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Biomedical subjects

M Motta

Publications and source records attributed to M Motta.

At least 181 records · Page 10Linked to original sources
PubMed1987

New approaches for the treatment of prostatic hypertrophy and cancer.

The present study reports the effects exerted by 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro metabolism of labelled testosterone, dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the prostate of adult male rats and in human benign prostatic hypertrophic (BPH) tissue. It has been found that 4-OH-A decreases the formation of DHT and of the diols. When testosterone is used as the substrate, the presence in the medium of 4-OH-A enhances the formation of delta-4-A and of 5-alpha-androstanedione (5-alpha-A); 4-OH-A does not inhibit the conversion of labelled DHT into the diols. Also, the transformation of labelled delta-4-A into 5-alpha-A is not modified by 4-OH-A. On the basis of these findings, it is suggested that 4-OH-A might represent a potential new agent for the prevention and/or treatment of human BPH.

Aged↗
PubMed1987

Ultrashort feedback control of luteinizing hormone-releasing hormone secretion in vitro.

The present experiments were performed to clarify whether LHRH might inhibit its own secretion via an ultrashort feedback mechanism acting directly on the hypothalamus. Using an in vitro system, mediobasal hypothalami (MBHs) of adult male rats were perifused in either the presence or absence of a LHRH agonistic analog [D-Ser(TBU)6,Des-Gly10] LHRH ethylamide shown not to cross-react in the LHRH RIA. In the first series of experiments, six MBHs per chamber were initially perifused with control medium and submitted to two K+ stimulations (110 mM) for 5 min every 30 min; the control medium was then replaced by medium containing the LHRH analog (5 microM), and three additional K+ pulses were applied. In the second series of experiments, a single MBH per chamber was exposed for the duration of the experiments to either control medium or medium containing the LHRH analog (5 microM). In both cases, pulses of K+ were applied to the tissue. The amounts of endogenous LHRH released both under basal conditions and after K+ stimulation were measured in the effluent (1 ml every 5 min) with a specific RIA. The results show that the LHRH analog inhibits basal secretion of endogenous LHRH from the MBH, and diminishes or abolishes the response to K+ stimulations. The specificity of the inhibitory effect exerted by the LHRH analog on LHRH secretion was shown by the inability of TRH to mimic the effect of the LHRH analog. The data are consistent with the hypothesis that LHRH, acting at a hypothalamic level, might participate in the control of its own release via an ultrashort feedback mechanism.

Animals↗
PubMed1987

Tamoxifen does not block the inhibitory effect of testosterone on FSH release in rats.

The aim of the present experiments was to analyze whether the inhibitory effect exerted by testosterone on FSH release might be mediated by the intracerebral transformation of the hormone into oestrogenic metabolites. Advantage has been taken of the availability of the potent antioestrogen tamoxifen. Two series of experiments have been performed. In the first one, adult male rats have been castrated and submitted, beginning immediately after surgery, to a 6-day treatment with testosterone propionate (2 mg/rat/day), tamoxifen (50 or 200 micrograms/rat/day) or testosterone propionate (2 mg/rat/day) plus tamoxifen (either 50 or 200 micrograms/rat/day). In the second experiment, adult male rats have been castrated and submitted to the same 6-day treatments, beginning 4 weeks following orchidectomy. In both experiments, the animals were killed 24 h after the last injection, and serum levels of FSH and LH have been measured by radioimmunoassays. The results have clearly shown that, in both experiments, the administration of testosterone results in a significant decrease of serum FSH and in a total suppression of LH release. The administration of tamoxifen, in either dose, does not modify the elevated serum FSH and LH levels present in the orchidectomized animals, and does not antagonize the inhibitory effect on FSH and LH secretion exerted by the concomitant treatment with testosterone propionate. It is concluded that testosterone inhibits FSH secretion in orchidectomized rats acting as such, and not following aromatization to oestrogens.

Animals↗
PubMed1986

Studies on the possible existence of two 5 alpha-reductases in the rat prostate.

