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P Garofalo

Publications and source records attributed to P Garofalo.

At least 19 recordsLinked to original sources
PubMed2002

[Hyperprolactinemia: from diagnosis to treatment].

Hyperprolactinemia means the presence of abnormally high values of prolactin. It's the most common clinical hypothalamic-hypophysis disorder. Amenorrhea and anovulation are the most usual clinical findings but we can find milder alterations of gonadal function as oligomenorrhea or luteal phase alterations. Galattorrhea appears in approx 30% of patients, but its presence in women with ovulation disorders is highly suggestive of hyperprolactinemia. Subjects with primary amenorrhea and delayed puberty can present hyperprolactinemia. Male hyperprolactinemia can cause hypogonadism (decreased testosterone levels), libido decrease, infertility due oligospermia and gynecomastia while galactorrhea rarely occurs. Accurate anamnesis is very important for a correct diagnosis. It's necessary to exclude pregnancy and primary hypothyroidism. The use of many drugs can be associated with hyperprolactinemia but the most common causes are idiopathic hyperprolactinemia and hypophysis secreting adenoma. Diagnostic examinations are: PRL, FT3, FT4, TSH in case of hypothyroidism, testosterone in men, eventually sampling GH, IGF, ACTH, cortisol, free urinary cortisol. Dynamic tests are used just for idiopathic hyperprolactinemia, but today their meaning is widely discussed. CAT and MNR are necessary to observe hypotalamus, hypophysis and optic chiasm. Twenty years ago the sole option for prolactinoma patients was adenomectomy, today idiopathic hyperprolactinemia can be treated with drugs, while prolactinoma can be treated with a pharmacological, surgical or radiological therapy.

Adolescent↗
PubMed1998

CR 2945: a novel CCKB receptor antagonist with anxiolytic-like activity.

The effects of CR 2945, an antranilic acid derivative member of a novel family of non-peptide CCKB receptor antagonists, have been compared with those of CAM-1028, an analogue of the CCKB receptor antagonist CI-988, L-365,260 a benzodiazepine derivative CCKB antagonist, CR 1795, an analogue of the CCKA receptor antagonist lorglumide and diazepam, a benzodiazepine receptor agonist, in several rodent screens sensitive to conventional anxiolytics. CR 2945 displayed nanomolar affinity for rat CCKB receptors and showed a selectivity ratio of about 9000 for the CCKB over the CCKA receptor. In ex-vivo binding studies, CR 2945, after i.v. and s.c. administration, inhibited the binding of [125I] (BH)-CCK8 in rat cortex homogenate with ID50s of 10.9 mg/kg and 13.5 mg/kg, respectively. In four rodent tests of anxiety (mouse black/white box, rat elevated plus-maze, rat elevated zero-maze and punished licking test in the rat) CR 2945 (0.1-10 mg/kg s.c. or orally) showed significant dose-dependent anxiolytic-like effects. The reference CCKB antagonist compounds CAM-1028 and L-365,260 showed an anxiolytic-like activity less robust than that of CR 2945 in the elevated zero-maze after s.c. administration, and these compounds were inactive in the elevated plus-maze after oral administration. The magnitude of the activity of CR 2945 was comparable to that of diazepam, but without signs of sedation and ataxia. Furthermore, a 7-day repeated treatment with CR 2945 at 10 mg/kg/day s.c. did not induce tolerance or withdrawal anxiety in rats. CR 1795 showed anxiolytic-like activity with a bell-shaped dose-response curve in the elevated zero-maze model in rats (0.1-10 mg/kg, orally and s.c.), whereas in the mouse black/white box test and in the rat elevated plus-maze test it was less effective. The results suggest that CR 2945 might be a promising alternative to the existing therapy of anxiety-related disorders.

Animals↗
PubMed1996

CR 2249: a new putative memory enhancer. Behavioural studies on learning and memory in rats and mice.

