Study of ethane level in exhaled breath in patients with age-related macular degeneration: preliminary study.

PURPOSE: A variety of factors have been implicated in the pathogenesis of age-related macular degeneration (ARMD), and oxidative stress plays an important role in the onset and progression of the disease. Breath ethane is now considered a specific and non-invasive test for determining and monitoring the trend of lipid peroxidation and free radical-induced damage in vivo. This test provides an index of the patients' overall oxidative stress level. We evaluated the breath ethane concentration in exhaled air in patients with advanced ARMD. METHODS: In this study, we enrolled 13 patients with advanced ARMD and a control group, and a breath analysis was carried out by gas chromatography. RESULTS: The mean ethane level in the ARMD patients was 0.82 ± 0.93 nmol/l (range: 0.01-2.7 nmol/l) and the mean ethane value in the control group was 0.12 ± 0.02 nmol/l (range: 0.08-0.16 nmol/l). The difference between the values of the 2 groups was statistically significant (p < 0.005). Receiver operating characteristic analysis showed an elevated area under the curve (0.831; 95% CI: 0.634-0.948), with a significance level of p < 0.0014 (area = 0.5). CONCLUSIONS: These preliminary results seem to indicate that breath ethane levels are higher in most patients with ARMD. The breath ethane test could thus be a useful method for evaluating the level of oxidative stress in patients with ARMD. To our knowledge, there are no data on this type of analysis applied to ARMD.

Omeprazole induces apoptosis in normal human polymorphonuclear leucocytes.

We investigated in vitro apoptosis in human polymorphonuclear neutrophils (PMN) induced by omeprazole. This drug, both in the native (OM) and acidified (OM-HCl) form, is a potent inducer of PMN apoptosis. The effect is time- and dose-dependent. OM-HCl is more efficient than OM in inducing PMN apoptosis. In fact, after 24 h incubation in vitro at 1 x 10(-4) M OM-HCl induces apoptosis in 70% of the cell population compared to 37% induced by OM. Apoptosis induced by both forms of the drug is caspase dependent being significantly reduced by pretreating cells with the caspase 3 inhibitor (DEVDH-CHO). However, some differences in the apoptosis mechanisms between the two forms of the drug seem to exist because PMN treatment with the specific caspase 8 inhibitor (Z-IETD-FMK) only blocks OM-HCl mediated apoptosis. We observed cleavage of caspase 8 only in the cells incubated with OM-HCl while the executioner caspase 3 was activated with both forms of the drug. Furthermore, pretreatment with GM-CSF, a known activator of intracellular survival pathways in PMN, partially protected cells from OM-HCl induced apoptosis but did not contrast the apoptotic effect of OM. Cysteine cathepsin proteases also seem involved in the apoptotic mechanism of both drug forms since the specific inhibitor E64d gave a significant protection. To verify if OM-HCl induced apoptosis was dependent on the sulfenamide bound with the cell sulfhydryl groups we used molecules with thiol groups such as beta-mercaptoethanol (beta-ME) and reduced glutathione (GSH). Reactions of OM-HCl with cellular sulfhydryl groups are strongly involved in both the triggering and evolving phase of the apoptotic mechanism since significant protection from apoptosis was obtained when PMN were pretreated for 1 h with beta-ME (lipid-permeable) or GSH (lipid-impermeable). These results show that OM and OM-HCl induce apoptosis in human PMN and suggest that the second binds the sulfhydryl groups, present on the cell membrane, to then penetrate the cell thus causing a further significant increase in apoptosis. OM-induced PMN apoptosis during the treatment of gastric inflammatory disease could be an advantage for the resolution of the phlogosis state. However, this aspect should be further elucidated to assess the optimal therapeutical regimen for gastric diseases which are related to infective agents.

[Occupational injuries and sickness absence: association with job demand, decision latitude, and life style in 2174 workers in the Veneto Region]. / Infortuni sul lavoro e assenze dal lavoro per malattia: associazioni con carico lavorativo, autonomia decisionale e stili di vita in 2174 lavoratori del veneto.

