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Biomedical subjects

L Gentile

Publications and source records attributed to L Gentile.

At least 19 recordsLinked to original sources

Recombinant human albumin supports development of somatic cell nuclear transfer embryos in mice: toward the establishment of a chemically defined cloning protocol.

Culturing embryos in different media is a useful approach to characterize their nature in regard to "memory" of the donor nucleus and its "reprogramming" after somatic cell nuclear transfer (SCNT). However, efforts to elucidate the mechanisms of reprogramming are seriously undermined when embryo culture conditions are not completely defined. Using recombinant human albumin (rHA) is a step toward establishing defined culture conditions for mouse cloning. Recombinant HA supports blastocyst formation of cumulus cell-derived clones at a rate comparable with two types of bovine serum albumin (BSA); following transfer of blastocysts to the genital tract, rates of development to midgestation (10.5 dpc) were indistinguishable. rHA also supports the derivation of germline competent embryonic stem (ES) cells from SCNT blastocysts at a substantial rate compared with BSA counterparts and with zygotic blastocysts. Unlike the developmental parameters, the gene expression patterns of clones cultured in rHA or BSA were not superimposed; identical patterns were observed for zygotic blastocysts in the two albumins. In summary, the present study demonstrates that (1) rHA can replace BSA, proving a defined protein source for SCNT in mice; (2) although using rHA is similar to BSA, it is not equal (rHA leaves a mark on gene expression of clones but not zygotes). Future studies that investigate reprogramming after SCNT will need to consider not only the implications of culture media for cloning but also the supplement choice.

Animals↗

Relationships between human serum resistin, inflammatory markers and insulin resistance.

OBJECTIVE: Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)). SUBJECTS: A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values. RESULTS: Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45). CONCLUSIONS: Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.

Biomarkers↗

Does C-reactive protein identify a subclinical metabolic disease in healthy subjects?

BACKGROUND: Highly sensitive C-reactive protein (hs-CRP) levels are significant predictors of subsequent diabetes and metabolic syndrome (MS). Owing the strong correlations between components of the MS and obesity with hs-CRP levels, previous studies about the associations of hs-CRP with insulin resistance might have been confounded by the inclusion of overweight or dysmetabolic subjects. DESIGN: Our aim was to evaluate the associations between hs-CRP levels and fasting insulin and insulin resistance (evaluated by the Homeostasis Model Assessment: HOMA IR) in a subgroup of subjects with normal body mass index (BMI) and without any metabolic abnormalities. Out of a cohort of 1658 middle-aged subjects, representative of the local sanitary districts of the province of Asti (north-western Italy) enrolled for metabolic screening: 241 (14.5%) showed normal BMI, glucose tolerance, blood pressure and waist values and no dyslipidaemia. RESULTS: In this subgroup of subjects, those with hs-CRP levels > or = 3 mg L(-1) showed significantly higher median insulin and HOMA-IR values (respectively: 20.4 vs. 6.0 pmol L(-1), and 0.8 vs. 0.2 microU mL(-1)x mmol L(-1)). In a multiple regression model, insulin and insulin resistance remained significantly and independently related to hs-CRP levels, after adjustments for age, sex, BMI, waist, alcohol consumption, level of physical activity and smoking habits. Very few individuals within lower fasting insulin quartiles showed hs-CRP values > or = 3 mg L(-1) when compared with approximately 60% of those within the highest quartile. CONCLUSIONS: The novel finding is that a state of low-grade systemic inflammation is present in normal BMI subjects who show subclinical insulin resistance but no other metabolic abnormalities.

Body Mass Index↗

Benign giant cell tumour of tendon sheaths in a European Lynx (Lynx lynx).

The histological, histochemical, immunohistochemical and ultrastructural features of a benign giant cell tumour (BGCT) of tendon sheaths in a 12-year-old male European lynx (Lynx lynx) are reported herein. The neoplastic mass involved the subcutaneous and inter-muscular tissues of the first, second, third and fourth digit of the left forelimb, from the phalanxes up to the carpus. The tumour appeared as a grey-whitish tissue mottled with darker areas, along with several scattered foci of orange colour. Histologically, the lesion consisted of a mixed population of numerous, multinucleated giant cells and epithelioid or spindle-shaped mononuclear cells embedded in a loose, highly vascular stroma. Neoplastic cells lined cleft formations and synovial-like projections into cystic spaces. No osteoid matrix could be detected. Haemorrhage and necrosis were also observed. The mononuclear and the giant cells were tartrate-resistant acid phosphatase and periodic acid-Schiff positive, being also immunohistochemically reactive for lysozyme and vimentin, with a few cells showing immunopositivity also for alpha-1-antitrypsin. Ultrastructurally, histiocyte-like cells, fibroblast-like cells and multinucleated giant cells were observed, but no virus-like particles could be detected in any of the above cell types. The BGCT of tendon sheaths, a fairly uncommon neoplasm in animals, has not been previously reported in the lynx.

