Journal de bioanalyse et de biomédecine

More than 100 years have passed by since the first description of AD by Alois Alzheimer; however the patients, presently; are dying in the same way in spite the technological advance. Our finding of the previously unknown capacity of the melanin´s human body to split and reform the water molecule, appointed as human photosynthesis by its analogies with photosynthesis in plants; constitutes a disruptive advance in the knowledge because means that glucose is not a source of energy, instead it is a biomass source only. If really glucose were a source of energy, then diabetic patients should be able to fly. It is out of discussion that glucose is the ideal building block; our body even makes nucleic acids with it. But energy, (anything that makes a change) is astonishingly taken from water. AD is an energy problem, not a biomass trouble. In this speech we are presenting the concept, the basis and the amazing therapeutic results in Alzheimer´s disease that the medical enhancement of Human Photosynthesis can give. Therefore the role of the CSF must be rethought due that water is so far the main source of energy of the CNS and the cerebral sulcus the best way to keep a close contact between neurons and water, therefore to the neuron cell water constitutes a source of energy that is easily affordable through the subarachnoid space and the ventricles. From now in ahead, the sacred role of glucose as source of energy is broken into small pieces. Human photosynthesis is a turning point in the understanding and treatment of the plague of the XXI century, the Alzheimer´s Disease.

The human hemoglobin (Hb) molecule (α₂β₂) has two types of α–β interface (i.e., α₁–β₁[and α₂–β₂] and α₁–β₂[and α₂–β₁]). The latter α₁–β₂(and α₂–β₁) interface is associated with cooperative O2 binding, and exhibits principal roles if the molecule goes from its deoxygenated to oxygenated quaternary structure. The role of the former α₁–β₁(and α₂–β₂) interface has been unclear for a long time. In this regard, important and intriguing observations have been accumulating, so that a new gaze can be focused on the α₁–β₁(and α₂–β₂) interface. Our most recent findings suggest that the α₁–β₁(and α₂–β₂) interface may exert delicate control of the intrinsic tilting capability of the distal (E7) His residues (i.e., α58His (E7) in the α chain and β63His (E7) in the β chain) depending on internal and external conditions of the erythrocyte to lead to degradation of Hb to hemichrome, and subsequent clustering of Heinz bodies within the erythrocyte. In the spleen, rigid intra-erythrocytic hemichrome inclusions (Heinz bodies) act as “sticking points”, so Heinz body-containing red cells become trapped and undergo hemolysis. In this article, we first provide our necessary basic experimental findings that led us to grasp molecular biosensing mechanisms inherent in human erythrocytes for the appreciation of aging and determination of their lifespan, and summarize their roles in physiology. We then discuss how these accomplishments contribute to deeper understanding of clinical aspects of drug-induced hemolytic anemia, defects in the intra-erythrocytic reducing system and unstable Hb disease, in which the mechanisms for acute hemolytic crisis cannot be explained on the basis of conventional views.

Introduction: Hepatic Ischemia-Reperfusion (I/R) injury contributes to organ injury and dysfunction after hepatic surgery and transplantation. I/R induce Kupffer cell activation, leading to the release of pro-inflammatory cytokines that promote injury, increase adhesion molecule expression, and facilitate polymorphonuclear neutrophil injury. Inularacemosa contains high concentrations of the flavonol glycosides, which has been shown effect on cardiac function and oxidative stress against isoproterenol – induced myocardial infarction. Historically, the roots were reputed to have Anti-inflammatory and Analgesic effects. The hepatoprotective activity of the drug against hepatic Ischemia/Reperfusion injury has not been reported yet.

Objective: To study the hepatoprotective effect of hydroalcholic extract of Inularacemosa at 200 and 400 mg/kg against hepatic ischemia/reperfusion injury.

Methodology: 24 male wistar rats were divided in to four groups. The normal control group, model control group and extract treated group at a dose of 200 and 400 mg/kg were orally fed with distilled water as vehicle for 21 days followed by ischemia/reperfusion on twenty second day. Blood and liver samples were obtained from all the animals on 22nd day for biochemical analysis of AST, ALT, ALP and LDH and histopathological studies were also performed.

Results: The results showed that the ischemia/reperfusion injury causes significant increase in the levels of AST, ALT, ALP and LDH in model control group indicating the cell damage and tissue injury whereas supplementation with hydroalcholic extract of Inularacemosa significantly reduced the elevated levels of above parameters. Histopathological analysis showed high degree of congestion and mild necrosis in model control group which was reduced to minimum levels in drug treated groups. Inularacemosa increased the free radicals scavenging activity in the early period of hepatic IR injury in rats.

Conclusion: Reduced level of liver enzymes and histopathological studies evident that Inularacemosa possesses beneficial effects on the hepatocytes in hepatic I/R injury.

Systemic hormone therapy of breast cancer often suffers from severe side effects mainly due to non-specific drug delivery. To overcome this limitation, we propose an effective strategy based on the association of the selective estrogen receptor down-regulator RU-58668 (RU) that acts as a pure hormone antagonist, with magnetic-fluidloaded liposomes (MFLs) which can be driven selectively into the tumors by a magnetic field gradient. MFLs consisted in 200-nm unilamellar phospholipid vesicles entrapping superparamagnetic iron oxide nanocrystals, fluorescently labeled and coated by poly(ethylene glycol) (PEG) chains ensuring long plasmatic half-life. Significant antitumoral activity of antiestrogen at doses usually sub-therapeutic was demonstrated against MCF-7 tumors xenografts in nude mice after weekly intravenous administration of RU-loaded MFLs followed by 4-hour exposure
to an external 0.44-T magnet (155 T/m magnetic field gradient). The magnetic accumulation of RU-MFLs at the origin of improved antitumor activity was checked in vivo by MRI using the magnetic fluid as intrinsic contrast agent, fibered confocal fluorescence microscopy to track the lipid vesicle structures, ex-vivo tumor histology by confocal fluorescence microscopy or iron oxide staining, and KI-67 immunostaining to reveal RU anti-proliferative activity. Our findings establish that magnetic targeting results in significant therapeutic benefit by highly concentrating RUloaded liposomes in the tumor tissue according to amplified EPR effect and significantly enhanced drug delivery at the intracellular level. The use of superparamagnetic liposomes to target magnetically estrogen antagonists offers a reliable direction to treat hormone-dependent breast tumors with possible combination of MRI diagnosis.

Here, we report spectrophotometric method for the determination of gabapentin through charge transfer complexes with σ and π acceptors and also with dye stuffs. The method involves ion-pair complex formation of gabapentin with ninhydrin, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyanoethylene, methyl orange and picric acid. The optimum conditions for the reactions and validation of described procedure have been studied. Resulting complexes absorb at 580, 315, 340, 464 and 342 nm in the Beer’s law range of 2-22, 32-80, 40-360, 12-96 and 15-135 μg mL-1 with correlation coefficient greater than 0.998 in each case respectively. The proposed method was applied successfully for the determination of gabapentin in pharmaceutical formulations. Satisfactory recovery values suggest that the method is reliable for the determination of gabapentin in pharmaceutical formulations without interference of excipients. In addition, the spectral characteristics including oscillator’s strength, dipole moment, ionization potential, energy of complexes, resonance energy and also the thermodynamic parameters i.e. association constant and Gibb’s free energy changes have been determined. Benesi-Hildebrand plots for each complex have been constructed. Further, solid charge transfer complexes of gabapentin were synthesized and characterized by IR spectroscopy.