The African introgression of Murciano Granadina goats has a Moroccan origin and displays remarkable levels of inter-individual variability.

There is evidence that Murciano Granadina (MG), the most important caprine dairy breed in Spain, has been introgressed by African goats, but the precise geographic origin of such introgression has not been identified yet. Moreover, an accurate estimate of the magnitude of this African introgression is lacking, since current estimates are based on small numbers of sampled individuals. The aim of our work was to tackle these two issues by genotyping 500 MG goats with the Goat SNP50 BeadChip and comparing their genotypes with those of reference populations from Spain (Bermeya), France (Saanen), Morocco (Barcha, Draa, Ghazalia, Noire de Atlas, Nord, Moroccan), Egypt (Barki, Oasis, Saidi), Algeria (Arabia, Makatia, M'Zabite, Kabyle), Tunisia (Tunisian native breeds) and Sudan (Desert, Nilotic, Taggar). The population of 500 MG goats was subdivided into 10 datasets of 50 individuals to ensure that sample sizes of the target (MG) and reference populations are balanced. Performance of an unsupervised ADMIXTURE analysis demonstrated that MG goats have a North African ancestry, with an average proportion of 4.4 ± 2.3%. Next, we did a supervised ADMIXTURE analysis that revealed that the Moroccan genetic component reaches a proportion of 4.01 ± 3.9% in MG goats, while the Algerian (0.001 ± 0.001%), Egyptian (0.2 ± 0.1%), Sudanese (0.1 ± 0.1%) and Tunisian (0.3 ± 0.4%) components are present in extremely small proportions. The historical circumstances of this introgression event are currently unknown, but several plausible scenarios are outlined. Moreover, our results show considerable inter-individual heterogeneity regarding the magnitude of the Moroccan introgression of MG goats (0%- 12% depending on the MG data set under analysis). This result implies that reliable estimates about the introgression of autochthonous livestock by exotic breeds can only be obtained by extensively sampling target populations.

Efficacy of bio- and neurofeedback for depression: a meta-analysis.

BACKGROUND: For many years, biofeedback and neurofeedback have been implemented in the treatment of depression. However, the effectiveness of these techniques on depressive symptomatology is still controversial. Hence, we conducted a meta-analysis of studies extracted from PubMed, Scopus, Web of Science and Embase. METHODS: Two different strings were considered for each of the two objectives of the study: A first group comprising studies patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. RESULTS: In the first group of studies including patients with MDD, the within-group analyses yielded an effect size of Hedges' g = 0.717, while the between-group analysis an effect size of Hedges' g = 1.050. Moderator analyses indicate that treatment efficacy is only significant when accounting for experimental design, in favor of randomized controlled trials (RCTs) in comparison to non RCTs, whereas the type of neurofeedback, trial design, year of publication, number of sessions, age, sex and quality of study did not influence treatment efficacy. In the second group of studies, a small but significant effect between groups was found (Hedges' g = 0.303) in favor of bio- and neurofeedback against control groups. Moderator analyses revealed that treatment efficacy was not moderated by any of the sociodemographic and clinical variables. CONCLUSIONS: Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field has still a large room for improvement in terms of research quality, the results presented in this study suggests that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.

Detecting the footprint of selection on the genomes of Murciano-Granadina goats.

