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Biomedical subjects

C Carella

Publications and source records attributed to C Carella.

At least 55 records · Page 3Linked to original sources
PubMed1998

Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha.

In 70 healthy subjects with a large age range, the relationships between plasma tumor necrosis factor-alpha (TNF-alpha) and body composition, insulin action, and substrate oxidation were investigated. In the cross-sectional study (n = 70), advancing age correlated with plasma TNF-alpha concentration (r = 0.64, P < 0.001) and whole body glucose disposal (WBGD; r= -0.38, P < 0.01). The correlation between plasma TNF-alpha and age was independent of sex and body fat (BF; r = 0.31, P < 0.01). Independent of age and sex, a significant relationship between plasma TNF-alpha and leptin concentration (r = 0.29, P < 0.02) was also found. After control for age, sex, BF, and waist-to-hip ratio (WHR), plasma TNF-alpha was still correlated with WBGD (r = -0.33, P < 0.007). Further correction for plasma free fatty acid (FFA) concentration made the latter correlation no more significant. In a multivariate analysis, a model made by age, sex, BF, fat- free mass, WHR, and plasma TNF-alpha concentrations explained 69% of WBGD variability with age (P < 0.009), BF (P < 0.006), fat-free mass (P < 0.005), and plasma TNF-alpha (P < 0.05) significantly and independently associated with WBGD. In the longitudinal study, made with subjects at the highest tertiles of plasma TNF-alpha concentration (n = 50), plasma TNF-alpha concentration predicted a decline in WBGD independent of age, sex, BF, WHR [relative risk (RR) = 2.0; 95% confidence intervals (CI) = 1.2-2.4]. After further adjustment for plasma fasting FFA concentration, the predictive role of fasting plasma TNF-alpha concentration on WBGD (RR = 1.2; CI = 0.8-1.5) was no more significant. In conclusion, our study demonstrates that plasma TNF-alpha concentration is significantly associated with advancing age and that it predicts the impairment in insulin action with advancing age.

Adult↗
PubMed1997

Insulin resistance and advancing age: what role for dehydroepiandrosterone sulfate?

The relationship between insulin resistance and aging is still debated. This study aims to investigate the role that age-related differences in plasma dehydroepiandrosterone sulfate (DHEAS) concentration may have on insulin action. For this reason, 75 subjects (42 men and 33 women) with a wide age range (21 to 106 years) were studied. In all subjects, plasma DHEAS and total testosterone concentrations were measured and a euglycemic clamp was used, but substrate oxidation was not determined in centenarians (n = 15). Plasma DHEAS correlated with age (r = -.77, P < .001) and whole-body glucose disposal (WBGD) (r = .57, P < .001). After controlling for age, sex, body fat, and waist to hip ratio (WHR), the association between plasma DHEAS and WBGD was still observed (r = .31, P < .005). Comparing subjects at the third tertile versus those at the first and second tertiles of plasma age-adjusted DHEAS concentration, the former group showed a weaker association between WBGD and age (r = -.38, P < .05) than the latter group (r = -.43, P < .002). The difference between the two regression lines was also significant (P < .03). After controlling for sex, body fat, and WHR, the association between plasma DHEAS and WBGD was dependent on the age of the subjects, being strong in adults (n = 30, age < 50 years, r = .69, P < .001), weak in old subjects (n = 30, age 51 to 99 years, r = .23, P < .05), and absent in centenarians (r = -.05, P < .88). With the subjects divided by sex throughout the different age groups, the univariate association between plasma DHEAS and WBGD was present in females (r = .43, P < .01) but not in males (r = .17, P < .32). Plasma total testosterone and insulin-like growth factor-1 (IGF-1) concentrations declined with advancing age and were significantly correlated with DHEAS and WBGD. In a multivariate analysis with WBGD as the dependent variable, a model including age, sex, body fat, WHR, DHEAS, total testosterone, and IGF-1 explained 66% of WBGD variability, with DHEAS significantly and independently associated with WBGD (P < .004). In conclusion, the negative relationship between advancing age and insulin action seems related to plasma DHEAS concentration. Differences in plasma total testosterone and IGF-1 concentrations may provide a further contribution to the relationship between DHEAS and WBGD.

