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Biomedical subjects

C Alafaci

Publications and source records attributed to C Alafaci.

35 records · Page 2Linked to original sources

L-acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain.

With ST200 as the commercial source of L-acetylcarnitine hydrochloride, 94 patients were enrolled in this study; 31 were assigned to placebo, 31 to ST200 at 0.5 g/die and 32 to ST200 at 1 g/die, the i.m. treatments being injected daily for 15 consecutive days. In general, concerning the efficacy assessment, the administration of ST200 at 1 g/die appeared to be better than ST200 at 0.5 g/die when compared with the placebo administration. Statistically significant differences were revealed by the comparison of ST200 at 1 g/die to placebo, for the following variables: a) total motility as rated at the end of the 15-day study and confirmed by intention-to-treat analysis, b) visual analogue scale for all the patients having observation at day 15, and c) the objective and subjective judgements on efficacy. Safety and tolerability were good over the entire course of the study.

Acetylcarnitine↗

Peritumoral edema in meningiomas: microsurgical observations of different brain tumor interfaces related to computed tomography.

Although generally benign tumors, meningiomas may be associated with extensive peritumoral brain edema as seen on computed tomographic scans. Fifty-two patients with intracranial meningiomas were studied, and the hypodense areas on computed tomographic scans were related to the intraoperative microsurgical findings and to the sizes of the tumors. We have identified three kinds of tumor-brain interfaces characterized by different difficulties in microsurgical dissection: smooth type, transitional type, and invasive type. These different microsurgical interfaces seem to correlate very precisely with computed tomographic images of halo-like and finger-like hypodense areas, allowing prediction of the microsurgical effort to be made in the surgery of meningiomas. The size of the tumor seems to be important in our subjects in determining the amount of edema produced. Indeed, a positive correlation (P < 0.001) was found between the sizes of the tumors and the extent of peritumoral hypodensity. A positive correlation (P < 0.002) also has been found between grade of edema and cortical penetration. Cerebral cortex disruption was systematically observed by us in invasive-type meningiomas and in 3 of 21 cases (14.3%) in transitional-type meningiomas. No penetration was observed in smooth-type meningiomas.

Blood-Brain Barrier↗

Combined systemic beta-interferon and thymostimulin administration for metastatic brain tumors. A brief report.

Interferon-beta (IFN-B) plus thymostimulin (Th) were administered for eight weeks, intravenously and by intramuscular route to eight patients with metastatic brain tumors. No patient had a complete response. One had a stable disease and seven a progressive disease during that time. The mechanisms of the action of IFN-B and Th, and the possible therapeutic value are discussed.

Aged↗

Cerebellopontine angle lipoma. Case report.

A cerebellopontine angle (CPA) lipoma in a 17 year-old woman is reported. The patient was admitted for evaluation of episodic vertigo, preauricolar pain and progressive hearing loss on the right ear. Auditory brain stem evoked potentials revealed an interwave latency increase on the right ear. Computerized Tomography and Magnetic Resonance Imaging showed a low density lesion and high intensity signal, respectively, in the right CPA. Reports of surgically treated lipomas of the CPA are extremely rare. Our patient underwent a right lateral suboccipital craniotomy and a subtotal resection of the lesion. Histological examination revealed a richely vascularized lipomatous tissue traversed by nerve fibers. The surgical indication for such rare lesion is discussed.

Adolescent↗

Tachykinins (substance P, neurokinin A, neuropeptide K, and neurokinin B) in the cerebral circulation: vasomotor responses in vitro and in situ.

The vasomotor responses of tachykinins have been studied in the cerebral vasculature of human, pig, cat, and guinea pig. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide K (NPK) induced concentration-dependent relaxations of precontracted cerebral arteries in all species when examined by a sensitive in vitro technique. In addition, the relaxant responses to SP, NKA, and NKB were studied in cat pial arterioles by peptide microapplication in situ. In human pial vessels, the order of relaxant potency was SP greater than NKB greater than NKA greater than NPK; in the pig middle cerebral artery, there was no difference in potency between the tachykinins; in the cat middle cerebral artery, SP = NKB greater than NKA = NPK; and in the guinea pig basilar artery, SP much greater than NPK = NKA greater than NKB. Responses induced by SP, NKA, and NKB in the cat were comparable in vitro and in situ. Removal of the endothelium abolished relaxation induced by all four tachykinins. The relaxant responses of guinea pig basilar arteries to SP, NKA, and NPK were competitively antagonized by the SP antagonist Spantide. However, Spantide lowered the Imax of the NKB concentration-response curve without any rightward shift, suggesting action at a different site than the other tachykinins. In the guinea pig basilar artery, the relaxation seems to be exerted via a NK-1 receptor subtype while the receptor subtype is more unclear in cerebral arteries from human, cat, and pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neuropeptide Y and vasoactive intestinal peptide in experimental subarachnoid hemorrhage: immunocytochemistry, radioimmunoassay and pharmacology.

