Biomedical subjects
Publications and source records attributed to A Caruso.
A new series of imidazolyn-5-one derivatives were synthesized. These compounds were screened for their analgesic, anti-inflammatory and antipyretic activities, as well as for their ulcerogenic potential, for behavioural effects and acute toxicity. Some of them showed higher analgesic activity than phenylbutazone (PBZ), but lower anti-inflammatory activity. Their ulcerogenic effect was lesser than that of the reference drug.
The methylation of 2H-pyridazino [4,5-b][1,4]benzothiazin-1(10H)-one-5,5-dioxide 2 and the oxidation of 2-methyl-2H-pyridazino[4,5-b][1,4]benzothiazin-1(10H)-one 3 produced the same compound 4. On the contrary, in the 2-dialkylaminoalkylic series, the dialkylamino-alkylation and the oxidation reactions, carried out on compounds 2 and 8 respectively, afforded derivatives 7 and 9. In addition, the behaviour to the oxidation of the corresponding 10-methyl and 10-dialkylaminoalkyl analogues is also described. The synthesized compounds were tested for their analgesic, antiexudative and anti-inflammatory activities. The pharmacological results showed that in general dialkylaminoalkyl derivatives are more active than methyl derivatives. In particular, compounds 7 b, 9 b and 11 c exhibited an analgesic activity comparable to that of phenylbutazone; moreover 10-substituted compounds 11 a, 11 b and 11 c, screened p.o. as anti-inflammatory agents in rats, resulted equipotent to phenylbutazone and more active than 2-substituted isomers. These activities are coupled with a high LD50 and a very low ulcerogenic potential.
Some carboxymethyl- and carboxy-derivatives of 7H- and 5H-1,2,4-triazolo [3,4-b][1,3,4] thiadiazine were prepared. Their structure are discussed on the basis of IR, NMR and mass spectra. The synthesized compounds were subjected to a preliminary pharmacological screening for antiinflammatory-analgesic activity and to microbiological test on various species of mycetes and bacteria.
The paper reports a case of diffuse placental hemangioma leading to intrauterine fetal death. Contrary to other cases reported in the literature, polyhydramnios, oligohydramnios and fetal malformations were not observed. The sole finding was a dilatation of the cardiac auricle, in particular on the right-hand side. It is hypothesised that fetal death was due to two concomitant factors: the severe hypoxemic state and the difficulty of venous drainage from the fetus to the mother owing to increased materno-fetal placental shunts.
Live-cell indirect immunofluorescence was used to detect HIV-associated antigens in fresh uncultured peripheral blood mononuclear cells from 29 HIV-seropositive subjects. Conventional fixed-cell immunofluorescence and live-cell immunofluorescence were run in parallel on each sample using monoclonal antibodies directed against HIV gag and env gene products. Sera from the same patients were also tested for HIV antigen by a sandwich enzyme immunoassay. Results strongly indicate that nondenaturing live-cell immunofluorescence is much more sensitive for detection of HIV-associated antigens and may be useful in the diagnosis of HIV infection as well as in the study of pathogenesis.
Some N-heterocyclic salicylamide derivatives were prepared by fusion of phenyl salicylate and heterocyclic amines, whereas other ones were synthesized by ring closure using N-salicyloyl-N'-anthranylhydrazine as starting material. All the compounds were tested for their analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effects, in order to ascertain if the N-substitution would offer any advantages. Some derivatives were more effective than salicylamide and ulcerogenic activity was variably lowered.
A stable hybridoma cell line secreting specific antibodies against human interferon-gamma (IFN-gamma) and designated IGMB-14 has been established. It belongs to the IgG1, kappa subclass and it reacts in Western blot with the 28 kDa and 56 kDa polypeptides present in two different affinity purified IFN-gamma preparations. Peripheral blood mononuclear cells (PBMC) from a healthy individual, stimulated in vitro by PHA, were analysed for IFN-gamma production both when viable and following fixation. The presence of cytoplasmic or surface IFN-gamma was visualized by an indirect immunofluorescence assay using monoclonal antibody (MAb) IGMB-14 and a single laser FACS-III fluorescence-activated cell sorter. The staining permitted the detection of newly synthesized cytoplasmic IFN-gamma molecules in lymphocytes at day 1 after PHA stimulation and surface IFN-gamma at day 2. IFN-gamma was expressed on almost all the CD4+ lymphocytes as shown by a double staining technique. The specificity of the reaction was confirmed by Western blots and abolishing IFN-gamma staining by pretreatment of MAb IGMB-14 with IFN-gamma. The presence of surface IFN-gamma was also visualized on freshly isolated PBMC from two patients suffering from measles and AIDS but not on PBMC from a healthy individual. The experiments showed that this immunofluorescent method is useful for the detection, enumeration, and phenotypic characterization of IFN-gamma-producing cells in vitro and, in addition, for evaluating the presence of PBMC expressing IFN-gamma on their surface during a viral disease.
