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The interplay of soft responsive particles, such as microgels, with nanoparticles (NPs) yields highly versatile complexes that show great potential for applications, ranging from plasmonic sensing to catalysis and drug delivery. However, the microgel–NP assembly process has not been investigated so far at the microscopic level, thus hindering the possibility of designing such hybrid systems a priori. In this work, we combine state-of-the-art numerical simulations with experiments to elucidate the fundamental mechanisms taking place when microgel–NP assembly is controlled by electrostatic interactions and the associated effects on the structure of the resulting complexes. We find a general behavior where, by increasing the number of interacting NPs, the microgel deswells up to a minimum size after which a plateau behavior occurs. This occurs either when NPs are mainly adsorbed to the microgel corona via the folding of the more external chains or when NPs penetrate inside the microgel, thereby inducing a collective reorganization of the polymer network. By varying microgel properties, such as fraction of cross-linkers or charge, as well as NP size and charge, we further show that the microgel deswelling curves can be rescaled onto a single master curve, for both experiments and simulations, demonstrating that the process is entirely controlled by the charge of the whole microgel–NP complex. Our results thus have a direct relevance in fundamental materials science and offer novel tools to tailor the nanofabrication of hybrid devices of technological interest.

Purpose: To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. Methods: Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007–2020) were retrospective evaluated. Results: The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor’s surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. Conclusion: This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed “one-size-fits-all model” is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.

Background: In our previous work, spiroxatrine was taken as reference compound to develop selective NOP ligands. Therefore, several triazaspirodecanone derivatives were synthesized. Here, we verify their selectivity towards other 5-HT1receptor subtypes and with respect to α2-AR (Adrenergic Receptors). Methods: Binding affinities were determined on cells expressing human cloned receptors for 5-HT1A/B/Dand α2A/B/Csubtypes. The Ki values were determined for those with at least 50% radioligand inhibition. Results: All our derivatives show a moderate affinity for α2subtypes, spanning from 5 to 7.5 pKivalues. Moreover, they show affinity values in a μM–nM range at the 5-HT1Areceptor, while they are practically inactive at 5-HT1Band 5-HT1Dsubtypes. Compound 11, the best of the series, has a 5-HT1ApKivalue of 8.43 similar to spiroxatrine but, notably, it has a 5-HT1Afavorable selectivity ratio of 52, 8 and 29, respectively over α2A, α2Band α2Cadrenoceptor subtypes. Conclusions: In this SAR study, a 5-HT1Aselective ligand has been identified in which a tetralone moiety replaced the 1,4-benzodioxane of spiroxatrine and the methylene linker to the triazaspirodecanone portion was maintained in position 2. Graphic abstract:

The aim of this study was to report the respiratory management of a cohort of infants admitted to a Pediatric Intensive Care Unit (PICU) over a 7-year period due to severe burn injury and the potential benefits of noninvasive ventilation (NIV). A retrospective review of all pediatric patients admitted to PICU between 2009 and 2016 was conducted. From 2009 to 2016, 118 infants and children with burn injury were admitted to our institution (median age 16 months [IQR = 12.2–20]); 51.7% of them had face burns, 37.3% underwent tracheal intubation, and 30.5% had a PICU stay greater than 7 days. Ventilated patients had a longer PICU stay (13 days [IQR = 8–26] vs 4.5 days [IQR = 2–13]). Both ventilation requirement and TBSA% correlated with PICU stay (r= .955, p< .0001 and r= .335, p= .002, respectively), while ventilation was best related in those >1 week (r= .964, p< .0001 for ventilation, and r= -.079, p= .680, for TBSA%). NIV was introduced in 10 patients, with the aim of shorten the invasive ventilation requirement. As evidenced in our work, mechanical ventilation is frequently needed in burned children admitted to PICU and it is one of the main factors influencing PICU length of stay. No difference was found in terms of PICU length of stay and invasive mechanical ventilation time between children who underwent NIV and children who did not, despite children who underwent NIV had a larger burn surface. NIV can possibly shorten the total invasive ventilation time and related complications.