The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR 2249), a new entity selected from a new series of glutamic acid derivatives, has been investigated in different paradigms for screening nootropics. CR 2249 ameliorated the memory retention deficit produced by scopolamine in step-through-type passive avoidance in rats and by electroconvulsive shock in step-down-type passive avoidance in mice. CR 2249 was also capable of improving performance in behavioural tests of learning and memory in the absence of cholinergic hypofunction or cognitive deficit. The activity was determined using different passive and active avoidance behavioural test procedures on rats. CR 2249 was active only when given 45 min before training and did not show any effect when administered immediately after the learning training or before the retention trial. No changes in the general behaviour or motor activity of the animals were observed, indicating that CR 2249 effects cannot be attributed to sensory-motor deficit. Microdialysis experiments have shown that CR 2249 significantly increased noradrenaline release in the hippocampus of freely moving rats and reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to hypothesize that CR 2249 memory effect might be mediated by a direct or indirect action on noradrenergic transmission. These behavioural results suggest that this new agent has clinical application in memory disorders.

Animals↗
PubMed1995

8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus.

The effect of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on spatial and non-spatial learning in a water maze was studied using two tasks of equal difficulty, with the same motor, motivational and reinforcement demands. Rats were examined for choice accuracy in a two-platform spatial discrimination task. Rats treated subcutaneously with 100 micrograms/kg 8-OH-DPAT were impaired in choice accuracy with no effect on latency. Treated rats made more errors of omission than controls only on days 1 and 2 of training. Infusion of 1 microgram/microliter spiroxatrine (SPX) or 5 micrograms/microliters of (+)WAY100135, two potent 5-HT1A receptor antagonists, in the CA1 region of the dorsal hippocampus antagonized the impairment in choice accuracy caused by 8-OH-DPAT. The effect on errors of omission on days 1 and 2 of training were not significantly modified by spiroxatrine or (+)WAY100135. Rats treated with 8-OH-DPAT were not impaired in their ability to learn a visual discrimination in a water maze. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus impairs spatial but not visual discrimination in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Thrombosis of parietal, but not striate, cortex impairs acquisition of a 14-unit T-maze in the rat.

We evaluated parietal cortex (PCTX) involvement in learning a shock-motivated, 14-unit T-maize in young F344 rats. In Experiment 1, each rat was placed into a stereotaxic instrument, and the scalp was retracted before either the photosensitive dye, rose bengal, or saline (CON) was provided via a jugular catheter. After 60 s, halogen lamps were used to illuminate the cranium bilaterally over PCTX for 40 min to activate the dye and generate a thrombus in dye-injected rats. Active avoidance pretraining in a straight runway occurred 12 days after surgery. Each rat was provided acquisition (ACQ) trials in the 14-unit T-maze 24-h later. The PCTX rats were impaired relative to CON in errors, run time, alternation errors, and shock frequency measures in the 14-unit T-maze, but not in shock duration. The thrombosis extended to areas comprising anteromedial and posterior PCTX, and also into the striate cortex (SCTX). In Experiment 2, rats were divided into four groups: a PCTX group that received bilateral illumination; PCTX+SCTX and SCTX groups that were illuminated at midline; and a CON group that received the surgery and either dye or illumination. Only PCTX differed from CON, with maze performance similar to Experiment 1. The thrombosis for the PCTX group in Experiment 2 was confined to anteromedial and posterior PCTX. Thus, PCTX, but not SCTX, was implicated in ACQ of this maze task, suggesting that PCTX might be involved in the robust age-related impairments in ACQ previously observed.

Age Factors↗
PubMed1994

Erythrocyte-depleted allogeneic human umbilical cord blood transplantation.

Cord blood is a recently recognized source of hematopoietic stem cells. It can be employed successfully to reconstitute hematopoiesis following allogeneic transplantation. One current drawback of cord blood as a treatment has been a risk of transfusion reactions attributable to ABO blood group mismatch. Removal of red cells from the cord blood has led to reduction of the stem cells by 30-50%. In this paper we report red cell depletion by a method that employs 3% gelatin to effectively sediment the erythrocytes and selectively deplete red cells but permits 94% recovery of nucleated cells and enrichment of colony-forming cells by granulocyte-macrophage colony-forming units, erythrocyte burst-forming units, and granulocyte-macrophage-megakaryocyte colony-forming units in the cord blood preparation. This technique has been employed in our study to remove red cells from the cord blood of a male infant delivered by cesarean section, which has permitted treatment of a female sibling suffering from leukemia. The recipient was 8 years old and weighted 36.7/kg. Complete HLA identity between the two siblings was established. A cord blood cell transplant of cryopreserved and later thawed cells (4 x 10(7) nucleated cells per kilogram) was administered to the patient after intensive myeloablative chemotherapy. The patient exhibited a prompt hematologic recovery (absolute neutrophil count > 500 by day 31, 100% male cells in bone marrow and peripheral blood by day 25) and has experienced a 13-month disease-free survival to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine-induced learning impairment of rats in a 14-unit T-maze.

