Intensive intervention for adolescents with autism spectrum disorder: comparison of three rehabilitation treatments.

INTRODUCTION: Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, characterised by difficulties in social communication and restricted, repetitive behaviours and interests. There are several rehabilitative interventions for individuals with ASD but the evidence of their effectiveness is low or moderate overall. The transition phase of ASD individuals from adolescence to adulthood represents an important challenge. Adults with ASD struggle to access employment or independent living. METHODS: In our study, we evaluated the effect of three different high-intensity interventions, namely Applied Behaviour Analysis (ABA), Treatment and Education of Autistic and Communication-Handicapped Children (TEACCH) and Behavioural Educational Intervention (BEI), in 93 ASD (levels 2 and 3) adolescents (age range 12-18 years). RESULTS: Our results showed that all adolescents with ASD reported an improvement of core symptoms, regardless of the type of treatment. CONCLUSIONS: A high intensity intervention ameliorates the core symptoms of ASD, enriching evidence of effectiveness regarding adolescents with ASD.KEY POINTSIndividuals with ASD need lifespan support and they struggle to access employment, independent living and community inclusion.There are several rehabilitative interventions for individuals with ASD but the evidence of their effectiveness in adolescents is insufficient.The main purpose of this study was to evaluate the possible enhancement produced by three intensive interventions (ABA, TEACCH, BEI) of symptom severity and adaptive functions.Results show that independently of the treatment, individuals with ASD decrease in ASD severity.Individuals who were treated with the BEI and TEACCH programmes reported improvements in the adaptive domains.

A pilot study for development of a novel tool for clinical decision making to identify fallers among ophthalmic patients.

BACKGROUND: Falls in the elderly is a major problem. Although falls have a multifactorial etiology, a commonly cited cause of falls in older people is poor vision. This study proposes a method to discriminate fallers and non-fallers among ophthalmic patients, based on data-mining algorithms applied to health and socio-demographic information. METHODS: A group of 150 subjects aged 55 years and older, recruited at the Eye Clinic of the Second University of Naples, underwent a baseline ophthalmic examination and a standardized questionnaire, including lifestyles, general health, social engagement and eyesight problems. A subject who reported at least one fall within one year was considered as faller, otherwise as non-faller. Different tree-based data-mining algorithms (i.e., C4.5, Adaboost and Random Forest) were used to develop automatic classifiers and their performances were evaluated by assessing the receiver-operator characteristics curve estimated with the 10-fold-crossvalidation approach. RESULTS: The best predictive model, based on Random Forest, enabled to identify fallers with a sensitivity and specificity rate of 72.6% and 77.9%, respectively. The most informative variables were: intraocular pressure, best corrected visual acuity and the answers to the total difficulty score of the Activities of Daily Vision Scale (a questionnaire for the measurement of visual disability). CONCLUSIONS: The current study confirmed that some ophthalmic features (i.e. cataract surgery, lower intraocular pressure values) could be associated with a lower fall risk among visually impaired subjects. Finally, automatic analysis of a combination of visual function parameters (either self-evaluated either by ophthalmological tests) and other health information, by data-mining algorithms, could be a feasible tool for identifying fallers among ophthalmic patients.

Adaptive response of Italian young adults with autism to the COVID-19 pandemic: A longitudinal study.

The COVID-19 pandemic has represented a hazardous situation for individuals with Autism Spectrum Disorder (ASD) and their families. The difficulties, following the COVID-19-derived lockdown, have involved working from home or loss of employment, and the demands of looking after their children without the daily support of specialists. The aim of this study was to evaluate the adaptive behaviour of young adult participants with ASD after the enforcement of lockdown measures in March 2020 in a specialised centre in central Italy, by administering the Italian form of the Vineland Adaptive Behaviour Scales Second Edition (VABS-II), at baseline as well as 6 months and 1 year after the lockdown. Participants with ASD who were not able to access their normal, in-person care - they were only followed at a distance (i.e. telehealth) - declined dramatically in their adaptive behaviour during the first months after the lockdown for some VABS-II dimensions such as the socialisation and daily living domains. The effects of the lockdown on adaptive behaviour remained after 1 year. Our results emphasise the need for immediate, continuous and personal support for people with ASD during and after the restrictions caused by the COVID-19 pandemic, in order to ensure at least partial recovery of adaptive functioning.

