Biomedical subjects

M Nicola

Publications and source records attributed to M Nicola.

At least 19 recordsLinked to original sources

PubMed2002

Effect of acute load of grapefruit juice on urinary excretion of citrate and urinary risk factors for renal stone formation.

The effect of citrus fruit juice ingestion on the risk of calcium oxalate stone formation is still debated. The present study was undertaken to investigate changes in urinary stone risk factors after administration of a soft drink containing grapefruit juice. Seven healthy subjects, with no history of kidney stones, were submitted to an acute oral load (20 ml/kg body weight over 60 min) of a soft drink containing grapefruit juice diluted (10%) in mineral water. After a 7-day wash-out period, each subject underwent an oral load with mineral water alone under the same conditions. Urine specimens were collected before (for 120 min) and after each oral fluid load (for 180 min). Urinary flow was significantly increased after both grapefruit juice (46+/-26 vs 186+/-109 ml/h, p = 0.01) and mineral water (42+/-16 vs 230+/-72 ml/h, p=0.001) compared to baseline. Compared to mineral water, grapefruit juice significantly (p=0.021) increased urinary excretion of citrate (25.8+/-9.3 vs 18.7+/-6.2 mg/h), calcium (6.7+/-4.3 vs 3.3+/-2.3 mg/h, p=0.015) and magnesium (2.9+/-1.5 vs 1.0+/-0.7 mg/h, p=0.003). Citrus fruit juices could represent a natural alternative to potassium citrate in the management of nephrolithiasis, because they could be better tolerated and cost-effective than pharmacological calcium treatment. However, in order to obtain a beneficial effect in the prevention of calcium renal stones a reduced sugar content is desirable to avoid the increase of urinary calcium due to the effect of sugar supplementation.

Adult↗

PubMed2001

Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation.

BACKGROUND: The NUP98 gene is involved in multiple rearrangements in haematological malignancy. The leukemic cells in an acute myeloid leukemia (AML) patient with a t(9;11)(p22;p15) were recently shown to have a fusion between the NUP98 gene and the LEDGF gene but it was not demonstrated that this fusion was recurrent in other leukaemia patients with the same translocation. RESULTS: We used RT-PCR to analyse the leukemic cells from an AML patient who presented with a cytogenetically identical translocation as the sole chromosomal abnormality. A NUP98-LEDGF fusion transcript was observed and confirmed by sequencing. The reciprocal transcript was also observed. The fusion transcript was not detectable during remission and recurred at relapse. The breakpoints in the NUP98 and LEDGF genes were different to those previously reported. The NUP98 breakpoint occurs in the intron between exons 8 and 9. It is the most 5' breakpoint reported in a translocation involving the NUP98 gene. All of the LEDGF gene is included in the fusion except for exon 1 which codes for the first 24 amino terminal amino acids. CONCLUSIONS: Our results show that fusion of the NUP98 and LEDGF genes is a new recurrent translocation in AML.

Acute Disease↗

PubMed2000

The angiogenesis marker ED-B+ fibronectin isoform in intracranial meningiomas.

Fibronectins (FNs), adhesive glycoproteins mainly expressed in the extracellular matrix, are polymorphic molecules whose various isoforms are dependent on alternative splicing patterns. The isoform containing the ED-B sequence and occurring in foetal and neoplastic tissues (oncofoetal or B+FN) has been previously recognized as a marker for angiogenesis. The distribution of this isoform was analyzed in a consecutive series of 134 surgically obtained intracranial meningiomas, using specific monoclonal antibodies. Oncofoetal FN was found to be widely distributed in the vessels of anaplastic meningiomas, with its expression being restricted in the vasculature of the typical subtypes. and absent in the neighbouring cerebral tissue. The ubiquitous vascular expression of B+FN in meningiomatous malignancies might provide a potential target for the in vivo delivery of angiosuppressive agents.

