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Biomedical subjects

C Nava

Publications and source records attributed to C Nava.

At least 19 recordsLinked to original sources

Effects of propranolol on GH responsiveness to repeated GH-releasing hormone stimulations in normal subjects.

The influence of beta-adrenergic blockade by oral propranolol on the variability of GH responses to GHRH and on GH responsiveness to repeated GHRH administrations was investigated. Eight normal volunteers underwent three tests on three separate occasions. Each test consisted of two administrations of 80 micrograms GHRH at 2-h intervals without other medication (test 1) or combined with oral administration of 80 mg propranolol 90 min before the first (test 2) or the second GHRH injection (test 3). In test 1 GH levels increased significantly after the first, but not the second GHRH bolus (net incremental area under the curve [nAUC], mean +/- SD: 1453 +/- 974 and 178 +/- 309 micrograms.l-1.(120 min)-1, respectively). In test 2 basal GH secretion was not influenced by propranolol administration, whereas the GH response to the first GHRH injection was significantly greater than in test 1 (2327 +/- 1814 micrograms.l-1.(120 min)-1; p less than 0.05). However, individual subjects showed the same variability of GH response as in test 1. The GH response to the second GHRH bolus remained negligible. In test 3 administration of propranolol 90 min before the second GHRH bolus led to a clear GH increase (690 +/- 1002 micrograms.l-1.(120 min)-1), not significantly different from the GH response to the first bolus (1796 +/- 1375 micrograms.l-1.(120 min)-1). However, only 4 subjects showed a marked restoration of the GH responsiveness to the second GHRH administration. In conclusion, oral administration of propranolol is able to increase GH responsiveness to GHRH without changing the great individual variability. The response to a repeated GHRH stimulation is only partially restored by propranolol.

Administration, Oral

Presynaptic modulation of the release of GABA by GABAA receptors in pars compacta and by GABAB receptors in pars reticulata of the rat substantia nigra.

The effect of GABA agonists and antagonists on K+-stimulated [3H]GABA release was studied to assess how presynaptic GABA receptors modulate GABA release. The release was affected in a quite different manner in the pars compacta and in the pars reticulata. Muscimol markedly inhibited the release from the pars compacta but had no effect on the release from the pars reticulata. Baclofen inhibited the release from the pars reticulata without affecting the release from the pars compacta. Bicuculline itself facilitated the release from the pars compacta but inhibited the release from the pars reticulata. Picrotoxin facilitated the release from the pars compacta and had no effect in the pars reticulata. The results suggest that the release of GABA from GABAergic terminals in the substantia nigra of the rat brain is modulated by GABAA autoreceptors in the pars compacta and by GABAB receptors in the pars reticulata.

Animals

Lymphocyte activation by B. subtilis spores.

The in vitro effect of Bacillus Subtilis spores (BSs) on lymphocyte activation was investigated by analyzing the kinetics of expression of the activation antigens MLR3, MLR4 and HLA-DR in cultures of peripheral mononuclear cells. It was found that BSs over a wide range of concentrations are capable of inducing an increased expression of these three markers and that at high BSs concentration the effect is both quantitatively and qualitatively similar to that induced by the mitogens PHA and ConA. These results suggest that T cells may be involved in the response to Bss.

Bacillus subtilis

Synthetic growth hormone-releasing hormone (GHRH 1-44) in the differential diagnosis between hypothalamic and pituitary GH deficiency.

GH response to an iv bolus of growth-hormone-releasing hormone (GHRH 1-44, 2 micrograms/kg iv) was evaluated in 17 prepubertal children with total GH deficiency (GHD), 6 with partial GHD and in 7 prepubertal normal but short children tested as control. GH response to conventional pharmacological (insulin and arginine or L-Dopa) and physiological stimuli (sleep test) and to GHRH test was also compared. GHRH-induced GH peak occurred at variable times and marked heterogeneity in magnitude of the individual responses to this peptide was observed in GHD patients and in controls. GH increases after GHRH with a peak greater than 10 ng/ml suggested an hypothalamic origin of the GHD in 12 patients (8 with total GHD and 4 with partial GHD). A significant difference (p less than 0.025) of GH peak mean following GHRH administration between total GHD children and normal short children was found. GH response to GHRH injection was usually higher than to conventional stimuli. Nevertheless GH peak following GHRH administration was lower than GH peak following conventional stimuli in 6 children (2 partial GHD children and 4 normal ones). A normal short child failed to respond to GHRH test performed twice. GHRH test is an important diagnostic tool in order to point out hypothalamic GHD.

Adolescent

Serum gonadotrophin pulsatile secretion in men with Prl-secreting and non-secreting pituitary tumours.