Wechsler Intelligence Scale for Adults - Fourth Edition profiles of adults with autism spectrum disorder.

AIM: In this study, we have compared 229 Wechsler Adults Intelligence Scale - Fourth Edition (WAIS-IV) cognitive profiles of different severity adults with autism spectrum disorder to verify the impact of several variables including sex, age, level of education and autism severity level in an Italian sample. Moreover, we wanted to find out the optimal cut points for the major intelligence quotients in order to discriminate autism severity levels. METHODS: Participants were recruited from two National Health System Center in two different Italian regions and were assessed with gold-standard instruments as a part of their clinical evaluation. According to DSM-5, cognitive domains were also measured with multi-componential tests. We used the Italian adaptation of WAIS-IV. We checked our hypotheses using linear regression models and receiver operating characteristics (ROC) curves. RESULTS: Our results showed that age and level of education have a strong impact on Verbal Comprehension (VCI) and Working Memory Indexes (WMI). Gender differences are relevant when considering the VCI and Processing Speed index (PSI) in which women obtained the best performance. These differences are still relevant when considering cut points of ROC because 69 resulted to be the optimal cut point for women, 65 for men. CONCLUSIONS: Few conclusions can be assumed only examining Full Scale Intelligence Quotient (FSIQ) scores as it includes many different information about broader cognitive abilities. Looking deeper at main indexes and their subtests findings are consistent with previous research on the disorder (moderate correlations of FSIQ, Perceptual Reasoning index, WMI and PSI with the participants' age), while other results are unforeseen (no effect of sex found on FSIQ score) or novel (significant effect of education on VCI and WMI). Using an algorithm predicting optimal cut point for discriminating through autism severity levels can help clinicians to better label and quantify the required help a person may need, a test cannot replace diagnostic and clinical evaluation by experienced clinicians.

Light-induced charge generation in polymeric nanoparticles restores vision in advanced-stage retinitis pigmentosa rats.

Retinal dystrophies such as Retinitis pigmentosa are among the most prevalent causes of inherited legal blindness, for which treatments are in demand. Retinal prostheses have been developed to stimulate the inner retinal network that, initially spared by degeneration, deteriorates in the late stages of the disease. We recently reported that conjugated polymer nanoparticles persistently rescue visual activities after a single subretinal injection in the Royal College of Surgeons rat model of Retinitis pigmentosa. Here we demonstrate that conjugated polymer nanoparticles can reinstate physiological signals at the cortical level and visually driven activities when microinjected in 10-months-old Royal College of Surgeons rats bearing fully light-insensitive retinas. The extent of visual restoration positively correlates with the nanoparticle density and hybrid contacts with second-order retinal neurons. The results establish the functional role of organic photovoltaic nanoparticles in restoring visual activities in fully degenerate retinas with intense inner retina rewiring, a stage of the disease in which patients are subjected to prosthetic interventions.

Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C.

OBJECTIVES: Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients. METHODS: One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI. RESULTS: TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027). CONCLUSIONS: In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.

Fibrosis staging in chronic hepatitis C: analysis of discordance between transient elastography and liver biopsy.

In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir > or = F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)-RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy-six of 286 (26.6%) had stage > or =F2 and TE < 7.1 kPa (false negative); 21 of 286 (7.3%) had stage or = 7.1 kPa (false positive). No patient with discordant results had cirrhosis. By Dale model, aspartate aminotransferase (AST) was found to be the unique variable significantly related (P = 0.046) with discordance between biopsy and TE. Discordance rate was 43.4% (82 patients) with AST < 1.5 x UNL vs 25.8% (25 patients) with AST > or = 1.5 x UNL (P = 0.004). False negative rate was 43.4 (82 patients) with AST < 1.5 x UNL vs 17.1% (13 patients) with AST > or = 1.5 x UNL (P < 0.001). Areas under the receiver operating characteristic (AUROC) for F > or = 2, according to AST < 1.5 x UNL vs > or = 1.5 x UNL were 0.738 (95% CI: 0.683-0.812) and 0.854(95% CI: 0.754-0.907). Transient elastography is not adequate on its own to rule out or to rule in significant fibrosis, as it is influenced by major variations in biochemical activity of liver disease. Liver stiffness, at low levels of AST, can underestimate fibrosis.

Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11).