Immunoreactive alpha-melanocyte stimulating hormone (IR-alpha-MSH)-like activity was measured by radioimmunoassay (RIA) in at term pregnancy amniotic fluid prior and after adsorption on a Sep-pak C18 cartridge. alpha-MSH activity was 3-4 times lower after Sep-pak purification but, unlike the levels of IR-alpha-MSH in the fluid analyzed in toto, increased linearly with the volume of fluid analyzed. Furthermore, fractionation by high pressure liquid chromatography (HPLC) revealed that IR-alpha-MSH recovered from the Sep-pak was due to several peptides rather than to a single peptide. The most abundant of them (50% of total activity) behaved like authentic des-acetyl-alpha-MSH. Since des-acetyl-alpha-MSH is also the most abundant alpha-MSH-like peptide in the fetal pituitary gland, the present results suggest that the fetal pituitary is a main source of des-acetyl-alpha-MSH in the amniotic fluid.
In a randomized prospective study, we investigated the effect of antenatal phenobarbital on neonatal intraventricular hemorrhage in 39 women destined to deliver babies of less than 32 weeks of gestation. The treatment group received an intravenous loading dose of 700 mg of phenobarbital, followed by a daily maintenance dose until delivery. The newborns were treated with phenobarbital for the first 96 h. Ultrasound examinations of the infants' heads were performed. Intraventricular hemorrhage was significantly less frequent in the treated group: 2 of 21 (9.5%) versus 9 of 18 (50%; p less than 0.006). Moreover no severe hemorrhage (grade 3-4) occurred in the treated babies: 0 of 21 versus 5 of 18 (27.7%; p less than 0.01).
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As a part of a study on analgesic and antiinflammatory active condensed heterocyclic compounds containing the pyrimidinic ring, a number of 6H-1,3,4-thiadiazolo [3',2':1,2]-5-oxopyrimido [5,4-b]indole and 1-phenyl-6H-1,2,4-triazolo [1',5':1,2]-5-oxopyrimido [5,4-b] indole were synthesized and tested. The results of pharmacological assays are reported and discussed.
Intracerebroventricular (i.c.v.) injection of (Asul,7)eel-calcitonin, a synthetic analogue of eel-calcitonin, at doses of 3 or 6 IU/rat, (but not at 1.5 IU/rat) determined analgesic activity, in male rats, as evaluated by the 'hot-plate' test. Also electrophysiological studies carried out on 13 neurons belonging to the nucleus raphe magnus (NRM) showed that i.c.v. administration of the same doses of (Asul,7)eel-calcitonin increased the spontaneous cellular firing rate. No modification of the discharge frequency was observed when 1.5 IU/rat (Asul,7)eel-calcitonin was used. Authors suggest that the analgesic activity induced by i.c.v. injection of (Asul,7)eel-calcitonin is due, at least in part, to mechanisms affecting NRM neurons.
Several distinct and high-conserved genes comprise the ras gene family of rodents and humans, i.e., rodent Harvey and Kirsten, and human Harvey, Kirsten and neuroblastoma. Transformation, either by a point-mutation resulting in a change in one amino acid of the 21 kDa ras gene product (p21), or by increased expression of ras p21, has been demonstrated to be mediated by members of this gene family. We report here the development of direct binding liquid competition radioimmunoassays for the detection and quantitation of the ras oncogene and proto-oncogene products. Using these radioimmunoassays and ras p21 purified from Escherichia coli containing the full-length T24 mutant human Harvey ras gene protein product as a standard, we have defined the actual amount of ras p21 per micrograms of total cellular protein, or per cell, in various ras transformed and 'normal' mammalian cell lines. One of the radioimmunoassays developed is group-specific, since the antigenic determinant recognized is shared by both the point-mutated and proto-forms of Harvey, Kirsten and neuroblastoma members of the ras gene family, while the second may be termed type-selective, since it recognizes an antigenic determinant localized primarily on the Harvey ras p21. Both radioimmunoassays are interspecies, since they detect a ras p21 antigenic determinant common to cells of human and rodent origin. These studies thus describe the first means for defining absolute values of any oncogene or proto-oncogene protein product. The assays described, when used in combination with specific c-DNA probes to define specific ras proto-oncogenes or point-mutated oncogenes being expressed, will now permit truly quantitative analyses of ras p21 expression in experimental cell culture systems, animal models and human biopsy material.