BACKGROUND: Stress was the most frequent (26,9%) health problem reported in a survey on the perception of working and health conditions in 5000 workers in the Veneto Region. OBJECTIVES: The aim of the study was to investigate in the Veneto Region the association between occupational stress and events occurred in the previous 12 months: occupational accidents, or sickness absence for 10 or more consecutive days. METHODS: Perceived occupational stress is correlated, according to Karasek's model, to high job demand (JD) and low decision latitude (DL). Using Karasek's questionnaire (to which questions on smoking and alcohol consumption were added), we examined 2174 subjects working in 30 companies with between 10 and 500 employees, who belonged to the occupational categories of industry and services that are more prevalent in the Veneto Region. The questionnaire was administered by the occupational physician during health surveillance. The subjects were classified on the basis of current exposure to psychosocial factors or, for subjects reporting an event, their exposure at that time. We identified the tertiles of JD and DL; data were submitted to the analysis of multiple logistic regression, estimating odds ratio (OR) and 95% confidence interval (CI). The population attributable risk (PAR) was calculated using the formula (pc (OR-1)/OR), where pc is the fraction of exposed cases. RESULTS: An elevated risk of occupational accidents was found in subjects with regular consumption of alcohol (OR = 2.0; IC = 1.2-3.5), in smokers smoking 10-20 (2.3; 1.3-3.8) or >20 cigarettes/day (3.8; 1.8-7.9), in the highest tertile of JD (2.29; 1.35-3.89) and in the lowest tertile of DL (1.6; 1.0-2.6). PAR was 37.6% for occupational factors (high JD and low DL), 44.5%for non-occupational factors (cigarette smoking and alcohol consumption), and 82.1% overall. The risk of sickness absence increased in subjects smoking 10-20 cigarettes (1.63 = 1.1-2.40), in the highest tertile of JD (1.5; 1.0-2.2) and in the lowest tertile of DL (1.6; 1.1-2.2). PAR was 26.1% for occupational factors (high JD and low DL), 7.6% for non-occupational factors (smoking), and 30.4% overall. While the risk of sick absence increased mainly with the reduction of DL, the risk of occupational accidents increased with increasing JD and, to a lesser extent, with decreasing DL. The current approach to accident prevention is based only on technical and administrative aspects, in spite of the fact that 80% of accidents are not attributable to malfunctioning of machinery. Injury prevention should address technical, personal and psychosocial risk factors together as a whole.

Effect of two-hour daily hemodialysis and sham dialysis on breath isoprene exhalation.

BACKGROUND: Isoprene, a volatile hydrocarbon produced by the human organism, is currently being extensively investigated because the mechanisms underlying its endogenous origin are unknown and because experiments suggest it is toxic and cancerogenous. Previous reports of increases in breath isoprene concentrations during 4-hour, thrice-weekly hemodialysis, but not during continuous ambulatorial peritoneal dialysis, prompted us to assess the behavior of isoprene in another dialytic modality, i.e., short daily hemodialysis (short DHD). Furthermore, in order to determine whether removal of solutes and/or contact of blood with the dialytic membrane influenced the metabolism of isoprene, we performed a sham short hemodialysis session in a subgroup of 8 patients (sham short HD), i.e., with blood flowing through a dialyzer but without dialysate and ultrafiltration. METHODS: The present study evaluates the effects of a two-hour short DHD and a two-hour session of sham HD on isoprene breath levels, as determined by gas chromatography before, during and after sessions. Parallel analyses of ambient air and monitoring of blood pressure and heart rate were performed. RESULTS: Both short DHD and sham DHD induced an increase in breath isoprene exhalation in all patients without being associated with significant hemodynamic variations. CONCLUSION: These findings suggest that the increase in breath isoprene after a session of hemodialysis is neither a reaction to mevalonate depletion nor to metabolic variations induced by the depurative effect, because these changes do not occur during sham HD. It is not related to hemodynamic changes because none were observed in this experimental model. The isoprene increase seems to be of metabolic origin and appears to be connected in some way with the extracorporeal circuit. These interesting findings provide a further impulse to study the biosynthetic pathways involved and to investigate the medical and biological significance of isoprene in humans.

[Historical Archives of Italian Nephrology. The form, evocative of function. A short historical review about the discovery of drugs from the most remote times to new trends in pharmacological sciences]. / Archivi storici della Nefrologia Italiana. Nella forma le sembianze della funzione. Una breve rivisitazione storica sulla scopertadei farmaci, dai tempi antichi sino alle più recenti tendenze nelle scienze farmacologiche.

