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S Racca

Publications and source records attributed to S Racca.

At least 37 records · Page 2Linked to original sources
PubMed1996

Serum polymerase chain reaction for cytomegalovirus DNA for monitoring ganciclovir treatment in AIDS patients.

The virological response to antiviral treatment of cytomegalovirus (CMV) infection in patients with AIDS can be monitored by the identification and quantification of CMV pp65 antigen in blood polymorphonuclear leukocyte cells (PMNL). To assess the value of nested polymerase chain reaction (PCR) in serum for therapy follow-up, we compared PCR and pp65 antigenemia results in 21 acquired immune deficiency syndrome (AIDS) patients with CMV infection, before and after 3 weeks of intravenous ganciclovir at standard doses. pp65 antigenemia was positive in 18/21 (86%) patients at the start of the therapy and in 2/15 (13%) at the end of therapy. CMV DNA was found in serum from 18/21 (86%) patients at the beginning of therapy and in 3/21 (14%) patients after 3 weeks of therapy. A clinical improvement was seen in 16/21 (76%) patients: 11/16 (69%) were negative by both PCR and antigenemia at the end of ganciclovir treatment. The sensitivity and specificity of serum PCR versus the antigenemia assay were 85% and 81%, respectively. Nested PCR on serum can be useful for treatment follow-up of CMV infection in patients with AIDS. It can be used where antigenemia cannot be performed and in retrospective studies.

AIDS-Related Opportunistic Infections↗
PubMed1995

Nested polymerase chain reaction for diagnosis and monitoring treatment response in AIDS patients with tuberculous meningitis.

OBJECTIVE: To investigate the usefulness of polymerase chain reaction (PCR) from cerebrospinal fluid (CSF) for rapid diagnosis and assessing treatment response of tuberculous meningitis (TBM) in AIDS patients. PATIENTS: Forty-four CSF samples from 10 patients with TBM confirmed by autopsy or by a culture of CSF (41 samples) and from two patients with highly probable TBM (three samples) were analysed. CSF specimens were collected before and during standard antituberculous treatment. CSF samples from 24 AIDS patients with autopsy evidence of other neurologic diseases were studied as controls. METHODS: A nested PCR amplifying a 123 base-pair fragment of the IS6110 sequence was developed. Heating to 95 degrees C for 15 min was used for pre-PCR treatment of samples. RESULTS: Detection limit was 10(2) colony-forming units per ml or 10 fg purified Mycobacterium tuberculosis DNA. M.tuberculosis DNA was detected in CSF from all the 12 confirmed or highly probable TBM cases. CSF was positive by nested PCR in 17 of 17 (100%) and 18 of 27 (67%) samples collected before and during therapy, respectively. Clinical and microbiological follow-up > or = 2 weeks was available for seven patients. PCR-positive CSF converted to M. tuberculosis DNA negative in four patients that showed improvement during treatment, but it remained positive in three patients who died of disseminated tuberculosis. All the CSF samples from the non-TBM controls were negative by nested PCR. CONCLUSIONS: Nested PCR for detection of M. tuberculosis DNA is specific for diagnosis of TBM and more sensitive than conventional bacteriology. Moreover, nested PCR could be a useful method for assessing treatment response in AIDS patients with TBM.

AIDS-Related Opportunistic Infections↗
PubMed1991

Potentiation of medroxyprogesterone acetate antineoplastic activity by histidine in rat mammary tumours.

The antitumour activity of arginine, histidine and medroxyprogesterone acetate (MPA) was studied in female rats with dimethylbenzanthracene (DMBA)-induced mammary adenocarcinomas. After 15 days of treatment, regression was observed in 4 of 19 (21%), 3 of 18 (16.7%) and 22 of 59 (37.3%) tumours taken from rats given arginine, histidine or MPA, respectively. A total of 17 rats with tumours that had been non-responsive to MPA were then treated with MPA plus histidine for 15 more days; the growth of 3 lesions (17.6%) was arrested, and 5 tumours (29.4%) regressed markedly. The antineoplastic activity of MPA was found to be related to the oestrogen-(ER) and progesterone-receptor (PgR) concentrations measured in the tumours before the start of treatment, whereas that of arginine and histidine appeared to be independent of receptor status. A significant reduction in serum prolactin (PRL) levels occurred in rats that were responsive to MPA alone or to MPA plus histidine. In tumours taken from the same rats, the PRL receptor content was also significantly increased in comparison with that in non-responsive tumours. In contrast, serum PRL levels increased significantly in rats with tumours that were non-responsive to MPA, whereas no change in serum PRL or PRL receptor levels was observed in rats treated with arginine or histidine. Histidine showed the ability to increase the number of ERs and PgRs in responsive tumours; this could have been responsible for the unexpected potentiation of MPA antineoplastic activity. In contrast, the levels of ER and PgR in uteri taken from the same rats were not modified. Furthermore, the addition in vitro of histidine to cytosols obtained from tumours of control animals did not influence ER and PgR concentrations. These results suggest that the effect of histidine on ER and PgR levels is probably specific for tumour tissue and is not due to a direct activity.

