Showing papers by "Marche Polytechnic University published in 1998"

EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex.

Abstract: High-affinity uptake of glutamate from the synaptic cleft plays a crucial role in regulating neuronal activity in physiological and pathological conditions. We have used affinity-purified specific polyclonal antibodies raised against a synthetic peptide corresponding to the C-terminal region of rabbit and rat EAAC1, a glutamate (Glu) transporter believed to be exclusively neuronal, to investigate its cellular and subcellular localization and whether it is expressed exclusively in glutamatergic cells of infragranular layers, as suggested by previous studies. Light microscopic studies revealed that EAAC1 immunoreactivity (ir) is localized to neurons and punctate elements in the neuropil. EAAC1-positive neurons were more numerous in layers II-III and V-VI, i.e. throughout all projection layers. Most EAAC1-positive neurons were pyramidal, although nonpyramidal cells were also observed. Some EAAC1-positive non-pyramidal neurons stained positively with an antiserum to GAD, thus demonstrating that EAAC1 is not confined to glutamatergic neurons. Non-neuronal EAAC1-positive cells were also observed in the white matter, and some of them stained positively with an antiserum to GFAP. Ultrastructural studies showed that EAAC1-ir was in neuronal cell bodies, dendrites and dendritic spines, but not in axon terminals, i.e. exclusively postsynaptic. Analysis of the type of axon terminals synapsing on EAAC1-ir profiles showed that 97% of them formed asymmetric contacts, thus indicating that EAAC1 is located at the very sites of excitatory amino acid release. Unexpectedly, EAAC1-ir was also found in a few astrocytic processes located in both the gray and the white matter. The localization of EAAC1 may explain the pathological symptoms that follow EAAC knockout (seizures and mild toxicity), as seizures could be due to the loss of EAAC1-mediated fine regulation of neuronal excitability at axodendritic and axospinous synapses, whereas the mild toxicity may be related to the functional inactivation of astrocytic EAAC1.

Synthetic full-length and truncated RANTES inhibit HIV-1 infection of primary macrophages.

Abstract: Objective: To evaluate the role of the selective forces exerted by the host on the HIV-1 structures involved in viral entry. Design and methods: The V3 region of the env gene was analysed in cell-free HIV-1 RNA from 17 infected subjects: 11 long-term non-progressors (LTNP) and six symptomless, typical progressor patients. To evaluate the potential biological significance of one of the rare variants detected in the LTNP, it was reproduced by recombinant PCR into a HIV-1 molecular clone. Results: The intrapatient divergence of the V3-loop sequences averaged 8.62% in LTNP and 5.29% in progressors, although LTNP displayed lower divergence from the clade B consensus than progressors (16.65 and 19.76%, respectively). The analysis of non-synonymous and synonymous substitutions indicated that selective pressure was exerted in this region in both LTNP and progressors. Individual peculiarities (unique and rare V3-loop variants) emerged, however, in most sequences from LTNP, and variants bearing mutations in a domain crucial for the V3-loop structure were more prevalent in LTNP (P = 0.0012). The pNL4-3-derived mutant reproducing a V3-loop variant detected in a LTNP was efficiently expressed upon transfection, but the mutant virus was nearly completely unable to infect CD4+ cell lines, activated primary peripheral blood lymphocytes, or monocyte-derived macrophages, suggesting that a defect impaired the entry phase of the replication cycle. Conclusions: The results indicate that host factors impose selective constraints on the evolution of the HIV-1 structures involved in viral entry. In LTNP, these factors are likely to force the virus into attenuated variants.

The natriuretic peptide system in obesity-related hypertension: new pathophysiological aspects.

