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Biomedical subjects

G Marucci

Publications and source records attributed to G Marucci.

At least 37 records · Page 2Linked to original sources

[Giant-cell reaction in the breast after fine-needle aspiration].

We report two cases in which fine needle aspiration (FNA) in the breast generated changes histologically mimicking malignant lesions. In both cases a population of giant cells was present; the cells were osteoclast-like in the first case and 'atypical' multinucleated stromal giant cells in the second. The underlying lesion was pseudoangiomatous stromal hyperplasia (PASH) in both cases. The reactive nature was confirmed by retracing the needle tract and by the uneventful follow-up of 7 or 2 years, respectively. We propose that giant cell reaction be included in the list of FNA-generated changes.

Biomarkers, Tumor↗

[Myoepithelial differentiation markers in salivary gland neoplasia].

Salivary gland tumors frequently present myoepithelial cell differentiation that is not always easily identified on routinely stained sections. Recently novel markers of myoepithelium have been studied, such as calponin (CALP), caldesmon (CALD), and smooth muscle myosin heavy chain. These markers, together with smooth muscle actin may be useful tools for identifying myoepithelial cells. We immunohistochemically studied a series of 23 benign and malignant salivary gland tumors using antibodies to these four markers. The tumors were classified as follows: pleomorphic adenoma (n = 8), basal cell adenoma (n = 3), myoepithelioma with plasmacytoid cells (n = 2), epithelial-myoepithelial cell carcinoma (n = 6) and adenoid cystic carcinoma (n = 4). All tumors were positive for at least one of the four markers. CALP and smooth muscle actin were the markers more frequently expressed. Positivity was mostly located in the myoepithelial cells that constitute the external layer of the glandular or tubular neoplastic structures. In poorly differentiated epithelial myoepithelial carcinomas, composed of solid sheets of neoplastic cells and sometimes of clear cells, immunohistochemical staining for myoepithelial markers evidenced rudimentary glandular structures. CALP and smooth muscle actin were positive in the two cases of myoepithelioma with plasmacytoid cells. In conclusion, the combined staining with four markers helps to disclose myoepithelial cell differentiation and can be a useful tool for the correct histopathological diagnosis of salivary gland tumors. Among the four markers studied, CALP and smooth muscle actin were the most useful to identify myoepithelial cell differentiation.

Actins↗

Pharmacological profile of enantiomerically pure chiral muscarinic agonists: desoxymuscarines.

The enantiomers desoxymuscarine 6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart force and rate) and M3 (ileum and bladder) receptor subtypes together with the enantiomers of the parent compound muscarine 1. The eutomers (+)-1 and (+)-6 and distomers (-)-1 and (-)-6 were also assayed in vivo on pithed rat. Affinity, relative efficacy and enantio-selectivity were also determined for the compounds under study at M2 (heart force and rate) and M3 (ileum and bladder), in order to investigate muscarinic receptor heterogeneity. The results of this study have been discussed in comparison with the data previously reported for the structurally related fluoromuscarine (+)-4 and difluoromuscarines (+)-5 and (-)-5.

Animals↗

Synthesis and pharmacological characterization of new chiral derivatives of muscarine and allo-muscarine.

Novel derivatives of natural muscarine and allo-muscarine, i.e. the benzyl ethers (-)-10 and (-)-12 and the benzoate (-)-13, were synthesized in very high enantiomeric excess. Target compounds were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart force and rate) and M3 (ileum and bladder) receptor subtypes. The derivatives under study were also assayed in vivo on pithed rat. In addition, muscarinic receptor heterogeneity was investigated by determining the affinity and the relative efficacy of compounds (-)-10, (-)-12 and (-)-13 at M2 (heart force and rate) and M3 (ileum and bladder) receptor subtypes.

Animals↗

Structure-activity relationship at alpha-adrenergic receptors within a series of imidazoline analogues of cirazoline.

Several analogues of cirazoline (2), a selective alpha1-adrenoreceptor agonist, were prepared and their pharmacological profiles studied. Although at the alpha1-adrenoreceptor all the compounds displayed a significant agonist activity, at the alpha2-adrenoreceptor they showed either agonist or antagonist activity depending on the nature of the phenyl substituent. The qualitative structure-activity relationship led us to the conclusion that the oxygen atom in the side-chain is essential for alpha1-agonist activity, while the cyclopropyl ring is not, and may be replaced by several groups. Of the groups studied, isopropoxy appears to be the best. Instead, the same substitution (i.e., isopropoxy for the cyclopropyl ring) at alpha2-adrenoreceptors causes a reversal of activity. On the other hand, the cyclopropyl ring seems to be important for alpha1-selectivity. Compound 20 is the most potent alpha1-agonist of the series, being equiactive with cirazoline on rat vas deferens and in pithed rat.