Artificial selection is one of the major forces modifying the genetic composition of livestock populations. Identifying genes under selection could be useful to elucidate their impact on phenotypic variation. We aimed to identify genomic regions targeted by selection for dairy and pigmentation traits in Murciano-Granadina goats. Performance of a selection scan based on the integrated haplotype score test in a population of 1183 Murciano-Granadina goats resulted in the identification of 77 candidate genomic regions/SNPs. The most significant selective sweeps mapped to chromosomes 1 (69.86 Mb), 4 (41.80-49.95 Mb), 11 (65.74 Mb), 12 (31.24 and 52.51 Mb), 17 (34.76-37.67 Mb), 22 (31.75 Mb), and 26 (26.69-31.05 Mb). By using previously generated RNA-Seq data, we built a catalogue of 6414 genes that are differentially expressed across goat lactation (i.e. 78 days post-partum, early lactation; 216 days post-partum, late lactation; 285 days post-partum, dry period). Interestingly, 183 of these genes mapped to selective sweeps and several of them display functions related with lipid, protein, and carbohydrate metabolism, insulin signaling, cell proliferation, as well as mammary development and involution. Of particular interest are the CSN3 and CSN1S2 genes, which encode two major milk proteins. Additionally, we found three pigmentation genes (GLI3, MC1R, and MITF) co-localizing with selective sweeps. Performance of a genome-wide association study and Sanger sequencing and TaqMan genotyping experiments revealed that the c.801C>G (p.Cys267Trp) polymorphism in the melanocortin 1 receptor (MC1R) gene is the main determinant of the black (GG or GC genotypes) and brown (CC genotypes) colorations of Murciano-Granadina goats.

Development and validation of the openness to the future scale: a prospective protective factor.

BACKGROUND: Most of the research on psychopathology has provided an incomplete picture of mental health by focusing on vulnerability factors and omitting the transversal processes that may explain human adapted functioning. Moreover, research has not sufficiently addressed prospective protective factors for mental health. New theoretical and empirical endeavors aim to incorporate this perspective, particularly in the realm of emotional disorders. A positive view of the future is an indispensable process in attaining desired goals and wellbeing. Openness to the Future is a construct characterized by positive affectivity towards the future, which can be a protective factor for mental health. Although some scales assess future orientations, the complexity of this concept has not yet been captured; therefore, there is a need for new instruments. This study presents the development and validation of a scale for measuring Openness to the Future in clinical (n = 412) and community (n = 890) samples. METHODS: Psychometric properties of the OFS were analyzed using Confirmatory Factor Analysis (CFA) and Item Response Theory (IRT) analyses, establishing cut-off points to better classify these two groups. Moreover, convergent and discriminant validity were examined by correlating the OFS with theoretically related constructs. RESULTS: Results support a unidimensional structure and indicate that the items function similarly across clinical and community samples. Moreover, the Openness to the Future scale shows good convergent and discriminant validity. CONCLUSIONS: These findings suggest that the Openness to the Future scale is a valid and brief measure of openness to the future for use with clinical and community samples, and it could help to fill a gap in the literature regarding attitudes towards the future and their implications. Openness to the Future is presented as an empirically feasible and theoretically consistent construct that includes both prospective and protective factors in the psychopathological chart.

Experience in geriatric patients at the Gastrointestinal Surgery Department of the Hospital Español, Mexico, 2013-2019. Five-year experience in GI surgery in geriatric patients.

INTRODUCTION: The aging of the population is one of the most widely studied and impactful social phenomena of this century. Up to 25% of all emergency hospital admissions can be due to diseases that require general surgery. AIMS: To describe the experience at the Department of Gastrointestinal Surgery of the Hospital Español, Mexico, in patients above 65 years of age. MATERIALS AND METHODS: A retrospective, observational, analytic, and cross-sectional study was conducted that included 595 medical records of geriatric patients that underwent surgical procedures, within the time frame of November 2013 and February 2019. RESULTS: A total of 52% (309) of the patients were men and 48% (286) were women. Mean patient age was 75.38 years, with a mode of 73 years, and a maximum age of 100 years. Mean hospital stay was 4.5 days. Postoperative complications presented in 12.77% of the patients, 3.02% of which were severe. Reoperation was required in 13 patients (0.02%). The perioperative mortality rate was 2.02%. CONCLUSIONS: The morbidity and mortality rates of the procedures that corresponded to general surgery in our case series were similar to those reported in the literature. A statistically significant number of patients underwent laparoscopic surgery, within the study period.

Squamous cell carcinoma of the lip. A retrospective study of 146 patients.

