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Biomedical subjects

P Franco

Publications and source records attributed to P Franco.

At least 19 recordsLinked to original sources
PubMed2006

Inhibitory effect of pasireotide and octreotide on lymphocyte activation.

Somatostatin (SST) regulates the function of the central and peripheral nervous system, the endocrine and exocrine organs, as well as the vascular and immune system. These actions are mediated by five specific membrane somatostatin receptors. This study compares the effects on human lymphocytes of two long-acting somatostatin analogues that have different receptor affinity: octreotide and pasireotide. Both analogues have an antiproliferative effect on human lymphocyte proliferation, but they act at different concentration and, while octreotide enhances IL10 and inhibits gamma IFN pasireotide inhibits IL2 and gamma IFN. In both sets of experiment the different behaviour of the two analogues could be due to their different affinity to the SSTR subtypes. Finally this study suggest that the growth inhibitory action of somatostatin analogues is an apoptotic phenomenon and it can be mediated by SSTR2a, in the case of octreotide, and by SSTR3 when pasireotide is used or it can be mediated by the heterodimerization of the two receptor.

Adult↗
PubMed2006

Effects of chimeric somatostatin-dopamine molecules on human peripheral blood lymphocytes activation.

BIM 23A761, selective for somatostatin receptors subtypes 2, 5 and the dopamine receptor subtype 2, and BIM 23A757 with affinity for SSTR2 and DAR2 were studied on human PBL proliferation and activation. BIM 23A761 was significantly more potent than specific SSTR and DAR2 agonists in suppressing lymphocyte proliferation induced by mitogen or alloantigen, while BIM 23A757 was more potent than specific SSTR2 and DAR2 agonists in suppressing antigen induced proliferation only. Both molecules displayed enhanced potency in suppressing IFNgamma and IL-6 secretion compared with the SSTR and DAR2 analogs, while only BIM 23A761 was able to inhibit IL-2 secretion and its effect is more potent than the control analogs. Furthermore BIM 23A761 inhibit cell progression into the S phase and then into the G2/M, while BIM 23A757 inhibited bromodeoxyuridine incorporation only during the S phase. Both chimeric molecules resulted significantly more effective than the respective controls.

Adult↗
PubMed2005

Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS.

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.

Apoptosis↗
PubMed2004

[Neurodevelopment of extremely low birthweight infants born in Erasmus Hospital between 1992 and 2001].

Survival of extremely low birth weight infants has dramatically improved in the last decade of the twentieth century. The objective of our study was to evaluate the neurological evolution of the surviving infants because frequent motor, sensitive and psychological disturbances are related. Prospective, longitudinal study in a population of newborns, nursed in our neonatal intensive care unit and born between 1992 and 2001 with less than 1.000 g and/or less than 28 weeks of gestational age (GA). Neurological assessment of outcome was made using the neurodevelopmental score (O.M.S. 1988) at 6, 9, 12, 18, 24 and 36 months. Neurological follow-up every year and neuropsychological testing at 3, 5 and 8 years. Only children with at least 2 years of follow-up were included. The children were grouped in 3 categories: M (major neurological handicap), m (minor neurological handicap), N (normal neurological outcome). To evaluate the evolution with time, we compared the results from the first period (1992 to 1996) to the second part of this decade (1997 to 2001). Mortality fell from 38% (27/70) in the first period (1992-1996) to 18% (8/44) in the second one (1997-2001) (p = 0.02) including neonates of less than 25 weeks GA. Neurodevelopmental status improved and severe brain lesions decreased (25% with intraventricular haemorrhage III & IV and cystic periventricular leukomalacia versus 6% in the second period) (p = 0.017). Major handicap fell from 26% (9/34) to 16% (5/31) and normal neurological evolution raised from 15% (5/34) to 48% (15/31) (p = 0.013). With the survival of newborns less than 28 weeks, the severe ocular complications increased: 6% (5/79). In conclusion, mortality and quality of life have significantly improved in the past 10 years in our service. Severe brain lesions have decreased under a better multifactorial management. Nevertheless when the gestational age of the surviving babies diminishes, ocular sequelae increase. We still think that prematurity remains a burden for the child, his family and the society.

Brain↗
PubMed2003

Sudden infant deaths: stress, arousal and SIDS.