Adult↗
PubMed1997

Thyroid hormone plasmatic levels in rats treated with serotonin in acute and chronic way.

Many experiments show that serotonin (5-HT) controls thyroidal function at hypothalamic level, inhibiting the TRH secretion. The majority of experiments are done in an acute way, consisting of a single serotonin dose injected intraperitoneally (i.p.) or intracerebroventricularly (ic) with the effect registered after a short time (usually 1 h) as in normal environmental conditions similar to the TSH stimulation test, that consists of transfer of the experimental animals from 30 degrees C to 4 degrees C for 30 min, thus inducing stimulation of the hypothalamus-hypophysis-thyroid axis. The aim of the present research was to study the correlation between 5-HT and the thyroidal function, measuring plasmatic thyroid hormone levels in rats i.p. treated in chronic (injected daily for 10 days with different doses of 5-HT), and in acute way (after 1 h from a single 2.0 mg/kg bw 5-HT dose) in normal environmental conditions to evidence the serotonin site action activity outside the blood-brain barrier. The results of the chronic experiment show an inhibitory effect of 5-HT, on T3 and T4 plasmatic level, only when it is injected at medium doses (0.2 and 0.4 mg/kg bw for T3, and 0.2 for T4), while the results of the acute experiment do not evidence any modification. These results show that in normal environmental conditions the outside 5-HT site action is active only when the 5-HT is injected chronically at defined doses, probably for a down-regulation phenomenon.

Animals↗
PubMed1997

Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function.

It has been demonstrated that healthy centenarians have more favorable anthropometric characteristics and insulin-mediated glucose uptake than aged subjects. The plasma insulin-like-growth factor I (IGF-I) concentration may account for such differences. Three groups of subjects were studied: 1) adults (< 50 yr; n = 30), 2) aged subjects (75-99 yr; n = 30), 3) centenarians (> 100 yr; n = 19). In all subjects, fasting plasma IGF-I, IGF-binding protein-3 (IGFBP-3), leptin, and lipid concentrations were determined; body composition was assessed by bioimpedance analysis; and insulin-mediated glucose up-take was evaluated by euglycemic hyperinsulinemic glucose clamp. IGF-I declined with advancing age, but no differences between aged subjects and centenarians were found. IGFBP-3 showed a trend similar to IGF-I, but lower values were present in centenarians than in aged subjects. Nevertheless, centenarians had a plasma IGF-I/IGFBP-3 molar ratio greater than that in aged subjects. Centenarians had also a whole body glucose disposal (WBGD) greater than that in aged subjects, but similar to that in adults. Mini Mental State Examination (27 +/- 2.1 vs. 18.3 +/- 3.1; P < 0.02) and Instrumental Activities Daily Living (26 +/- 2.6 vs. 8.4 +/- 4.1; P < 0.001) scores were significantly different in aged subjects and centenarians, respectively. In centenarians, the plasma IGF-I/IGFBP-3 molar ratio correlated with the body mass index (r = -0.55; P < 0.009); the amount of body fat (r = -0.62; P < 0.003); fat-free mass (r = 0.56; P < 0.008); fasting plasma leptin (r = -0.63; P < 0.004), triglycerides (r = -0.58; P < 0.01), free fatty acid (r = -0.64; P < 0.005), and low density lipoprotein cholesterol (r = -0.59; P < 0.009) concentrations; Mini Mental State Examination (r = 0.53; P < 0.0.03); and WBGD (r = 0.64; P < 0.005). All correlations were independent of daily fat and carbohydrate intake and WBGD (P < 0.05 for all). No significant correlations between the plasma IGF-I/IGFBP-3 molar ratio and plasma total (r = 0.31; P = NS) and high density lipoprotein cholesterol (r = 0.34; P = NS) concentrations were present. The correlation between the plasma IGF-I/IGFBP-3 molar ratio and WBGD persisted after adjustment for body fat, fasting plasma insulin concentration, daily carbohydrate and fat intake, and daily physical activity (r = 0.55; P < 0.009), but not after further adjustment for plasma free fatty acid concentration (r = 0.30; P = 0.17). In conclusion, healthy centenarians have plasma IGF-I/IGFBP-3 molar ratio greater than aged subjects. A more elevated plasma IGF-I/IGFBP-3 molar ratio might improve insulin action and plasma lipid concentration in centenarians.