In order to investigate the possible influence of prolactin (Prl) at the hypothalamic level, serum LH and FSH pulsatility was studied in 16 male patients with prolactinomas, normally LH responders to GnRH (group A): 8 of them were untreated (group A1) and 8 had undergone previous unsuccessful pituitary treatments (group A2). In 7 patients the study was repeated when serum Prl was normalized by bromocriptine treatment (group B). For comparison the secretory pattern of LH and FSH was studied in 6 male patients with non-secreting pituitary tumours (group C). All parameters of LH pulsatile secretion (i.e. arithmetic mean of the single concentration, coefficient of variation from the mean value, frequency of peaks, amplitude of pulses expressed as either absolute or per cent value) were significantly lower in patients of groups A1, A2 and C than in normal subjects and no difference was found between the three groups. Furthermore the 7 patients with prolactinomas studied both before and after bromocriptine-induced Prl normalization showed no difference in all the parameters of LH pulsatility in both conditions. No significant abnormalities of FSH secretory pattern were found in the patients of groups A1, A2, B and C in comparison to normal subjects. In all groups of patients mean serum testosterone basal levels were significantly lower than in normals, while the mean oestradiol-17 beta basal concentration was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma

Skin pathology in industrial workers exposed to synthetic corticosteroids.

Systemic and cutaneous side effects observed in some workers of a company producing synthetic corticosteroids are described. The production process and the results of clinical and laboratory investigations are shown. A high incidence of skin and internal disorders (erythema, telangiectasia, acne, purpuric lesions and inhibition of the pituitary-adrenal axis) were found.

Acne Vulgaris

RBE of spleen CFU-S to low dose rate Cf-252 or photon radiation in vivo.

The biological effects of low dose rate (LDR) Cf-252 radiation were compared to LDR Cs-137 photon radiation and acute 60Co radiation. The RBEn for endogenous CFU-S in vivo was 2.1 for neutron radiation at a dose rate of 9.9 cGy/hr of Cf-252 radiation. The value was consistent with previous in vitro experiments where a value of 2.1 was found. For the low doses and low dose rates studied, we tested an acute assay dose following the LDR irradiation to determine dose-effect and RBEn. Organ size shrinkage and regeneration patterns after LDR Cf-252 and Cs-137 were also studied and showed greater growth delay for Cf-252 irradiated lympho-hemopoietic tissues.

Animals

Excess of beta-subunit of thyrotropin (TSH) in patients with idiopathic central hypothyroidism due to the secretion of TSH with reduced biological activity.

alpha-Subunit and beta-subunit of TSH were measured in the sera of five patients with idiopathic central hypothyroidism due to the secretion of biologically inactive TSH, in seven normal controls matched for bone age and sex, and in five subjects with mild primary thyroid failure before and after TRH (200 micrograms, iv) stimulation. Basal serum alpha-subunit concentration in patients did not differ from that in normal controls (mean +/- SD, 0.40 +/- 0.20 vs. 0.38 +/- 0.28 ng/ml; P, NS), whereas TSH and TSH-beta were significantly higher in patients (TSH, 1.51 +/- 0.74 vs. 0.59 +/- 0.53 ng/ml, P less than 0.025; TSH-beta, 0.56 +/- 0.18 vs. 0.10 +/- 0.02 ng/ml, P less than 0.001). The concentration of TSH-beta was also significantly higher in patients with central hypothyroidism than in subjects with mild primary thyroid failure (0.56 +/- 0.18 vs. 0.24 +/- 0.08 ng/ml; P less than 0.01), although serum TSH levels did not differ in the two groups (1.51 +/- 0.74 vs. 2.16 +/- 0.52 ng/ml; P, NS). alpha-Subunit was significantly higher in primary hypothyroid subjects (1.50 +/- 0.87, P less than 0.05 compared with patients with central hypothyroidism). After TRH, alpha-subunit, TSH, and TSH-beta net increases (peak) were significantly higher in patients with central hypothyroidism than in normal controls (alpha-subunit: 0.95 +/- 0.5 vs. 0.47 +/- 0.19 ng/ml, P less than 0.05; TSH: 7.1 +/- 3.1 vs. 2.9 +/- 1.8 ng/ml, P less than 0.005; TSH-beta: 0.89 +/- 0.35 vs. 0.22 +/- 0.18 ng/ml, P less than 0.005), whereas they did not significantly differ from those recorded in hypothyroid controls. The beta/alpha ratio, which was 1.67 +/- 0.86 in patients and 0.35 +/- 0.18 in normal controls (P less than 0.005), slightly decreased after TRH to 1.24 +/- 0.78 in patients, but remained unchanged in normal controls (0.39 +/- 0.1). After TRH the alpha-subunit peak occurred at 20 min both in patients and in controls, whereas TSH and TSH-beta peaked at 60 min in patients and at 20 min in controls. One patient was given oral TRH (40 mg/day for 4 weeks). The beta/alpha ratio fell from 1.85 to 0.13. Interestingly, serum thyroid hormones, which did not increase after iv TRH and after the first doses of oral TRH, showed a definite increase. Sera from two patients were filtered on Sephadex G-100: in one of them TSH-beta eluted in the same position as labeled reference standard, whereas in the other one radioimmunoassayable TSH-beta eluted near the void volume. The above data indicate that in patients with idiopathic central hypothyroidism due to biologically inactive TSH there is an excess of circulating TSH-beta and suggest that TRH is implicated in the secretion of TSH of full biological potency.

