Early alterations of the behavioural structure of mice affected by Duchenne muscular dystrophy and tested in open-field

Present study has been carried out to assess whether early alterations of the behavioural structure may be detected in mice affected by Duchenne muscular dystrophy (DMD). To this purpose, both quantitative and T-pattern analysis (TPA) were used to analyse the behaviour of two groups of male, two months old mice, 18 MDX and 18 normal as control, tested in an open-field apparatus. T-pattern analysis is a multivariate technique able to reveal hidden structural features of behaviour and, in particular, its temporal characteristics. As to quantitative analyses, mean durations evidenced a significant increase of Walking, Modified Climbing and Rearing and a significant reduction of Immobile-Sniffi…

Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides

Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylati…

Effects of Substantia Nigra pars compacta lesion on the behavioral sequencing in the 6-OHDA model of Parkinson’s disease

The basal ganglia circuitry plays a crucial role in the sequential organization of behavior. Here we studied the behavioral structure of the animals after 21 days of 6-OHDA-induced lesion of the dopaminergic nigrostriatal system. Frequencies and durations of individual components of the behavioral repertoire were calculated; moreover, whether a temporal organization of the activity was present, it was investigated by using T-pattern analysis, a multivariate approach able to detect the real-time sequential organization of behavior. Six sham-depleted and six rats with unilateral 6−OHDA-lesion of the Substantia Nigra pars compacta were used. As to quantitative evaluations, the comparison betwe…

Recurring sequences of multimodal non-verbal and verbal communication during a human psycho-social stress test: A temporal pattern analysis

Abstract Background The Trier Social Stress Test (TSST) is a widely used protocol to study human psycho-social stress responses. Quantitative reports of non-verbal behaviors have been carried out by means of the Ethological Coding System for Interviews (ECSI). However, no data have described whether and how non-verbal and verbal behaviors take part in the composition of multimodal sequences of communication during the test. Method Five non-verbal ECSI categories and four verbal behaviors related with communication were included in the Ethogram. A focal sampling was employed to ensure a high temporal resolution of the behavioral annotation. T-Pattern Analysis was employed to detect statistic…

Synthesis and antimicrobial activity of new 1-R-3-(2-Piridyl)-4-nitroso-5 carboxiethyl-1H-Pyrazoles

SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF NEW 1-R-3-(2-PIRIDYL)- 4-NITROSO- 5-CARBOXIETHYL-1H-PYRAZOLES. Stefania Aielloa , Carmelo Massimo Maidab, Fabio Venturellab, Diego Planetac Marco Giammancod, M.Milicib a Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo bDipartimento di Scienze per la Promozione della Salute G. D’ Alessandro, Università degli Studi di Palermo cDipartimento dei Sistemi Agro-Abientali,Università degli Studi di Palermo d Dipartimednto di Studi Giuridici, Economici, Biomedici e Psicosociopedagogici delle Scienze Motorie e Sportive, Università degli Studi di Palermo Corresponding author: Stefania Aiello, Dipartimento di Scie…

Antitumoural properties of benzannelated seven-membered 5-fluorouracil derivatives and related open analogues. Molecular markers for apoptosis and cell cycle dysregulation.

Attention is increasingly being focussed on the cell cycle and apoptosis as potential targets for therapeutic intervention in cancer. We prepared a series of bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in addition to six- and 14-membered aminal structures and acyclic compounds. All the cyclic aminals provoked a G0/G1-phase cell cycle arrest, whereas Ftorafur, a known prodrug of 5-FU, and 1-[2-(2-hydroxymethyl-4-nitrophenoxy)-1-methoxyethyl]-5-fluorouracil (11) induced an S-phase cell cycle arrest. Al…

Structural analyses in the study of behavior : From rodents to non-human primates

Ajuts: J-BL's research was funded by Natural Sciences and Engineering Research Council of Canada (NSERC, Discovery Grant #: 2015-06034 to J-BL). MC, SA, and GC's research was funded by a grant from the University of Palermo, Italy. The term " structure " indicates a set of components that, in relation to each other, shape an organic complex. Such a complex takes on essential connotations of functionally unitary entity resulting from the mutual relationships of its constituent elements. In a broader sense, we can use the word " structure " to define the set of relationships among the elements of an emergent system that is not determined by the mere algebraic sum of these elements, but by the…

Impulsivity and physical activity: A T-Pattern detection of motor behavior profiles.