Abstract: The association between obesity and hypertension is well known but the pathophysiology of weight-related changes on blood pressure is still a matter of debate. Although obesity-related hypertension is considered to be sodium-sensitive, little attention has been given to a possible pathophysiological role of Atrial Natriuretic Peptides (ANP) and their receptors (NPr) system. Since the early phase of weight loss induced by very-low-calorie diet or fasting is followed by a significant increase in diuresis and natriuresis together with an increase in circulating ANP, we focused our attention on the possible role of adipose tissue in mediating these changes. We first demonstrated that human and rat adipose tissue contain high levels of mRNA specific for both type A (NPr-A), which is biologically active, and type C (NPr-C) which is biologically inactive, receptors. We then demonstrated in the rat that fasting exerts a tissue-specific and gene-specific suppression of NPr-C gene expression in adipose tissue that appears to be accompanied by an increased biological activity of ANP. These experimental observations were confirmed in man studying gene expression of NPr-A and NPr-C in adipose tissue obtained through subcutaneous peri-umbilical needle aspiration in obese and non-obese hypertensive patients. We found that NPr-A: NPr-C mRNA ratio was significantly lower in obese hypertensive patients as compared with non-obese hypertensives. These findings suggest that overxpression of the clearance receptor in the obese may trap more molecules of circulating ANP so reducing their biological activity at renal level. More recent results were obtained in obese hypertensive patients in whom the intravenous bolus injection of ANP (0.6 mg/kg body weight) was performed before and after four days of very-low-calorie diet which induced a weight loss accompanied by a significant reduction of BP and an increase in the urinary excretion of cGMP. The infusion of ANP after low-calorie diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis and natriuresis significantly increased only after caloric restriction and the effects of ANP infusion on BP were more pronounced. Taken together our studies suggest that the abundance of NPr-C in adipose tissue may play a significant role in explaining at least part of the sodium retention characteristic of obesity associated hypertension.

CD38 Functions Are Regulated Through an Internalization Step

Abstract: The endocytosis of the human CD38 molecule has been investigated in normal lymphocytes and in a number of leukemia- and lymphoma-derived cell lines. CD38 internalization was followed using radioiodinated Abs in an acidic elution endocytosis assay to monitor the effects of cross-linking on internalization processes and to quantify the ratio of the internalized molecule. Second, conventional, confocal, and electron microscopies were used to evaluate the morphologic effects induced by ligation of the molecule with Abs mimicking the natural ligand(s). The results demonstrated that internalization is a reproducible phenomenon following CD38 ligation with both agonistic and nonagonistic specific Abs and involving only a fraction of the entire amount of the surface molecule. It is independent from signal transduction as can be inferred by the observation that 1) both agonistic and non agonistic Abs are effective and 2) the dynamic of internalization is much slower than that of cellular signaling. Morphologic studies demonstrated that endocytosis induced as a result of CD38 ligation presents a very specific pathway consisting of subcellular organelles fundamental to the processing of the complex. Our data indicate that down-regulation by endocytosis may be, in parallel with shedding, a regulatory element in activation and adhesion processes mediated by CD38. However, internalization seems not to be a key step in triggering intracellular signaling; more likely, it is a negative feedback control mechanism which interrupts signal transduction or cell-cell cross-talks mediated by membrane CD38.

Factors affecting hemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: A single center experience

Abstract: BACKGROUND AND OBJECTIVE: While the minimum number of CD34+ cells required for complete and long-lasting engraftment is quite well established, there is not general agreement about the optimal number of CD34+ per kg needed in order to obtain engraftment as rapidly as possible. In the present study we assess factors affecting hemopoietic recovery and the optimal peripheral blood progenitor cell (PBPC) number for rapid engraftment in patients treated with high-dose therapy. DESIGN AND METHODS: We enrolled 80 consecutive patients affected by hematologic and non-hematologic malignancies treated with a median of 10 chemotherapy courses (range 3-38). PBPC collection was performed after mobilization with high-dose chemotherapy and G-CSF 5 micrograms/kg/day. The circulating and harvested CD34+ cells were recognized in the cytofluorimetric CD45+/CD14- lymphocyte gate. After myeloablative therapy, PBPC infusion was followed by G-CSF 5 micrograms/kg/day from day +5 until WBC > or = 5.0 x 10(9)/L. Univariate and multivariate Cox analyses were performed to investigate factors affecting hemopoietic recovery. The Kaplan-Meier probabilities of hemopoietic reconstitution were compared by log-rank test to assess the optimal CD34+ cell number for rapid engraftment. RESULTS: We performed a median of two apheresis (range 1-4) per patient and we infused a median of 6.1 x 10(6) CD34+ cells/kg (range 0.5-30.5). Absolute neutrophil count (ANC) > 0.5 x 10(9)/L was reached after 11 days (range 8-15). The only factor affecting granulocyte recovery proved to be the CD34+ cell number; 5.0 to 7.8 x 10(6) CD34+ cells/kg allowed a significantly faster granulocyte recovery than 20 x 10(9)/L) and 50 x 10(9)/L platelets were reached after 12 (range 8-24) and 15 days (range 9-40), respectively. The CD34+ cell number was also the only factor affecting platelet recovery; the number of 5.0 to 7.8 CD34+ cells/kg allowed a significantly faster platelet recovery than the lower dose, whereas a higher number did not. No late graft failures were observed. Patients receiving 5.0 to 7.8 x 10(9) CD34+ cells/kg had a significantly shorter duration of neutropenia, fewer platelet transfusions and less time spent in hospital than those receiving lower number did, whereas patients transplanted with a higher number had no advantage. INTERPRETATION AND CONCLUSIONS: When G-CSF is employed both for PBPC mobilization and after PBPC transplantation, the CD34+ cell number is the only factor that affects hemopoietic recovery. Moreover, > 5.0 x 10(6) CD34+ cells/kg is the optimal number for obtaining rapid platelet recovery and reducing the costs of HDT but there is no advantage exceeding the threshold of 7.8 x 10(6) CD34+ cells/kg.