The image, the imaginary and the imagined are more than ever the guide in pharmacological research, and predominate in the expectations of discovering, designing and producing a potential drug. The concept of ""form"" is now corroborated and implemented by the most recent and astounding acquisitions on the existing relationship in biology between form, structure and function. This article is a brief historical reconstruction of how the ""form"" has represented, from the most remote times, a fundamental guiding criterion in the choice of potential pharmacological remedies, and how in times of biotechnology and informatics the design and development of new drugs is based on the assumption that the form-function requisite is among the most promising trends in pharmacological sciences and drug discovery, in the nephrology field too.

Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.

[Historical Archives of Italian Nephrology. The gout as a paradigmatic example of the ancient humoral theory of diseases]. / Archivi storici della Nefrologia Italiana. La gotta come paradigma e superamento dell'antica teoria umorale delle malattie.

Gout is one of the oldest known diseases. The term derives from the Latin "gutta", which means "a drop" This word expresses and describes, as no other term can, a method of interpreting the pathologies that have been with us for more than 2000 yrs. The theory of humoral disturbance goes back to the time of Hippocrates. This paper is a historical review of gout, with particular attention given to the interpretation of the origins of clinical, articular and renal involvement allowing us paradigmatically to sum up all the stages in the evolution of the etiopathogenetic and nosographic concepts of medicine through the ages.

Age sensitivity to organophosphate-induced delayed polyneuropathy. Biochemical and toxicological studies in developing chicks.

Young animals are resistant to organophosphate-induced delayed polyneuropathy (OPIDP). The putative target protein in the nervous system for initiation of OPIDP in the adult hen is an enzyme called Neuropathy Target Esterase (NTE), which is dissected by selective inhibitors among nervous tissue esterases hydrolysing phenyl valerate (PV). We report here that the pool of PV-esterases sensitive to paraoxon was different in peripheral nerves of chicks as compared to that of hens while that of brain and spinal cord was not. NTE activity decreased with age in brain, spinal cord and peripheral nerve, but its sensitivity to several inhibitors remained unchanged. In the adult hen more than 70% inhibition of peripheral nerve NTE by neuropathic OPs is followed by deficit of retrograde axonal transport, axonal degeneration and paralysis. Similar NTE inhibition in 40-day-old or younger chicks however is not followed by changes in retrograde axonal transport nor by OPIDP. Chicks aged 60 to 80 days are only marginally sensitive to a single dose of DFP otherwise clearly neuropathic to hens. In vitro and in vivo phosphorylation by DFP and subsequent aging of brain NTE is similar both in chicks and in hens. The recovery of NTE activity monitored in vivo after inhibition by DFP is faster (half-life of about 3 days) in chick peripheral nerves as compared to chick brain, hen brain and hen peripheral nerve (half-life of about 5 days). It is concluded that the reduced sensitivity to OPIDP in chicks is not due to differences in OP-NTE interactions. The resistance might be explained by a more efficient repair mechanism, as suggested by the faster recovery of peripheral nerve NTE activity.

Organophosphate polyneuropathy in chicks.

Young animals are resistant to organophosphate-induced delayed neuropathy (OPIDP), although biochemical changes on Neuropathy Target Esterase (NTE) caused by neuropathic organophosphorus esters (OP) are similar to those observed in the sensitive hen. We report here that the resistance of chicks to single doses of neuropathic OPs is not absolute because ataxia was produced in 40-day-old chicks by 2,2-dichlorovinyl dibutyl phosphate (DBDCVP, 5.0 or 10.0 mg/kg s.c.) and by diisopropyl phosphorofluoridate (DFP, 2.0 mg/kg s.c.). However, the clinical picture was different from that usually seen in hens; spasticity and complete recovery being the main features. alpha-Tolyl sulphonyl fluoride (PMSF, 300 mg/kg s.c.) promoted both DBDCVP neuropathy (5.0 or 10.0 mg/kg s.c.) and non-neuropathic doses of DFP (1.5 mg/kg s.c.) or DBDCVP (1.0 mg/kg s.c.). The lowest promoting dose of PMSF given 24 hr after 1.5 mg/kg of DFP was 30 mg/kg. Higher doses had a more severe effect but no further increase of OPIDP severity was obtained with doses ranging from 90 to 300 mg/kg. PMSF (30 mg/kg) protected 40-day-old chicks from subsequent doses of neuropathic OPs even when a promoting dose of PMSF followed. At 60 days of age, chicks' resistance to OPIDP decreased because lower doses of neuropathic OPs became effective and, similarly to hens, PMSF did not fully protect from subsequent promotion. In 40-day-old chicks the threshold of NTE inhibition for OPIDP development was 95-97% (DBDCVP 5.0 mg/kg). When promotion followed initiation, the minimal effective inhibition of NTE for initiation by neuropathic OPs was about 90%. In 36-day-old chicks, PMSF (300 mg/kg) promoted OPIDP when given up to 5 days after DFP (1.5 mg/kg) when residual NTE inhibition in brain and sciatic nerve was about 40%. We conclude that chicks' resistance to OPIDP might reflect either a less effective initiation by phosphorylated NTE or a more efficient repair mechanism or both, and also that promotion is likely to involve a target other than NTE.

