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Biomedical subjects

A Ricci

Publications and source records attributed to A Ricci.

At least 163 records · Page 9Linked to original sources

Autoradiographic localization of dopamine D2-like receptors in the rabbit pulmonary vascular tree.

In the present study, the pharmacological characteristics and the anatomical localization of dopamine D2-like receptor sites in the extraparenchymal and in the intraparenchymal portion of the rabbit pulmonary artery were investigated using combined radioligand binding and light microscope autoradiography with [3H]-spiroperidol (spiperone) as a ligand. The ligand was bound to sections of the pulmonary artery in a manner consistent with the labelling of dopamine D2-like receptors with an equilibrium dissociation constant (Kd) of about 2.4 +/- 0.07 nmol/l and a maximum density of binding sites of 65 +/- 4.5 fmol/mg tissue. In contrast, binding experiments made with sections of rabbit lung did not allow the evaluation of specific binding. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia of extraparenchymal branches of rabbit pulmonary artery and of large and, to a lesser extent, of medium-sized intraparenchymal branches of the pulmonary artery. No silver grains were found within small branches of the pulmonary artery or of the pulmonary vein. Development of adventitial silver grains was inhibited by compounds active at dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, (-)-sulpiride and bromocriptine than to displacement by N-propyl-norapomorphine, quinpirole or clozapine suggests that the [3H]-spiroperidol binding sites observed in extraparenchymal, large and medium-sized branches of the pulmonary artery belong, probably, to the dopamine D2 receptor subtype. The possible pre-junctional localization of these sites is discussed.

Animals↗

Influence of long-term treatment with L-deprenyl on the age-dependent changes in rat brain microanatomy.

The present study was designed to assess whether treatment with the monoamine oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documented to increase both mean and maximum survival in aged rats as well as sexual performance and cognitive function, has any effect on the age-related microanatomical changes occurring in the rat brain. Male Sprague-Dawley rats received a subcutaneous injection of 0.25 mg/kg L-deprenyl every other day from the 19th to the 24th month of age. Age-matched control rats were injected with saline, whereas 11-month-old untreated rats were used as an adult reference group. Both body and brain weight were increased as a function of age, and they were unaffected by treatment with L-deprenyl. The density of nerve cell profiles in the frontal cortex, in the CA-1 and CA-3 subfields of the hippocampus, in the dentate gyrus and in the cerebellar cortex were decreased in aged rats in comparison with adult rats. The density of nerve cell profiles in the above brain areas of L-deprenyl-treated rats was not significantly higher in comparison with age-matched control animals with the exception of Purkinje neuron profiles. The intensity of Nissl's staining, which may be related to the protein synthetic capabilities of nerve cells, is reduced within pyramidal neurons of the hippocampus and Purkinje neurons of the cerebellar cortex of aged rats. The intensity of Nissl's staining in L-deprenyl-treated rats was not different from adult rats. Lipofuscin deposition was significantly increased within the cytoplasm of pyramidal neurons of the frontal cortex, of the CA-3 subfield of the hippocampus and of Purkinje neurons of the cerebellar cortex. L-Deprenyl administration decreased lipofuscin accumulation within the cytoplasm of the above mentioned nerve cell types. The density of sulphide-silver staining in the intrahippocampal pathway of mossy fibres, which participate in the elaboration of passive avoidance responses, is decreased in aged rats. Treatment with L-deprenyl counters this age-related reduction. The above results suggest that long-term treatment with L-deprenyl is able to counter the expression of some microanatomical changes typical of aging brain.

Aging↗

Pharmacological characterization and autoradiographic localization of dopamine D1-like receptors in the thymus.

The present study was designed to identify the pharmacological profile and the anatomical localisation of dopamine D1-like receptor sites in the rat thymus using [3H]SCH 23390 as a ligand. [3H]SCH 23390 was specifically bound to sections of the thymus. Binding was time, temperature and concentration-dependent belonging in the range of concentrations of radioligand used to a single class of high affinity sites. The dissociation constant was 1.6 nM and the maximal density of binding sites averaged to 170 fmol/mg tissue. The pharmacological profile of [3H]SCH 23390 binding to sections of the rat thymus is consistent with the labelling of dopamine D1-like sites. Dopamine was able to compete with [3H]SCH 23390 binding to sections of rat thymus in the range of nanomolar concentrations. This suggests the labelling of dopamine D5 receptor sites. Light microscope autoradiography revealed the localisation of [3H]SCH 23390 binding sites primarily in the cortex of the thymus and in lesser amounts at the level of thymic corpuscles. The possible functional significance of dopamine D1-like receptors in the rat thymus is discussed.

