Role of mast cells in health: daily rhythmic variations in their number, exocytotic activity, histamine and serotonin content in the rat thyroid gland.

A chronobiologic transverse study on rat thyroid has been carried out to investigate whether mast cells and their content in biogenic amines normally undergo daily variations and whether these are related to circadian activity of the gland. The mean number of mast cells per microscopic field presents daily variations ranging from 10.9 +/- 3 to 14.6 +/- 3.8 in males and from 8.4 +/- 1.9 to 14.8 +/- 3 in females: these variations show a circadian trend in both sexes, with a 12 hrs period and two peaks at about 11:10/23:10. The mean percentage of degranulated mast cells per microscopic fields shows daily variations ranging from 51 +/- 11 to 60.4 +/- 14.2 in males and from 49.8 +/- 12.5 to 58.3 +/- 13.6 in females; these variations present a circadian rhythm with a 24 hrs period and a mean peak at 02:00. The histamine content of the gland varies in 24 hrs from 20.93 +/- 1.19 micrograms/g w w to 38.08 +/- 1.7 micrograms/g w w, without any sex-related difference: these variations show a rhythmic trend with a 12 hrs period and two peaks at 09:10/21:10. Serotonin content of thyroid presents circadian variations from 15.98 +/- 0.83 to 23.23 +/- 0.61 micrograms/g w w, with a 12 hrs period and two peaks at 04:20/16:20. Whereas the variations of mast cell exocytosis and of serotonin content seem to be chronobiologically linked to circadian variations of gland activity, evaluated on the basis of free and total tetraiodothyronine serum levels, the variations of mast cell number appear to be related to those of thyroid and blood histamine. The present data support the hypothesis that mast cell activity should not be considered as only linked to inflammation or allergic responses.

Histamine uptake by human normal neutrophils in vitro.

The uptake of different concentrations of (2.5-3H) histamine by normal human neutrophils at 37.5 degrees C in a tris-albumin buffer was determined at 20, 60 and 90 min of incubation. Uptake was correlated with the concentration of amine and incubation time with a saturation-like curve. On the basis of these results, it is suggested that neutrophils play a role in the regulation of histamine plasma levels.

The possible use of radioiodinated metaiodobenzylguanidine (MIBG) in medullary thyroid carcinoma.

The value of radioiodinated metaiodobenzylguanidine (MIBG) in imaging thyroid medullary carcinoma (MTC) was investigated (18 studies) in 12 patients with proven MTC. Calcitonin (CT), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were also determined. The patients were divided into two groups. Group I comprised 7 patients who had relapsed; two of them were also studied before total thyroidectomy. In the 2 cases studied before total thyroidectomy 123/131I-MIBG imaged the primary tumor (partially) and the residual tumor involved lobe. The residual/recurrent tumor present in 4 and some of the remote metastases in 3 out of 5 were detected. Group II includes 5 patients studied postoperatively with no evidence of disease. A residual tumor in one of the 2 patients without evidence of disease on the basis of conventional diagnostic modalities but with elevated tumor markers was visualized; the outcome was correctly negative in 3. One patient underwent treatment with 131I-MIBG. A total dose of 27.1 GBq (733 mCi) was given. Relief of pain and partial regression of the lesions was achieved.

Ocular aspects in biotinidase deficiency. Clinical and genetic original studies.

There are two distinct forms of multiple carboxylase deficiency. A neonatal onset form is due to deficiency of holocarboxylase-synthetase. A later onset form in which neurological abnormalities are seen as well as those of the skin and hair is due to biotinidase deficiency. It is the purpose of this report to describe a patient with biotinidase deficiency who presents bilateral optic atrophy. The dosage of biotinidase enzyme in the patient's serum and in other members of his family confirms the autosomal recessive transmission of this condition.

Circadian rhythm in prostatic acid phosphatase (PAP): a potential tumor marker rhythm in prostatic cancer (PCa).

In order to define circadian states for an earlier diagnosis and for optimal response to treatment, the possibility of a circadian rhythm in serum PAP was investigated in subjects with and without prostatic cancer. Two groups of subjects were investigated: a. 12 patients affected by PCa, further subdivided in two subgroups: 1. without metastasis (6 patients) and 2. with metastatic disease (6 patients); b. 9 age-matched healthy control subjects. Controls and PCa patients were synchronized before starting the study with standardized meal times and nocturnal rest (22(00) to 06(00) ). Venous blood samples were drawn at prearranged hours (00(00), 04(00), 08(00), 12(00), 16(00), 20(00) ) for 24 consecutive hours. Each serum sample was assayed for PAP. Data on each group and subgroup were evaluated by conventional statistical analysis and by 'single' and 'population mean cosinor' to define rhythm parameters. PCa patients, as a single group, did not show a significant circadian PAP rhythm. A statistically significant circadian PAP rhythm was however detected in the subgroup without metastasis, on the contrary no rhythm was detected in the subgroup with metastatic disease. The potential of these rhythms as marker of cancer is noted.

Toward a medical prolepsis by chronobiology.

