Genes controlling polyunsaturated fatty acid synthesis are developmentally regulated in broiler chicks.

1. The objective of this study was to characterise the regulation of the pathways that synthesise long-chain polyunsaturated fatty acids (PUFA) on developing adipose deposits in broiler embryos and chicks. Subcutaneous adipose depots were harvested from embryos and embryonic d E13, E15 and E17. Subcutaneous, abdominal and crop (neck) adipose, as well as liver, were collected at 7 and 14 d post-hatch. 2. Targeted RNA sequencing was used to quantify expression of 6 elongation of very long-chain fatty acid (ELOVL) genes, two isoforms of stearoyl-CoA desaturase (SCD and SCD5), and three fatty acid desaturases (FADS1, FADS2, and FADS6) in each depot and in the liver. Expression levels of marker genes for fatty acid oxidation and adipogenesis (peroxisome proliferator-activated receptor gamma (PPARG)) were quantified. Fatty acid composition of subcutaneous adipose was analysed using gas chromatograph-mass spectrometry (GC/MS). 3. Genes in the PUFA synthetic pathway were differentially expressed across developmental ages and between depots. These include elongase and desaturase genes, that have not previously been characterised in chicken. Correlation analyses identified subsets of co-regulated genes and fatty acids and highlighted relationships that may influence adipose metabolism and development. 4. It was concluded that PUFA synthesis is an active and dynamically regulated pathway in developing adipose deposits in the broiler chick. These data highlighted potential novel roles for specific elongase and desaturase genes in adipose deposition and metabolism.

Feeding increasing amounts of ruminally protected choline decreased fatty liver in nonlactating, pregnant Holstein cows in negative energy status.

The objectives were to determine the optimal feeding amount of choline in a ruminally protected form to reduce the triacylglycerol (TAG) concentration in liver and to increase TAG in blood plasma of dairy cows. Pregnant, nonlactating multiparous Holstein cows (n = 77) were blocked by body condition score (3.59 ± 0.33) and assigned to treatment at 64 ± 10 d before calculated calving date. Dietary treatments were top-dressing of 0, 30, 60, 90, or 120 g/d of ruminally protected choline (RPC; Balchem Corp., New Hampton, NY) ions to supply the equivalent of 0, 6.5, 12.9, 19.4, and 25.8 g/d of choline ions. Diets were formulated to exceed nutrient requirements for maintenance and pregnancy and fed in ad libitum amounts for the first 5 d. From d 6 to 15, cows were restricted to consume approximately 31% of their net energy requirements to simulate early lactating cows in negative energy balance. Methionine intake was maintained throughout each 15-d period. Liver was biopsied at 5 and 14 d and analyzed for TAG and glycogen. Blood was sampled on d 5 and 14 and plasma analyzed for glucose, insulin, cholesterol, ß-hydroxybutyrate, long-chain fatty acids, and haptoglobin. On d 14, a mixture of saturated long-chain fatty acids, ground corn, and dried molasses (50:37:13) was offered (908 g, as-is basis) 10 h after the single daily feeding. Blood samples were collected for 19 h and plasma analyzed for TAG and cholesterol to assess apparent absorption of dietary fat. Mean dry matter intake and energy balance decreased from means of 9.5 to 3.3 kg/d and from 0.6 to -9.2 Mcal of net energy for lactation/d during the ad libitum and restricted feeding periods, respectively. Plasma concentrations of the lipid-soluble choline biomolecules, namely total phosphatidylcholines, total lysophosphatidylcholines, and sphingomyelin, increased with choline supplementation. Feed restriction increased plasma concentrations of ß-hydroxybutyrate and free long-chain fatty acids, whereas those of glucose, insulin, and total cholesterol decreased. During feed restriction, concentration of hepatic TAG and plasma haptoglobin decreased linearly, whereas concentration of hepatic glycogen tended to increase quadratically with increasing intake of RPC. After fat supplementation, mean plasma concentration of TAG increased by an average of 21% with intake of RPC ions, peaking at intakes of ≥6.5 g/d of RPC ion. In summary, feeding RPC ions to cows in negative energy balance had increasing lipotropic effects on the liver when consumed up to 25.8 g/d, whereas feeding only 6.5 g/d increased concentrations of hepatic glycogen and TAG in the blood.