Adult↗
PubMed1995

Melatonin and the pituitary-thyroid axis status in blind adults: a possible resetting after puberty.

OBJECTIVE: Increased levels of free thyroid hormones have been previously described in prepubertal blind subjects and have been thought to be a consequence of a partial target organ refractoriness due to the early and prolonged lack of light perception. The aim of this study was to clarify whether this abnormality is permanent or transient and the interrelationships between melatonin and thyroid hormone secretion. MEASUREMENTS: Total and free thyroid hormones, TSH, thyroxine-binding globulin (TBG), reverse triiodothyronine (rT3) and melatonin were measured in plasma samples obtained at 0800 h (two hours after lights-on) in a group of 11 totally (group 1) and 16 partially (group 2) blind adult patients and in 10 age-matched healthy subjects. RESULTS: Both totally and partially blind patients showed melatonin levels higher than in controls (330 +/- 106 pmol/l, group 1 and 361 +/- 159 pmol/l, group 2, respectively; controls: 53 +/- 12 pmol/l, P < 0.001 vs both groups), but fT4, fT3, T4, T3 TSH, rT3 and TBG concentrations showed no significant differences from controls. CONCLUSIONS: A possible resetting of pituitary-thyroid axis regulation can occur in blindness after puberty; variations of melatonin secretion could play a role in this. The inhibitory effect of melatonin on thyroid gland function found in animals does not seem to occur in humans. Elevated melatonin levels, both in patients with total blindness and in those with light perception only, suggest that more complex mechanisms other than light signalling are involved in the changes of melatonin secretion in blindness.

Adolescent↗
PubMed1995

Longitudinal study of antibodies against thyroid in patients undergoing interferon-alpha therapy for HCV chronic hepatitis.

Seventy-five patients (50 M, 25 F), affected by chronic hepatitis caused by hepatitis C virus (HCV), without clinically overt thyroid disease, underwent r-interferon (IFN)-alpha-2a treatment (3-6 MU, 3 times/week) for 12 months. They were tested for thyroid function and for thyroid autoantibodies before (A), 6 (B) and 12 (C) months after the beginning of treatment and after 6 (D) months off therapy. Antithyroglobulin antibodies (Tg-Ab) and TSH were measured by IRMA, antiperoxidase antibodies (TPO-Ab), free T3 (FT3) and free T4 (FT4) by RIA, thyrotropin receptor antibodies (TR-Ab) by RRA. None of the patients showed TR-Ab positivity throughout the study. The number of the patients with one or both antithyroid antibodies progressively increased during treatment (A 10.7%; B 26.7%; C 45.3%) and decreased when off therapy (D 22.7%) with none of them positive for Tg-Ab alone (TPO-Ab 6.7%; Tg-Ab+TPO-Ab 16%). Tg-Ab increased during rIFN (median: A 29.0; B 35.0; C 73.0 U/ml) but decreased when off therapy (D 29.0 U/ml). Instead, TPO-Ab significantly increased throughout the study (A 1.0; B 3.0; C 6.0; D 7.0 U/ml). However, some patients showed for the first time an appearance of antibodies when off therapy. Five patients showed both antibodies and thyroid dysfunction: 2 at B, 2 at C, and 1 at D. Only 1 developed mild transient hyperthyroidism while the other 4 developed hypothyroidism, persistent however only in 1 case. Our study confirms that rIFN-alpha-2a frequently induces thyroid autoimmunity. TPO-Ab seems more useful than Tg-Ab in monitoring the immunological response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: beneficial effect of beta-blockade.

