An elevated extracellular concentration of D‐glucose (i.e. hyperglycaemia) inhibits cell proliferation and incorporation of the endogenous nucleoside thymidine into DNA in human umbilical vein endothelial cells (HUVECs). Cells in their log‐phase of growth (3.7 ± 0.3 days, n = 27) incubated for 30 min with 25 mM D‐glucose, but not with equimolar concentrations of L‐glucose or D‐mannitol, exhibited reduced [³H]thymidine incorporation and cell growth rate, with no change in cell viability (> 98%), total DNA, protein content or cell volume. Incubation with D‐glucose activated protein kinase C (PKC), endothelial NO synthase (eNOS), p42 and p44 mitogen‐activated protein kinases (p42/44^mapk), but inhibited superoxide dismutase (SOD). Incubation with D‐glucose also increased cGMP and cAMP levels. The effect of D‐glucose was blocked by the PKC inhibitor calphostin C, the MAP kinase kinase 1/2 (MEK1/2) inhibitor PD‐98059, the eNOS inhibitor L‐NAME, the protein kinase G (PKG) inhibitor KT‐5823 and the protein kinase A (PKA) inhibitor KT‐5720. In the presence of 5 mM D‐glucose, [³H]thymidine incorporation and cell growth were reduced by the PKC activator phorbol 12‐myristate 13‐acetate (PMA), the NO donor S‐nitroso‐N‐acetyl‐L,D‐penicillamine (SNAP), dibutyryl cGMP, dibutyryl cAMP and the Ca²⁺ ionophore A‐23187. The effect of A‐23187 was blocked by calphostin C and PD‐98059. D‐Glucose‐dependent inhibition of thymidine incorporation and cell proliferation is associated with increased PKC, eNOS, and MEK1/2, but decreased SOD activity, and higher intracellular levels of cGMP, cAMP and Ca²⁺ in HUVECs. These are cellular mechanisms which may reduce endothelial cell growth in pathological conditions such as in diabetes mellitus or hyperglycaemia.

1 Adenosine transport was measured in human cultured umbilical artery smooth muscle cells, isolated from non‐diabetic or gestational diabetic pregnancies, under basal conditions and after pretreatment in vitro with insulin. 2 Adenosine transport in non‐diabetic smooth muscle cells was significantly increased by insulin (half‐maximal stimulation at 0.33 ± 0.02 nm, 8 h) and characterized by a higher maximal rate (V_max) for nitrobenzylthioinosine (NBMPR)‐sensitive (es) saturable nucleoside transport (17 ± 5 vs. 52 ± 12 pmol (μg protein)⁻¹ min⁻¹, control vs. insulin, respectively) and maximal binding sites (B_max) for [³H]NBMPR (0.66 ± 0.07 vs. 1.1 ± 0.1 fmol (μg protein)⁻¹, control vs. insulin, respectively), with no significant changes in Michaelis‐Menten (K_m) and dissociation (K_d) constants. 3 In contrast, in smooth muscle cells from diabetic pregnancies, where the values of V_max for adenosine transport (59 ± 4 pmol (μg protein)⁻¹ min⁻¹) and B_max for [³H]NBMPR binding (1.62 ± 0.16 fmol (μg protein)⁻¹) were significantly elevated by comparison with non‐diabetic cells, insulin treatment (1 nm, 8 h) reduced the V_max for adenosine transport and B_max for [³H]NBMPR binding to levels detected in non‐diabetic cells. 4 In non‐diabetic cells, the stimulatory effect of insulin on adenosine transport was mimicked by dibutyryl cGMP (100 nm) and reduced by inhibitors of phosphatidylinositol 3‐kinase (10 nm wortmannin), nitric oxide synthase (100 μmN^G‐nitro‐l‐arginine methyl ester, l‐NAME) or protein synthesis (1 μm cycloheximide), whereas inhibition of adenylyl cyclase (100 μm SQ‐22536) had no effect. 5 Wortmannin or SQ‐22536, but not l‐NAME or cycloheximide, attenuated the inhibitory action of insulin on the diabetes‐induced stimulation of adenosine transport. 6 Protein levels of inducible NO synthase (iNOS) were similar in non‐diabetic and diabetic cells, but were increased by insulin (1 nm, 8 h) only in non‐diabetic smooth muscle cells. 7 Our results suggest that adenosine transport via the es nucleoside transporter is modulated differentially by insulin in either cell type. Insulin increased adenosine transport in non‐diabetic cells via NO and cGMP, but inhibited the diabetes‐elevated adenosine transport via activation of adenylyl cyclase, suggesting that the biological actions of adenosine may be altered under conditions of sustained hyperglycaemia in uncontrolled diabetes.

Serotonin plays a central role regulating mood and on the development of depressive disorders. To study whether 5HTTLPR functional polymorphisms in the serotonin transporter gene or the Monoamine oxidase A gene (uMAOA) were risk markers for depression. The Composite International Diagnostic Interview (CIDI) was applied to 1,062 consultants in primary health care centers aged between 18 and 75 years to establish the diagnosis of depression. A sample of saliva was obtained for DNA extraction and genetic analyses. No association between the presence of depressive disorders and 5HTTLPR (ss) or uMAOA (3/3) risk genotypes was found. Psychological abuse and the presence of two or more life events were found to be predictors of depression in the studied sample. In this study, 5HTTLPR and uMAOA polymorphisms were not risk factors for depression. However, psychological abuse and the presence of two or more life events were risk factors for depressive disorders.

Introduction: Risk factors associated to depression have been extensively studied, though there is a lack of prospective studies on factors that predict the incidence of depression in healthy people. There is not a predictive equation that incorporates genetic factors is not available. Method: A cohort study, prospective, with baseline assessments at 12 months was carried out on a random sample of attendees in primary care centers form the Concepción Province, Chile (n = 1,596). Eight psychosocial factors were measured and the genotyping of the uMAO and 5-HTTLPR in SLC6A4 as genetic factors polymorphisms was also carried out. The outcome variable was the presence/absence of depression at 12 months follow-up. A predictive model for depression was obtained by means of analyses of binary logistic regression. Results: Genetic variables have no statistically significant relation with the variable depression at 12 months follow up. Variables such as gender, educational level, satisfaction with living conditions, personal background of depression, self perception of both physical and mental health and satisfaction with relationship are related to the onset of depression in the follow up. Conclusions: Outcomes will allow identifying vulnerable people among the primary care attendees, who could participate in prevention programs. The study of further genes will be necessary in order to improve the predictive capacity of the model.