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P Gilli

Publications and source records attributed to P Gilli.

At least 37 records · Page 2Linked to original sources

Stereochemistry of serotonin receptor ligands from crystallographic data. Crystal structures of NAN-190.HBr, 1-phenylbiguanide, MDL 72222 and mianserin.HCl and selectivity criteria towards 5-HT1, 5-HT2, and 5-HT3 receptor subtypes.

The crystal and molecular structures of the following serotoninergic drugs have been determined: (1) 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide hemihydrate (NAN-190.HBr), C23H28N3O3+.Br-.1/2H2O, M(r) = 483.42, monoclinic, C2/c, a = 21.916 (4), b = 15.207 (2), c = 14.052 (2) A, beta = 101.56 (1) degree, V = 4588 (1) A3, Z = 8, Dx = 1.40 Mgm-3, lambda (Mo K alpha) = 0.71069 A, mu = 1.823 mm-1, F(000) = 2008, T = 295 K, R = 0.035 for 2617 observed reflections; (2) N-phenylimidocarbonimidic diamide (1-phenylbiguanide), C8H11N5, M(r) = 177.21, monoclinic, P2(1)/c, a = 9.781 (2), b = 35.040(5), c = 11.000 (2) A, beta = 97.72(1) degree, V = 3736(1)A3, Z = 16, Dx = 1.26 Mg m-3, lambda (Mo K alpha) = 0.71069 A, mu = 0.084 mm-1, F(000) = 1504, T = 295 K, R = 0.070 for 3407 observed reflections; (3) 8-methyl-8-azabicyclo[3.2.1]oct-3yl 3,5-dicholorobenzoate (MDL 72222), C15H17Cl2NO2, M(r) = 314.21, triclinic, P1, alpha = 8.480 (3), b = 9.840 (3), c = 10.158 (4) A, alpha = 90.04 (3), beta = 111.77 (3), gamma = 105.07(3) degrees, V = 755.6(5) A3, Z = 2, Dx = 1.38 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.430 mm-1, F(000) = 328, T = 295 K, R = 0.070 for 1685 observed reflections; (4) 1, 2, 3, 4, 10, 14b-hexahydro-2-methyldibenzo[c.f]pyrizino[1, 2-alpha]azepine hydrochloride (mianserin. HCl), C18H21N2+. Cl-, M(r) = 300.83, monoclinic, P2(1)/a, a = 9.014 (2), b = 14.917 (2), c = 12.412 (2) A, beta = 108.84 (1) degree, V = 1579.5 (5) A3, Z = 4, Dx = 1.26 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.237 mm-1, F(000) = 640, T = 295 K, R = 0.063 for 1493 observed reflections. A systematic structural analysis of the present compounds and others known to interact with the 5-HT1, 5-HT2 and 5-HT3 receptors allows to identify their similarities with the endogenous ligand serotonin (5-HT) and the stereochemical differences which determine selectivity for the various receptor subtypes. The pharmacophoric feature for 5-HT receptor binding is identified in a constant-length vector linking an aromatic ring with a protonated nitrogen, while specific affinities for receptorial subtypes and the nature of the effect appear to be modulated by the dimensions of the substituents at nitrogen.

Biguanides↗

The determination of plasma transferrin receptor as good index of erythropoietic activity in renal anemia and after renal transplantation.

Both the plasma determinations of erythropoietic (EPO) and transferrin receptor (TfR) would provide a good characterization of anemia especially when mixed erythron disorders underlie, such as in renal failure. Immunologic assays of EPO and TfR, as well as standard hematologic determinations (hematocrit, reticulocyte count, serum iron, transferrin, ferritin) were performed in patients with chronic renal failure (CRF), in regular dialysis treatment (RDT) and in transplanted (TX) patients. In nonanemic TX patients both EPO and TfR ranged normally, whereas in anemic TX ones (Hct < 40%) both values were increased suggesting the physiologic response both of the kidney and of the erythron to decreased red cell mass. In transitory posttransplant erythrocytosis the increased values of TfR, with normal EPO values, would hypothesize a defective feedback to EPO release. Both EPO and TfR values were found increased in TX patients with adult polycystic kidney disease with persistent erythrocytosis (Hct > 50%), thus confirming previous observations. In CRF and RDT patients, all anemic, both EPO and TfR were normal, even though significantly low with respect to the degree of anemia. In RDT seriously anemic patients, the administration of recombinant human EPO induced different patterns of bone marrow response. We conclude that the determination of TfR would provide further information on renal anemia since the receptor increase mostly preceded the rise of Hct, evidencing those patients who will not have an effective bone marrow response to the therapy.