The relation between impulsivity and physical activity has been scantly investigated. Actually, during physical activity, several goals are achieved on the basis of a certain dose of impulsiveness. This study detects motor and interactive behavior profiles from athletes with traits of impulsiveness, moderate impulsiveness and non-impulsiveness, performing open motor tasks concerning material, space and interaction behaviors. A specific test was administered to assess the impulsivity profiles of athletes; then the Observational System of Motor Skills, Space, Time and Interaction (OSMOSTI), was used to observe and detect movement sequences patterns throughout T-Pattern detection and analysis …

Qualitative comparision of olive oil mediterranean

SYNTHESIS AND SAR STUDIES OF NEW 3-METHYL-5-(5-PROPYL-1H-1-R'-3-PYRAZOLYL)-1H-1-R-4-NITROSOPYRAZOLES AS ANTIMICOTIC AGENTS.

4-cyanopirazoles derivatives as a new class of compounds with potent antifungal activity

Introduction We have reported that some 4-nitrosopyrazoles derivatives displayed in vitro and in vivo potent antifungal activity at no cytotoxic concentration and some of these compounds were 4 times more potent than Amphotericine B and Fluconazole respectively against Cryptococcus Neoformans and C. Krusei. We reported also that the absence of NO group or its replacement with NO2 or NH2 groups gave compounds devoid of antimycotical activity. Aim of the work To better understand the mechanism of action and with the aim of identifying the chemical features responsible for the action, we synthesized and tested a new class of compounds in which the 4-NO group was replaced with 4-CN group having…

Studies on the apoptotic activity of natural and synthetic retinoids: discovery of a new class of synthetic terphenyls that potently support cell growth and inhibit apoptosis in neuronal and HL-60 cells.

New terphenyl derivatives have been synthesized and tested for their effect on cell survival in serum-free cultures. These compounds protected HL60 cells from death and supported their growth with an activity higher than that of the natural 14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic activity on neuronal cells, proving them as possible candidates for the treatment of neurodegenerative and ischemic diseases.

Gli effetti dell'Acamprosato sulla rimodulazione della trasmissione glutammatergica eccitatoria ed il suo impiego nel trattamento del craving da alcolismo nel territorio dell'Azienda Sanitaria Provinciale 1 di Agrigento

Treatment with acamprosate is a valid tool to complement psychotherapy as it does not cause addiction, abuse or withdrawal of its suspension and does not interfere with other medications that patients often alcoholics must take. To evaluate the effectiveness, our study evaluated the effects of Acamprosate compared to γ-hydroxybutyrate in clinical-physiological and social health in a way indicator of a possible therapeutic success in terms of abstinence from alcohol and social reintegration. A total of 36 patients were observed, of which 5, 4 men and 1 woman at the Drug Addiction Service (Servizio Tossicodipendenze, Ser.T) Alcamo, and 31, 21 men and 10 women at the Ser.T of Palermo. As regar…

T-pattern detection and analysis for the discovery of hidden features of behaviour

Abstract Background The behaviour of all living beings consists of hidden patterns in time; consequently, its nature and its underlying dynamics are intrinsically difficult to be perceived and detected by the unaided observer. Method Such a scientific challenge calls for improved means of detection, data handling and analysis. By using a powerful and versatile technique known as T-pattern detection and analysis (TPA) it is possible to unveil hidden relationships among the behavioural events in time. Results TPA is demonstrated to be a solid and versatile tool to study the deep structure of behaviour in different experimental contexts, both in human and non human subjects. Conclusion This re…

MONITORING AND USE OF ANTIMYCOTICS FOR SYSTEMIC USE SUPPLIED BY THE STATE HOSPITAL PHARMACY OF MARSALA (TP), ITALY: MYCAMINE® (MICAFUNGIN)

Micafungin is an antimycotic drug and represents an important addition to the available therapies for the treatment of systemic fungal infections. Micafungin is used in the treatment of invasive candidiasis, oesophageal and prophylaxis of Candida infections. It inhibits, in a non-competitive way, the synthesis of 1,3-b-D-glucan, a component of fungal cell wall and is rapidly distributed into the tissues. It has a high-rate bond with respect to plasma protein; the above mentioned bond is independent from the concentration of the drug. It is metabolized through the liver, being not subject to intense metabolic transformations until the excretion. There is no evidence of systemic accumulation …

Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole

New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, none of the new compounds approached 5 in terms of antitumor potency. For 5, binding to the aryl hydrocarbon receptor appeared to be necessary but not sufficient for growth inhibition.