Synthesis and photophysical properties of a bichromophoric system hosting a disaccharide spacer.

The synthesis of an efficient energy donor-acceptor system is reported, together with its photophysical properties. The bichromophoric species has been conceived to show potentialities for biological applications since a biocompatible disaccharide spacer, constituted of d-galactose and d-glucose derivatives, was used in compound 12 to connect two BODIPY units with different absorption/emission properties. The luminescence spectrum in acetonitrile of 12 shows an intense fluorescence band with a maximum at about 770 nm that is almost identical to that of the lowest-energy BODIPY, regardless of the excitation wavelength used. The quantum yield is 0.2 with an excited state lifetime of 2.5 ns. Excitation and ultrafast transient absorption spectroscopy demonstrates that a very efficient energy transfer takes place in 12 from the highest-energy lying BODIPY subunit to the lowest-energy emissive BODIPY moiety, with a time constant of about 31 ps. Noteworthily, the emission of 12 falls in the near infrared window, suitable for potential biological applications.

Choline absorption and evaluation of bioavailability markers when supplementing choline to lactating dairy cows.

The metabolites of choline have a central role in many mammalian biological processes, and choline supplementation to the periparturient dairy cow improves hepatic lipid metabolism. However, variability in responses to choline supplementation has highlighted a lack of understanding of choline absorption in the lactating dairy cow. Our objective was to determine net choline absorption by measuring net portal fluxes of choline and choline metabolites in cows receiving either dietary supplements of rumen-protected choline (RPC) or abomasal delivery of choline (ADC). We also evaluated markers for choline bioavailability by examining relationships between net portal absorption of choline and choline metabolites in plasma and milk. Five late-lactation Holstein cows were used in a 5×5 Latin square design, with 5-d treatment periods and a 2-d interval between periods. Treatments were (1) control (0g/d of choline), (2) 12.5g/d of choline fed as RPC, (3) 25g/d of choline fed as RPC, (4) 12.5g/d of choline provided as ADC, and (5) 25g/d of choline provided as ADC. At the end of each 5-d period, milk was sampled and 9 blood samples were collected simultaneously from an artery and portal vein at 30-min intervals. Plasma, milk, and feed ingredient concentrations of acetylcholine, betaine, free choline, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine, and sphingomyelin were quantified by hydrophilic interaction liquid chromatography-tandem mass spectrometry. With an increasing dose of ADC, the net portal flux of free choline increased and regression analysis indicated 61% net absorption of the infused dose. Among the choline metabolites, only concentrations of betaine, free choline, and phosphocholine increased in both arterial plasma (3.9, 1.9, and 0.4 times, respectively) and milk (2.5, 1.4, and 1.0 times, respectively) with 25g/d of ADC relative to the control. For RPC, the net portal flux of free choline was low relative to ADC (13%), which was similar to the relative difference observed in the concentrations and yields of milk free choline and betaine (averaged 21%). When evaluating markers for choline bioavailability, betaine was the leading candidate. Betaine in plasma and milk (alone or in combination with phosphocholine) was strongly associated with net free choline portal flux (coefficient of determination ranging from 0.64 to 0.79). In summary, free choline supply to the lactating dairy cow increases only specific choline metabolites in plasma and milk, which can be potential markers for choline bioavailability.

A Bodipy as a luminescent probe for detection of the G protein estrogen receptor (GPER).

