On the Formation of Interstellar CH- Anions: Exploring Mechanism and Rates for CH2 Reacting with H.

We present accurate ab initio calculations on the structural properties of a gas-phase reaction of possible interest for Saturn's outer atmosphere chemistry, in which the CH2 molecule has been detected. In the present study, that molecule is made to react with the H- anion to form the CH- species, one considered as a possible intermediate in ionic processes networks. The results indicate that this reaction is markedly exothermic and proceeds with the formation of an intermediate, which occurs via only a shallow barrier below the reagents and progresses directly to the product region. The corresponding rate coefficients of reactions are also computed by making use of the variational transition state theory modeling and found to efficiently lead to the formation of the final anion even at the lower temperatures of interstellar medium conditions.

Modeling Ionic Reactions at Interstellar Temperatures: The Case of NH2- + H2 ⇔ NH3 + H.

Structural features and enthalpy details are presented for the title reactions, both for the exothermic (forward) path to NH3 formation and for the endothermic (reverse) reaction to NH2- formation. Both pathways have relevance for the nitrogen chemistry in the interstellar medium (ISM). They are also helpful to document the possible role of H- in molecular clouds at temperatures well below room temperature. The structural calculations are carried out using different ab initio methods and are further employed to obtain the reaction rates down to the interstellar temperatures detected in earlier experiments. The reaction rates are obtained from the computed minimum energy path (MEP) using the variational transition-state theory (VTST) approach. The results indicate very good accord with experiment results at room temperature, while measured low temperature data down to 8 K are well described using an appropriately modified VTST approach. This is done by employing a temperature-dependent scaling, from room temperature conditions down to the lower ISM temperatures, which acknowledges the noncanonical behavior of the fast, barrierless exothermic reaction. The reasons for this behavior and the need for improving on the VTST method when used away from room temperatures are discussed.

Formation of cyanopolyyne anions in the interstellar medium: the possible role of permanent dipoles.

The possibility of attaching near-threshold electrons to N-terminated carbon chains, like those observed in the outer envelopes of carbon-rich stars, is examined via accurate quantum chemistry orbital structures evaluation and quantum scattering analysis of the corresponding extra-electron wavefunctions at meV energies. It is shown that the differences in the signs and sizes of the permanent dipole moments which exist for both the neutral and anionic species of the C(n)N series of molecules play a significant role in suggesting or excluding possible energy paths to permanent anion formations of cyanopolyynes, for which the cases with n from 1 to 7 are examined in more detail.

Calculation of electron interaction models in N2 and O2.

Cosmic rays have the potential to significantly affect the atmospheric composition by increasing the rate and changing the types of chemical reactions through ion production. The amount and states of ionization, and the spatial distribution of ions produced are still open questions for atmospheric models. To precisely estimate these quantities, it is necessary to simulate particle-molecule interactions, down to very low energies. Models enabling such simulations require interaction probabilities over a broad energy range and for all energetically allowed scattering processes. In this paper, we focus on electron interaction with the two most abundant molecules in the atmosphere, i.e., N2 and O2, as an initial step. A set of elastic and inelastic cross section models for electron transportation in oxygen and nitrogen molecules valid in the energy range 10 eV - 1 MeV, is presented. Comparison is made with available theoretical and experimental data and a reasonable good agreement is observed. Stopping power is calculated and compared with published data to assess the general consistency and reliability of our results. Good overall agreement is observed, with relative differences lower than 6% with the ESTAR database.

A study of selected fragmentation paths of the ethyne dication: theory and experiment.

The fragmentation of the C(2)H(2)(2+) dication, formed upon inner shell ionization and the subsequent Auger decay, has been studied by means of Auger electron-ion and Auger electron-ion-ion coincidence spectroscopy at four different kinetic energies of the Auger electron. The experimental investigation of three fragmentation paths leading to the C(2)H(+)/H(+), C(2)(+)/H(+) and C(+)/H(+) pairs has been complemented by theoretical calculations of the Potential Energy Surfaces (PES). It is found that when the amount of internal energy of the dication increases this is mainly transferred into the kinetic energy of the fragments of the second step of the dissociation.

