Herbal supplements in pregnancy: unexpected results from a multicentre study.

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.

Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines.

Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.

An analysis of the factors influencing the paediatrician-parents relationship: the importance of the socio-demographic characteristics of the mothers.

BACKGROUND: The paediatrician-parents meeting is not always characterized by mutual understanding and final satisfaction. Anxiety and preconceptions of the parents and clinicians may have consequences for the formulation of the diagnosis, for the pharmacological prescription, for the therapeutic alliance. METHODS: We performed a survey in collaboration with a representative sample of Italian paediatricians and mothers in the Veneto region to investigate the influence of paediatricians' and families' socio-demographic characteristics on some clinical aspects of the visit and on their relationship. The survey consisted of a first 7-item anonymous questionnaire addressed to paediatricians and to mothers. An univariate analysis (Pearson chi(2)-test) was applied. RESULTS: A total of 276/527 family paediatricians and 2567/5270 mothers completed the questionnaire. The 69.7% of responding paediatricians reported that mothers are very anxious during the visit and require a therapy (especially antibiotics). However, only 9.74% of mothers said they required a therapy, mainly the younger mothers with a lower level of education. The mothers reported that they were satisfied with the time devoted and the explanations given by paediatrician. The main information sources for mothers are personal experience or health care providers' advice, with a marginal role for mass-media, mentioned especially by the younger, with a lower level of education and less experienced mothers. CONCLUSIONS: Our experience suggests that maternal anxiety and physicians' interpretation of parental expectations are important factors to take into account during the visit. The paediatricians are not always good predictors of parental expectations. Younger mothers, with a lower level of education and with less experience need more time, more information and support by paediatricians. They are more likely to request therapy, are less satisfied, more easily influenced and likely to follow mass-media advice, rather than a reliable source of information.

Urinary nitrite/nitrate concentrations and total antioxidant capacity in patients with chronic hepatitis C in therapy with interferon and ribavirin.

In this study we tried to elucidate the role of nitric oxide (NO) in chronic hepatitis C in relation to antioxidant status, since the mechanisms by which hepatitis C virus (HCV) causes cell damage and the factors underlying its resistance to therapy are not well understood. Before and after one and six months of therapy with alpha-interferon and ribavirin, we measured nitrite/nitrate urinary levels, total antioxidant capacity and selenium serum concentrations in 14 patients with chronic hepatitis C and in 9 healthy subjects. Before therapy, mean urinary nitrite/nitrate levels of patients were not different from those of healthy subjects, but after a 6-month treatment with alpha-interferon and ribavirin, these NO metabolites were higher in virologically negative patients (responders). Moreover, while no changes in selenium were observed in all patients, total antioxidant capacity was significantly higher in non-responders and well correlated with hyperuricemia (due to cell damage) observed in these subjects. Instead, uric acid decreased as free molecule in serum in responders, while we found the excretion of high NO levels as nitrite/nitrate. Our data allow us to hypothesize a role for NO as predictive of the success of therapy, since nitrite/nitrate increase in the urine of some patients precedes disappearance of the virus observed at the end of therapy.

Plasma nitrite/nitrate and erythropoietin levels in cross-country skiers during altitude training.

BACKGROUND: The aim of this study was to evaluate the effects of training at altitude on plasma nitrite/nitrate and erythropoietin levels since previously it has been reported an interaction of the NO/cGMP system in erythropoietin production. METHODS: Nine physically trained cross-country male skiers, usually living at 800-1200 m altitude, underwent 6 days of intensive training at a moderate altitude of 3100 m preceeded by 2 days of acclimatisation. Six team-managers, selected as controls, did not undergo any regular physical activity in the last 5 years and during the altitude period. Haematological parameters, erythropoietin and nitrite/nitrate were measured prior to reach the place at altitude, at the end of the period at moderate altitude and 7 days after returning at home. RESULTS: Haematocrit significantly increased in controls after 8 days at altitude. Erythropoietin levels significantly increased after the intensive altitude training only in trained subjects (13.1+/-1.7 vs 6.7+/-1.7 mU x ml-1, p<0.001). Nitrite/nitrate baseline values were significantly higher in trained subjects compared to untrained (49.9+/-17.9 vs 25.4+/-2.8 micromol x l(-1), p<0.01); the altitude period significantly increased nitrite/nitrate levels, in untrained subjects, to the same values observed in trained subjects under control conditions (47.0+/-10.3 micromol x l(-1)). CONCLUSIONS: In our experimental conditions we demonstrated the influence of hypoxia on Epo levels in athletes sustaining a short-term training and the role of a regular physical activity (partly independent from altitude hypoxia) on NO production.