Biomarkers, Tumor↗

PubMed2000

[Peyronie's disease: ultrasonographic follow-up of ESWT].

The application of a small-sized lithotriptor for the extracorporeal shock-wave treatment (ESWT) of La Peyronie's disease (PD) was originally suggested by Butz, in 1996. In November 1996 we started to use this method with the aim of checking its tolerability and effectiveness. From April 1998, we standardized our protocol treatment as follow: higher treatment frequency: each every other day; higher energy density value: at least level "4" (= 0.11 mJ/sqmm). From March 1998 to May 2000, 82 patients with PD, aged between 44 and 74 (average age 53.8) were treated according to this protocol. A case history was drafted for each patient and they all underwent an objective examination, a dynamic ultrasonic scan of the penis and a photograph of the penis after drug-induced erection. The complaint had lasted for a period of time varying from a minimum of 3 to a maximum of 120 months (average time 23.3 months). 44 patients reported painful erections and 78 patients showed bending of the penis during erection. The pre-treatment dynamic ultrasonic scan of the penis revealed plaques with calcific features in 36 patients, while for the remaining 46 cases the ultrasonic images were compatible with fibrotic thickening. On completion of the 4th treatment session, the patients were given a questionnaire to fill in so that we could obtain a subjective evaluation of the results achieved. All the patients underwent photograph and dynamic ultrasonic scan of the penis (both performed after drug-induced erection, pre- and post treatment). Slight alteration often appeared on the skin of the penis (petechias), which disappeared spontaneously within 48 hours. On completion of the 4th treatment session, 37 patients out of 82 (45%) reported subjective improvement described as "stoppage" in the progression and/or partial regression of the disease" with a filling of a saller size of the plaque on-self examination. As far as concerns pain, this symptom disappeared in 31 out of the 44 patients concerned (70.4%). At the clinical check, based on the ultrasonic scans carried out after ESWT, in 34 cases of 82 (41%), it was possible to note a reduction in the echogenicity or in the size of the treated plaque. In 32 patients (39%) an unchanged plaque was observed, and in 16 case a larger plaque or a calcific evolution was established. For what the bending of the penis concerns, the comparison between the photographs revealed a reduction of the curvature in 24 patients out of 78 (30.7%). Of the 46 patients in whom the disease had non-calcific characteristics, according to the ultrasonic scans, 21 (46%) showed improved disease since in 25 (54%) the treated plaque had stabilized or worsened. In the group of 36 patients with the calcific plaques, 13 (36%) improved while 23 (64%) resulted unchanged or worsened.

Adult↗

PubMed1999

The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.

We determined the breakpoint genes of the translocation t(4;11)(q21;p15) that occurred in a case of adult T-cell acute lymphocytic leukemia (T-ALL). The chromosome 11 breakpoint was mapped to the region between D11S470 and D11S860. The nucleoporin 98 gene (NUP98), which is rearranged in several acute myeloid leukemia translocations, is located within this region. Analysis of somatic cell hybrids segregating the translocation chromosomes showed that the chromosome 11 breakpoint occurs within NUP98. The fusion partner of NUP98 was identified as the RAP1GDS1 gene using 3' RACE. RAP1GDS1 codes for smgGDS, a ubiquitously expressed guanine nucleotide exchange factor that stimulates the conversion of the inactive GDP-bound form of several ras family small GTPases to the active GTP-bound form. In the NUP98-RAP1GDS1 fusion transcript (abbreviated as NRG), the 5' end of the NUP98 gene is joined in frame to the coding region of the RAP1GDS1 gene. This joins the FG repeat-rich region of NUP98 to RAP1GDS1, which largely consists of tandem armadillo repeats. NRG fusion transcripts were detected in the leukemic cells of 2 other adult T-ALL patients. One of these patients had a variant translocation with a more 5' breakpoint in NUP98. This is the first report of an NUP98 translocation in lymphocytic leukemia and the first time that RAP1GDS1 has been implicated in any human malignancy.