BACKGROUND: Squamous cell carcinoma of the lip (SCCL) accounts for 90% of all tumours of the oral cavity. We present a series of 146 patients with SCCL studied in our hospital. OBJECTIVE: To evaluate and identify the primary tumour parameters related to local and lymph node recurrence. METHODS: We retrospectively analysed the clinical characteristics, surgical procedures and tumour recurrences of the 146 patients diagnosed with SCCL in Hospital Universitario Fundación Alcorcón (Spain). RESULTS: A total of 122 of the 146 patients (91.7%) showed tumour stage ≤ T1N0M0 at diagnosis, and 11 (8.3%) showed stage >T1N0M0. Local recurrences were observed in 11 of the 146 patients (7.5%), and five patients (3.4%) developed lymph node metastases during follow-up. Kaplan-Meier survival analysis showed an increased tumour size to imply a greater risk of local recurrence (P = 0.025). The probability of local recurrence over the 24 months of follow-up was 1% for tumour stages ≤ T1N0M0 and 20% for stages ≥ T1N0M0. There appears to be a greater tendency towards local relapse in male patients, in smokers, patients living in rural areas, in lower lip tumours and in those patients showing infiltration at physical exploration. Eleven patients (8%) died during follow-up, although in only two of them (18%), SCCL was the cause of death. CONCLUSION: The low tumour stage of our patients may explain the few local and lymph node disease recurrences seen in our study. We have shown tumour size to be directly related to the probability of local recurrence.

Management of congenital cytomegalovirus infection: an evidence-based approach.

UNLABELLED: Abstract Despite cytomegalovirus being the most common congenital infection leading to psychomotor impairment and sensori-neural hearing loss, little is known about early identification and management of congenitally infected neonates. This article reviews the literature and devises an algorithm for identification and management of these neonates. CONCLUSION: Application of the current knowledge in the management of congenital cytomegalovirus infected neonates could be beneficial, until further evidence is available.

Optiflow vs Vapotherm as extended weaning mode from nasal continuous positive airway pressure in preterm infants ≤ 28 weeks gestational age.

INTRODUCTION: Current evidence supports nasal continuous positive airway pressure (NCPAP) weaning. Heated humidified high-flow nasal cannula (HHFNC) reduces NCPAP time in infants less than 28 weeks gestational age (GA) without increasing morbidity. The aim of the study was to compare the two most frequently used HHFNC devices in weaning from NCPAP. METHODOLOGY: We performed a retrospective matched-pair case-control study of infants less than or equal to 28 GA born in a single tertiary neonatal center managed with Optiflow or Vapotherm after being weaned from NCPAP. Patients were matched for antenatal steroid doses, delivery mode, birth plurality, GA, birthweight, gender, surfactant doses, length of mechanical ventilation, and length of NCPAP. Outcome measures were duration of HHFNC, low-flow nasal cannula, nasal bridge lesions, pneumothorax, bronchopulmonary dysplasia, postnatal steroids, necrotizing enterocolitis, sepsis, intraventricular hemorrhage, retinopathy of prematurity, length of stay, discharge weight, and mortality. Results were displayed as median (interquartile range) or ratio (percentage). Statistical analysis was performed using Mann-Whitney U and χ2 tests. RESULTS: 70 patients were recruited retrospectively. Thirty-five infants were weaned from NCPAP to Optiflow and 35 infants to Vapotherm with gestational ages and birthweights of 27 GA (26-27) and 1010 g (835-1165) and 27 GA (26-28) and 960 g (788-1191), respectively. There was no statistically significant difference in any outcome measure. Infants managed with Vapotherm required a not statistically significant shorter length of time on HHFNC and low-flow nasal cannula. CONCLUSIONS: Optiflow and Vapotherm seem to be equally effective and safe for weaning from NCPAP. However, infants weaned to Vapotherm appear to spend less time on non-invasive respiratory support.

Dropping out of a transdiagnostic online intervention: A qualitative analysis of client's experiences.

