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.

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.

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.

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.

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.

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.

Diagnostic value of subependymal pseudocysts and choroid plexus cysts on neonatal cerebral ultrasound: a meta-analysis.

BACKGROUND AND OBJECTIVE: Subependymal pseudocysts and choroid plexus cysts are seen in newborns on cerebral ultrasound. Clinicians are unsure whether these findings are related to an underlying disease which affects long-term outcome and requires medical intervention. In an attempt to establish the diagnostic value of cystic lesions on cerebral ultrasound and guide clinical management we searched the medical literature and performed a meta-analysis. METHODS: We performed a systematic literature review and summarised the data on the value of subependymal pseudocysts or choroid plexus cysts for the diagnosis of chromosomal anomalies or congenital infections. Sensitivity, specificity, predictive values and likelihood ratios were calculated for single, multiple, unilateral and bilateral cysts. RESULTS: 305 patients with cystic lesions were retrieved. Bilateral cysts, irrespective of their number, had a sensitivity of 88% and negative predictive value of 94% for a congenital infection or genetic disorder. Unilateral single cysts had a specificity of 92% for normal microbiological and genetic results. Bilateral multiple subependymal pseudocysts or choroid plexus cysts had a positive likelihood ratio of 9.1 for a chromosomal anomaly or congenital infection. Unilateral cysts had a negative likelihood ratio of 0.2 for a congenital infection or chromosomal anomaly. There was a chance of 1 in 4-5 for a congenital infection or chromosomal anomaly if bilateral multiple subependymal pseudocysts or choroid plexus cysts were found. CONCLUSIONS: Bilateral multiple subependymal pseudocysts or choroid plexus cysts suggest an underlying disease. Further investigations should be undertaken even if the patient is otherwise normal. Parents of well newborns with a single cyst should be reassured.

[Pitfalls in the diagnosis of congenital hyperinsulinism: a case report and review of the literature]. / Pitfalls bei der Diagnose des kongenitalen Hyperinsulinismus: Ein Fallbericht und Ubersicht der Literatur.

BACKGROUND: Congenital hyperinsulinism is the most common cause for recurrent hypoglycaemia in neonates and infants. Uncontrolled hypoglycaemia leads to seizures and long-term cerebral damage. Often, the diagnosis is delayed because of nonspecific symptoms and confusing laboratory results. PATIENT: We report a patient with hyperinsulinism who was initially wrongly diagnosed as having idiopathic cerebral convulsions and treated accordingly. CONCLUSIONS: Diagnosis of congenital hyperinsulinism is based on a strong suspicion and a thorough family history. Normal random blood glucose or random insulin levels are not helpful in excluding this disease.

Can treatment with somatostatin analogs replace neurosurgery?

There is an ongoing controversy on first-line treatment in acromegaly. Although transsphenoidal surgery has always traditionally been considered the first option, the evolution of new medical treatments is now challenging the clinical paradigm. In fact, somatostatin analogs are highly effective, convenient, avoid the growth of tumors or even shrink them, and also have the advantage of preserving normal pituitary function. On the other hand, when successful, neurosurgery has the advantage of eliminating long-term medical treatment and is less expensive. This manuscript discusses the pros and cons of both treatments.

Effects of extracellular matrix on the morphology and behaviour of rabbit auricular chondrocytes in culture.

Isolated chondrocytes dedifferentiate to a fibroblast-like shape on plastic substrata and proliferate extensively, but rarely form nodules. However, when dissociation is not complete and some cartilage remnants are included in the culture, proliferation decreases and cells grow in a reticular pattern with numerous nodules, which occasionally form small cartilage-like fragments. In an attempt to reproduce this stable chondrogenic state, we added a cartilage protein extract, a sugar extract, and hyaluronan to the medium of previously dedifferentiated chondrocytes. When protein extract was added, many cartilaginous nodules appeared. Hyaluronan produced changes in cell phenotype and behaviour, but not nodule formation. Protein extract has positive effects on the differentiation of previously proliferated chondrocytes and permits nodule formation and the extensive production of type-II collagen. A comparison with incompletely dissociated chondrocyte cultures suggests that the presence of some living cells anchored to their natural extracellular matrix provides some important additional factors for the phenotypical stability of chondrocytes on plastic surfaces. In order to elucidate if it is possible that the incidence of apoptosis is related to the results, we also characterized the molecular traits of apoptosis.