The involvement of noradrenaline (NA), neuropeptide Y, (NPY), 5-hydroxytryptamine (5-HT), acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) has been examined in the late phase of spasm after an experimental subarachnoid hemorrhage (SAH) in a rat model. Immunocytochemistry and radioimmunoassay of blood vessels from the circle of Willis did not show significant differences in NPY- and VIP-like immunoreactivity 2 days post SAH as compared to control vessels. The postjunctional effects of NA, NPY, 5-HT, ACh and VIP were studied two days after SAH using a sensitive in vitro system. NPY induced contractions were significantly (p less than 0.01) weaker (lower Emax) in SAH as compared to control rats while the relaxant responses to ACh and VIP were slightly increased after SAH. These observations reveal that in a rat model of SAH, with an approximately 20% in vivo constriction at two days, dynamic changes occur in cerebral artery reactivity despite any obvious change in sympathetic or parasympathetic perivascular nerve networks.

Acetylcholine↗

Endothelin: an endothelium-derived vasoactive peptide and its possible role in the pathogenesis of cerebral vasospasm.

The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline injected controls. Endothelin elicited strong concentration-dependent contraction of rat basilar artery segments. The response was slow in onset and long lasting. The endothelin-induced contraction was much stronger in the SAH compared to control animals. Our findings suggest a role of the peptide in the pathophysiology of cerebral vasospasm.

Animals↗

Evidence that calcitonin gene-related peptide contributes to the capsaicin-induced relaxation of guinea pig cerebral arteries.

Pretreatment with capsaicin caused a depletion of substance P (SP)-, neurokinin A (NKA)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from the trigeminal ganglion, dura mater and cerebral arteries. The effect of capsaicin on isolated basilar arteries of guinea pig resulted in a biphasic relaxant response of histamine precontracted vessels. The first phase of the capsaicin-induced relaxation was absent in capsaicin-treated guinea pigs. Furthermore, repeated administration of capsaicin decreased the first but not the second phase of relaxation, supporting the view that a stored agent was released, while the second phase probably was due to a direct effect of capsaicin per se. The biphasic effect was not modified by the SP antagonist Spantide in a concentration that blocks tachykinin response (3.10(-6) M), nor by removal of the endothelium. There was no significant difference in pD2 values (-log concentration eliciting half maximum relaxation) between relaxations induced by SP, NKA, neurokinin B, neuropeptide K or CGRP in capsaicin pretreated as compared to vehicle-treated animals. These results are in support of the assumption that CGRP is involved in the capsaicin-induced relaxation caused by release of vasoactive agents from sensory afferent nerves.

Animals↗

Enhanced vasoconstrictor effect of endothelin in cerebral arteries from rats with subarachnoid haemorrhage.

The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline-injected controls. Endothelin elicited concentration-dependent contractions of rat basilar artery segments. The endothelin-induced contractions were much stronger in the SAH compared to control animals, which suggests a role in the pathophysiology of cerebral vasospasm.

Animals↗

Origin and postnatal development of nerves showing 5-hydroxytryptamine-like immunoreactivity supplying major cerebral arteries of the rat.

Nerve plexuses showing 5-hydroxytryptamine (5-HT)-like immunoreactivity (5-HTLI) have been demonstrated in all the major cerebral arteries of the rat using fluorescence immunohistochemistry on whole-mount stretch preparations. Following bilateral superior cervical ganglionectomy, nerves disappeared from all the vessels studied with the exception of the vertebral and basilar arteries where fibres remained. Using image analysis, the density of nerves containing 5-HTLI showed little change between vessels from 3 to 4-week-old and 6 to 7-week-old animals, in contrast to another study which has shown marked reductions in 5-HT-immunoreactive neuronal cell bodies in the superior cervical ganglion over the same period of early development. It was concluded that while the terminals of cerebrovascular nerves retain the capacity to synthesise and/or store 5-HT throughout life, their cell bodies may lose this function soon after birth.

