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G Amato

Publications and source records attributed to G Amato.

At least 55 records · Page 3Linked to original sources
PubMed2000

Stereochemical course of the biotransformation of isoprene monoepoxides and of the corresponding diols with liver microsomes from control and induced rats.

The stereochemical course of the biotransformation of isoprene by liver enzymes from control and induced rats has been determined. Between the two primarily formed metabolites, 2-methyl-2-vinyloxirane (2) and isopropenyloxirane (3), epoxide 2 is rapidly transformed into the corresponding vicinal racemic diol 4, predominantly through a nonenzymatic hydrolysis reaction. At variance, epoxide 3 is mainly biotransformed into the diol 5 by microsomal epoxide hydrolase (mEH) to give, before 50% conversion, selectively (R)-3-methyl-3-butene-1,2-diol, 5. The hydrolysis competes with the oxidation of the monoepoxide 3 to the corresponding diepoxides 6. Epoxidation of 3 catalyzed by P450 is characterized by a moderate stereoselectivity which, however, was strongly dependent on P450 induction. Treatment of rats with phenobarbital (PB) (an inducer of P450 2B1 and 3A) leads to threo-(2R,2'R)-6 with a high selectivity, while with pyrazole (Pyr) (an inducer of P450 2E1), the formation of both erythro-(2S,2'R)- and threo-(2R,2'R)-6 is favored. The mEH-catalyzed hydrolysis of diepoxides 6 proceeds, although with a moderate turnover rate, with substrate and product diastereo- and enantioselection by nucleophilic attack on the more substituted oxirane ring to give selectively (2R,3S)-3,4-epoxy-2-methyl-1,2-diol (7). Both diols 4 and 5 may be further oxidized on their double bond by P450. These reactions, which occur at a slow rate and are dependent on P450 induction with PB and Pyr, may be negligible in the overall isoprene biotransformation. On the other hand, the epoxydiol 7, which is formed by hydrolysis of diepoxides 6 but it is itself not hydrolyzable, may play an important role in the isoprene toxicity.

Animals↗
PubMed2000

Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

Adult↗
PubMed2000

Optical coherence tomography in the assessment of retinal pigment epithelial tear.

PURPOSE: To study the findings of optical coherence tomography (OCT) in retinal pigment epithelial (RPE) tears. METHODS: Sixteen eyes of 16 consecutive patients with age-related macular degeneration complicated by RPE tear were studied using OCT. Fluorescein angiography also was performed. Thirteen eyes were at the acute stage and three eyes were at the scarring stage, still with a recognizable tear. RESULTS: Optical coherence tomography identified an RPE detachment (PED) with focal interruption of the RPE in all cases. Optical coherence tomography always highlighted a peculiar non-dome-shaped profile of the serous PED, as opposed to that of the PED not complicated by an RPE tear. A very intense hyperreflectivity was observed in the OCT scans performed through the retracted RPE. A deep hyperreflectivity under the line corresponding to the RPE was evident in the area of the bare choroid. No choroidal neovascularization could be visualized using OCT, either at the acute or at the scarring stages. CONCLUSIONS: Optical coherence tomography, a noncontact, noninvasive imaging technique, may be a useful tool, complementary to fluorescein angiography, in the clinical assessment of RPE tears.

Aged↗
PubMed2000

Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections.