Animals↗

Plasma nitrotyrosine levels, antioxidant vitamins and hyperglycaemia.

AIMS: Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury, in diabetes are limited and discordant; the amount of antioxidants might represent a possible explanation for the discordant results. The aim of this paper is to evaluate the association between plasma NT levels and glucose tolerance status, according to antioxidant vitamin intakes. METHODS: In three hundred men randomly selected from a population-based cohort, NT levels were measured and dietary intake assessed by a food-frequency questionnaire. Results NT values were similar in patients with diabetes (n = 34), impaired fasting glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with lower than recommended daily intakes of antioxidant vitamins C and A, NT levels were significantly higher in the diabetic patients. In a multiple regression model, after adjustments for age, body mass index (BMI) and smoking habits, NT levels were significantly associated with fasting glucose in patients with lower intakes of vitamin C (beta = 11.4; 95% CI 1.3-21.5) and vitamin A (beta = 14.9; 95% CI 3.9-25.9), but not in subjects with lower intake of vitamin E. CONCLUSION: A significant positive correlation between NT levels and fasting glucose is evident only in the presence of a reduced intake of some antioxidant vitamins. These findings might explain, at least in part, the discrepant results of previous studies and, if confirmed by further studies, suggest a simple measure (a balanced diet) to alleviate the increased oxidative stress of diabetes.

Age Factors↗

Single-cell quantitative RT-PCR analysis of Cpt1b and Cpt2 gene expression in mouse antral oocytes and in preimplantation embryos.

Fatty acids represent an important energy source for preimplantation embryos. Fatty acids oxidation is correlated with the embryo oxygen consumption which remains relatively constant up to the 8-cell stage, but suddenly increases between the 8-cell and morula stages. The degradation of fatty acids occurs in mitochondria and is catalyzed by several carnitine acyl transferases, including two carnitine palmitoyl transferases, CPT-I and CPT-II. We have carried out a study to determine the relative number of transcripts of Cpt1b and Cpt2 genes encoding for m-CPT-I and CPT-II enzymes, during mouse preimplantation development. Here we show that Cpt1b transcripts are first and temporally detected at the 2-cell stage and reappear at the morula and blastocyst stage. Cpt2 transcripts decrease following fertilization to undetectable levels and are present again later at the morula stage. These results show that transcription of both Cpt1b and Cpt2 is triggered at the morula stage, concomitantly with known increasing profiles of oxygen uptake and fatty acids oxidation. Based on the number of Cpt2 transcripts detected, we could discriminate the presence of two groups of embryos with high and low number of transcripts, from the zygote throughout preimplantation development. To further investigate if the establishment of these two groups of embryos occurs prior to fertilization, we have analyzed the relative number of transcripts of both genes in antral and ovulated MII oocytes. As for preimplantation embryos, MII oocytes show two groups of Cpt2 expression. Antral oocytes, classified according to their chromatin configuration in SN (surrounded nucleolus, in which the nucleolus is surrounded by a rim of Hoechst-positive chromatin) and NSN (not surrounded nucleolus, in which this rim is absent), show three groups with different numbers of Cpt2 transcripts. All NSN oocytes have a number of Cpt2 transcripts doubled compared to that of the group of MII oocytes with high expression. Instead, SN oocytes could be singled out into two groups with high and low numbers of Cpt2 transcripts, similar to those found in MII oocytes. The results of this study point out a correlation between the timing of fatty acids oxidation during preimplantation development and the expression of two genes encoding two enzymes involved in the oxidative pathway. Furthermore, although the biological meaning for the presence of two groups of oocytes/embryos with different levels of Cpt2 transcripts remains unclear, the data obtained suggest a possible correlation between the levels of Cpt2 expression and embryo developmental competence.

Animals↗

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.

Adult↗

[New aesthetic results with auricular prosthesis: two case reports].

The extrinsic and intrinsic coloration of maxillo-facial silicone elastomers has always been a challenge for the clinician in order to obtain a perfect, durable integration with the surrounding skin tissues. This preliminary report describes the method for obtaining good aestethetic results for maxillo-facial prosthesis. This study shows the aesthetic results of a new silicone for the laboratory technique of creating color of the basis for a maxillo-facial prosthesis, with a good matching with human skin. The technique is useful for the direct extrinsic coloration of the surface onto the skin of the patient by means of the RTV version of the same silicone. The technological properties of this material also make it easy to reproduce the emerging profile of the prosthesis from the human skin, avoiding anaesthetic overcounturings. The 12 month follow-up shows excellent and stable aesthetic results, which are not influenced by home care procedures and by the weathering effect on color and on physical properties.

Adult↗

Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes.

