To bridge or not to bridge: Moral Judgement in Cocaine Use Disorders, a case-control study on human morality.

BACKGROUND: In the "Dual-Process theory", morality is characterized by the interaction between an automatic-emotional process, mediated by the Anterior Cingulate Cortex (ACC) and linked to personal-deontological decisions, and a rational-conscious one, mediated by the Dorso-Lateral Prefrontal Cortex (DLPFC) and linked to impersonal-utilitarian decisions. These areas are altered by chronic use of cocaine, with a possible impact on moral decision-making. OBJECTIVE: To evaluate the difference between a group of Cocaine Use Disorder (CUD) patients and a control group in moral decision-making. METHODS: Subjects with CUD were compared to an equal-sized healthy group regarding their moral decision-making. Trolley and Footbridge Moral Dilemmas were administered to each group. The quality of the answer (yes or no) and the time needed to answer were recorded. RESULTS: The recruited group includes 72 subjects, 36 with CUD and 36 healthy subjects (average age of 39.51 ± 9.89). In the Trolley dilemma, almost all the subjects (97.3%) answered "yes", while in the Footbridge dilemma CUD subjects answered "yes" more often (52.7%) than the healthy group (19.4%). CONCLUSION: For strong emotional dilemmas (Footbridge), cocaine users answered "yes" with a higher frequency compared to healthy subjects, highlighting a wider utilitarian tendency in decision-making and a poor emotional participation.

The effectiveness of domestic cook on inactivation of murine norovirus in experimentally infected Manila clams (Ruditapes philippinarum).

AIM: The aim of this work was to evaluate the efficacy of domestic cooking in inactivating Manila clams experimentally infected with murine norovirus (MNV). METHODS AND RESULTS: A cooking pan was modified to enable electronic temperature probes to be positioned to record both flesh and environment temperature. Manila clams were infected with 10(4) TCID 50% ml(-1) of MNV. The infected whole-in-shell clams, divided into three replicates, were cooked on an electric stove, and groups of nine clams were removed from the pan at fixed intervals. Pools of three digestive glands were examined by virus isolation to ascertain residual viral load. CONCLUSION: Results showed that 10 min of cooking by a traditional domestic method at a temperature close to 100°C, for at least 2 min, can completely devitalize the MNV in infected clams. This is generally the time needed for the majority of valves to open up. SIGNIFICANCE AND IMPACT OF THE STUDY: At present, it is highly recommended to label all lagoon products as 'requiring cooking before consumption', but no specifications are given on how long and at what temperature they should be cooked. Our results can provide the consumer with useful indications on how to cook clams to prevent any risk of foodborne illness.

Effect of polysaccharides from Opuntia ficus-indica (L.) cladodes on the healing of dermal wounds in the rat.

In traditional medicine extracts of polysaccharide-containing plants are widely employed for the treatment of skin and epithelium wounds and of mucous membrane irritation. The extracts of Opuntia ficus-indica cladodes are used in folk medicine for their antiulcer and wound-healing activities. The present study describes the wound-healing potential of two lyophilized polysaccharide extracts obtained from O. ficus-indica (L.) cladodes applied on large full-thickness wounds in the rat. When topically applied for 6 days, polysaccharides with a molecular weight (MW)>10(4)Da from O. ficus-indica cladodes induce a beneficial effect on cutaneous repair in this experimental model; in particular the topical application of O. ficus-indica extracts on skin lesions accelerates the reepithelization and remodelling phases, also by affecting cell-matrix interactions and by modulating laminin deposition. Furthermore, the wound-healing effect is more marked for polysaccharides with a MW ranging 10(4)-10(6)Da than for those with MW>10(6)Da, leading us to suppose that the fine structure of these polysaccharides and thus their particular hygroscopic, rheologic and viscoelastic properties may be essential for the wound-healing promoter activity observed.

Late childbearing and its impact on adverse pregnancy outcome: stillbirth, preterm delivery and low birth weight.