Currently, replacement recombinant GH (rGH) therapy in GH-deficient (GHD) adults is performed in daily injections. This modality of treatment is not complied with by the totality of GHD patients, who are supposed to receive life-long replacement. The aim of our study was to compare daily vs. thrice weekly (TIW) rGH injection effects on lipid profile, body composition, bone metabolism, and bone density in 34 GHD patients (13 women and 21 men; median age, 39 yr; range, 30-55 yr) randomly assigned to different therapeutic regimens. Group A included 18 patients receiving daily rGH injections, and group B included 16 patients receiving TIW injections of rGH. The starting dose of rGH was 10 microg/kg x day in both groups. Subsequently, the dose was adjusted to maintain serum insulin-like growth factor I (IGF-I) concentrations in the normal age-adjusted range. IGF-I levels were assessed before and after 1, 3, 6, and 12 months of rGH treatment, and lipid profile, body composition, bone metabolism, and bone density were evaluated before and after 6 and 12 months of treatment. Thirty-four healthy subjects served as controls. In the basal condition, lipid profile, body composition, bone metabolism, and bone density were significantly different in patients compared to controls. Conversely, patients included in groups A and B had similar serum IGF-I levels, lipid profile, body composition, bone metabolism, and bone density. After 3 months of rGH treatment, IGF-I levels were normalized in 15 of 18 patients (83.3%) in group A and in 7 of 16 patients (43.7%) in group B (chi2 = 4.21; P = 0.04). At this time point, serum IGF-I levels in patients in group A (202+/-57.5 microg/L) were significantly higher than those in patients in group B (155+/-45.1 microg/L; P = 0.001). After 6 months of therapy, serum IGF-I levels were normalized in all patients and were similar in both groups (223+/-35.2 vs. 212+/-41.4 microg/L, A vs. B, respectively). IGF-I levels remained normal until the 12-month follow-up. After 6 months of rGH replacement, total cholesterol, low density lipoprotein cholesterol, triglycerides, bioelectrical impedance, and body fat mass were significantly reduced, whereas high density lipoprotein cholesterol levels and lean body mass were significantly increased in both groups of patients, without any difference between them. No further change in lipid profile and body composition was observed after 12 months of treatment. Serum bone GLA protein and procollagen III levels were significantly increased after 6 months, and a downward trend was observed after 12 months of rGH replacement. However, a slight, but significant, increase in bone mineral density was observed in both groups only after 12 months (P = 0.0001). All patients in group B had good compliance to the TIW treatment, whereas 5 patients in group A had poor compliance to the treatment (chi2 = 3.2; P = 0.07). In conclusion, our randomized, prospective, and controlled study confirmed that rGH therapy with TIW injection regimen is effective in normalizing IGF-I levels and improving lipid profile, body composition, bone metabolism, and bone density. It also demonstrated that this efficacy is comparable to that observed in patients treated with daily rhGH therapy, with few side-effects and good compliance.

Adult↗
PubMed2000

Parity as a thyroid size-determining factor in areas with moderate iodine deficiency.

Among the factors that may influence thyroid size, pregnancy and its goitrogenic effect have been widely investigated, but thyroid volume and pregnancy have never been compared retrospectively, and there are no data on the possible relationship between thyroid size and parity. The purpose of this work was to evaluate the effects of pregnancy on thyroid volume in a moderate iodine deficiency area, to assess the possibility of a relationship between thyroid size and parity status in healthy females. A group of 208 nongoitrous healthy women underwent thyroid volume estimation by ultrasound examination. All subjects were euthyroid and negative for thyroid autoantibodies. They were assigned to different groups, according to the number of completed pregnancies. Five groups were formed (0, 1, 2, 3, 4 or more term pregnancies). Mean thyroid volume increased progressively among the groups: group 0 (14.8 +/- 0.7 mL); group I (16.0 +/- 0.9 mL); group II (17.1 +/- 0.6 mL); group III (18.2 +/- 0.6 mL); group IV (20.3 +/- 0.9 mL). The increment in thyroid volume was statistically significant between group 0 and groups III (P: < 0.01) and IV (P: < 0.001), and also between group I and group IV (P: < 0. 05). No independent effect of body weight and age on thyroid volume was seen. Our results indicate that, in an area with moderate iodine deficiency, the goitrogenic effect of pregnancy is not fully reversible. Moreover, the statistically significant increase in thyroid volume, observed in relation to parity, is the first clinical demonstration of a cumulative goitrogenic effect of successive pregnancies, providing a strong argument to increase the iodine supply during pregnancy, even in conditions with moderate iodine deficiency.

Adult↗
PubMed1999

A molecular phylogeny of four endangered Madagascar tortoises based on MtDNA sequences.