Expression modes of urinary N-acetyl-beta-D-glucosaminidase in patients with chronic renal insufficiency.

BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity has emerged as potentially useful early marker of renal tubular injury. This activity is usually evaluated in random urine samples and is related to urinary creatinine concentration. Reports about the lack of correlation between NAG activity of 24-h urines and activity of random urine samples in some clinical and experimental situations led us to study the correlation existing between different procedures for expressing urinary NAG in patients with chronic renal insufficiency. METHODS: Thirty samples of 24-h urine and 30 random urine samples from chronic renal insufficiency patients were collected. The activity of urinary NAG was examined fluorimetrically. RESULTS: The following correlations were observed: (1) r = 0.431 (P = 0.017) for activity in random urine samples and total activity in 24-h urines); (2) r = 0.281 (P = 0.005) for activity in random samples and activity, expressed as U/l, in 24-h urines. CONCLUSIONS: The data show that collection of urine excreted over the whole day and evaluation of total daily excretion of NAG seems the method of choice, at least for patients with chronic renal insufficiency.

Effect of antiorthostatic hypokinetic/hypodynamia on urinary endothelin-1 and N-acetyl-beta-D-glucosaminidase excretion in rats.

In an experimental model with rats in head-down suspension, plasma levels and urinary excretion of endothelin-1 (ET-1) and urinary excretion of N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30; NAG) were determined. Significant variations in time in the effective plasma ET-1 levels in the superior and inferior cava vessel blood of animals maintained for 6 days in hypogravity with respect to controls were observed. We not only found a transient increase in urinary NAG activity but also that the levels of U-ET-1 increased during head-down suspension. The simultaneous evaluation at urinary level of these two parameters could be an indication that there are different sites of renal parenchymal involvement or injury during antiorthostatic hypokinesis.

N-acetyl-beta-D-glucosaminidase activity in urine of dental personnel.

BACKGROUND: Dental personnel is exposed to several potential nephrotoxic agents. Urinary N-acetyl-beta-d-glucosaminidase (U-NAG) activity has emerged as a sensitive marker of early nephrotoxicity. METHODS: U-NAG was evaluated, by fluorimetric assay, in urine from 30 healthy subjects and 30 dental personnels. RESULTS: The median value of U-NAG activity (133.5 U/mmol urinary creatinine (U-Cr) in urines of dental personnel was not statistically different (P>0.05) from activity (100.7 U/mmol U-Cr) of control urines. CONCLUSIONS: The results suggest that, for dental personnel, exposure to potential nephrotoxic agents is not usually high enough to increase U-NAG activity.

Omeprazole induces apoptosis in jurkat cells.

We report for the first time a potent apoptotic effect of omeprazole (OM). Apoptosis was induced in Jurkat cells in a time and concentration-dependent mode. Caspase 3 and PARP were rapidly cleaved in response to OM, but apoptosis was only partially inhibited by the caspase 3 inhibitor DEVD-CHO. OM also induced an early lysosomal destabilization which increased progressively and was correlated with a parallel increase in apoptotic cells. The cysteine protease inhibitor E64d gave strong protection against apoptosis thus proving the involvement of lysosomal enzymes in OM-induced apoptosis whereas, it did not impede the caspase 3 cleavage. Instead ZVAD-fmk, a general caspase inhibitor, also able to inhibit cathepsin activity, protected cells completely from OM-induced apoptosis. It therefore seems that both caspases and cysteine cathepsins are involved in the execution stage of OM-induced apoptosis.