BACKGROUND: Nephronophthisis (NPHP), a rare recessive cystic kidney disease, is the most frequent genetic cause of chronic renal failure in children and young adults. Mutations in nine genes (NPHP1-9) have been identified. NPHP can be associated with retinal degeneration (Senior-Løken syndrome), brainstem and cerebellar anomalies (Joubert syndrome), or liver fibrosis. METHODS: To identify a causative gene for the subset of patients with associated liver fibrosis, the authors performed a genome wide linkage search in a consanguineous family with three affected patients using 50K SNP microarrays and homozygosity mapping. RESULTS: The authors obtained a significant maximum parametric LOD (logarithm of odds) score of Z(max) = 3.72 on chromosome 8q22 and identified a homozygous missense mutation in the gene MKS3/TMEM67. When examining a worldwide cohort of 62 independent patients with NPHP and associated liver fibrosis we identified altogether four novel mutations (p.W290L, p.C615R, p.G821S, and p.G821R) in five of them. Mutations of MKS3/TMEM67, found recently in Meckel-Gruber syndrome (MKS) type 3 and Joubert syndrome (JBTS) type 6, are predominantly truncating mutations. In contrast, the mutations detected here in patients with NPHP and associated liver fibrosis are exclusively missense mutations. This suggests that they may represent hypomorphic alleles, leading to a milder phenotype compared with the more severe MKS or JBTS phenotype. Additionally, mutation analysis for MKS3/TMEM67 in 120 patients with JBTS yielded seven different (four novel) mutations in five patients, four of whom also presented with congenital liver fibrosis. CONCLUSIONS: Hypomorphic MKS3/TMEM67 mutations cause NPHP with liver fibrosis (NPHP11). This is the first report of MKS3 mutations in patients with no vermian agenesis and without neurological signs. Thus NPHP, JBTS, and MKS represent allelic disorders.

Active coating and modified-atmosphere packaging to extend the shelf life of Fior di Latte cheese.

In this work the combination of active coating and modified-atmosphere packaging (MAP) was used to prolong the shelf life of Fior di Latte cheese. The active coating was based on sodium alginate (8% wt/vol) containing lysozyme (0.25 mg/mL) and EDTA, disodium salt (Na(2)-EDTA, 50 mM). The MAP was made up of 30% CO(2), 5% O(2), and 65% N(2). The speed of quality loss for the Fior di Latte cheese, stored at 10 degrees C, was assessed by monitoring pH and weight loss, as well as microbiological and sensorial changes. Results showed that the combination of active coating and MAP improved Fior di Latte cheese preservation, increasing the shelf life to more than 3 d. In addition, the substitution of brine with coating could allow us to gain a double advantage: both preserving the product quality and reducing the cost of its distribution, due to the lower weight of the package.

Shelf life of Stracciatella cheese under modified-atmosphere packaging.

The aim of this work is to evaluate the shelf life of Stracciatella cheese packaged in a protective atmosphere, using 4 different CO(2):N(2):O(2) gas mixtures [50:50:0 (M1), 95:5:0 (M2), 75:25:0 (M3), and 30:65:5 (M4) vol/vol] and stored at 8 degrees C. Cheese in traditional tubs and under vacuum were used as the controls. Results showed that the modified-atmosphere packaging, in particular M1 and M2, delayed microbial growth of spoilage bacteria, without affecting the dairy microflora, and prolonged the sensorial acceptability limit.

FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations.

Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission. Major clinical manifestations affect cardiovascular and skeletal apparatuses and ocular and central nervous systems. We analyzed FBN1 gene in 99 patients referred to our Center for Marfan Syndrome and Related Disorders (University of Florence, Florence, Italy): 85 were affected by MFS and 14 by other fibrillinopathies type I. We identified mutations in 80 patients. Among the 77 different mutational events, 46 had not been previously reported. They are represented by 49 missense (61%), 1 silent (1%), 13 nonsense (16%), 6 donor splice site mutations (8%), 8 small deletions (10%), and 3 small duplications (4%). The majority of missense mutations were within the calcium-binding epidermal growth factor-like domains. We found preferential associations between The Cys-missense mutations and ectopia lentis and premature termination codon mutations and skeletal manifestations. In contrast to what reported in literature, the cardiovascular system is severely affected also in patients carrying mutations in exons 1-10 and 59-65. In conclusion, we were able to detect FBN1 mutations in 88% of patients with MFS and in 36% of patients with other fibrillinopathies type I, confirming that FBN1 mutations are good predictors of classic MFS.

