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1.
Eur J Radiol ; 81(12): 3737-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-21893392

ABSTRACT

The hip and its disorders represent a clinical, diagnostic and therapeutic challenge greater than any other joints. Clinical symptoms are usually non specific and provocative maneuvers are sometimes unreliable, pain might be referred even from other joints and many times accurate assessment need imaging techniques. New surgical options, especially the latest development of hip arthroscopy has open horizons for treating intraarticular disorders. In this review article we will review basic clinical assessment and what we need as orthopeadic surgeons from radiology.


Subject(s)
Diagnostic Imaging/methods , Hip Joint/diagnostic imaging , Hip Joint/pathology , Joint Diseases/complications , Joint Diseases/diagnosis , Humans , Preoperative Care/methods , Radiography , Ultrasonography
2.
Farmaco ; 56(10): 791-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11718273

ABSTRACT

After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia.


Subject(s)
Glycine/antagonists & inhibitors , Indoles/chemical synthesis , Animals , Binding Sites/drug effects , Indoles/pharmacology , Male , Mice , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/therapeutic use , Rats , Rats, Sprague-Dawley , Seizures/prevention & control , Stroke/prevention & control , Structure-Activity Relationship
3.
Arch Pharm (Weinheim) ; 332(8): 271-8, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10489537

ABSTRACT

A novel series of indole-2-carboxylate analogues of GV150526 (1) in which the propenoic double bond was substituted with different "probes" or replaced by a isosteric cyclopropyl moiety were synthesized and evaluated for their affinity profile in order to obtain further information on the pharmacophoric model of the glycine binding site associated to the NMDA receptor.


Subject(s)
Binding Sites/drug effects , Glycine/antagonists & inhibitors , Indoles/chemistry , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Glycine/metabolism , Indoles/chemical synthesis , Indoles/pharmacology , Mice , Stereoisomerism , Structure-Activity Relationship
4.
Arch Pharm (Weinheim) ; 332(3): 73-80, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10228452

ABSTRACT

A novel series of indole-2-carboxylate analogues of GV 150526 (1) in which the terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2 -carboxylic acid 6b and 3-[2-(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-c arboxylic acid 6l were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (Ki = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after systemic administration by inhibition of convulsion induced by NMDA in mice.


Subject(s)
Amantadine/analogs & derivatives , Excitatory Amino Acid Antagonists/chemical synthesis , Indoles/chemical synthesis , Norbornanes/chemical synthesis , Receptors, Glycine/drug effects , Receptors, N-Methyl-D-Aspartate/drug effects , Amantadine/chemical synthesis , Amantadine/pharmacology , Animals , Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Indoles/pharmacology , Ligands , Mice , Models, Molecular , N-Methylaspartate/pharmacology , Norbornanes/pharmacology , Receptors, Glycine/antagonists & inhibitors , Seizures/chemically induced
5.
Arch Pharm (Weinheim) ; 332(2): 55-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10191715

ABSTRACT

A novel series of 3-carbamoylethynyl-2-carboxyindoles, antagonists acting at the strychnine-insensitive glycine binding site associated with the NMDA receptor, has been synthesised. This new versatile approach involves the introduction of a 2-chloroethenyl moiety in position C-3 with subsequent derivatisation of the terminal carboxyl group, followed by an unusual elimination of HCl to afford the ethynyl functionality. This novel series of glycine antagonists was evaluated in terms of in vitro affinity at the glycine binding site and the most potent compound was tested in vivo in the NMDA-induced convulsions model in mice.


Subject(s)
Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Glycine/antagonists & inhibitors , Indoles/chemical synthesis , Indoles/pharmacology , Animals , Binding Sites , Glycine/metabolism , Male , Mice , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Structure-Activity Relationship
6.
J Med Chem ; 40(6): 841-50, 1997 Mar 14.
Article in English | MEDLINE | ID: mdl-9083472

ABSTRACT

A series of indole-2-carboxylates bearing suitable chains at the C-3 position of the indole nucleus was synthesized and evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. 3-[2-[(Phenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2-carboxyl ic acid (8) was an antagonist at the strychnine-insensitive glycine binding site (noncompetitive inhibition of the binding of [3H]TCP, pA2 = 8.1) displaying nanomolar affinity for the glycine binding site (pKi = 8.5), coupled with high glutamate receptor selectivity (> 1000-fold relative to the affinity at the NMDA, AMPA, and kainate binding sites). This indole derivative inhibited convulsions induced by NMDA in mice, when administered by both iv and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The effect of the substituents on the terminal phenyl ring of the C-3 side chain was investigated. QSAR analysis suggested that the pKi value decreases with lipophilicity and steric bulk of substituents and increases with the electron donor resonance effect of the groups present in the para position of the terminal phenyl ring. According to these results the terminal phenyl ring of the C-3 side chain should lie in a nonhydrophobic pocket of limited size, refining the proposed pharmacophore model of the glycine binding site associated with the NMDA receptor.