Thyroid-stimulating hormone (TSH) suppressive therapy with levothyroxine (L-T4) may cause adverse cardiac effects such as rhythm disturbances and ventricular hypertrophy. The latter is a predisposing condition to diastolic dysfunction. Thus, this study was designed to assess the effect of long-term TSH suppressive therapy on cardiac diastolic function. Because beta-blockade is known to reduce ventricular hypertrophy in patients on L-T4 therapy, we also tried to determine whether the addition of a beta-blocker to L-T4 improved diastolic function. Twenty-five patients (21 female and 4 male; mean age 41 +/- 10 yr) on TSH suppressive therapy for 3-9 yr (9 for differentiated carcinoma and 16 for nontoxic goiter) and 20 control subjects were studied. A subgroup of 10 patients, selected for the presence of symptoms and signs of adrenergic overactivity, was treated for 4 months with the beta-blocker bisoprolol (4.25 +/- 1.2 mg/day), and their maintaining L-T4 therapy was unchanged. In the patient group, left ventricular mass was significantly increased (P < 0.001), isovolumic relaxation time was prolonged (P < 0.001), and early diastolic filling velocity was markedly reduced (P < 0.001), whereas late diastolic filling was increased (P < 0.005). Consequently, the early-to-late diastolic flow velocity ratio was markedly decreased (P < 0.001). These alterations were more pronounced in the subgroup of patients with evidence of adrenergic overactivity. In these patients, beta-blockade induced a significant regression of cardiac hypertrophy and improved diastolic dysfunction. In particular, isovolumic relaxation time decreased (P < 0.01) and the early-to-late flow velocity ratio increased significantly (P < 0.01). Both indices reached values after beta-blockade that were no longer different from those of asymptomatic patients. It is concluded that long-term L-T4 therapy increases myocardial mass and causes relevant diastolic dysfunction, particularly in those patients with evidence of mild hyperthyroidism and adrenergic overactivity. Both myocardial hypertrophy and diastolic dysfunction are significantly improved by adrenergic beta-blockade.

Adult↗
PubMed1994

Control of adrenergic overactivity by beta-blockade improves the quality of life in patients receiving long term suppressive therapy with levothyroxine.

Several symptoms and signs of hyperthyroidism are frequently shared by patients receiving L-T4 suppressive therapy. The aim of this study was to evaluate whether a beta-adrenergic blocking drug could reduce the severity of these symptoms and signs in these patients, as previously reported in patients with hyperthyroidism. Eleven patients (mean age, 42 +/- 11 yr; 10 females and one male) affected with differentiated thyroid carcinoma or nontoxic goiter were selected from a more numerous group of patients receiving suppressive therapy based on the presence of palpitations, increased heart rate, left ventricular systolic function, and other symptoms mimicking exaggerated beta-adrenergic activity. In these patients the cardioselective beta-blocking drug bisoprolol was added to the L-T4 suppressive therapy at a dose of 2.5-5 mg/day. Blood samples were collected for the determination of thyroid hormones and TSH concentration during L-T4 therapy and after 3 and 6 months of associated L-T4 plus bisoprolol therapy. Cardiac function was assessed by clinical evaluation, standard and Holter electrocardiogram, as well as one- and two-dimensional echocardiography. Furthermore, we applied the symptom-rating scale previously used by Klein et al. in hyperthyroid patients to assess the quality of life in our group of patients. Our findings show that the addition of bisoprolol to L-T4 suppressive therapy produces a normalization of heart rate, which was significantly increased during TSH suppressive therapy, and the disappearance of atrial arrhythmias with considerable reduction of palpitations. Furthermore, bisoprolol produced an effective improvement in measures of the hyperthyroid symptom scale, with significant reduction of the mean score. The echocardiographic data showed an increased left ventricular mass index with significantly enhanced systolic function at the basal evaluation. After 6 months of combined L-T4 plus bisoprolol therapy, left ventricular mass index normalized, and the indices of left ventricular systolic function were reduced, with a tendency to normalize. Further studies conducted on a larger series of patients are required to verify the long term implications of cardiac parameter variations on cardiovascular morbidity and mortality. Our results, however, show that the addition of bisoprolol to L-T4 suppressive therapy improves the quality of life in those patients with clinical features of enhanced adrenergic activity.