Effect of chitosan on the rheological and sensorial characteristics of Apulia spreadable cheese.

The effect of chitosan on the rheological and sensorial properties of Apulia spreadable cheese during storage time was evaluated. The investigated spreadable cheese samples were stored at 4 degrees C. Storage modulus (G'), loss modulus (G''), tandelta, and the overall sensorial quality of the spreadable cheese were monitored for 24 d. Moreover, moisture content, pH, color, and lactic acid bacteria during storage time were evaluated. Results indicate that statistically significant differences in G', G'', and tandelta values and in the sensorial scores exist between the control sample and the spreadable cheese samples with chitosan. In particular, chitosan improved the rheological and sensorial properties of the spreadable cheese, particularly its softness. Moreover, its addition influenced the physicochemical properties of the investigated spreadable cheese during storage time, without affecting the dairy microflora.

Cytokine gene expression and production by human LPS-stimulated mononuclear cells are inhibited by sulfated heparin-like semi-synthetic derivatives.

BACKGROUND: The K5 polysaccharide obtained from Escherichia coli strain 010:K5:H4 is a polymer of the disaccharidic unit formed by D-glucuronic acid and N-acetylglucosamine. This structure is akin to N-acetylheparosan, the precursory polymer of heparin and of heparan sulfate. This structural affinity with N-acetylated heparin and with de-sulfated heparin makes the K5 polysaccharide extremely useful for the preparation of sulfated heparin-like semi-synthetic derivatives. It has been demonstrated that heparins are able to inhibit tissue factor and cytokine production and expression by human monocytes. OBJECTIVE: The aim of this study was to evaluate the effects of four different heparin-like semi-synthetic derivatives on inflammatory cytokine production and expression by human mononuclear cells. RESULTS: The simultaneous addition of lipopolysaccharide (LPS; 0.2 and 10 micro g mL(-1)) and the K5 polysaccharide did not inhibit interleukin (IL)-1beta, IL-6 or tumor necrosis factor (TNF)-alpha production by stimulated mononuclear cells. IL-1beta, IL-6 and TNF-alpha concentrations in supernatants of LPS-stimulated mononuclear cells were not influenced by the addition of N,O-sulfated K5 polysaccharide (K5-N, OS) and epimerized N-sulfated K5 polysaccharide (K5 NS epi) at 5 and 10 microg mL(-1), whereas the addition of epimerized N,O-sulfated K5 polysaccharide (K5-N, OS epi) (5 and 10 microg mL(-1)) and O-sulfated K5 polysaccharide (K5-OS) (5 and 10 microg mL(-1)) to LPS-stimulated cells caused a significant dose-dependent inhibition of IL-1beta, IL-6 and TNF-alpha. All sulfated heparin-like semi-synthetic derivatives did not influence the IL-10 production by LPS-stimulated mononuclear cells. In LPS-stimulated cells (0.2 and 10 microg mL(-1)), K5-OS or K5-N, OS epi at 5 and 10 microg mL(-1) markedly decreased TNF-alpha mRNA expression. CONCLUSIONS: These results indicate that the sulfated heparin-like semi-synthetic derivatives K5-OS and K5-N, OS epi are able to inhibit both expression and production of inflammatory cytokines, whereas they do not influence the anti-inflammatory cytokine IL-10, suggesting a potential role for these products as modulators of inflammatory reactions.

Prevalence of factor V Leiden mutation in non-European populations.

A difference in the prevalence of venous thromboembolism (TE) in major human groups has been described and an uneven distribution of FV Leiden mutation over the world has recently been reported. We investigated FV Leiden mutation in 584 apparently healthy subjects mostly from populations different from those previously investigated: 170 Europeans (Spanish, Italians), 101 sub-saharan Africans (Fon, Bariba, Berba, Dendi), 115 Asians (Indonesians, Chinese, Tharus), 57 Amerindians (Cayapa), 84 Afroamericans (Rio Cayapa, Viche), and 57 Ethiopians (Amhara, Oromo). The mutation was detected in only 1/115 Asian (Tharu) and in 5/170 Europeans (4 Italians, 1 Spanish). These data confirm that in non-Europeans the prevalence of FV mutation is at least 7 times lower than in Europeans and provide indirect evidence of a low prevalence not only of the FV Leiden gene but also of other genes leading to more severe thrombophilia. Finally, findings from the literature together with those pertaining to this study clearly show a marked heterogeneity among Europeans.