Adolescent↗

PubMed1994

Synthesis and free radical scavenging properties of the enantiomers of erdosteine.

The synthesis of enantiomers R and S of erdosteine, a derivative of homocysteine-gamma-thiolactone, and the NMR studies for the determination of the enantiomeric excess with chiral shift reagent on the more soluble ethyl esters, are described. Pharmacological data relative to the free radical scavenging properties of the R and S enantiomers are reported. In particular, it has been documented that the S isomer is more effective than R isomer in protecting mice against lethal doses of paraquat (substance able to form free radicals when administered by i.p. route).

Animals↗

PubMed1993

High dose hydroxyurea in collection of Philadelphia chromosome-negative stem cells in chronic myeloid leukaemia.

High dose hydroxyurea (HU) was used in a pilot study to assess its efficacy in mobilizing Philadelphia (Ph) chromosome negative progenitor cells in chronic myeloid leukaemia (CML). Five patients received 12 g/M2 oral HU in divided doses. Side effects were minimal, allowing outpatient administration. Nine to fourteen days later 4 patients achieved a mean leukocyte nadir of 3.5 x 10(9)/L (Range 2.4-4.9) and a mean platelet nadir of 99 x 10(9)/L (Range 95-108). Peripheral blood mononuclear cells (PB-MNC) sampled prior to the HU priming were 100% Ph positive. Between 10 and 18 days post HU, 3 patients achieved a marked reduction (80-100%) in the number of Ph positive metaphases in PB-MNC collected by apheresis. One patient failed to achieve any Ph suppression. Polymerase chain reaction analysis (PCR) for the bcr-abl fusion product remained positive in all samples. Rapid rises in CFU-GM numbers were associated with a return to 100% Ph positive metaphases however slower rises represented recovery with predominantly Ph negative cells, allowing apheresis collection of these cells. We conclude that HU induces a reproducible leukocyte nadir with sufficient stem cell mobilization for potential autologous transplantation. Higher doses of HU together with early and intensive apheresis is required to maximize Ph negative progenitor cell harvests.

Aged↗

PubMed1991

Pharmacological properties of a novel class of 5-HT3 receptor antagonists.

The pharmacological profile of six representative members of a novel class of 5-HT3 receptor antagonists is described. The compounds are esters and amides of benzimidazolone-1-carboxylic acid with a basic azabicycloalkyl moiety (compounds 1-3) and their respective ethyl derivatives (compounds 4-6). In isolated preparations (rabbit heart and guinea pig ileum) all compounds antagonized the 5-HT3 receptor-mediated effects of serotonin, with potencies comparable with those of the reference compounds, ICS 205.930 and GR 38032F (-log IC50 9.30-11.9 and 6.8-8.20, in heart and ileum, respectively). In the anaesthetised rat, all agents potently inhibited the Bezold-Jarisch reflex whether given i.v. or i.d. I.v. administration of compounds prevented cisplatin-induced emesis in dogs (ID50 ranging from 3.7 to 147 micrograms/kg). All agents accelerated gastric emptying of solids in rats (ED50 about 10-160 micrograms/kg i.p.). In addition, compounds 4 and 5 were able to stimulate 5-HT4 receptors in the isolated guinea pig ileum, as well as enhance contractile activity in the Heidenhain gastric pouch of dogs, showing clearcut prokinetic properties.

Animals↗

PubMed1991

Azabicycloalkyl benzimidazolone derivatives as a novel class of potent agonists at the 5-HT4 receptor positively coupled to adenylate cyclase in brain.