Phase change contrast agents for ultrasound (US) imaging consist of nanodroplets (NDs) with a perfluorocarbon (PFC) liquid core stabilized with a lipid or a polymer shell. Liquid ↔ gas transition, occurring in the core, can be triggered by US to produce acoustically active microbubbles (MBs) in a process named acoustic droplet vaporization (ADV). MB shells containing polymerized diacetylene moiety were considered as a good trade off between the lipid MBs, showing optimal attenuation, and the polymeric ones, displaying enhanced stability. This work reports on novel perfluoropentane and perfluorobutane NDs stabilized with a monolayer of an amphiphilic fatty acid, i.e. 10,12-pentacosadiynoic acid (PCDA), cured with ultraviolet (UV) irradiation. The photopolymerization of the diacetylene groups, evidenced by the appearance of a blue color due to the conjugation of ene-yne sequences, exhibits a chromatic transition from the nonfluorescent blue color to a fluorescent red color when the NDs are heated or the pH of the suspension is basic. An estimate of the molecular weights reached by the polymerized PCDA in the shell, poly(PCDA), has been obtained using gel permeation chromatography and MALDI-TOF mass spectrometry. The poly(PCDA)/PFC NDs show good biocompatibility with fibroblast cells. ADV efficiency and acoustic properties before and after the transition were tested using a 1 MHz probe, revealing a resonance frequency between 1 and 2 MHz similar to other lipidic MBs. The surface of PCDA shelled NDs can be easily modified without influencing the stability and the acoustic performances of droplets. As a proof of concept we report on the conjugation of cyclic RGD and PEG chains of the particles to support targeting ability toward endothelial cells.

Propranolol is a popular β adrenergic antagonists that, together with pindolol, binds also to serotoninergic receptors, namely 5-HT1A/B. In this work the rigidification of the propranolol structure by locking its hydroxyl group within a 1,3-dioxolane ring was investigated. Constrained derivatives of propranolol were synthesized, fully characterized and tested for their affinity at β-adrenoreceptors and 5-HT1A/B/Creceptors using radioligand binding assay. The constrained derivatives were inactive, as expected, at β1/2/3adrenergic receptors. Although less expected, these derivatives failed to bind also to 5-HT1A/B/Creceptors. The rigidification of propranolol is detrimental for 5-HT1AR activity.

Oxidative stress and inflammation play a role in the physiopathology of insulin resistance, diabetes and cardiovascular disease. A single high-fat, high-carbohydrate (HFHC) meal induces an increase in inflammatory and oxidative stress markers in peripheral blood mononuclear cells (PBMC). Previous studies have shown that orange juice is able to prevent this response by inhibiting toll like receptors (TLR) expression and endotoxemia. Our goal was to study the proteome response in PBMC after the consumption of a HFHC meal consumed with water, orange juice or an isocaloric beverage (water with glucose). Twelve healthy individuals completed the protocol in a crossover design, and blood samples were obtained before and 1, 3, and 5 h after consumption. Proteomic profile, glucose, insulin, lipid and cytokines levels were investigated. The glycemic and insulinemic response was higher when the meal was consumed with glucose, while there was no difference in the response between water and orange juice. Proteome analysis in PBMC was carried out using TMT ten-plex. A total of 3813 proteins, originating from 15 662 peptides were identified. Three proteins showed significantly altered expression in the three treatments: apolipoprotein A-II, ceruloplasmin and hemopexin. When the HFHC meal was consumed with water there was an increase in some inflammatory pathways such as the Fc-gamma receptor dependent phagocytosis and the complement cascade, but the immune system as a whole was not significantly altered. However, when the meal was consumed with glucose, the immune system was up regulated. Among the pathways induced after 3 h were those of the adaptive immune system and cytokine signaling. Five hours after the meal, pathways of the complement cascade and classical antibody mediated complement activation were up regulated. When the meal was consumed with orange juice there was an up regulation of proteins involved in signal transduction, DNA replication and cell cycle. The promyelocytic leukemia protein (PML) showed a 28.2-fold increase. This protein was down regulated when the meal was consumed with water. Regarding the immune system, several of the pathways induced by glucose were down regulated when the meal was consumed with orange juice: proteins involved with the adaptive immune system and cytokine signaling. Therefore, we have shown that orange juice can not only suppress diet induced inflammation, but also regulate the expression of proteins such as PML, which may play a key role in the regulation of metabolism.

