetermined minimum amplitude value (amplitude-dependent speed of sound) as well as at the lowest point of this curve before it reaches the predetermined minimum amplitude (first minimum speed of sound). Although the amplitude-dependent speed of sound was similar in the two groups (1381.9 +/- 11.8 m/s in group A and 1390.9 +/- 17.8 m/s in group B), the first minimum speed of sound was clearly different (1446.1 +/- 8.9 m/s in group A and 1503.3 +/- 10.9 m/s in group B; P < 0.001). This study shows that ultrasonography could be used to identify alterations in bone quality, such as osteomalacia, but further studies need to be carried out before this method can be introduced into clinical practice.

RBE-LET relationships for cell inactivation and mutation induced by low energy protons in V79 cells: further results at the LNL facility.

PURPOSE: RBE-LET relationships for cell inactivation and hprt mutation in V79 cells have been studied with mono-energetic low-energy proton beams at the radiobiological facility of the INFN-Laboratori Nazionali di Legnaro (LNL), Padova, Italy. MATERIALS AND METHODS: V79 cells were irradiated in mono-layer on mylar coated stainless steel petri dishes, in air. Inactivation data were obtained at 7.7, 34.6 and 37.8 keV/microm and hprt mutation was studied at 7 7 and 37.8 keV/microm. Additional data were also collected for both the end points with the proton LET already considered in our previous publications, namely 11.0, 20.0 and 30.5 keV/microm. RESULTS: A maximum in the RBE-LET relationship for cell inactivation was found at around 31 keV/microm, while the RBE for mutation induction increased continuously with LET. CONCLUSIONS: The proton RBE-LET relationship for cell inactivation is shifted to lower LET values compared with that for heavier ions. For mutation induction, protons of LET equal to 7.7keV/microm gave an RBE value comparable with that obtained by helium ions of about 20 keV/microm. Mutagenicity and lethality caused by protons at low doses in the LET range 7.7-31 keV/microm were proportional, while the data at 37.8 keV/microm suggest that this may not hold at higher LET values.

PIGE-PIXE analysis of medicinal plants and vegetables of pharmacological importance.

PIGE and PIXE techniques were employed to the study of elemental constituents of some traditional medicinal plants generally used in curing many diseases and ailments in southwestern Nigeria. Analyses were also carried out on commonly edible vegetables of medicinal and pharmacological importance. PIGE measurements were carried out using 3.5-MeV collimated protons from the 7 mV CN Van-de-Graaff accelerator of INFN, LNL, Legnaro (Padova), Italy, whereas the PIXE measurements were carried out using 1.8 MeV from the 2.5 MV AN 2000 Van-de-Graaff accelerator of the same laboratory. The results show that many of the medicinal plants contain elements of cardinal importance in human metabolism. The results from the vegetables also show the presence of vital elements that are needed for growth and development. In addition, some of the toxic elements, which include As, Cd, Hg, and so forth, were not detected. However, some of the recipes contain trace amounts of Pb at very low concentrations. This calls for proper control of dose rates in some samples to prevent the attendant negative cumulative effects.

[Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection]. / L'imaging diagnostico e le implicazioni terapeutiche nelle infezioni polmonari del paziente affetto da HIV1.

We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.

A study of the radiobiological effectiveness with track etch detectors.

CR-39 nuclear track detectors have been used in this experiment to study the killing effect of low energy protons on V79-753B Chinese hamster cells and to monitor the proton beam. The estimated surviving fractions and the beam parameters are comparable to those found with conventional electronic devices. The surviving fractions fitted by the linear quadratic model support the idea of single-hit mechanism for the cell killing.

Selenium status and plasma glutathione peroxidase in patients with IgA nephropathy.

The abnormal proliferation of mesangial cells with IgA deposition in the glomeruli characterizes primitive mesangial glomerulonephritis (IgA nephropathy, IgAN); this disease reduces the normal renal parenchyma while renal function becomes progressively impaired. The possible role of selenium has never been considered in evaluating factors involved in the pathogenesis of IgAN. In this work we compared the Se status of 14 IgAN patients (8 with normal renal function, IgAN NRF; 6 with impaired renal function, IgAN IRF) to that of 14 normal individuals (CG NRF) before and after an oral supplementation with selenite (0.13 mol Se/kg b.w./day for 60 days). The following indices of Se status were measured: Se in plasma and urine samples by PIXE; glutathione peroxidase activity in the cytosol of platelets (PLTs-GSH-Px) and of erythrocytes (RBCs-GSH-Px). Both concentrations and activities of plasma glutathione peroxidase (pl-GPx), a selenoenzyme mainly synthesized in and secreted by the kidney, were measured in plasma samples and results compared among groups. IgAN patients showed lower pl-Se and lower activities of selenoenzymes than normal controls before Se supplementation (p < 0.001). These findings suggest that an impaired Se status coexisted with the proliferation of mesangial cells in patients. Selenite induced PLTs-GSH-Px activity in all individuals (p < 0.001), but no variation was observed in RBCs-GSH-Px activity or in the concentration of pl-GPx in the plasma. On the other hand, selenium induced pl-GPx activity in CG NRF (p < 0.001) and in IgAN NRF (p < 0.01), but poorly stimulated pl-GPx activity in IgAN IRF (p = n.s.). However, only 17% and 25% of the pl-GPx activity of normal controls was measured in the plasma of IgAN IRF and IgAN NRF patients, respectively (p < 0.001). In conclusion, selenite only partially restored a normal Se status in patients whose low pl-GPx activity probably reflects an impaired synthesis of this protein as a consequence of reduced normal functioning of the parenchyma in kidneys affected by IgA nephropathy.