Cytokine gene expression in human LPS- and IFNgamma-stimulated mononuclear cells is inhibited by heparin.

In addition to its well-understood anticoagulant activity, heparin is known to modulate a variety of biological functions including immunologic responses. In order to investigate whether heparin influences the humoral immunity by interacting with cellular elements and affecting gene expression in blood circulating cells. we studied the effect of heparin on IL-1beta, IL-6 and TNFalpha mRNAs in human lipopolysaccharide-(LPS)- or interferon-gamma(IFN-gamma)-stimulated mononuclear cells. The study of mRNA was carried out by an initial PCR screening followed by a Northern blot quantitative analysis. Heparin (0.5 U/ml) turned out to inhibit all three cytokine gene expressions. The mRNA decrease was 37 +/- 6% for IL-1beta, 53 +/- 3% for IL-6 and 47 +/- 4% for TNFalpha with LPS stimulus. No differences could be observed in the inhibitory effect of heparin on IFNgamma-stimulated cells. This effect of heparin was confirmed in a subset of experiments performed on purified monocytes. These results suggest an important immunosuppressive effect of heparin on cell-mediated immune responses.

Tissue factor reduction and tissue factor pathway inhibitor release after heparin administration.

Elevated plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) and large amounts of monocyte procoagulant activity (PCA) have been documented in unstable angina (UA) patients. In in vitro experiments heparin is able to blunt monocyte TF production by inhibiting TF and cytokine gene expression by stimulated cells and after in vivo administration it reduces adverse ischemic outcomes in UA patients. TF and TFPI plasma levels and monocyte PCA have been investigated in 28 refractory UA patients before and during anticoagulant subcutaneous heparin administration (thrice daily weight- and PTT-adjusted for 3 days) followed by 5000 IU X 3 for 5 days. After 2-day treatment, immediately prior to the heparin injection, TF and TFPI plasma levels [(median and range): 239 pg/ml, 130-385 pg/ ml and 120 ng/ml, 80-287 ng/ml] were lower in comparison to baseline samples (254.5 pg/ml, 134.6-380 pg/ml and 135.5 ng/ml, 74-306 ng/ml). Four h after the heparin injection TF furtherly decreased (176.5 pg/ml, 87.5-321 pg/ml; -32.5%. p<0.001) and TFPI increased (240.5 ng/ml, 140-450 ng/ml; +67%, p<0.0001). After 7-day treatment, before the injection of heparin, TF and TFPI plasma levels (200 pg/ml, 128-325 pg/ml and 115 ng/ml, 70-252 ng/ml) significantly decreased (p<0.05) in comparison to the pre-treatment values. On the morning of the 8th day, 4 h after the injection of heparin TF plasma levels and monocytes PCA significantly decreased (156.5 pg/ml, 74-259 pg/ml and from 180 U/105 monocytes, 109-582 U/10(5) monocytes to 86.1 U/10(5) monocytes, 28-320 U/10(5) monocytes; - 38% and -55% respectively) and TFPI increased (235.6 ng/ml, 152-423 ng/ ml; +70%, p<0.001). In conclusion, heparin treatment is associated with a decrease of high TF plasma levels and monocyte procoagulant activity in UA patients. These actions of heparin may play a role in determining the antithrombotic and antiinflammatory properties of this drug.

Monitoring of low-molecular-weight heparins in cardiovascular disease.

Thrombin generation is a key event in the pathophysiology of coronary syndromes and provides the rationale for treatment with anticoagulants. Unlike standard heparin, low-molecular-weight heparin (LMWH) has little effect on activated partial thromboplastin time. LMWH treatment has been monitored by measurement of anti-Factor Xa activity, but this may not accurately reflect the anticoagulant action because LMWHs also inhibit Factor II. The Heptest is a clotting assay that is sensitive to both anti-Xa and anti-IIa activity, as well as inhibition of the extrinsic pathway by LMWH-stimulated release of tissue factor pathway inhibitor. The plasma thrombin neutralization assay has also been used to measure LMWH and to detect low concentrations to which chromogenic assays are insensitive. In the clinical setting, monitoring the anti-Xa activity in patients treated with LMWH after acute deep vein thrombosis offered no advantages over a standard weight-adjusted dose. Moreover, in acute coronary syndromes there is no increase in major hemorrhage rates with weight-adjusted LMWH. Monitoring of LMWH concentrations may be advisable in the presence of comorbid conditions carrying an increased risk of hemorrhage, such as renal disease, advanced age, severe over- or underweight, or a history of previous bleeding episodes.