Adult↗
PubMed1993

Pituitary glycoprotein hormones in chronic renal failure: evidence for an uncontrolled alpha-subunit release.

Chronic renal failure affects the secretion of pituitary glycoprotein hormones by mechanism(s) that are still unknown. In this study, we evaluated serum concentrations of TSH, free thyroid hormones (FT4, FT3), LH, FSH, testosterone (T), and alpha-subunit (alpha-SU) in 25 uremic patients (19 males and 6 females), both in basal conditions and after stimulatory and inhibitory tests. Basal TSH levels were in the normal range, while FT4 and FT3 were significantly lower than in controls. Basal LH and FSH levels were clearly elevated. The LH levels measured by RIA were significantly higher than those measured by a "two-site" IRMA (48.9 +/- 16.5 vs 18.0 +/- 8.6 U/L) due to alpha-SU cross-reactivity in RIA. FSH bioactivity was normal in all patients. Serum T was normal in all but 3 males, without any correlation with LH and FSH levels. Serum alpha-SU concentrations were significantly elevated (5.5 +/- 3.0 vs 0.4 +/- 0.2 microgram/L). Of 17 patients, the TSH response to TRH was normal in 9 and impaired in 8, whereas alpha-SU response was normal in 5 and impaired in 12. In 8 male patients, TRH plus GnRH caused a normal LH and FSH response in 4 patients, while the increase of alpha-SU was normal in only one patient and significantly lower than expected in subjects with comparable basal alpha-SU levels in the remaining 7. In 2 patients, the combined suppression test with T undecanoate and T3 completely blocked TSH secretion and reduced both LH and FSH release by 30%, while serum alpha-SU levels did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study.

Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce thyroid alterations. In this longitudinal study the thyroid function was investigated during lithium treatment over a period of 12 months in 12 euthymic bipolar patients with a normal thyroid function and absence of thyroid antibodies. Nine of the 12 patients were further studied on the 15th month, 5 of these 9 on the 18th month and 4 of the last-mentioned 5 on the 24th month. The mean basal and TRH-stimulated TSH values during lithium therapy were significantly higher as compared to those at the beginning of the treatment. More particularly, during lithium therapy, a significant increase of basal TSH over the normal range was found in 10 out of the 12 patients. A rise of TRH-stimulated TSH was found in 11 out of the 12 patients. The impairment of the hypothalamic-pituitary-thyroid (HPT) axis was transitory in the majority of cases. Two patients developed a nodular goiter during the treatment. Plasma T3, T4, FT3 and FT4 levels did not change during the treatment. Thyroid antibodies remained undetectable. The conclusions of the study are twofold: 1) Subclinical hypothyroidism during lithium therapy is much more frequent than previous cross-sectional studies suggest; 2) Thyroxine replacement in lithium-treated patients is advisable in order to prevent subclinical hypothyroidism and the risk of a subsequent goiter.

Adult↗
PubMed1993

Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine.