We have investigated the effect of intake of two different orange juices from Citrus sinensiscv. “Cara Cara” and cv. “Bahia” on faecal microbiota and metabolome using an integrated meta-omics approach. Following a randomized crossover design, healthy subjects daily consumed 500 mL of orange juice from Cara Cara or Bahia juices or an isocaloric control drink. Stools were collected at baseline (T0) and after a week (T7) of intervention. Operational taxonomic units (OTUs) were pyrosequenced targeting 16S rRNA, and faecal metabolites were analyzed by an untargeted metabolomics approach based on 1H NMR spectroscopy. The major shift observed in microbiota composition after orange juice intake was the increased abundance of a network of Clostridia OTUs from Mogibacteriaceae, Tissierellaceae, Veillonellaceae, Odoribacteraceae, and Ruminococcaceae families, whose members were differently affected by Cara Cara or Bahia juice consumption. A core of six metabolites such as inositol, choline, lysine, arginine, urocanic acid, and formate significantly increased in Cara Cara compared to the Bahia group.

GM1 ganglioside is known to be involved in the amyloid-associated diseases and it is a crucial factor for the assembly of amyloid proteins on lipid-rafts, which are lipid structures located on the synaptic plasma membranes. Due to its slow aggregation rate, we employed salmon calcitonin (sCT) as a suitable probe representative of amyloid proteins, to study the interaction between this class of proteins and a membrane model. Here, we prepared a neuronal membrane model by depositing onto mica two Langmuir-Blodgett films in liquid-condensed phase: the outer monolayer was characterized by high content of GM1 (50%) and minority parts of cholesterol and POPC (25–25%), while the inner one by plain POPC. To deeply investigate the interaction of sCT with this model and the role-played by GM1, we prepared the outer leaflet adding sCT at a concentration such that the number of proteins equals that of GM1. Atomic Force Microscopy revealed the occurrence of two distinct kinds of flat surfaces, with globular aggregates localized exclusively on top of the highest one. To unravel the nature of the interaction, we studied by ζ-potential technique liposomes composed as the outer leaflet of the model. Results demonstrated that an electrostatic interaction sCT-GM1 occurred. Finally, to investigate the interaction thermodynamics between sCT and the outer leaflet, Langmuir films as the outer monolayer and containing increasing content of sCT were studied by compression isotherms and Brewster Angle Microscopy experiments. Based on the all body of results we propose an interaction model where GM1 plays a pivotal role.

We have recently reported a novel class of selective 5-HT1A agonists among which GF449 emerged for its high potency and almost full agonist activity (pKi 5-HT1A = 8.8; pD2 = 9.22, %Emax = 91.6). In order to quantify GF449 in rat plasma and brain, a sensitive LC-MS/MS method was developed and validated. Solid phase extraction (SPE) or a combined protein precipitation SPE permitted an efficient analyte recovery and sample clean-up. Multiple reaction monitoring (MRM) was used to track both GF449 and its internal standard (IS), MM189. GF449 was determined and quantitated to nanomolar concentrations in both plasma and brain matrix (LOQs = 0.0025 nmol/mL). Specificity was ensured using three further MRM qualifier transitions for both analyte and IS. Linearity was found in the range of 0.0025 nmol/mL to 1.00 nmol/mL (R2 = 0.9965) and from 0.0025 nmol/mL to 50 nmol/mL (R2 = 0.9999) for plasma and brain respectively. Intraday trueness ranged from 94.0% to 117.5% for brain and from 93.7% to 108.1% for plasma, while precision values were within 3.0% - 6.7% and 2.5% - 9.2% for plasma and brain respectively. The interday trueness of plasma ranged from 89.6% to 107.7% and the precision values (CV%) ranged from 4.6% to 7.5%. Interday trueness and precision (CV%) of the brain ranged from 94.3% to 101.2% and from 1.6% to 11.5% respectively. The method was validated in accordance with the EMEA guidelines and was successfully applied to plasma and brain samples obtained from rats treated with a 10 mg/kg single oral dose of GF449, thus demonstrating its applicability to preclinical pharmacokinetic studies.