Phenylmethanesulfonyl fluoride delays the recovery from crush of peripheral nerves in hens.

Several esterase inhibitors (carbamates, phosphinates and sulfonyl halides) have been shown to promote organophosphate-induced delayed polyneuropathy (OPIDP). The mechanism of promotion is not understood, but indirect evidence suggests impairments of peripheral nerve repair. Also, other toxic neuropathies, such as those caused by 2,5-hexanedione in hens and bromophenylacetylurea in rats, have been reported to be promoted by phenylmethanesulfonyl fluoride (PMSF). Hen sciatic nerve was crushed at the bifurcation. Either mild or heavy pressure was applied by forceps obtaining a mild and rapidly recovering lesion (possibly myelinic) or a more severe, long-lasting lesion (possibly axonal), respectively. Hens were then treated with PMSF (120 mg/kg s.c. or 200 mg/kg s.c. x 2, 24 h apart) either before (5-48 h) crush or afterwards (5-48 h). Controls received vehicle only. Animals were observed for reappearance of digit movements, and standing and walking ability. PMSF treatment did not change the clinical outcome when animals received a mild crush. In hens receiving the more severe crush the reappearance of digit movements and the complete clinical recovery were observed after 43 +/- 14 and 63 +/- 9 days, respectively. In animals treated with PMSF there was a significant delay in both reappearance of digit movements (56 +/- 11 days when PMSF was given 24 and 48 h before crush, and 55 +/- 10 days, when given 24 and 48 h after crush) and in clinical recovery (75 +/- 15 and 80 +/- 18 days, respectively). It is concluded that traumatic axonopathy as well as toxic neuropathies can be promoted by PMSF. Moreover, it appears that PMSF promotion involves a target and a mechanism which are present in healthy axons and do not need to be activated by the insult to the axon.

Clinical expression of organophosphate-induced delayed polyneuropathy in rats.

Single doses of certain organophosphates (OP), such as dibutyl-2,2-dichlorovinyl phosphate (DBDCVP) cause organophosphate-induced delayed polyneuropathy (OPIDP) in hens. Clinical effects correlate with inhibition of neuropathy target esterase (NTE) which is considered the target for this toxicity. Pre-treatment with non-neuropathic NTE inhibitors, such as phenylmethanesulfonyl fluoride (PMSF), protects from OPIDP. However, when given after OPs, these compounds promote OPIDP. Chicks are relatively resistant to OPIDP despite high NTE inhibition. It has also always been reported that rats represent a species which is resistant to OPIDP and that they might develop morphological but not clinical signs of OPIDP. We report here that clinical OPIDP can be produced in 3.5- and 6-month-old rats by DBDCVP (5 mg/kg s.c.) and that it correlates with high (> 90%) NTE inhibition. When PMSF (120 mg/kg s.c. x 2) was given after DBDCVP, OPIDP was promoted. Pretreatment with PMSF protected from OPIDP. We conclude that resistance to OPIDP in the rat is age-related, as it is in the hen.

Plasma sulfate concentration and hyperhomocysteinemia in hemodialysis patients.

BACKGROUND: Severe hyperhomocysteinemia is common in hemodialysis patients, who also present a dramatic increase in plasma concentrations of sulfate, one of the main products of methionine and cysteine catabolism. The aim of this study was to verify the relationship between high plasma sulfate levels and cysteine or homocysteine concentrations in hemodialysis patients. METHODS: Plasma sulfate, cysteine and homocysteine concentrations and some renal efficiency parameters were determined in 18 patients with end-stage renal failure, all undergoing 4h hemodialysis three times a week. The pattern of post-dialysis rises on plasma concentrations of sulfate, cysteine and homocysteine was established. RESULTS: Plasma sulfate, cysteine and homocysteine levels were significantly higher in patients than in normal controls. Plasma sulfate concentrations positively correlated with cysteinemia (p = 0.031; r = 0.482) which, in turn correlated with homocysteinemia (p = 0.042; r = 0.460). Sulfate levels also correlated with blood creatinine (p = 0.004; r = 0.630), nitrogen (p = 0.000; r = 0.899), protein (p = 0.014; r = 0.555), and albumin (p = 0.003; r = 0.642). Post-dialysis rises in sulfate and cysteine were detected some hours before homocysteine. CONCLUSION: The results suggest that high sulfate levels, due mainly to impaired renal function, are involved in the altered metabolism of homocysteine in hemodialysis patients.

