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Biomedical subjects

M Morelli

Publications and source records attributed to M Morelli.

At least 37 records · Page 2Linked to original sources

[Pregnancy management in women with thalassemia].

Thanks to the improvement of the techniques of assisted fecundation, of the obstetric management and of the fetal and neonatal monitoring now it's possible for a woman suffering from beta-thalassemia to have a child. Our purpose is to stress the importance to control the high maternal and fetal risk through the monitoring of several scales. The problems, connected with pregnancy of beta-thalassemic women are discussed, emphasizing the connection between pregnancy management and gestational and neonatal outcome. A variety of problems should be considered such as the informed consent about maternal and fetal risks, the problems caused by infectious agents or due to the use of some antiviral; the difficulties connected with heart and endocrine diseases are also discussed. Personal experience, from 1995 to 1999, on 4 beta-thalassemic pregnant women (three with the intermediate type and one with the major type) is reported.

Female↗

Induction of Fos-like-immunoreactivity in the central extended amygdala by antidepressant drugs.

The induction of the early gene c-fos was evaluated through Fos immunohistochemistry in areas belonging to the extended amygdala after acute administration of two antidepressants, citalopram and imipramine. Both citalopram and imipramine at the dose of 5 and 20 mg/kg, respectively, induced Fos-like immunoreactivity (FLI) in the central amygdaloid nucleus, lateral division of the bed nucleus of the stria terminalis (BSTL), and interstitial nucleus of the posterior limb of the anterior commissure (IPAC). The shell of the nucleus accumbens, which forms a continuum with the central extended amygdala, showed a decrease of FLI after administration of either citalopram or imipramine. The mechanism of action and the brain areas affected by antidepressants are still a matter of debate. By showing that the central extended amygdala is a common site of action for two different antidepressant types, these results provide new insight into the mechanism of action of antidepressants.

Adrenergic Uptake Inhibitors↗

Increased striatal expression of glutamate decarboxylase 67 after priming of 6-hydroxydopamine-lesioned rats.

Previous single exposure (priming) to a dopamine receptor agonist greatly enhances the contralateral turning behaviour elicited by dopamine D1 receptor agonists in unilaterally 6-hydroxydopamine lesioned rats. In the present study we have investigated the levels of glutamate decarboxylase 67 and glutamate decarboxylase 65 messenger RNA in the striatum of 6-hydroxydopamine-lesioned rats primed with L-3,4-dihydroxyphenylalanine (L-DOPA) and challenged with the D1 receptor agonist SKF 38393, three days thereafter. As previously reported, levels of glutamate decarboxylase 67 messenger RNA increased in the striatum denervated by the 6-hydroxydopamine lesion as compared with the intact one. Striatal glutamate decarboxylase 67 messenger RNA levels, measured three days after priming with L-DOPA (50 mg/kg), further increased in the lesioned striatum while were not modified in the intact one. Administration of SKF 38393 (3 mg/kg) elicited a more intense contralateral turning behaviour in primed than in drug-naive 6-hydroxydopamine-lesioned rats but did not induce any change in striatal glutamate decarboxylase 67 messenger RNA. In contrast, striatal levels of glutamate decarboxylase 65 messenger RNA were not modified by either 6-hydroxydopamine lesions or priming with L-DOPA. The results show that priming with L-DOPA induces long-lasting changes in GABAergic neurons of the 6-hydroxydopamine-lesioned striatum. These changes might play a role in the increased behavioural response of striatal D1 receptors induced by priming.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Involvement of adenosine A2A receptors in the induction of c-fos expression by clozapine and haloperidol.

Acute administration of the atypical antipsychotic clozapine induced a regional pattern of c-fos expression characterized by an increase in Fos-like-immunoreactivity (FLI) in the prefrontal and prelimbic/infralimbic cortices, nucleus accumbens, and lateral septum and a weak activation of FLI in the striatum. Haloperidol, similarly to clozapine, increased FLI in the nucleus accumbens and lateral septum, but it did not induce FLI in prefrontal and prelimbic/infralimbic cortices. Moreover, haloperidol increased FLI in the striatum. To gain insight into the mechanism by which clozapine and haloperidol induced FLI in these brain structures, we evaluated whether blockade of adenosine A2A receptors could influence these effects. The selective and high-affinity A2A receptor antagonist SCH 58261 (5 mg/kg) completely abolished FLI induced by clozapine (20 mg/kg) in all subdivisions of the nucleus accumbens (rostral pole, shell and core) and striatum, but did not affect the number of Fos-like positive neurons in the prefrontal, prelimbic/infralimbic cortices, and lateral septum. SCH 58261 (5 mg/kg) reduced FLI induced by haloperidol (0.1 mg/kg) in the striatum, lateral septum, and all nucleus accumbens subdivisions. In contrast, FLI induced by 0.5 mg/kg of haloperidol in the shell and core of the nucleus accumbens was not affected by SCH 58261. The results show that adenosine A2A receptors participate in the induction of FLI by clozapine and haloperidol and support the concept that A2A receptors are involved in the mediation of antipsychotic effects.

