Química Medicinal

Theexternal electrostatic field (ESF) leads to an increase of oxidative modification of proteinsand lipids in blood and in other tissues, as well as to changes in activity of pro- and anti-oxidative enzymes. The mechanism of such a response to the exposure of this physical factor is not well understood. In this paper the data on the influence of external ESF of 200 kV/m on carbonylation of plasma proteins and hemolysis of blood in vitro are presented. In order to clarify the role of blood cells in the development of oxidative processes in the plasma, ESF exposures were applied both to the whole blood and to the prior obtained plasma. In addition, samples were placed in closed and in open tubes, which allow to determine the role of air oxygen and air ions in the development of expected processes. It was shown that under the influence of external ESF plasma proteins’ carbonylation increased only when the whole blood was exposed to ESF and not the plasma alone. This indicates that the pro-oxidative processes, observed in plasma after ESF exposure, are mediated by the blood cells. Further, lysis and deformation of red blood cells were observed. Moreover, the deformation of red blood cells was most pronounced around monocytes and polymorph nuclear leukocytes, indicating the importance of these cells in the observed processes. The free air exchange had no significant effect on the results of experiments. Thus, in vitro experiments have shown that the effects of an ESF to oxidative processes in blood have been likely mediated by the activation of phagocytes independently from air ionization.

In-depth chromatographicinvestigation on the hexane extract of Byrsonima crassifolia led to the identification of eight new guaianolides. Structural elucidation was established on the basis of spectral data as; byrsonina C (1) to byrsonina J (8). In vitro inhibitory activity of the 1-8 on advanced glycationend products (AGEs), analysis of protein gels (SDS-PAGE) profile and by matrix assisted laser desorption ionization (MALDI) coupled to time of flight (TOF) analyzers mass spectra (MALDI lineal TOF MS) were evaluated. Guaianolides exhibited glycation inhibitory activity similar to that of aminoguanidine. The major mechanism implied in the inhibition of protein glycation by compounds 1-8 was attributed to their ability to react with carbonyls. SDS-PAGE profiles displayed inhibition of AGE generation, through inhibition of the crosslinked formation of AGEs, which was detectable for MALDI linear TOF MS as an intensity reduction of the dimerized band. We conclude that guaianolidesfrom Byrsonima crassifolia can efficiently inhibit AGEs formation and oxidative damage elicited by monosaccharides, suggesting that may prevent AGEs-mediated interaction with multiple targets involved in the pathogenesis of diabetes.

A serendipitous observation during a student class practical with liquid nitrogen led me to propose that a variant of cubic ice crystallizingon the silica helium thermometer bulb had distorted it. Pauling argued the H-bonds in hexagonal ice retain entropy at 0K. Recent evidence for a ferroelectric transition in ‘ice XIc’ at ~72 K validates that suggestion. This paper introduces a lifetime’s research based on three axioms:

1. Proton ordered ice crystallized in liquid nitrogen undergoes a ferroelectric transitionat ~72 K releasing latent energy as ~4μ laser light, ‘ice light’, matching phosphodiester bond energy.

2. Ice crystallizing in liquid nitrogen on Earth's poles during a primordial ice age released ice light. Polarised by multiple reflectionin ice clouds and surface ice, it photo-phosphorylated nucleotidesin tropical waters, creating a ‘noodle soup’ of chiral DNA. Some formed ‘transport DNA’s, tDNAs, tRNA analogues.

3. tDNAs used an ice light powered mechanism to actively transported substrates into Oparin’s ‘coacervate’ proto-cells.

The resulting model for the origin of life makes predictions consistent with scientific research. Applying evolutionary and thermodynamicprinciples reveals life’s atomic alphabet, molecular vocabulary and metabolic grammar, predating protein synthesis evolving. It offers new perspectives on metabolism, bioenergetics, genetics, endocrinology and tissue differentiation:

• Dietary prevention of health disorders including: heart attacks, cancers, diabetes and Alzheimer’s disease.

• Energy coupling for N-fixation and power generation.

• Medical diagnosis pre-empting pharmaceutical interventions.

‘Minions’, DNA-protein complexesevolved to pack chromosomes and facilitate their replication, are bound by proton ordered H-bonds using a 63-character alphabet to store information as 18-letter words. Similar words resonate and nerve fibres act as wave guides, explaining brain function. Trace element supplements and AI modelled on ‘minions’ could improve health and create user-friendly IT. These proposals are consistent with science, philosophy and tradition.