Animals↗

Dopamine D5 receptors in human peripheral blood lymphocytes: a radioligand binding study.

In the present study we have investigated, using radioligand binding techniques and the dopamine receptor antagonist [3H]SCH 23390 as a ligand, the existence of specific dopamine D1-like receptors in human peripheral blood lymphocytes. [3H]SCH 23390 binding to human peripheral blood lymphocytes was time-, temperature-, concentration-dependent and of high affinity with a dissociation constant value (Kd) of 0.58 +/- 0.05 nM and a maximum binding density (Bmax) of 11.02 +/- 0.3 fmol/5 x 10(6) cells. The binding was also reversible. Pharmacological analysis displacement curves of [3H]SCH 23390 binding with dopamine competing with the radioligand in the submicromolar range suggests that peripheral blood lymphocytes express dopamine D5 receptors rather than dopamine D1 receptors. These results, which are consistent with studies performed with molecular biology techniques, suggest that dopamine may modulate peripheral blood lymphocyte activity. Radioligand binding techniques, applied to lymphocyte receptor studies for their feasibility and flexibility may be used to investigate the possible relationship between the immune and dopaminergic systems. Moreover, they could be employed as a tool in Parkinson's disease, migraine, schizophrenia and hypertension research.

Adult↗

Prediction of mortality in mild to moderately symptomatic patients with left ventricular dysfunction. The role of the New York Heart Association classification, cardiopulmonary exercise testing, two-dimensional echocardiography and Holter monitoring.

In order to investigate the value of peak oxygen consumption (peak VO2) in predicting mortality in mild to moderately symptomatic patients with left ventricular dysfunction, we studied 103 NYHA II/III class patients with a left ventricular ejection fraction (LVEF) < or = 40%. Heart failure was due to coronary artery disease (CAD) in 39 patients, idiopathic dilated cardiomyopathy in 54, hypertension in eight and surgically corrected valvular disease in two. The following variables were analysed: age, cause of heart failure (CAD vs no CAD), NYHA class, peak VO2, LVEF, left ventricular end-systolic volume index (LVESVI), ventricular tachycardia (VT) on Holter monitoring and the use of antiarrhythmic drugs. Statistical analysis was performed by Cox's proportional-hazards regression model. During a mean follow-up period of 20 months, there were 25 deaths. The estimated cumulative probabilities of survival were 88%, 73% and 58% at 1, 2 and 3 years, respectively. Cox's model identified CAD (P = 0.01), NYHA III class (P = 0.04) and LVEF (P = 0.02) as independent, statistically significant predictors of mortality. Peak VO2 had only a marginal statistical significance (P = 0.07). Age, LVESVI, VT on Holter monitoring and use of antiarrhythmic drugs were not related to mortality. These data can be important in patient clinical management and clinical trial design.

Adult↗

Dopamine D1 and D2 receptors in the human ureter and urinary bladder: a radioligand binding and autoradiographic study.

OBJECTIVE: To analyse the pharmacological profile and the anatomical localization of the dopamine D1 and D2 receptors in sections of the pelvic part of the ureter and of the fundus of the urinary bladder. PATIENTS, MATERIALS AND METHODS: Samples of the pelvic part of the ureter and of the fundus of the urinary bladder were taken in men (age range 61 +/- 4 years) who were undergoing lower urinary tract surgery. Biochemical characterization and autoradiographical techniques were used on frozen sections of the ureter or the urinary bladder. [3H]-SCH 23390 was used as a ligand of dopamine D1 receptors and [3H]-spiroperidol as a ligand of dopamine D2 receptors. RESULTS: [3H]-SCH 23390 and [3H]-spiroperidol were bound by specific sections of the ureter and of the urinary bladder. The pharmacological profile of the binding was consistent with the labelling of D1 and D2 receptors respectively. Light microscope analysis of the localization of D1 and D2 receptors revealed the accumulation of the two radioligands in the tunica muscularis of the ureter or of the urinary bladder. CONCLUSION: A possible role of the dopaminergic system in the control of urine flow and of some dysfunctions of the lower urinary tract is suggested.