Blood conservation with tranexamic acid in total hip arthroplasty: a randomized, double-blind study in 40 primary operations.

We performed a randomized, double-blind study on the effect of tranexamic acid on blood loss and blood transfusions in 40 primary total hip arthroplasties. Tranexamic acid, 10 mg/kg body weight, or placebo, was given intravenously just before the operation. Blood loss during the operation and postoperatively into the drains was recorded, as also were blood hemoglobin concentrations. Ultrasound examination 1 week postoperatively was done to estimate the blood loss due to remaining hematomas. Total (operation + drain) blood loss was 0.76 (95 CI 0.63-0.89) L in the tranexamic acid group as compared to 1.0 (CI 0.81-1.2) L in the placebo group (p = 0.03). The number of blood transfusions during the day of operation was 2 vs. 10 (p = 0.07) and the total number during the hospital stay was 5 vs. 13 (p = 0.2). 1 patient in each group had a pulmonary embolism.

Prediction of the disposition of midazolam in surgical patients by a physiologically based pharmacokinetic model.

The aim of this study was to predict the disposition of midazolam in individual surgical patients by physiologically based pharmacokinetic (PBPK) modeling and explore the causes of interindividual variability. Tissue-plasma partition coefficients (k(p)) were scaled from rat to human values by a physiologically realistic four-compartment model for each tissue, incorporating the measured unbound fraction (f(u)) of midazolam in the plasma of each patient. Body composition (lean body mass versus adipose tissue) was then estimated in each patient, and the volume of distribution at steady state (V(dss)) of midazolam was calculated. Total clearance (CL) was calculated from unbound intrinsic CL, f(u), and estimated hepatic blood flow. Curves of midazolam plasma concentration versus time were finally predicted by means of a perfusion-limited PBPK model and compared with measured data. In a first study on 14 young patients undergoing surgery with modest blood loss, V(dss) was predicted with an only 3.4% mean error (range -24-+39%) and a correlation between predicted and measured values of 0.818 (p < 0.001). Scaling of k(p) values by the four-compartment model gave better predictions of V(dss) than scaling using unbound k(p). In the PBPK modeling, the mean +/- standard deviation (SD) prediction error for all data was 9.7 +/- 33%. In a second study with 10 elderly patients undergoing orthopedic surgery, hemodilution and blood loss led to a higher f(u) of midazolam. The PBPK modeling correctly predicted a marked increase in V(dss), a smaller increase in CL, and a prolonged terminal half-life of midazolam, as compared with findings in the first study. Interindividual variation in the disposition of midazolam could thus in part be related to the physiological characteristics of the patients and the f(u) of the drug in their plasma.

Pharmacokinetics of intrathecal transferrin-ricin a chain immunotoxin.

We have studied the pharmacokinetics of an anti-transferrin receptor immunotoxin following intrathecal (i.t.) and intravenous (i.v.) bolus inoculation in healthy rats. After i.t. inoculation of 4.9 microg transferrin-ricin A-chain (Tfn-RTA) we have measured the immunotoxin concentration in the cerebrospinal fluid (CSF), in the brain tissue and in the peripheral blood. After i.v. administration of 4.9 microg Tfn-RTA the concentration of Tfn-RTA immunotoxin was evaluated in the peripheral blood. We found that the clearance of Tfn-RTA from the CSF is rapid (9.1 microLmin(-1)), the immunotoxin then diffuses into the brain tissue and in the peripheral blood where it reaches concentrations below the MTC50 (Minimum Toxin Concentration 50%). The rate of immunotoxin elimination from the peripheral blood following either i.v. or i.t. administration are similar (kel = 0.0021 min(-1) vs. 0.0025 min(-1)). Thus, in the healthy rat the immunotoxin does not accumulate following i.t. inoculation, reaching non toxic concentrations in the brain tissue and in the peripheral blood, whereas in the CSF as well as at the interface CSF/brain tissue the immunotoxin may reach potentially therapeutic concentrations. In conclusion we believe that the i.t. inoculation of an immunotoxin could be considered a potentially useful route of administration in the treatment of leptomeningeal carcinomatosis.

Cytokine and nitric oxide levels in a rat model of immunologic protection from adjuvant-induced arthritis.