T-patterns in the study of movement and behavioral disorders

Aim of the present review is to offer an outline of the application of T-pattern analysis (TPA) in the study of neurological disorders characterized by anomalies of movement and, more in general, of behavior. TPA is a multivariate technique to detect real time patterns of behavior on the basis of statistically significant constraints among the events in sequence. TPA is particularly suitable to analyse the structure of behavior. The application of TPA to study movement and behavioral disorders is able to offer, with a high level of detail, hidden characteristics of behavior otherwise impossible to detect. For its intrinsic features, TPA is completely different not only from quantitative eva…

The control of abstinence in the treatment of alcohol dependence: the use of acamprosate in relapse prevention

"The alcoholism can also deal with drug treatments." This is the message that emerges from the press conference of presentation of Campral, trade name of acamprosate, a neuromodulator specifically indicated in the maintenance of abstinence in alcohol-dependent patients.Alcoholism is a disease characterized by: craving, loss of control, tolerance and physical dependence.For many years the prevention of relapse in use of alcohol after detoxification was supported almost exclusively by psychosocial procedures and techniques with modest success. Treatment with acamprosate is a valid tool to complement psychotherapy as it does not cause addiction, abuse or withdrawal of its suspension and does n…

Sintesi e studi QSAR di nuovi derivati 3(5)-(2-X)-1R-1H-4-nitrosopirazoli: una classe di composti con potente attività antifungina in vitro.

New more polar symmetrical choline kinase inhibitors II: Study of setting up a new scaffold for the cancer therapy

RELATIONSHIP BETWEEN MAXIMAL FAT OXIDATION AND OXYGEN UPTAKE: COMPARISON BETWEEN PATIENTS WITH TYPE 2 DIABETES AND HEALTHY SEDENTARY SUBJECTS

Purpose Carbohydrate and fatty acids are the dominant fuels oxidized for energy production during exercise. Their contribution is influenced by intensity of exercise, with a progressive increase in the relative contribution of carbohydrate oxidation to energy expenditure, whereas the absolute rate of fat oxidation increases from low to moderate intensities of exercise and declines as exercise becomes more intense. In patients with type 2 diabetes (T2D) the altered metabolism and the lower capacity to sustain efforts changed the choice and regulation of energy substrates for oxidation. Purpose of our study was to assess the relationship between the highest value of fat oxidation rate (FATmax…

3,5-DIIODO-L-THYRONINE-INDUCED MODIFICATION IN PITUITARY-THYROID AXIS IN RATS FED HIGH-FAT DIET. A PRELIMINARY REPORT

Experimental observations highlight that the administration of 3,5-diiodo-L-thyronine (T2) may decrease the body weight and the plasma levels of cholesterol and triglycerides and may prevent the onset of hepatic steatosis in rats fed diets rich in lipids (HFD). On the basis of these findings we have carried out some in vivo studies to evaluate the effects of increased levels of T2 on pituitary thyroid axis function in HFD rats. Fifteeen Wistar male rats were divided in 3 groups. The first group (N) was fed with a standard diet. The second group (G) was fed with a diet high in fat (HDF), while the third group (GT2) was additionally administered intraperitoneally with T2 (70 ug/100g body weig…

Effects of chronic nicotine on the temporal structure of anxiety-related behavior in rats tested in hole-board.