Recent experimental evidence indicates that central 5-HT4 receptors which are positively coupled to adenylate cyclase, are stimulated by a family of 2-methoxy-4-amino-5-chloro substituted benzamide derivatives. These compounds are also potent stimulants of the gastro-intestinal motility. In this study the ability of three azabicycloalkyl benzimidazolone derivatives, BIMU 1, BIMU 8, and DAU 6215 (structural formulas are given in the text), to stimulate cAMP formation in colliculi neurons in primary culture have been tested. Two of the compounds, BIMU 1 and BIMU 8, which show prokinetic activity in various animal models, were also good agonists at the 5-HT4 receptors, whereas DAU 6215, a drug devoid of prokinetic activity, was only a weak, partial agonist at 5-HT4 receptors. The rank order of their potencies as compared with those of 5-HT and cisapride was as follows: BIMU 8 = cisapride greater than 5-HT greater than BIMU 1 greater than DAU 6215. The efficacies of BIMU 8 and cisapride were comparable (133 +/- 9% and 124 +/- 8% of the maximal 5-HT efficacy, respectively), whereas BIMU 1 and DAU 6215 elicited, respectively, only 72 +/- 11% and 16 +/- 4% of the maximal 5-HT effect. The activities of the azabicycloalkyl benzimidazolone derivatives and 5-HT on cAMP formation were not additive and ICS 205-930 antagonized the stimulatory effect of these compounds with low potency (pKi = 6.1-6.4), further strengthening the notion of interaction with 5-HT4 receptors. In addition, cross desensitization between the effects of 5-HT and the azabicycloalkyl benzimidazolones on adenylate cyclase was noted, another argument in favor of an interaction of these drugs on 5-HT4 receptors.

Adenylyl Cyclases↗

PubMed1991

Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation.

The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.

Animals↗

PubMed1991

Synthesis and biological evaluation of new muscarinic receptor antagonists bearing cyclic amidines as cationic heads.

Two classes of compounds, bearing a cyclic amidino moiety instead of the tertiary amino group of the classical antimuscarinic drugs like hexahydrodifenidol 3 were synthesized. Affinities (KD) for the three pharmacologically defined M1, M2 and M3 mAChR subtypes were measured in radioligand binding assays and in functional in vitro studies (KB) in guinea pig ileum and left atrium. The results showed that the replacement of the tertiary amino group in structural analogues of 3 with a cyclic amidino moiety afforded potent antimuscarinic compounds. The selectivity shown for smooth muscle preparations suggests their usefulness as antispasmodics.

Amidines↗

PubMed1990

Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives as highly potent 5-HT3 receptor antagonists.

A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid esters and amides containing a basic azacyclo- or azabicycloalkyl moiety has been synthesized and evaluated for 5-HT3 antagonistic activity in a radioligand binding assay ([3H]ICS 205930) and in the 5-HT-induced von Bezold-Jarisch reflex in the rat. It was found that endo-substituted azabicycloalkyl derivatives (e.g. 7a, 12a, 12b) were much more active than the corresponding exo analogues (e.g. 7b, 12h, 12i) or azacycloalkyl compounds. Amidic derivatives 12a, 12b, 12c, 12e, 13b, and 13c proved to be about 10 times more active than the corresponding ester derivatives 7a, 11a, 7c, 7d, 8a, and 8b. In particular, compound 12a (DA 6215) showed a Ki = 3.8 nM in the binding test and an ED50 = 1 nM/kg iv in the von Bezold-Jarisch reflex assay, an activity comparable to that of the reference compound 2 (ICS 205930, Ki = 2 nM, ED50 = 2.1 nM/kg). IR spectroscopy studies in the solid state and in CHCl3 solution revealed the existence of an intramolecular hydrogen bond in 13b, taken as a model compound for this class of substances. A molecular modeling study showed that 12a, in its internal hydrogen-bound conformation, well matches a recently proposed pharmacophoric model for 5-HT3 antagonist activity.

Animals↗

PubMed1990

Synthesis of a new class of 1,4-dihydropyridines having a hydroxamic ester group in position 3 with a potential calcium antagonistic activity.

