Biotechnological approaches to enhance the biosynthesis of ginkgolides and bilobalide in Ginkgo biloba

Ginkgo biloba is one of the oldest living tree species and its extracts or powdered leaves are one of the best selling herbal preparations. The main bioactive constituents are flavonoids and the terpene trilactones, ginkgolides and bilobalide, which are responsible for their pharmacological activity. However, there are many difficulties for ginkgo leaves supply and the chemical synthesis is far from of being applicable for commercial-scale production. G. biloba cell cultures have arisen as a useful alternative source of pharmacologically active terpene trilactones. This review sheds light on the chemistry and biosynthesis of terpene trilactones with the aim of increasing the production of these high value compounds by biotechnological approaches. Different biotechnological strategies to improve ginkgolides and bilobalide production will be discussed, including screening and selection of in vitro ginkgo cultures, cell differentiation levels of these cultures, optimization of culture conditions, feeding and elicitation strategies. Special attention will be paid in developing new methodologies to enhance ginkgo cell biomass and provide high amounts of these bioactive terpene trilactones using large-scale cell cultures.     

Urea’s Effect on the Ribonuclease A Catalytic Efficiency: A Kinetic, 1H NMR and Molecular Orbital Study

Understanding of protein–urea interactions is one of the greatest challenges to modern structural protein chemistry. Based in enzyme kinetics experiments and ¹H NMR spectroscopic analysis we proposed that urea, at low concentrations, directly interacts with the protonated histidines of the active center of RNase A, following a simple model of competitive inhibition. These results were supported by theoretical analysis based on the frontier molecular orbital theory and suggest that urea might establish a favorable interaction with the cationic amino acids. Our experimental evidence and theoretical analysis indicate that the initials steps of the molecular mechanism of Urea–RNase A interaction passes through the establishment of a three center four electron adduct. Also, our results would explain the observed disruption of the ¹H NMR signals corresponding to H12 and H119 (involved in catalysis) of the RNase A studied in the presence of urea. Our interaction model of urea–amino acids (cationic) can be extended to explain the inactivation of other enzymes with cationic amino acids at the active site.     

Prevalencia de sobrepeso y obesidad en niños y adolescentes de 2 a 16 años

ObjectivesTo estimate the prevalence of obesity and overweight in children and adolescents in our city and to investigate the associated factors.Subjects and methodsA cross-sectional study of 1317 children and adolescents aged 2-16 years. Multistage probability sampling was used to select three groups of subjects: 411 aged 12 to 16 years, 504 aged 6 to 12 years, and 402 aged 2 to 6 years. Body mass index was calculated, and obesity and overweight were diagnosed using the threshold levels of the International Obesity Task Force for children and adolescents. Parents were asked about eating habits, health, social, and demographic aspects. Results are given as percentages (95% confidence interval). The relationship between obesity and overweight and the different variables was studied using multiple logistic regression. The adjusted odds ratio (OR) was calculated.ResultsAmong children and adolescentes aged 2-16 years, 9.5% (8.0%-11.0%) were obese and 22.4% (23.3%-24.6%) were overweight. Of subjects aged 12-16 years, 8.5% (5.9%-11.2%) were obese and 20.5% (16.7%-24.3%) were overweight. In the groups aged 6-12 years and 2-6 years, rates of obesity and overweight were 11.6% (8.9% -14.3%) and 31.0% (27.0-35.0) and 8.0% (5.4%-10.6%) and 13.6% (10.3%-16.9%) respectively. Obesity or overweight was associated to age (OR 1.21; P< 0.001), maternal obesity (OR 10.99; P= 0.008), a birthweight higher than 4 kg (OR 2.91; p 0.002), and formula feeding (OR 1.82; P= 0.005).ConclusionObesity and overweight in children and adolescents are highly prevalent problems in our city.     

Aportaciones de los tests de supresión de cortisol al conocimiento de los trastornos psiquiátricos: revisión narrativa de la literatura

Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1 mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for deteting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis.Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker.     

Saponins from the roots of Chiococca alba and their in vitro anti-inflammatory activity

Five triterpenoidal saponins were isolated from the roots of Chiococca alba (L.) Hitchc. (Rubiaceae). Two of the saponins, chiococcasaponin III (3-O-β-d-glucopyranurosyl-3β-hydroxyolean-12,15-dien-28-oic acid 28-O-β-d-xylopyranosyl (1 → 4)-α-l-rhamnopyranosyl (1 → 2)-α-l-arabinopyranosyl ester) and chiococcasaponin IV (3-O-β-d-glucopyranurosyl-3β-hydroxyolean-12,15-dien-28-oic acid 28-O-α-l-rhamnopyranosyl (1 → 2)-α-l-arabinopyranosyl ester) were new and their structures were elucidated on the basis of extensive application of NMR techniques and high resolution electrospray mass spectrometry together with acid hydrolysis product analysis. As part of our investigations on the chemical profile and pharmacological activity of the roots of C. alba, we report the results of the evaluation of the activity of the saponin fractions against in vitro lipopolysaccharide-induced inflammation. The results found, strongly support the fractions I, III and IV as having anti-inflammatory properties.