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Biomedical subjects

G Valenti

Publications and source records attributed to G Valenti.

At least 19 recordsLinked to original sources

Aquaporin-2 excretion and renal function during the 1st week of life in preterm newborn infants.

In many preterm infants, a characteristic pattern of fluid and electrolyte homeostasis occurs during the 1st week of life, consisting of three phases: prediuretic, diuretic, and postdiuretic. In this study, we evaluated the possible role of aquaporin-2 (AQP2) in renal concentrating ability and correlated it with other markers of the renal function in healthy preterm infants. Daily urine and spot blood samples were collected from 9 healthy preterm (32 +/- 1 weeks) infants at postnatal ages 1, 3, and 7 days. Urine and serum osmolality, creatinine, electrolytes, and AQP2 excretion were measured. All infants showed a significant (about 7%) weight loss on day 3 associated with a more than threefold increase in urine output without a significant change in fluid intake (diuretic phase). The creatinine clearance increased on day 3, indicating an increase in glomerular filtration rate. Interestingly, on day 3, the level of total excreted AQP2 (pmol/h) was significantly higher when compared to day 1 and day 7, and the same tendency was observed for urine osmolality. To conclude, the observed increase in urine osmolality and creatinine clearance during the diuretic phase, paralleled by an increase in total AQP2 excretion, suggests that AQP2 can contribute to the urinary concentrating ability early in postnatal life.

Aquaporin 2↗

Correlates of bone quality in older persons.

PURPOSE OF THE STUDY: In a population-based sample of older persons, we studied the relationship between tibial bone density and geometry and factors potentially affecting osteoporosis. METHODS: Of the 1260 participants aged 65 years or older eligible for the InCHIANTI study, 1155 received an interview and 915 (79.2%) had complete data on tibial QCT scans and other variables used in the analysis presented here. The final study population included 807 persons (372 men and 435 women, age range 65-96 years) after exclusion of participants affected by bone diseases or treated with drugs that interfere with bone metabolism. RESULTS: In both sexes, calf cross-sectional muscle area (CSMA) was significantly and independently associated with total bone cross-sectional area (tCSA) and cortical bone cross-sectional area (cCSA) but not with trabecular or cortical volumetric bone mineral density (vBMD). Bioavailable testosterone (Bio-T) was independently associated with both trabecular and cortical vBMD in both sexes. In women, independently of confounders, 25(OH)-vitamin D was positively associated with tCSA and cortical vBMD, while PTH was negatively associated with cortical vBMD. IL-1 beta was negatively correlated with cortical vBMD in women, while TNF-alpha was associated with enhanced bone geometrical adaptation in men. CONCLUSIONS: Physiological parameters that are generically considered risk factors for osteoporosis were associated with specific bone parameters assessed by tibial QCT. Factors known to be associated with increased bone reabsorption, such as 25(OH)-vitamin D, PTH and Bio-T, affected mainly volumetric BMD, while factors associated with bone mechanical stimulation, such as CSMA, affected primarily bone geometry. Our results also suggested that pro-inflammatory cytokines might be considered as markers of bone resorption.

Aged↗

Small bowel evisceration after laparoscopic cholecystectomy: report of an unusual case.

With the rapid development of laparoscopic surgery particularly in cholecystectomy, despite its own advantages, an ever increasing number of reports describe the appearance of new pathologies, due to laparoscopic approach. Evisceration is a rare complication previously described in gynecological obstetric procedures and only once in laparoscopic cholecystectomy. The case of a small bowel evisceration after laparoscopic cholecystectomy in a patient with a multifactorial etiology is presented: weakness area in the umbilical region, intractable cough in the first postoperative day and disruptive tear of the fascia to remove 2 large-size stones. The conclusion is drawn that, according to the literature, holes greater than 5 mm in diameter should be closed at fascial level and we believe that the removal of the gallbladder from epigastric holes is important, in order to avoid an enlargement and rupture of the umbilical port.

Aged↗

Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting.

