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Biomedical subjects

G Solinas

Publications and source records attributed to G Solinas.

At least 19 recordsLinked to original sources

Corticotropin-releasing hormone directly stimulates thermogenesis in skeletal muscle possibly through substrate cycling between de novo lipogenesis and lipid oxidation.

The mechanisms by which CRH and related peptides (i.e. the CRH/urocortin system) exert their control over thermogenesis and weight regulation have until now focused only upon their effects on brain centers controlling sympathetic outflow. Using a method that involves repeated oxygen uptake determinations in intact mouse skeletal muscle, we report here that CRH can act directly on skeletal muscle to stimulate thermogenesis, an effect that is more pronounced in oxidative than in glycolytic muscles and that can be inhibited by a selective CRH-R2 antagonist or blunted by a nonselective CRH receptor antagonist. This thermogenic effect of CRH can also be blocked by interference along pathways of de novo lipogenesis and lipid oxidation, as well as by inhibitors of phosphatidylinositol 3-kinase or AMP-activated protein kinase. Taken together, these studies demonstrate that CRH can directly stimulate thermogenesis in skeletal muscle, and in addition raise the possibility that this thermogenic effect, which requires both phosphatidylinositol 3-kinase and AMP-activated protein kinase signaling, might occur via substrate cycling between de novo lipogenesis and lipid oxidation. The effect of CRH in directly stimulating thermogenesis in skeletal muscle underscores a potentially important peripheral role for the CRH/urocortin system in the control of thermogenesis in this tissue, in its protection against excessive intramyocellular lipid storage, and hence against skeletal muscle lipotoxicity and insulin resistance.

Adenylate Kinase↗

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity.

Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely: the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport),the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recentlythe stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes). This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity.

CCAAT-Enhancer-Binding Proteins↗

Oral health condition in an Italian preschool population.

AIM: This was to describe caries experience in Sardinian kindergarten children and the possible association with social, behavioural and dietary factors. METHODS: 418 kindergarten children (209 males, 209 females), aged 2.5-6.5 years, were enrolled. Dental status (dmft, dmfs) and presence of plaque were recorded by one calibrated examiner. Social, behavioural and dietary factors were investigated with an ad hoc prepared questionnaire. STATISTICS: These were descriptive and associations between caries experience and background variables were tested using chi square test. Logistic regression models were built up to assess the odds ratios (ORs) of caries prevalence and background variables. RESULTS: The caries experience rate was 29.9% of the total sample. The mean dmfs index was 3.26+/-7.37. The ds mean value was statistically higher in males at 3.41 versus 2.23 in females. Dmfs and sub indices were very high skewed in the total sample and in all age groups. Presence of plaque was recorded in 142 subjects (34.0%) and it was related to caries experience (20.1% without caries and 13.9% with caries) but not statistically significant. In logistic analysis, the socioeconomic status families were positively associated with caries experience OR=1.4 (95% CI: 1.2-1.9). Subjects with high sweet foods consumption showed a higher risk (60%) of caries experience than those not OR=1.6 (95% CI: 1.1-2.3). Children who cared for themselves regarding oral hygiene habits showed a lower risk for caries (OR=0.4 95% CI: 0.2-0.7). CONCLUSION: This study documented widespread neglect of dental health of preschool children in Sardinia. Untreated decayed teeth dominated the dmfs score among examined population, indicating a high rate of treatment needs.

Child↗

Epidemiology of hydatidosis in the province of Sassari, Italy.

Cystic echinococcosis is endemic in certain parts of the world, including Sardinia, Italy. It was performed a study in the province of Sassari in order to evaluate the incidence of the infection in man and the effects of control programs since 1964 to 2002. Data obtained by surgical records, hospital discharge forms, radiological and pathological files were collected using a case report form. During the years 1964-2002, 2702 new cases were identified (average annual incidence: 17 per 100,000) and 1981 (73.3%) were submitted to surgical treatment. In 57.3% municipalities no cases were observed during the years 1998-2002. Males are more affected (56.2%), mostly farmers-shepherdess (68.6 per 100,000) and pensioners (59.6 per 100,000). Control measures led to a significant decline in the incidence rate of hydatidosis during the period 1964-2002, dropping by 27.6 per 100,000. The mean age of surgical patients increased during the years of surveillance, such as the surgical liver/lung ratio as a consequence of a cohort effect. The durability of control programs is the corner stone for obtaining a significant decrease of this infection.

