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Biomedical subjects

L Marinelli

Publications and source records attributed to L Marinelli.

At least 19 recordsLinked to original sources
PubMed2006

Creutzfeldt-Jakob disease presenting as corticobasal degeneration: a neurophysiological study.

Creutzfeldt-Jakob disease (CJD) can occasionally present with a clinical picture resembling a corticobasal degeneration (CBD). Transcallosal inhibition, as tested by focal transcranial magnetic stimulation, is frequently absent or highly disrupted in CBD patients. We report a case of CJD presenting at the beginning of the disease as a CBD in which the ipsilateral silent period (iSP) was present and well detectable. This brief report shows that study of the iSP may be a useful diagnostic tool in order to differentiate CBD from syndromes presenting with similar clinical features.

Creutzfeldt-Jakob Syndrome↗
PubMed2006

Endocrine and ovarian responses to prolonged adrenal stimulation at the time of induced corpus luteum regression.

The endocrine and ovarian responses to prolonged adrenal stimulation at the time of corpus luteum (CL) regression were studied in non-lactating non-pregnant Friesian cows. Cows were synchronized with two cloprostenol (PG) injections 11 days apart (second PG referred as time 0). Experiment 1 was carried out on five animals in two phases with a resting period in between. Between -48 and 84 h, animals received 12 injections of either saline (CTR) or adrenocorticotrophic hormone (ACTH) agonist (Synacthen; SYN) every 12 h. Cortisol (C), progesterone (P4), oestradiol (E2) and LH were analysed in the blood samples collected every 8-12 h between days -3 and 4. Pulsatile LH release was studied 4 h before and 4 h after naloxone administration beginning at 96 h. Experiment 2 was carried out on four cows in a cross-over experimental design (two phases, with a resting period in between). Treatments were performed by administering either saline (CTR) or Synacthen (SYN) every 12 h between -36 and 24 h. The concentrations of C, P4 and E2 were measured in blood plasma every 4-12 h from days -3 to 3, then every day from days 5 to 9. In both experiments, ovaries were examined by ultrasonography every 1-3 days. ACTH administration induced a significant increase (p < 0.001) of plasma C lasting for 7 days (experiment 1), and for 3-4 days (experiment 2). Plasma C returned to baseline levels within 6 days (expt 1) or 36 h (expt 2) after treatment interruption. During the SYN phase, LH pre-ovulatory surge was not detectable. During the CTR phase, naloxone administration induced a significant increase (p < 0.05) of average LH concentrations that was not evident during the SYN phase. The dominant follicle development was retarded and mean plasma E2 concentrations were significantly lower during the SYN phase (p < 0.01). Luteolysis was completed within 2 days. However, P4 decline between 0 and 4 h was slower (p < 0.01) during the SYN phase. Our results indicate that, under prolonged adrenal stimulation, follicular development is delayed and LH release is impaired, which are independent of CL function.

Adrenocorticotropic Hormone↗
PubMed2005

Dyskinesias predict the onset of motor response fluctuations in patients with Parkinson's disease on L-dopa monotherapy.

The aim of the study was to investigate the relationship between dyskinesias and motor fluctuations in patients with Parkinson's disease on l-dopa monotherapy. We identified 116 patients on l-dopa monotherapy treated between 1965 and 1992 and followed until death. Dyskinesias occurred in 102 patients. Of these, 48 only developed dyskinesias while 54 had both dyskinesias and motor fluctuations. Among patients with both complications, 49 developed dyskinesias before fluctuations, and only five had dyskinesias after the onset of fluctuations. Our findings suggest that dyskinesias predict the onset of motor fluctuations, and may share a common pathophysiological mechanism.

Age of Onset↗
PubMed2004

Plasma steroid variations in bull calves repeatedly treated with testosterone, nortestosterone and oestradiol administered alone or in combination.

The aim of this work was to investigate the secretion of dehydroepiandrosterone (DHEA), testosterone (T), dihydrotestosterone (DHT) and oestradiol (E) as biological markers in response to illegal administration of testosterone, 19-nortestosterone (N) and oestradiol, either alone or in combination. Twenty male Friesian calves (age 13-14 months) were allotted to a control group (n = 5), and five experimental groups (n = 3) each. Each experimental animal was repeatedly injected with one of the following hormonal treatments: E, T, N, T+E and N+E. Circulating DHEA, T, DHT and E were determined by radioimmunoassay. The administration of T alone did not induce any variation in plasma DHEA, T, DHT and E, which were similar to those in the control group. In contrast, DHEA, T and DHT were on average significantly lower in the T+E and N-treated groups (p < 0.01), whereas the administration of N+E resulted in the reduction of plasma T and DHT without any modification of plasma DHEA. The administration of E alone or in combination increased circulating levels of E but did not affect androgen plasma profiles. The results indicate that plasma levels of T do not permit detection of illegal treatments because plasma androgens always remained within the physiological range. Illegal E treatment could be detected in blood samples when they were collected at least every 20 days.