OBJECTIVES: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) causes an acute stress response characterized by changes in the levels of several hormones, which might play a role in the high complication rate experienced by older patients after CABG. Thus, the aim of the study was to investigate changes in the circulating levels of anabolic and catabolic hormones in old people undergoing CABG with CPB. DESIGN: Intervention case study. METHODS: 19 patients (12 males, 7 females) aged 70.1 +/- 6.1 yr (age range 62-80) with coronary artery disease and an ejection fraction <40% who underwent cardiac surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E2), total testosterone (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and 1, 2, 3, 4, and 30 days after CABG. RESULTS: After surgery, serum IGF-I levels decreased (p<0.001), while levels of Cort, DHEAS and E2 significantly increased in both men and women. Alterations in Te levels differed between the two sexes with a significant decline in men and a significant increment in women. CONCLUSION: CABG with CPB resulted in a dramatic drop in Te levels in old men and a significant decline in IGF-I in both sexes. Serum Cort levels also significantly increased in both sexes. These hormonal changes may, at least partially, explain why the elderly need prolonged rehabilitation after CABG.

Aged↗

Altered expression of aquaporin 4 and H(+)/K(+)-ATPase in the stomachs of peptide YY (PYY) transgenic mice.

BACKGROUND INFORMATION: The hormone PYY (peptide YY), synthesized by endocrine cells in the pancreas, ileum, colon and stomach has widespread inhibitory effects on gastrointestinal and pancreatic fluid secretion. Transgenic mice expressing a viral oncoprotein under the control of the PYY gene 5'-flanking region develop well-differentiated colonic endocrine tumours producing mainly PYY and enteroglucagon. In the present study, we investigated the expression of AQP4 (aquaporin 4) water channel and H(+)/K(+)-ATPase in stomachs from both control and transgenic mice. RESULTS: Semi-quantitative RT (reverse transcriptase)-PCR showed an increase in the AQP4 transcript compared with control mice. Quantitative Western-blot analysis of stomachs from control and transgenic mice confirmed a significant increase in the 30 kDa AQP4 protein in transgenic mice. In control mice, AQP4 is specifically expressed in the basolateral membrane of gastric parietal cells, located in the basal region of the fundic glands. This particular location suggests that parietal cells in the base region of gastric pits might have a major role in water transport when compared with the more superficial parietal cells. Interestingly, immunofluorescence studies on transgenic mice revealed that the quantitative increase of AQP4 expression was actually due to an increase in the number of AQP4-expressing epithelial cells rather than to a higher expression of AQP4 in parietal cells. In fact, immunofluorescence experiments using the specific antibody raised against the AE2 isoform of Cl(-)/HCO3- exchanger specifically expressed in parietal cells confirmed that the number of parietal cells was comparable in both PYY and control stomachs. Moreover, in transgenic mice, a parallel significant decrease in the expression of H(+)/K(+)-ATPase was observed, as revealed by RT-PCR, quantitative immunoblotting and immunofluorescence. CONCLUSIONS: In the present study, we demonstrate that the sustained inhibition of gastric secretion due to tumours producing PYY/enteroglucagon in transgenic mice is associated with an increase in AQP4 expression and a down-regulation of H(+)/K(+)-ATPase in parietal cells that acquire the characteristics of basal parietal cells. The absence of H2 receptors-mediated signalling due to the inhibition of histamine release from ECL (enterochromaffin-like) cells by PYY may be in part responsible for the observed increase in the number of parietal cells expressing AQP4.

Animals↗

The hormonal pathway to frailty in older men.

Frailty, which is a state of high vulnerability that imparts a high risk of developing adverse health outcomes, affects many elderly subjects, especially men and women aged 80 yr and older (1). Although many different definitions of frailty have been proposed (2), a large portion of the recent literature has focused on the definition developed by L. Fried et al. (1) using the data from the Cardiovascular Health Study. Although this definition has not been officially recognized as the "gold standard" for the diagnosis of frailty, nonetheless most of the studies on frailty in the last 5 yr have used this definition. Several mechanisms have been hypothesized to have an important role in the development of frailty, including inflammation, coagulation and oxidative stress (3). Many authors implicate age-related hormonal changes to be directly or indirectly involved in the development of the frailty syndrome (4). Alterations in hypothalamic- pituitary-testicular, hypothalamic-pituitary-adrenal (HPA) and GH-IGF-I axes that accompany aging have been associated with single components of frailty, such as reduced muscle strength, bone strength or poor mobility (5, 6). However, most of these studies have focused on single hormonal changes rather than evaluating the parallel effect of aging on multiple hormonal axes. In addition, no interventional studies have specifically targeted frail older subjects (7). Since frailty by definition is a multi-system disorder, it is unlikely that changes in one axis (leading to a change in a single hormone) will explain the complexity of the dysregulation leading to frailty. Therefore, global measures of endocrine dysregulation that can discriminate between specific endocrine diseases and endocrine senescence should be developed. Observational and interventional studies will be needed to better define the role of "hormonal dysregulation", alone and in combination with other pathways, in the development of frailty in older men.