The prevalence of weight disorders among school-aged children is an increasing phenomenon and it is of great importance to identify the characteristics of individuals at risk of gaining or retaining weight. This study aimed to examine the prevalence of weight disorders and their tracking over a 3-year period in a sample of Italian children. Body mass, body height and selected skinfold thicknesses were assessed in 355 children at the age of 7 and 10 years. Tracking of body mass index (BMI), inverted BMI (iBMI) and skinfold-based body fat were analyzed and the relationships between changes in BMI and body fat were examined. Children presenting with overweight or obesity at 7 years old showed a trend toward lower weight categories at 10 years old. Conversely, a trend to become overweight was observed among normal weight boys, and a trend to become underweight was observed among normal weight girls. BMI, iBMI and body fat showed good levels of tracking, with high correlations between measurements performed at 7 and 10 years of age. Furthermore, BMI and iBMI changes were correlated to body fatness changes. The present study shows the importance of carefully following children’s development over time because weight disorders may appear even in previously normal weight children.

A series of 1,3-oxathiolane-based nucleoside analogs 5-methyl substituted was synthesized and tested as potential antiviral agents. Structural characterization and C2-C4 / C2-C5 relative stereochemistry assignments were performed by NMR experiments. All tested isomers were found to be inactive and cytotoxic.

A stopped‐flow bidimensional recycle HPLC (sf‐BD‐rHPLC) configuration has been used to investigate simultaneously the stereo and chemical stability of labile chiral compounds. The single enantiomers of a racemate can be separated on chiral column (first dimension) and each one can be trapped in the achiral column (second dimension) that works as reactor.By filling the achiral column with the appropriate aqueous buffers it is possible to evaluate the stability of the trapped enantiomer toward aqueous buffer itself. It was possible to recycle the reaction products formed in the chiral column (first dimension) where they are separated by a second six valve port. The reaction rate constants were calculated for the different processes occurred in the achiral column by means of corresponding peak areas. The method was applied to a pharmacological active compound: (±)7‐chloro‐5‐ethyl‐3‐methyl‐3,4‐dihydro‐2H‐benzo[1,2,4]thiadiazine 1,1‐dioxide ((±)‐1) to evaluate enantiostability and hydrolysis in conditions similar to those of biological fluid. A classical batchwise kinetic method was used to calculate rate constants of hydrolysis and enantiomerization at the same temperature and in the same solvents used in sf‐BD‐rHPLC. The good agreement of the results obtained validate the novel procedure developed. Furthermore, the results generated off‐line were used to determine the influence of solvents on the racemization of (±)‐1. Chirality, 2011. © 2011 Wiley‐Liss, Inc.

In the attempt to define more accurately structure−affinity relationships for σ1 and σ2 ligands, we synthesized and tested on σ subtype receptors a series of aralkyl derivatives of 4-benzylpiperidine, in which the effect of modifications on the aralkyl moiety was studied in a systematic way. The affinity of the compounds here described varied to a great extent, with a σ2/σ1 selectivity ranging from 0.1 to 9. Thus, to confirm the ability of the piperazine derivative to bind to σ1 receptors in a different way than piperidines, we synthesized and tested a series of piperazine compounds; the comparison of their affinity with that of the corresponding piperidines strongly supports the possibility of a different binding mode. While the compounds here described are on the whole selective for σ vs serotonin 5-HT1A and dopamine D2 receptors, 9aa, 9ba and 9ab possess a remarkable affinity for both σ and 5-HT1A receptors, with Ki in the nanomolar range, and are selective with respect to D2 receptors. They displayed also a partial agonist profile in a human 5-HT1A [³⁵S]GTPγS binding assay, suggesting their potential use as atypical antipsychotic agents.

The α- and β-methyl derivatives of 2-phenylethylimidazoline (compounds 7 and 8) and the corresponding enantiomers were prepared and tested with the purpose of studying the role played by the ethylene bridge in modulating I1- and I2-IBS selectivity. The α-methylation appeared to be extremely critical regarding the affinity and selectivity for the I1-IBS subtypes (I1/I2 = 186 for imidazoline 7) and the stereospecificity of interaction (eudismic ratio (S)-(−)-7/(R)-(+)-7 = 5888). Instead, even if in a more limited fashion, the β-methylation tended toward I2-IBS selectivity (I2/I1 = 50 for imidazoline 8). The unsubstituted compound 4 (I2/I1 = 1479) proved to be considerably more potent and selective with respect to I2-IBS subtypes.