Anabolic Agents↗
PubMed2003

Impairment of transcallosal inhibition in patients with corticobasal degeneration.

OBJECTIVE: To evaluate the motor function of the transcallosal pathways in patients with clinical diagnosis of corticobasal degeneration (CBD). METHODS: In a group of 7 patients (4 males, 3 females; mean age 70.6 years) with clinical diagnosis of probable CBD (and in 8 age-matched normal controls) we evaluated the suppression of the ongoing voluntary EMG activity in the opponens pollicis muscle induced by focal transcranial magnetic stimulation (TMS) of the ipsilateral hand motor cortex. Such ipsilateral silent period (iSP) is mediated from one motor cortex to the contralateral side via a transcallosal pathway. In addition, CBD patients were investigated with magnetic resonance imaging (MRI) and neuropsychological assessment. RESULTS: iSP was normal in 4 CBD patients, while it was bilaterally disrupted in the other 3. MRI showed an atrophy of the corpus callosum (middle-posterior part of the trunk) in the CBD patients with iSP disruption. Neuropsychological evaluation showed in patients with iSP impairment a decrease of verbal fluencies associated with an impairment of attentive function. CONCLUSIONS: A proportion of CBD patients shows physiological evidence of impaired callosal motor function and atrophy of the corpus callosum on MRI, possibly correlated to dysphasic and cognitive disorders.

Aged↗
PubMed2003

Evaluation of cabergoline and buserelin efficacy for oestrous induction in the bitch.

The purpose of this work was to compare two different protocols of oestrous induction, using either a dopamine agonist (cabergoline) or a GnRH agonist (buserelin) in anoestrus bitches. The clinical trial involved 22 Beagle bitches, randomly allotted to two treatment groups: group A (n = 12) was orally administered cabergoline (Galastop(R); Centralvet-Vetem, Milan, Italy; 5 microg/kg SID), until the onset of cytological oestrus or for a maximum of 30 days and group B (n = 10) was treated with buserelin acetate, (Suprefact(R); Aventis Pharma, Milan, Italy), administered subcutaneously t.i.d., at 1.5 microg/kg for 11 days and 0.75 microg/kg for the following 3 days. Blood samples were collected twice a week to measure progesterone and prolactin concentration. Both cabergoline and buserelin produced a significant early decline in prolactin concentration (p < 0.01), but the effect of cabergoline lasted longer. Progesterone concentration was significantly affected by buserelin administration, showing a significant increase (p < 0.01) from day 3 to day 6 of treatment. Cabergoline confirmed its effectiveness in inducing oestrus as 10 of 12 bitches responded to the treatment, were mated and whelped. On the contrary, oestrus was observed in only three of 10 buserelin-treated bitches and in two of them 7 and 13 days after the end of treatment. These same two bitches accepted mating and conceived. The results suggest that in a clinical setting, dopaminergic treatment is the treatment of choice as it yields more consistent results and involves a much easier administration protocol.

Administration, Oral↗
PubMed2002

Correlations among body temperature, plasma progesterone, cortisol and prostaglandin F2alpha of the periparturient bitch.

The results of this study suggest that, besides the irrelevant role of body temperature measurement to predict the impending parturition in the bitch, progesterone and 15-ketodihydroprostaglandin F2alpha plasma level records could be more suitable to detect the approaching whelping in this species. More interesting was the statistically significant substantial increase in body temperature beginning 12 h after the onset of parturition. Therefore, if any significant increase in body temperature is recorded at the end of pregnancy without the beginning of the expulsion of fetuses, it could indicate problems at parturition. In this study, cortisol levels increased significantly at the time of delivery and remained high 12 h after the beginning of parturition, decreasing within 36 h after the onset of whelping. 15-ketodihydro-prostaglandin F2alpha levels increased significantly 24 h before parturition and again at the onset of whelping. Progesterone levels decreased significantly, starting 24 h before the onset of whelping and remained low after delivery.

Animals↗
PubMed2001

Differential modulation of motor evoked potential and silent period by activation of intracortical inhibitory circuits.