BACKGROUND AND DESIGN: Conflicting data exist about uric acid levels in type 2 diabetes mellitus, as low levels were found in diabetic patients, while elevated serum uric acid is a feature of hyperinsulinemia and impaired glucose tolerance. The present study was addressed to evaluate the relation between uric acid and metabolic parameters, creatinine clearance and albumin excretion rate in a cohort of type 2 diabetic patients. RESULTS: Hyperuricemic patients were older and had higher values of body mass index (BMI), systolic and diastolic blood pressure, triglycerides, albumin excretion rate, C-peptide and prevalence of hypertension, metabolic syndrome and macroalbuminuria and lower values of high-density lipoprotein (HDL)-cholesterol, creatinine clearance and glycated haemoglobin (HbA1c). The correlations between uric acid levels and triglycerides, BMI, systolic blood pressure, albumin excretion rate, C-peptide, creatinine clearance, HDL-cholesterol and HbA1c remained significant in a multiple regression analysis after adjustment for age, sex and duration of diabetes. After performing multiple logistic regression analyses, uric acid levels were independently associated with hypertension [odds ratio (OR) = 1.8; 95% confidence interval (CI) 1.6--2], after adjustment for age, sex, duration of diabetes and macroalbuminuria (OR = 1.5; 95% CI 1.1--2.0), after adjustment for age, sex, HbA1c levels, creatinine clearance, duration of diabetes and blood pressure levels and the metabolic syndrome (OR = 1.6; 95% CI 1.5--1.8), after adjustment for age, sex and creatinine clearance. CONCLUSIONS: In type 2 diabetes, hyperuricemia seems to be associated with the insulin-resistant syndrome and with early onset or increased progression to overt nephropathy, while hypouricemia is associated with worse metabolic control, hyperfiltration and a late onset or decreased progression to overt nephropathy.

Aged↗

Low HDL-cholesterol: a component of the metabolic syndrome only in the presence of fasting hypertriglyceridemia in type 2 diabetic patients.

The relation between isolated low HDL-cholesterol and the components of the metabolic syndrome is poorly known in type 2 diabetes. We evaluated cardiovascular risk parameters in type 2 diabetic patients with low HDL-cholesterol, compared to those with low HDL-cholesterol and hypertriglyceridemia, isolated hypertriglyceridemia and normal lipid parameters. Patients with low HDL-cholesterol/high triglycerides had higher BMI (29.6 +/- 5.7 vs 27.9 +/- 4.4 or vs 28.1 +/- 5.2 kg/m(2) ), prevalence of obesity (69% vs 55% or vs 54%), higher levels of uric acid (339.0 +/- 83.3 vs 303.3 +/- 95.2 or vs 303.3 +/- 89.2 micromol/l) and C-peptide (0.76 +/- 0.40 vs 0.63 +/- 0.33 or vs 0.63 +/- 0.36 nmol/l) and number of components of the metabolic syndrome (27% patients with all the components) compared to patients with isolated low HDL-cholesterol or normal subjects, respectively. A similar pattern of values was evident in patients with isolated hypertriglyceridemia. With logistic regression analysis, BMI and uric acid levels were significantly associated with the presence of hypertriglyceridemia (both isolated or associated with low HDL-cholesterol), while patients with isolated low HDL-cholesterol and those without dyslipidemia displayed a similar more favourable metabolic pattern. These results indicate that low HDL-cholesterol is a component of the metabolic syndrome only in the presence of fasting hypertriglyceridemia in type 2 diabetic patients.

Aged↗

Relationship of residual beta-cell function, metabolic control and chronic complications in type 2 diabetes mellitus.

As the relationships between C-peptide levels and metabolic control and chronic complications are poorly known in type 2 diabetes, due to the slow decline of beta-cell function, we evaluated these associations in a cohort of type 2 diabetic patients. After excluding insulin-treated subjects, 1,533 patients were divided according to their C-peptide fasting levels in quartiles. Patients within the lowest C-peptide quartile showed significantly higher duration of diabetes, prevalence of retinopathy and values of HDL-cholesterol, albumin excretion rate and HbA1c, while BMI, diastolic blood pressure, percentages of hypertension and metabolic syndrome, and values of triglycerides and uric acid were significantly higher in the highest C-peptide quartile. The associations between C-peptide and duration of diabetes, AER, HbA1c, retinopathy and the components of the metabolic syndrome remained significant, after multiple adjustments. In conclusion, these data support the hypothesis that a reduced insulin secretion is associated with a longer duration of diabetes and a greater prevalence of microvascular complications, while higher insulin levels are associated with the components of the metabolic syndrome.

Aged↗

Influence of a familial history of diabetes on the clinical characteristics of patients with Type 2 diabetes mellitus.

