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Biomedical subjects

G C Botta

Publications and source records attributed to G C Botta.

At least 19 recordsLinked to original sources

In vitro cleavage by asbestos fibers of the fifth component of human complement through free-radical generation and kallikrein activation.

Chrysotile and crocidolite fibers incubated in normal human plasma (NHP) generated from the C5 component of complement C5a-type fragments that stimulated polymorphonuclear leukocyte (PMN) chemotaxis. Absorption of NHP with antiserum against C5a totally abolished neutrophil chemotactic activity. Asbestos fibers also produced C5a small peptides in the presence of ethylene glycol bis(beta-aminoethyl ether) N,N,N'N'-tetraacetic acid (EGTA) but not ethylene diamine tetraacetic acid (EDTA). Activation of C5 was significantly inhibited when asbestos fibers were pretreated with iron chelators such as sodium dithionite (DTN), deferoxamine (DFX), or ascorbate (AA). Concentration-related inhibition of C5 activation was also observed when asbestos fibers were added concurrently to plasma in the presence of DFX, 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl scavenger, or aprotinin (APR), a specific protease inhibitor. Further, chrysotile and crocidolite significantly increased plasma kallikrein activity. Data demonstrate that asbestos-induced C5 activation plays a role in inflammatory reactions characteristic of asbestosis through mechanisms involving iron ions, hydroxyl radicals, and oxidized C5-ike fragments. The ferrous ions present at the asbestos fiber surface trigger this activation and catalyze, via Fenton reaction, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same asbestos fibers, yielding an oxidized C5a with the same functional properties as C5a.

Adult↗

Role of iron in asbestos-body-induced oxidant radical generation.

Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.

Asbestos↗

Undiagnosed Mirizzi's syndrome: a word of caution for laparoscopic surgeons--a report of three cases and review of the literature.

The Mirizzi syndrome is often undiagnosed before surgery and can carry a high risk of iatrogenic damage to the common bile duct when encountered during open or, especially, laparoscopic surgery. Endoscopic management has recently been reported, but this treatment can be performed only when there is a high index of suspicion based on clinical criteria that the condition is present and therefore suggests the indication for endoscopic retrograde cholangiopancreatography (ERCP). This is not always the case. Consequently, in a considerable percentage of patients, the syndrome is discovered only after the bile ducts have been damaged during surgery. Three cases of Mirizzi's syndrome were observed in our experience of 896 laparoscopic cholecystectomies (0.3%). All patients were without typical symptoms, and the syndrome was unsuspected in spite of preoperative intravenous cholangiography. All patients required conversion to an open procedure, with two injuries of the common bile duct (a complete transection and a tear) being promptly repaired. We conclude that when this syndrome is suspected or found during surgery, the surgeon should follow these guidelines: (1) perform intraoperative cholangiography when possible, even through the gallbladder wall; and (2) dissect the gallbladder from above and, if necessary, open it to extract the stone. Dissection of Calot's triangle should never be attempted. Great expertise is required to complete the operation laparoscopically. The reported cases in the literature refer to a high percentage of conversion, underlining the technical difficulties and making this syndrome, when undiagnosed and unsuspected, a real challenge for laparoscopic surgeons.

Adult↗

Aerobiological analysis in a salami factory: a possible case of extrinsic allergic alveolitis by Penicillium camembertii.

A 39-year-old man was hospitalized with a history of fatigue, dyspnoea and low grade fever which seemed to be related to his working environment. The patient was employed in a salami factory, working near the area where the salami are seasoned with fungal inocula. Chest X-ray showed diffuse initial changes of reticulonodular pattern that disappeared after a brief course of steroids therapy. Precipitating antibodies to Penicillium notatum and Aspergillus fumigatus were found both in plasma and bronchoalveolar lavage fluid. This, together with the finding of a lymphocytic alveolitis with CD4+ depletion and CD8+ increase, suggested the possibility of extrinsic allergic alveolitis of fungal aetiology. Qualitative and quantitative monitoring with an impinger of both the working and outside environment for aerial fungal concentration demonstrated a very high level of contamination (up to 1.14x10(9) fungal propagules m-3 of air) and an inside/outside ratio from 21 to about 2000. Penicillium camembertii was the most common species found in all the indoor sites (60-100% of the fungal load). The patient's BALF and serum both displayed precipitating antibodies to P. camembertii from the powder used for the inoculum and the air samples. These results together with the patient's working history gave some evidence of relationship between the indoor P. camembertii concentration and the patient's symptoms.

Adult↗

Wollastonite fibers in vitro generate reactive oxygen species able to lyse erythrocytes and activate the complement alternate pathway.