Animals↗
PubMed1988

High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer.

Correlations between anti-neoplastic activity of medroxyprogesterone acetate (MPA), on the one hand, and serum prolactin (PRL) levels as well as tumour PRL and insulin receptor content, on the other, were investigated in female rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours. Changes in liver PRL receptor concentrations were also studied. MPA was injected for 15 days. Regression was observed in 16 out of 50 (32%) tumours from rats treated with MPA. Twenty-seven out of 50 (54%) continued to grow regardless of treatment. Stasis was seen in the remaining 7 tumours (14%). Serum PRL levels increased significantly in rats with tumours which were non-responsive to MPA. Concentration of PRL receptors in the liver of all animals was reduced by MPA treatment. A remarkable increase occurred only in those mammary tumours which responded to therapy. The concentrations of PRL receptors in the tumours non-responsive to MPA were similar to those detected in control tumours. Unlike PRL receptors, tumour insulin receptor levels were not modified by MPA treatment. Five out of 14 tumours (35.7%), previously growing in spite of MPA administration, regressed when bromocriptine was added to MPA. A significant reduction in serum PRL levels occurred in all rats undergoing the latter treatment. No difference was observed between responsive and non-responsive animals; on the contrary, the PRL receptor content of responsive tumours increased significantly in comparison with that of non-responsive tumours.

Adenocarcinoma↗
PubMed1988

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors.

UNLABELLED: We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modifications induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17 beta-estradiol (E2) at both low (0.1 micrograms/kg) and high (20 micrograms/kg) doses confirmed its ability to increase the number of striatal 3H-Spiperone (3H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E2, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophyseal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. IN CONCLUSION: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of its antiestrogenic activity.

Animals↗
PubMed1988

Effects of medroxyprogesterone acetate on serum prolactin levels and liver prolactin binding capacity in the rat.

Modifications in liver prolactin (PRL) receptor levels and serum PRL concentration induced by administration of medroxyprogesterone acetate (MPA) were investigated in rats of both sexes. MPA induced a reduction both of the levels of PRL in the serum and of liver PRL receptors in the female rat. The reduction of the number of PRL receptors caused by MPA was rapid and almost complete after 10 days of treatment and appeared earlier than that of serum PRL levels. Furthermore the MPA-induced decrease in PRL receptors was specific, since insulin binding to the same liver membranes was not affected. MPA given simultaneously with oestradiol (which increases both the number of liver PRL receptors and the serum PRL levels in the male rats) was able to counteract the increase in PRL binding induced by oestradiol. On the contrary, the oestrogen-induced increase in serum PRL was not affected by MPA treatment. Similar results were obtained using tamoxifen, a well known antioestrogenic drug. In conclusion, our results show that the reduction of PRL receptor levels induced by MPA in rat liver is specific, not correlated to serum PRL concentration, and seems to depend on the antioestrogenic activity of the drug.

Animals↗
PubMed1985

Estrogen and progesterone receptors in the human vagina.

Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues.

Adult↗
PubMed1985

Effects of medroxyprogesterone acetate on DMBA-induced mammary tumors.

Rats with DMBA-induced mammary tumors were treated for 30 days i.m. with medroxyprogesterone acetate (MPA) at doses of 7.5, 15 or 75 mg/kg. Complete regression (disappearance of tumor) was observed in 60% and 20% of tumors from rats treated with 75 or 15 mg/kg MPA respectively. Partial regression (50% decrease in tumor area) was found in the remaining 20% of tumors from rats treated with 15 mg/kg MPA. The dose of 7.5 mg/kg MPA resulted in being devoid of effectiveness. Estrogen receptor (ER) levels were significantly reduced at all doses of MPA injected both in responsive and non-responsive tumors. However, only tumors with ER levels above 15 fmol/mg before therapy resulted in being responsive to MPA treatment. Progesterone receptors were so reduced at the end of the experiment as to not be detectable in all treated groups. It was concluded that MPA is effective as an antitumoral drug also in DMBA-induced mammary tumors and that this effect is at least in part related to ER levels before treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Effects of long-term administration of high doses of medroxyprogesterone acetate on hormone receptors and target organs in the female rat.