Glutathione-Homocystine Transhydrogenase (GHTHase) was characterized from Aspergillus flavipes as a novel enzymeof high specificity to reduce homocystine to homocysteine using GSH as hydrogen donor. GHTHase was further conjugated to mono-functional carboxyl polyethylene glycol (PEG) to improve its catalytic properties for various therapeutic uses especially against homocystinuria. The biochemical properties of free and PEG-GHTHase were assessed. The enzyme molecular mass was increased by 1.2 % (from 80 to 95 kDa) by PEG conjugation. The free and PEG-GHTHase have the same pH stability (6.5-8.0) and thermal stability (T1/2 1.0-1.3 h, at 50°C). Kinetically, the affinity and catalytic efficiency of PEG-GHTHase was decreased by 15% to GSH as hydrogen donor for reduction of homocystine than free enzyme. PEG-GHTHase has a slightly stability for suicide inhibitor as propargylglycine, hydroxylamine and iodoacetate. Upon proteolysis, the free enzyme retains less than 10% of its initial activity, comparing to 85.8 % of PEG-GHTHase upon trypsinand acid protease digestion for 30 min in vitro. From the pharmacokinetics properties in New Zealand rabbits, the half-life time of free and PEG-GHTHase was 10.0-12.2 h. Upon external infusion of NADH (20 μM) after 24 h of initial enzymes dosing, the half-life times of the enzymes were increased to 10 h. The biochemical and hematological parameters upon enzymes infusion were relatively not affected along the tested period. In vivo, GHTHase exhibits higher affinity to methionine and cysteine. Based on in vitro and in vivo biochemical properties, PEG-GHTHase could be a reliable enzyme in reduction of homocystine using GSH as electron donor. We assume, with more crystallographic studies, that GHTHase will be a new finding against various disorders-dependent homocystinuria.

Background: Allopathic physicians are relatively unfamiliar with Complementary and Alternative Medicine (CAM) but they’re in common use. A cross sectional survey was conducted to understand physician’s perception of it.

Method: All 385 physicians from St. John’s Medical College & Hospital, Bangalore were approached. Data were collected using anonymised questionnaires on its use, perceptions, recommendation and inclusion in medical curricula. Responses were analysed according to their experience (<5, 5-10 & >10 years) and qualifications (specialists with: MD, MS, MCh, DM, Diploma or GPs with MBBS and Fellowship).

Results: Responses were received from 247 (64%) of physicians. 173/38/36 (70/15/15%) had <5/5-10>10 years’ experience, half were specialists, half GPs. Their mean age was 33 years, 114 (46%) were males. 168/169/152/133/91/84 (68/68/53/54/37/34/27%) reported their patients used CAM for chronic diseases/consult their patients about CAM/said their patients informed them about it/considered it may be useful but harmful/that it increases side effects of allopathic medication/ that it worsens the condition. 67 (27%) physicians recommended it. Yoga/meditation, 57/47 (23/19%) were commonest. Most, 97/143/154/98 (39/58/62/40%) disagree with using it when allopathyis ineffective/disagree with including it in medical curricula/disagree on training doctors about it/do not recommend it.

Conclusion: CAM is used ubiquitously, especially for chronic diseases. Allopathic doctors need knowledge about them and their appropriate use for better outcomes.

Quartz Crystal Microbalance (QCM) is known as a surface sensitive analytical device capable of on-line monitoring of interfacial reactions. To study the interaction between interleukin-6 (IL-6) and its soluble receptor (sIL-6R), as well as the effects of propyl gallate on IL-6/sIL-6R binding based on it, a QCM was employed to monitor the binding responses. In the experiments, sIL-6R was immobilized on the surface of QCM substrate, then different concentrations of IL-6 were added onto the substrate, respectively. The response frequency shift caused by the binding between IL-6 and sIL-6R was recorded. The results showed that sIL-6R was immobilized on the substrate surface with the density of 3.43 ng/mm2, IL-6 then bound to the immobilized sIL-6R specifically. FAST fit program was used to analyse the data obtained of the association of IL-6 and immobilized sIL-6R, fitting it to the biphasic kinetic equations. Kinetic constantsfor IL-6 binding to sIL-6R were determined from the plots of Kon versus the concentration of IL-6, kass=3.41×104 M-1 s-1, kdiss=1.80×10-2 s-1, thus, KD=5.28×10-7 M, KA=1.89×106 M-1. Furthermore, the effects of propyl gallate (PG) on interaction of IL-6 with sIL-6R were studied. The results showed that PG was able to enhance the binding between IL-6 and sIL- 6R. We propose that the interaction between IL-6 and sIL-6R is one of the targets which PG can act on in vivo. The QCM offers an effective way and a new clue to the study on the mechanism of propyl gallate at molecular level.