Abstract The present study aimed to assess the behavioral effects of chronic treatments of different doses of nicotine by using both quantitative and multivariate T-pattern analysis (TPA), which can reveal hidden behavioral structures, in Sprague-Dawley rats tested in the hole-board apparatus. To this purpose, nicotine ditartrate was administered at the doses of 0.1, 0.5 and 1 mg/kg i.p., three times per day, for 14 consecutive days. As to quantitative evaluations, we observed significant reductions in the mean durations and mean frequencies of walking, climbing, immobile-sniffing and rearing in comparison to control. A significant reduction of edge-sniff and head-dip mean frequencies was a…

Sinthesys and Antifungal Activity of New 3(5)-methyl-5(3)-(2-thiophenyl and 2-furanyl)-1H-1-R-4-cyanopyrazoles

Synthesis of new 2,2′-disubstituted 5,5′-dimethyl-4,4′-bitriazoles and 2-(4-Triazolyl)quinoxalines

Thermal rearrangement of 3-acylisoxazole arylhydrazones allowed facile preparation of 2H-1,2,3-triazoles which were firstly reacted with isoamyl nitrite and then with an opportune arylhydrazine to produce the corresponding α-hydroxyiminohydrazones 8a-h. The reaction of compounds 8a-h with phosphorus pentachloride afforded the desired 4,4′-bitriazoles 1a-h. The α-hydroxyiminoketone derivative 7 or the α-diketone 14 reacted easily with 1,2-phenylenediamine to afford 1,2,3-triazoles 2a-c bearing the quinoxaline moiety at position 4. Improved yields of the quinoxalines 2a-c were obtained when 1,2-phenylenediamine was reacted with the dioxime 15.

Vitamin D in cancer chemoprevention

Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Results and conclus…

Combining Quantitative and Qualitative Data in the Study of Feeding Behavior in Male Wistar Rats

The first step in a behavioral study is represented by the organization of a suitable ethogram, that is, a formal description of individual components of the behavior. Then, each component of such a behavioral repertoire can be quantified (e.g., how many times it occurs, its duration, percent distribution, latency, etc.). However, it is our contention that the possibility to describe the behavior of a living being by means of hundreds or even thousands of numbers concerning isolated components, disjointed from the comprehensive behavioral architecture, does not imply the possibility to use those numbers to reconstruct the meaning of behavior. Such a level of comprehension requires a qualita…

Substituent effects on the reaction mode between 2-hydroxybenzyl alcohol derivatives and MEM chloride:synthesis and mechanistic aspects of seven-and ten-membered benzo-fused O,O-acetals

Abstract The synthesis of (RS)-2- or (RS)-3-methoxy-2,3-dihydro-5H-1,4-benzodioxepins and (RS)-5- or (RS)-3-methoxy-2,3,5,6-tetrahydro-8H-benzo-[1,4,7]-trioxecins has been developed. The mechanism of such a reaction via the boron trifluoride etherate-promoted transformation of 2-(methoxyethoxymethoxy)benzyloxyacetaldehyde dimethyl acetals or 2-(methoxyethoxymethoxymethyl)phenyloxyacetaldehyde dimethyl acetals has been proposed. Transannular versions of the reaction results in the facile ring contraction of 12-membered intermediates to the 10- and to 7-membered benzene-fused O,O-acetals. The characterization of the by-products strongly supports the mechanisms proposed.

Antitumoural Properties of Benzannelated Seven -Membered 5-fluorouracil Derivatives and Related Open Analogues. Molecular Markers for Apoptosis and Cell Cycle Dysregulation

Attention is increasingly being focussed on the cell cycle and apoptosis as potential targets for therapeutic intervention in cancer. We prepared a series of bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in addition to six- and 14-membered aminal structures and acyclic compounds. All the cyclic aminals provoked a G0/G1-phase cell cycle arrest, whereas Ftorafur, a known prodrug of 5-FU, and 1-[2-(2-hydroxymethyl-4-nitrophenoxy)-1-methoxyethyl]-5-fluorouracil (11) induced an S-phase cell cycle arrest. Al…

4-Nitrosopyrazole Derivatives as a New Class of Compounds with Potent in vitro Antifungal Activity

Synthesis and Antimicrobial Activity of New 1,5-Dimethyl-3-Heteroaryl.1H-4-ONN-Azoxycyanides

Synthesis and antimicrobial activity of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles.

