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R Guerrini

Publications and source records attributed to R Guerrini.

212 records · Page 12Linked to original sources
PubMedDate not supplied

Delta-selective opioid peptides containing a single aromatic residue in the message domain: an NMR conformational analysis.

The sequence of deltorphin I, a delta-selective opioid agonist, has been systematically modified by inserting conformationally constrained C alpha, alpha disubstituted apolar residues in the third position. As expected, substitution of Phe with Ac6c, Ac5c and Ac3c yields analogues with decreasing but sizeable affinity. Surprisingly, substitution with Aib yields an analogue with almost the same binding affinity of the parent compound but with a greatly increased selectivity. This is the first case of a potent and very selective opioid peptide containing a single aromatic residue in the message domain, that is, only Tyr1. Here we report a detailed conformational analysis of [Aib3]deltorphin I and [Ac6c3]deltorphin I in DMSO at room temperature and in a DMSO/water cryomixture at low temperature, based on NMR spectroscopy and energy calculations. The peptides are highly structured in both solvents, as indicated by the exceptional finding of a nearly zero temperature coefficient of Val5 NH resonance. NMR data cannot be explained on the basis of a single structure but it was possible to interpret all NMR data on the basis of a few structural families. The conformational averaging was analysed by means of an original computer program that yields qualitative and quantitative composition of the mixture. Comparison of the preferred solution conformation with two rigid delta-selective agonists shows that the shapes of [Aib3]deltorphin I and [Ac6c3]deltorphin I are consistent with those of rigid agonists and that the message domain of opioid peptides can be defined only in conformational terms.

Animals↗
PubMedDate not supplied

Sequential occurrence of benign partial epilepsy and childhood absence epilepsy in three patients.

We first report 3 patients who experienced absence epilepsy (mean age at onset: 6.3 years; range: 4-9) 1-4 years after recovering from an electroclinical picture characteristic of benign childhood partial epilepsy (BCPE). All patients were put on monotherapy with sodium valproate, and their long-term course was excellent with remission of absences and normalization of EEG recordings. The exceptionality of our observation favors the hypothesis that BCPE and absence epilepsy are distinct entities.

Adolescent↗
PubMedDate not supplied

Structure-activity studies on nociceptin/orphanin FQ: from full agonist, to partial agonist, to pure antagonist.

A heptadecapeptide (Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln) was identified from rat brain and from porcine brain as a ligand for OP4, a new G-protein coupled receptor that is similar in sequence to opioid receptors. The OP4 receptor is widely expressed in the nervous system where it mediates a broad range of physiological functions. The new peptide, nociceptin (NC), has a primary sequence recalling that of opioid peptides. Despite the homologies (a) of the OP4 receptor with known opioid receptors, especially the OP2 (kappa) receptor, and (b) of NC with opioid peptides, particularly dynorphin A, the two biological systems have different anatomical locations and chemical requirements for activation. NC does not bind to opioid receptors, and mammalian opioid peptides do not interact with the OP4 receptor. The presence of Phe in position 1 and Arg in position 8, appear to be instrumental to exclude NC from interacting with the opioid receptors. Contrary to opioid peptides which strikly require Tyr in position 1, the active core that activates the OP4 appears to be towards the centre of the peptide molecule and includes Phe4. Based on the message/address model, several changes have been made in the N-terminal tetrapeptide Phe-Gly-Gly-Phe (message) and a few also in the C-terminal of the template NC(1-13)-NH2, a fragment that acts as a full agonist both in vitro and in vivo. Subtle changes of the N-terminal sequence, especially at Phe1, led to the discovery of peptide antagonists ([Phe1 psi (CH2-NH)Gly2[-NC(1-13)-NH2 and [Nphe1[-NC(1-13)-NH2). The first compound has been widely used to characterize NC actions in the periphery and in the central nervous system. It has been shown to act mainly as an antagonist outside the brain and as an agonist in the central nervous system. [Nphe1[-NC(1-13)-NH2- on the contrary, acts as antagonist both in the periphery and in the brain. These first peptide prototypes may soon be followed by non-peptide compounds, some of which, are already described in patient literature.