Aged↗

Pharmacological characterization and autoradiographic localization of dopamine receptors in the portal vein.

1. Dopamine (DA) and DA receptor agonists exert a variety of effects on the cardiovascular system through interaction with specific DA receptors, including decreases in blood pressure and heart rate. 2. The decrease in blood pressure is due primarily to arterial vasodilation. This phenomenon is due to the stimulation of both postjunctional (D1-like or DA1) and prejunctional (D2-like or DA2) receptors causing respectively relaxation of arterial smooth muscle and decrease of the sympathetic vasoconstriction tone. 3. In view of the lack of detailed information on the existence of DA receptors in venous tissue, we have analysed D1-like and D2-like receptors in the rat portal vein using radioligand binding techniques associated with light microscope autoradiography. 4. No D1-like receptors were demonstrated in sections of the rat portal vein, whereas the D2-like receptor ligand, [3H]-spiroperidol, was bound to sections of the vein in a manner consistent with the labelling of D2-like sites. Anatomically, D2-like sites were located within the tunica adventitia, including the adventitia-media border, and in the endothelium. 5. These findings suggest the existence of D2-like but not D1-like receptor sites in the rat portal vein. D2-like sites of the tunica adventitia are probably prejunctional and involved in the modulation of sympathetic outflow. The functional significance of endothelial D2-like sites, if any, should be clarified in future studies.

Animals↗

Loss of dopamine D1-like receptors in the umbilical artery of pre-eclamptic subjects.

1. The influence of pre-eclampsia on the density and pattern of dopamine D1-like receptors was studied in frozen samples of the placental end of the umbilical artery by using radioligand binding and autoradiographic techniques in combination. 2. Analysis was performed on normotensive (n = 10) and pre-eclamptic subjects (n = 9) undergoing caesarean delivery, using [3H]-SCH 23390 as a ligand. Pre-eclamptic patients received a low salt diet and were treated with magnesium sulphate and hydralazine. The possibility that this treatment may cause changes in the density of dopamine D1-like receptors was evaluated by treating male Wistar rats in the same way and by determining [3H]-SCH 23390 binding in sections of the kidney which represents an organ containing dopamine D1-like receptors. 3. The density of dopamine D1-like receptors of the umbilical artery, which are probably vasodilatory, was decreased in pre-eclamptic compared with normotensive subjects. In contrast, the affinity of the radioligand for dopamine D1-like receptors was not statistically different between normotensive and pre-eclamptic subjects. Low salt diet, magnesium sulphate and hydralazine treatment did not affect [3H]-SCH 23390 binding to sections of rat kidney. This suggests that changes in the density of dopamine D1-like receptors in pre-eclamptic patients are a specific phenomenon not dependent upon antihypertensive measures. 4. Analysis of the pharmacological profile of [3H]-SCH 23390 binding to sections of the umbilical artery both in normotensive and pre-eclamptic subjects indicates the labelling of dopamine D5 receptors. 5. These findings collectively suggest that the dopaminergic vasodilatory tone in the umbilical artery is impaired in pre-eclampsia. The possible significance of these data should be clarified in future studies.

Adult↗

The effects of insulin on plasma mevalonate concentrations in man.

Mevalonate production is a limiting step in cholesterol synthesis. We studied the effects of insulin on plasma mevalonate concentrations during a 3-hour euglycemic hyperinsulinemic clamp study in 10 healthy males starting at 9 h a.m. after 14 h of fasting. Physiological variations in plasma mevalonate were evaluated on a different day from 9 to 12 h a.m. under saline infusion. During the clamp studies, slight but significant decreases were noted for VLDL-triglyceride and VLDL-cholesterol at 120 and 180 min (p < 0.05) and for apolipoprotein B-100 from 60 min on (p < 0.05). Plasma mevalonate decreased significantly by 34 and 41% at 120 and 180 min, respectively (p < 0.001), while the mean percent decrease due to diurnal variations was 12% at 12 h a.m. In conclusion, hyperinsulinemia in the presence of euglycemia acutely decreases the circulating levels of mevalonic acid, the immediate product of HMG CoA reductase in the cholesterol pathway.

Adult↗

Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex.