Adult↗

Skeletal muscle mitochondrial oxidative capacity and uncoupling protein 3 are differently influenced by semistarvation and refeeding.

We investigated, in skeletal muscle mitochondria isolated from semistarved and refed rats, the relation between the protein expression of uncoupling protein 3 (UCP3) and mitochondrial oxidative capacity, assessed as state 4 and state 3 respiration rates in presence of substrates that are either non-lipids (glutamate, succinate) or lipids (palmitoyl CoA, palmitoylcarnitine). During semistarvation, when whole-body thermogenesis is diminished, state 3 respiration was lower than in fed controls by about 30% independently of substrate types, while state 4 respiration was lower by 20% only during succinate oxidation, but UCP3 was unaltered. After 5 days of refeeding, when thermogenesis is still diminished, neither state 4, state 3 nor UCP3 were lower than in controls. Refeeding on a high-fat diet, which exacerbates the suppression of thermogenesis, resulted in a two-fold elevation in UCP3 but no change in state 4 or state 3 respiration. These results during semistarvation and refeeding, in line with those previously reported for fasting, are not in support of the hypothesis that UCP3 is a mediator of adaptive thermogenesis pertaining to weight regulation, and underscore the need for caution in interpreting parallel changes in UCP3 and mitochondrial oxidative capacity as the reflection of mitochondrial uncoupling by UCP3.

Animal Feed↗

Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings.

OBJECTIVE: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. METHODS: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. RESULTS: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. CONCLUSIONS: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

Adult↗

Periodontal status in an Italian young adult population. Prevalence and relationship with periodontopathic bacteria.

To determine the prevalence of periodontitis in an Italian young adult population and the relationship with Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque. A full-mouth periodontal and oral examination was performed in 70 subjects. Dental and behaviour habits were assessed with a standardised questionnaire. Subgingival plaque samples were collected from the deepest pocket of the first molars in each quadrant with a sterile curette. A. actinomycetemcomitans, P. gingivalis and P. intermedia were detected using a multiplex polymerase chain reaction. At subject level, the prevalence of bleeding on probing, calculus, normal pocket depth (PD), PD > 5mm and bacterial positivity were 44.8%, 43.3%, 22.9%, 11.4% and 95.7%, respectively. At quadrant level bacterial prevalence was 79.4%; P. intermedia was the most common bacteria (79.0%); A. actinomycetemcomitans had a prevalence of 40.8%. A significant linear trend across categories of gingival conditions (healthy, bleeding on probing, calculus presence) was detected for P. intermedia (p = 0.0038) and A. actinomycetemcomitans (p = 0.00005) proportions. No significant association was observed between pathogenic bacteria and PD, nor with behavioural attitudes. Gingival conditions are found to be a good predictors (VPP = 85%) for periodontopathic bacteria. For the Italian population, as no data are present, prospective longitudinal studies are needed to examine the relationship between PD and bacteria presence with periodontal disease onset and/or progression.

Actinobacillus Infections↗

Multiple sclerosis distribution in northern Sardinia: spatial cluster analysis of prevalence.

BACKGROUND: A heterogeneous geographic distribution of MS has been reported among different ethnic groups, and also within small communities. Epidemiologic studies conducted over the past two decades using repeated assessments clearly show that Sardinia is at high risk for MS, with a prevalence of 150 per 100,000 in 1997. OBJECTIVE: To present spatial analysis of the disease prevalence to disclose possible "hot" or "cold" spots of disease, further allowing correlations with risk factors. METHODS: A spatial analysis of the whole province of Sassari, in northern Sardinia, at a microgeographic level (i.e., in the 89 administrative communes and 6 linguistic areas) was conducted. Because of the small number of cases per commune and to overcome random variability, a hierarchical Bayesian approach was adopted. The distribution of prevalent cases by commune of residence on December 31, 1997 and from age 5 to 15 years was analyzed. RESULTS: A clustering pattern was found in the southwestern communes of the province based on geographic distribution by both prevalence and residence at age 5 to 15 years. A west-to-east gradient also was observed. CONCLUSIONS: This study highlights a hot spot of MS in the southwestern part of Sassari province, bordering with the commune of Macomer, where MS was once hypothesized as having occurred as an epidemic. Interestingly, these areas of MS clustering comprise the Common Logudorese linguistic domain. The Catalan area, linguistically and genetically distant from the remaining Sardinian domains, does not show such high estimates. Because MS is not a single-source infectious disease, this study may help test the hypothesis that a widely and evenly spread environmental (infectious?) agent may produce disease in subgroups of genetically more susceptible individuals in areas at higher inbreeding rates, wherein a disease mode of inheritance could be better investigated.