In the first group of experiments, the in vitro metabolism of labelled testosterone has been studied in the ventral prostate of young (2 months) and old (15 and 22 months) male rats. It has been found that the prostate of 2-month-old animals converts testosterone into dihydrotestosterone (5 alpha-androstane-17 beta-ol-3 one, DHT) and into the diols (5 alpha-androstane-3 alpha-17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol) with considerable yields. The prostate of young animals is also able to convert testosterone into delta 4-androstenedione (delta 4-A), 5 alpha-androstanedione (5 alpha-A) and androsterone (A); however, the amounts of these metabolites are lower than those of DHT and the diols. It has been found that ageing induces major alterations in the prostatic metabolism of testosterone. In particular, a progressive and significant decrease in the formation of DHT and of the diols has been found in animals of 15 and 22 months of age. Advancing age induces, on the contrary, an increase of the formation of delta 4-A and of the 5 alpha-reduced metabolites of the 17-keto series (5 alpha-A + A). In the second group of experiments, the effects exerted by 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro metabolism of labelled testosterone and delta 4-A in the ventral prostate of adult male rats have been studied. It has been found that 4-OH-A, when added to the incubation media, decreases the formation of DHT and of the diols, when labelled testosterone is used as the substrate. The presence in the media of this steroid enhances the formation of delta 4-A and of 5 alpha-A. The transformation of labelled delta 4-A into 5 alpha-A is not modified by the presence in the medium of 4-OH-A. From the two groups of experiments, it is concluded that in the ventral prostate of the rat there are two different 5 alpha-reductase isoenzymes, one sensitive to age and to the inhibitory effect of 4-OH-A (and which is responsible for the conversion of testosterone into the 5 alpha-reduced metabolites of the 17-OH series, DHT and the diols), and a second one, insensitive to age and to the effects of 4-OH-A, which affects the conversion of delta 4-A into 5 alpha-A.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1986

In vitro metabolism of testosterone in the rat prostate: influence of aging.

The in vitro metabolism of labelled testosterone has been studied in the ventral prostate of young (2 months) and old (15 and 22 months) male rats. It has been found that the prostate of 2-month old animals converts testosterone into dihydrotestosterone (5-alpha-androstane-17-beta-ol-3-one, DHT) and into the diols (5-alpha-androstane-3-alpha,-17-beta-diol and 5-alpha-androstane-3-beta,17-beta-diol) with considerable yields. The prostate of young animals is also able to convert testosterone into delta-4-androstenedione (delta-4-A), 5-alpha-androstanedione (5-alpha-A) and androsterone (A); however, the amount of these metabolites are lower than those of DHT and the diols. Aging induces major alterations in the prostatic metabolism of testosterone. In particular, a progressive and significant decrease in the formation of DHT and of the diols has been found in animals of 15 and 22 months of age. Advancing age induces, on the contrary, a progressive and significant increase of the formation of delta-4-A. The total amounts of 5-alpha-reduced metabolites of the 17-keto series (5-alpha-A + A) are higher at 15 and 22 months than at 2 months of age. This increase appears to result from an enhanced formation of 5-alpha-A at 15 months, and of A at 22 months. The present data show that aging exerts important effects on the metabolism of testosterone in the ventral prostate of the rat. The results may help explaining why the old rat does not develop spontaneously the syndrome of benign prostatic hypertrophy (BPH), as it occurs in other species (dogs and humans).

Aging↗
PubMed1986

Effect of 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A) on the 5 alpha-reduction of androgens in the rat prostate.

The present study reports the effects exerted by 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A), three steroids known to inhibit the aromatization of androgens to estrogens, on the in vitro metabolism of labelled testosterone (T), dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the ventral prostate of adult male rats. It has been found that ATD, in the concentration tested, does not influence the conversion of labelled T into DHT, but decreases the formation of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol (diols). On the contrary, 4-OH-A and 4-Ac-A simultaneously decrease the formation of DHT and the diols. When T is used as the substrate, the presence in the medium of these three steroids enhances the formation of delta-4-A and of 5 alpha-androstanedione (5 alpha-A). ATD, but not 4-OH-A and 4-Ac-A inhibits the conversion of labelled DHT into the diols. The transformation of labelled delta-4-A into 5 alpha-A is not modified by either ATD or 4-OH-A, while 4-Ac-A exerts only a small inhibition. These results suggest that the three aromatase inhibitors tested are able to profoundly modify the metabolism of T in the ventral prostate of the rat. In particular: 4-OH-A and 4-Ac-A are able to inhibit the conversion of T into DHT; ATD is able to inhibit the conversion of DHT into the diols; ATD and 4-OH-A do not inhibit the process of 5 alpha-reduction of delta-4-A into 5 alpha-A, while 4-Ac-A exerts only a minor effect. It is suggested that in the ventral prostate of the rat there are two different 5 alpha-reductase isoenzymes, one sensitive to the inhibitory effect of the steroid tested and which is responsible for the conversion of T into the 5 alpha-reduced metabolites of the 17-OH series (DHT and the diols), and a second one, insensitive to the effects of the three steroids, which affects the conversion of delta-4-A into 5 alpha-A.