BACKGROUND: The role of parental ageing on the incidence of adverse pregnancy outcome is based on increased morbidity and obstetric problems during pregnancy and delivery in old mothers, and on the accumulation of spontaneous harmful mutations for continuous cell divisions during spermatogenesis in old fathers. The aim of this study is to estimate the impact of paternal and maternal ageing on the risk of adverse pregnancy outcome. DATA AND METHODS: From the group of 3,616,622 Italian singletons born in 1990-1996 we estimated the risks of stillbirth, preterm birth (<37 weeks of gestation) in live births, and low birth-weight (< 2.3 Kg) in live full-term births. The risks were estimated as a function of maternal and paternal ageing through logistic regression models, which included, as covariates, parity (1st, 2nd, > or =3rd) and family education (low, < or =8 years of schooling for both parents; high, >8 years for at least one parent). Parental ages were examined as quantitative (in one year classes) or categorical factors (in three classes: fathers 20-29, 30-39, > or =40; mothers 20-29, 30-34, > or =35). RESULTS AND CONCLUSIONS: We found that, compared with 20-29-year old parents, mothers > or =30 years and fathers > or =40 years are at risk of adverse pregnancy outcome. The effects are more relevant for preterm births and greater in the least than in the most favourable birth conditions, i.e., in first-born children of less educated families than in second-born children of highly educated families. For the risk of a preterm delivery, the odds ratio is OR = 1.32 [1.28-1.36] in mothers aged 30-34 years, and OR=1.97 [1.88-2.07] in mothers 235 years in the least favourable conditions, and OR = 1.14 [1.10-1.18] and OR = 1.56 [1.22-1.27] respectively, in the most favourable conditions. The impact of paternal ageing is smaller but significant in fathers > or =40 years: for the risk of a preterm birth, the odds ratio is OR = 1.40 [1.33-1.47] in the least favourable conditions, and OR = 1.14 [1.08-1.21] in the most favourable conditions. This last, baseline risk might be indicative of a paternal genetic component associated with childbearing in advanced age.

Late paternity and stillbirth risk.

BACKGROUND: The role of paternal ageing on the incidence of some genetic diseases in offspring depends on the hypothesis that spontaneous mutations accumulate due to continuous cell divisions during spermatogenesis. We examined the effect of paternal age on the complex multifactorial character, stillbirth. METHODS: In 3,619,647 Italian singletons born in 1990-1996 we evaluated stillbirth risk as a function of paternal ageing by means of multiple logistic regression models, which included maternal age and family education, as categorical covariates and interactions. The categorical risk was estimated for mothers and fathers beyond threshold ages of 35 and 40 years, respectively. RESULTS: Stillbirth risk increases with paternal ageing in mothers > or =30 years old, and maternal age and family education modify the impact. In families with low education, the risk accounts for odds ratio (OR) 1.015 [95% confidence interval (CI) 1.01-1.02] in mothers aged 30-34 years, and for OR 1.032 (95% CI 1.02-1.04) in mothers aged > or =35 years; in families with higher education the risk accounts for OR 1.008 (95% CI 1.00-1.02) and OR 1.025 (95% CI 1.01-1.04), respectively, in mothers aged 30-34 and > or =35 years. In these latter families, for mothers aged <35 and fathers > or =40 years the risk accounts for OR 1.12 (95% CI 1.00-1.25). CONCLUSIONS: The effect of paternal ageing on stillbirth risk is revealed in mothers aged > or =30 years and is modified by family education. In mothers aged 30-34 years from families with high education, the increase imputable to paternal ageing might be indicative of a genetic component.

Effect of the exposure to gentamicin and diltiazem on the permeability of model membranes.

Preliminary observations showed that the calcium-antagonist diltiazem enhances the 'in vitro' bactericidal action of the aminoglycoside gentamicin, especially against Gram-positive bacteria. To verify if a non-specific interaction of these two drugs with biomembranes may play a role in their synergic effect on bacterial cells, we have studied the effect of exposure to gentamicin, in the absence or presence of diltiazem, on the release of carboxyfluorescein (CF) trapped in phosphatidylcholine (PC) unilamellar vesicles (LUVs) used as model membranes. A significant leakage of trapped CF from PC LUVs was registered when liposomes were treated with gentamicin and diltiazem together, employed at doses (50 and 100 microg/ml, respectively) unable to affect CF release if applied alone; the combined effect of gentamicin and diltiazem was synergic and not cumulative. The present findings demonstrate that the simultaneous exposure to gentamicin and diltiazem may induce significant alterations in the permeability of phospholipid membranes and, so, very likely, in functional properties of bacterial membranes, targets of their action.

In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents.