Four of the five tortoise species in Madagascar, Pyxis arachnoides, P. planicauda, Geochelone radiata, and G. yniphora, are endemic and on the verge of extinction. Their phylogenetic relationships remain controversial and unresolved. Here we address the phylogeny of this group using DNA sequences for the 12S and 16S rDNA and cyt b genes in mitochondrial DNA. As outgroups we used two species of Geochelone, pardalis (mainland Africa) and nigra (Galápagos), as well as a more distant North American tortoise, Gopherus polyphemus. We conclude that the two Pyxis species are sister taxa and are imbedded in the genus Geochelone, rendering this latter genus paraphyletic. There is moderate support for the sister status of the two Madagascar Geochelone and for the monophyletic origin of all four endemics, suggesting a single colonization of the island. The separation of Madagascar from other land masses (90-165 mya) predates the origin of the endemic tortoises (estimated to be 14-22 mya). This suggests founding by rafting, a process known to have occurred with other tortoises. The derived morphological divergence of the Pyxis species in a relatively short period of time (13-20 my) stands in contrast to the notoriously slow rate of morphological evolution in most lineages of Chelonia.

Animals↗
PubMed1999

Lack of insulin-like growth factor binding protein-3 variation after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization.

OBJECTIVE: To investigate serum and follicular fluid (FF) insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in superstimulated cycles in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Naples. PATIENT(S): Thirty-two patients with regular menses and tubal and/or male factor infertility and 21 patients with PCOS undergoing IVF. INTERVENTION(S): The IVF program used leuprolide acetate suppression followed by sequential hMG in the subsequent cycle. After follicular development, hCG administration was followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): E2, GH, IGF-I, and IGFBP-3 assayed by RIA and immunoradiometric assay. RESULT(S): The controls and patients with PCOS showed similar increases in E2 and GH titers in response to FSH stimulation. Serum IGF-I did not change in either group and was equivalent in the FF. Patients with PCOS had a higher FF IGFBP-3 titer and did not show the decrease in serum IGFBP-3 levels of the control group after FSH stimulation. CONCLUSION(S): The apparent failure of IGFBP-3 reduction in patients with PCOS alters IGF-I bioavailability. Increased sequestration of IGF-I affects ovarian steroidogenesis and may explain the poor response to gonadotropin stimulation.

Adult↗
PubMed1999

Captive breeding, reintroduction, and the conservation genetics of black and white ruffed lemurs, Varecia variegata variegata.

A character-based phylogenetic species concept approach was used to examine conservation unit status for three wild populations of black and white ruffed lemurs, Varecia vareigata variegata, from Betampona (N = 3), Manombo (N = 6), and Ranomafana (N = 14), Madagascar. Population aggregation analysis was performed on 548 bp from the control region (D-loop) of the mitochondrial DNA (mtDNA). Twenty-one diagnostic sites were found to differentiate the Betampona (northern) population from the Manombo/Ranomafana (southern) populations. Additionally, individuals from the North American captive population (N = 11) and from Parc Ivoloina, Madagascar (N = 6) were examined for the same mtDNA fragment. The captive animals more closely resembled the southern populations and the Parc Ivoloina animals were more similar to the northern population. However, the inclusion of these ex situ animals reduced the number of diagnostic sites differentiating the northern and southern populations. Our genetic data were used to assess the ongoing management strategy for reintroducing individuals into the Betampona population and for introducing new founders into the ex situ population. This study demonstrates the utility of combining genetic information with a consideration of conservation priorities in evaluating the implementation of management strategies.

Animal Husbandry↗
PubMed1999

Inhibitory effect of exogenous oxytocin on ACTH and cortisol secretion during labour.

Complex mechanisms which are still not completely defined, are responsible for the spontaneous onset of labour: an essential role is attributed to endocrine factors. A massive increase, even three times higher than normal physiological values of ACTH and cortisol, has been reported during labour. Similar behaviour has also been recorded for oxytocin at the end of pregnancy as well as during labour. The relationship between oxytocin and the adrenal axis are still debated thus the goal of our study was to attempt to clarify this rapport. Sixty-two women at the end of a term-pregnancy agreed to participate in this study: 46 were innoculated with oxytocin (syntocinon) every 20 minutes for 1 hour; 16 were administered a natural placebo every 20 minutes for 1 hour (control group). ACTH and cortisol values from plasma samples were taken every 20 minutes and analyzed. Our results demonstrated an inhibitory effect of exogenous oxytocin on ACTH and cortisol release. This inhibitory effect, as shown by our results, is time and dose-related. High oxytocin levels, as during exogenous infusion, could induce an effect opposite a normal physiologic one.