We report the rational design, based on docking simulations, and synthesis of the first fluorescent and selective probe of GPER for bioimaging purposes and functional dissecting studies. It has been conceived as a Bodipy derivative and obtained by accessible and direct synthesis. Its optical properties have been measured in different solvents, showing insensitivity to their polarity. Its binding to GPER was achieved by competition assays with [3H]E2 and [5,6-3H] nicotinic acid in ER-negative and GPER-positive SkBr3 breast cancer cells. SkBr3 cells, transfected with a GPER expression vector containing a FLAG tag, were used to confirm that the fluorophore binds to GPER in a specific manner.

The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk.

The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk.

A phylogeny for North American Mallocybe (Inocybaceae) and taxonomic revision of eastern North American taxa.

A multigene phylogenetic assessment of North American species of Mallocybe is presented based on analyses of rpb1, rpb2, ITS, and 28S rDNA nucleotide data. This framework enables a systematic revision of the genus for 16 eastern North American species and captures taxonomic and phylogenetic diversity in a global context. A grade of two unusual and poorly known North American species stems from the most recent common ancestor of the genus that gives rise to three core subgroups named here as clades Unicolores, Nothosperma, and Mallocybe. The grade of taxa includes the poorly known Lepista praevillosa from Florida and a new species from the southern Appalachians, M. montana, both of which appear to be narrow-range endemics. Clade Nothosperma is characterized by Australian and New Zealand species, whereas clade Unicolores is composed of six species from eastern North America and East Asia. Clade Mallocybe is dominated by numerous north temperate taxa and constitutes the sister group to clade Nothosperma. These major clades are distinguished by a combination of phylogeny, morphology, geographic distribution, and ecology. In addition, four North American species are described as new: M. leucothrix, M. luteobasis, M. montana, and M. tomentella. Several names originating in North America, long ignored or misunderstood in the literature, are revitalized and established by type comparisons and modern reference material collected from or near type localities. In addition, 11 species were subjected to mass spectrometry muscarine assays, none of which contained detectable amounts of muscarine except for two: M. sabulosa and M. praevillosa. This confirms a diffuse phylogenetic distribution of muscarine within the genus. Taxonomic descriptions are presented for 16 species, several synonymies proposed, and four new combinations made. A key to species of eastern North American Mallocybe is presented, along with illustrations of important diagnostic features. Citation: Matheny PB, Kudzma LV, Graddy MG, Mardini SM, Noffsinger CR, Swenie RA, Walker NC, Campagna SR, Halling R, Lebeuf R, Kuo M, Lewis DP, Smith ME, Tabassum M, Trudell SA, Vauras J (2023). A phylogeny for North American Mallocybe (Inocybaceae) and taxonomic revision of eastern North American taxa. Fungal Systematics and Evolution 12: 153-201. doi: 10.3114/fuse.2023.12.09.

Throwing velocity and kinematics in elite male water polo players.

AIM: Fifty-three members of the Italian Men Water Polo Team were filmed using two synchronized cameras, while they were shooting a goal. Considering the differences in body mass, height, training strategies and the technical-tactical features of the players, the aims of this study were to employ video-analysis techniques in order to investigate selected kinematic parameters in water polo throwing, and to provide comprehensive quantitative information on the throwing movement in relation to the different team player positions. METHODS: Video analysis was used to estimate the elbow angle at release, the shoulder angle at follow through, the back and head height at ball release, trunk rotation angle and ball velocity at release. RESULTS: Ball release velocities ranged from 21.0 to 29.8 m/s (average value 25.3±1.4 m/s), for field players. Goal keepers show the lowest team values (average 21.7±0.3 m/s). Similar to previous study results, ball release was typically reached just prior to the elbow approaching full extension (151.6±3.6°), and the follow through shoulder angle was 143±5.9°. CONCLUSION: No significant statistical difference was recorded between injured and non-injured athletes. No positive association was demonstrated between physical characteristics (body mass and height) and ball velocity.

Autoinducer-2 is produced in saliva-fed flow conditions relevant to natural oral biofilms.