Topically-applied antioxidant drugs represent a successful strategy for protecting the skin against UV-mediated oxidative damage. However, they can afford to the skin a satisfactory photoprotection only if able to permeate through the stratum corneum and thus to reach deeper cutaneous layers. Caffeic and ferulic acids, dissolved in saturated aqueous solutions at pH 3 or 7.2, have been tested for their capability to permeate through excised human skin mounted in Franz cells. At both pH values, ferulic and, at a lower degree, caffeic acids appeared able to permeate through the stratum corneum. The known higher lipophilicity of ferulic acid may explain the fact that it permeates through the stratum corneum better than caffeic acid. However, vehicle pH values proved to have no influence on biophenol skin permeation profile; this observed lack of pH effect may reflect the drug higher concentration attainable in saturated solutions at high pH. On the basis of the findings obtained in these in vitro experiments, we designed the schedule of a series of in vivo experiments, carried out to evaluate the ability of caffeic and ferulic acids to reduce, in healthy human volunteers, UVB-induced skin erythema, monitored by means of reflectance spectrophotometry. Caffeic and ferulic acids, dissolved in saturated aqueous solution pH 7.2, proved to afford a significant protection to the skin against UVB-induced erythema. To conclude, we have confirmed, by means of in vitro and in vivo experiments, that caffeic and ferulic acids may be successfully employed as topical protective agents against UV radiation-induced skin damage; however their skin absorption is not influenced by the pH of the formulation.

Antioxidant effectiveness as influenced by phenolic content of fresh orange juices.

Several fresh orange juices, obtained from five different Citrus sinensis (L.) Osbeck varieties (three pigmented varieties, Moro, Sanguinello, and Tarocco, and two blond varieties, Valencia late and Washington navel), were subjected to antioxidant profile determination (including total polyphenols, flavanones, anthocyanins, hydroxycinnamic acids, and ascorbic acid). The antioxidant activity of these juices was then assessed by means of different "in vitro" tests (bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical; peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, on mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles; scavenging activity against nitric oxide; total antioxidant status). All orange juices tested showed an evident antioxidant effect. Our findings indicate the following: (1) the antioxidant efficiency of orange juices may be attributed, in a significant part at least, to their content of total phenols, (2) while ascorbic acid seems to play a minor role; (3) the antioxidant activity of orange juices is related not only to structural features of phytochemicals contained in them, but also to their capability to interact with biomembranes; (4) finally, as to pigmented juices, their antioxidant efficiency appears to be widely influenced by the anthocyanin level. One could speculate that the supply of natural antioxidant phenols through daily consumption of orange juice might provide additional protection against in vivo oxidation of cellular biomolecules.

[Biological and clinical characteristics of granular lymphocyte proliferation. Review of the literature and personal experience]. / Caratteristiche biologiche e cliniche delle proliferazioni di linfociti granulari. Revisione della letteratura ed esperienze personali.

The Authors, on the basis of reports from the literature and their personal experience, describe the morphological, immunophenotypic, genotypic and functional features of Large Granular Lymphocytes (LGL). An increased number of the these particular types of lymphocytes may be observed in different pathological conditions and may be interpreted as a reactive process to a possible underlying antigenic stimulation. However, a significant and prolonged increase in LGL's may also identify the existence of a true definite Lymphoproliferative disorder (LGL-PD). It is now well known that phenotypically LGL-PD may be present in two different variants: a CD3+ form, which is more frequent, and a CD3-variant. The former usually is characterized by T-cell receptor monoclonal rearrangement, while CD3- NK cells are frequently polyclonal. However also this latter variant may express clonality and in this case the clinical course is particularly aggressive. Although LGL-PD is a distinct clinical disorder, the Authors underline the extreme variability of the clinical course and the need therefore to adopt a policy of "wait and see" before taking into consideration the choice of different therapeutic options, which are often disappointing and provide remission of only brief duration.

Changes in the permeability of the blood-brain barrier following sodium dodecyl sulphate administration in the rat.

The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvasculature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 microg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]alpha-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, Ki, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.

Recommended procedures for the classification of acute leukaemias.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Recommended procedures for the classification of acute leukaemias. International Council for Standardization in Haematology (ICSH).

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia.

Epidoxorubicin vs idarubicin containing regimens in intermediate and high grade non-Hodgkin's lymphoma: preliminary results of a multicentric randomized trial.