The changes in oestrogen, progesterone and prolactin receptor levels in target organs, and the macroscopic and microscopic modifications of uterus, ovary, adrenal and pituitary gland induced by long-term administration of high doses of medroxyprogesterone acetate (MPA) were investigated in female rats. Medroxyprogesterone acetate was injected i.m. for 30 days at daily doses of 7.5, 15 and 75 mg/kg. Oestrogen and/or progesterone-binding capacities were remarkably reduced at all doses of MPA used both in the uterus and pituitary gland. Furthermore, MPA caused a very evident reduction in the weight of pituitary glands, ovaries, adrenals and uterus. In all MPA-treated rats corpora lutea were absent from the ovaries, whereas the adrenals showed a significant reduction in the thickness of the cortex. In accordance with this, there was no evidence of ACTH-producing cells in the pituitary glands. Prolactin-producing cells were also absent, while GH-producing cells were present. Serum prolactin levels were significantly reduced at all doses of MPA used. A dramatic reduction of prolactin receptor concentrations was observed in the liver and the ovaries of MPA-treated rats. The results suggest that MPA acts as an antioestrogenic drug both by reducing the number of oestrogen receptors in target tissues and by changing the structure (and perhaps the function) of those organs (pituitary glands, ovaries and adrenals) which are, directly or indirectly, a source of oestrogens. The decreased synthesis of prolactin and the reduction of the number of prolactin receptors (which, on the contrary, are both increased by oestrogens) might be considered as additional antioestrogenic effects of MPA.

Adrenal Glands↗
PubMed1983

Effects of bromocriptine and dopamine on the binding of estradiol to its uterine cytoplasmic receptors.

The in vivo and in vitro effects of bromocriptine on the binding of estradiol 17 beta to its specific uterine receptors were studied in both mature and immature rats. A single i.p. injection of bromocriptine reduced the specific estradiol-receptor interaction in adult rats, while it resulted ineffective in prepubertal animals. The effect of bromocriptine in mature rats was dose-dependent and evident only when using a dose of at least 0.70 mg/kg. Experiments in vitro also showed that in mature rats bromocriptine affected the estradiol-receptor interaction inducing a decrease in binding, which is well correlated to the concentration used. On the contrary, no effect of bromocriptine in vitro was observed when using cytosol obtained from uteri of immature rats. Very similar results were obtained in experiments in vitro when using dopamine instead of bromocriptine. Our results suggest that apparently there are two forms of estrogen receptors, one present both in prepubertal and pubertal age and the other present only in mature animals. The latter is the type of receptor sensitive to both bromocriptine and dopamine and presumably develops under the control of hormonal factors, which are only present at puberty.

Animals↗
PubMed1983

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives.

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol-receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time. The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.

Animals↗
PubMed1980

Effects of estrogens P-1496 and P-1560 on the binding of estradiol with rat uterine estrogen receptors.

The interference of two weak estrogens (P-1496 and P-1560) on the binding of estradiol with uterine estrogen receptors is comparatively studied. Both P-1496 and P-1560 decrease the estradiol binding capacity, but P-1560 is less effective than P-1496. Since P-1496 is a more potent estrogenic substance than P-1560, the results obtained confirm that the uterotrophic activity of estrogens is related to the binding capability to uterine estrogen receptors.

Animals↗
PubMedDate not supplied

Interleukin 2 up-regulates glucocorticoid receptor number in human peripheral blood mononuclear cells and the osteosarcoma cell line Saos-2 in vitro.

Glucocorticoids are well-recognized modulators of immunocytes and osteoblasts via specific receptor-mediated mechanisms. We have evaluated the in vitro effect of interleukin 2 (IL-2) on the expression of glucocorticoid receptors (GRs) in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors and osteoblast-like Saos-2 cells. Aliquots of PBMC or Saos-2 cells were incubated for 20 h in the presence or absence of recombinant human IL-2 (100 IU/mL) at 37 degrees C. After incubation, a [3H]dexamethasone radioligand-binding assay and Scatchard analysis were used to determine GR-binding parameters in both cell populations. Saos-2 cells basally express higher numbers of GR than PBMCs. After IL-2, a significant increase in GR number was found for both PBMCs and Saos-2 cells. The relative increase was higher in Saos-2 cells; in PBMCs, the apparent affinity fell to almost half. These data represent an additional piece of evidence that cytokine and steroid hormones may act in a complementary way to regulate specific cell functions.

Adult↗