Adult↗

Prevention of hepatitis C virus in dialysis units.

To understand how to prevent the diffusion of hepatitis C virus (HCV) in dialysis units, 289 chronic dialysis patients treated in a renal department from the beginning of 1990 to June 30, 1993, were studied. Patients were screened monthly for alanine aminotransferase values and every 3 months for anti-HCV antibodies. At the beginning of the study the prevalence of anti-HCV antibodies was 24.7%. Two study groups were defined. In the first, anti-HCV-positive patients were treated on separate machines; in the second, 13 anti-HCV-positive and 13 negative patients shared the same machines. Patients in the study were treated with traditional dialysis, employing low-permeability membranes and disposable dialysate circuits on machines without an ultrafiltration control device. The 'universal precautions' were rigorously applied. The use of blood transfusions was markedly reduced. Although new patients starting dialysis treatment revealed a high frequency of HCV positivity (10.8%), the overall prevalence of HCV infection in the department did not increase during the follow-up period. Furthermore, no seroconversion was found in patients on dialysis treatment, not only in the section where anti-HCV-positive patients were treated on separate machines, but also in the section where anti-HCV-positive and anti-HCV-negative patients shared the same machines. The possibility of an intradialytic diffusion of HCV appeared to be very low and the treatment of infected patients on separate machines not strictly necessary.

Alanine Transaminase↗

Continuing loss of vertebral mineral density in renal transplant recipients.

This cross-sectional study examined bone abnormalities by digital radiography, bone densitometry and biochemical tests in 44 clinically asymptomatic renal transplant recipients 6-195 months after renal transplantation. Abnormal radiographs were obtained in 40 of the 44 patients. Dual-energy X-ray absorptiometry (DXA) performed at the lumbar spine (L2-L4)/showed a negative Z score in all patients, ranging from -1 to -1.9 in 28 patients and less than -2.0 in 16 patients. The severity of osteopenia increased with the length of time after transplantation and there was a significant correlation with parathyroid hormone values in patients with normal and low glomerular filtration rates. Our data suggest that decreased bone density values (Z score less than -2) are present in about one-third of patients with renal transplants. Bone loss appears to continue after transplantation. Steroid therapy and immunotherapy are probably the cause of this bone loss. Bone mineral measurements alone are helpful in identifying asymptomatic patients with low bone mass after transplantation.

Absorptiometry, Photon↗

Familial interstitial nephropathy without hyperuricemia.

Progressive hereditary nephropathy is described in 6 members of a single family. Renal biopsies, performed in 3 patients, revealed tubular atrophy, interstitial fibrosis, and lymphomonocytic infiltration associated with severe vascular lesions. These features were disproportionately serious when related to age, arterial pressure, and renal function. Similar familial nephropathy has been reported in the literature, generally in association with gout or asymptomatic hyperuricemia. The patients described here had normal blood concentrations of uric acid. It is proposed that the members of the present group of patients are suffering from the same interstitial nephropathy as that described in the literature and that the hyperuricemia found by other investigators is coincidental and does not play a pathogenetic role.

Adult↗

Lipoprotein abnormalities in hypertriglyceridaemic patients on long-term haemodialysis.

OBJECTIVES: To analyse by ultracentrifugation in a zonal rotor the plasma lipoproteins in hypertriglyceridaemic patients on long-term haemodialysis. DESIGN: Case-control study. SETTING: Tertiary referred care centre. SUBJECTS: Ten consecutive hypertriglyceridaemic patients on haemodialysis and 12 consecutive healthy controls. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein cholesterol concentrations, lipoprotein physical properties and compositions, apolipoprotein concentrations. RESULTS: Hypertriglyceridaemia in patients undergoing haemodialysis is characterized by an increased amount of small and slow floating very-low density lipoproteins (VLDL), higher concentrations of intermediate density lipoproteins (IDL) and small and dense low-density lipoprotein (LDL) particles; reduced levels of high-density lipoproteins (HDL), in particular of HDL2. The lipoprotein composition of such patients indicates reduced cholesterol ester and increased triglyceride content. Compared to controls, they have lower levels of plasma apolipoprotein A-I and A-II and higher B, C-II, C-III and E values. CONCLUSIONS: The lipoprotein abnormalities observed in hypertriglyceridaemic patients undergoing haemodialysis have recently been associated with an increased incidence of vascular complications and may in part explain the high incidence of vascular disease reported in these subjects.

Aged↗