DNA double strand break production and rejoining in V79 cells irradiated with light ions.

Low energy protons and other densely ionizing light ions are known to have RBE>1 for cellular end points relevant for stochastic and deterministic effects. The occurrence of a close relationship between them and induction of DNA dsb is still a matter of debate. We studied the production of DNA dsb in V79 cells irradiated with low energy protons having LET values ranging from 11 to 31 keV/micrometer, i.e. in the energy range characteristic of the Bragg peak, using the sedimentation technique. We found that the initial yield of dsb is quite insensitive to proton LET and not significantly higher than that observed with X-rays, in agreement with recent data on V79 cells irradiated with alpha particles of various LET up to 120 keV/micrometer. By contrast, RBE for cell inactivation and for mutation induction rises with the proton LET. In experiments aimed at evaluating the rejoining of dsb after proton irradiation we found that the amount of dsb left unrepaired after 120 min incubation is higher for protons than for sparsely ionizing radiation. These results indicate that dsb are not homogeneous with respect to repair and give support to the hypothesis that increasing LET leads to an increase in the complexity of DNA lesions with a consequent decrease in their repairability.

DNA double-strand breaks induced by low energy protons in V79 cells.

The initial production of DNA double-strand breaks (dsb) was determined in V79 Chinese hamster cells irradiated with proton beams of 3.24, 1.50 and 0.88 MeV, corresponding to values of unrestricted LET evaluated at the cell midplane of 10.9, 20.0 and 30.5 keV/micron, respectively. X-rays were used for comparison. Dsb were measured with the low speed sedimentation technique in neutral sucrose gradients. The initial yield of dsb rose linearly with the dose and did not significantly depend on the proton LET, in contrast with the results obtained in previous studies for cell inactivation and mutation induction. Also, no significant differences for dsb induction were found between protons and X-rays. Two possible explanations, not necessarily mutually exclusive, are proposed: (1) dsb are not the only lesions involved in cellular effects; and (2) the initial number of dsb is not the only important parameter since a fundamental role is played by the degree of clustering, i.e. the association of dsb with other dsb or other types of damage.

Accuracy of bioelectrical impedance analysis in estimation of extracellular space in healthy subjects and in fluid retention states.

Bioelectrical impedance analysis (BIA) is a noninvasive method recently introduced for body fluid evaluation in healthy subjects. The purpose of this paper is to verify the reliability of bioelectrical measurements in extracellular water (ECW) prediction in healthy subjects and in fluid retention states. We studied 40 subjects (19 males and 21 females) aged 21-81 years; 22 were healthy subjects, 12 were affected by chronic heart failure, and 6 by chronic renal failure. In all subjects resistance (R) and reactance (Xc) at 1 and 50 kHz corrected for height were compared with ECW measured by the bromide dilution method. Our results suggested a different behavior of the current in fluid-retention states with respect to healthy subjects. ECW was best predicted by resistance at 1 kHz corrected for height, group (considered as dummy variable), weight and gender (R2 = 0.89, p < 0.001, SEE = 1.7 liters). The bioelectrical impedance analysis at 50 kHz explained the 89% of ECW variability when resistance and reactance corrected for height are considered with gender group and weight (R2 = 0.89, p < 0.001, SEE = 1.7 liters). In conclusion, the bioelectrical method at 1 kHz can be considered sufficiently accurate in ECW prediction in healthy subjects and in fluid retention states. Also, the bioelectrical impedance analysis at 50 kHz is useful for predicting ECW, but his role must be further investigated.

Plasma selenium and glutathione peroxidase activities in individuals living in the Veneto region of Italy.

In order to assess the Se status in individuals living in the Veneto region, a series of related measurements was performed. These included plasma selenium by PIXE and glutathione-peroxidase (GSH-Px) activities in plasma, red blood cells and platelets. Individuals were either normals or people suffering from various liver diseases. Moreover, an oral supplement of sodium selenite was given to 13 patients suffering from stable chronic renal failure (CRF) in parallel to 26 normals: data on plasma GSH-Px and on serum creatinine and creatinine clearance were collected either before or after supplementation. Results were in support of a relatively low selenium status: mean +/- SD plasma Se values of normals (0.82 +/- 0.17mumol/L, n = 82) were comparable to data observed in European regions where Se deficiency was already known. Even lower values were observed in those with liver diseases. Among enzyme activities, the distribution of the data of platelet GSH-Px was in further support of low Se status in the evaluated individuals. After Se supplementation, both normals and CRF patients showed a significant increase in the creatinine clearance, reflecting an improvement of the glomerular filtration rate. We suggest that more extensive surveys of the Se status should be carried out in Italy; moreover, Se supplementation may be advisable in individuals affected with moderate impairment of renal function.