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.

Stable and functional regeneration of pancreatic beta-cell population in nSTZ-rats treated with tungstate.

AIMS/HYPOTHESIS: Sodium tungstate has recently emerged as an effective oral treatment for diabetes. We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential. METHODS: Sodium tungstate was administered via drinking water to healthy and neonatal streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was removed and morphometric and immunocytochemical studies were carried out. The molecular mechanism of tungstate's action was also studied. RESULTS: In nSTZ rats administration of this compound normalised glycaemia, and increased insulinaemia and islet insulin content. Blood glucose concentrations were normalised as early as on day 4 of treatment, and tungstate treatment produced a partial recovery of beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal. Morphometric studies showed that the increase in beta-cell mass was not due to beta-cell hypertrophy but to hyperplasia, with an increase in islet density in treated diabetic rats. Tungstate treatment increased extra-islet beta-cell replication without modifying intra-islet beta-cell replication rates. Moreover, the treatment induced increases in insulin-positive cells located close to ducts; and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38. CONCLUSION/INTERPRETATION: These observations indicate that tungstate treatment is able to regenerate a stable, functional pancreatic beta-cell population which leads to and maintains normoglycaemia.

Evidence of expression of endotoxin receptors CD14, toll-like receptors TLR4 and TLR2 and associated molecule MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells.

CD14, a GPI-linked membrane protein, is a component of the lipopolysaccharide (LPS) receptor complex, one of the pattern-recognizing receptors (PRR) expressed by myeloid lineage cells. Here we report that CD14, the functionally linked toll-like receptor molecules, TLR2 and TLR4, and the associated molecule MD-2 are expressed in endocrine cells of the human pancreatic islets. CD14 expression in human pancreatic islets was determined by immunofluorescence staining of tissue sections and primary cultures, and confirmed by flow cytometry of dispersed normal islets and SV40-transformed islet cells (HP62). The latter cells synthesized and secreted CD14 in response to lipopolysaccharide (LPS) in a time- and dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR)-Southern was positive for CD14, TLR2, TLR4 and MD-2 in human pancreas, purified islets and HP62 cells. In vitro experiments using rat islets (also positive for CD14 by RT-PCR) and HP62 cells showed that LPS regulates glucose-dependent insulin secretion and induces inflammatory cytokines [interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF)-alpha]. The functional expression of CD14 and associated molecules in islet beta cells adds a new pathway that islet cells may follow to adjust their function to endotoxaemia situations and become vulnerable to the inflammatory events that occur during diabetogenic insulitis.

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.

Estimation of pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in beagle dogs.

In this paper, an empirical Bayes methodology was used to determine the pharmacokinetic profile of sodium tungstate in beagle dogs after multiple oral dosing using the P-PHARM computer program. The population estimation algorithm used in P-PHARM is an EM-type procedure. Sodium tungstate was administered orally, three times a day, (i) for 11 days (21 and 42 mg/kg per day) to 18 dogs (nine males and nine females) and (ii) for 13 weeks (15, 30 and 60 mg/kg per day) to 28 dogs (14 males, 14 females). Six other dogs received the compound intravenously (25 and 50 mg/kg). Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. After oral administration, F (0.61+/-0.086 vs. 0.48+/-0.093), and normalized (to a 7-mg/kg dose of sodium tungstate) AUC (54+/-8.4 vs. 41.2+/-8.5 mg/l x h), C(max) (10.6+/-0.49 vs. 8.5+/-0.57 microg/ml) and C(min) (3.04+/-0.23 vs. 2.04+/-0.22 microg/ml), were higher in male than in female dogs. However, the introduction of the gender in the final model did not contribute statistically to an improvement of the fit of the population pharmacokinetic model. In males, t(1/2) elimination averaged 3.1+/-0.56 vs. 2.6+/-0.18 h in females. The duration of treatment did not modify statistically the pharmacokinetic parameters. After repeated multiple oral administration of 15-60 mg/kg per day of sodium tungstate, tungsten plasma concentrations increased in proportion to dose. No dose-dependent changes in pharmacokinetic parameters occurred.

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.

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.