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Biomedical subjects

A R Gagliardi

Publications and source records attributed to A R Gagliardi.

At least 19 recordsLinked to original sources
PubMed2007

Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus.

BACKGROUND: Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes. METHODS: Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH), cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta-triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol-5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol-5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection. RESULTS: The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx. CONCLUSIONS: ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients.

Adolescent↗
PubMed2000

Suramin analogs inhibit human angiogenesis in vitro.

BACKGROUND: Suramin is a polysulfonated naphthylurea that inhibits tumor cell proliferation and angiogenesis, but the widespread use of this drug has been limited by significant neurologic toxicity. A series of suramin analogs that may exhibit less toxicity in vivo have been synthesized. We hypothesized that these novel analogs would have antiangiogenic properties equal to or greater than those of suramin when evaluated in an in vitro human placental vein angiogenesis model. METHODS: Human placental veins (n = 72 per group) were cultured in a 0.3% fibrin clot for a period of 14 days. Three suramin analogs (NF 145, NF 248, NF 293) and suramin were tested at 56 and 560 microM concentrations to determine their effect on the development of an angiogenic response. Experiments were repeated for each analog on veins from three different placentas. The percentage of wells that initiated an angiogenic response was calculated and compared with initiation in a control group (n = 141). RESULTS: The three suramin analogs inhibited angiogenesis in a dose-dependent fashion, with all compounds exhibiting near-complete inhibition of angiogenesis at 560 microM. The effects of these analogs were equal to or greater than those of suramin. CONCLUSION: Suramin analogs with structural alterations inhibit human angiogenesis at concentrations equivalent to those seen in vivo. These analogs may be more effective antiangiogenic agents than suramin and may have less potential for toxicity.

Animals↗
PubMed1998

Uptake of suramin by human microvascular endothelial cells.

We have demonstrated for the first time that suramin is taken up by human dermal microvascular endothelial (HMEC-1) cells by an active process involving the caveolae system. The uptake of suramin was time-dependent and reduced by more than 90% when incubated in the presence of albumin or at 4 degrees C. Suramin uptake was also inhibited when incubated in the presence of filipin and digitonin, both potent cholesterol-binding agents, but not in the presence of probenecid. The [3H]suramin taken up by the HMEC-1 cells was located primarily within the nucleus, followed by the cytoplasmic fraction. The presence of suramin in these cellular compartments suggests that this drug may act through intracellular mechanisms.

Antineoplastic Agents↗
PubMed1998

Suramin analogues with a 2-phenylbenzimidazole moiety as partial structure; potential anti HIV- and angiostatic drugs, 2: Sulfanilic acid-, benzenedisulfonic acid-, and naphthalenetrisulfonic acid analogues.

The synthesis of suramin analogues bearing a 2-phenyl-benzimidazole moiety is described. Aminoarene sulfonic acids 2a-e are acylated with 3,4-dinitrobenzoyl chloride 3 yielding the amides 4a-e which are hydrogenated to the corresponding diamines 5a-e. These are treated with 3-nitrobenzaldehyde, yielding the azomethines 7a-e and their isomers 8a-e and 9a-e. Key step in the synthesis of the target compounds 12a-e is the oxidation of the azomethines with oxygen to the benzimidazoles 10a-e. These are hydrogenated to the amines 11a-e reacting with phosgene to yield the symmetric ureas 12a-e. Results of the anti-HIV, cytostatic, and antiangiogenic screening are presented.

Anti-HIV Agents↗
PubMed1998

Antiangiogenic and antiproliferative activity of suramin analogues.

The purpose of this study was to test the ability of 70 polyanionic analogues of suramin to inhibit angiogenesis. The ID50, the dose that produced 50% inhibition of angiogenesis, was determined for suramin and each of the analogues by measuring the ability of various amounts to inhibit angiogenesis in vivo in the chick egg chorioallantoic membrane (CAM) assay. Of the 70 analogues, 11 had antiangiogenic activities similar to suramin and an additional 7 were significantly more potent than suramin. All seven of these analogues were from the naphthalenetrisulfonic acid group and contained large urea groups. The benzene sulfonic and disulfonic acid analogues were less active inhibitors of angiogenesis than the naphthalenetrisulfonic acid analogues. Replacement of the naphthalenetrisulfonic acid groups by aliphatic carboxylic acids or benzoic acid gave analogues with very little antiangiogenic activity. In subsequent experiments, the antiproliferative activity of selected analogues on basic FGF (bFGF)-stimulated growth of immortalized human microvascular endothelial cells in vitro was determined. Analogues that inhibited angiogenesis to a greater extent than suramin in the CAM assay generally showed a greater antiproliferative effect on bFGF-induced growth of human microvascular endothelial cells. These results suggest that some of the polyanionic analogues may be potent therapeutic agents for cancers and angiogenesis-dependent diseases.

Animals↗
PubMed1991

[Late effects on the hypothalamo-pituitary function after the treatment of parasellar tumors].