Adrenocorticotropic Hormone↗
PubMed1998

Oxidation of methyl- and ethyl- tertiary-butyl ethers in rat liver microsomes: role of the cytochrome P450 isoforms.

Methyl t-butyl ether (MTBE) and ethyl t-butyl ether (ETBE) are commonly used in unleaded gasoline to increase the oxygen content of fuel and to reduce carbon monoxide emissions from motor vehicles. This study was undertaken to investigate: (1) the effect of administration to rats of ETBE and its metabolite, t-butanol, on the induction and/or inhibition of hepatic P450 isoenzymes; (2) the oxidative metabolism of MTBE and ETBE by liver microsomes from rats pretreated with selected P450 inducers and purified rat P450(s), (2B1, 2E1, 2C11, 1A1). ETBE administration by gavage at a dose of 2 ml/kg for 2 days induced hepatic microsomal P4502E1-linked p-nitrophenol hydroxylase and the P4502B1/2-associated PROD and 16beta-testosterone hydroxylase, verified by immunoblot experiments. t-Butanol treatments at doses of 200 and 400 mg/kg i.p. for 4 days did not alter any liver microsomal monoxygenases. Both MTBE and ETBE were substrates for rat liver microsomes and were oxidatively dealkylated to yield formaldehyde and acetaldehyde, respectively. The dealkylation rates of both MTBE and ETBE were increased c. fourfold in phenobarbital (PB)-treated rats. In rats pretreated with pyrazole, an inducer of 2E1, only the demethylation of MTBE was increased (c. twofold). When the oxidations of MTBE and ETBE were investigated with purified P450(s) in a reconstituted system, it was found that P4502B1 had the highest activities towards both solvents, whereas 1A1 and 2C1 were only slightly active; P4502E1 had an appreciable activity on MTBE but not against ETBE. Metyrapone, a potent inhibitor of P450 2B, consistently inhibited both the MTBE and ETBE dealkylations in microsomes from PB-treated rats. Furthermore, 4-methylpyrazole (a probe inhibitor of 2E1) and anti-P4502E1 IgG showed inhibition, though modest, only on MTBE demethylation, but not on ETBE deethylation. Inhibition experiments have also suggested that rat 2A1 may exert an important role in MTBE and ETBE oxidation. Taken together, these results indicate that 2B1, when expressed, is the major enzyme involved in the oxidation of these two solvents and that 2E1 may have a role, although minor, in MTBE demethylation. The implications of these data for MTBE and ETBE toxicity remain to be established.

Air Pollutants↗
PubMed1998

Insulin-like growth factor binding protein-3 reduction in follicular fluid in spontaneous and stimulated cycles.

OBJECTIVE: To investigate serum and follicular fluid insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in spontaneous and in superstimulated cycles. DESIGN: Estradiol, GH, IGF-I, and IGFBP-3 were evaluated in serum and in follicular fluid during spontaneous and stimulated cycles. SETTING: Department of Obstetrics and Gynecology, University of Naples, Naples, Italy. PATIENT(S): Ninety-two patients with regular menstrual cycles and tubal and/or male factor infertility undergoing treatment with an IVF program. INTERVENTION(S): The superstimulated IVF program uses leuprolide acetate suppression followed by hMG in a sequential manner in the subsequent cycle. After sufficient follicular development, hCG was administered, followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): Growth hormone, IGF-I, and IGFBP-3 were assayed by RIA and immunoradiometric assay techniques. RESULT(S): Growth hormone levels in serum and in follicular fluid were higher after FSH-stimulated cycles than after physiologic cycles. Serum and follicular fluid IGF-I did not change during physiologic and FSH-stimulated cycles. Serum IGFBP-3 decreased only in FSH-stimulated cycles. Levels of IGFBP-3 in follicular fluid were lower than serum levels in late follicular phase both in physiologic and in FSH-stimulated cycles. CONCLUSION(S): Reduction of IGFBP-3 is an important mechanism allowing a larger local availability of free IGFs, which modulate the response of follicles to gonadotropin stimulation. This effect is amplified in stimulated cycles.

Adult↗
PubMed1998

Effects of intraaccumbens microinjections of quinopirole on head turning and circling movement in the rat.