Amino Acid Sequence↗
PubMedDate not supplied

Reflex seizures are frequent in patients with Down syndrome and epilepsy.

In a retrospective study of 30 Down syndrome (DS) patients with epilepsy, we found 6 cases (20%) with reflex seizures. One patient had benign myoclonic epilepsy of infancy with clinical photosensitivity. The other 5 cases had all startle-induced epileptic seizures and a form of symptomatic epilepsy. Three patients had a Lenox-Gastaut syndrome, one had generalized symptomatic epilepsy, and one had partial symptomatic epilepsy (PSE). Reflex epilepsy was also used as a classification category in the PSE case, as most or all seizures were stimulus-related in this patient. Seizures precipitated by stimuli were stereotyped in 4 patients, but 2 patients responded to stimuli with different types of seizures. The actual occurrence of reflex seizures in DS patients with epilepsy is probably underestimated. These cases seem to confirm previous reports showing deficiencies in cortical inhibition in the brain of DS patients.

Brain↗
PubMedDate not supplied

Trisomy 12p syndrome: a chromosomal disorder associated with generalized 3-Hz spike and wave discharges.

Three cases (2 boys, 1 girl) of trisomy 12p syndrome are reported. In two, the disorder is caused by a malsegregation of a maternal translocation, the karyotype being 46,XY,der(18),t(12;18)(p11;q23) (case 2) and 46,XX,-10,+ der(10),t(10;12)(p15;p11) (case 3). Case 1 is a de novo case with a regular trisomy 12p in the fibroblasts: 47,XY + (12pter----12 cen. . .?) and a mosaic trisomy 12p in lymphocytes: 46,XY/47,XY, + (12pter----12 cen. . .?). In all cases, the EEG showed 3-Hz generalized spike and wave (SW) discharges. Generalized epilepsy with myoclonic seizures was present in two patients (cases 1 and 2), who may be considered to have a symptomatic generalized epilepsy with a specific etiology. Case 3 has shown only febrile seizures. Any association between the excess of genetic material and the EEG trait "generalized SW" might not be a chance occurrence in this disorder; however, both EEG findings and clinical features (seizure type and frequency) in the 23 cases reported in the literature are too scanty to allow confirmation of such an association.

Brain↗
PubMedDate not supplied

Compulsive somatosensory self-stimulation inducing epileptic seizures.

Three children who had been diagnosed as having infantile spasms with major psychomotor retardation were referred for the persistence of series of spasm-like seizures, which were resistant to antiepileptic drug treatment, beyond infancy. Serial seizures were elicited by a compulsive self-stimulating behavior that was documented by long-term video-polygraphy. These behaviors implicated proprioceptive inputs: tapping on the chin in one case, flexion and external rotation of the leg with dislocation of the femur in one case, a particular posturing of the body followed by rhythmic shaking of the head in the last case. This clinical picture seems to constitute a particular type of outcome for infantile spasms and is particularly resistant to therapy.

Cerebral Cortex↗
PubMedDate not supplied

Central precocious puberty in 48,XXYY Klinefelter syndrome variant.

We report the first case of central precocious puberty in a patient with 48,XXYY Klinefelter syndrome variant. We also report clinical characteristics, growth pattern, endocrine data and pathological testicular findings. The patient did not receive medical care for his precocious pubertal development, because of adequate height prognosis, and reached normal height for both his target height and Klinefelter patients. Since precocious puberty seems to occur in Klinefelter syndrome and its variants, we advise karyotype analysis in boys with mental retardation, gynecomastia, small testes and precocious onset of puberty.

Abnormalities, Multiple↗
PubMedDate not supplied

Syndromes of bilateral symmetrical polymicrogyria.