OBJECTIVES: To investigate the effect of activation of intracortical inhibitory circuits, as tested by short interval (3 ms) paired-pulse transcranial magnetic stimulation (TMS) with a conditioning-test paradigm, on the electromyographic (EMG) pause (silent period, SP) following the motor evoked potential (MEP) in normal subjects. METHODS: SPs and MEPs were recorded from the right first dorsal interosseous (FDI) muscle during a tonic voluntary contraction (from 70 to 90% of the maximum). Using a focal coil, we compared the SP duration after single-pulse TMS, paired-pulse TMS and single-pulse TMS of reduced intensity such as to evoke MEPs matched in size to the conditioned ones after paired-pulse TMS. In addition, we compared in a control experiment the duration of the SP following matched size MEPs evoked, respectively, by focal TMS with preferential activation of indirect I1- or I3-waves. RESULTS: SP duration after paired-pulse TMS was significantly longer than after single-pulse TMS evoking MEPs of a similar size. In no case the SP duration was longer when focal TMS preferentially activated I1-waves. CONCLUSIONS: The conditioning sub-threshold stimulus is more powerful in reducing the MEP size than in cutting down the subsequent EMG silence, suggesting that the neural circuits underlying MEP and SP are, at least in part, different.

Adult↗
PubMed2000

Plasma levels of amyloid beta 40 and 42 are independent from ApoE genotype and mental retardation in Down syndrome.

In Down syndrome (DS) brain an early, selective accumulation of amyloid beta (Abeta) peptides ending at residue 42 (Abeta42) occurs. Whether this event depends on an altered processing of amyloid beta precursor protein (APP) or on defective clearance is uncertain. To investigate this issue, we measured Abeta species 40 and 42 in plasma from 61 patients with DS, 77 age-matched normal controls, and 55 mentally retarded subjects without chromosomal abnormalities. The Abeta 40 and 42 plasma levels were then correlated with apolipoprotein E (apoE) genotypes in all groups of cases, and with I. Q. and Mini Mental Status Examination values in DS subjects. Both Abeta species were significantly elevated in DS compared to control groups, and the extent of their increase reflects that expected from APP gene overexpression. Plasma levels of Abeta 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS subjects. The results indicate that accumulation and clearance of plasma and cerebral Abeta are regulated by different and independent factors.

Adolescent↗
PubMed2000

Full length alpha-synuclein is present in cerebrospinal fluid from Parkinson's disease and normal subjects.

Several clues suggest that alpha-synuclein, a presynaptic protein, plays a central role in the pathogenesis of idiopathic Parkinson's disease (PD). To search a peripheral marker of PD, we analyzed presence and amount of alpha-synuclein in CSF from 12 PD patients and 10 neurologically normal subjects. The protein was extracted from CSF samples through immunoprecipitation and immunoblotting with different specific anti-alpha-synuclein antibodies. We identified a 19 kDa band that corresponds to monomeric alpha-synuclein, given its comigration with homologue human recombinant peptide as well as with the protein extracted from cerebral cortex of normal subjects. The amount of CSF 19 kDa alpha-synuclein did not significantly vary in PD and normal cases. These findings have two implications: (a) full length alpha-synuclein is released by neurons in the extracellular space; (b) alpha-synuclein does not appear a peripheral marker of PD pathology.

Biomarkers↗
PubMed2000

Synthesis, molecular modeling, and opioid receptor affinity of 9, 10-diazatricyclo[4.2.1.1(2,5)]decanes and 2,7-diazatricyclo[4.4.0. 0(3,8)]decanes structurally related to 3,8-diazabicyclo[3.2. 1]octanes.

Various lines of evidence, including molecular modeling studies, imply that the endoethylenic bridge of 3,8-diazabicyclo[3.2. 1]octanes (DBO, 1) plays an essential role in modulating affinity toward mu opioid receptors. This hypothesis, together with the remarkable analgesic properties observed for N(3) propionyl, N(8) arylpropenyl derivatives (2) and of the reverted isomers (3), has prompted us to insert an additional endoethylenic bridge on the piperazine moiety in order to identify derivatives with increased potency toward this receptor class. In the present report, we describe the synthesis of the novel compounds 9,10-diazatricyclo[4.2. 1.1(2,5)]decane (4) and 2,7-diazatricyclo[4.4.0.0(3,8)]decane (5), as well as the representative derivatives functionalized at the two nitrogen atoms by propionyl and arylpropenyl groups (6a-e, 7a-d). Opioid receptor binding assays revealed that, among the compounds tested, the N-propionyl-N-cinnamyl derivatives 6a and 7a exhibited the highest mu-receptor affinity, and remarkably, compound 7a displayed in vivo (mice) an analgesic potency 6-fold that of morphine.