Mitogen-activated protein kinases and apoptosis in PIN

Abstract: Mitogen-activated protein (MAP) kinases are key elements of the signalling systems needed to transduce different extracellular messages into cellular responses. At least three parallel MAP kinase pathways have been identified: one, stimulated by serum and growth factors to activate extracellular signal-regulated protein kinases (ERKs) by dual tyrosine and threonine phosphorylation, triggers cell proliferation or differentiation; the other two, induced by a variety of cellular stresses to activate c-jun N-terminal kinases (JNKs) and reactivating kinase (p38/RK), result in growth arrest and induction of apoptosis. Mitogen-activated protein kinase phosphatases (MKPs) inactivate MAP kinases through dephosphorylation and, thus, can modulate the MAP kinase pathways. Expression of JNK-1, ERK-1, p38/RK and MKP-1 proteins was investigated by immunohistochemistry and expression of MKP-1 mRNA by in situ hybridisation in 50 cases of high-grade prostatic intraepithelial neoplasia (PIN), thought to represent the precursor of prostate cancer. The frequency of apoptotic cells was also determined in these cases. Overexpression of the three MAP kinases and MKP-1 mRNA was found in all cases of high-grade PIN compared with normal prostate. Immunoreactivity for MKP-1 protein was found to be as intense as in normal glands in 30% and weaker in 56% of the PIN cases. Fourteen per cent of PIN cases did not stain with MKP-1 antibody. The proportion of apoptosis was significantly higher (P < 0.008) in PIN lesions that did not express MKP-1 protein than in those that did. These results are consistent with our previous demonstration of preferential inhibition of the apoptosis-related kinases by MKP-1 and further support the contention that MKP-1, even in PIN, may shift the balance existing between cell proliferation and death. When expressed, it may inhibiting those pathways that lead to apoptosis.

Controlling Nonlinear Dynamics in a Two-Well Impact System.

Abstract: To exploit all potentialities of the optimal control procedure, the analysis initiated in Part I focuses on the system response under one-side control, an excitation which furnishes high gain though, roughly, controlling only one part of the phase space. Many bifurcational and control items related to the unsymmetric and pulsed nature of the excitation are deeply investigated. A nonclassical kind of homoclinic bifurcation is identified and it is discussed how it may lead to major regularity. The system response is very rich, and the main local and global phenomena of the dynamics are analyzed in detail through combined use of bifurcation diagrams and attractor-basin phase portraits. Both the confinement of steady dynamics in the controlled potential well and their successive transition from confined to scattered are studied, and it is discussed how they are obtained through comparison with the case of harmonic excitation. It is shown that the two investigated optimal excitations permit to increase the amplitude level for confined to scattered dynamics and to regularize the steady dynamics, although in a different manner. The analysis shows the effectiveness — in "average" sense — of the proposed method for controlling nonlinear dynamics.

Reproducibility and Clinical Value of the Trough-to-Peak Ratio of the Antihypertensive Effect: Evidence From the Sample Study

Abstract: The objectives of our study were to assess the reproducibility of the trough-to-peak ratio (T/P) and to see whether a high T/P is accompanied by more organ protection or vice versa. The study included 175 (mean+/-SD age, 51+/-9 years) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular (LV) hypertrophy taken from the SAMPLE study (Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation), an open-label multicenter study. The study included a 3-week washout pretreatment period, a 12-month treatment period with lisinopril (n=84) or lisinopril plus hydrochlorothiazide (n=91) once daily, and a 4-week placebo follow-up period. Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index (LVMI) were obtained before and after 3 and 12 months of treatment. T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough (changes in the last 2 hours of the monitoring period) by those at peak (average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake) after 3 and 12 months of treatment. Average 24-hour blood pressure was similarly reduced at 3 and 12 months. Trough blood pressure changes at 3 and 12 months were closely correlated, as were the corresponding peak blood pressure changes. However, the 3- and 12-month T/Ps correlated to a lesser degree (r /=0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment.