AIMS: We evaluated the ability of a dual-species community of oral bacteria to produce the universal signalling molecule, autoinducer-2 (AI-2), in saliva-fed biofilms. METHODS AND RESULTS: Streptococcus oralis 34, S. oralis 34 luxS mutant and Actinomyces naeslundii T14V were grown as single- and dual-species biofilms within sorbarods fed with 25% human saliva. AI-2 concentration in biofilm effluents was determined by the Vibrio harveyi BB170 bioluminescence assay. After homogenizing the sorbarods to release biofilm cells, cell numbers were determined by fluorometric analysis of fluorescent antibody-labelled cells. After 48 h, dual-species biofilm communities of interdigitated S. oralis 34 and A. naeslundii T14V contained 3.2 x 10(9) cells: fivefold more than single-species biofilms. However, these 48-h dual-species biofilms exhibited the lowest concentration ratio of AI-2 to cell density. CONCLUSIONS: Oral bacteria produce AI-2 in saliva-fed biofilms. The decrease of more than 10-fold in concentration ratio seen between 1 and 48 h in S. oralis 34-A. naeslundii T14V biofilms suggests that peak production of AI-2 occurs early and is followed by a very low steady-state level. SIGNIFICANCE AND IMPACT OF THE STUDY: High oral bacterial biofilm densities may be achieved by inter-species AI-2 signalling. We propose that low concentrations of AI-2 contribute to the establishment of oral commensal biofilm communities.

Serum OPG and RANKL levels before and after intravenous bisphosphonate treatment in Paget's disease of bone.

Paget's disease of bone (PDB) is a focal disorder of bone remodeling characterized by increased osteoclast-mediated bone resorption. Even though increasing evidence indicates enhanced nuclear factor-kB (NF-kB) signaling as a common mechanism involved in PDB and other related disorders, few studies investigated circulating osteoprotegerin (OPG) and receptor of activator of NF-kB-ligand (RANKL) levels in PDB patients. In this study we explored the relationships between OPG or RANKL levels and bone turnover markers in a group of patients with PDB, before and after intravenous bisphosphonate treatment (pamidronate 60 mg). Both OPG and RANKL were markedly elevated in PDB patients with respect to control groups (healthy or osteoporotic postmenopausal women and elderly men) and were positively associated with bone turnover markers. Higher levels of these cytokines were observed in polyostotic than monostotic PDB cases. The ratio between RANKL and OPG was more than 3-fold higher in PDB patients than in controls. Interestingly, in the group of patients treated with pamidronate, we found an increase in OPG levels that become statistically significant after 3 and 6 months from treatment. A trend toward a decrease in RANKL levels after treatment was also observed. The RANKL/OPG ratio was significantly reduced after 3 and 6 months of therapy. In contrast, in patients classified as non-responders, OPG and RANKL levels after pamidronate infusion did not significantly differ with respect to pre-treatment values. Thus, the positive effect of amino bisphosphonates in the treatment of PDB may be due to either direct or indirect suppression of RANKL-induced bone resorption through decreased RANKL and increased OPG production.

Circulating gastrin and ghrelin levels in patients with colorectal cancer: correlation with tumour stage, Helicobacter pylori infection and BMI.

Many studies have pointed out a possible role of gut peptides, including gastrin and ghrelin, in the pathogenesis and natural history of gastrointestinal malignancies, one of the most common death cause in the Western world. The objective of this work is to check gastrin and ghrelin serum levels in patients with colorectal cancer according to tumour's location, stage, Helicobacter pylori infection and BMI, in order to understand the two peptides' behaviour through the tumour's natural history and evaluate their assay's use in research and clinical practice. Twenty-nine subjects affected by colorectal cancer and 50 healthy controls were studied. Circulating gastrin and ghrelin levels and H. pylori serum antibodies were assessed by radioimmunologic assay and ELISA method. Gastrin and ghrelin serum levels were respectively slightly higher and significantly lower in colon cancer patients than in controls. Gastrin levels were higher in patients carrying left colon cancer and H. pylori infection while ghrelin levels were lower in both these groups. Both hormones' serum levels decreased from tumour earlier to later stages. Significant differences persisted in the correlation between BMI and ghrelin levels in controls but not in patients. Additional studies are necessary to ascertain the significance of gastrin and ghrelin opposite behaviour in colon cancer probably linked with interferences in endocrine pathways involving other gut peptides in this compromised condition.