AIMS: To evaluate the roles of maternal and paternal diabetes and diabetes in relatives other than parents on the clinical characteristics in Type 2 diabetes mellitus. METHODS: A total of 2,113 Type 2 diabetic patients were recruited, and those with diabetic mothers, diabetic fathers, diabetic relatives other than parents and no known diabetic relatives, were considered separately. RESULTS: The prevalence of diabetes in the mother, father and other relatives was 25.5, 6.5 and 21.2%, respectively. No difference in the clinical characteristics was found in patients with diabetes in the mother or father. Patients with parental diabetes were significantly younger, with higher LDL-cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis than those without familial diabetes; on multiple logistic regression, only age (P = 0.0003), age at diabetes diagnosis (P = 0.0014) (inverse association), and LDL-cholesterol (P = 0.030) remained significantly associated with parental diabetes. Patients with diabetic relatives other than parents displayed significantly higher total and LDL-cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis that those with no known diabetic relatives; on multiple logistic regression, only age at diabetes diagnosis was inversely associated with diabetes in relatives other than parents (P = 0.013). CONCLUSIONS: The data do not indicate a different influence of maternal and paternal diabetes on the clinical characteristics of Type 2 diabetic patients, while there is evidence that parental diabetes brings to an earlier onset of the disease and higher LDL-cholesterol values; the presence of diabetes in relatives other than parents constituted a small risk for earlier manifestation of the disease.

Age of Onset↗

Hemimandibular hyperplasia: treatment strategies.

Hemimandibular hyperplasia is a well-defined, rare asymmetrical mandibular malformation. It is characterized by diffuse enlargement of the condyle, the condylar neck, and the ramus and body of the mandible. Because the anomaly begins before puberty, it is understandable that the maxilla follows the downward growth of the mandible. Pathogenesis is due most likely to clear hyperactivity in the condyle, which can be documented histologically with an actively proliferating cartilage. Therapy is largely based on the patient's age. The authors present their series of nine individuals with hemimandibular hyperplasia treated with various surgical methods between 1992 and 1994. A therapeutic approach called orthopedic maxillary management applied to two of the nine patients is presented. The objective is to maintain the occlusal maxillary plane in a correct position in growing patients. All clinical results, except one, were satisfying and showed good postoperative stability.

Adolescent↗

Sex- and BMI-related differences in risk factors for coronary artery disease in patients with type 2 diabetes mellitus.

There are contrasting data about the relationship between obesity and macrovascular complications in type 2 diabetes mellitus, and it is not known if risk factors for coronary artery disease are different in normal weight and overweight or obese patients. All 2113 patients with type 2 diabetes mellitus referring to the Diabetic Clinic of Asti were studied. Patients were divided into tertiles of body mass index, according to their sex (BMI < 26.9; >/= 26.9 and < 31.4; >/= 31.4 kg/m(2) for females and BMI < 25.7; >/= 25.7 and < 28.8; >/= 28.8 kg/m(2) for males). Age, BMI, duration of diabetes, blood pressure, HbA(1c) total cholesterol, HDL-cholesterol, LDL-cholesterol, and prevalence of insulin treatment and hypertension were higher in females, whereas exercise, alcohol intake, smoking habits and prevalence of dyslipidemia were higher in males. An increase in BMI was associated with an increase in HbA(1c), number of cigarettes/day, blood pressure, triglycerides, C-peptide, prevalence of hypertension and dyslipidemia, and with a decrease in age, duration of diabetes and HDL-cholesterol values. In spite of an apparently worse cardiovascular risk profile, females showed a 50% lower prevalence of CAD than males and the prevalence of CAD was not significantly different in obese compared to other BMI categories. Multiple logistic regression showed that risk factors for CAD were different in males and females and similar in the lower tertiles of BMI, while different in the highest. In obese females, risk factors for CAD were age, reduced HDL-cholesterol and increased HbA(1c) levels; in males they were years of smoking and duration of diabetes. These data suggest that in type 2 diabetes, risk factors for CAD are different in the two sexes and in patients with the highest BMI compared to the normal and overweight subjects; blood glucose control and duration of diabetes seem more important than conventional cardiovascular risk factors in obese patients.

Age Factors↗

Semirigid fixation of the mandible in bimaxillary orthognathic surgery: stability after 18 months.

The stability of osteosynthesis with the use of semirigid mandibular fixation was evaluated in 15 patients who underwent bimaxillary procedures for correction of Class III malocclusion. All patients received rigid fixation (4 miniplates and screws) in the maxilla. Cephalometric evaluation was performed before the operation, immediately after the operation, and at least 18 months after the operation. At the 18-month follow-up, a mean mandibular relapse of 2.2 mm, associated with an additional advancement of the maxilla of 0.27 mm, was observed. The dental relationship was substantially correct. Stability of mandibular fragments in this sample of patients depended on the stability of the maxilla. In addition, neither clinical damage to the temporomandibular joint nor lesions to the neurovascular bundle were detected.

Adult↗