In the present study we investigated the correlation between the progression of adjuvant arthritis induced by Mycobacterium butyricum and the production of nitric oxide and some pro- and anti-inflammatory cytokines in arthritic rats and in rats treated with low intra-peritoneal doses of Mycobacterium 3 and 10 days after arthritis induction. The intra-peritoneal administration of Mycobacterium antigen significantly inhibited disease development. Compared to healthy rats, a rise in serum and peritoneal pro-inflammatory cytokines was observed in all arthritic rats already from the 14 day. The treatment with intra-peritoneal Mycobacterium was associated with a significant reduction in IL-6 serum concentrations and a slight decrease of IFN-gamma production by peritoneal macrophages. Nitrite/nitrate plasma and peritoneal levels were significantly higher in all arthritic rats. Intra-peritoneal administration of Mycobacterium caused a further increase in nitrite/nitrate plasma concentrations, while no differences were evident in nitric oxide production by peritoneal macrophages. From our data it is evident that among the variables here investigated, IL-6 seems to be the more representative marker of the disease and of the treatment effect. A possible role of nitric oxide as a modulator rather than a direct mediator in this model of inflammation is discussed.

CD23 and CD69 expression on human neutrophils of healthy subjects and patients with peripheral arterial occlusive disease.

In this work we studied, on human neutrophils from healthy donors and patients with peripheral arterial occlusive disease, the expression of CD23 and CD69 and the modulatory effects of IFN-gamma, GM-CSF and IL-4. Neutrophils were isolated from 9 patients and 9 healthy subjects and cultured for 24 h in absence or presence of IFN-gamma (1000 U/ml), GM-CSF (10 U/ml) and IL-4 (10 ng/ml). Expression of CD23 and CD69 was analyzed by FACScan cytofluorimeter. Neutrophils of both patients and healthy donors resulted negative for CD23 and CD69 expression immediately after isolation. After 24 h without stimuli, neutrophils from some patients and healthy donors expressed CD23 and CD69. IFN-gamma and GM-CSF had opposite effects on these two antigens, down-regulating CD23 and up-regulating CD69. IFN-gamma, GM-CSF and IL-4 were not able to induce CD23 expression, while CD69 expression was induced in some negative healthy donors and patients by IFN-gamma, GM-CSF and IL-4 respectively. From our data, we identified two subpopulations of neutrophils that, independently from the vascular pathology, showed a different behaviour towards temperature and some cytokines.

Symptomatic and asymptomatic deep vein thrombosis after total hip replacement. Differences in phlebographic pattern, described by a scoring of the thrombotic burden.

The aim was to describe the phlebographic pattern of asymptomatic and symptomatic deep vein thrombosis (DVT) after total hip replacement by the use of a scoring system in 102 consecutive patients (54 asymptomatic, 48 symptomatic). The DVTs were scored from 1 to 3, and registered in a scoring system dividing the deep veins into 12 separate segments. The asymptomatic patients had a significantly lower total mean DVT score of 3.7 compared to 9.1 in the symptomatic group of patients. The mean ratio of the DVT scores in the deep muscle veins in conjunction with the superficial femoral vein in relation to the total mean score was significantly higher in the asymptomatic patients (74.9%) compared to the symptomatic group (62.4%). A direct sign of DVT, displayed as a filling defect, was seen on the phlebogram in 116 of the 119 legs, and concomitant nonfilling in other vein segments was noted in 6% of the asymptomatic patients, while in the symptomatic group this was the case to a significantly higher level, namely, 46%. A subgroup of asymptomatic patients operated unilaterally, with bilateral DVT had a significantly higher total mean DVT score on the operated side (4. 6) compared to the unoperated side (3.4). The total mean DVT score increased with time after surgery in the group of symptomatic patients. A low total mean DVT score with a predominance of DVT in, or in the connection to, the deep muscle veins is displayed among the asymptomatic patients. This is significantly different from the symptomatic patients who have more extensive DVTs, especially when diagnosed several weeks postoperatively, and frequently with edema and occlusive DVT.

Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty.

We performed a randomized double-blind study on the effect of tranexamic acid on postoperative blood loss and blood transfusions in 39 primary THR operations. Tranexamic acid was given at the end of the operation and 3 hours later. Ultrasound examination 1 week later was performed to measure the occurrence of deep hematomas. In contrast to previous findings in knee arthroplasty, the administration of tranexamic acid failed to give a significant reduction in the postoperative blood loss. This lack of effect was possibly related to the fact that the drug was administered too late. In 11 of the 20 patients receiving tranexamic acid, blood transfusion was not necessary, this being the case in 4/19 in the placebo group (p = 0.05). The occurrence of postoperative deep venous thromboses was similar in the tranexamic acid and placebo groups.