BACKGROUND: In recent years many therapeutic regimens have been designed in order to improve response rate and response duration in non-Hodgkin's lymphoma (NHL). In 1991 the Italian Lymphoma Study Group (GISL) started a prospective randomized trial on treatment of aggressive and advanced NHL, focused on the efficacy of two Pro-MACE-CytaBom (P-C) derived protocols. METHODS: From April 1991 to March 1993, 243 cases of intermediate and high grade NHL (Groups D-H according to the Working Formulation) in stage I bulky, II-IV have been registered from 19 institutions and randomized to receive 6 courses of either epidoxorubicin, 30 mg/m2 (P-E) or idarubicin, 6 mg/m2 (P-I) containing P-C. The present study deals with the results of an interim analysis of the first 96 cases enrolled up to December 1991 (median follow up of surviving cases 19 months, range 15-23), in terms of overall response rate, toxicity and dose intensity of the two schedules, and overall survival. RESULTS: The overall response rate was: 55 CR (64.0%), 15 PR (17.4%), 5 NR (5.8%) and 11 PG (12.8%). The actuarial survival rate was 61% at 24 months. Hematological and non-hematological toxicity was comparable in the two arms. Dose intensity was high and similar for the two schedules (90% vs 89%). CONCLUSION: This interim analysis demonstrates that in aggressive NHL both P-C derived schedules with epidoxorubicin or idarubicin are effective, safe and well tolerated, also when used in a large multicentric setting.

Selective involvement of monocytes by acquired myeloperoxidase deficiency in a case of chronic myelomonocytic leukemia.

The authors describe a case of chronic myelomonocytic leukemia in which a myeloperoxidase (MPO) deficiency of circulating monocytes was first detected by automated differential cell counting, and subsequently confirmed by cytochemical and immunocytochemical investigations. MPO activity in neutrophil granulocytes from the same case was found to be normal. MPO deficiency in monocytes appeared to be associated with impaired phagocytic capacity and, based on the results of immunophenotypic and ultrastructural studies, was most likely attributable to a partial maturation arrest of monocytes. The present case suggests that MPO deficiency in myelodysplastic syndromes may have its origin in a number of different pathogenetic mechanisms.

Epididymal lymphoma. A case report.

Primary epididymal lymphoma is an unusual observation. Only 2 cases of non-Hodgkin's lymphoma of the epididymis have been previously reported. We describe the clinical and pathologic features and management of a primary high-grade malignant lymphoma of the epididymis in which a tentative diagnosis of lymphoma was made on the basis of cytologic examination and immunochemical staining of the material obtained from an aspiration needle biopsy.

Cytogenetic findings in terminal large cell transformation in a case of Sézary syndrome.

A long-lasting case of Sézary syndrome, whose chromosomal pattern had been repeatedly investigated during a follow-up period of several years, was studied in the terminal transforming phase, which took place more than 5 years after the initial diagnosis. To the best of the authors' knowledge, this appears to be the first instance of cytogenetic studies carried out in a large cell transformation of cutaneous T-cell lymphoma. The results clearly indicate that the atypical large cells seen in the transforming phase were clonally derived from the pre-existing cerebriform cells. Newly detected relevant cytogenetic findings were: a) drop of tumor cell ploidy from hypotetraploid to hypotriploid, with striking chromosomal imbalance; b) additional structural aberrations of chromosomes 2 and 7, which had been already preferentially involved in the earlier phases, and involvement of the previously unaffected chromosomes 1, 3, and X; and c) presence in 100% of the abnormal metaphases of a large HSR on the long arm of chromosome 17.

HPLC analysis of oleuropein and some flavonoids in leaf and bud of Olea europaea L.

Reversed phase high-performance liquid chromatography was applied for qualitative and quantitative analysis of secoiridoid oleuropein and some flavonoids in leaf and bud extracts of Olea europaea L. The RP-HPLC procedure is rapid and reproducible. The results of quantitative analysis, correlated with pharmacological activity, are reported here.

High-performance liquid chromatography of flavonoids in Crataegus oxyacantha L. IV. Reversed-phase high-pressure liquid chromatography in flower, leaf and bud extractives of Crataegus oxyacantha L.

RP-HPLC has been used for qualitative and quantitative analysis of some flavonoids in flowers, leaves and bud extracts of Crataegus oxyacantha L. Peak identification was obtained by comparison with retention times of pure standard substances and by UV analysis. Luteolin, luteolin-3', 7-diglucoside, apigenin, apigenin-7-O-glucoside and rutin have been identified and determined.