Long term follow-up of patients submitted to treatment of parasellar tumours region is important for the detection of late therapeutic complications. In this study the authors conducted an evaluation of six patients with craniopharyngioma, one with germinoma, one with meningioma, and one epidermoid cyst. All above tumours were localized at parasellar region. Six out of nine patients had been treated both by surgery and by radiotherapy and the other three surgically only, on an average 3.8 +/- 3.2 years before this observation was carried out. Five patients were female with their ages average 24.3 +/- 18.8 years old. Evaluation consisted: in the first place, an intravenous infusion of thyrotropin-releasing hormone (TRH, 200 micrograms), gonadotropin-releasing hormone (GnRH, 100 micrograms), and insulin tolerance test (0.1 IU/Kg, regular insulin); and secondly, in measurements of pituitary hormones secretion at different time points--0, 20, 40, 60 and 80 minutes. We found both diminished response of growth hormone and cortisol in all the patients. Seven out of nine patients did not have adequate response to follicle-stimulating hormone. Three out of nine responded unsatisfactory to luteinizing hormone. Four out of nine showed inadequate responses to prolactin as well as, two out of eight to thyrotropin. We concluded that: (a) growth hormone and cortisol deficiency are the most frequent finding in these patients; (b) post-radiotherapy lesions can be located in the hypothalamus or pituitary, or even in both; (c) hypophysial and hypothalamic cells sensitivity to irradiation is different, according to their respective hormones; and (d) it is necessary a frequent endocrinologic follow-up of patients to detect late hormonal deficiencies.

Adolescent↗
PubMed1990

Nutrition and somatomedin. XXI. Insulin-like growth factor-I and somatomedin inhibitor in streptozotocin-diabetic rats: relation to ketogenesis and gluconeogenesis.

Diabetes is associated with a fall in serum insulin-like growth factor-I (IGF-1) and a rise in somatomedin inhibitor, a circulating factor(s) of approximately 30,000 MW that is released by the liver and can antagonize both somatomedin and insulin action. Levels of inhibitor correlate with levels of glucose, beta-hydroxybutyrate, and weight loss. To study pathways that could underlie the fall in IGF-1 and rise in inhibitor, the effects of metabolic inhibitors on circulating metabolic fuels, serum IGF-1, and serum somatomedin inhibitor activity were studied. Rats given streptozotocin exhibited weight loss of 14% +/- 0.1%, glucose 457 +/- 26 mg/dL, and beta-hydroxybutyrate (BOHB) 6.3 +/- 0.5 mmol/L. Somatomedin inhibitor was separated from IGF-1 by size exclusion HPLC at pH 3; IGF-1 was measured by RIA, and somatomedin inhibitor by cartilage bioassay. Diabetic animals exhibited a fall in IGF-1 to 76% of normal (P less than .02) and a rise in inhibitor to 270% of normal (P less than .01). 3-Mercaptopicolinic (3-MPA) acid, an inhibitor of gluconeogenesis, lowered glucose to 68 +/- 2 mg/dL and BOHB to 0.96 +/- 0.09 mmol/L (both P less than .01 v diabetic), but levels of inhibitor did not fall. Nicotinic acid, an inhibitor of lipolysis, did not affect glucose but reduced BOHB to 0.42 +/- 0.02 mmol/L; somatomedin inhibitor fell 19% below diabetic levels (NS) but remained above normal (P less than .01). In contrast, inhibition of fatty acid oxidation with methyl-2-tetradecylglycidate reduced glucose to 191 +/- 18 mg/dL but lowered BOHB to normal, 0.16 +/- 0.02 mmol/L, accompanied by normalization of somatomedin inhibitor levels (152% +/- 33% of normal, NS). Below 1.0 mmol/L BOHB, somatomedin inhibitor and BOHB were strongly correlated (r = .67, P less than .001); no comparable relation was found with glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of clonidine on growth and plasma somatomedin C levels of young rats.

To study the effects of clonidine on growth and plasma somatomedin C (SmC) levels, 42 male Wistar rats aged 28 days and weighing 75 to 105 g were given clonidine (1.5 micrograms/ml in drinking water), or filtered water alone and were weighed weekly. After 0, 4 and 8 weeks, the animals were sacrificed under ether anesthesia, their length was measured and blood was collected by cardiac puncture for measurement of SmC concentration. Growth and the weight/length ratio were lower, and plasma SmC levels (mean +/- SEM) were greater in the treated groups after 4 (616 +/- 44.7 vs 433.2 +/- 39.38 ng/ml, P less than 0.01) and 8 (595.2 +/- 28.3 vs 412.66 +/- 39.01 ng/ml, P less than 0.01) weeks of treatment, suggesting that clonidine treatment increased growth hormone secretion. In other experiments, treated animals showed increased food intake only during the first week of treatment and decreased epididymal fat weight after 3 weeks (1.412 +/- 0.0536 vs 1.6 +/- 0.1336 mg/100 g body weight, P less than 0.01). The results suggest that clonidine acts at the level of the central nervous system involving transitory modulation of food intake, as well as on the regulation of energy metabolism.

Animals↗
PubMed1988

[Giant parasellar aneurysm simulating pituitary tumor].

