Constituents of the essential oil of Achillea wilhelmsii from Iran

Constituents of the essential oil of Achillea wilhelmsii L. growing wild in Kerman-Iran were studied by TLC, GC, and GC/MS methods. The main components of the monoterpene fraction of the oil were camphor, borneol, linalool, 1,8-cineole, chrysanthenol acetate, and carvacrol. The percentage of the identified sesquiterpenoid components was relatively high and constituted 29% of the oil.     

Intermolecular phosphorylation of insulin receptor as possible mechanism for amplification of binding signal

Clustering of cell-surface insulin receptors has led to the speculation that intermolecular phosphorylation of unoccupied receptors catalyzed by ligand-occupied receptors within the cluster could be a mechanism by which the insulin-binding signal is amplified. We examined whether insulin receptors can be phosphorylated by an intermolecular mechanism. In this study, we used highly purified insulin receptors isolated from rat liver plasma membranes and human placental membranes. Rat liver insulin receptors were "activated" by incubation with 10 nM insulin in the presence of ATP. Subsequent to removal of insulin by immunodepletion, these receptors were used as an enzyme source to study phosphorylation of unphosphorylated "substrate" human receptors. Initially, we found no evidence that the addition of activated rat receptors increased phosphorylation of human receptors, when assessed by immunoprecipitation with a human-specific monoclonal antibody. To examine the possibility that these negative results were due to insufficient receptor concentration, activated human receptors were mixed with unphosphorylated substrate receptors at concentrations up to 60 micrograms/ml. In this study, we found that addition of activated receptors resulted in increased phosphorylation of the substrate receptors at the highest concentrations employed. These are the first data indicating that insulin receptors per se are capable of intermolecular phosphorylation. In vivo, this could be the initial step in amplifying the insulin-binding signal.     

Fetal and maternal plasma homocysteine levels during the second half of uncomplicated pregnancy

Objective: To measure fetal and maternal plasma homocysteine (Hcy) concentrations in uncomplicated pregnancies.

Methods: Paired maternal venous and fetal umbilical cord blood (n?=?81) samples were evaluated for plasma Hcy and vitamin B₁₂ levels, in addition to eight neonatal umbilical cord blood samples obtained immediately following delivery.

Results: Both fetal and maternal Hcy concentrations were positively correlated with advancing gestational age (ρ?=?0.44, p?<?0.0001; and ρ?=?0.27, p?<?0.05, respectively). Fetal plasma Hcy concentrations [2.2?µmol/l (IQR: 2.0–3.2)] were significantly lower than both neonatal umbilical vein [5.0?µmol/l (IQR: 4.4–6.5); p?<?0.001] and maternal plasma Hcy levels [4.4?μmo/l (IQR: 3.4–5.4); p?<?0.001]. In addition, Hcy values at term were higher in the umbilical vein compared with the umbilical artery [5.0?μmol/l (IQR: 3.4–5.4) versus 4.2?μmol/l (IQR: 3.7–5.5), respectively; p?=?0.016]. Significant correlation was noted and between fetal and maternal Hcy levels (ρ?=?0.50, p?<?0.0001), while fetal Hcy was negatively correlated with maternal B₁₂ concentrations (ρ?=??0.32, p?<?0.001).

Conclusions: Fetal Hcy levels were significantly lower than maternal and neonatal levels and correlated with gestational age across the second half of pregnancy.     