Wollastonite fibers were tested in vitro for their ability to produce reactive oxygen species (ROS) with two different systems: a cell-free reactive mixture containing deoxyribose and a polymorphonuclear leukocyte suspension. After adding the fibers, we measured the thiobarbituric acid-reactive substances produced by deoxyribose degradation and luminol-enhanced chemiluminescence, respectively. Compared with asbestos, wollastonite fibers produced higher ROS levels both in the PMN suspensions and in the cell-free reactive mixtures. A large amount of these ROS were not hydroxyl radicals. Indeed we obtained remarkable differences in ROS generation between unground and ground wollastonite fibers and negative results with fibers modified with ferric chloride and dithionite. In addition, ROS generation was partially inhibited (by 46-54%) in the reactions performed in the presence of 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl radical scavenger. Wollastonite fibers were also analyzed for their ability to lyse erythrocytes and activate complement. Hemolytic potency was about twice that of chrysotile and half that of crocidolite. The levels of complement activation (via the alternate pathway) were about four-fifths of those measured in zymosan-activated plasma (a typical stimulus used to activate the alternate pathway), equal to those obtained with crocidolite, and two-thirds of those found with chrysotile. The addition of DMTU markedly reduced both these activities. Since asbestos fiber toxicity is mainly due to hydroxyl radical generation, our results indicate that wollastonite fibers are probably less toxic than asbestos fibers.

Adult↗

Exposure to cobalt and nickel in the hard-metal production industry.

OBJECTIVE: The shortage of cobalt (Co) on the metal market forced the industry to add nickel (Ni) to Co as a binding agent for the sintering of hard metal. This change enabled us to study (1) the exposure to Ni powder and (2) the effect of Ni on Co uptake (and vice versa). METHODS: Equal amounts of Co and Ni were used in the mixture in a plant employing 50 workers. Both personal ambient-air samples and single-void urine samples were taken twice in the same week, i.e., on Monday and Thursday. Atomic absorption spectroscopy (AAS) was used for analyses. RESULTS: The airborne availability of Ni (mean value 41.65 +/- 6.29 micrograms/m3) was 2-fold that of Co (mean value 21.85 +/- 24.25 micrograms/m3), although the two series of data (n = 20) were significantly correlated. Even if the Co and Ni urinary concentration values (n = 45) recorded on Monday morning and Thursday evening were significantly correlated, at the end of the week there was a 3-fold increase, specifically, from 7.3 to 22.28 micrograms/l, in Co elimination (a significant difference) and a 30% increase in Ni elimination from 11.98 to 15.83 micrograms/l. Moreover, on Monday morning, 90% of Ni urinary concentration values were higher than those of Co as opposed to only 33% on Thursday evening. In the six cases in which both airborne and urine determinations were performed on the 2 days, no significant relationship was found between external exposure and biological monitoring data. CONCLUSIONS: Although Ni uptake was variable, it was generally low, whereas Co uptake was substantial, as had previously been observed in the same plant when Co was the only binder under use. It was therefore possible to rule out any influence of Ni exposure on Co uptake and to suggest the contrary, as has been demonstrated in bacterial species and in rats using everted intestinal sacs.

Adult↗

[Renal transplant from living donor. Experience of the Parma Center].

BACKGROUND AND AIMS: The scarce availability of organs and the excellent results obtained using living donors, due to the improved degree of compatibility between donor and recipient, the short period of organ storage and the possibility of choosing the ideal surgical "timing", in the authors' opinion justify the use of living donors from a clinical and ethical-moral point of view. METHODS: Between April 1986 and December 1996 a 406 renal transplants were performed; of these, 10 patients received grafts from living donors. Preliminary screening consisted in a careful clinical and immunological evaluation to evaluate the operating risk, good compatibility with the recipient and the perfect bilateral function of the kidney. RESULTS: The 10 donors had no postoperative mortality or morbidity, no alterations of renal function, and no onset of hypertension and/or proteinuria in the immediate post-operative period or at a distance. The organ and patient survival rate (including a follow-up of between 2 and 54 months, mean 25 months) was 100%. CONCLUSIONS: The authors suggest that living donors represent a valid alternative in uremic patients. This therapeutic act must be carried out in complete respect for ethical, moral and legislative principles and must be based on a careful clinical selection to minimise the risks of donation and to guarantee the maximum benefit for the recipient. It is to be hoped that further improvements are made in immunodepressive treatment, and above all an appropriate increase in transplants from cadaveric donors, making the use of living donors superfluous since this practice maims a perfectly healthy individual.

Animals↗

[Neoplasms and kidney transplantation. Case contribution].