The prevalence of the Sudden Infant Death Syndrome (SIDS) has dropped in most countries following the development of education campaigns on the avoidance of preventable risk factors for SIDS. These include factors in the infant's micro environment, such as prenatal passive smoking, administration of sedative drugs, prone sleep, high ambient temperature or sleeping with the face covered. Sleep laboratory studies have shown that these risk conditions contribute to the development of respiratory and autonomic disorders and reduce the child's arousability. The opposite effects were seen when studying factors protective from SIDS, such as breastfeeding or the use of a pacifier. In victims of SIDS, similar breathing, autonomic and arousal characteristics were recorded days or weeks before their death. It is concluded that in some infants, already immature control mechanisms can be aggravated by environmental factors.

Arousal↗
PubMed2002

Sudden infant deaths: from epidemiology to physiology.

The incidence of sudden infant death syndrome (SIDS) has dropped significantly in most countries following the development of education campaigns on the avoidance of risk factors for SIDS. However, questions have been raised about the physiological mechanism responsible for the effects of these environmental risk factors. Since 1985, a series of prospective, multicentric studies have been developed to address these questions; over 20,000 infants were recorded during one night in a sleep laboratory and among these, 40 infants eventually died of SIDS. In this review, the following methods were employed: sleep recordings and analysis, monitoring procedure, data analysis of sleep stages, cardiorespiratory and oxygen saturation, scoring of arousals, spectral analysis of the heart rate and the determination of arousal thresholds, and statistical analysis and the results including sleep apneas, arousals and heart rate and autonomic controls in both future SIDS victims and normal infants were introduced separately. In addition, the physiological effect of prenatal risk factors (maternal smoking during gestation) and postnatal risk factors (administration of sedative drugs, prone sleeping position, ambient temperature, sleeping with the face covered by a bed sheet, pacifiers and breastfeeding) in normal infants were analyzed. In conclusion, the physiological studies undertaken on the basis of epidemiological findings provide some clues about the physiological mechanisms linked with SIDS. Although the description of the mechanisms responsible for SIDS is still far from complete, it appears to involve both arousal responses and cardiac autonomic controls during sleep-wake processes.

Autonomic Nervous System↗
PubMed2001

Developmental characteristics of apnea in infants who succumb to sudden infant death syndrome.

We compared the breathing characteristics of 40 infants who subsequently died of sudden infant death syndrome (SIDS) with those of 607 healthy infants matched for sex and age. The infants were between 2 and 19 wk old at the time of recording. Compared with the control group, the infants who died of SIDS experienced significantly more frequent episodes of obstructive and mixed sleep apnea. The duration of the apneic episodes did not exceed 15 s. Moreover, the SIDS group had a greater proportion of infants with obstructive and mixed apneic episodes than did the control group. In both groups, the frequency of episodes among male infants with apnea was greater than that among female infants. After the age of 9 wk, the proportion of male infants with episodes of obstructive apnea was greater in the SIDS group than in the control group. The frequency of apneic episodes decreased with age. The rate of decrease was significantly greater in the control subjects than in the SIDS group. This finding was made mainly in male infants. The present study provides further indirect evidence for a slower maturation of respiratory control in some infants who ultimately die of SIDS.

Female↗
PubMed2001

Evaluation of the contribution to enantioselectivity of quinine and quinidine scaffolds in chemically and physically mixed chiral selectors.

Three "dimeric" C(9)-carbamates of quinine (QN) and quinidine (QD), that is, QN-QN, QD-QD, and QN-QD (chemically prepared mixture of the two cinchona-derived subunits), separated by an ethylene spacer were synthesized and used as chiral selectors for HPLC and capillary electrophoresis (CE) for the resolution of chiral acids. The chiral recognition abilities of these dimers and of several physically prepared mixtures thereof were compared in order to estimate the contribution of every cinchona scaffold to the overall enantioselectivity. The diverse phenomena observed in nonaqueous capillary electrophoresis (NACE), either using the selector added to the background electrolyte (BGE) in the total filling or partial filling mode, led us to rationalize, taking into account the relative mobilities of the chiral selectors in the capillary. The chromatographic and electrophoretic properties were compared with those of the corresponding "monomeric" QN and QD carbamates.