1,3-Dioxolane-based compounds (2−14) were synthesized, and the pharmacological profiles at α1-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Compound 9, with a pA2 of 7.53, 7.36, and 8.65 at α1A, α1B, and α1D, respectively, is the most potent antagonist of the series, while compound 10 with a pA2 of 8.37 at α1D subtype and selectivity ratios of 162 (α1D/α1A) and 324 (α1D/α1B) is the most selective. Binding assays in CHO cell membranes expressing human cloned α1-adrenoceptor subtypes confirm the pharmacological profiles derived from functional experiments, although the selectivity values are somewhat lower. Therefore, it is concluded that 1,3-dioxolane-based ligands are a new class of α1-adrenoceptor antagonists.

We describe a rare congenital malformation of the spine known as ‘butterfly’ vertebra, which is classified as a congenital developmental anomaly in the early embryonic period, resulting in a sagittally cleft vertebral body. In our case, the anomaly affects an adult female and involves the fifth lumbar vertebra and first sacral vertebra; it is not associated with other anomalies of the spine. Copyright © 2002 John Wiley & Sons, Ltd.

We describe a rare congenital malformation of the spine known as ‘butterfly’ vertebra, which is classified as a congenital developmental anomaly in the early embryonic period, resulting in a sagittally cleft vertebral body. In our case, the anomaly affects an adult female and involves the fifth lumbar vertebra and first sacral vertebra; it is not associated with other anomalies of the spine. Copyright © 2002 John Wiley & Sons, Ltd.

A number of derivatives structurally related to cirazoline (1) were synthesized and studied with the purpose of modulating α2-adrenoreceptors selectivity versus both α1-adrenoreceptors and I2 imidazoline binding sites. The most potent α2-agonist was 2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole (7), whose key pharmacophoric features closely matched those found in the α2-agonist 2-(3-exo-(3-phenylprop-1-yl)-2-exo-norbornyl)amino-2-oxazoline (15).³⁰ (S)-(−)-7 was the most potent of the two enantiomers, confirming the stereospecificity of the interaction with α2-adrenoreceptors. This eutomer was tested on two algesiometric paradigms and, because of the interaction with α2-adrenoreceptors, showed a potent and long-lasting antinociceptive activity, since it was abolished by the selective α2-antagonist RX821002.

Abstract: The aim of this paper is to propose a theoretical “multi-phase” strategy for analysing in dynamic terms the territorial impact of agricultural and environmental EU policy measures. This approach should also allow to evaluate the adjustment capability of farms as a function of the characteristics of different territories. The proposed methodology is illustrated by an example using data relative to the 41 provinces of Northern Italy. In the first step, a multivariate statistical analysis (MSA) consisting in Principal Component Analysis and Cluster Analysis leads to the identification of homogeneous clusters of territorial units. The territorial mapping is conditional to a predetermined set of indicators that takes into account different aspects of agricultural development. In a second step, Positive Mathematical Programming (PMP) allows to introduce the impact of agricultural policies (compensatory payments, price changes, etc.) returning different scenarios of land use and agricultural profitability. According to the outputs of the PMP, the third step consists in a new MSA for detecting any changes in the territorial mapping. Convergence analysis can then synthesise the impact of the different policy options.

Abstract: The aim of this paper is to propose a theoretical “multi-phase” strategy for analysing in dynamic terms the territorial impact of agricultural and environmental EU policy measures. This approach should also allow to evaluate the adjustment capability of farms as a function of the characteristics of different territories. The proposed methodology is illustrated by an example using data relative to the 41 provinces of Northern Italy. In the first step, a multivariate statistical analysis (MSA) consisting in Principal Component Analysis and Cluster Analysis leads to the identification of homogeneous clusters of territorial units. The territorial mapping is conditional to a predetermined set of indicators that takes into account different aspects of agricultural development. In a second step, Positive Mathematical Programming (PMP) allows to introduce the impact of agricultural policies (compensatory payments, price changes, etc.) returning different scenarios of land use and agricultural profitability. According to the outputs of the PMP, the third step consists in a new MSA for detecting any changes in the territorial mapping. Convergence analysis can then synthesise the impact of the different policy options.

Methylation of the carbon atom C1 of compound 1, a potent and not selective muscarinic antagonist, was carried out. The resulting diastereomers were separated and the corresponding racemate further resolved to give four enantiomers, which were tested both as hydrogen oxalate and methiodide salts. The pharmacological results obtained at M1, M2and M3muscarinic receptor subtypes, show that methylation at C1, depending on the stereochemistry, increases antagonist potency, having thus the same effect of nitrogen quaternization. These results may well lead to the development of new potent antimuscarinic drugs lacking a cationic head.