INTRODUCTION: An important concern in Internet-based treatments (IBTs) for emotional disorders is the high dropout rate from these protocols. Although dropout rates are usually reported in research studies, very few studies qualitatively explore the experiences of patients who drop out of IBTs. Examining the experiences of these clients may help to find ways to tackle this problem. METHOD: A Consensual Qualitative Research study was applied in 10 intentionally-selected patients who dropped out of a transdiagnostic IBT. RESULTS: 22 categories were identified within 6 domains. Among the clients an undeniable pattern arose regarding the insufficient support due to the absence of a therapist and the lack of specificity of the contents to their own problems. CONCLUSIONS: The analyzed content has direct impact on the clinical application of IBTs. A more tailored manage of expectations as well as strategies to enhance the therapeutic relationship in certain clients are identified as the two key elements in order to improve the dropout in IBTs. Going further, in the mid and long run, ideographic interventions would be vital. The present study permits to better grasp the phenomenon of dropout in IBTs and delineate specific implications both in terms of research, training and practice.

Signals derived from glucose metabolism are required for glucose regulation of pancreatic islet GLUT2 mRNA and protein.

Pancreatic islet GLUT2 mRNA is known to be regulated in vitro and in vivo by glucose. We have investigated several potential mechanisms mediating the response of islet GLUT2 to glucose. GLUT2 mRNA and protein were measured from isolated rat islets cultured for up to 24 h under selected conditions. Glucose at 11 mM stimulated GLUT2 mRNA 10-fold compared with 2 mM glucose, with no additional increase at 16.7 mM glucose, whereas maximal 4-fold induction of the protein was attained with 16 mM glucose. Time course studies showed a 2.5-fold induction of GLUT2 mRNA apparent after only 8 h of culture at 16.7 mM glucose. Glycolysis inhibitor mannoheptulose suppressed the stimulatory effect of 16.7 mM glucose on GLUT2 mRNA and protein. Metabolizable sugars mannose and glyceraldehyde enhanced transporter mRNA levels, in contrast with the lack of stimulation by nonmetabolizable 2-deoxy-D-glucose. Stimulation by different sugars and glycolysis inhibition led to analogous changes of proinsulin mRNA, suggesting that common signaling mechanisms are shared in glucose regulation of proinsulin and GLUT2 gene expression. Preexposure to mannoheptulose, however, failed to suppress glucose-stimulated insulin release. Tunicamycin, a glycoprotein synthesis inhibitor, did not block the effect of 16 mM glucose on GLUT2 mRNA levels. RNA and protein synthesis inhibitors actinomycin and cycloheximide abolished the enhancing effects of high glucose on GLUT2 mRNA. These findings indicate that glucose metabolism, but not glycoprotein synthesis or substrate interaction with the transporter protein, is instrumental in the stimulatory effects of glucose on beta-cell GLUT2 mRNA accumulation. In addition, ongoing RNA and protein synthesis are required for this effect.

Effects of tungstate, a new potential oral antidiabetic agent, in Zucker diabetic fatty rats.

Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 +/- 16 mg/dl). The animals became normoglycemic for approximately 10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at approximately 200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 +/- 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liver-pyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity.

4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.

We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 activity exerts an antidiabetic action in Goto-Kakizaki rats.

In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations, we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition, incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors in antidiabetic therapy.

Organelle distribution in chick neuroepithelial cells: effects of colchicine and cytochalasin B.