The efficacy of the insulin infusion pump (CSII) in pregnancy was examined in 12 diabetic patients and compared with intermittent insulin therapy (IIT). In patients poorly controlled on IIT constant and rapid equilibrium was achieved with CSII (mean of glucose levels: CSII versus IIT = 84 versus 137 mg/dl; S.D. = 36 versus 63 mg/dl; mean amplitude of glycemic excursion (MAGE) = 65 versus 112 mg/dl. In patients well controlled on IIT, CSII led to a reduction in the variation of glucose excursions (S.D. = 29 versus 36 mg/dl; MAGE = 48 versus 76 mg/dl). CSII generally produced a reduction of 20-37 per cent of daily insulin dose (in three cases there was an increase of dose with the achievement of glycemic control). Furthermore in CSII treated-patients amniotic glucose, insulin and C-peptide concentrations were found to be in the normal range (22.1 +/- 10.1 mg/dl; 5.2 +/- 2.7 microU/ml; 1.25 +/- 0.71 ng/ml, respectively). All infants were born at or near-term, had no macrosomia or neonatal problems. It is concluded that CSII is a highly efficient way to achieve normal glucose levels in pregnancy, not only in type I, but also in type II or gestational diabetes.
The effects of different doses of Asu(1,7) eel-calcitonin, peripherally injected, on gastric secretion were studied in conscious Brattleboro rats, which are genetically deficient in vasopressin. Moreover, we evaluated the activity of this analogue on gastric ulcer formation by restraint stress. We found that 5 IU/kg Asu(1,7) eel-calcitonin decreased gastric secretion and inhibited the development of stress-induced ulcers in Brattleboro rats. These data suggest that vasopressin does not play a role in the gastrointestinal activity of Asu(1,7) eel-calcitonin.
Ten patients with hypothalamic amenorrhea (HA) were treated to induce ovulation with i.v. pulsatile Gn-RH. Twentysix cycles were administered with doses ranging from 2.5 (A; no. = 10) to 5 (B; no. = 13) to 10-12.5 micrograms/90 min (C; no. = 3). Ovulation rate was 80% in A, 92.3% in B and 100% in C and pregnancy rate 25% in A and 41.6% in B. Furthermore, both the onset of ovarian response and follicular growth were found to be more suitable in groups B and C with respect to group A. Estradiol pattern as well as mid-luteal progesterone plasma levels were superimposable in the different groups. It is concluded that all doses used are effective in inducing ovulation in HA patients. However, small pulsatile doses (2.5 micrograms/90 min) might constitute a critical threshold for adequate ovarian response.
Productive infection of permissive cell cultures by HIV has been detected by different assays of which the measurement of reverse transcriptase (RT) activity has been considered highly specific and sensitive. Here we describe the production and characterization of a mouse hybridoma cell line, MB12, secreting monoclonal antibodies to HIV p24, the major core protein, and the use of this monoclonal antibody to develop a type specific indirect liquid competitive radioimmunoassay (RIA) capable of providing earlier detection of the replicating virus than the RT assay. This assay also provides a quantitative analysis of HIV p24, which can be used to study the viral replication in permissive cell cultures. The ease of methodology and the adaptability of the competitive RIA to various assay conditions make this immunoassay suitable for the study of HIV expression in infected cell cultures.
IIV FSH was administered to eight women with PCOD to induce ovulation. These patients had been previously treated unsuccessfully with CC or IM gonadotropins. The drug was administered by a pump at 120-minute intervals. Dosage was 1 ampule Metrodin (75 IU of FSH less than 0.11 IU of LH)/day. Eight cycles of treatment were effected. With the IIV regimen, ovulation rate was 75% (six cycles). Two multiple pregnancies and one abortion (mola vescicularis) were observed. Preovulatory E2 plasma levels and the number of follicles recruited per cycle varied from 530 to 3800 pg/ml and from 4 to 15, respectively. Maximal follicular diameter was between 16 and 28 mm. LH levels significantly decreased, while FSH levels were unchanged, resulting in a decrease of LH/FSH ratio. It is concluded that the IIV FSH regimen offers an additional modality for the induction of ovulation in PCOD patients. Further clinical trials with alternative regimens are needed, however, to identify the optimal dosage and frequency of administration of the drug.