Evidence for membrane affinity of the C-terminal domain of bovine milk PP3 component.

Component PP3 is a phosphoglycoprotein isolated from bovine milk with unknown biological function, which displays in its C-terminal region a basic amphipathic alpha-helix, a feature often involved in membrane association. According to that, the behaviour of PP3 and of a synthetic peptide from the C-terminal domain (residues 113-135) was investigated in lipid environment. Conductance measurements indicated that the peptide was able to associate and form channels in planar lipid bilayers composed of neutral or charged phospholipids. Electrostatic interactions seemed to promote voltage-dependent channel formation but this was not absolutely required since the pore-forming ability of the 113-135 C-terminal peptide was also detected with the zwitterionic lipid bilayer. Additionally, a spectroscopic study using circular dichroism argues that the peptide adopts an alpha-helical conformation in interaction with neutral or charged micelles. Thus, the conducting aggregates in bilayers might be composed of a bundle of peptides in helical conformation. Besides, similar conductance measurements performed with the whole PP3 protein did not induce any channel fluctuations. However, with the latter, an early breakdown of the bilayers occurred, a finding that can be tentatively explained by a massive incorporation of PP3. In the light of the present results, it could be inferred that PP3 membrane attachment may be achieved by oligomerization of the C-terminal amphipathic helical region.

Alberta Breakthrough Pain Assessment Tool: A validation multicentre study in cancer patients with breakthrough pain.

BACKGROUND: Cancer-related breakthrough pain (BTP) is a common and quite challenging pain syndrome, with significant impact on quality of life. To date, no widely recognized and validated tool for the diagnosis and evaluation of BTP exists. The Alberta Breakthrough Pain Assessment Tool (ABPAT) underwent a validation process during its development, but no experience of its implementation in clinical practice has been reported. METHODS: ABPAT was tested in a cohort of cancer patients suffering from chronic severe cancer-related pain in order to assess its acceptability and efficacy as a tool for the characterization of BTP. RESULTS: A total of consecutive 249 patients from seven different centres were included in a 2-month study period and all completed the questionnaire; 231 out of the 249 (92.8%) stated that questions were easily understandable and 217 out of the 249 (87.1%) stated that the tool allowed to explain extensively the BTP problem. Physician-patient correlation tests about baseline BTP intensity and BTP relief by medication showed statistical significance at the level of p = 0.001 and p = 0.0001, respectively. Evaluation of the efficacy of BPT medication revealed a 78.2% of patients declaring a good relief from BTP, with a significant reduction of mean BTP numeric rating scale score (p = 0.0001), but only 55.9% of patients responded to be satisfied about time for onset of the relief. CONCLUSIONS: In this study, ABPAT resulted to be a well-accepted tool for BTP assessment and characterization in a relatively large cohort of cancer patients. It is effective in discovering the unmet needs of cancer patients and in exploring the outcomes of BTP treatment.

Spontaneous and anti-Fas-induced apoptosis in lymphocytes from HIV-infected patients undergoing highly active anti-retroviral therapy.