Enantioselective HF loss promoted by resonant two-photon ionization of supersonically expanded (R)-1-phenyl-2,2,2-trifluoroethanol clusters.

(R)-1-phenyl-2,2,2-trifluoroethanol and its hydrogen bonded adducts with achiral (water, tetrahydrofuran) and chiral solvent molecules ((R)- and (S)-butan-2-ol, (R)- and (S)-3-hydroxy-tetrahydrofuran) have been ionized by resonant two-photon absorption. The presence of photofragments, attributable to the occurrence of a hydrogen fluoride loss reaction, has been interpreted with the aid of theoretical predictions at the DFT level of theory with the inclusion of dispersive terms. The HF elimination process takes place by a mechanism involving the preliminary C(alpha)-H hydrogen transfer to an hydroxyl oxygen assisted by the solvent molecule which is followed by extrusion of the HF molecule. The calculated energy barriers depend on the type of solvent as well as on its configuration and are consistent with the observed fragmentation ratios.

Signature of surface periodicity in the electronic structure of Si(1 1 1)-(7 × 7).

The surface electronic structure of Si(1 1 1)-[Formula: see text] has been studied by angle-resolved photo electron spectroscopy. Replicas of the S 1 surface state are found in correspondence with several [Formula: see text] unit cells in the reciprocal space. This observation resolves in a direct way the long-standing dichotomy between the structural and electronic properties of the system previously discussed on the basis of the [Formula: see text] or [Formula: see text] R30° surface models.

Growth hormone in inflammatory bowel disease.

Crohn's disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract characterized by chronic relapsing inflammation and catabolism. Growth hormone/insulin-like growth factor-I axis is important in inflammatory bowel disease, because of the effects on epithelial cell kinetics, collagen deposition and immunomodulation. The potential of growth hormone as a therapeutic option in inflammatory bowel disease has been proven in various clinical settings. Acquired growth hormone resistance in inflammatory bowel disease seems to be mediated by a combination of undernutrition and active inflammation. In particular, proinflammatory cytokines, such as TNF-a and interleukin-6, have been implicated as potential mediators of growth hormone resistance. The introduction of anti-TNF-alpha monoclonal antibodies has proven very efficacious in patients with inflammatory bowel disease. By reducing cytokines levels in inflammatory cells of intestinal mucosa, infliximab could interfere with cytokine-induced growth hormone resistance. Recent in vivo data have shown that acquired growth hormone resistance in patients with inflammatory bowel disease may be reversed after the administration of anti-TNF-alpha therapy.

A New Anisotropic Charge-Equilibration Method for Self-Assembly of Organics on Metal Surface: d-Alaninol on Cu(100).

The supramolecular chemistry at surfaces has been extensively studied by quantum and classical computational models in order to simulate and reproduce the correct energetics and structures of adsorbed molecules on surfaces at various coverages. We have developed a classical tool able to sample the configuration space overcoming the topological constraints of the standard classical molecular dynamics. Our model is based on the charge equilibration procedure combined with an anisotropic pairwise atomic interaction where an angular dependence, with respect to the metal surface, is explicitly taken into account. The d-alaninol molecule has been chosen as a prototype of a flexible and multifunctional chemical compound which can form manifold complex configurations upon absorption on a metal surface. A detailed analysis of molecular structures and energetics of partial and full coverage has been carried out. The experimental STM image of the monolayer is correctly reproduced by our calculations, indicating that this new approach represents a step forward in the efficient simulation of complex molecular self-assembly.

Dexamethasone inhibition of interferon-alpha 2-induced stimulation of cortisol and growth hormone secretion in chronic myeloproliferative syndrome.