BACKGROUND AND PURPOSE: A number of anatomicoclinical syndromes have been described in which bilateral symmetrical polymicrogyria is the underlying morphologic abnormality. We retrospectively reviewed the clinical, epileptic, and morphologic manifestations of bilateral symmetrical polymicrogyria in 21 patients to determine whether certain areas are at particular risk for these syndromes. METHODS: Clinical records and brain MR studies of 21 patients with bilateral symmetrical polymicrogyria were reviewed to confirm the presence and determine the location of polymicrogyria and to qualitatively correlate location with developmental, neurologic, and epileptic histories. The locations we found were compared with published reports of bilateral symmetrical polymicrogyria to determine whether these locations were random or whether predilections exist for certain areas. RESULTS: Analysis revealed six patients with bilateral frontal polymicrogyria, nine with bilateral perisylvian polymicrogyria, one with bilateral parietal polymicrogyria, one with bilateral parasagittal parieto-occipital polymicrogyria, two with bilateral frontal polymicrogyria and bilateral perisylvian polymicrogyria, one with bilateral perisylvian and bilateral parasagittal parieto-occipital polymicrogyria, and one with bilateral perisylvian, bilateral parieto-occipital, and bilateral parasagittal parieto-occipital polymicrogyria. Symptom complexes were non-specific, but seemed additive according to the regions of brain involved. CONCLUSION: Bilateral symmetrical polymicrogyria has a propensity to develop in specific regions of the cerebral cortex. When the regions are extensive, the areas involved often appear to be simple topological additions of those regions. These locations and the identification of several familial cases raise the possibility that genetic mechanisms influence the development of these malformations in some patients.

Brain Damage, Chronic↗
PubMedDate not supplied

Molecular dynamics conformations of deltorphin analogues advocate delta opioid binding site models.

Multi-site binding models for the delta opioid receptor were studied in vitro with [3H]DPDPE as the labeled ligand using analogues of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) altered at position 4. Modifications included a change in chirality (L- to D-Asp4), increased length of the anionic side-chain (Glu4), elimination of the charged group (Abu4), addition of an anionic group (Gla4), and change in backbone conformation (Pro4). All of the peptides had relatively high delta affinities (0.09 to 1.15 nM); the major variability in delta selectivity resided in changes in mu affinities (1.6 to 530 nM). Three analogues (Glu4, D-Asp4 and Pro4) revealed better fits to two-site binding models (Hill coefficients < 0.850 with narrow 95% confidence intervals and P < 0.0001). Deltorphin C and analogues containing Gla4 and Abu4 (which were weakly delta selective), as well as deltorphin A (H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2), fitted one-site binding models. Molecular dynamics simulations performed on deltorphin C and Abu4 exhibited similarities in the tertiary structure of their low energy conformers, while differing from the three-dimensional structures of the analogues containing Glu4, D-Asp4 and Pro4 substitutions. The data provide support that the three-dimensional architecture of an opioid peptide is an important factor in the designation of delta opioid receptor subtypes.

Amino Acid Sequence↗
PubMedDate not supplied

[The evolution of epilepsy in the most common genetic forms with mental retardation (Down's syndrome and the fragile X syndrome)].

Some chromosomal abnormality syndromes carry a higher risk of seizures than that found in the general population. Down's syndrome is considered to be the first and the most frequent chromosomal abnormality causing mental retardation. In spite of numerous reports and epidemiological surveys, the outcome of epileptic syndromes in patients with Down's syndrome (DS) is still largely unknown. We retrospectively studied 34 DS patients with epilepsy (14M; 20F). Epileptic syndromes were classified as: infantile spasms, 10 cases, i.e. 31%; Lennox-Gastaut syndrome, 5 cases, 15.5%; symptomatic generalized epilepsy, 1 case; idiopathic generalized epilepsy, 6 cases, 17.6%; partial symptomatic epilepsy, 10 cases, i.e. 31%. In 2 patients the epilepsy was unclassifiable. In all the patients the following evolutive particularities were noted: a) the infantile spasms to have a relatively mild prognosis, as 8/10 patients remained seizure-free, 3 of whom without treatment; b) no patient experienced febrile convulsions prior to the onset of epilepsy; c) Lennox-Gastaut syndrome had a relatively late onset (mean age 10 years, range 8-11.5); d) 7 patients (20.6%) developed reflex seizure. The fragile X syndrome is considered to be the second most frequent chromosomal abnormality causing mental retardation. The prevalence of epilepsy varies from 9.1% to 45% in the different series. In order to evaluate the prevalence rate of epilepsy and the previously hypothesized association with a particular electroclinical picture, we retrospectively studied 90 fragile X syndrome patients (80M, 10F) aged 4 to 25 years (mean age 13y6m).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