To investigate the effects of long term thyroid hormone suppressive therapy on the heart, 20 patients were evaluated by noninvasive techniques. Of them, 10 were athyreotic after surgery for differentiated thyroid cancer, and 10 had diffuse or nodular goiter. The mean age of the group was 39 +/- 11 yr. Twenty age- and sex-matched subjects served as controls. The mean dose of levothyroxine was 163 +/- 34 micrograms daily. Plasma TSH was undetectable in all patients. Mean serum T4, free T4, and sex hormone-binding globulin were significantly higher (P < 0.001), whereas mean serum T3, free T3, and osteocalcin did not differ from control levels. Cardiac evaluation consisted of a standard 12-lead electrocardiogram, an ambulatory electrocardiographic monitoring (Holter), and an echocardiographic study. Two patients showed abnormal electrocardiograms for left ventricular hypertrophy. Holter demonstrated an increase in average heart rate (84 +/- 7 vs. 70 +/- 6 beats/min; P < 0.01). Prevalence of atrial premature beats was higher in the patient group than in the control group (100% vs. 60%; P < 0.006). The echocardiogram showed an increased left ventricular mass index in the patient group (97 +/- 24 vs. 80 +/- 18 g/m2; P < 0.02). Furthermore, left ventricular systolic function was enhanced, with higher values of fractional shortening (38 +/- 7% vs. 34 +/- 4%; P < 0.05) and rate-adjusted velocity of shortening (1.2 +/- 0.13 vs. 1.05 +/- 0.14 circumferences/sec; P < 0.01). These findings indicate that long term levothyroxine therapy at suppressive doses markedly affects cardiac function.

Adult↗
PubMed1993

Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses.

The effects of recombinant GH doses (10 micrograms/kg.day, 3 times a week for 6 months) lower than those previously used in the treatment of GH-deficient adults (GHDA) on body composition, bone mineral content, and heart structure and function were investigated in seven (six males and one female, aged 25-27 yr) GHDA. They were studied before treatment, after treatment, and 6 months after stopping therapy, and findings were compared with those for 20 sex-, age-, and body mass index-matched healthy controls. Before treatment, GHDA showed a significant reduction in insulin-like growth factor-I levels, an increase in bioimpedance and fat mass percentage, a reduction of bone density at both distal and proximal sites, a decrease in bone Gla-protein and procollagen III levels, and significant cardiac impairment supported by a reduction of left ventricular mass index and left ventricular systolic function with decreased fractional shortening and rate-adjusted mean velocity of circumferential fiber shortening. GH treatment normalized insulin-like growth factor-I levels, body composition and echocardiographic findings, but not bone density. Six months after stopping therapy, all parameters investigated returned to the pretreatment conditions. Our results suggest that prolonged GH deficiency induces alterations in body composition and bone metabolism and density, and impairment of cardiac structure and function in adult life. GH replacement therapy for 6 months, despite the low doses used by us, is able to improve all previously impaired biochemical and clinical features, except for bone density. This improvement disappears 6 months after the withdrawal of therapy.

Adult↗
PubMed1992

Hyperprolactinemia and lens opacities.

We report the presence of lens opacities in patients with prolactin-secreting microadenomas of the pituitary gland. The occurrence of lens opacities was related to prolactin serum levels and appeared only in women. The mechanism by which prolactin induces cataract is not known, although this hormone could affect the lens's permeability to ions, water, sugars, and amino acids. Moreover, the lens opacities found in women but not in men seem to indicate synergism with estrogens.

Adult↗
PubMed1987

Phenotype heterogeneity among hemizygotes in a family biochemically screened for adrenoleukodystrophy.

We report on two clinically, neurologically normal relatives of a boy affected by adrenoleukodystrophy (ALD); they were found repeatedly to have the biochemical defect of an ALD hemizygote. The assay consisted in the determination of very-long-chain fatty acids in lyophilized and reconstituted plasma. While no evidence of neurologic disease (leukodystrophy or myeloneuropathy) was present in these hemizygotes, adrenocortical insufficiency provoking compensatory high ACTH release was found in both. These findings should be taken into consideration when counseling families in which cases with clinically expressed ALD are represented in several generations.

Adrenoleukodystrophy↗