Evolutionary adaptations in four hippoboscid fly species belonging to three different subfamilies.

Lipoptena cervi (Linnaeus, 1758), Lipoptena fortisetosa Maa, 1965, Hippobosca equina Linnaeus, 1758, and Pseudolynchia canariensis (Macquart, 1840) (Diptera: Hippoboscidae) are haematophagous ectoparasites that infest different mammal and bird species and occasionally attack humans. They are known for the health implications they have as vectors of pathogens to humans and animals, and for the injuries they inflict on their host's skin. This study focused on the morphological structures evolved by parasites in terms of their biology and the different environment types that they inhabit. To this aim, we examined four hippoboscid species, as well as their hosts' fur (ungulate and horse), and feather (pigeon) through light and Scanning Electron Microscopy (SEM) observations in order to highlight the main morphological features that evolved differently in these flies and to explain the effect of hosts' fur/feather microhabitats on the morphological specializations observed in the investigated ectoparasites. The studied species showed main convergent characters in mouthparts while remarkable differences have been detected on the antennal sensillar pattern as well as on the leg acropod that displayed divergent characters evolved in relation to the host.

Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting.

INTRODUCTION: Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified. METHODS: An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. RESULTS: Chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC = 0.92 p < 0.0001). CONCLUSIONS: Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome.

Comparative morphology of the deer ked Lipoptena fortisetosa first recorded from Italy.

Hippoboscidae flies parasitize various animal species. Knowledge about these insects remains sparse, although they are known to cause stress and damage to their hosts, and can also accidentally infest humans, causing different sanitary risks. Research conducted in Tuscany assessing the biology and distribution of Lipoptena cervi (Linnaeus, 1758) (Diptera: Hippoboscidae), the most common ectoparasite of ungulates in Italy, revealed the presence of Lipoptena fortisetosa Maa, 1965 in Italy for the first time. This study includes a morphological comparative description of L. cervi and L. fortisetosa, emphasizing the peculiar differences between the two species to facilitate their accurate identification. The most pertinent morphological differences between the two species are highlighted, such as the external features of the antennae, distribution of bristles, and different features in the external genitalia. In both species, scanning electron microscopy of mouthparts revealed strong adaptive convergence in the feeding apparatus. Modified palps and a very thin proboscis are described in relation to feeding behaviour.

Relationship between Methacholine Challenge Testing and exhaled nitric oxide in adult patients with suspected bronchial asthma.

Usually, hyperresponsiveness to inhaled methacholine is considered closely associated with a diagnosis of bronchial asthma. Recently, it has been clearly pointed out that bronchial hyperreactivity (BHR) is not a constant feature of asthma and that this condition is not always related to airways inflammation. In the present study we evaluated 42 Patients (21 positive and 21 negative for bronchial hyperreactivity, BHR) with the aim to determine the effect of Methacholine Challenge Testing (MCT) on the levels of exhaled nitric oxide (NO). Higher FeNO levels were found before methacholine provocation in the group that eventually resulted positive to the challenge, while after the challenge in both groups FeNO decreased in similar way, with no statistical difference. These data confirm that MCT is a relevant test for asthma diagnosis, but it is not always related to the severity of bronchial inflammation, while FeNO levels in our study have limited clinical significance when evaluated out of asthma exacerbation.

Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.

The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.

Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles.

A number of selected imidazo[2,1-b]thiazoles entered the screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) and one of these compounds, 2-chloro-6-phenylimidazo[2,1-b]thiazole, showed antitubercular activity. On this basis we planned the synthesis of new analogues bearing a substituted ring at the 6 position. For one compound only (2-chloro-6-p-chlorophenylimidazo[2,1-b]thiazole) the 5-nitroso derivative was also prepared. The antitubercular activity of these compounds was compared with the known analogues lacking the chlorine at the 2 position. 5-Nitroso-6-p-chlorophenylimidazo[2,1-b]thiazole showed potent antitubercular activity.

Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones.

The synthesis of 3-(5-imidazo]2,1-blthiazolylmethylene)-2-indolinones, analogs of compounds recently published, is described. The EIZ isomerism was studied by means of nuclear Overhauser effect experiments and X-ray crystallography. All the compounds were tested as potential antitumor agents. They were also tested as potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine if the antitumor activity was related to this mechanism of action. The results showed that under certain substitution conditions (5-methoxy group for the indole benzene ring and 2-methyl group for the imidazothiazole system), an interesting antitumor activity was found for some compounds. From the analysis of the antitumor data, 3-1(2,6-dimethylimidazo[2,1-bJ-thiazol-5-yl)methylenel-5-methoxy-2-indolinone was the most active of the whole series.

Potential antitumor agents. Part 29(1): synthesis and potential coanthracyclinic activity of imidazo[2,1-b]thiazole guanylhydrazones.

This paper reports the synthesis of new imidazo[2,1-b]thiazole guanylhydrazones which were tested as potential antitumor agents. Three of these derivatives (those bearing a 3- or 4-nitrophenyl group) were the most potent and one of these showed a mild effect as CDK1 inhibitor. These same three derivatives were also tested as positive inotropic agents and two of them were more potent than amrinone at 10(-5) M. These two guanylhydrazones could be useful coanthracyclinic agents.

Synthesis and antisecretory activity of 6-substituted 5-cyanomethylimidazo[2,1-b]thiazoles and 2,6-dimethyl-5-hydroxymethylimidazo[2,1-b][1,3,4]thiadiazole.