Nutritional supplementation with copper in the rat. I. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils.

OBJECTIVE AND DESIGN: The aims of the work were: 1) to confirm the preliminarily observed anti-arthritic potential of a 200 ppm copper-supplemented diet in the rat: 2) to study the impact of the nutritional treatment and of the experimental pathology on neutrophil activity. ANIMALS AND CELLS: Two hundred female Sprague-Dawley rats were used. Polymorphonuclear leukocytes were isolated from these animals for the ex vivo studies. TREATMENT: Control-rats were maintained on a standard diet containing 5 ppm of copper. Supplemented-rats were kept on a diet containing 200 ppm of the metal. METHODS: Mycobacterium butyricum-induced arthritis was studied. Flame atomic absorption spectroscopy was used to assess copper and zinc levels. The "microplate-assay" technique was used to determine serum lysozyme concentration (lysis of Micrococcus lysodeikticus cell walls), as well as neutrophil O2- generation (superoxide dismutase-inhibitable reduction of ferricytochrome-c), and adhesion (activity of the membrane enzyme acid phosphatase). The results were statistically evaluated by the Student's t test. RESULTS: The nutritional copper-supplementation: 1) significantly inhibited the adjuvant-arthritis development (33% +/- 5, P<0.01); 2) did not modify lysozyme secretion or superoxide production; 3) significantly decreased the percentage of cell adhesion by an average of 41% +/- 19 (P<0.01). CONCLUSIONS: The copper-supplemented diet has an anti-arthritic effect which may be also primed by the effect of copper on the expression of the neutrophil cell-adhesion molecules.

Influence of an acute exercise on neutrophil and platelet adhesion, nitric oxide plasma metabolites in inactive and active subjects.

In this work we studied the influence of an acute exercise either on nitrite/nitrate plasma levels or on neutrophil and platelet adhesion in inactive and active subjects. Twelve healthy subjects (6 inactives and 6 actives) exercised on a racing cycle ergometer performing stepwise increases in intensity until reaching, within 5 min, a heart rate of 150 beats x min(-1) which represents an oxygen consumption of about 75 % of the individual maximum rate of oxygen uptake. From peripheral venous blood samples (drawn from all subjects before, immediately after the end of exercise, and 1 hour later) neutrophils and platelets were isolated to test plate adhesion, and nitrite/nitrate concentrations were measured in the plasma. Immediately after the acute exercise, in active subjects we observed a significant decrease in the percentage of neutrophil adhesion (7.96+/-2.38 vs. 14.10+/-3.14), associated with an increase in nitrite/nitrate plasma levels (81.38+/-10.76 vs. 41.08+/-8.13 micromol x l(-1)), restored by a 40 min pre-incubation with NG-nitro-L-arginine methyl ester (L-NAME). In unstimulated platelets we observed a significant lower percentage of platelet adhesion in active subjects compared to inactives after exercise. With thrombin or adenosine 5'-diphosphate as agonists platelet adhesion did not result significantly different in active subjects compared to inactives. In conclusion, our data show that physical exercise can induce changes in some cell activities, even if transient, and favour the generation of nitric oxide. The lower adhesion of neutrophils and platelets induced by regular exercise could be an important goal in the prevention of vascular and inflammatory diseases.

Expression of FCepsilonII/CD23 on human neutrophils isolated from rheumatoid arthritis patients.

CD23, the low affinity receptor for IgE, is a 45 kilodalton molecule belonging to the C-type lectin family, some members of which have been identified as adhesion molecules. Since it has been described upregulated in different cells in chronic inflammatory diseases and in rheumatoid arthritis in particular, where neutrophils are directly involved in tissue damage, our interest, in this work, has been focused on the expression and regulation of this antigen on neutrophil membrane. We studied 22 patients suffering from rheumatoid arthritis and 22 healthy control subjects. CD23 expression on neutrophil membrane was analyzed by immunofluorescence. Neutrophils of 9 out of 22 patients expressed CD23 molecules, neutrophils of 11 out of 22 patients expressed CD23 only after 24 h of incubation in RPMI; only 2 out of 22 patients did not express the CD23 antigen on neutrophil membrane either after isolation or after a 24 h incubation. On the contrary neutrophils isolated from healthy subjects did not express CD23 molecules upon isolation. Only in 7/22 control subjects neutrophils resulted positive after 24 h of incubation in RPMI. Moreover, we found that in our experimental conditions the presence of IFN-g or GM-CSF alone or in combination with IL-4 inhibited CD23 expression during the 24 h incubation. Our results show that there is a strong association between neutrophil ability to express CD23 and rheumatoid arthritis, and that such expression may be regulated by GM-CSF, IFN-gamma and IL-4.