Seven cases of compromised pituitary fossa at the conventional skull X-ray, who had the final diagnosis of giant aneurysm of the intracavernous portion of the carotid artery (6 cases) and one of the anterior communicating artery, are reported. The main findings were: headache (7/7), complex ophthalmoplegia involving the III, IV and VI cranial nerves (5/7), compromised V cranial nerve (4/7) and eyeball pain (4/7). Other manifestations were: meningeal signs (2/7), unilateral blindness (1/7), hemiparesis (1/7), cacosmia (1/7) and inferior bitemporal quadrantanopsia (1/7). Five patients with intracavernous carotid artery aneurysm showed benefits with progressive occlusion of the internal carotid artery at the cervical level. One died before surgery. The case with anterior communicating artery aneurysm improved after its surgical clipping. Our data, in accord with the literature, support the conclusion that the differential diagnosis of aneurysms in the parasellar region remains a very difficult task. The accurate final diagnosis requires cerebral angiography and the surgical treatment with progressive occlusion at the cervical portion of the internal carotid artery has a relatively low risk with promising results.

Adult↗
PubMed1985

Pentavalent antimonial inhibition of the osmotic effect of oxytocin on the isolated toad bladder.

The inhibition of osmotic stimulated water flow in the isolated toad bladder by 0.1 mM sodium stibogluconate (pentavalent antimony) is described. Pentavalent antimony on the serosal surface significantly inhibited oxytocin-induced water flow but when the drug was added to the mucosal surface only the effect of low oxytocin concentrations was reduced. The phosphodiesterase inhibitor pentoxifylline, when present on the serosal side, blocks the effect of pentavalent antimony on stimulated water flow. No effect was detected when indomethacin was present on the serosal side. It is suggested that phosphodiesterase activation might play a role in the mechanism of pentavalent antimonial inhibition of oxytocin-induced water flow in the isolated toad bladder. The effect obtained when sodium stibogluconate on the serosal side was replaced with antimony pentachloride (SbCl5) supports the view that the metal in the molecule is responsible for the inhibition of the effect of oxytocin.

Animals↗
PubMed1984

GAPO syndrome: report of three affected brothers.

We present a sibship of three brothers affected with the GAPO syndrome. This is a rare and very characteristic autosomal-recessive trait whose main manifestations are growth retardation, alopecia, pseudo anodontia, and optic atrophy. So far nine affected individuals are known (4 males and 5 females). Two of them, the patient of Andersen and Pindborg cited in Tipton and Gorlin [1983] and one of the cases of Wajntal et al [1982], died at 39 and 37 years respectively.

Alopecia↗
PubMed1983

[Hereditary hemorrhagic telangiectasia. Report of a case].

A case of hereditary hemorrhagic teleangiectasia (HHT) or Rendu-Osler-Weber disease with neurological involvement is reported. The patient presented a diffuse cortical dysfunction with seizures after a gastric haemorrhage disturbance. The authors could not find vascular malformations of brain or pulmonary arteriovenous fistula (PAVF), so a anoxic encephalopathy followed a shock or a microangiopathic dysfunction is postulated. The main neurological manifestations of HHT are discussed, emphasizing in the first place the role of the PAVF on the genesis of cerebral hypoxemia and brain abscess and occasionally a cerebral thrombosis caused by polycythemia and in the second place the vascular malformations of brain and spinal cord. The portal-systemic encephalopathy may also occur as a neurological complication in few cases.

Arteriovenous Malformations↗
PubMed1981

Structural aberration of the X chromosome in a patient with gonadal dysgenesis: an approach to karyotype-phenotype correlation.

An 18-year-old female with some stigmata of pure dysgenesis had a chromosome constitution of 46,X,dir dup(X) (pter leads to q27: :q21 leads to qter). The abnormal chromosome was always late replicating. The clinical and cytogenetic picture is compared with that of patients with X;X translocation and some problems of karyotype-phenotype correlation are discussed.

Adolescent↗
PubMed1978

Trisomy 8 syndrome.

Clinical and dermatoglyphic data on a male patient with complete trisomy 8 are reported and compared with those of other known cases of trisomy 8. The more discriminating findings for this condition are skeletal anomalies, restricted articular function, and speech problems.

Adult↗
PubMedDate not supplied

The effect of a lectin from the venom of the snake, Bothrops jararacussu, on tumor cell proliferation.

Lectins have been used extensively as histochemical probes to describe changes in tumor cell surface and are known to influence the growth of cancer cells. In this study, we determined the effect of a lectin from the venom of Bothrops jararacussu (BJcuL) on the proliferation of a number of established human cancer cell lines. The growth of eight cancer cell lines was inhibited in a dose-related manner in the presence of BJcuL lectin. This lectin was most potent as an inhibitor of growth in renal (Caki-1 and A-498) and pancreatic (CFPAC-1) cancer cell lines with 50% inhibitory concentrations (IC50) of 1-2 mM. Melanoma (Wm115) and prostate (PC-3) cancer cells showed IC50 values of 7.9 and 8.5 mM, respectively, in the presence of BjcuL lectin whereas colon (Caco-2) and breast (MCF7) cancer cell lines showed no effect. Our results suggest that BJcuL lectin is an effective inhibitor of cell growth in some cancer cell lines.

Breast Neoplasms↗