This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechanism by which IFN-alpha 2 stimulates cortisol and GH secretion in humans. We compared the pattern of IFN-alpha 2-induced cortisol and GH release with that elicited after the same challenge given subsequent to pretreatment with dexamethasone (Dex). We studied eight patients affected by a chronic myeloproliferative syndrome (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1 mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha 2 stimulated the release of both cortisol and GH in each patient with a significant increment vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol secretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a modulation of the activity of the hypothalamic-pituitary axis rather than through a direct effect at the level of the adrenal cortex. After Dex plus saline administration, no significant effect was observed on plasma GH levels, which remained low. Dex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or both) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells or whether the cytokine exerts a stimulatory action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH secretion in adult human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Menstrual irregularity in women with acromegaly.

Menstrual irregularity is common in women with acromegaly, occurring in 40-84%. Although it has been attributed to gonadotropin deficiency and/or PRL excess, it has not been evaluated in detail, and its pathogenesis is not well understood. To explore the various possible pathogenic mechanisms, we have analyzed the clinical, endocrinological, and radiological characteristics of 47 women with active acromegaly within the reproductive age range (15-41 yr) with respect to their menstrual pattern; 9 patients (19%) had normal cycles, 7 (15%) had oligomenorrhea, 29 (62%) had amenorrhea, and 2 (4%) had polymenorrhea. Compared to patients with normal cycles (n = 9), patients with menstrual irregularity (oligo/polymenorrhea or amenorrhea; n = 38) were more hirsute, had lower serum estradiol (normal: median, 76.5 pmol/L; range, 20-570; menstrual irregularity: median, 283; range, 140-431; P < 0.01), and sex hormone-binding globulin (SHBG; normal: median, 19.6 nmol/L; range, 5-52; menstrual irregularity: median, 48; range, 18-60; P < 0.01), but similar testosterone levels; in addition, patients with amenorrhea had higher serum GH (normal: median, 100 mU/L; range, 8.8-400; amenorrhea: median, 30; range, 10.7-120; P < 0.05). PRL levels in excess of 1000 mU/L were found in 16 of the 38 patients with menstrual irregularity compared to only 1 of the 9 patients with normal cycles. Patients with menstrual irregularity had a greater impairment of anterior pituitary function than patients with normal cycles. Acromegalic patients who were defined as estrogen sufficient (estradiol, >140 pmol/L) had clinical baseline endocrine profiles and LH responses to GnRH stimulation similar to those in patients with polycystic ovarian disease. There was a positive correlation between GH levels and tumor size (r = 0.35; P < 0.05) and an independent inverse correlation between GH and SHBG levels (r = -0.6; P < 0.01), which persisted even in patients who were estrogen sufficient, but there was no correlation between GH and estradiol levels; in addition, there was a negative correlation between estradiol levels and tumor size (r = -0.42; P < 0.05). Thirty-five of the patients with menstrual irregularity had meso- or macroadenomas and 3 had microadenoma, whereas 6 of the 9 patients with normal cycles had microadenomas. In conclusion, menstrual irregularity is common in women with acromegaly (81% of our patients). Amenorrheic patients have higher GH levels, are mainly estrogen deficient, and tend to have larger tumors than patients with normal cycles. However, the independent negative correlation between GH and SHBG levels suggests that GH may, directly or indirectly, lead to a fall in SHBG, possibly determined by the hyperinsulinemia known to occur in acromegaly. Low SHBG levels may contribute to the menstrual disturbance seen in acromegaly in addition to any gonadotropin deficiency or hyperprolactinemia and may account for hirsutism in the presence of normal testosterone levels.

Thyroid cancer in suppressed contralateral lobe of patients with hot thyroid nodule.

We studied 60 patients with thyrotoxicosis due to single toxic nodule. At surgery in 3 patients (5%) a papillary carcinoma has been detected in the contralateral suppressed lobe. Thyroid function tests and thyroid scan confirmed thyrotoxicosis. Thyroid stimulating hormone (TSH) was undetectable in all patients. It is common opinion that differentiated thyroid tumour growth is TSH dependent. On the basis of our study two hypotheses are possible: (1) the development of thyroid carcinoma precedes the adenoma and suppressed TSH levels inhibit tumour growth; (2) suppressed TSH levels do not protect patients from the occurrence of cancer. In the evaluation of hot thyroid nodule we suggest careful ultrasonographic control in order to look for nodules outside the adenoma. A complete surgical examination of the whole thyroid gland is required and intraoperative biopsies are advocated in abnormal areas.

