Classification of drug molecules for oxidative stress signalling pathway

In humans, oxidative stress is involved in the development of diabetes, cancer, hypertension, Alzheimers’ disease, and heart failure. One of the mechanisms in the cellular defence against oxidative stress is the activation of the Nrf2‐antioxidant response element (ARE) signalling pathway. Computation of activity, efficacy, and potency score of ARE signalling pathway and to propose a multi‐level prediction scheme for the same is the main aim of the study as it contributes in a big amount to the improvement of oxidative stress in humans. Applying the process of knowledge discovery from data, required knowledge is gathered and then machine learning techniques are applied to propose a multi‐level scheme. The validation of the proposed scheme is done using the K‐fold cross‐validation method and an accuracy of 90% is achieved for prediction of activity score for ARE molecules which determine their power to refine oxidative stress.Inspec keywords: cancer, cellular biophysics, biochemistry, drugs, molecular biophysics, proteins, learning (artificial intelligence), medical computingOther keywords: oxidative stress, Nrf2‐antioxidant response element signalling pathway, ARE signalling pathway, diabetes, cancer, hypertension, Alzheimers’ disease, heart failure, machine learning techniques, K‐fold cross‐validation method, ARE molecules     

Blood mercury in workers exposed to the preparation of mercury cadmium telluride layers on cadmium telluride base

Study was conducted in a group of 32 persons engaged in liquid phase epitaxial growth of mercury cadmium telluride (MCT) layers for nearly 11 years. Airborne mercury concentrations in work environment have been exceeding the threshold limit value of 0.05 mg/m3 recommended by ACGIHD. Hg concentration in workplace during peak working hours remained between 0.04-0.08 mg/m3. Findings were compared with 32 unexposed referents. Mercury value was estimated 1.60 +/- 0.20 (mean +/- SD) in control, and in Phase I and II, 10.72 +/- 1.34 ng Hg/ml and 8.08 +/- 1.15 ng Hg/ml of blood respectively. Results indicate a fall in blood mercury level during the second phase of study. But the values did not return to normal even after a gap of 3 months. An individual who met with a mercury accident showed 226 ng Hg/ml of blood which decreased to 25 ng/ml after 3 months. It is inferred from the present study that Hg level has increased significantly in MCT workers during working period, and also in non-working period, the values were higher than controls.     

Spectral engineering of terahertz quantum cascade lasers using focused ion beam etched photonic lattices

Focused ion beam etching has been used to introduce one-dimensional photonic lattices, of periods 9.11, 9.24, 9.44 /spl mu/m, between the cleaved facets of three 4.44 THz Fabry-Perot quantum cascade lasers. Singlemode lasing has been achieved at precisely defined wavelengths of 67.59, 68.48, 70.00 /spl mu/m, respectively.     

Metanil yellow: a bifunctional inducer of hepatic phase I and phase II xenobiotic-metabolizing enzymes

Metanil yellow, a non-permitted food colour, has been found in various foodstuffs. The induction potential of metanil yellow on hepatic microsomal cytochrome P-450 (P-450)-dependent monooxygenases and cytosolic detoxification enzymes, namely, glutathione S-transferase (GST) and quinone reductase (QR), was investigated. Oral administration of metanil yellow (430 mg/kg body weight) to four animals for seven days caused significant induction of hepatic P-450 (48%) and its dependent aryl hydrocarbon hydroxylase (100%) activity and cytosolic GST (136%) and QR (92%) activities. Parenteral administration of metanil yellow (80 mg/kg body weight) to another set of four animals for 3 days resulted in higher induction of ethoxyresorufin-O-deethylase (228%) as compared to other monooxygenases (64-92%), while GST and QR were also found to be induced (59-95%). Spectra of metanil yellow-induced microsomes showed an increase in P-450 with a shift of 2.2 nm in the soret region. The results suggest that metanil yellow acts as a bifunctional inducer of specific isozymes of P-450 and cytosolic enzymes and thus may involve the cytosolic aryl hydrocarbon (Ah) receptor for this type of induction.     

Determination of rifampicin and isoniazid in pharmaceutical formulations by HPLC

A liquid chromatographic procedure for the analysis of Rifampicin (RIF) and Isoniazid (INH) in pharmaceutical dosage forms utilizing reverse phase chromatography was developed. Isolation of analytes was carried out under isocratic conditions with a octadecylsilane column and an aqueous mobile phase containing Methanol (75%) and 0.02 M Disodium Hydrogen Orthophosphate (25%) with pH 4.5 adjusted with orthophosphoric acid. The detection was done at 254 nm.