[Tranexamic acid reduces the blood loss in knee arthroplasty--if it's administered at the right time]. / Tranexamsyra vid knäledsplastik sparar blod--om den ges vid rätt tidpunkt.

Blood loss in total knee arthroplasty is some-times profuse and often necessitates transfusion which is associated with a risk of disease transmission and immunological burden to the recipient. The fibrinolytic system is activated during surgery, an activation augmented by the tourniquet often used in knee arthroplasty. We have found tranexamic acid, a well-known fibrinolytic inhibitor, to reduce blood loss by half in total knee arthroplasty, and the need of transfusion by two thirds. For optimal efficacy, the tranexamic acid should be administered as prophylaxis before release of the tourniquet. We have found no adverse effects of the drug.

Increased endogenous nitric oxide production induced by physical exercise in peripheral arterial occlusive disease patients.

The effects of 14-day physical exercise or iloprost treatment (0.5-2 ng/Kg/min) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease (Fontaine Stage II). Peripheral venous blood samples and 4-h urine samples were collected before, immediately after 14 days of therapy and 7-10 days after therapy in order to evaluate neutrophil adhesion, nitrite/nitrate and cGMP excretion rates. A longer pain free walking distance was observed after exercise, compared to iloprost (>500 m in 3/10 subjects). Urinary nitrite/nitrate, as well as cGMP concentrations, significantly increased after exercise. Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion. No variations were observed in these parameters in iloprost treated patients. The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise. The results from the present and previous observations indicate that, besides pharmacological treatments, a regular aerobic exercise improves peripheral arterial occlusive disease.

Biotransformation and cytotoxic properties of NO-donors on MCF7 and U251 cell lines.

Previous studies have shown a role for nitric oxide (NO) as a cytotoxic effector. In the present work, two chemically different NO-donors such as glyceryl trinitrate (GTN) and S-nitroso-N-acetylpenicillamine (SNAP) were evaluated for both NO release and cytostatic/cytotoxic properties. Nitrite accumulation in the supernatant of MCF-7 and U251 cell lines indicated a greater and quickly release of NO derived from SNAP. A time-course of hemoglobin absorption spectral changes showed a greater release of NO derived from GTN in presence of cells compared to the values observed in the media, confirming that the release of NO by GTN can be enzymatic and non-enzymatic. On the contrary, SNAP generated NO without contribution of cellular components and saturated oxyhemoglobin quickly, within 2 hours. Both NO-donors inhibited thymidine incorporation in a similar manner and dose-dependently in U251 cells, but not in MCF-7 cells, where SNAP at the highest tested dose of 1000 microM induced only a 33% cytostatic effect. About trypan blue exclusion test, after 24 h GTN and SNAP, releasing similar amounts of NO, showed comparable cytotoxic effects on U251 cells (50% dead cells), but not on MCF-7 cells, where GTN resulted more cytotoxic. From our data, the "in vitro" antitumoral activity of NO-donors seems to be related to the type of tumor cell lines, to the amount and duration of NO release.

Neutrophil behavior following exposure to in vivo or in vitro zinc in normal and acutely-inflamed rats: studies on lysozyme secretion, superoxide anion release and platelet adhesion.

The mechanism was studied of the anti-inflammatory effect of oral zinc (114 mg/kg/day of elemental metal, given for 14 days) on the development of the carrageenan-induced paw oedema of the rat, and the impact of in vivo treatment on the activity of neutrophils isolated from the blood of inflamed and non-inflamed animals. The effects of the in vitro incubation with the metal on either non-inflamed or inflamed neutrophils coming from zinc-untreated rats were also examined. It was found that the administration of oral zinc inhibited markedly the process of ex vivo adhesion of the cells obtained from the inflamed rats (an observation confirmed by the in vitro experiments). In vitro release of lysozyme and superoxide anion productions were measured: in the absence of zinc, the 30' of pre-incubation carried out before stimulating with PMA did not influence the cell's reactivity of the non-inflamed neutrophils. It was, on the contrary, capable of significantly reducing that of the inflamed ones. As a consequence, it is quite difficult to properly interpret the data obtained studying the activity of the cells exposed to the metal in vitro.