Animals↗

Differential induction of Fos-like-immunoreactivity in the extended amygdala after haloperidol and clozapine.

The extended amygdala is composed of the central and medial amygdaloid nucleus which through the sublenticular extended amygdala (SLEA) and the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) merge into the bed nucleus of stria terminals (BST). Based on anatomical connections with limbic areas, the extended amygdala has been proposed to play an important role in cognitive and affective processes. This study examines the effect of the atypical antipsychotic clozapine and the classical antipsychotic haloperidol on Fos-like-immunoreactivity (FLI) induction in areas belonging to the extended amygdala. Acute administration of clozapine (10-20 mg/kg) induced FLI in the central amygdaloid nucleus, IPAC, SLEA, and BST lateral division and, as previously described, in areas connected to the extended amygdala, such as the prefrontal cortex and nucleus accumbens shell. In contrast, acute administration of haloperidol (0.1-1 mg/kg) failed to induce FLI in the BST lateral division and SLEA but increased FLI in the IPAC. A small increase in FLI was observed in the central amygdaloid nucleus after 0.1 but not after 1 mg/kg of haloperidol. The present results, showing a preferential influence of clozapine, as compared to haloperidol, in the extended amygdala propose a new brain structure involved in the pharmacological effects of atypical antipsychotics.

Amygdala↗

A mechanical comparison of the immediate stability of three fixation devices used in wrist arthrodesis: a cadaveric study.

This study was designed to determine which of 3 fixation devices used in wrist arthrodesis provides the greatest immediate stability along 2 axes of movement. Twenty cadaver wrists were mechanically tested. Group 1 consisted of 7 wrists stabilized using a 2.3-mm Steinmann pin. Six wrists from the second group were immobilized with a 9-hole, 3.5-mm AO dynamic compression plate. The third group consisted of 7 wrists stabilized with an 8-hole, short-bend, precontoured low-contact dynamic compression plate. Stiffness and fracture force were determined in both forced flexion and forced pronation. The results showed that the Steinmann pin was the least stable of the 3 constructs in both axes of movement. No differences were observed between the 2 compression plates for either of the 2 axes of movement.

Arthrodesis↗

[The radial artery in coronary surgery: the midterm clinical and angiographic results and the variation in vasoreactivity over time].

OBJECTIVE: To evaluate the mid-term angiographic results of radial artery grafts used for myocardial revascularization. METHODS: The first 68 consecutive surviving patients who received a radial artery graft proximally anastomosed to the aorta at our institution were restudied in a five-year follow-up (mean 59 +/- 6.5 months); 48 of these patients had already undergone an early angiographic examination. The response of the radial artery to the endovascular infusion of serotonin was evaluated one and five years after surgery and the mid-term status of the radial artery grafts was correlated with the degree of stenosis of the target vessel and with the Ca(++)-channel-blocker therapy. RESULTS: The patency and perfect patency rates of the radial artery five years after the operation were 91.9 and 87.0% respectively. All radial artery grafts that were patent early after surgery remained patent at mid-term follow-up and in seven patients early parietal irregularities disappeared after five years. The early propensity to graft spasm after serotonin challenge decreased markedly at mid-term follow-up. The continued use of Ca(++)-antagonists after the first postoperative year did not affect the status of the radial artery graft, whereas the severity of target-vessel stenosis markedly influenced the angiographic results. CONCLUSIONS: The mid-term angiographic results of RA grafts used for myocardial revascularization are excellent. A correct surgical indication is essential, whereas continued therapy with Ca(++)-antagonists after the first year does not influence the mid-term angiographic results.

Aged↗

Posterior-septal pseudo-pseudoaneurysm with limited left-to-right shunt: an unexpected easy repair.

Cardiac rupture represents a fatal complication of acute myocardial infarction within the first two weeks. In exceptional cases, the postinfarction rupture of the myocardium is not transmural but remains circumscribed within the wall itself as a cavity joined to the left ventricle through a narrow neck. This finding is usually defined as pseudo-pseudoaneurysm. We report a rare case of postinfarction posterior pseudo-pseudoaneurysm of the left ventricle, perforated into the right ventricle. This unusual anatomy resulted, over a period of several years, by progressive intramural dissection of the surrounding necrotic myocardium with late formation of a large, partially fibrotic chamber, communicating either with left and right ventricles. Despite correct preoperative diagnosis was not achieved by 2D echocardiography, pulsed Doppler and contrast ventriculography, a successful surgical treatment was possible with a really good outcome.