Clinical implications of HIV dynamics and drug resistance in macrophages.

Abstract: Macrophages are widely recognized as the second major target of HIV in the body. The cellular characteristics of such resting cells markedly affect the dynamics of virus lifecycle, that is slower but far more prolonged that in lymphocytes. In addition, the limited concentrations of endogenous nucleotide pools in macrophages downregulate the enzymatic activity of reverse transcriptase. As a consequence, both the anti-HIV activity and the development of resistance to antiviral drugs in macrophages are substantially different than those found in activated lymphocytes. These peculiar characteristics of virus replication and efficacy of antiviral drugs in macrophages have a natural in vivo counterpart in extralymphoid tissues, where macrophages account for the majority of cells infected by HIV. Furthermore, the replication of HIV in macrophages of testis and central nervous system is far less affected by antiviral drugs than in lymph nodes, because of the presence of natural barriers that markedly diminish the concentration of such drugs. For all these reasons, HIV infection of macrophages should be taken into account in therapeutic strategies aimed to achieve an optimal therapeutic effect in all tissue compartments where the virus hides and replicates.

Localized amyloidosis and gastrointestinal lymphoma: a rare association.

Abstract: Aims: Five cases of primary gastrointestinal (GI) lymphoma (three in the stomach, one in the ileum (IPSID) and one in the colon) associated with localized AL amyloidosis were studied to identify morphological or immunohistochemical features which could explain the amyloid deposition. Methods and results: All the cases were low-grade marginal zone B-cell lymphomas; one case of gastric lymphoma and the IPSID also had a high-grade component. The lymphomas had a monoclonal plasma cell population, with different light and heavy-chain type expression in the five cases. Plasma cell differentiation was closely associated with the amyloid deposits. The latter were an incidental microscopic finding in one case, but produced tumoral masses in the others. Conclusions: The presence of amyloid in primary GI lymphoma is rare, but can have diagnostic value. In the present study, neither particular features of the lymphomatous proliferation nor specific agents are identified. Therefore, the factors predisposing to amyloid deposition require elucidation.

Posterior spinal artery infarct

Abstract: Acute medullary syndrome developed in a patient in whom glue had been inadvertently injected into the right posterior radiculomedullary artery during endovascular occlusion of a spinal dural arteriovenous fistula at T-11. MR imaging 40 days after the procedure showed signal changes and contrast enhancement in the posterior and right lateral column at T10-11. Circumscribed signal changes in the same areas without contrast enhancement were seen 4 months later. MR imaging was able to show this posterior spinal artery infarct.

Apoptosis in Prostatic Adenocarcinoma following Complete Androgen Ablation

Abstract: Objective: To analyze the cell death phenomenon in prostate cancer following complete androgen ablation. Methods: The frequency and location of apoptotic bodies (

Epidemiology and Treatment of Otitis Media with Effusion in Children in the First Year of Primary School

Abstract: In this multicentre study we evaluated the prevalence and risk factors of otitis media with effusion (OME) in Italian school-children and the effectiveness of medical treatment of chronic OME with a new cephalosporin, ceftibuten. During two winter periods, 3413 children, aged 5 to 7 years, were examined for the presence of OME by means of pneumotoscopy and a portable, hand-held tympanometer. The prevalence of asymptomatic OME was 14.2%, with no difference as regards sex, age, month of examination or geographic area. Younger children had significantly more bilateral than unilateral effusion. A recent episode of acute otitis media and previous tonsillectomy or adenoidectomy were associated with an increased risk of OME in multivariate logistic regression models. The presence of OME was unrelated to such factors as birthweight, prematurity, sibling or parental history of allergy, duration of daycare attendance, family history of ear infections. After 12 weeks, 26.6% of children with OME still had middle-ear ...

Early increase of CD4+ CD45RA+ and CD4+ CD95- cells with conserved repertoire induced by anti-retroviral therapy in HIV-infected patients.