Some central effects in mice of compounds related to nicotine.

1. Some hydroxy-, amino-, and methoxy- phenylalkyltrimethylammonium compounds, beta-pyridylmethyl- dimethylamine and pyrrolidine, and beta-pyridylethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (-)-nicotine.2. The o- and m- hydroxybenzyl-, o-hydroxyphenethyl- and m-hydroxyphenylpropyl- trimethylammonium compounds improved performance; (-)-nicotine, in one-quarter of the dose, had similar effects. The m- and p-hydroxyphenethyl-, o-hydroxyphenylpropyl- and o- and p- aminobenzyl, and o-, m-, and p- aminophenethyl-trimethylammonium compounds impaired performance.3. (-)-Nicotine and m-hydroxyphenylpropyltrimethylammonium appeared also to enhance memory consolidating processes.4. The central actions of some of the compounds suggest that the possibility that they can penetrate into the central nervous system should not be ruled out even though they are quaternary salts.5. No correlation was found between the effects of the compounds on avoidance learning and on the frog rectus muscle. Though the differences may be due to differences in access to the central nervous system, it is also possible that the receptors associated with learning processes are different from those in the frog rectus and possibly more specialized.

Expression of menin gene mRNA in pituitary tumours.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant inherited disorder characterised by the combined occurrence of parathyroid, endocrine pancreas and anterior pituitary tumours. The gene responsible for MEN 1, the menin gene, a putative tumour-suppressor gene located on human chromosome 11q13, has been cloned. To investigate the role of the menin gene in sporadic anterior pituitary tumorigenesis, its mRNA was assessed in a group of pituitary tumours. METHODS: Menin gene expression, along with glyceraldehyde phosphate dehydrogenase (GAPDH) gene expression, has been studied in a group of normal pituitaries and in 23 pituitary tumours not associated with the MEN 1 syndrome. The pituitary tumours included 4 prolactinomas, 11 growth-hormone-secreting tumours and 8 non-functional tumours. Total RNA was extracted from the normal pituitaries and tumours, and cDNA was synthesised with standard reverse transcriptase methods. Duplex polymerase chain reaction (PCR) was standardised in order to quantify the expression of the menin gene using intron-spanning primers across exons 9 and 10 in relation to the 'house-keeping' gene GAPDH. The PCR products were separated on agarose gel and densitometric analysis of the bands allowed semi-quantification. RESULTS: There was no evidence for a change in menin gene expression in any of the pituitary tumours when compared with normal pituitaries. CONCLUSIONS: These studies complement previous work on mutational analysis, and do not suggest a major role for the menin suppressor gene in sporadic pituitary tumorigenesis.

Induction of nitric oxide synthase and interleukin-1beta, but not heme oxygenase, messenger RNA in rat brain following peripheral administration of endotoxin.

Previous studies have suggested that both nitric oxide (NO) and carbon monoxide (CO) are important modulators of the inflammatory response, while more recent data have implicated both gases as regulators of hypothalamic neuroendocrine function, particularly the hypothalamo-pituitary-adrenal axis. We have, therefore, investigated the modulation of the transcripts for the synthetic enzymes for both NO and CO following the intraperitoneal administration of lipopolysaccharide, serotype B5 055, over the course of 24 h. The mRNA for type I or neuronal nitric oxide synthase (nNOS), and type II or inducible (iNOS), and heme oxygenase1 ('inducible') and heme oxygenase2 ('constitutive'), were reverse transcribed to cDNA, amplified by the polymerase chain reaction, and then quantified using a co-amplified internal standard, beta-actin. This allowed for assessment of relative changes in transcript concentration. In addition, these were compared to changes in expression of the cytokine, IL-1beta. Finally, absolute levels of the synthetic enzyme transcripts were assessed by means of co-amplification in the presence of varying amounts of mutant templates in a competitive PCR reaction. Our data revealed rapid induction of IL-1beta, iNOS and HO1 in the liver, returning to baseline at 24 h. In the hypothalamus, all transcripts were present under basal conditions, but only IL-1beta and iNOS were induced by the LPS. We conclude that hypothalamic IL-1beta and iNOS can be induced by a non-lethal dose of endotoxin, and are, thus, in a position to mediate certain of the neuroendocrine consequences to inflammatory stress.