Clonidine and benazoline are two structurally related imidazolines. Whereas clonidine binds both to α2-adrenoceptors (α2R) and to I1imidazoline receptors (I1R), benazoline showed a high selectivity for imidazoline receptors. Although the α2R are negatively coupled to adenylate cyclase, no effect on cAMP level by activation of I1R has been reported so far. We therefore aimed to compare the effects of clonidine and benazoline on forskolin-stimulated cAMP levels in cell lines expressing either I1R only (PC12 cells), α2R only (HT29 cells), or I1R and α2R together (NG10815 cells). Clonidine proved able to decrease the forskolin-stimulated cAMP level in the cells expressing α2R and this effect could be blocked by rauwolscine. In contrast, in cells lacking these adrenoceptors, clonidine had no effect. On the other hand, benazoline and other I1receptor-selective imidazolines decreased forskolin-stimulated cAMP level in the cells expressing I1R, in a rauwolscine- and pertussis toxin-insensitive manner. These effects were antagonized by clonidine. According to these results, we demonstrated that 1) α2R and I1R are definitely different entities because they are expressed independently in different cell lines; 2) α2R and I1R are both implicated in the cAMP pathway in cells (one is sensitive to pertussis toxin and the other is not); and 3) I1R might be coupled to more then one transduction pathway. These new data will be essential to further understand the physiological implications of the I1R and the functional interactions between I1receptors and α2-adrenoceptors.

Clonidine and benazoline are two structurally related imidazolines. Whereas clonidine binds both to alpha(2)-adrenoceptors (alpha(2)R) and to I(1) imidazoline receptors (I(1)R), benazoline showed a high selectivity for imidazoline receptors. Although the alpha(2)R are negatively coupled to adenylate cyclase, no effect on cAMP level by activation of I(1)R has been reported so far. We therefore aimed to compare the effects of clonidine and benazoline on forskolin-stimulated cAMP levels in cell lines expressing either I(1)R only (PC12 cells), alpha(2)R only (HT29 cells), or I(1)R and alpha(2)R together (NG10815 cells). Clonidine proved able to decrease the forskolin-stimulated cAMP level in the cells expressing alpha(2)R and this effect could be blocked by rauwolscine. In contrast, in cells lacking these adrenoceptors, clonidine had no effect. On the other hand, benazoline and other I(1) receptor-selective imidazolines decreased forskolin-stimulated cAMP level in the cells expressing I(1)R, in a rauwolscine- and pertussis toxin-insensitive manner. These effects were antagonized by clonidine. According to these results, we demonstrated that 1) alpha(2)R and I(1)R are definitely different entities because they are expressed independently in different cell lines; 2) alpha(2)R and I(1)R are both implicated in the cAMP pathway in cells (one is sensitive to pertussis toxin and the other is not); and 3) I(1)R might be coupled to more then one transduction pathway. These new data will be essential to further understand the physiological implications of the I(1)R and the functional interactions between I(1) receptors and alpha(2)-adrenoceptors.

Several analogues of cirazoline (2Chart 1), a selective α1-adrenoreceptor agonist, were prepared and their pharmacological profiles studied. Although at the α1-adrenoreceptor all the compounds displayed a significant agonist activity, at the α2-adrenoreceptor they showed either agonist or antagonist activity depending on the nature of the phenyl substituent. The qualitative structure–activity relationship led us to the conclusion that the oxygen atom in the side-chain is essential for α1-agonist activity, while the cyclopropyl ring is not, and may be replaced by several groups. Of the groups studied, isopropoxy appears to be the best. Instead, the same substitution (i.e., isopropoxy for the cyclopropyl ring) at α2-adrenoreceptors causes a reversal of activity. On the other hand, the cyclopropyl ring seems to be important for α1-selectivity. Compound 20is the most potent α1-agonist of the series, being equiactive with cirazoline on rat vas deferens and in pithed rat.