Adult

Clinical use of pre- and postsurgical evaluation of abnormal GH responses in acromegaly.

The criteria by which acromegalic patients are considered "cured" after surgical therapy are still controversial. Since the abnormal growth hormone (GH) increase after the administration of some agents has been demonstrated to be characteristic of the tumoral somatotrophs, its disappearance after surgery may be taken as an index of the complete removal of the tumor. Serum GH increases after thyrotropin-releasing hormone (TRH, 200 micrograms intravenously), gonadotropin-releasing hormone (Gn-RH, 100 micrograms intravenously), and sulpiride (100 mg intramuscularly) injected during dopamine infusion (DA-Slp test), were evaluated in 68 acromegalic patients before and after transnasosphenoidal adenomectomy, and every 12 to 18 months during a follow-up period of 6 months to 11 years (average 42 months). Forty-two patients had abnormal responses to at least one test before surgery: 32 out of 68 (47%) to TRH, six out of 40 (15%) to Gn-RH, and 20 out of 28 (71%) to the DA-Slp test. Of 18 patients who underwent all three tests, 78% had abnormal responses to at least one of them. Twenty-three patients became unresponsive after surgery, and none of them had a recurrence or became abnormally responsive again during the follow-up period. Three out of six patients with postoperative serum GH levels between 5.1 and 10 ng/ml and three out of six patients with postoperative serum GH levels between 2.1 and 5 ng/ml remained abnormally responsive: one of them relapsed 1 year after the operation. The abnormal responses were lost in all 11 patients whose postoperative serum GH levels were below 2 ng/ml, and abnormal responses were maintained in all the patients in whom surgery was considered unsuccessful because postoperative serum GH levels were higher than 10 ng/ml. The TRH, Gn-RH, and DA-Slp tests should thus be considered useful tools in verifying the total removal of an adenoma. The reappearance of active acromegaly in the patient with low postoperative GH levels, who was still responsive to TRH, should be regarded as a reactivation and not a true recurrence of the disease.

Acromegaly

Effect of bromocriptine and metergoline in the treatment of hyperprolactinaemic states.

The effects of bromocriptine or metergoline treatment were evaluated in 80 hyperprolactinaemic patients (62 women and 18 men). The patients were subdivided into 4 groups: group A) 16 women with idiopathic hyperprolactinaemia; group B) 19 women with untreated Prl-secreting microadenomas; group C) 27 women with unsuccessfully operated prolactinomas; group D) 18 men with unsuccessfully treated macroprolactinomas. Sixty-eight patients were given bromocriptine (2.5-20 mg/day) for 3-58 months and 33 patients were given metergoline (4-16 mg/day) for 3-19 months. Bromocriptine and metergoline were equally effective in the treatment of functional hyperprolactinaemia and of untreated microadenomas, while bromocriptine showed a more potent Prl-lowering effect than metergoline in patients with higher Prl levels and large prolactinomas; both drugs restored the gonadal function to a similar extent, though metergoline was effective in some cases, even in the absence of full Prl suppression. Bromocriptine seems to exert an antitumoral effect, as documented by CT scan in some patients with macroadenomas, but the precise role of both drugs with respect to dose, length of treatment and effectiveness after withdrawal needs to be evaluated further.

Adenoma

PRL action on E2 ovarian secretion.

5 Amenorrhea hyperprolactinemic women in previous intermittent treatment with bromocryptine, received bromocryptine for three periods of 5, 4, 3 days; each treatment phase was followed by a ten days suspension. During treatment and during suspension FSH, LH, PRL and E2 were tested. There was no significative variation of FSH and LH; PRL lowered during treatment and reached basal values during suspension. Ovarian response (E2) varies with PRL levels. There was a statistically significative negative correlation between PRL and 17-beta-E2.

Adult

[Direct skin tests in the prevention of allergic reactions in surgical patients (500 cases)].

The methodology used to diagnose drug allergy in 500 surgical patients is described. After an introduction in which the choice of this method is justified, the used methods are shown in detail with the tested active pharmacological principles (it is a group of drugs for pre, intra and post-surgery use). The tested patients have been clinically watched during all their stay in hospital. The results achieved are shown, as well as the good mutual relation between anamnesis and clinical progress with the answers obtained from the tests. The detailed analysis of skin-reactions showed that positive answers against penicillin (in more than 37% of the tested cases) clearly prevailed over other drugs (petidinum about 12%; propanididum about 10%) etc. Skin-test positivity against prometazinum (6%) is stressed as being quite considerable, considering its prevalent anthistaminic pharmacological effect. The work ends showing how this method, if correctly used, can give good results which can be compared with the results achieved by other more sophisticated methodologies. The kind of test is recommended to be adopted by other hospitals to reduce the incidence of immunological pathogenesis diseases which is more and more frequent.

Drug Hypersensitivity