Characterization of Changes due to pH Variations in Beta Peptide (25–35) Leading to Alzheimer’s Disease

International Journal of Peptide Research and Therapeutics - The effect of various concentrations of amyloid beta peptide (ABP) in different pH (pH 2, 6, 7, 8, 10) in aging at different time...     

Role of Arogh, a polyherbal formulation to mitigate oxidative stress in experimental myocardial infarction

Antioxidant role of Arogh in isoproterenol induced myocardial infarction in rats has been studied. The activity of heart tissue antioxidants like glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase were significantly decreased in isoproterenol administered group. The activity of ceruloplasmin and levels of glutathione, vitamins E and C were also found to be substantially decreased in serum with a concomitant rise in lipid peroxide levels after isoproterenol exposure to rats. The synergistic effect of Arogh pretreatment, significantly suppressed the alterations induced by isoproterenol alone in rats.     

Antinociceptive pattern of flavone and its mechanism as tested by formalin assay

Flavone, dextrose and long swim stress exhibited antinociception. Degree of antinociception was greater with long swim stress as compared to flavone or dextrose. Combination of these treatments resulted in potentiation of antinociception. Naloxone (opioid antagonist; 5 mg/kg i.p.) antagonised flavone or long stress induced antinociception showing opioid medicated mechanism, however, failed to reverse the potentiated antinociceptive component recorded in long stressed animals which received flavone and dextrose. Antinociceptive activity of flavone, dextrose and long swim stress which was documented by acetic acid assay has been confirmed in the present study. Role for opioid system in this action has been demonstrated. Therefore, formalin test can also be considered as an useful assay procedure for testing flavonoids. However, like acetic acid assay this assay procedure also has the limitation that it is unable to detect minor changes in the degree of antinociception produced by physiological interventions such as long swim and dextrose.     

Crystal structures of disordered Z-type helices

The X-ray crystal structures of a decamer sequence d(CGCGTACGCG)₂ and a tetradecamer sequence d(CGCGCGTACGCGCG)₂ are presented here. Both sequences are alternating pyrimidine-purine repeat sequences and they form disordered, pseudo-continuous left handed Z-type helices. They demonstrate interesting variants of the ‘bundles of columns of helices’ mode of packing.     

Modulation by insulin rather than blood glucose of the pain threshold in acute physiological and flavone induced antinociception in mice

The present study investigated the cause effect relationship between glycemic and algesic states. The hypo- and hyperglycemic conditions were induced physiologically through exercise (3 min swim at room temperature 28 degrees - 30 degrees C) and external dextrose (2 g/kg, ip) administration respectively in mice. Besides, flavone (50 mg/kg, sc) a known antinociceptive drug was chosen to study such a cause effect relationship. The anti-nociception was assessed by acetic acid assay, blood glucose measured using glucometer (Ames) and serum insulin by radioimmunoassay. The findings revealed that irrespective of the glycemic state whether hypo-, hyper, or euglycemic induced by swim stress, dextrose or flavone per se respectively, significant antinociceptive response was recorded. Pretreatment with flavone (50 mg/kg, sc) always exhibited a tendency to reverse the hyperglycemia, if any, but enhanced the antinociceptive response either after swim stress or after dextrose. These data support the contention that changes in the glycemic state in acute condition is not responsible for antinociceptive response and thereby suggesting dissociation between these two parameters. Extended studies estimating serum insulin level after the above mentioned maneuvers showed a significant rise whenever antinociceptive response was recorded irrespective of the glycemic state. It is suggested that serum insulin level, a hormonal parameter rather than the blood glucose level, which is a metabolic parameter, appears more reliable. It appears that the changes in serum insulin level produced by various treatments may have a relationship with the antinociceptive response. However, this study has the limitation that the results can apply only for acute conditions and extrapolation to clinical conditions is debatable.     

Comparison of X-ray crystal structures of a tetradecamer sequence d(CCCGGGTACCCGGG)2 at 1.7 Å resolution

We present here a comparison of three different X-ray crystal structures of DNA tetradecamer sequence d(CCCGGGTACCCGGG)₂ all at about 1.7 Å resolution. The sequence was designed as an attempt to form a DNA four-way junction with A-type helical arms. However, in the presence of zinc, magnesium, and in the absence of any metal ion, it does not take up the junction structure, but forms an A-type double helix. This allowed us to study possible conformational changes in the double helix due to the presence of metal ions. Upon addition of the zinc ion, there is a change in the space group from P4₁2₁2 to P4₁. The overall conformation of the duplex remains the same. There are small changes in the interaction of the metal ions with the DNA. In the zinc-bound structure, there are two zinc ions that show direct interaction with the N7 atoms of terminal G₁₃ bases at either end of the molecule. There are small changes in the interhelical contacts. The consequence of these differences is to break some of the symmetry and change the space group.