Lupus anticoagulant and monocyte procoagulant activity in polyabortive women.

Monocyte stimulation may be induced by various agents. Monocytes generate procoagulant activity (PCA) in response to stimulation; they widely interact with the hemostatic system and participate in thrombin formation. Extensive placental thrombotic infarction has been implicated in fetal death in polyabortive patients with lupus anticoagulant (LA). We investigated 38 polyabortive women: 17 LA negative (LA-) and 18 LA positive (LA+). We compared the results with 25 clinically normal women. After four hours of incubation, the mean value of monocyte PCA in the LA+ women was significantly higher than in either the LA- or the control group (p < 0.0001). The monocyte PCA was out of the range of the controls in 9 of the 18 LA+ women. No correlation was observed between the levels of LA and monocyte PCA (r = 0.02; p = 0.94). No differences were found in monocyte PCA increase when induced by LA-, LA+ or control plasma; in all cases the increase was about five-six fold. Our results indicate that an increased monocyte PCA is present in some LA+ polyabortive women, thus suggesting that monocyte activation might be involved in the formation of thrombotic placental infarction and the consequent fetal loss in some patients. It might also suggest that these patients, in particular, could benefit from corticosteroid treatment, which is known to inhibit the formation of monocyte PCA.

Sex related differences in platelet TxA2 generation.

Platelet lipid composition, c arachidonic acid (AA) metabolism by platelets (stimulated with thrombin), serum thromboxane (Tx)B2 production and plasma lipid composition were investigated in 53 healthy females (18-45 years) and 65 males (19-45 years) with similar dietary habits. In males, serum TxB2 production and cholesterol platelet membrane levels were found significantly higher (p less than 0.001 and p less than 0.05) than in females. No differences were observed between the two groups in the AA conversion through cyclo-oxygenase and lipoxygenase pathways or in the platelet phospholipid fatty acid composition. These findings indicate that in males the platelet proaggregatory capacity is greater than in females and the higher platelet TxB2 production does not depend on a larger AA availability or on enzyme activation for its conversion. The increased TxB2 production may be, at least in part, induced by functional differences such as a different membrane cholesterol content inducing, in its turn, an increased microviscosity and/or higher number of platelet receptors for thrombin.

Cyclooxygenase and lipoxygenase metabolite synthesis by polymorphonuclear neutrophils: in vitro effect of dipyrone.

Functional activity of polymorphonuclear neutrophils (PMN) is associated with the metabolism of Arachidonic Acid (AA) released from membrane phospholipids. In this study the in vitro effect of dipyrone, a non steroidal anti-inflammatory drug, on the production of AA metabolites through cyclooxygenase (CO) and lipoxygenase (LO) pathways by stimulated PMN has been investigated. PMN isolated by counterflow centrifuge elutriator were greater than 98% pure and viable. Metabolite production was evaluated by RIA of Thromboxane A2 (TxA2), Prostaglandin E2 (PGE2), Leukotriene B2 (LTB4) and Leukotriene C4 (LTC4) after PMN stimulation with calcium ionophore A 23187 (20 microM). The levels of beta-thromboglobulin (RIA) lower than 5 ng/ml allowed us to rule out activation of residual contaminant platelets. In these experimental conditions, in the absence of dipyrone the products (ng/10(6) cells) of AA metabolism were LTB4 (3.51 +/- 0.22), LTC4 (0.81 +/- 0.08), TxB2 (0.144 +/- 0.025) and PGE2 (0.150 +/- 0.017). Incubation with dipyrone induced changes of PGE2 and TXB2 production in a dose dependent fashion (r = 0.83 and r = 0.87, p less than 0.001), obtaining already at the lowest drug concentration (5 micrograms/ml) a significant inhibition (33 and 40% for TxB2 and PGE2 p less than 0.005). No significant changes of LTB4 and LTC4 production have been observed. The results of this study indicate that dipyrone relevantly affects CO metabolite synthesis by stimulated PMN at concentrations comparable to those reached in therapeutic use. The inhibition of PGE2 synthesis which is present in inflamed tissues and actively participates in inflammatory reactions, could contribute to the therapeutic anti-inflammatory action of dipyrone.