The pharmacological characteristics and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of the human adrenal cortex using radioligand binding and autoradiographic techniques. [3H]SCH 23390 was used as a ligand of D1-like receptors, whereas [3H]spiroperidol was used to label D2-like receptors. No specific [3H]SCH 23390 binding was detectable in sections of the human adrenal cortex. On the other hand, [3H]spiroperidol was bound to sections of the adrenal gland in a manner consistent with the labelling of dopamine D2-like receptor sites. The binding was time, temperature and concentration dependent, belonging in the range of concentrations of the radioligand used for a single class of high-affinity sites. The dissociation constant (Kd) averaged 2.7 nmol/l, whereas the maximum density of binding sites (Bmax) was 160 nmol/mg tissue. Experiments on the pharmacological specificity of [3H]spiroperidol binding to sections of the human adrenal cortex revealed that clozapine was the most powerful displacer of [3H]spiroperidol from sections of the human adrenal cortex. This suggests the presence in the human adrenal cortex of dopamine receptors of the D4 subtype. Light microscope autoradiography showed the highest density of specific [3H]spiroperidol binding sites in the zona glomerulosa and to a lesser extent in the zona reticularis. Only sparse [3H]spiroperidol binding sites were localized in the zona fasciculata. The possible functional consequences of this localization of dopamine D2-like receptor sites in the human adrenal cortex are discussed.

Adrenal Cortex↗

Influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats (SHR). Twelve week male SHR were used in this study. One group was treated with a daily dose of 5 mg/Kg of darodipine, while the control group of SHR was treated with placebo. Age-matched normotensive Wistar Kyoto (WKY) rats were used as a reference group. After 12 weeks of treatment the rats were sacrificed. The brains and the hearts were removed, embedded in resin, cut and used for light microscope analysis. Darodipine treatment reduced blood pressure in SHR. Morphometric analysis of different sized pial and coronary arteries revealed decreased arterial lumen in SHR in comparison with WKY rats. The area occupied by the tunica media and the media-to-lumen ratio were increased in SHR in comparison with WKY rats. In darodipine-treated rats the area occupied by the arterial lumen was increased in comparison with control SHR, whereas the area occupied by the tunica media and the media-to-lumen ratio were decreased. Pial arteries were more sensitive than coronary arteries to darodipine treatment. Medium and small sized pial and coronary arteries were most sensitive to darodipine treatment. Large-sized coronary artery branches were unaffected by pharmacological treatment. The above results suggest that treatment of SHR with darodipine is able to reduce high blood pressure and to counter the development of structural changes of pial and coronary arteries noticeable in SHR. The higher sensitivity of the cerebral vasculature to darodipine treatment is discussed.

Animals↗

Quantitative image analysis study of the cerebral vasodilatory activity of nicardipine in spontaneously hypertensive rats.

The effect of the Ca2+ channel blocker nicardipine on the circle of Willis and the different sized pial arteries was assessed in 20-week-old spontaneously hypertensive rats (SHR) using quantitative image analysis techniques. Normotensive Wistar Kyoto (WKY) rats were also used as a normotensive reference group. In SHR a significant increase of systolic blood pressure (SBP) is noticeable in comparison with WKY rats. The media-to-lumen ratio was increased in the circle of Willis arteries, large sized (diameter > than 150 microns), medium sized (diameter between 150 and 50 microns) and small sized (diameter < than 50 microns), pial artery branches. An increase in the thickness of the tunica media and a luminal narrowing was also seen in medium and small sized pial arteries of SHR in comparison with WKY rats. Treatment with an oral dose of 10 mg/Kg of nicardipine 3 h before the sacrifice significantly reduced SBP in SHR. The drug was without effect on circle of Willis and on large sized pial arteries. Moreover, treatment with nicardipine reduced the thickness of the tunica media, the media-to-lumen ratio and increased the luminal area in medium and small sized pial artery branches. These findings show that treatment of SHR with nicardipine significantly reduces SBP and causes a moderate vasodilatation of arteries regulating cerebrovascular resistance. This property may be useful in avoiding generalized or exaggerated cerebrovascular dilatation which could be accompanied by impaired brain perfusion in hypertension.

Animals↗

[Wash and non-wash system in the perioperative recovery of blood in prosthetic surgery: ultrastructural assessment of corpuscular blood components].