Journal Article↗
PubMed2001

Ambient temperature is associated with changes in infants' arousability from sleep.

STUDY OBJECTIVE: To evaluate the influence of ambient temperature on infants' arousability from sleep. DESIGN: Two groups of healthy infants with a median age of 11 weeks were recorded polygraphically during one night: 31 infants were studied at 24 degreesC and 31 infants at 28 degreesC. To determine their arousal thresholds, the infants were exposed to white noises of increasing intensities during REM and NREM sleep. Arousal thresholds were defined by the auditory stimuli needed to induce arousals. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The arousal thresholds decreased across the night in the infants sleeping at 24 degreesC (p=.017). The finding was not found for the infants sleeping at 28 degreesC. When analyzing the arousal responses according to time of the night, it was found that the auditory thresholds were significantly higher at 28 degreesC than at 24 degreesC between 03:00 hr and 06:00 hr (p=.003). These findings were only seen in REM sleep. CONCLUSION: High ambient temperature could add to the difficulty to arouse from REM sleep in the late hours of the night.

Acoustic Stimulation↗
PubMed2001

Covalently bonded polysaccharide derivatives as chiral stationary phases in high-performance liquid chromatography.

Polysaccharide derivatives have been extensively used as chromatographic chiral selectors in chiral stationary phases (CSPs) for the separation of enantiomers by HPLC. When coated onto a silica matrix, they represent nowadays one of the most popular type of CSPs. However, they are only compatible with a limited choice of solvents. The main drawback of these CSPs is related to the solubility of the chiral selector in a number of solvents, which limits their applicability. The different attempts which have been described up to now to overcome this problem by covalently fixing the chiral selector to a matrix are reviewed in this paper.

Chromatography, High Pressure Liquid↗
PubMed2001

Separation of enantiomers: needs, challenges, perspectives.

Chiral drugs, agrochemicals, food additives and fragrances represent classes of compounds with high economic and scientific potential. First the present implications of their chiral nature and necessity of separating enantiomers are summarised in this article. In the following a brief overview of the actual approaches to perform enantioseparations at analytical and preparative scale is given. Challenging aspects of these strategies, such as problems associated with data management, choice of suitable chiral selectors for given enantioseparations and enhanced understanding of the underlying chiral recognition principles, are discussed. Alternatives capable of meeting the requirements of industrial processes, in terms of productivity, cost-effectiveness and environmental issues (e.g., enantioselective membranes) are critically reviewed. The impact of combinatorial methodologies on faster and more effective development and optimisation of novel chiral selectors is outlined. Finally, the merits and limitations of most recent trends in discrimination of enantiomers, including advances in the fields of sensors, microanalysis systems, chiroptical methods and chemical force microscopy are evaluated.

Stereoisomerism↗
PubMed2001

Development of stereoselective nonaqueous capillary electrophoresis system for the resolution of cationic and amphoteric analytes.

A stereoselective ion-pair nonaqueous capillary electrophoresis (NACE) method employing the partial filling technique with N-derivatized amino acids, e.g., (R)- and (S)-3,5-dinitrobenzoyl-leucine (DNB-Leu), as chiral selector for the separation of "pseudoenantiomeric" cinchona alkaloid derivatives and other structurally related basic compounds like the enantiomers of mefloquine is presented. Originating from NACE with cinchona alkaloid derivatives as chiral counterions, this method was developed by application of the reciprocity principle of chiral recognition, which was proven to be valid for stereoselective ion-pair capillary electrophoresis (CE). A variety of basic and amphoteric selectands (SAs) could be well resolved. Thereby, the separation was primarily based on stereoselective ion-pair formation of corresponding SA stereoisomers and mobility differences of free and complexed (ion-paired) SAs. Additionally, in the case of diastereomeric SAs, naturally existing mobility differences between the diastereomers played also a role, but was shown by control experiments with racemic DNB-Leu and without selector (SO) to be of minor contribution to overall separation selectivity. Due to its simplicity, speed, and good reproducibility, the established method can be utilized for fast screening of cationic as well as amphoteric chiral compounds, and therefore is a valuable tool in the development of new chiral selectors and chiral stationary phases. Small sample amounts of the SO (4-5 mg) and only analytical amounts of SAs are needed, and about 20-50 compounds per day can be tested.