Adolescent↗

Visual and auditory event-related potentials in sporadic amyotrophic lateral sclerosis.

OBJECTIVES: To investigate the relationship between amyotrophic lateral sclerosis (ALS) and cognitive function by means of oddball event-related potentials (ERPs) and to determine the usefulness of this methodology in the cognitive status assessment of physically disabled patients. METHODS: Visual and auditory oddball ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive battery of neuropsychological (NP) tests assessed intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills. RESULTS: All patients performed visual and auditory ERPs and 75% of cases showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the entire psychometric evaluation with significant impairment on tests of executive function and attention. A significant correlation between delayed visual (P<0.04) and auditory (P<0.04) P300 latency and impaired NP tests was found. CONCLUSIONS: In agreement with literature data, our findings confirm the hypothesis of cognitive impairment in ALS patients especially on attention and executive functions suggesting a more extensive degeneration beyond the motor areas. ALS causes severe physical disabilities and such a condition may interfere with NP testing. Thus, the P300 seems to be a useful tool for the assessment of cognition and attention when severe physical deficits are present.

Adult↗

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy.

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population.

Humans↗

Sheep oestrosis (Oestrus ovis Linné 1761, Diptera: Oestridae) in Sardinia, Italy.

Oestrosis, the nasal myiasis of sheep and goats, is caused by the larvae of Oestrus ovis L. 1758 (Diptera, Oestridae) that develop from the first to the third stage larva in the nasal cavities and frontal sinuses of affected animals. The authors report the results of an epidemiological study of oestrosis of sheep in Sardinia, Italy. Heads of 6-month to 10-year-old Sardinian sheep (n=566) from 124 free-ranging flocks were examined for the presence and location O. ovis larvae from December 1996 to November 1997. Larvae were collected, counted, and larval stages were identified. O. ovis larvae were found in 100% of examined flocks and in 91% (514/566) of examined sheep. The monthly prevalence ranged from 69% in May to 100% in July. First stage larvae were found in 82% (463) of all heads examined, second stage larvae in 65% (367) and third stage larvae in 10% (56). The majority of sheep harboured first stage larvae, with prevalences of over 80% throughout most of the study period. The prevalence of O. ovis found in this study of Sardinian sheep is the highest reported in the Mediterranean area. The high percentage of first stage larvae found throughout the entire study period may be due to a brief period of decreased rate of larval maturation, in particular in December 1996 (96%) and January-October 1997 (94%). Third stage larvae were consistently present, often however, with extremely low prevalences compared to total larval burden.

Animals↗

Multiple sclerosis prevalence among Sardinians: further evidence against the latitude gradient theory.

A descriptive epidemiological survey was extended to the whole province of Sassari, northern Sardinia between latitudes 40 degrees 30' N and 41 degrees N. Results showed a crude total prevalence rate of 144.4 per 100000 on prevalence day (31 December 1997), and an onset-adjusted prevalence rate of 149.7 per 100000. The total average annual incidence rate was 4.9 per 100000 for the whole time interval studied (1968-1997), having increased from 2.0 in 1968-1972 to 6.8 in the last quinquennium considered. A substantial improvement in MS case ascertainment due to the introduction of new diagnostic procedures might account for such rates in Sardinia as well as in other Italian regions. However, when comparing our data with those obtained in the province of Ferrara, in the same time frames (1968-1997), a nine-fold versus a five-fold increase of MS prevalence was detected in Ferrara and Sassari, respectively. MS incidence temporal trend also notably increased in Sassari, but remained substantially stable in Ferrara. The progressive shortening of the time interval between clinical onset and diagnosis, and the proportion of benign-mild MS cases, were similar in both studies, thus suggesting a similar diagnostic accuracy. In our opinion, the repeatedly assessed increase of MS frequency in our province, at least partially does represent an actual rise of MS risk among Sardinians, thus disproving the latitude gradient-based theory (i.e. prevalence rates correlate with geographical latitudes) and supporting the hypothesis of a "Sardinian focus" of MS in a genetically susceptible population.