Phenserine ((-)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer.

Acetylcholinesterase↗
PubMed1992

The long-acting cholinesterase inhibitor heptyl-physostigmine attenuates the scopolamine-induced learning impairment of rats in a 14-unit T-maze.

Heptyl-physostigmine (heptyl-Phy), a new carbamate derivative of physostigmine (Phy), has been assessed for potential clinical value by evaluating its in vitro activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), its duration of in vivo activity against rat plasma AChE, and its effects on attenuating a scopolamine-induced impairment in learning performance of young rats in a 14-unit T-maze. Heptyl-Phy demonstrated potent cholinesterase inhibition, with activity similar to that of Phy against AChE, IC50 values 21.7 +/- 2.0 nM and 27.9 +/- 2.4 nM, respectively, and significantly greater than that of Phy against BChE, IC50 values 5.0 +/- 0.1 nM and 16.0 +/- 2.9 nM, respectively. Heptyl-Phy achieved maximum AChE inhibition of 92.5% at 60 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, heptyl-Phy at 1.0, 1.5, 2.0 or 3.0 mg/kg, or vehicle was administered i.p. to 52 3-month-old male Fischer-344 rats 60 min prior to maze training. Thirty minutes prior to training, each animal received either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg). Only a 2.0 mg/kg dose of heptyl-Phy significantly reduced the number of errors in scopolamine-treated rats. The other doses did not improve any aspect of maze performance. Although the therapeutic window of heptyl-Phy did not appear wide enough for clinical use, the longer duration of action of heptyl-Phy would appear beneficial.

Acetylcholinesterase↗
PubMed1992

Reduced density of NMDA receptors and increased sensitivity to dizocilpine-induced learning impairment in aged rats.

About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4 months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a dose-dependent impairment in maze performance. Deficiencies were manifested as increases in errors, in runtime from start to goal, and in the number and duration of shocks received. In contrast, young rats exhibited no detrimental effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in these rats revealed a marked age-related decline in NMDA receptor binding in hippocampus. A significant correlation was observed between errors in the maze and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e., rats that made the most errors had the highest level of NMDA receptor binding. Thus, compared to young rats, aged rats were more sensitive to the behavioral effects of NMDA receptor antagonism and they showed a hippocampal loss of [3H]glutamate in binding, which may be related to the increased sensitivity to dizocilpine. The positive correlation between poor maze performance and NMDA receptor binding suggests that the behaviors assessed involve complex interactions between NMDA receptors and other neuronal systems in the hippocampus.

Aging↗
PubMed1992

Complex maze performance in young and aged rats: response to glucose treatment and relationship to blood insulin and glucose.

In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24-25 month) and young (6-7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant (ps less than 0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4-6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations (ps less than 0.05) were observed between maze errors and baseline glucose levels, r(21) = -.62, and peak glucose response, r(19) = .49. However; within the aged group, significant correlations (ps less than 0.01) with maze errors emerged only for baseline glucose, r(13) = -.69, and peak insulin response, r(13) = -.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Effect of lifelong hypocaloric diet on discrete memory of the senescent rat.

The memory retention abilities of aged rats fed different diets were assessed in two different avoidance tasks. The standard passive avoidance procedure revealed an age-related memory impairment in old rats fed a standard diet (ST), whereas old rats fed a hypocaloric diet (HY) behaved similarly to young animals. To clarify whether this deficit could be attributed only to cognitive decay and not other factors, such as the tendency of old rats to prefer darkness to light more than young and adult animals, a multiple passive avoidance task was performed. This test offers rats the possibility to escape to a dark chamber in which they have never been shocked, and thus provides a means of checking factors other than memory retention abilities. All the old rats showed a more marked preference to escape to darkness compared to young and adult animals. However, senescent animals fed a ST diet had poor memory retention abilities compared to aged animals fed the HY diet, and young and adult rats. The results of this test confirmed the findings of the standard passive avoidance task.

Aging↗
PubMed1991

NMDA receptor channel antagonism by dizocilpine (MK-801) impairs performance of rats in aversively motivated complex maze tasks.