Carbamates↗
PubMed2001

Assessment of inertial and gravitational inputs to the vestibular system.

A new device for the assessment of instantaneous angular and linear accelerations of the head is presented, which is based on four linear tri-axial accelerometers suitably attached to the head by an helmet. A procedure for reproducible helmet placement and calibration is given. A method is also illustrated to work out the different linear accelerations sensed by the vestibular organs in the left and right labyrinths and the components of the angular acceleration sensed by their semicircular canals. The computation is based on few individual parameters describing the helmet position with respect to external landmarks and on the average internal position and orientation of the vestibula. The purpose is to study the components of internal inertial forces, which represent the primary inputs to the vestibular system devoted to equilibrium and oculomotor control. The system is designed to be of easy application during rehabilitation exercises and in clinical environment during diagnostic and therapeutic manoeuvres. The prototype is tested with simple free movements such as "yes", "no", and gait.

Acceleration↗
PubMed2001

Phosphorylation of seminal vesicle protein IV on Ser58 enhances its peroxidase-stimulating activity.

In this study we show that SV-IV, a major immunomodulatory, anti-inflammatory, and sperm immunoprotective protein secreted from the rat seminal vesicle epithelium, acts in vitro as a substrate of protein kinase C (PKC) competing efficiently with H1 histone, a very well known PKC substrate. Electrospray mass spectrometry (ES-MS) analysis demonstrated that approximately 10% of the native SV-IV molecules were phosphorylated by PKC and that such a modification involved only a single serine residue (Ser58) out of the 22 occurring in the protein. Interestingly, this modification produced a substantial enhancement (approximately 50%) of the native SV-IV's ability to stimulate the activity of both horseradish peroxidase (POD) and selenium-dependent glutathione peroxidase (GPX), an enzyme that is known to protect the mammalian spermatozoa from oxidative stress and loss of motility in the female genital tract following ejaculation. In contrast, the phosphorylation of SV-IV on Ser58 did not produce any effect on the anti-inflammatory properties of SV-IV, as measured by its ability to inhibit the phospholipase A2.

Amino Acid Sequence↗
PubMed2001

Reduced arousals following obstructive apneas in infants sleeping prone.

A decreased arousability and an increased risk for sudden infant death syndrome (SIDS) have been shown in infants sleeping prone. Obstructive apnea, a known risk factor for SIDS, is less often terminated by an arousal reaction in infants than in adults. The effect of body position on the arousal reaction to spontaneous respiratory events had not been previously studied in infants. The aim of our study was to see if body position has an influence on the frequency and delay of the arousal reaction to obstructive apnea. All obstructive events recorded during two successive nights in 20 infants sleeping one night prone and one night supine were studied. During the supine recording 153 obstructive events were detected, and 217 were detected during the prone session. Prone sleep was not associated with an increased frequency of obstructive apneas. Total sleep time was 382 min (range, 283-456) supine and 423 min (range, 325-521) prone (p = 0.003). Obstructive events duration was 6.5 s (range, 3-21.5) when sleeping supine and 8 s (range, 3.5-30.5) when prone (p = 0.002). Behavioral arousal were found in 57.5 % of obstructive events recorded supine and in 31.3 % of those seen prone (p < 0.001). Arousal occurred after 8 s (range, 0-21) from the start of the obstructions when supine and 10.5 s (range, 3.5-23.5) when prone (p = 0.001). Sighs were found in 34 % of supine obstructive events and in 44.7 % of those prone (p = 0.040). A reaction, i.e. arousal or sigh, was found in 91.5 % of supine events and 76 % of those prone (p < 0.001). We conclude that when sleeping supine, infants arouse to obstructive events more often and after shorter delay than when prone.

Adult↗
PubMed2000

Characterization of doubly substituted polysaccharide derivatives.

Derivatives of cellulose, amylose and chitosan, bearing simultaneously 10-undecenoyl and arylaminocarbonyl or benzoyl groups were characterized by the combined use of 1H NMR and elemental analysis. The mathematical manipulation of elemental analysis data permits the calculation of the degree of substitution for each kind of substituent. The method was validated and is applicable to other derivatives.

Algorithms↗