The purpose of the present study was to analyse the replicability of the scoring of discontinuous traits. This was assessed on a sample of 100 skulls from the Frassetto collection (Dipartimento di Biologia Evoluzionistica Sperimentale of Bologna University) analysed through intraobserver comparisons: the discontinuous traits were determined on the same skulls and by the same observer on 3 separate occasions. The scoring was also assessed through interobserver comparisons: 3 different observers performed an independent survey on the same skulls. The results show that there were no significant differences in the discontinuous trait frequencies between the 3 different scorings by the same observer, but there were sometimes significant differences between different observers. Caution should thus be taken in applying the frequencies of these traits to population research. After an indispensable control of material conditions (subject age included), consideration must be given to standardisation procedures between observers, otherwise this may be an additional source of variability in cranial discontinuous trait scoring.

The aims of the present study were: (1) to supply further knowledge about variations in nonmetric cranial traits in relation to sex, age and laterality and (2) to evaluate biological distance between samples from a recent population. The incidence of 18 nonmetric variants of the cranium were determined in 3 adult samples of 394 skulls of known sex from North Sardinia (Sassari, Alghero and Ozieri); for the Sassari sample (n = 200) age at death was also known. Some significant sex differences were observed. Age did not appear to influence the frequency of the discontinuous traits but did for legibility. Side differences may provide important information about environmental influences. The interpopulation analysis indicates a stronger relationship between samples that are geographically closer (Sassari and Alghero), in accordance with other studies, strengthening the hypothesis of the validity of the use of nonmetric traits in the study of the peopling of a territory.

Analysis of digital and palmar dermatoglyphics in an Italian mountain population was carried out. Dermatoglyphic variability was particularly investigated in samples from four different valleys. Microgeographical differences in qualitative and quantitative traits among valleys were found. The relationship between degree of endogamy and dermatoglyphic differences is discussed. The biological repercussion of isolation in the history of this Apennine population is also pointed out by means of comparisons with a nearby plains population characterized by low inbreeding.

A series of 2- trans -styryl-imidazoline ( tracizoline ) congeners were designed and tested to develop 2-D and 3-D QSAR models for their binding to imidazoline (I 2 ) receptor. The important role of lipophilicity was assessed by classical 2-D QSAR study (Hansch approach) and by comparative molecular field analysis (CoMFA) with the inclusion of the molecular lipophilicity potential (MLP), as an additional descriptor, besides standard steric and electrostatic fields. Results from these studies were compared to those obtained in a previous modeling study of I 2 receptor ligands and integrated into a new, comprehensive model, based on about sixty I 2 receptor ligands. This model revealed, at the three-dimensional level, the most significant steric, electrostatic, and lipophilic interactions accounting for high I 2 receptor affinity.

The Fourier transform Raman vibrational spectra of five ancient molar teeth (burial periods ranging from 150 to about 6000 years ago) were analysed in comparison with a modern deciduous canine of an infant. The observed Raman bands were assigned to inorganic (carbonato-apatite) and organic (proteinaceous) components. The spectroscopic measurements show that only in the case of enamel (external surface) do the bands due to the organic component decrease in intensity in relation to the duration of burial, while the intensities of the bands due to the inorganic component remain constant in all the samples, ancient and modern. The I2941/I960 intensity ratio of the stretching mode νsCH2 of the organic component and ν1(PO4)^3- of the inorganic component was chosen as a spectroscopic parameter to be correlated with the burial period of the teeth. A gradual decrease in the curve of I2941/I960 vs. tooth age was observed in the case of enamel but not for the dentine; this feature is related to the peculiar structure of the enamel. © 1997 by John Wiley & Sons, Ltd.

An der eisenzeitlichen Bevölkerung von Monte Bibele (Bologna, Italien) wird der Gesundheitszustand untersucht. Am häufigsten ist die Wirbelsäule von krankhaften Veränderungen betroffen: Gespaltener Atlas, Spina bifida des Sacrums, Sacralisation des 5. Lumbarwirbels, Arthrose. Auch im Hüft-, Ellbogen-, Schulter- und Kniebereich konnte Arthrose beobachtet werden. Brüche sind nicht selten. Ebenso konnten Periostitis and Osteoporose sowie ein vermutlicher Fall von Akromegalie beobachtet werden. Die Mehrzahl der in der Bevölkerung von Monte Bibele vorhandenen pathologischen Veränderungen dürften auf Alterungsprozesse oder auf Belastung durch körperliche Arbeit zurückzuführen sein.