[Reduced ex vivo production of superoxide anion by polymorphonuclear leukocytes during therapy with omeprazole. A pharmacological effect?]. / Ridotta produzione "ex vivo" di anione superossido da parte dei leucociti polimorfonucleati durante terapia con omeprazolo. Un effetto farmacologico?

Among available drugs, omeprazole is the one that cures gastric acid secretion-related pathologies, including reflux oesophagitis which responds poorly to H2-receptor antagonists, most rapidly and efficaciously. This marked therapeutic action is thought to reflect the drug's capacity to adequately control parietal hydrochloric acid secretion. Our data suggest an omeprazole effect on human neutrophil function too. Neutrophils are more or less a constant, and often conspicuous anatomo-pathological component of the phlogistic processes associated with gastric acid secretion. A direct or indirect effect exerted by omeprazole on leukocyte function would be of great scientific-biological and therapeutic interest. Furthermore, it would contribute to marking the drug superior in terms of more rapid relief of the symptoms and range of therapeutic action.

[Leukocyte procoagulant activity and chemotherapeutic agents: comparison between the effects of adriamycin and epiadriamycin on the procoagulant lympho/monocytic activity in vitro]. / Attività procoagulante leucocitaria e farmaci chemioterapici: comparazione tra gli effetti dell'adriamicina e dell'epiadriamicina sull'attività procoagulante linfo/monocitaria "in vitro".

It is well known that a number of antineoplastic agents are able to induce procoagulant cellular activity and tissue factor not only in neoplastic cells but also in normal, monocyte/macrophage cells, and some of them, including adriamycin, even increase procoagulating activity of the factor already expressed, providing a further example of the possible co-participation of chemotherapy in the onset of thrombotic complication in cancer patient. Epirubicin is an analogue of adriamycin but differs strikingly in terms of its collateral effect, in particular being less cardiotoxic. To the authors' knowledge there are no data regarding the possible effect of epirubicin on lympho/monocyte procoagulant activity. This study shows that not only adriamycin but also epirubicin is able to increment the level of lympho/monocyte procoagulant activity "in vitro", with a dose-dependent effect, and to synergize with bacterial endotoxin in increasing this leukocyte activity, although the effect is significantly greater in the case of adriamycin. The importance of these findings at practical and clinical level remains to be defined, in particular in the length of the different pharmacokinetic behavior of these two chemotherapeutic agents and in the context of those neoplastic diseases for which adriamycin and Epirubicin treatment is most frequently used.

[Leukocytic procoagulant activity and chemotherapeutic drugs: the comparative effects of cisplatin and carboplatin on lympho-/monocytic procoagulant activity in vitro]. / Attività procoagulante leucocitaria e farmaci chemioterapici: effetti comparativi del cisplatino e del carboplatino sull'attività procoagulante linfo/monocitaria in vitro.

It is well known that a number of chemotherapeutic agents are able to induce procoagulating activity not only in neoplastic cells but also in normal, monocyte/macrophage cells, and some of them, including cisplatin, even increase procoagulating activity of the factor already expressed, providing a further example of the possible co-participation of chemotherapy in the onset of thrombotic complications in cancer patients. Carboplatin is an analogue of cisplatin but differs strikingly in terms of its collateral effects, in particular being less oto- and nephrotoxic. To the authors' knowledge there are no data regarding the possible effect of carboplatin on lympho/monocyte procoagulating activity. This study shows that not only platin but also carboplatin is able to increment the levels of lympho/monocyte procoagulating activity in vitro, with a dose-dependent effect, and to synergize with bacterial endotoxin in increasing this leukocyte activity, although the synergic effect is significantly greater in the case of carboplatin. The importance of these findings at a practical and clinical and clinical level still remains to be defined, in particular in the light of the different pharmacokinetic behaviour of these two chemotherapeutic agents and in the context of those neoplastic diseases for which cisplatin and carboplatin treatment is most frequently used.