Abstract: Administration of anti-retroviral drugs induces a decrease of viral load associated with increase of CD4+ cell count in most HIV-infected patients. To investigate the early changes in CD4+ cell phenotype induced by anti-retroviral therapy, six patients with CD4+ cell count > 100/mm3 and never treated with anti-HIV therapy were enrolled and blood samples collected several times within 14 days from the initiation of therapy with Zidovudine plus Didanosine. CD4+ cell count and HIV viraemia were investigated at each time point, as well as the expression of CD45RA, CD45RO and CD95/Fas molecules on CD4+ cells, and the T cell receptor (TCR) Vbeta repertoire of CD4+ cells. All patients showed a rapid and dramatic decrease in viral load with a corresponding increase of CD4+ cell count. The main remodelling of CD4+ cell subpopulations took place in the first 14 days of therapy, and consisted of: (i) increased CD4+CD45RA+/CD4+CD45RO+ ratio; (ii) decrease of CD95/Fas expression. The rise in absolute number of CD4+CD45RA+ cells was paralleled by an increase of CD4+CD95/Fas- cells and accounted for most of the early increment of CD4+ cell count. The TCR Vbeta repertoire of CD4+ cells was conserved after anti-HIV therapy, with the exception of two patients with expanded CD4+Vbeta12+ cells, which also tested CD45RA+ and CD95/Fas-. These experiments show that newcomer CD4+ lymphocytes are CD45RA+CD95/Fas- cells, suggesting that blocking HIV replication causes an early and antigen-independent proliferation of possibly 'naive' cells unprimed for CD95/Fas-mediated apoptosis. These cells expressed a conserved and widespread TCR repertoire, suggesting that their capability for antigenic recognition is intact.

Elevata frequenza della infezione da virus dell'epatite C nei pazienti con linfoma non-Hodgkin all'esordio. Risultati preliminari di uno studio multicentrico italiano.

Abstract: 143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

Evaluation of mean right atrial pressure by two-dimensional and Doppler echocardiography in patients with cardiac disease.

Abstract: Background Several approaches have been used for noninvasive estimation of right atrial pressure (RAP), but, no currently available method has gained any definite validation. The purpose of this study was to evaluate the accuracy of two-dimensional and Doppler echocardiography in estimating mean RAP in patients with cardiac disease. Methods We examined the relation of mean RAP to right atrial size and function, size and respiratory changes of inferior vena cava and Doppler parameters of tricuspid and hepatic vein flow in 114 consecutive patients (77 men, 37 women; mean age 57 +/- 12 years) with various cardiac diseases undergoing cardiac catheterization. Echocardiographic studies were performed within 24 hours before catheterization (mean interval 6 +/- 3 hours). Patients were assigned to 3 groups according to the values of mean RAP (group 1, 12 mmHg). Results Mean RAP ranged from 3 to 20 mmHg (mean 9.1 +/- 4.3 mmHg). It correlated most strongly with the collapsibility index of inferior vena cava (IVCCI) (r = -0.76), minimal inspiratory diameter of inferior vena cava (r = 0.72) and deceleration time of early tricuspid flow (DT) (r = -0.61). Discriminant analysis demonstrated that IVCCI and DT were major determinants of mean RAP with 81.6% of cases correctly assigned to study groups: 96% of patients of group 1 and 87% of patients of group 3 were identified, whereas the accuracy in identifying the patients of group 2 was lower (46%). An IVCCI > 45% was the best cutoff point in predicting a mean RAP or = 15 mmHg. The best multivariate equation predicting mean RAP was: mean RAP = 23.3 - 0.2 IVCCI -0.026 DT (r = 0.80, R2 = 0.64). This equation was 81% sensitive and 84% specific in detecting a mean RAP 12 mmHg. Conclusions Mean RAP can be estimated noninvasively by two-dimensional and Doppler echocardiography. The combined analysis of IVCCI and DT provides an accurate prediction on mean RAP 12 mmHg, whereas the prediction of intermediate values is less accurate.