Aged, 80 and over↗

The pathway of partial androgen deficiency of aging male.

The well documented age-related decline in serum testosterone (T) in men as the basis of the partial androgen deficiency of aging male (PADAM) syndrome is a typical multifactorial phenomenon. Aging per se can reduce T secretion through several different mechanisms, such as a primary impairment of the testes, the pituitary gland and the neurohypothalamic component, and age-associated changes in peripheral steroid metabolism. Together, these factors define the so called "idiopathic pathway". Generally, the decline in T is exacerbated by many other age-associated clinical conditions that can interfere with T metabolism: these represent the "secondary pathway". Most people experience a PADAM syndrome in which idiopathic and secondary components are simultaneously present. The different multifactorial pathway mechanisms are reviewed in this paper.

Adult↗

Clinical implications of the reduced activity of the GH-IGF-I axis in older men.

During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.

Aged↗

Thyroid disease in the elderly: sex-related differences in clinical expression.

Thyroid diseases are more prevalent in females. This notion is mostly derived from studies conducted in adult subjects, but the knowledge of the relationship between sex and thyroid disease is becoming important for the epidemiological study of aging population. Aging has been proposed to represent a trigger for the development of autoimmune phenomena resulting in the production of both organ- and non-organ-specific antibodies. Studies on the relationship between sex and thyroid autoimmunity in elderly subjects have shown that the age-related prevalence of antithyroid autoantibodies is greater in women >60 yr of age. An increased prevalence of hypothyroidism has been demonstrated in the elderly population. Several factors may affect prevalence, but virtually all studies report higher prevalence rates for either overt or subclinical hypothyroidism in women with advancing age. This gender-related difference, however, has not been demonstrated for hospitalized patients. Difficulties are encountered in the attempt to estimate a sex-related difference in the prevalence of hyperthyroidism in elderly subjects. In most cases, Graves' disease and toxic multinodular goiter represent the cause of the disease with relative proportions depending on iodine intake. However, data on the prevalence of this disorder and on its sex-related frequency are significantly affected by underlying nodularity and functional autonomy. This phenomenon may be even more pronounced when excess iodine intake occurs and when patients are treated with iodine-containing drugs and thyroid hormone therapy. Subclinical hyperthyroidism is more common in women than in men, especially in subjects >70 yr. Both overt and subclinical hyperthyroidism arise from underlying thyroid nodular disease. The low-T3 syndrome is common in the elderly. Due to the fact that the low-T3 syndrome is often derived from underlying diseases, it is difficult do define a sex-related difference in its prevalence. However, in unselected elderly home-dwellers, an independent association of low-T3 syndrome with male gender has been shown. Aging represents an important factor to define the aggressiveness of thyroid carcinomas. Both follicular and anaplastic histotypes of thyroid cancer are more frequently found in elderly subjects. In aging subjects, male sex seems to be highly correlated with the risk of thyroid cancer. In conclusion, epidemiological data from the aging population confirms that men are less affected by thyroid disease than women. However, male sex may represent a risk factor for thyroid cancer in elderly population and this observation should be carefully considered in the evaluation of thyroid nodules in the elderly.

Aged↗

The relationship between testosterone and molecular markers of inflammation in older men.

Aging is accompanied by a pro-inflammatory state expressed by the increasing levels of inflammatory cytokines, including interleukin-6 (IL- 6), tumor necrosis factor alpha (TNF-alpha) and interleukin- 1beta (IL-1beta). At the same time, aging is associated with a decrease in serum testosterone (T) levels. There is evidence from many experimental studies that IL-6, TNF-alpha and IL-1beta inhibit T secretion by their influence on the central (hypothalamic-pituitary) and peripheral (testicular) components of the gonadal axis. On the other hand, observational and interventional studies suggest that T supplementation reduces inflammatory markers in both young and old hypogonadal men. Preliminary data from 473 older male participants of the InCHIANTI population showed a significant inverse relationship between T and soluble IL-6 receptor (sIL-6r) levels (a soluble portion of the IL-6 receptor that may enhance the biological activity of IL-6) but not with other markers of inflammation. This study, together with previous observations, suggests that a close relationship exists between the development of a pro-inflammatory state and the decline in T levels, two trends that are often observed in aging men. In the context of this paradigm, we discuss androgen deprivation therapy, a treatment used in men with metastatic prostate cancer as an ideal model to improve our understanding of the relationship between T and inflammatory markers. We advocate the notion that changes in inflammatory markers and T in aging men are causally linked. However, longitudinal and interventional studies are needed to confirm that T can be used therapeutically, based on its anti-inflammatory properties.