Adrenergic alpha-Agonists↗

[4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]-trimethylammonium (McN-A-343)-related compounds. Effect of the butynyl chain inclusion into an aromatic unit on the potency for muscarinic receptors.

A series of derivatives of the known M1 selective muscarinic receptor agonist McN-A-343 (1) was designed with the aim of investigating the effects of structural variations on both the butynyl chain and the phenyl ring of 1. The butynyl chain was replaced with an aromatic spacer, and the effects of such a modification on the stereoelectronic properties of the molecules were theoretically studied and considered compatible with muscarinic receptor affinity. Substituents on the phenyl ring of 1 were selected so as to vary their electronic and hydrophobic properties. This design strategy did not produce muscarinic M1 receptor agonists more potent than the prototype 1, even if some analogues displayed functional selectivity for different muscarinic receptor subtypes. Compounds 3 and 7 were selective agonists towards muscarinic M3 receptors, while compounds 14, 16 and 18 were selective muscarinic M2 receptor agonists. The most interesting derivative was 8, a full agonist at muscarinic M3 receptors devoid of activity at both muscarinic M1 and M2 subtypes. The pharmacological profile of the series was further characterized by studying the anticholinesterase and miotic activities of some representative compounds. Compounds 3-8 turned out to be weak acetylcholinesterase inhibitors, while derivatives 4, 6, 8 and 11 were able to significantly reduce the pupillary diameter in rabbit, indicating 8 as an effective miotic agent.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

[Hyperkeratosis follicularis et parafollicularis in cutem penetrans (Kyrle's disease). Description of a case].

A case of hyperkeratosis follicularis et parafollicularis in cutem penetrans Kyrle's disease in a 41-year-old woman is described. It was a recurrence of a lesion surgically removed and originally diagnosed as invasive squamous cell carcinoma. Kyrle's disease is a rare dermatosis and should not be confused with neoplastic conditions i.e. squamous cell carcinoma. Pathologists should be aware of such conditions in order to avoid misdiagnosis, which can imply over treatment for the patient.

Adult↗

[Malignant glial tumor with skeletal muscle differentiation. Description of a case].

A case of CNS gliomyosarcoma, in a 71-year-old female with skeletal muscle differentiation is presented. The tumor was composed by two cell types: one showed features typical of glial cells, the other was constituted by elements having immunohistochemical positivity with desmin, sarcomeric actin, myoglobin and myogenin antisera. It is postulated an origin from a cell capable of dual differentiation.

Actins↗

[Heterotopic mesenteric ossification. Description of a case].

We describe a case of heterotopic mesenteric ossification presented in a 25 year-old male who underwent laparotomy for a fire-gun injury. Two weeks later he experienced small bowel obstruction and for this reason he has been operated five times with removal of segments of small bowel. Now, nine months later, he needs ileostomy to avoid another obstruction.

Adult↗

Structure-activity relationships in 1,4-benzodioxan-related compounds. 6. Role of the dioxane unit on selectivity for alpha(1)-adrenoreceptor subtypes.

WB 4101-related benzodioxans 3-9 were synthesized, and their biological profiles at alpha(1)-adrenoreceptor subtypes and 5-HT(1A) serotoninergic receptors were assessed by binding assays in CHO and HeLa cells membranes expressing the human cloned receptors. Furthermore, receptor selectivity of selected benzodioxan derivatives was further determined in functional experiments in isolated rat vas deferens (alpha(1A)) and aorta (alpha(1D)) and guinea pig spleen (alpha(1B)), in additional receptor binding assays in rat cortex membranes containing alpha(2)-adrenoreceptors and 5-HT(2) serotoninergic receptors, and in rat striatum membranes containing D(2) dopaminergic receptors. An analysis of the results of receptor binding experiments for benzodioxan-modified derivatives 3-9 showed high affinity and selectivity toward the alpha(1a)-adrenoreceptor subtype for compounds 3-5 and 7 and a reversed selectivity profile for 9, which was a selective alpha(1d) antagonist. Furthermore, the majority of structural modifications performed on the prototype 1 (WB 4101) led to a marked decrease in the affinity for 5-HT(1A) serotoninergic receptors, which may have relevance in the design of selective alpha(1A)-adrenoreceptor antagonists. The exception to these findings was the chromene derivative 8, which exhibited a 5-HT(1A) partial agonist profile.

Adrenergic alpha-Agonists↗

Synthesis and antagonistic activity at muscarinic receptor subtypes of some 2-carbonyl derivatives of diphenidol.

A series of 2-carbonyl analogues of the muscarinic antagonist diphenidol bearing 1-substituents of different lipophilic, electronic, and steric properties was synthesized and their affinity for the M2 and M3 muscarinic receptor subtypes was evaluated by functional tests. Two derivatives (2g and 2d) showed an M2-selective profile which was confirmed by functional tests on the M1 and M4 receptors. A possible relationship between M2 selectivity and lipophilicity of the 1-substituent was suggested by structure-activity analysis. This work showed that appropriate structural modification of diphenidol can lead to M2-selective muscarinic antagonists of possible interest in the field of Alzheimer's disease.