Analgesics↗
PubMed2000

Lipoperoxidation is selectively involved in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by extensive neurofibrillary tangle (NFT) formation and neuronal loss in selective neuronal populations. Currently, no clues to the biological events underlying the pathological process have emerged. In Alzheimer disease (AD), which shares with PSP the occurrence of NFTs, advanced glycation end products (AGEs) as well as oxidation adducts have been found to be increased in association with neurofibrillary pathology. The presence and the amount of lipid and protein oxidation markers, as well as of pyrraline and pentosidine. 2 major AGEs, was assessed by biochemical, immunochemical, and immunocytochemical analysis in midbrain tissue from 5 PSP cases, 6 sporadic AD cases, and 6 age-matched control cases. The levels of 4-hydroxynonenal (HNE) and thiobarbituric acid reactive substances (TBARS), 2 major products of lipid peroxidation, were significantly increased by 1.6-fold (p < 0.04) and 3.9-fold (p < 0.01), respectively, in PSP compared with control tissues, whereas in AD only TBARS were significantly increased. In PSP tissue the intensity of neuronal HNE immunoreactivity was proportional to the extent of abnormal aggregated tau protein. The amount of protein oxidation products and AGEs was instead similar in PSP and control tissues. In AD, a higher but not significant level of pyrraline and pentosidine was measured, whereas the level of carbonyl groups was doubled. These findings indicate that in PSP, unlike in AD, lipid peroxidation is selectively associated with NFT formation. The intraneuronal accumulation of toxic aldehydes may contribute to hamper tau degradation, leading to its aggregation in the PSP specific abnormal filaments.

Aged↗
PubMed1999

Tyrosine kinase A-nerve growth factor receptor is antigenically present in dystrophic neurites from a variety of conditions but not in Alzheimer's disease.

Tyrosine kinase A (TrkA), a high affinity receptor for nerve growth factor (NGF), is activated during differentiation and regeneration of selective neuronal population. We investigated presence, distribution and expression of TrkA in frontal cortex from cases with Alzheimer's disease (AD), normal aging and a variety of conditions (AIDS, cystic fibrosis, cerebral infarcts) in which neuroaxonal dystrophy occurs. TrkA was immunocytochemically detected in 90% of dystrophic neurites surrounding amyloid deposits in normal aging, as well as in all not amyloid-related dystrophic neurites identified by ubiquitin immunoreactivity. Conversely, the amyloid associated dystrophic neurites were not TrkA reactive in AD tissue. The levels of TrkA protein and mRNA in AD frontal cortex did not significantly differ from those of non-demented aged controls. The absence of TrkA activation in amyloid associated neurites in AD, but not in normal aging, indicates a different reaction of neuronal tissue to amyloid (protein (Abeta) deposition, and suggests that other factors, besides Abeta, mediate neuronal degeneration in AD.

AIDS Dementia Complex↗
PubMed1999

Accuracy in naturally occurring anabolic steroid assays in cattle and first approach to quality control in Italy.

This study assessed the accuracy of 16 commercial and three self-produced kits and drew the basis for using an external quality control (EQC) system. The commercial kits were mainly developed for blood sex steroid determination in humans but also have been used in cattle. Parallelism, recovery and precision tests were performed for progesterone (P4), testosterone (T) and oestradiol (E2) assays. Moreover, anonymous QC samples were sent to be analysed to some Italian laboratories. All kits showed a fair degree of parallelism (P < 0.01), even though 2/7 kits for T and 1/6 kits for E2 determination showed a regression coefficient (r2) lower than 0.98. For P4, an acceptable range of accuracy was achieved in the recovery test only by 1/6 kits; two kits showed fair or great overestimation and two kits considerable underestimation. For T, an acceptable range of accuracy was achieved only by 1/7 kits. For E2, 4/6 kits presented a variable degree of underestimation and two kits showed great overestimation. In the intra-assay precision test quite good repeatability was achieved only using samples with high hormone concentrations. While assaying samples with low concentrations we found a number of RSD > 10%. Moreover, the laboratories participating in the EQC produced statistically different (P < 0.05) results, particularly for high and medium concentrations. In conclusion, the use of commercial kits for screening naturally occurring sex steroid concentrations in cattle blood, in the case of suspected illegal treatments, requires preventive validation procedures and the development of an opportune EQC system.

Anabolic Agents↗
PubMed1999

Anti-endothelial autoantibodies in patients with sudden hearing loss.

OBJECTIVES/HYPOTHESIS: Sudden hearing loss (HL) can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune diseases. Studies in autoimmune animal strains showing HL have reported changes in the cochlear stria vascularis. The authors investigated the presence of antiendothelial cell antibodies (AECA) to see if immune-mediated vasculitis may play a role in human sudden HL. STUDY DESIGN: A prospective study in patients with sudden HL. METHODS: Fifteen consecutive patients (mean age, 32 y) affected by sudden HL and 14 normal subjects were included. Patients with familial deafness and metabolic diseases were excluded. Extensive audiovestibular, imaging, microbiological, immunological, and routine examinations were performed. AECA were detected on rat kidney tissue sections on the sera collected at -20 degrees C. RESULTS: AECA were positive in 8 of 15 patients (53%) (2 of 5 men and 6 of 10 women), thus differing significantly from the normal control population, in which only 2 of 14 tested AECA positive (P = .023). CONCLUSIONS: In patients with sudden HL, immune-mediated vascular damage can have a pathogenetic role and AECA might represent a serological marker of vasculitis.

Adolescent↗