Androgens↗
PubMed1986

Role of arachidonate metabolism on the in vitro release of luteinizing hormone and prolactin from the anterior pituitary gland: possible involvement of lipoxygenase pathway.

The aim of the present study was to evaluate whether arachidonic acid metabolism may play a role on luteinizing hormone (LH) and prolactin (PRL) release directly at the pituitary level. To this purpose, exogenous arachidonic acid, alone or in presence of inhibitors of cyclooxygenase (indomethacin:IND) and lipoxygenase pathways (nordihydroguaiaretic acid:NDGA), was added to perfused rat anterior pituitary cells. PGE, PGF alpha, LH and PRL levels present in the eluate were assayed with specific RIA methods. Both PGE and PGF alpha show a dose-related response after the addition of increasing doses of arachidonic acid. The addition of 0.05 mM arachidonic acid induces an increase of LH and PRL. The addition of IND to the perfusion medium highly potentiates the stimulatory effects induced by arachidonic acid on LH and PRL release. On the contrary, the addition to the medium of either NDGA or IND plus NDGA completely reverses the stimulatory action induced by arachidonic acid alone. The present results suggest that: adenohypophyseal cells are able to metabolize exogenous arachidonic acid; arachidonic acid induces an elevation in LH and PRL levels; lipoxygenase pathway metabolite(s) are likely involved in these activities, and the site of action of arachidonic acid is at the pituitary level.

Animals↗
PubMed1986

In vitro effects of an aromatase inhibitor on 5 alpha-reductase activity in human hypertrophic prostatic tissue.

To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT), 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstan-3 beta, 17 beta-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4-14C-T as substrate, in the presence of 4-OH-A (10(-8) to 10(-6) M); the amounts of the 5 alpha-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), a known inhibitor of the 5 alpha-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily. Both 4-OH-A and 4-MA induced significant and dose-related decreases in the formation of both DHT and the diols. The degree of inhibition induced by the different concentrations of 4-OH-A and 4-MA were 31, 41, 72% and 57, 87, 97%, respectively. The decreased formation of the diols was a consequence of the decreased availability of DHT (the immediate precursor of the diols) and was not due to direct effects of the inhibitors on the 3-hydroxysteroid dehydrogenases; both 4-OH-A and 4-MA were totally unable to modify the conversion of DHT to the diols, when 4-14C-DHT was used as substrate. Thus, 4-OH-A inhibits the process of 5 alpha-reduction of T in BPH tissue. This molecule might represent a potential new agent for the prevention and/or treatment of human BPH.

5-alpha Reductase Inhibitors↗
PubMed1986

Morphine stimulates prolactin release in normal but not in castrated male rats.

Morphine (200 micrograms/rat) was injected intraventricularly (i.v.t.) into normal and into long-term castrated (4 weeks) adult male rats. Animals were killed 10, 20, 40 and 60 min after treatment. In normal animals, the treatment with morphine resulted in a significant increase of serum prolactin concentrations at all time intervals considered. However, the i.v.t. injection of 200 micrograms morphine/rat into castrated rats did not exert any significant effect on prolactin release at any time interval considered. When morphine (200 micrograms/rat) was administered i.v.t. together with the specific opioid receptor blocker naloxone (7.5 or 15 micrograms/rat) the stimulatory effect of morphine on prolactin release was diminished at 10 min, and totally blocked at 20 min. Naloxone given alone did not influence serum prolactin concentrations. The results suggest that the presence of endogenous androgens is essential to permit the stimulatory effect of morphine on prolactin release.

Animals↗
PubMed1986

Testosterone metabolites do not participate in the control of hypothalamic LH-releasing hormone.

To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormone (LHRH) in orchidectomized rats might be explained by the conversion of the hormone into either its 5 alpha-reduced or oestrogenic metabolites, testosterone, 5 alpha-androstan-17 beta-ol-3-one (DHT), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) (2 mg/rat per day for 6 days) and oestradiol (0.1, 0.5, 1.0 and 5.0 micrograms/rat per day for 6 days) were injected into castrated male rats. After 6 days the rats were killed and serum LH levels and intrahypothalamic LHRH stores measured using specific radioimmunoassay procedures. Testosterone and its 5 alpha-reduced metabolites were used in either the free alcohol or the propionate form (dipropionates in the case of the diols); oestradiol was used as oestradiol-17 beta or in the benzoate form. Treatment with testosterone, DHT, 3 alpha-diol and 3 beta-diol resulted in a significant decrease in serum LH levels; all the 5 alpha-reduced testosterone derivatives were more effective than testosterone in this respect. Testosterone and DHT propionates suppressed LH release following orchidectomy totally; 3 alpha-diol and 3 beta-diol dipropionates were less effective. Testosterone increased intrahypothalamic LHRH stores, this effect being much higher after testosterone propionate, i.e. when intrahypothalamic LHRH stores were restored to pre-castration levels. None of the 5 alpha-reduced steroids was capable of modifying the low intrahypothalamic levels of LHRH found following orchidectomy; only 3 alpha-diol dipropionate exhibited some activity, but this was much lower than that of testosterone propionate. Oestradiol-17 beta was totally ineffective in decreasing serum LH in orchidectomized animals; in contrast, oestradiol benzoate progressively decreased serum LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstane-3,17-diol↗
PubMed1985