To determine the involvement of the N-methyl-D-aspartate (NMDA) receptor in shock-motivated complex maze performance, the drug dizocilpine (DIZO; a.k.a. MK-801) was administered a) to naive, 3-month-old male F-344 rats prior to acquisition (AQ) in the 14-unit T-maze (Experiment 1), and b) to well-trained 11-month-old male F-344 rats prior to testing in a delayed-matching-to-sample (DMTS) task in the detour maze (Experiment 2). For Experiment 1, rats first were pretrained in a straight runway on one-way active avoidance (13/15 correct avoidances) for a maximum of 30 trials. On the following day, either DIZO 0.025 (n = 8), 0.05 (n = 8), 0.1 (n = 8), mg/kg, or saline (SAL; n = 15) was administered subcutaneously (SC) 20 min prior to 15 AQ trials in the shock-motivated 14-unit T-maze. The highest dose disrupted all measures of maze performance including errors, alternation errors, runtime, shock duration and frequency, but also produced marked motor ataxia. The 0.05-mg/kg group displayed significant impairment in AQ of this task but only on the cognitive measures, errors and alternation errors, and the 0.025-mg/kg group was impaired on the alternation measure only. One week later, the 15 SAL rats were divided into 2 groups and tested on retention with either SAL or 0.05 mg/kg DIZO. No effects on maze performance were observed. For Experiment 2, after receiving extensive pretraining in the shock-motivated detour maze, 7 rats were exposed to a novel sequence of 4 problems (P) during each of 7 daily sessions. Performance was evaluated 20 min after SC injection of either DIZO--0.025, 0.05, 0.125 mg/kg, or SAL. The 0.125-mg/kg dose caused extreme motor ataxia which precluded testing during that session. The 0.05-mg/kg but not the 0.025-mg/kg dose significantly disrupted performance on both error and trials to criterion measures. Both problem and interaction effects were significant. Disruption was most evident on two specific problems, those involving a side change from the first to second detour. Also, rats had more difficulty switching sides from problem to problem (few errors on P-1 and most on P-4), suggesting proactive interference effects. In sum, DIZO was observed to significantly disrupt performance in both mazes in a dose-related manner similar to effects observed in previous studies following administration of the anticholinergic drug scopolamine. For the 14-unit T-maze, the present results simulate age-related deficits previously found in acquisition of that task.

Aging↗
PubMed1987

Peripheral effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenylpyridinium ion (MPP+) in the rat.

The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenyl-pyridinium ion (MPP+) on catecholamine concentrations was tested in some peripheral organs of the rat. Acute injection of either compound caused a marked depletion of heart noradrenaline (NA). MPP+ had more effect than the parent compound. MPTP had no effect on adrenal catecholamines while its metabolite was effective, but only after several hours. Repeated MPTP and MPP+ injections (20 mg/kg X 5) resulted in marked depletion of heart NA and adrenal gland adrenaline. Clear recovery was observed in both organs 10 days after treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

The prognostic value of thyroid function tests in predominantly non-alcoholic cirrhotic patients: a prospective investigation.

The prognostic value of thyroid function parameters (T3, T4, rT3 and the rT3:T3 ratio) and common liver tests (serum bilirubin, albumin and prothrombin activity) was investigated on hospital admission in 100 consecutive patients with predominantly non-alcoholic liver cirrhosis. Twenty-nine out of 100 patients had a well compensated cirrhosis and their mean values of thyroid tests were similar to those of 40 healthy controls. A low T3 syndrome was found in the remaining 71 decompensated patients. In these thyroid function parameters were correlated with serum bilirubin and prothrombin activity. Moreover mean values of all thyroid and liver tests, except serum albumin, were significantly different between survivors and nonsurvivors at 3 months. To evaluate the best cut-off value which allowed to predict the outcome of patients, the Receiver Operating Characteristics (ROC) curves were generated for each test by plotting the values obtained in survivors at 3 months (true positives) vs nonsurvivors (false positives). By holding the false positive errors within 10%, the highest percentage of true positive results (i.e. patients dead at 3 months) was observed for the rT3:T3 ratio, rT3 and serum bilirubin at a cut-off point of 0.841, 55 ng/dl and 3.5 mg/dl, respectively. According to the above cut-offs the rT3:T3 ratio had the best positive predictive value (74%; 95% confidence limits 60-90%) in comparison to rT3 and bilirubin.

Adult↗