The synthesis of imidazo[2,1-b]thiazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, related to known antiulcer agents, is reported. 5-Cyanomethyl-6-methylimidazo[2,1-b]thiazole showed significant antisecretory activity in the isolated rabbit gastric glands assay.

4-Aminopyridine derivatives with antiamnesic activity.

Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.

Imidazo[2,1 -b]thiazolylmethylene- and indolylmethylene-2-indolinones: a new class of cyclin-dependent kinase inhibitors. Design, synthesis, and CDK1/cyclin B inhibition.

Compounds containing a 2-indolinone moiety linked to imidazothiazole and indole fragments were studied as cyclin-dependent kinase inhibitors. The activity of all the new derivatives was tested in vitro against CDK1/cyclinB and the selectivity towards two other kinases was determined for the most promising compounds. The binding mode of one representative compound was investigated by means of a three-dimensional model of the inhibitor-CDK1 complex. The work allowed us to identify (2-chloroindolyl)methylene-2-indolinone as a new lead of a class of CDK1/cyclinB inhibitors, whose potency can be improved by the introduction of suitable variations on the basic molecular skeleton.

Potential coanthracyclinic activity of pyridylmethylene-2-indolinones.

The paper reports the cytotoxic activity of pyridylmethylene-2-indolinones previously described as cardiotonics and the synthesis of three analogs of the most potent cytotoxic agent. Some of these compounds could be useful, when associated with anthracyclines, to reduce the cardiotoxicity of these potent antitumor drugs.

In vivo cardiotonic activity of pyridylmethylene-2-indolinones.

The synthesis of 5-chloro-3-pyridylmethylene-2-indolinone is reported. This compound was subjected to an in vivo cardiotonic assay with 10 analogs whose synthesis and in vitro cardiotonic activity were previously reported. All the compounds tested (except the 5-hydroxyindole derivative) showed significant positive inotropic activity. The 3-pyridyl derivative without substituents at the indole system was the most active of the whole series.

In vivo cardiotonic activity of aryl- and pyridyl-substituted fused imidazoles.

Two new imidazo[2,1-b]thiazoles related to sulmazole were synthesized and subjected to an in vivo cardiotonic assay with 14 analog compounds which gave the best results in previously reported in vitro tests. The data obtained show that three substituents (3-pyridyl, 4-pyridyl and 2,5-dimethoxyphenyl group) are useful pharmacophoric groups in modulating the in vivo cardiotonic activity of the fused imidazoles considered.

Potential antitumor agents. 25 [1]. Synthesis and cytotoxic activity of 3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones.

The Knoevenagel reaction between 2-indolinones and 2-chloroindolaldehydes gave 3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones which were tested as potential antitumor agents on cultures of HeLa cells. 2-Chloro derivatives with at least one unsubstituted NH group, are promising candidates for further investigation.

Antitumor activity of an alkylating derivative of dipyridamole.

Synthesis of 2,6-Bis[bis(2-chloroethyl)amino]-4,8-dipiperidino-pyrimido [5,4-d]pyrimidine (DIP-C1) was carried out, and the new derivative showed cytotoxic activity comparable to other alkylating drugs on cultured P388 leukaemia cells and HeLa cells. The present paper reports the effects of DIP-C1 on respiration of Ehrlich ascites tumor cells and on survival of the mice implanted with Ehrlich ascites tumor cells. The compound showed a significant activity in both experimental models.

Potential antitumor agents. 24. Synthesis and pharmacological behavior of imidazo[2,1-b]thiazole guanylhydrazones bearing at least one chlorine.

In connection with a previous research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other hand, the most active cardiotonic agents were devoid of the phenyl ring.

Synthesis and fungicide activity of 2,3-dihydroimidazo [2,1-b]thiazole-5-carboxamides.

The synthesis and characterization of carboxamides prepared from 6-substituted 1,1-dioxo-2,3-dihydroimidazo[2,1-b]thiazole-5-carboxylic acids is reported. The results from a fungicide test showed that the two most active amides are those arising from 2-aminopyridine.

Thienylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase.

The synthesis of 6-substituted 5-(thienylvinyl)imidazo[2,1-b]thiazoles and 6-thienylimidazo[2,1-b]thiazoles is reported. These compounds were tested as specific inhibitors of the NADH: ubiquinone (UBQ) reductase activity of NADH dehydrogenase in mitochondrial membranes. The 6-thienylimidazo[2,1-b]thiazoles were more potent in mammalian than in nematode mitochondria and had an average titer of 0.11 mM for 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole (10). This compound is noncompetitive with the ubiquinone substrate and interacts with a site which is mutually exclusive with that of rotenone but nonexclusive with that of piericidin and several other inhibitors of NADH dehydrogenase. In the series of 5-(thienylvinyl)imidazothiazoles, the hydrobromide of (E)-6-chloro-5-(2-thienylvinyl)imidazo[2,1-b]thiazole (E-5.HBr) was found to be more potent as an inhibitor of the NADH:UBQ activity (IC50 = 15-17 microM) than the 6-thienylimidazoles such as 10. The inhibitory action of E-5.HBr and its analogs is different from that of compound 10 as indicated by the mutual exclusivity with other inhibitors and the relative inhibition of the activity with various electron acceptors.