The intracellular distribution of mitochondria, cytoplasmic inclusions and rough endoplasmic reticulum cisternae of chick neuroepithelial cells was investigated at neurulation stages 6, 8, 10 and 12. These neuroepithelial cells were subdivided into three zones: apical, median and basal and the distribution percentages of distribution of these organelles were obtained. Mitochondrial distribution was related to the energy supply that mitochondria provide for apical microfilament contraction. Cytoplasmic inclusions were distributed preferentially in the apical zone of the neuroepithelial cells during the four stages. Rough endoplasmic reticulum cisternae were homogeneously distributed in the three zones at stages 10 and 12, but at stages 6 and 8 there are more elevated percentages of rough endoplasmic reticulum in the apical zones than in the other zones. Experimental treatments with colchicine and cytochalasin B does not modify the patterns of mitochondria and rough endoplasmic reticulum cisternae but alters the distribution of cytoplasmic inclusions. Finally, there is a correlation in the normal neurulating neuroepithelial cells between the distributions of mitochondria and rough endoplasmic reticulum distribution and between the distributions of mitochondria and cytoplasmic inclusions distribution. This relationship is retained in the treated neuroepithelial cells.

Hexokinase and glucokinase activity in cross-linked and permeabilized pancreatic islets.

The activities of hexokinase and glucokinase were measured in cross-linked and permeabilized rat pancreatic islets. After exposure to dimethyl suberimidate (20 mM) and digitonin (0.4 mM), the activity of hexokinase represented about half of that found in homogenates of freshly isolated islets. The K(m) of hexokinase for D-glucose and the Ki for its inhibition by D-glucose-6-phosphate were similar, however, in the cross-linked and permeabilized islets and in homogenates of freshly isolated islets. Glucokinase activity also was documented in the cross-linked and permeabilized islets, it being less sensitive than hexokinase activity to inhibition by D-glucose-6-phosphate. At a high concentration of D-glucose (16.7 mM), the phosphorylation of the hexose failed to be increased by D-fructose-1-phosphate, whether in the absence or presence of D-glucose-6-phosphate. These findings indicate that the intrinsic properties of hexokinase isoenzymes are preserved in cross-linked islets, but suggest that the cross-linking of proteins prevents the activation of glucokinase by its regulatory protein.

Immunocytochemical study of pancreatic islet revascularization in islet isograft. Effect of hyperglycemia of the recipient and of in vitro culture of islets.

We studied the revascularization process of isogeneic islets grafted into the kidney subcapsular space of streptozotocin-induced diabetic and nondiabetic rats by a double-labeling, indirect immunofluorescence technique using a rabbit antiserum to human factor VIII-related antigen (which identifies endothelial cells) and a guinea pig anti-insulin antiserum (which labels pancreatic beta cells). Freshly isolated islets contained a network of capillary endothelial cells, whereas 1-week-cultured islets at 37 degrees C have completely lost their intra-islet endothelial cells. Overnight cultured islets contained only occasional endothelial cells. When these islets were grafted under the kidney capsule of nondiabetic rats, they rapidly acquired a new endothelial cell lining as demonstrated by the positivity of staining for factor VIII-related antigen at day 5 after implantation. On the other hand, 1-week-cultured islets failed to become fully revascularized until day 7 after transplantation. Streptozotocin-induced diabetic rats grafted with 1000 islets normalized their blood glucose values (< 11 mM/L) 2-4 weeks after implantation, whereas transplantation of 2500-3000 islets resulted in normoglycemia after 4.7 +/- 2 days (mean +/- SD). Nevertheless, hyperglycemia of the recipient did not adversely affect the process of revascularization of islet isografts which initiated at day 3 and was almost completed by day 5 after implantation.

Nuclear response of pancreatic islets to interleukin-1 beta.