Short-range interactions within molecular complexes formed in supersonic beams: structural effects and chiral discrimination

One- and two-color, mass-selected R2PI spectra of the S1<--S0 transitions in the bare chiral chromophore R-(+)-1-phenyl-1-propanol (R) and its complexes with a variety of alcoholic solvent molecules (solv), namely methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, S-(+)-2-butanol, R-(-)-2-butanol, 1-pentanol, S-(+)-2-pentanol, R-(-)-2-pentanol, and 3-pentanol, were recorded after a supersonic molecular beam expansion. Spectral analysis, coupled with theoretical calculations, indicate that several hydrogen-bonded [R.solv] conformers are present in the beam. The R2PI excitation spectra of [R.solv] are characterized by significant shifts of their band origin relative to that of bare R. The extent and direction of these spectral shifts depend on the structure and configuration of solv and are attributed to different short-range interactions in the ground and excited [R.solv] complexes. Measurement of the binding energies of [R.solv] in their neutral and ionic states points to a subtle balance between attractive (electrostatic and dispersive) and repulsive (steric) forces, which control the spectral features of the complexes and allow enantiomeric discrimination of chiral solv molecules.

Acute and subacute effects of endotoxin on hypothalamic gaseous neuromodulators.

Although two-way communication between the hypothalamus and the immune system in now well established, particularly for the hypothalamo-pituitary-adrenal axis, the role of the gaseous neurotransmitters nitric oxide (NO) and carbon monoxide (CO) is much less well understood in terms of hypothalamic function. These agents are an important part of the peripheral inflammatory response; and their synthetic enzymes, NO synthase (NOS) and heme oxygenase (HO), respectively, have been localized to the hypothalamic PVN and SON. The induced generation of both NO and CO leads to the suppression of CRH and vasopressin, the major stimulators of the HPA. Thus, the addition of hemin to hypothalamic explants is maximally active at 1 microM in attenuating the release of CRH and vasopressin, and this dose is also most effective in generating biliverdin and associated CO. CO generation is also able to stimulate cyclooxygenase to produce prostaglandin E2, an established intermediary in the cytokine-stimulated activation of the HPA. Finally, inducible NOS mRNA is specifically induced in the hypothalalmus in response to endotoxin, in parallel to interleukin-1. These data provide increasing evidence in favor of NO and CO as counterregulatory agents in the HPA response to immune activation.

Chiral discrimination of 2,3-butanediols by laser spectroscopy.

The resonance enhanced two-photon ionization time-of-flight (R2PI-TOF) excitation spectra of supersonically expanded complexes of isomeric 2,3-butanediols with a suitable chromophore, i.e. R-(+)-1-phenyl-1-propanol, represent powerful means for structurally discriminating the diol moiety and for investigating the nature of the intra- and intermolecular interactions involved in the complexes.

Cholesterol and serotonin indices in depressed and suicidal patients.

BACKGROUND: Prolactin and cortisol responses to d-fenfluramine challenge of central serotonin are reduced in depressed and suicidal patients. Low serum cholesterol levels are also reported in suicidal behavior. Thus, we examined for a relationship between serum cholesterol and fenfluramine challenge responses in patients with depression and/or attempted suicide. METHODS: We studied 12 patients and six controls. Blood was drawn for baseline serum cholesterol and the d-fenfluramine challenge test performed. RESULTS: Serum cholesterol levels were significantly lower in suicidal patients than in either non-suicidal patients or controls. However, neither the prolactin nor cortisol responses to d-fenfluramine correlated significantly with serum cholesterol levels. CONCLUSION: No relationship was found between serum cholesterol and these peripheral indices of serotonergic function.