Aged↗

D1-Receptor-related priming is attenuated by antisense-meditated 'knockdown' of fosB expression.

Administration of dopamine receptor agonists to rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway produce changes in the denervated striatum that enable a subsequent injection to elicit more vigorous circling. The molecular basis for this behavioural phenomenon, termed priming, is unknown. D1-receptor-related priming has been associated with a profound elevation of immediate-early gene (IEG) expression in the denervated striatum. Since immediate-early genes encode known transcriptional regulating factors, this observation has led to the suggestion that IEG induction may play a role in the gene signaling pathways which mediate priming. In the present study, we addressed the role of induction of the IEG fosB in dopamine agonist-induced priming by examining whether inhibition of the synthesis of FosB proteins (FosB and DeltaFosB) by intrastriatal delivery of an antisense oligonucleotide to fosB reduced apomorphine-induced priming. Intrastriatal delivery of an antisense, but not a random, oligonucleotide to fosB 18 and 6 h before apomorphine reduced the ability of this mixed D1¿D2-like receptor agonist to prime circling induced by the specific D1-like receptor agonist SKF 38393. Immunohistochemical analysis revealed that only the antisense oligonucleotide blocked apomorphine-induced increases in FosB-like immunoreactivity in the denervated striatum. In contrast, apomorphine-induced increases in JunB-, NGFI-A- and Fos2-16-like immunoreactivities were unaffected by either the antisense or random oligonucleotides, indicating that the antisense oligonucleotide attenuated apomorphine-induced priming by selectively blocking the synthesis of FosB proteins. Taken together, these findings suggest that fosB induction in the denervated striatum plays a role in mediating D1-receptor-related priming. Dopamine replacement therapy for Parkinson's disease is often complicated by the development of dyskinetic side effects. Results from the present study suggest that D1-receptor-mediated increases in fosB expression may be involved in those intracellular events responsible for the generation of these debilitating side effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Silicone rubber/hydrogel composite ophthalmic inserts: preparation and preliminary in vitro/in vivo evaluation.

The present report describes the development and in vitro/in vivo testing of rod-shaped mucoadhesive ophthalmic inserts fitting the upper or lower conjunctival fornix. Cylindrical devices (diameter 0.9 mm, length 6-12 mm, weight 3-8 mg) all containing 0.8 mg oxytetracycline HCl (OXT) were prepared from appropriate mixtures of silicone elastomer, OXT and sodium chloride as release modifier. A stable polyacrylic acid (PAA) or polymethacrylic acid (PMA) interpenetrating polymer network (IPN; 30 or 46% w/w) was grafted onto the inserts' surface by treatment with a mixture of acrylic (or methacrylic) acid and ethylene glycol dimethacrylate in xylene at 100 degrees C. Mucoadhesion studies in vitro showed that the mucoadhesive properties increased significantly with increasing thickness of the IPN layer. The inserts were tested for drug release in vitro, and for drug release and retention in rabbit eyes. The presence of IPN, as well as of NaCl, in general increased the drug release rate. The PMA-grafted devices released OXT at lower rates when compared with the PAA-grafted ones. A nearly zero-order release rate for about 1 week was observed in vitro for some types of inserts. When tested in rabbits, some IPN-grafted inserts maintained in the lacrimal fluid a OXT concentration of 20-30 microg/ml for several days: the in vitro minimum inhibitory concentration values (MIC 90%) of OXT against micro-organisms responsible of common ocular infections range from 0.8 to 2.0 microg/ml, while MIC 90% values in the range 14-50 microg/ml have been indicated for Pseudomonas aeruginosa. The ocular retention of IPN-grafted samples was significantly higher with respect to ungrafted ones. The presently described mucoadhesive silicone inserts might prove efficient therapeutic systems for chemotherapy of ocular bacterial infections, such as trachoma.

Animals↗

Motor stimulant effects of caffeine in 6-hydroxydopamine-lesioned rats are dependent on previous stimulation of dopamine receptors: a different role of D1 and D2 receptors.