AIM: The authors aimed to perform an ultrastructural morphological analysis of blood recovered using wash and non-wash systems in patients undergoing full cement-free hip replacement in order to evaluate the integrity of the various blood corpuscle components. EXPERIMENTAL PROTOCOL: An open prospective study in patients undergoing full cement-free hip replacement at the Orthopedics Division of S. Orsola-Malpighi Policlinico in Bologna. Materials of S. Orsola-Malpighi Policlinico in Bologna. MATERIALS AND METHODS: Blood recovered postoperatively using a non-wash system was studied in 6 patients. In a further 3 patients perioperatively recovered blood was studied after washing using Cell Saver Haemolite 2 before reinfusion. Red globules, white globules and plaelets were isolated from blood collected using these two different recovery systems and analysed by SEM. RESULTS: Study of the ultrastructural morphology of various corpusculated blood fractions. DISCUSSION AND CONCLUSIONS: From the data in our possession it appears that the ultrastructural morphology of the various corpuscle components of blood in subjects undergoing postoperative recovery is better preserved using a non-wash system. There was no sign of "polluting" material in terms of adipose cells or free bone fragments in either group.

Blood Cells↗

[Esthetic suture of the lower limbs after a saphenous vein graft in cardiac surgery. Polydioxanone vs Vicryl].

The vena saphena magna is widely used as a passage during myocardial revascularisation surgery (CABG). The preparation of the vein involves a long incision on the thigh and leg which is routinely closed using a continuous suture thread in Vicryl of the subcutis and continuous intradermal suture of the cutis. The authors retrospectively evaluated the functional and esthetic results of intradermal suture performed using two different types of reabsorbable thread: PDS II and Vicryl. A total of 178 patients underwent CABG surgery at the Heart Surgery Division of Tor Vergata University of Rome during the period January-September 1992. Mean age was 63 year +/- 7 (SD), 140 were males and 38 females. PDS II 3/0 was used for intradermal suture in 88 patients, whereas Vicryl 3/0 was used in 90. There were no significant differences between the two groups with regard to age, sex, number of grafts, associated pathologies or wound length. After 1-9 months (mean 5.6 months) the surgical wound on the saphenectomized limb was evaluated. It was found that compared to Vicryl the use of PDS II presented a higher incidence of keloids (p > 0.05). This was probably due to the greater reaction provoked in the dermis by the monofilament compared to twisted thread. The authors conclude that the use of a reabsorbable twisted thread, such as Vicryl or Vicryl Rapid, is preferable owing to the higher rate of compliance and lower incidence of complications.

Aged↗

New heterocyclic derivatives of benzimidazole with germicidal activity--XI--Experimental validation of OSAR prediction on antibacterial and antimycotic activity of benzimidazole derivatives.

In continuation of previous studies, Authors describe the synthesis of three new derivatives of 2-(5'-nitro-2'-furyl) benzimidazole, having hydroxy, methoxy or amino group at position 5. The new compounds, synthesized as suggested by a previous chemometric study, were tested in vitro against 5 Gram + and 4 Gram- strains and the mycete C. albicans. Two derivatives (R = OH, NH2) showed a good degree of antibacterial activity, especially the 5-hydroxy derivative, but they were practically inactive against the mycete; these results are in agreement with the prediction of chemometric study.

Anti-Bacterial Agents↗

New heterocyclic derivatives of benzimidazole with germicidal activity--XII--Synthesis of N1-glycosyl-2-furyl benzimidazoles.

Over the last decade, several derivatives of benzimidazole have been synthesized; some of them turned out to have a good antimicrobial activity; however, all of them were not soluble in water. Therefore the N1-heterosides of four derivatives of 2-(2'-furyl) benzimidazole, chosen from those with the highest biological activity have been now synthesized. These compounds were expected to have some new properties, including a good water-solubility and a higher or at least similar biological activity; furthermore, taking into account some previously published data on similar molecules, an antileukemic activity was expected. However, no one of these hypothesis was confirmed experimentally.

Animals↗

New heterocyclic derivatives of benzimidazole with germicidal activity. X-In vivo toxicity of 5-fluoro-2-(5'-nitro-2'-furyl)-benzimidazole (F-O-NO2); preliminary observations.

The in vivo toxicity of 5-fluoro-2-(5'-nitro-2'-furyl) benzimidazole vehiculated in liposomes (L-FONO2), induced in mice by intraperitoneal injection, was evaluated. Toxicity was tested looking at the liver and kidney damage by determining some specific functional parameters (seric urea, seric GPT and urinary beta-NAG): no modifications were observed after administration of L-FONO2 for seven days.

Acetylglucosaminidase↗