Neuroendocrine effects of some amphibian peptides.

The effect of dermorphin and sauvagine, two new peptides originally isolated from amphibian skin, on the release of gonadotropins and prolactin was studied "in vivo" and "in vitro." The intraventricular administration of dermorphin to castrated male rats induces a significant decrease in serum LH, but not FSH, levels. Subcutaneous, as well as intraventricular, injections of dermorphin to normal male rats induce a statistically significant increase in serum prolactin levels, which is counteracted by naloxone. In the isolated and dispersed rat pituitary cell preparation, the addition of dermorphin to the media does not induce any alteration in prolactin output. Intraventricular administrations of sauvagine are ineffective in influencing the secretion of both LH and FSH. This peptide is also unable to modify it when tested "in vitro". On the contrary, subcutaneous injections of sauvagine to either normal male or lactating rats decrease serum prolactin levels. This prolactin inhibitory effect is also present "in vitro." These results suggest that dermorphin and sauvagine modulate the secretory activity of the anterior pituitary gland. However, the mechanism of control is different: dermorphin needs the mediation of brain structures, while sauvagine acts directly at the pituitary level.

Amphibian Proteins↗
PubMed1985

Effect of naloxone on luteinizing hormone, follicle-stimulating hormone, and prolactin secretion in the different phases of the estrous cycle.

It is becoming increasingly clear that the effects exerted by opioid agonists and antagonists on the release of gonadotropins and of PRL may vary according to the endocrine milieu. To investigate this issue further, female rats with a regular 4-day estrous cycle have been injected sc with the opioid antagonist naloxone at different hours of the day, during each of the various days of the estrous cycle. The animals were killed 20 min after the sc administration of naloxone (2.5 mg/kg dissolved in 0.9% saline solution) at 1000 and 1600 h on the first and second day of diestrus and at 1000, 1200, 1400, 1600, 1800, and 2000 h on proestrus and estrus. Animals were killed by decapitation, and trunk blood was collected and assayed for LH, FSH, and PRL. The data obtained from naloxone-treated animals were compared to those derived from controls injected sc with 0.9% saline solution and killed at the same time intervals. The sc injections of naloxone stimulated LH release in every phase of the estrous cycle; however the magnitude of the responses was highly variable. Increases of the order of 700-1.000% were observed during the 2 days of diestrus, at 1000 and 1400 h of the day of proestrus, and at 1600, 1800, and 2000 h of the day of estrus. Much higher responses (of the order of 2.700-3.300%) were observed at 1600 h of the day of proestrus and at 1000, 1200, and 1400 h of the day of estrus. The LH response to naloxone appeared to be obliterated at 1800 and 2000 h of the day of proestrus. Serum levels of FSH and PRL were not affected by the treatment at any of the time intervals considered. These findings suggest that, in normally cycling adult female rats, naloxone exerts a stimulatory effect on LH release during each day of the estrous cycle; that the stimulatory effect of naloxone is minimal at the time of the spontaneous proestrous LH surge; and that the effect of naloxone on LH release is, on the contrary, maximal just before the spontaneous proestrous LH surge and up to 1400 h of the day of estrus. The observation that naloxone does not affect FSH and PRL release underlines once more that the central mechanisms controlling LH, FSH, and PRL secretion are different.

Animals↗
PubMed1985

Induction of precocious puberty in the female rat after chronic naloxone administration during the neonatal period: the opiate 'brake' on prepubertal gonadotrophin secretion.