Caffeine has been reported to induce contralateral rotational behaviour in rats bearing a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway. In order to define the role of dopamine receptors in the mediation of this behaviour, we have evaluated the influence of previous exposure to a dopamine receptor agonist and the importance of the time elapsed from the 6-hydroxydopamine lesion on the rotational behaviour induced by caffeine. Separate groups of rats lesioned with 6-hydroxydopamine 2 weeks previously were exposed to four administrations of the D1/D2 receptor agonist apomorphine (0.3 mg/kg s.c.) (primed) or vehicle (drug-naive). Three days later, all rats received caffeine (30 mg/kg s.c.). Drug-naive 6-hydroxydopamine-lesioned rats did not rotate in response to caffeine, while rats primed with apomorphine rotate contralaterally in response to caffeine. When apomorphine priming was paired to the same environment (hemispherical bowls) where rats received caffeine, rotational behaviour was significantly higher than that obtained in rats primed in an unpaired environment (cylinders). Repeated priming with the D2/D3 receptor agonist quinpirole (0.2 mg/kg s.c.) induced a totally context-dependent contralateral rotation in response to caffeine, while caffeine contralateral rotation was not dependent from the context after repeated priming with the D1 agonist SKF 38393 [1-phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol hydrochloride, 3 mg/kg s.c.]. Caffeine-mediated contralateral rotation was also evaluated in rats lesioned with 6-hydroxydopamine 12 weeks previously and exposed to four administrations of apomorphine or vehicle. As for rats repeatedly exposed to vehicle or apomorphine 2 weeks after 6-hydroxydopamine lesioning, caffeine failed to induce contralateral rotation in drug-naive rats, while it did induce a partially context-dependent contralateral rotation in apomorphine-primed rats. Different from rats receiving apomorphine priming 2 weeks after 6-hydroxydopamine lesioning, in 12 week-lesioned rats, caffeine also induced contralateral rotation after one priming with apomorphine (0.3 mg/kg s.c.), a condition which fails to induce context-dependent rotation. Administration of selective antagonists of A1 (8-cyclopentyl-1,3-dipropylxanthine), (DPCPX) or A2A (5-amino-2-(2-furyl)-7-(3-phenylpropyl)-pyrazolo[4,3-e]-1 ,2,4-triazolo[5c]pirimidine), (SCH 58261) adenosine receptors failed to induce contralateral rotation either alone or in combination in 12 week-6-hydroxydopamine-lesioned rats repeatedly primed with apomorphine. All together, the results indicate that: (i) caffeine does not induce any contralateral rotation in drug-naive 6-hydroxydopamine-lesioned rats; (ii) priming with a dopamine agonist enables caffeine to induce contralateral rotation, this rotation is, however, context independent only after priming with a selective D1 agonist; (iii) contralateral rotation in response to caffeine is dependent on the time from the 6-hydroxydopamine lesion; (iv) blockade of A1 and A2A adenosine receptors with selective antagonists does not induce contralateral rotational behaviour in 6-hydroxydopamine-lesioned rats.

Animals↗

Inhibitory influence of soleus massage onto the medial gastrocnemius H-reflex.

It has previously been reported that the soleus Hoffmann (H-)reflex is diminished in amplitude during a massage of the ipsilateral triceps surae. A question arises as to the origin of this decrease. The purpose of this study was to determine whether massage does indeed diminish motoneuronal excitability or whether the decrease is an artefact associated with the experimental procedures, i.e. saturation of the transmission capacity of the afferent pathway. H-reflexes and the corresponding muscle (m-)responses were recorded from the medial gastrocnemius (MG) muscle during a 3-minute massage of the ipsilateral soleus muscle in 12 neurologically healthy adults during 4 control conditions (C1, C2, C4, C5) and 1 experimental (C3-massage) condition. Peak-to-peak mean amplitudes of the MG H-reflex obtained during massage were significantly reduced in comparison to all control values recorded while the subjects were at rest. These results suggest that massage does indeed diminish motoneuronal excitability, since these effects were not restricted to the homonymous motoneurone pool, but could also be demonstrated for a close synergistic muscle, uninvolved in the massage.

Adult↗

[Gastrointestinal hemorrhage].

Acute digestive system haemorrhage is a recurrent cause of hospitalization. As to the upper segment of the digestive system, ulcerous peptic disease is often the cause of this pathology, above all in Western Countries. As to the lower segment, colic diverticula and angiodysplasy represent the most common cause. Bleeding usually clears up spontaneously or with hemodynamic pharmacological help. In some cases, the situation does not improve because of bleeding persistence, so more complex diagnostic and therapeutic techniques are necessary. Instrumental diagnostics is based on endoscopy (once with flexible optical fibre instruments, now with videoendoscopy) whose diagnostic effectiveness is inversely proportional to the latency since the haemorrhagic occurrence. Success is evident in 90-95% of the cases within the first twelve hours. Mesenteric angiography and scintigraphy with marked erythrocytes can solve difficult diagnosis and topographic location on some serious occasions. In every case the risk of complication and death is closely related to the haemorrhagic consistency, the flow of the bleeding, the basic disease, the age and the presence of chronic diseases. The authors examine a personal survey taken from the hospitalization in their own ward during a period of a year.

Adult↗