Medicine today strongly aims at prevention and optimization of diagnosis and therapy Studies tried staging and standardization of clinical trials in diseases and made search of markers for early diagnosis, prognosis and therapy. Moreover, risk factors and other variables such as predictors are now investigated more often in groups or populations of apparently healthy subjects, especially for such diseases as atherosclerosis and neoplasia. This new aspect of increasing interest may be defined as medical prolepsis (from the Greek pi rho ómicron lambda eta psi iota zeta = anticipated idea). It includes early signals of disease (protopathology) as well as other signals the host shows as defence or alarm reaction. Hence, we suggest a chronobiological approach in this field, which allows to quantify health and reveals more subtle differences in many physiological variables. According to these views, we reported studies concerning humoral markers and other parameters considered as risk factors both in atherosclerosis and in some endocrine tumors.

Thyroxine and triiodothyronine levels in thyroid vein blood and in thyroid tissue of patients with autonomous adenomas.

Thyroxine (T4) and triiodothyronine (T3) concentrations were measured in peripheral and thyroid vein blood and in nodular and extranodular thyroid tissue from twenty-four patients with autonomous thyroid nodules (AFTN); fifteen of these patients showed clinical signs of hyperthyroidism and nine were euthyroid. Thirteen patients with solitary non-functioning thyroid adenomas who were clinically euthyroid, served as controls; samples of thyroid vein blood and normal thyroid tissue being obtained from the contralateral lobe. T4 (189.4 +/- 27.2 nmol/l) and T3 (7.05 +/- 2.03 nmol/l) concentrations were significantly higher in the thyroid vein blood of patients with AFTN compared with controls (T4 = 119 +/- 9.1 nmol/l, P less than 0.05; T3 = 2.3 +/- 0.21 nmol/l, P less than 0.01) whereas peripheral levels in the two groups were similar. The T3 concentrations (10.56 +/- 4.12 nmol/g wet tissue) in autonomously-functioning thyroid nodular tissue were significantly higher than those of extranodular (1.9 +/- 0.62 nmol/g wet tissue, P less than 0.01) and normal thyroid tissue (2.63 +/- 0.43 nmol/g wet tissue, P less than 0.05). The T4 levels were not different in the tissues examined. The concentrations of T4 and T3 in thyroid vein blood did not show any significant correlation with the hormone levels in thyroid tissue.

Mammary cancer risk: circulating TSH and prolactin, fibrocystic breast disease in chronoepidemiologic perspective.

Classical epidemiology associates human breast cancer with several risk factors including, among others, so-called preclinical hypothyroidism, fibrocystic disease of the breast (FM), and hyperprolactinemia. Relationships among FM, hyperprolactinemia, and thyroid function are of interest because of the possibility of multiple risk combinations. Prolactin and TSH (the latter as a presumed index of preclinical hypothyroidism) undergo rhythmic changes and hence should be chronobiologically investigated. Serum samples obtained at 4-hour intervals throughout a 24-hour span from 23 healthy women and from 25 women with FM (histologically verified) here summarized suggest that circadian mesor-hyperprolactinemia is a feature associated with FM. In a broader context, however, such impressions and an often considered modest impairment of thyroid function in some patients must be viewed in the light of new chronobiologic rules. These include a reciprocity of the circannual amplitudes of TSH and prolactin in relation to breast cancer risk, revealed by cooperative studies. A yet broader chronoepidemiologic view reveals that the reciprocal relation of the circannual amplitudes of circulating TSH and prolactin is (sex) inverted in patients with cancer of the prostate.

[Circadian changes in serum prolactin in a group of apparently healthy subjects]. / Variazioni circadiane della prolattina serica in un gruppo di soggetti apparentemente sani.

Serum immunoreactive prolactin was evaluated in 16 female and 5 male apparently healthy subjects aged 21-76 yr. After a period of synchronisation, with sleep from 22 to 5 and standardized meals at 8-8.30, 12-12.30, 17.30-18, venous blood samples were taken at 4, 8, 12, 16, 20 and 24. The radioimmunological data were processed using an ordinary chronogram technique and quantified by mean cosinor method. A significant (p less than 0.05) circadian rhythm was noted, with an acrophase at 1.45, amplitude of 2.17 and Mesor 6.89. Chronobiological studies are thus needed to determine the best normal temporal values of prolactin when setting control standards in pathological situations.

Evaluation of the operative parameters for a human prolactin radioimmunoassay in serum.

A sensitive homologous radioimmunoassay (RIA) for human prolactin (hPRL) was evaluated. The experimental parameters of this double antibody solid phase (DASP)-hPRL-RIA are discribed. The RIA measures concentrations of hPRL as low as 1 ng/ml of human serum and allows repetitive measurements and accurate delineation of serum hPRL. The assay is specific for hRPL; only HGH shows a weak cross-reaction. The antigen recovery tests are quantitative. The serum concentrations of hPRL in a group of randomly selected male and female individuals averaged 6.7 +/- 3.3 ng/ml, respectively. In a chronobiological study performed on 21 subjects (5 male and 16 female), a statistically significant rhythm with a 24-h period was detected.