A number of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles 6a-g (7b-f) were synthesized and tested for antibacterial and antifungal activity. Some of these compounds displayed antifungal activity at non-cytotoxic concentrations. Derivative 6c was 9 times more potent in vitro than miconazole and 20 times more selective against C. neoformans. 6c was also 8- and 125-fold more potent than amphotericin B and fluconazole, respectively. None of the compounds was active against bacteria. Preliminary structure-activity relationship (SAR) studies showed that the NO group at position 4 of the pyrazole ring is essential for the activity. Lipophilicity of the pyrazole moiety, N-a…

FLUORINATED 2-PHENYLBENZOXAZOLES AS POTENT AND SELECTIVE ANTITUMOUR AGENTS.

The synergistic apoptotic effects of thiophenfurin, an inosine monophosphate dehydrogenase inhibitor, in combination with retinoids in HL60 cells

New effective cytotoxic agents and combinations are urgently needed in cancer treatment. The enzyme inosine monophosphate dehydrogenase is a potentially useful target for drug development, since its activity has been shown to be amplified in malignant cells. Thiophenfurin, an inhibitor of the enzyme synthesized by us, is endowed with a significant apoptotic activity in promyelocytic leukaemia HL60 cells. Since retinoids were successfully employed in the treatment of patients with leukaemia, demonstrating significant differentiation-inducing and apoptotic effects, we carried out this study to evaluate the effects of the combination of thiophenfurin and several retinoid molecules, acting in d…

GLI EFFETTI DELL’ACAMPROSATO SULLA RIMODULAZIONE DELLA TRASMISSIONE GLUTAMMATERGICA ECCITATORIA ED IL SUO IMPIEGO NEL TRATTAMENTO DEL CRAVING DA ALCOLISMO NEL TERRITORIO DELL’A.S.P. 1 AG

Secondo l’OMS definiamo l’alcolismo quel disturbo a genesi multifattoriale (bio-psico-sociale) associato all’assunzione episodica e/o cronica di bevande alcoliche con presenza o meno di dipendenza capace di determinare una sofferenza multidimensionale che si manifesta in maniera diversa da Soggetto a Soggetto. L’assunzione cronica di alcol modifica la normale attività neuronale attraverso il potenziamento dell’attività inibitoria del GABA e l’inibizione dell’effetto eccitatorio del Glutammato che induce il neuro-adattamento attraverso una over-espressione dei recettori del glutammato in modo da ripristinare l’equilibrio del sistema in presenza di alcol. Quando l’assunzione di alcol viene in…

NEW 5-DIMETHYL-3-HETEROARYL-1H-4-ONN-AZOXYCYANIDES: SYNTHESIS AND ANTIMICOTICAL ACTIVITY.

In the field of infectious diseases, in the last years an increasingly high importance is ascribed to mycosis as causes of illness and mortality in particularly susceptible patients: leukemia, organ transplant, AIDS and immunosuppressed patients, creating clinical and epidemiological problems. Although several drugs are available, antifungal spectrum is still limited especially for invasive infections, which often have fatal results. We previously reported the antifungal activity of a series of products, in which the 1,5-dimethyl-4-(cyano-NNO-azoxy)pyrazol-3-yl and 1,3-dimethyl-4-(cyano-NNO-azoxy)pyrazol-5-yl moieties were linked to pyridine, pyrazole, isoxazole, thiophene and the furan rin…

Exploring the Molecular Basis of Selectivity and Pharmacological Profile of Ligands with Metabotropic Glutamate Receptor

New Medium Oxacyclic O,N-Acetas and Related Open Anologues:Biological Activities

Attention is increasingly being focussed on the cell cycle and apoptosis as potential targets for therapeutic intervention in cancer. Taking 1-[(2-oxepanyl)]-5-fluorouracil previously prepared by us, we committed ourselves to increase the lipophilicity of this upper cyclohomologue of Ftorafur and prepared a series of bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in addition to six- and to 14-membered aminal structures and acyclic compounds. All the cyclic aminals provoked a G(o)/G(1)-phase cell cycle a…

Stilbene-based anticancer agents: Resveratrol analogues active toward HL60 leukemic cells wit a non-specific phase mechanism