The method is unique in analysing Rifampicin precisely in combination with Isoniazid particularly in liquid formulation. The method is specific and can distinctly isolate the degradation product in suspension.     

Landau parameters and thermodynamic properties of liquid helium II

The variation of the Landau parameters with density and hard-core diameter is calculated for liquid helium using interparticle potentials composed of a hard core followed by a combination of a repulsive and an attractive Gaussian potential, and a hard core followed by a Lennard-Jones potential. Calculations are done only for high-density boson systems. The calculations of specific heat and entropy show good agreement with the experimental results in the very low-temperature region (T<1.0 K) and for the Gaussian potential only.     

Severe hypercalcemia caused by Milk‐Alkali syndrome requiring urgent hemodialysis – Tums by the ton

An increased frequency of the Milk‐Alkali syndrome in the last several years has been noticed related to increasing use of calcium carbonate as a phosphate binder in CKD patients, as an antacid or as calcium supplementation. We present a case of severe hypercalcemia secondary to Milk‐Alkali syndrome that precipitated acute renal failure requiring urgent hemodialysis. A 59-year‐old male with history of hypertension, diabetes mellitus, and acid reflux presented to the ER with confusion, lethargy, nausea, vomiting, and diarrhea. His family relayed a history of recent indigestion and relief with Tums. He was taking several tablets at short intervals to self‐treat the indigestion. At the time of presentation, patient was confused and noted to be dehydrated. Lab findings were significant for elevated BUN/Cr‐ 121 mg/dl/11.1 mg/dl (baseline Cr 1.1 mg/dl few months ago), bicarbonate 38 mg/dl, calcium 16.7 mg/dl, ionized Ca of 1.76 mmol/L, iPTH 10 pg/ml, PTHrP 0.7 pg/ml. Medical management with intravenous fluids and furosemide showed no improvement in renal failure, or calcium level. Patient was then started on hemodialysis with 2.0 mmol/L calcium in the dialysate the next day. There was gradual improvement in patient's mental status, calcium values, and renal failure over the ensuing 2 weeks.
Discussion and Conclusions:  The diagnosis of Milk‐Alkali syndrome is made on the basis of history. Metabolic abnormalities involved in this syndrome are hypercalcemia with low to normal PTH and Vit. D levels, renal failure, and metabolic alkalosis. Failed medical management required acute dialysis in this patient. Acute hemodialysis in such a case could be life saving. Due to increasing use of calcium carbonate for dyspepsia and osteoporosis, patients should be made aware of these severe, potentially life-threatening adverse effects.     

Evolutionary dynamics of genetic variation in Epstein-Barr virus isolates of diverse geographical origins: evidence for immune pressure-independent genetic drift

The question whether immune pressure exerted by cytotoxic T lymphocytes (CTLs) can influence the long-term evolution of genetically stable viruses such as Epstein-Barr virus (EBV) has generated considerable scientific interest, primarily due to its important implications for the overall biology of the virus. While arguing for a role of CTLs in the evolution of viruses, it is important to differentiate between genetic variation in virus and immune recognition of these variant virus by CTLs. To assess the role of genetic selection in the long-term evolution of EBV, we have analyzed a large panel of type 1 EBV isolates from African, Southeast Asian, Papua-New Guinean (PNG), and Australian Caucasian individuals. Seven different regions of the EBV genome, which include nine CTL epitopes restricted through a range of HLA class I alleles, were sequenced and compared. Although numerous nucleotide changes were identified within these isolates, comparison of synonymous and nonsynonymous substitutions in the CTL epitope indicated that the genetic variation was generated mostly independently of immune selection pressure. Surprisingly, an inverse correlation between genetic variation within certain CTL epitopes and the frequency distribution of HLA alleles that present the CTL epitopes was seen, suggesting that the evolutionary pressures on the CTL epitopes of the virus may be toward their conservation rather than their inactivation. Furthermore, molecular evolutionary genetic analysis of nucleotide sequences revealed that viral isolates from PNG are evolving as a lineage distinct from isolates from African, Southeast Asian, and Australian Caucasian individuals.