Adult↗

Immunogenetic heterogeneity of multiple sclerosis in Sardinia.

Multiple sclerosis (MS) predisposition is thought to be influenced by a complex, yet unclear interaction of genetic and environmental factors. Studying ethnically selected populations may reduce genetic and environmental heterogeneities and help clarify the underlying mechanisms of MS susceptibility. Sardinians kept a homogeneous genetic structure and have among the highest MS frequency rates worldwide. Interestingly, MS in Sardinia is linked to otherwise rare HLA alleles. In this light, recent findings from epidemiological and immunogenetic studies of Sardinian MS are presented. Results confirm that, likely due to significant genetic differences at a microgeographic level, even in this homogeneous population MS is immunogenetically heterogeneous and tends to preferentially cluster in some more archaic areas of the island.

Female↗

Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk.

OBJECTIVES: To update prevalence and incidence rates of MS among Sardinians. MATERIALS AND METHODS: The present work is a "spider" kind of population based survey, conducted over the interval 1968-97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). RESULTS: A crude total prevalence rate of 144.4 per 100,000, an onset-adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993-7 were found. CONCLUSION: Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS "Sardinian focus" as related to its latitude.

Adolescent↗

Maturation and translation mechanisms involved in the expression of a myb gene of rice.

We have isolated two overlapping cDNAs coding for a MYB-related protein expressed in aerobic and anaerobic rice (Oryza sativa) roots and coleoptiles. Analysis of their sequences reveals some peculiar features, suggesting the presence of post-transcriptional regulation events: an upstream ORF, two unspliced introns and a putative leucine zipper in the ORF coded by the unspliced RNA. Transient expression in protoplasts indicates that the upstream ORF inhibits expression of a downstream coding sequence. Finally, we demonstrated that anoxia, in roots, increases the ratio between the spliced and the unspliced mRNA and affects the expression of other myb-related genes.

Gene Expression Regulation, Developmental↗

Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone-releasing hormone on the pituitary-adrenal axis and on growth hormone secretion in dementia.

Alterations of neuroendocrinological indices determined by the impaired regulating effects of cholinergic neurotransmission have been described in primary dementia. In this study we have evaluated the effects of acetylcholinesterase inhibition by pyridostigmine on growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7 patients with primary degenerative dementia and in 8 sex- and age-matched controls. Demented subjects showed higher cortisol basal levels and lower ACTH levels than controls. Pyridostigmine increased the GH response to GHRH in both groups, the effect being significantly enhanced in patients. An increase of ACTH and cortisol levels was found in both groups after pyridostigmine and CRH administration. Pyridostigmine pretreatment significantly increased the ACTH response to CRH in controls but not in patients. The obtained data may indicate that a muscarinic receptor upregulation and an impairment of somatostatinergic function are operative in the regulation of GH secretion in dementia. An underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the responses of ACTH and cortisol to CRH in this disorder.

Adrenocorticotropic Hormone↗

A case of hyperglycemic hyperosmolar non-ketotic coma during anesthesia: a possible cause of failed re-awakening.

The case of a non diabetic 6-year-old boy affected by Down's syndrome, who developed hyperosmolar hyperglycemic non-ketotic coma following the infusion of hypertonic dextrose solution during general anesthesia for a surgical procedure for cryptorchidism is reported. Following surgery, the patient remained deeply comatose and generalized seizures occurred. Hyperosmolarity due to hyperglycemia and acidosis were reduced by administration of insulin at low rate, hypotonic saline and sodium-bicarbonate solutions. The patient's clinical conditions promptly improved following normalization of blood glucose levels. An oral glucose tolerance test performed three months later was normal. The authors emphasize the potential risk of hyperosmolar hyperglycemic non-ketotic coma also in non diabetic patients treated with hypertonic dextrose solutions, during surgery events.

Anesthesia, General↗