Animals↗

5-HT-containing nerves to major cerebral arteries of the gerbil originate in the superior cervical ganglia.

This study has shown that over 95% of the 5-hydroxytryptamine (5-HT)-containing nerves to major cerebral arteries in the gerbil share a common origin with noradrenergic cerebrovascular nerves in the superior cervical ganglia. A small group of 5-HT-containing and noradrenergic nerves to the vessels of the posterior brain circulation had a different origin, which may be either central or peripheral. The pial blood vessels of the gerbil appeared to have no 5-HT-containing nerve supply. The effects of unilateral superior cervical ganglionectomy on 5-HT-containing and noradrenergic nerves to the arteries of the circle of Willis were different. Our results showed total loss of 5-HT-containing nerves on the vessels ipsilateral to the ganglionectomy combined with ca. 50% reductions of nerve density on the vessels of the contralateral side. There were no contralateral reductions of noradrenergic nerve density in parallel experiments although again the ipsilateral side was totally denervated. We suggest that 5-HT-containing cerebrovascular nerves are differently distributed as well as being in some way more sensitive to nerve damage compared to noradrenergic cerebrovascular nerves. The relationship between a combined serotonergic and noradrenergic vasoconstrictor control of large cerebral blood vessels and serotonergic vasodilation of small pial blood vessels is discussed.

Afferent Pathways↗

Cerebral perivascular serotonergic fibres have a peripheral origin in the gerbil.

The origin of serotonergic nerves supplying the large cerebral vessels of the gerbil has been investigated after bilateral superior cervical ganglionectomy. Immunohistochemical techniques were applied to whole-mount stretch preparations of the cerebral vessels. Removal of both ganglia resulted in the complete loss of immunoreactive fibres in the vessels supplied by the internal carotid artery and in a marked reduction of fibres innervating vessels of the vertebro-basilar system, indicating that most of the cerebrovascular serotonergic nerves have a peripheral sympathetic origin in the gerbil. The contrast with the central origin of serotonergic perivascular nerves claimed in the rat is discussed.

Animals↗

Perivascular nerve types supplying cerebral blood vessels of the gerbil.

The present study shows that cerebral blood vessels of the gerbil resemble other species in being richly supplied by NA-, 5-HT- and NPY-containing nerves. By contrast, the peptidergic nerves containing SP, CGRP and VIP are less dense. The results of superior cervical ganglionectomy show that the SCG is the principal source of NA-, NPY- and 5-HT containing cerebrovascular nerve fibres in the gerbil. The substances seem likely to coexist in some perivascular nerve fibres.

Animals↗

Histochemical and immunohistochemical study of noradrenergic, serotonergic and peptidergic innervation of the cerebral circulation.

Using fluorescence histochemistry, we have examined the origin of noradrenaline (NA)-, 5-hydroxytryptamine (5-HT)- and neuropeptide Y (NPY)-containing perivascular nerve fibres supplying the major cerebral arteries of the gerbil, and the effect of superior cervical ganglionectomy on their cerebrovascular density and distribution. Bilateral ganglionectomy resulted in a complete loss of these perivascular nerve types in the anterior circulation, while a few fibres still persisted in the posterior circulatory bed. In addition, we demonstrate the presence of both 5-HT- and NPY-positive cell bodies in the superior cervical ganglion (SCG) of adult gerbils, suggesting that the main origin of cerebrovascular 5-HT- and NPY- (as well as NA-) containing nerve fibres is in the SCG.

Animals↗

Peritumoral subarachnoid hemorrhage in microsurgical transitional interface type meningioma: may the interface play a role?

The evidence of an intracranial hemorrhage from a meningioma, in comparison with bleeding from different intracranial tumours, is very infrequent. The pathophysiological mechanisms that can explain the possibility of bleeding from meningiomas have not been yet completely clarified. We report a case of a left parasagittal meningotheliomatous meningioma, situated in the premotor cortex, presenting with a peritumoral hemorrhage, at the interface between the meningioma and the brain parenchyma, and strictly confined within the subarachnoid space. A detailed immunohystochemical study of the tumour was performed. The neuroradiological and neurosurgical analysis of the tumour-to-brain interface, served to understand the pathophysiology of this uncommon behaviour. Other possible pathomechanisms explaining bleeding from meningiomas, in the light of the more recent literature are discussed.

Humans↗