Animals↗

[Quality control of the "M. Malpighi" Anatomy, Histology, and Pathologic Cytology Section, Oncology Department, University of Bologna, Bellaria Hospital].

The quality control scheme in use at the Department of Anatomic Pathology of the University of Bologna-Bellaria Hospital Since 1993 a quality assurance (QA) scheme has been set up in our Department, modified from the protocol in use at the Department of Pathology of Yale University and published by J. Rosai in his textbook. A QA committee has been appointed and each member is responsible for a specific branch of the total workload; the areas involved are: 1. review of frozen section diagnoses with the final diagnoses 2. randomized review of biopsies (1:25) 3. quality control of cytological cases 4. quality control of specimen adequacy 5. quality control of immunohistochemistry and in situ Hybridization 6. quality control of the cytogenetics laboratory 7. quality control of autopsies All data collected from january 1996 to february 1999 have been reviewed and analyzed in order to provide references for other laboratories and for the purpose of monitoring our laboratory' performance.

Hospitals, University↗

[Orbital embryonal rhabdomyosarcoma in adults. Report of 2 cases].

Rhabdomyosarcoma (RMS) is the most frequent sarcoma of infancy. Embryonal RMS is generally correlated with a better response to chemotherapy. In the present paper two cases of embryonal RMS of the orbit affecting adult patients are reported. Both patients are male, aged 22 and 24 years respectively. In Case 1 the lesion arose primitively in the orbit, in Case 2 the orbit was affected by secondary involvement. Both patients presented a rapid response to chemotherapy, with reduction of the neoplastic mass and regression of symptoms.

Adult↗

Synthesis and pharmacological characterization of enantiomerically pure muscarinic agonists: difluoromuscarines.

The four homochiral 4-deoxy-4,4-difluoromuscarine stereoisomers (difluoromuscarines) were prepared in very high enantiomeric excess. A convenient sequence based on the use of natural as well as "unnatural" ethyl lactate allowed the synthesis of target compounds, whose absolute configuration is dictated by that of the starting synthon. Quaternary ammonium salts (+)-5, (-)-5, (-)-6, and (+)-6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart) and M3 (ileum and bladder) muscarinic receptor subtypes. The eutomer (+)-5 and distomer (-)-5 were also tested in vivo on pithed rat, and their muscarinic activity at the M1 receptor subtype was compared with those of racemic muscarine [(+/-)-1] and (2S,4R,5S)-4-deoxy-4-fluoromuscarine [(+)-4]. Further pharmacological parameters such as affinity, relative efficacy, and enantioselectivity have been determined for compounds (+)-5 and (-)-5 at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The four homochiral difluoromuscarines behave as muscarinic agonists in all the tests with a potency trend which is different from that previously observed with the 4-deoxy-4-fluoromuscarines and (+/-)-1, thus indicating the intervention of the second fluorine atom on the receptor-ligand interaction. Moreover, the second fluorine atom produces significant differences in the affinity and relative efficacy values of compounds (+)-5 and (-)-5 at M2 and M3 subtypes, which could be attributed to a heterogeneity between the muscarinic receptors mediating heart rate and heart force and those involved in the contraction of ileum and bladder.

Animals↗

SAR studies on the potent and selective muscarinic antagonist 2-ethylthio-2,2-diphenylacetic acid N,N-diethylaminoethyl ester.

Molecular modification of the potent and selective muscarinic antagonist 2-ethylthio-2,2-diphenylacetic acid N,N-diethylaminoethyl ester was performed in order to identify M2 selective antagonists able to cross the blood brain barrier and potentially useful in the treatment of Alzheimer's disease. Modifications included substitution or hydrogenation of one of the phenyl rings as well as their incorporation in a tricyclic system. In general the changes introduced were detrimental for both affinity and selectivity. Only a modest M2 selectivity is present in some compounds that, on the other hand, carry a quaternary ammonium group which precludes their penetration into the brain.

Analgesics↗

Synthesis and structure-activity relationship studies in a series of 2-substituted 1,3-dioxolanes modified at the cationic head.

To develop ligands that may be useful in exploring muscarinic receptor heterogeneity, we synthesized a series of analogues of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine oxalate and methiodide bearing a modified cationic head. These compounds, when tested on tissues containing the three subtypes M1, M2, and M3, behaved as muscarinic antagonists whose results showed that different substituents on the quaternary and tertiary nitrogen affect affinity and selectivity in different ways. In particular comparison of the affinities of these ligands with those of the reference compounds points out that compounds bearing an ethyl substituent improve the affinity of the molecule at the three subtypes while compounds bearing a phenethyl substituent are more selective for the M3 sites.

Amines↗