Effect of chlorpropamide on glucose transport in rat adipocytes in the absence of changes in insulin binding and receptor-associated tyrosine kinase activity

In an attempt to elucidate the cellular mechanism(s) by which sulfonylureas exert their extrapancreatic hypoglycemic effects, various parameters of insulin action were examined in vitro, using rat adipocytes maintained in a biochemically defined medium. Cells were maintained for 20 hours in the absence or presence of 175 micrograms/mL chlorpropamide and insulin binding, hexose transport, glucose metabolism, and insulin receptor tyrosine kinase activity were compared. Chlorpropamide treatment had no effect on insulin binding, altering neither receptor number nor affinity. However, the sulfonylurea did enhance 2-deoxyglucose transport in both the absence (17%, P less than .01) and presence (20%, P less than .01) of insulin. Furthermore, glucose metabolism as measured by the conversion of glucose (0.2 mmol/L) to CO2 and total lipids was also significantly increased by chlorpropamide treatment in both the absence (30%, P less than .01) and presence (31%, P less than .05) of insulin. Potentiation of insulin-stimulated transport or metabolism was not explained by an increase in the basal state alone because the incremental responses to 40 ng/mL insulin were potentiated by 19% (P less than .01) and 25% (P less than .05), respectively. Activity of the insulin receptor kinase was unchanged as evaluated by autophosphorylation of partially purified receptors, phosphorylation of an artificial substrate and by phosphorylation of the receptor in situ. These studies demonstrate that the sulfonylurea, chlorpropamide, stimulates glucose transport and potentiates insulin's effect on this process by acting at a site(s) beyond insulin receptor binding and phosphorylation.     

Simultaneous double-isotope autoradiographic measurement of local cerebral glucose metabolic rate and acid-base status in rat brain

We developed a double-isotope autoradiographic method for the simultaneous measurement of the local cerebral metabolic rate for glucose (1CMRG) and index of regional acid-base status (rABI) in single brain slices using [2-¹⁴C]deoxy-D-glucose (DG) and 5,5-dimethyl-[2-¹⁴C]oxazolidine-2,4, dione (DMO). After iv isotope administration, paper chromatography separates plasma DMO from DG activity using a methanol-methylene chloride solvent system. Initial tissue autoradiograms depict regional DMO plus DG and DG metabolite distribution. After 14 days in a well-ventilated hood, 97.5 ±0.5% of all DMO is lost from tissue sections by sublimation, and a second autoradiogram depicts DG plus DG metabolite distribution. Retention of brain lipids does not alter beta-particle self-absorption, avoiding problems associated with isotope extraction with solvents. Autoradiograms are digitized and converted to isotope-content images. The second autoradiogram is used for lCMRG computation. After subtracting the second regional isotope-content value from the first, the DMO content is obtained and used to compute rABI. Application of this method to normal animals yields expected values for lCMRG and rABI. This method is amenable to whole-slice digitization and creation of functional images of lCMRG and ABI followed by pixel-by-pixel correlations of the two variables, making this a potentially valuable tool for the investigation of the relationships between glucose metabolism and brain acid-base balance.     

Serotonergic modulation of suicidal behaviour: integrating preclinical data with clinical practice and psychotherapy

Many studies have provided important information regarding the anatomy, development and functional organization of the 5-HT system and the alterations in this system that are present within the brain of the suicidal patient. There is also a growing interest in genetic factors associated with suicide, since these may lead to the emergence of personality traits that prove to be long-term predictors of suicidal behaviour. This review will focus on presenting the scientific literature on the role of the serotonergic system in suicidal behaviour as well as dysfunctional attitudes and personality traits associated with the suicidal patient. The association of the serotonin transporter gene, the 5-HT2 receptors and its metabolite 5-hydroxyindoleacetic acid with suicidal behaviour and animal models that may capture the complexity of suicidal behaviour will be discussed. Finally, the relationship between neurobiological models and psychotherapeutic interventions for suicide prevention will be considered with a focus on Schema Therapy (an approach that has shown particular promise in the treatment of suicidal individuals with personality disorders), aiming to invite the reader to integrate some aspects of the neurobiology of human suicidal behaviour into a model of suicide that can be used in a clinical encounter.     

Contagion of Temporal Discounting Value Preferences in Neurotypical and Autistic Adults

Journal of Autism and Developmental Disorders - Neuroeconomics paradigms have demonstrated that learning about another’s beliefs can make you more like them (i.e., contagion). Due to social...