Several stilbenes, related to known resveratrol, have been synthesized and tested for their anticancer effect on HL60 leukemia cell line, taking particular care of the cell cycle analysis. The most potent compound was the known (Z)-3,4',5-trimethoxystilbene (6b) which was active as apoptotic agent at 0.24 microM. Differently from other stilbenes (including resveratrol) that induced a prevalent recruitment of cells in S phase of cell cycle, we found a peculiar behavior of 6b that caused a decrease of cells in all phases of cell cycle (G0-G1, S, and G2-M) and a proportional increase of apoptotic cells. The potent pro-apoptotic activity shown by compound 6b and its effects on cell cycle make t…

The impact of chronic daily nicotine exposure and its overnight withdrawal on the structure of anxiety-related behaviors in rats: Role of the lateral habenula.

Tobacco smoking is a serious health problem worldwide and a leading cause of mortality. Nicotine, the addictive component of tobacco, affects a range of emotional responses, including anxiety-related behaviors. Although perceived by smokers to be anxiolytic, evidence suggests that smoking increases anxiety and that mood fluctuates with nicotine intake. Thus, nicotine addiction may depend on easing the psychobiological distress caused by its abuse. The lateral habenula (LHb) has been implicated as a neural substrate for acute nicotine-induced anxiety, but its role in anxiety-like behaviors associated with chronic nicotine exposure has not been explored. Here, we assessed the effect of chroni…

Different Representation Procedures Originated from Multivariate Temporal Pattern Analysis of the Behavioral Response to Pain in Wistar Rats Tested in a Hot-Plate under Morphine

Temporal pattern analysis is an advanced multivariate technique able to investigate the structure of behavior by unveiling the existence of statistically significant constraints among the interval length separating events in sequence. If on the one hand, such an approach allows investigating the behavioral response to pain in its most intimate and inner features, on the other hand, due to the meaning of the studies on pain, it is of relevant importance that the results utilize intuitive and easily comprehensible ways of representation. The aim of this paper is to show various procedures useful to represent the results originating from the multivariate T-pattern analysis of the behavioral re…

Synthesis and in vitro antimicrobial activities of new (cyano-NNO-azoxy) pyrazole derivatives

The antibacterial and antifungal activity of a series of products, in which the 1,5-dimethyl-4-(cyano- NNO-azoxy)pyrazol-3-yl and 1,3-dimethyl-4-(cyano-NNO-azoxy)pyrazol-5-yl moieties were linked to pyridine, pyrazole, isoxazole, thiophene and the furan ring, were examined. No molecule displayed activity against the Gram-negative bacteria tested. Conversely, some compounds displayed activity against two Staphylococcus aureus strains, including the methicillin resistant strain. All compounds displayed interesting antifungal activity, the most active compound of the series being the thiophene derivative 7a. This compound’s activity against Candida krusei and Candida glabrata (MIC = 0.25 and 0…

Meccanismi immunologici e molecolari del danno epatico da farmaci

I polimorfismi genetici e/o i fattori ambientali, ad esempio l’alcol e/o i farmaci concomitanti, contribuiscono alla suscettibilità individuale nel determinare il danno epatico da farmaci. L’HLA si è dimostrato essere uno dei più importanti predittore di suscettibilità individuale anche per quei farmaci per i quali questa non era stata mai sospettata.

Synthesis and Biological Properties of Benzothiazole, Benzoxazole, and Chromen-4-one Analogues of the Potent Antitumor Agent 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610, NSC 721648)

New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, none of the new compounds approached 5 in terms of antitumor potency. For 5, binding to the aryl hydrocarbon receptor appeared to be necessary but not sufficient for growth inhibition.

Effects of 3,5-diiodo-L-thyronine on the liver of high fat diet fed rats

Experimental studies have highlighted that the administration of 3,5-diiodo-L-thyronine (T2) to rats fed diets rich in lipids induces a decrease of cholesterol and triglycerides plasma levels and body weight (BW) without inducing liver steatosis. On the basis of these observations we carried out some experimental <em>in vivo</em> studies to assess the effects of multiple high doses of T2 on the pituitary thyroid axis of rats fed diet rich in lipids. Fifteen male Wistar rats were divided into three groups of five animals each. The first group (N group) received standard diet, the second group was fed with a high fat diet (HFD group), while the third group (HFDT2 group) was additi…