This study was designed to evaluate whether nucleus accumbens dopamine D2 receptors are involved in the initiation of the movement, as distinguished from its execution. For this purpose, the effects of the quinpirole-induced increase of nucleus accumbens dopamine D2 receptor activity were observed on specific parameters of the circling behavior and of its first stage, the head-turning (HT) movement. The experiments were performed on rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the pars compacta of the substantia nigra and d-amphetamine i.p. (3 mg/kg). Bilateral intraaccumbens microinjections of quinpirole (1, 5, and 10 microg/0.5 microl), an agonist of the D2 receptor family, were performed on three groups of animals. Bilateral saline (0.5 microl) was injected in a fourth group as control. An additional control experiment, with quinpirole (10 microg/0.5 microl) bilaterally injected in accumbens without d-amphetamine i.p., was also performed in a further group of 6-OHDA-lesioned animals. By means of a videoanalysis system, HT duration, angle, and speed were analyzed. Modifications of the circling rate (increase), HT duration (decrease), HT angle (decrease or increase according to the dose), and HT speed (increase) were observed. Moreover, a very close head-to-tail position and a very short-diameter type of turn were also evidenced. Similar modifications, even if different in amplitude and in % distribution, were observed following bilateral quinpirole in accumbens without d-amphetamine i.p. The results indicate a close relationship among head-turning speed, type of turn, and position of the animal in the circling motor sequence. We conclude that D2 receptor family in nucleus accumbens is involved in the initiation of movement as distinguished from its execution.

Animals↗
PubMed1998

Inhibitory effect of A10 dopaminergic neurons of the ventral tegmental area on the orienting response evoked by acoustic stimulation in the cat.

The effect of bilateral electric stimulation of A10 dopaminergic neurons of the ventral tegmental area (80-300 microA, 20-50 Hz, 0.1-0.5 ms, 2 s duration) on latency and duration of the orienting response, evoked by acoustic stimuli (4500-8000 Hz, 2 s), was studied in the cat. A10 neuron stimulation, simultaneous with the acoustic one, was performed with threshold parameters inducing minimal behavioral signs (head searching movement, sniffing, increase in alertness). By means of a videoanalysis system, a statistically significant increase, both of latency and duration of the response, was observed. The possible role of dopamine was studied administrating sulpiride (20 mg/kg i.p.), a dopaminergic antagonist prevalently acting on the mesolimbic-mesocortical system. In this condition, the disappearance of A10 neuron effect occurred. Sulpiride injection did not affect the parameters of the orienting response to acoustic stimulus alone, suggesting a direct effect on A10 dopaminergic neurons. Moreover, when saline administration was carried out, no significant modification of the effects, obtained following A10 neuron activation, was observed. The data suggest that A10 dopaminergic neurons, origin of the mesolimbic-mesocortical system, may be involved in the control of the response to sensory stimuli, likely by influencing sensorimotor integration processes. An involvement in the inhibitory regulation of the switching of attention is also discussed.

Acoustic Stimulation↗
PubMed1998

Stereochemistry of the biotransformation of 1-hexene and 2-methyl-1-hexene with rat liver microsomes and purified P450s of rats and humans.

The epoxidation of 1-hexene (1a) and 2-methyl-1-hexene (1b), two hydrocarbons present in the ambient air as pollutants, is catalyzed by some human and rat P450 enzymes. The enantioselectivities of these processes, when the reactions were carried out using rat and human liver microsomal preparations, were modest and dependent on both P450 composition and substrate concentrations. Various P450 isoforms (rat P450 2B1 and human P450 2C10 and 2A6) catalyzed the double bond oxidation of 1a and 1b with different product enantioselectivities. In the case of 1a, a moderately enantioselective hydroxylation at the allylic C(3) with the formation of 1-hexen-3-ol (4a) by microsomes from control or preinduced rats was also observed. The oxidation of this metabolite was, in turn, catalyzed by rat liver microsomes and mainly by rat P450 2C11, leading exclusively to the formation of 1-hexen-3-one, with no double bond epoxidation being observed. The stereochemical course of the microsomal epoxide hydrolase-catalyzed hydrolysis of the epoxy alcohols, threo-(+/-)- and erythro-(+/-)-1, 2-epoxyhexan-3-ol, theoretically expected to be formed from 4a, has been investigated.

Alkenes↗