Aged↗

Ultrasound-guided fine-needle capillary biopsy of thyroid nodules, coupled with on-site cytologic review, improves results.

Fine-needle aspiration biopsy represents the most reliable test for cytologic evaluation of thyroid nodules. However, inadequate samples may occur leading to a repetition of the procedure with the consequence of patients' discomfort and poor compliance. In this paper, we present results from biopsy of thyroid nodules obtained by combining: (1) ultrasound (US) guidance, (2) no-aspiration technique, and (3) on-site review of specimens. A total of 465 nodules were biopsied in 307 patients. Solitary nodules and multinodular goiter were present in 36.8% and 63.1% of patients, respectively. After collection, each sample was smeared in duplicates, one of which was stained with hematoxylin and checked on-site by a cytopathologist. In cases of inadequate smears, biopsies were immediately repeated. All slides were then processed for final cytologic results, which were reported as benign in 427 nodules (91.8%), malignant in 12 nodules (2.5%), with follicular proliferation or suspicious for malignancy in 23 nodules (4.9%). Inadequate final cytology was reported in 3 nodules (0.6%). No statistically significant relationship was found between nodule size and adequacy of specimens. We conclude that the combination of US guidance, capillary collection with no-aspiration technique, and on-site review of slides, characterizes an advantageous method for thyroid nodule fine-needle biopsy.

Biopsy, Fine-Needle↗

Neuroendocrine hypothesis of aging: the role of corticoadrenal steroids.

The age-related modifications of neuroendocrine secretions normally capable of integrative activity in the whole body might partly promote and amplify many aging phenomena. The quantitative and qualitative changes of hypothalamus-pituitary-adrenal axis are a significant example. The dampening of cortisol and dehydroepiandrosterone (DHEA) circadian fluctuation and the progressive decrease of DHEA/cortisol ratio are at the basis of multiple clinical implications: the shift from anabolic to catabolic status, the activation of atherosclerosis progression, the deterioration of immune competence, the impairment of cognitive and affective performances and the glico- and lipometabolic disorders. The hypothesis of a DHEA supplementation strategy comes out from these premises.

Adrenal Cortex Hormones↗

Evaluation of the circadian profile of peripheral plasma galanin concentrations in normal subjects.

Galanin administration can influence pituitary function principally resulting in an increase in GH secretion. However, the role of circulating GAL levels in human endocrine function is still unknown. In the present study we simultaneously measured the circadian profiles of GAL, ACTH and GH in peripheral blood of ten adult subjects. Plasma samples were collected through an intravenous catheter at 0800, 1200, 1600, 2000, 2200, 2400, 0200, 0400 hours. The results were statistically evaluated by the cosinor analysis technique. A significant circadian rhythm of both plasma ACTH (p < 0.001) and GH levels (p < 0.03) was found with acrophases occurring at 0753 hrs and 0131 hrs for ACTH and GH, respectively. On the contrary, no significant rhythm was found in plasma GAL levels, indicating that no correlations exist between GAL and either GH or ACTH circadian profiles. Furthermore, the simultaneous assay of both GAL and GH plasma levels during a nocturnal frequent sampling performed in four volunteers showed the presence of peaks in GAL levels which, however, were not concomitant to the peaks in GH levels. These data demonstrate the lack of rhythmicity in the circadian profile of plasma GAL levels in healthy human subjects. The role of GAL in human endocrine function remains unknown and these results suggest that, in spite of the well documented increase in plasma GH concentrations following the intravenous administration of GAL, physiologically circulating levels of GAL are likely not involved in the regulation of GH secretion.

Adrenocorticotropic Hormone↗

Effects of vitamin A administration on serum thyrotropin concentrations in healthy human subjects.