OBJECTIVE: The aim of this study was to investigate susceptibility to spontaneous or anti-Fas-induced apoptosis in peripheral blood mononuclear cells (PBMC) from HIV-positive patients before and during highly active anti-retroviral therapy (HAART). DESIGN: A longitudinal study was performed on 12 evaluable patients on HAART. This cohort was analysed prior to and at week 2, 4, 8, 16 and 24 after beginning HAART. Variations in CD4 and CD8 cells, viral load, susceptibility to spontaneous or anti-Fas-induced apoptosis in the presence of IL-2, IL-4 or IL-12 were studied. Expression of Fas and Bcl-2 were also assessed. METHODS: Levels of HIV RNA were determined by a quantitative reverse transcription-PCR assay. Apoptosis was evaluated by staining isolated nuclei with propidium iodide followed by multiparameter flow cytometry analysis. RESULTS: Spontaneous apoptosis of PBMC was promptly inhibited after the start of treatment. Similarly, anti-Fas-induced apoptosis diminished greatly during treatment. Expression of Fas decreased significantly, while that of Bcl-2 remained statistically unchanged during the first 24 weeks of therapy. Levels of apoptosis correlated inversely to CD4 cell counts and directly to viral load in a highly significant way. Expression of Fas was directly correlated to apoptosis. Interleukin (IL)-2, but not IL-4 or IL-12, protected PBMC of HIV-positive individuals from spontaneous or anti-Fas-induced apoptosis before and during HAART. CONCLUSION: These results suggest that regulation of apoptosis and of Fas expression are involved in immunoreconstitution during HAART.

Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women.

This study examines the influence of circulating insulin-like growth factor-1 (IGF-1) and serum leptin on bone mass as well as modulation of bone mass during skeletal development. Moreover, an inverse relationship between IGF-1 and leptin is reported. To evaluate the effects of serum IGF-1 and serum leptin on bone mass in healthy postmenopausal women, and the possible role of IGF-1 in leptin production, we studied a population of 123 women, aged 39-82 years. Bone mineral density (BMD) was determined by whole-body dual-energy X ray absorptiometry, which also enables measurement of body composition. Bone metabolism was assessed by measuring serum total alkaline phosphatase (TAP) and urinary hydroxyproline/creatinine (HP/Cr) excretion. IGF-1 correlated significantly with age (r = -0.28, p < 0.01) and years since menopause (r = -0.24, p < 0.01). A negative correlation was also found with weight and body mass index (r = -0.15, p < 0.05 and r = -0.19, p < 0.05, respectively). Leptin values were strongly correlated with weight (r = 0.7, p < 0.01), BMI (r = 0.7, p < 0.01), fat mass (r = 0.77, p < 0.01), and lean mass (r = 0.39, p < 0.01); a significant correlation was found with total body BMD (r = 0.29, p < 0.01), TAP (r = 0.15, p < 0.05), and HP/Cr (r = 0.18, p < 0.05). After adjustment for BMI, the significance of these relationships disappeared, demonstrating the lack of effect of serum leptin on BMD and bone turnover independent of body weight. On the other hand, the relationship between BMD and fat mass remained statistically significant after adjusting for serum leptin (r = 0.15, p < 0.05). Controlling for BMI eliminated the significant inverse correlation between IGF-1 and leptin; significant differences in leptin levels were found among women in the lower and higher quartile of IGF-1, suggesting that leptin production may be inhibited only at high values of serum IGF-1. We conclude that serum IGF-1 and serum leptin have no direct effect on bone mass and bone turnover.

Leptin and body composition in healthy postmenopausal women.

BACKGROUND: Leptin has been proposed to be involved in central control of adiposity and fat distribution but the role of this peptide is controversial. The aim of our study was to test the relationship between serum leptin and body composition, fat distribution, and some biochemical markers such as fasting insulinemia and lipoproteins in a population of healthy Italian postmenopausal women. METHODS: One hundred and twenty-three postmenopausal women (62.1+/-8.7 years) were evaluated. Body composition (fat and lean mass) was assessed by dual-energy X-ray absorptiometry (DXA). Two regions of interest were determined for regional fat analysis. Serum leptin and insulinemia were measured by radioimmunoassay, lipoproteins with colorimetric methods and apolipoproteins nephelometrically. RESULTS: Plasma leptin levels are strongly related to total fat mass, in grams (r=0.73, p<0.001) or as a percentage of soft tissue (r=0.75, p<0.001), and to adiposity, calculated as ratio between lean and fat mass (r=0.76, p<0.001). A significant correlation was also found between serum leptin and central fat distribution (r=0.29, p<0.01). As concerns biochemical markers, serum leptin was significantly related to fasting insulin (r=0.38, p<0.001), total cholesterol (r=0.29, p<0.01), Apolipoprotein-B (r=0.35, p<0.001), and triglycerides (r=0.22, p<0.05). When corrected for total fat mass, the partial correlation coefficients remain significant for percentage of total body fat (r=0.27, p<0.01), adiposity (r=0.23, p<0.01), and fat proportion in android region (r=0.18, p<0.05). CONCLUSIONS: These data indicate that leptin levels are related to adiposity and fasting insulin levels; indeed fast insulin mantains significant correlation with leptin (r=0.23, p<0.01) after controlling for fat mass. Android distribution of fat mass in elderly women is associated with leptin concentration.