Studies were undertaken using the opiate receptor antagonist naloxone to examine the hypothesis that endogenous opiates may have a restraining effect on prepubertal gonadotrophin secretion and may be involved in the maturation of the central nervous system mechanisms regulating the onset of puberty in the female rat. Naloxone (2.5 mg/kg) administered intraperitoneally every 6 h to female rats from day 1 to day 10 of postnatal life significantly (P less than 0.001) advanced the age of onset of puberty assessed in terms of the day of vaginal opening and first oestrus (32.3 +/- 0.2 vs 40.8 +/- 0.4 days in control saline-treated animals). Animals so treated with naloxone showed significantly (P less than 0.001) higher levels of FSH (761.4 +/- 87.6 vs 483.8 +/- 57.2 micrograms/l in control animals) and LH (562.8 +/- 57.4 vs 351.3 +/- 43.3 micrograms/l in control animals) at the first late pro-oestrus and a significantly (P less than 0.001) higher number of ova released at first oestrus (12.4 +/- 0.4 vs 8.1 +/- 0.3 in controls). Body weight at first oestrus was significantly (P less than 0.001) lower in the naloxone-treated animals, an indication that these animals were much younger. The weights (per 100 g body wt) of the ovaries and uteri at the first oestrus were significantly (P less than 0.01) higher in the naloxone-treated rats than in the controls. However, there were no significant differences in the weights of the adrenals and anterior pituitary glands between the two groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Inhibitor to factor V in severe factor V congenital deficiency. A case report.

A case of severe factor V deficiency that developed an inhibitor to factor V following the treatment with fresh frozen plasma (FFP) is described. The patient had a CRM-negative form of factor V congenital deficiency: no factor V antigen could be assayed in her plasma. A sister who supposedly had a severe factor V deficiency died as a result of a severe posttransfusional hepatitis. Two other members of the family were found to be heterozygotes. After several exposures to FFP, the propositus became refractory to the treatment with the appearance of a low titre inhibitor (5 units) which, nevertheless, could not be overcome by plasma infusions.

Blood Coagulation↗
PubMed1984

Alpha-globin gene deletions associated with alpha A and alpha G Philadelphia in an Algerian family that includes two Hb G homozygotes.

An Algerian family with a high degree of consanguinity and including two homozygotes for Hb-G Philadelphia is presented. Whether homozygotes or heterozygotes, all subjects displayed microcytosis (with various degrees of poikilocytosis) and a moderately depressed alpha-globin chain synthesis. Hb H and Heinz bodies were absent. DNA mapping revealed the presence of a 3.7 kb deletion resulting from the rightward type of recombination event between alpha 2 and alpha 1 genes on both the alpha A/ and the alpha G/ chromosomes. Such data indicate that the -alpha A/ and -alpha G/ haplotypes are involved and suggest that the -alpha G/ haplotype, which is very rare in Algeria, has an African Black origin. In subjects with genotype (-alpha A/-alpha G) or (-alpha G/-alpha G), the output of the remaining alpha genes is sufficiently high to avoid the appearance of Hb H. This situation contrasts with that reported in an Algerian patient, who had a (-alpha A/-alpha A) genotype but who was producing Hb H (Whitelaw et al. 1980). The data collected from this family suggest that the -alpha A/ haplotypes are heterogeneous in Algerians.

Algeria↗
PubMed1984

Dermorphin stimulates prolactin secretion in the rat.

The effect of dermorphin, a new opioid peptide originally isolated from amphibian skin, on the release of prolactin (Prl) was studied in vivo and in vitro. In vivo experiments: subcutaneous administrations of different doses of dermorphin ranging from 0.1 to 5 mg/kg body weight to normal male rats induce a statistically significant, dose-related increase in serum Prl levels. Pretreatment with the specific opioid antagonist, naloxone (2 mg/kg i.p.) completely prevents the rise in serum Prl, induced by 2 mg/kg of dermorphin. In normal male rats, the intraventricular injection of 0.25 micrograms/kg of dermorphin is not able to induce any significant changes in serum Prl levels 10 min after injection. Serum Prl levels show a significant enhancement 30 min after the administration of this dose of dermorphin, and return to control values at 60 min. On the contrary, 1 microgram/kg of dermorphin significantly elevates Prl concentrations 10 min after injection, leaving serum Prl levels unchanged 30 and 60 min after the administration. Naloxone (25 and 100 micrograms/kg) alone does not substantially modify serum Prl concentrations at any time interval considered. Treatment with either dose of naloxone performed together with either 0.25 or 1 microgram/kg of dermorphin completely counteracts the stimulatory effect of the peptide at all time intervals in which dermorphin was active when given alone. In orchidectomized (3 weeks) rats, the intraventricular administration of dermorphin at the dose of 0.25 micrograms/kg appears effective in enhancing Prl levels only 30 min after treatment. No statistically significant modifications are observed at 10 and 60 min with this dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma.

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.

Adult↗