BACKGROUND: The incidence of malignancies after transplantation is higher when compared with expected cancer in control patients, particularly skin and female genital cancer, non-Hodgkin's disease and Kaposi's sarcoma. The aim of this study is to evaluate the frequency and the efficacy of the treatment of cancer following renal transplantation. METHODS: A retrospective analysis of 404 recipients was performed and it showed the onset of 15 cancers (8 skin cancers, 3 Kaposi's sarcomas, 2 renal carcinomas, 1 urotelioma and 1 colon cancer) in 11 patients (3.7%). At the time of diagnosis, the mean period of immunosuppressive therapy (7 cases of double therapy, 4 cases of triple therapy) was 44.8 months. Skin cancer (53.3%) and Kaposi's sarcoma (20%) were the most frequent in personal experience as reported in literature. Neither lymphomas, nor female genital cancers were detected. RESULTS: All the cases were surgically treated, except patients with Kaposi's sarcoma, whose immunosuppressive therapy was reduced without alteration of renal function. Death-rate was 0.25% (1 case), the remaining patients show no signs of local recurrence or metastasis with preserved renal function except for the patient with renal carcinoma of the transplanted kidney, who underwent nephrectomy and returned in replacement therapy. CONCLUSIONS: The conclusion is drawn that the research of relationship between type of immunosuppressive therapy and cancer incidence and careful clinical and instrumental examination of transplant patients may contribute to reduce the onset of neoplastic degenerations and lead to an early diagnosis.

Antineoplastic Agents↗

Transplantation of horseshoe kidneys: a report of four cases.

OBJECTIVE: To increase the awareness of the successful use of horseshoe kidneys in renal transplantation. PATIENTS AND METHODS: Two donors were found to have horseshoe kidneys; these were divided at the midline and transplanted into four recipients. RESULTS: All four recipients had a delayed return of renal function; all eventually functioned with no complications related to the horseshoe kidney. CONCLUSION: Transplantation of horseshoe kidneys has been performed infrequently but they should be considered as suitable for transplants, considering the shortage of cadaver donors and, when possible, should be divided at the isthmus and the halves transplanted into two recipients.

Adult↗

Absorption and excretion of cobalt in the hard metal industry.

Absorption and excretion of cobalt in the hard metal industry was investigated by means of ambient air and urine measurements in three factories with high levels of environmental cobalt pollution. In the presence of poor hygiene conditions and permission to smoking during work, there was no relationship between cobalt ambient air and cobalt urine concentrations. Such a finding was therefore attributed to a substantial skin contact. A simple experiment of skin exposure to freshly mixed or waste powder on volunteers identified a ten-fold increase of cobalt in urine in the post-exposure samples, thus confirming the contribution of dermal exposure as a route of entry. An improvement in the hygiene of the working conditions helped to investigate the relationship between exposure and excretion level. Cobalt uptake through the different routes of entry may be substantial, and requires a more prolonged exposure-free period so that the excretion rate can be reduced to the reference population level.

Absorption↗

Airborne fibrous and non-fibrous particles in a silicon carbide manufacturing plant.

Silicon carbide (SiC) fibre generation is reported to occur during commercial SiC crystal production. Dust levels and fibre concentrations were measured by static sampling in an Italian plant operating 24 Acheson furnaces. X-ray Diffraction (XRD) was used to assess the quartz content in the dust collected. Optical microscopy (OM) and scanning electron microscopy (SEM) were used for fibre counting and identification of fibres. Only alpha-quartz was identified, but airborne concentrations were found to be higher than the concentration of crystalline silica reported in other similar studies. Two types of fibre, coarse and fine, were identified by OM and SEM: for both, only the peak of silicon (Si) was evident at energy dispersive X-ray analysis (EDXA). Coarse fibres are irregular in shape, with a diameter greater than 5 microns. Fine (respirable) fibres are straight, regular in shape, with a typical diameter between 1 and 2 microns. Fine fibre concentration does not appear to be related either to total dust or to total fibre concentration. It cannot therefore be predicted from the nature of the various processes involved.

Air Pollutants, Occupational↗

Evidence of pulmonary tropism of bamifylline and its main active metabolite.

The extent of the extraplasmatic tropism of bamifylline (Bamifix) was evaluated in the rat and in man by assaying concentrations of bamifylline and of its main active metabolite AC-119 in lung tissue and plasma. After a single oral and intravenous administration of bamifylline in the rat, the ratio between pulmonary and plasma concentrations was between 2.0 and 3.2 for bamifylline, and between 4 and 15 for AC-119 during the observation period considered. On the other hand, the same ratios, calculated after the oral and intravenous administration of theophylline, ranged between 0.20 and 0.39. In studies on man, samples of plasma and lung tissue were obtained during surgery in subjects affected by pulmonary neoplasia and previously subjected to therapy with bamifylline according to the usual dosage scheme. The ratios between tissue and plasma concentrations, at the steady-state and in conditions of equilibrium between the compartments, were 9.4 for bamifylline and 34.7 for its active metabolite. The particular tissue tropism of bamifylline, that appears to be due to its high lipophilic character, could partly explain its high therapeutic index.

Animals↗