The mechanisms by which interleukin-1 (IL-1) exerts destructive action on the pancreatic islet beta-cells remain elusive. Fragmentation of DNA leading to the activation of poly(ADP-ribose) synthetase was investigated in the present study, by assessing the nuclear response to cytokines in rat pancreatic islets. Nuclear fractions display Mg(2+)-dependent poly(ADP-ribose) synthetase activity catalyzing the incorporation of [adenine-U-14C]NAD, with Ka and Km for Mg2+ and NAD amounting to 0.86 mM and 0.43 mM, respectively. Exposure of the nuclear fraction to rIL-1 beta (10 IU/ml) provoked DNA strand breaks and increased nuclear poly(ADP-ribose) synthetase activity (148.4%, P < 0.01). In intact islets, this nuclear response was observed after 18 h culture in medium containing rIL-1 beta, with a concomitant decrease in NAD (88.5%). Brief periods of pre-incubation (90 min) with rIL-1 beta were unable to induce any nuclear activity. Under these conditions, the presence of IFN-alpha (24 U/ml) and TNF (120 U/ml) was necessary to induce a response to rIL-1 beta. Under the latter experimental conditions, a decrease in NAD content was also observed. The nuclear effects of IL-1 beta were modified by nicotinamide (10 mM), an inhibitor of poly(ADP-ribose) synthetase. It is thus conceivable that an increase in poly(ADP-ribose) synthetase activity together with DNA break is implicated in the beta cytotoxic effect of interleukin-1 beta.

Metabolic and functional studies on isolated islets in a new rat model of type 2 diabetes.

In a new experimental type 2 diabetic syndrome, a 40% reduction of pancreatic beta cells was observed by morphometric analysis. In diabetic islets, as compared to control islets, insulin release was decreased in response to high glucose but not to other stimuli, and total glucose oxidation and utilization were unchanged or slightly reduced. The extent of metabolic and functional impairment appeared proportional to the beta-cell loss. However, a substantial decrease was found in protein level and activity (by 77 and 60%, respectively, versus controls) of mitochondrial FAD-glycerophosphate dehydrogenase (mGDH), the key enzyme of the glycerophosphate shuttle. Interestingly, in diabetic islets, as recently reported for mGDH-deficient transgenic mice, definite functional alterations (mainly in response to D-glyceraldehyde) were only obtained upon pharmacological blockade of the second shuttle (i.e. malate-aspartate) responsible for mitochondrial transfer of reducing equivalents. In conclusion, in this diabetes model with reduction of beta-cell mass, the islets, despite decreased mGDH amount and activity, appear metabolically and functionally active in vitro, likely through the intervention of adaptive mechanisms, yet prone to failure in challenging situations.

Differential Behavior Between Isolated and Aggregated Rabbit Auricular Chondrocytes on Plastic Surfaces.

A knowledge of the behavior of chondrocytes in culture is relevant for tissue engineering. Chondrocytes dedifferentiate to a fibroblast-like phenotype on plastic surfaces. Dedifferentiation is reversible if these cells are then cultured in suspension. In this report a description is given of how when chondrocyte aggregates formed in suspension are next seeded on plastic, most of them attach as round or polygonal cells. This morphological differentiation, with synthesis of type II collagen, is stable for long culture periods. This simple method can be of use as a model for studies of chondrocyte behavior on plastic. The results indicate that in addition to culture conditions, such as cell isolation method or cell density, chondrocyte behavior on plastic depends on the presence of aggregates.

P2 receptor agonists stimulate insulin release from human pancreatic islets.

Although P2 receptors for adenosine 5'-triphosphate (ATP) and/or adenosine 5'-diphosphate (ADP) have been characterized in mammalian pancreatic beta cells, no evidence for an insulin-secreting effect of P2 receptor agonists has been reported as yet in humans. The present study aimed at investigating whether P2 receptor agonists could stimulate insulin release in human pancreatic islets obtained from brain-dead organ donors. Experiments were performed using different glucose concentrations and insulin was measured by radioimmunoassay. When the glucose concentration (8.3 mmol/L) was slightly stimulating for insulin release, alpha,beta-methylene ATP (200 micromol/L) and ADPbetaS (50 micromol/L) similarly amplified insulin secretion: both compounds induced a threefold increase in insulin response. In the presence of a nonstimulating glucose concentration (3.0 mmol/L), only alpha,beta-methylene ATP could induce a significant 1.4-fold increase in insulin release, ADPbetaS being completely ineffective. These results give evidence that P2 receptor agonists are effective in stimulating insulin release in humans, the effect of the P2Y agonist being essentially glucose dependent.