Expression of ornithine decarboxylase gene in elderly human monocytes.

The proliferative capacity of the immune system is impaired in elderly subjects and the expression of various genes involved in cell cycle progression is reduced in PHA stimulated lymphocytes during the aging process. Macrophages play a fundamental role in the immune system response. It has recently been demonstrated that the process of macrophage activation is accompanied by a rapid, transient rise of ornithine decarboxylase (ODC) mRNA levels. In fact, the ODC gene seems to be involved in macrophage activation and differentiation. The authors demonstrated that the steady-state levels of ODC mRNA and the correlated superoxide anion production are lower in the monocytes of elderly subjects with respect to those in young subjects used as control. These results confirmed the impaired immune function of the elderly.

Senile diabetes and bone mineral density.

Bone mineral density was determined in a series of 67 elderly diabetics (38 males and 29 females) and 40 non-diabetic elderly subjects (20 males and 20 females) at the third medial and tenth ultradistal of the non-dominating radius using an X-ray densitometer (DEXA). Bone metabolism markers (Ct, PTH, HOP, UCA, AP, Vit-25-OH-D, BGP) were also measured. Our results indicate that there is no significant difference in values of BMD and the bone metabolism markers studied between diabetic and non-diabetic elderly subjects. We believe that senile diabetes is not a risk factor of onset and maintenance of senile osteoporosis.

Altered laboratory thyroid parameters indicating hypothyroidism in elderly subjects.

The altered laboratory thyroid parameters indicating hypothyroidism were evaluated in a series of 3015 subjects over 65 years of age by determining total T3, total T4 and TSH. In addition, clinical signs of hypothyroidism were recorded in a subsample of 300 randomly selected elderly. Our results showed a high prevalence of altered laboratory thyroid parameters indicating hypothyroidism of 17.88%, whereas the real prevalence (both clinical and laboratory) is 1.00% with a female/male ratio of 2.00. The most frequent laboratory alterations was the so-called 'alerted pituitary' status'. The most common clinical signs of hypothyroidism involved the nervous system. We conclude that it is very difficult to diagnose hypothyroidism in the elderly and that the most indicative laboratory alterations seem to be TSH values above 3 IU/ml determined using the IRMA method.

Altered laboratory thyroid parameters indicating hyperthyroidism in elderly subjects.

The most common laboratory alterations of thyroid function indicating hyperthyroidism were evaluated in a series of 3015 subjects over 65 years of age by determining total T3, total T4 and TSH. Ultrasound and scintigraphy of the thyroid were performed where necessary. Our results showed a high prevalence of laboratory alterations hyperthyroidism type of around 8.09%, whereas the real prevalence (both clinical and laboratory) is 2.00% with a female/male ratio of 2.00. The most frequent hyperfunctioning thyreopaty is thyroidal adenoma (50%), followed by toxic multinodular goiter (33%) and Basedow's disease (17%). The most common clinical signs of hyperthyroidism involve the neuromuscular system and are often present in the so called 'euthyroid' elderly subject. We conclude that it is very difficult to diagnose hyperthyroidism in the elderly on clinical and laboratory grounds. The most significative laboratory thyroid parameter indicating hyperthyroidism seems to be TSH values below 0.2 IU/ml determined using the ultrasensitive IRMA method.