Retinoids play an important role in the regulation of normal growth and development. Their biological action is mediated by a nuclear receptor that belongs to the steroid/thyroid hormone receptors superfamily. Retinoic acid has been shown to inhibit the secretion and synthesis of thyrotropin (TSH); however, little is known on the effects of retinoids on TSH secretion in normal human subjects. In the present study, we evaluated serum TSH concentration following both vitamin A (vit A) and the combined vit A and triiodothyronine (T(3)) administration. Basal and thyrotropin-releasing hormone (TRH)-stimulated TSH serum concentrations were measured in healthy young subjects in the following experimental conditions: (1) after 10 days of treatment with vit A orally administered as retinol at a dose of 50,000 IU/d; (2) after 10 days of oral placebo (PL) treatment; (3) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of PL treatment; and (4) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of vit A treatment. Serum TSH concentrations were also measured during vit A administration in healthy elderly subjects according to the following protocol: (1) after 10 days of treatment with PL; and (2) after 10 days of treatment with vit A at the same dose used for young subjects. In young subjects, basal serum TSH levels were found to be similar in the 4 different treatment conditions. In the same group of subjects, each of the 4 experimental conditions induced an increase in serum TSH, which rose from basal values of 1.80 +/- 0.31 to a peak of 11.92 +/- 1.75 microIU/mL (P <.001) during the PL treatment, from basal values of 1.81 +/- 0.22 to a peak of 10.81 +/- 1.00 microIU/mL (P <.001) during vit A treatment, from basal values of 1.72 +/- 0.28 to a peak of 9.92 +/- 1.10 microIU/mL (P <.001) during PL + T(3) treatment, and from basal values of 1.79 +/- 0.30 to a peak of 9.51 +/- 1.12 microIU/mL (P <.001) during vit A + T(3) treatment. The 2-way repeated measure analysis of variance revealed no significant differences among treatments. In old subjects, basal serum TSH levels were similar in the 2 experimental conditions and were not different from those observed in young subjects. In these subjects, serum TSH levels increased significantly in response to the TRH stimulus from basal values of 2.16 +/- 0.3 to a peak of 10.27 +/- 0.55 microIU/mL (P <.001) during PL treatment and from basal values of 2.10 +/- 0.51 to a peak of 7.82 +/- 1.4 microIU/mL (P <.001) during vit A treatment. No significant effects of treatment were found in this group of subjects on TRH-induced TSH levels; however, TSH responses were somewhat lower during vit A treatment with a difference close to statistical significance. These results suggest that TSH secretion is poorly affected by vit A administration in healthy human subjects; the data also indicate that any cooperation between T(3) and vit A is unlikely to occur in the regulation of TSH secretion.

Administration, Oral↗

Pituitary function in chronic heart failure in the elderly.

Heart failure is a complex syndrome characterized by the activation of hemodynamic, immunologic and neurohormonal systems, which have beneficial effects in the short run, but will ultimately lead to secondary end-organ damage with worsening of LV remodeling and subsequent cardiac decompensation. A very important role seems to be played by modifications of the pituitary hormone systems. Due to the neurohormonal activation there is an increase in the activity in the renin angiotensin system, in the adrenergic nervous system, and in the cytokine system. In heart failure there is a decrease in many anabolic hormones, such as a decrease of GH and IGF-I, of DHEA/DHEAS with normal or increased F, and a decrease of LH and sex steroids, resulting in an important catabolic drive, capable of contributing to the development of cardiac failure and to sarcopenia and/or cachexia, frequently observed in the advanced stages of the disease. However, these hormone alterations have been described in relatively young patients with chronic heart failure, since the mean age of all the subjects studied was of about 60 yr and none of the studies have specifically addressed this issue in the very old patients, who represent the largest portion of population affected by this pathological condition. The role of hormone replacement therapy needs to be verified in a population of elderly patients with heart failure.

Aged↗

Adrenopause: an imbalance between dehydroepiandrosterone (DHEA) and cortisol secretion.

Several clinical signs might be related to the decline of DHEA secretion in aged people: sarcopenia, osteopenia, atherosclerosis progression, impairment of cognitive and affective performances, deterioration of immunocompetence are the most significant evidences. In addition, in aged people this clinical condition might be worsened by the concomitant relative glucocorticoid excess which develops in an age related manner. All together, these clinical signs construct the corpus of a syndrome named adrenopause. DHEA replacement therapy might find its indication besides the obvious condition of primary and secondary corticoadrenal insufficiency in those aged patients with typical signs of adrenopause accompanied by magnified decline of DHEA and relative excess of cortisol. Two further indications for aged patients might be represented by those with chronic inflammatory diseases, especially when long term treated with glucocorticoids and those who undergo surgical procedures.

Adrenal Cortex Hormones↗