Two dosage interferon-alpha 2b maintenance therapy in patients affected by low-risk multiple myeloma in plateau phase: a randomized trial

Abstract: BACKGROUND AND OBJECTIVE: The role of interferon (IFN) in the remission phase of multiple myeloma (MM) is still an open question, particularly for its scheduling and the subset of patients who could benefit from this approach. The present randomized multicenter study was designed to compare two schedules of IFN maintenance therapy in order to assess the difference in effectiveness and tolerance. DESIGN AND METHODS: This prospective randomized multicenter study was attempted to assess the best schedule of IFN administration in the maintenance treatment of MM in plateau phase with regard to progression free survival (PFS) and toxicity. The second aim was defining the difference between the two schedules in overall survival (OS) and identifying the critical dose of IFN therapy needed to prolong plateau phase and survival. We enrolled 52 patients affected with low-risk MM (i.e. with serum beta 2-microglobulin 3.0 g/dL); 27 patients (group A) were randomly assigned to receive IFN alpha-2b 3 megaunits (MU) subcutaneously three times a week and 25 patients (group B) 3 MU/day until disease progression. RESULTS: Median progression free survival (PFS) was 11.9 months in group A and 38.3 months in group B (p = 0.0038). Median survival was 63.2 months in group A and 61.9 months in group B (p = 0.489). However, those patients who were given an IFN dose > or = 30 MU/month experienced a significantly longer PFS and survival than the other patients. Seventeen patients (32.7%) discontinued therapy and sixteen patients (30.8%) reduced IFN alpha-2b dose because of severe side effects without having a significant difference between the two schedules. INTERPRETATION AND CONCLUSIONS: Our results show that patients treated with IFN alpha 3 MU/day had a significantly longer remission duration than patients treated with IFN alpha 3 MU three times weekly. Moreover, an IFN dose is probably critical for obtaining a longer survival in patients affected with low-risk MM. Since the patients' discomfort during a IFN maintenance therapy was frequently experienced the quality of their lives should be carefully taken into account.

Nitrenium ions. Part 4.1 Reactivity and crystal structure of 1-methyl-2-phenyl-3-N-benzoyloxyindole iminium perchlorate and reactivity of N,N-dimethylamino-p-N-benzoyloxyaniline nitrenium chloride with 2-phenylindole

Abstract: 1-Methyl-2-phenyl-3-nitrosoindole and N,N-dimethyl-p-nitrosoaniline react with benzoyl chloride to form salts behaving like iminium and nitrenium ions respectively. The structure of the ion formed in the case of the nitrosoindole was elucidated by X-ray analysis. The charge density distribution of both ions was calculated on the basis of the structure parameters and by AM1 calculations and their reactivity was interpreted on the basis of structural parameters and the calculated distribution of their positive charge.

Central Bank Reputation and Conservativeness

Abstract: In a monetary game played by the private sector and a central bank (CB), who has private information, reputation may not completely solve the CB time inconsistency problem. An alternative solution is CB conservativeness. The optimal degree of CB conservativeness is solved in both the reputational and non-reputational regime, and reputation is proved to be a substitute for conservativeness. Unless reputation works perfectly, the public can always gain from a conservative CB. Our model offers a unified framework to analyze both CB reputation and conservativeness. Our result can explain why low-reputation CBs find it worthwhile to peg the exchange rate to the currency of a high-reputation CB and why a highly reputable CB, like the Bundesbank, can afford to miss monetary targets more often than a less reputable CB.

Prospects for cutaneous wound healing in ageing skin. a working hypotesis : chitosan and ceramides

Abstract: In elderly people the cutis is characterised by structural fragility due to causes ranging from the thinning of the lipid-epithelial stratum to reduced derma! vascularisation, in particular, reduction in the content of all lipids due mainly to sphingolipids and ceramides, especially at the leve! of the stratum comeum and in the extracellular matrix because of greater degradation and reduced synthesis. We set out to investigate the functional implications of a molecular association of lipopolysaccarides applied to elderly people wound healing with a veiw to re-estabilishing the cutaneous microenvironment which in these subjects is unbalanced and at risk. Water-soluble chitosans in the class of N-carboxyalkyl chitosans possess antimicrobial activity including candidacidal activity, and regenerated chitins and watersoluble chitosans are being used as wound dressings which facilitate the formation of new, ordered tissue. Basecl on these observations, the combined action of ceramides and chitosan appears to meet the requirements of the elderly, and may constitute in vivo a natural association capable of improving the cutaneous microenvironment.

Central Banking as a Political Principal-Agent Problem

Abstract: Due to their ties with elected leaders, central bankers may pursue policies that are not in society's best interests. Consequently, the relationship between the public and the central bank can be characterized as a principal-agent problem. An inflation and a stabilization bias arise as a result of this agency problem and the magnitudes of these biases depend on the political environment. Various institutional proposals for eliminating these biases are examined, and we find that central bank independence and performance contracts work best. However, we argue that central bank independence is preferable for resolving the agency problem.