The synthesis of new 1,4-dihydropyridines having a hydroxamic acid or hydroxamic ester group in position 3 is described. Pharmacological evaluation included calcium antagonistic activity in the guinea pig Taenia coli test and acute toxicity. The compounds had not a calcium antagonistic activity, if compared with other well known DHP utilized as standard, so the pharmacological tests were not furtherly studied.

Animals↗

PubMed1987

Synthesis and calcium antagonistic activity of a new class of 1,4-dihydropyridines having an alkoxyimino group in position 3.

The synthesis of new 1,4-dihydropyridines having an alkoxyimino group in position 3 is described. Pharmacological evaluation included calcium antagonistic activity in the guinea pig Taenia coli test, acute toxicity and oral antihypertensive activity in SHR. The compounds had a remarkable calcium antagonistic activity in vitro and low toxicity, but no antihypertensive activity in vivo, probably due to an unfavourable pharmacokinetic profile.

Animals↗

PubMed1986

[Pseudoxanthoma elasticum].

Four young female patients with Pseudodixanthome elasticum are reported, corresponding to the Grönblad and Strandberg syndrome. The dysplastic derangement of the elastic fibers with a potentially systemic compromise is considered, which explains the multiorganic character of the disease. We conferred to the skin changes the means of a marker that obligates an exhaustive study and follow-up of the patients to make visceral affectations.

Adolescent↗

PubMed1980

Synthesis of N-alkoxybenzoylmorpholinols as possible metabolites of trithiozine.

The synthesis of some possible metabolites of trithiozine, a new antisecretory-antiulcer drug, is reported. The metabolite 4-(3,4,5-trimethoxybenzoyl)-2-morpholinol (III a) was prepared by oxidative cyclization of the corresponding diethanolamine derivative (II a). Similarly, 4-syringoyl-2-morpholinol (III c) was also obtained and both were converted into the methyl ethers (IV a, c), respectively. The same oxidative approach, starting from the alcohol (VII), afforded the isomeric 4-(3,4,5-trimethoxybenzoyl)-3-morpholinol (IX a) in low yields; therefore a four step process, involving the acid hydrolysis of the acetal intermediate (XII a) was preferred. In the course of the synthetic work 4-(3,4,5-trimethoxybenzoyl)-3-morpholone (V), a potential metabolite itself, was also prepared.

Anti-Ulcer Agents↗

PubMed1979

[Morphologic and pathologic findings in teeth and jaws from the middle bronze age (Pitten, Lower Austria)].

The detailed examination of the masticating apparatus of 18 skulls from the Middle Bronze Age in Pitten (Lower Austria) revealed numerous pathological findings of the teeth. Most remarkable were frequency and extent of dental abrasions. In addition to it, indications on inflammatory processes in the marginal parodontium were obtained, combined with partly immense formations of concrements on the surfaces of the teeth. The incidence of dental caries was relatively low. Abnormal positions of the teeth and pathological processes concerning the development of dentition as well as the eruption of the wisdom teeth could be observed repeatedly. Conclusions on insufficiences of the oral hygiene in this time follow especially from the concrement findings and from the inflammatory reactions of the marginal parodontium.

Adult↗

PubMed1977

[Pneumatosis cytoides coli. Conservative treatment with oxygen breathing (author's transl)].

Investigations in a 51-year old female patient suffering from severe tenesmus and therapy resistant diarrhoea led to a diagnosis of pneumatosis cystoides coli. After 4 days of treatment with continuous oxygen breathing there was dramatic clinical improvement and an incomplete radiological remission. This new method is an important step forward in the treatment of pneumatosis coli. The only potential side effect is pulmonary oxygen toxicity. Thus limitation of oxygen treatment to the shortest time necessary for abolishing symptoms is recommended. Oxygen breathing is a safe, simple and effective treatment of pneumatosis coli and may replace the currently performed surgical resection of the involved intestinal segments.

Colonic Diseases↗