Subject(s)
Excitatory Amino Acid Antagonists/pharmacology , Glycine Agents/pharmacology , Glycine/antagonists & inhibitors , Indoles/pharmacology , Animals , Binding Sites , Binding, Competitive , Carboxylic Acids , Cerebral Cortex/drug effects , Excitatory Amino Acid Antagonists/chemical synthesis , Excitatory Amino Acid Antagonists/chemistry , Excitatory Amino Acid Antagonists/metabolism , Glycine/metabolism , Glycine Agents/chemical synthesis , Glycine Agents/chemistry , Glycine Agents/metabolism , Indoles/chemical synthesis , Indoles/chemistry , Indoles/metabolism , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , N-Methylaspartate/pharmacology , Rats , Receptors, Glutamate/metabolism , Structure-Activity Relationship , Strychnine/pharmacology
7.
Ital J Gastroenterol ; 28(1): 28-30, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8743071

ABSTRACT

A case of hepatic epithelioid haemangio-endothelioma is described in a 42-year-old female who presented with abdominal pain and hepatomegaly. The radiographic finding showed multiple hepatic lesions in both lobes. Diagnosis was based on the liver biopsy. The tumour cells were immunoreactive with factor VIII related antigen and vimentine. A liver transplantation was performed. Although at the time of diagnosis there was no clinical evidence of metastasis, the intra-operatorive examination revealed multiple mesenteric and pulmonary neoplastic nodules. The patient is alive and well seven months after liver transplantation.


Subject(s)
Hemangioendothelioma, Epithelioid/surgery , Liver Neoplasms/surgery , Liver Transplantation , Adult , Biopsy , Female , Hemangioendothelioma, Epithelioid/diagnosis , Hemangioendothelioma, Epithelioid/epidemiology , Hemangioendothelioma, Epithelioid/secondary , Humans , Liver/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Lung Neoplasms/secondary , Mesentery , Peritoneal Neoplasms/secondary
8.
Ital J Gastroenterol ; 25(1): 9-12, 1993 Jan.
Article in English | MEDLINE | ID: mdl-7679014

ABSTRACT

Des-gamma-carboxyprothrombin level was measured by enzyme immunoassay in the plasma of 39 patients suffering from hepatocellular carcinoma and 26 controls. Two of these were anticoagulated by warfarin and revealed very high positive values; the remaining 24, 8 healthy subjects and 16 patients with cirrhosis or chronic hepatitis, were negative. Values indicating pathology were found in 56.40% of patients suffering from hepatocellular carcinoma. All malignancies presenting diameter < or = 3 cm were negative, while high positive levels were found in patients with more advanced neoplasia. The alpha-fetoprotein was increased in 43.58% of the patients with hepatocellular carcinoma and in 6.25% of controls with chronic liver diseases. Positive values for both des-gamma-carboxyprothrombin and alpha- fetoprotein were detected in 12/39 patients. An increase of sensitivity (from 43.58 to 69.23%) in detecting hepatocellular carcinoma was found by the complementary use of the two markers relative to sole use of alpha-fetoprotein.


Subject(s)
Biomarkers, Tumor/blood , Biomarkers , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Protein Precursors/analysis , Prothrombin/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/metabolism , Diagnosis, Differential , Female , Hepatitis, Chronic/diagnosis , Humans , Immunoenzyme Techniques , Liver Cirrhosis/diagnosis , Liver Neoplasms/blood , Liver Neoplasms/metabolism , Male , Middle Aged , Sensitivity and Specificity , alpha-Fetoproteins/analysis
9.
Dig Dis Sci ; 36(12): 1741-5, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1748044

ABSTRACT

IgG antibodies against Mycobacterium paratuberculosis protoplasmic antigen were looked for by an enzyme immunosorbent assay in patients with Crohn's disease, Ulcerative colitis, active pulmonary tuberculosis, past pulmonary tuberculosis, and in healthy controls. Serum reactivity for these antibodies was not correlated to PPD skin test positivity without history of mycobacterial disease. A cutoff based on the mean absorbance value of a pool of healthy blood donors was chosen. Positive values were found in 12/24 (50%) patients with active pulmonary tuberculosis and 2/10 (20%) skin-test-positive subjects with past pulmonary tuberculosis as expected, because antigenic sharing is common among different mycobacteria. The control group of blood donors showed borderline positivities in 3/149 cases (2.01%). Positive values were found in 4/108 (3.70%) patients with Crohn's disease and 2/40 (5%) with ulcerative colitis. We conclude that our data do not support a causal relationship between the M. paratuberculosis and Crohn's disease, but occasional patients with inflammatory bowel diseases show unexpected positivities for these mycobacterial antibodies.


Subject(s)
Antibodies, Bacterial/analysis , Crohn Disease/microbiology , Mycobacterium avium subsp. paratuberculosis/immunology , Adolescent , Adult , Aged , Colitis, Ulcerative/immunology , Colitis, Ulcerative/microbiology , Crohn Disease/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Tuberculin Test , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology
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