A study of paraoxonase1 (PON1) activities,HDL cholesterol and its association with vascular complication in type 2 diabetes mellitus

The aim of this study is to find out the clinical relevance of estimating serum paraoxonase1 (PON1) arylesterase and PON1 lactonase activity in type 2 diabetes mellitus patients in relation to the development of vascular complications. We have investigated the fasting blood glucose level, HDL cholesterol levels, PON1 arylesterase and PON1 lactonase activities in 80 type 2 diabetes mellitus (DM) patients (DM without complication n?=?40, DM with vascular complication n?=?40) and compared with 40 healthy age- and sex-matched controls. PON1 arylesterase (ARE) and lactonase (LACT) activities in DM patients with complications (ARE?=?60.615?±?15.510 KU/L, LACT?=?18.056?±?4.215 U/L) are decreased significantly than in DM without complications (ARE?=?93.507?±?21.813 KU/L, LACT?=?32.387?±?8.918 U/L) which are also decreased significantly as compared to controls (ARE?=?159.94?±?45.87 KU/L, LACT?=?50.625?±?6.973 U/L). Logistic regression analysis is applied for assessing predictive utility for diabetic complications demonstrated a significant contribution of PON1 lactonase (Naglekerke’s R ²?=?0.625, AUC?=?0.907) and arylesterase (Naglekerke’s R ²?=?0.427, AUC?=?0.853) activities. Decreased PON1 lactonase and arylesterase activities may be considered as an additional risk factor for the development of vascular complications in type 2 DM.     

Melatonin and serotonin: Mediators in the symphony of plant morphogenesis

Melatonin and serotonin are important signaling and stress mitigating molecules that play important roles across growth and development in plants. Despite many well‐documented responses, a systematic investigation of the entire metabolic pathway (tryptophan, tryptamine, and N‐acetylserotonin) does not exist, leaving many open questions. The objective of this study was to determine the responses of Hypericum perforatum (L.) to melatonin, serotonin, and their metabolic precursors. Two well‐characterized germplasm lines (#4 and 112) created by mutation and a haploid breeding program were compared to wild type to identify specific responses. Germplasm line 4 has lower regenerative and photosynthetic capacity than either wild type or line 112, and there are documented significant differences in the chemistry and physiology of lines 4 and 112. Supplementation of the culture media with tryptophan, tryptamine, N‐acetylserotonin, serotonin, or melatonin partially reversed the regenerative recalcitrance and growth impairment of the germplasm lines. Quantification of phytohormones revealed crosstalk between the indoleamines and related phytohormones including cytokinin, salicylic acid, and abscisic acid. We hypothesize that melatonin and serotonin function in coordination with their metabolites in a cascade of phytochemical responses including multiple pathways and phytohormone networks to direct morphogenesis and protect photosynthesis in H. perforatum.     

Prediction of biological behaviour of human breast cancer using multiple parameters. A preliminary study

Prediction of early metastases in individual patients has been attempted by combined evaluation of a battery of recognised parameters such as blood vessel invasion (BVI) of tumor cells, Barr body frequency (BBF), plasminogen activator (PA), collagenase, estradiol receptors (ER), progesterone receptors (PgR), and peroxidase activity (PRA) in 18 malignant and 3 benign (control) breast tumors. Since breast tumor cells spread through the blood vessels, the cases were divided into BVI (+) and BVI (-) groups. Results show that in the former group, all the cases had poor prognosis and two even had distant metastases within one year. In BVI (-) group, 9 out of 12 appeared to have good prognosis.     

Locating the functional and anatomical boundaries of human primary visual cortex

The primary visual cortex (V1) can be delineated both functionally by its topographic map of the visual field and anatomically by its distinct pattern of laminar myelination. Although it is commonly assumed that the specialized anatomy V1 exhibits corresponds in location with functionally defined V1, demonstrating this in human has not been possible thus far due to the difficulty of determining the location of V1 both functionally and anatomically in the same individual. In this study we use MRI to measure the anatomical and functional V1 boundaries in the same individual and demonstrate close agreement between them. Functional V1 location was measured by parcellating occipital cortex of 10 living humans into visual cortical areas based on the topographic map of the visual field measured using functional MRI. Anatomical V1 location was estimated for these same subjects using a surface-based probabilistic atlas derived from high-resolution structural MRI of the stria of Gennari in 10 intact ex vivo human hemispheres. To ensure that the atlas prediction was correct, it was validated against V1 location measured using an observer-independent cortical parcellation based on the laminar pattern of cell density in serial brain sections from 10 separate individuals. The close agreement between the independent anatomically and functionally derived V1 boundaries indicates that the whole extent of V1 can be accurately predicted based on cortical surface reconstructions computed from structural MRI scans, eliminating the need for functional localizers of V1. In addition, that the primary cortical folds predict the location of functional V1 suggests that the mechanism giving rise to V1 location is tied to the development of the cortical folds.     

The acquisition and application of absorption, distribution, metabolism, and excretion (ADME) data in agricultural chemical safety assessments

A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. Incorporation of pharmacokinetic studies describing absorption, distribution, metabolism, and excretion is an essential tool for improving the design and interpretation of toxicity studies and their application for safety assessment. A tiered approach is described in which basic pharmacokinetic studies, similar to those for pharmaceuticals, are conducted for regulatory submission. Subsequent tiers provide additional information in an iterative manner, depending on pharmacokinetic properties, toxicity study results, and the intended uses of the compound.     

Malignant peripheral nerve sheath tumors of the head and neck: A clinicopathological study

Twenty-seven cases of malignant peripheral nerve sheath tumors involving the head and neck region over a period of 7 years were reviewed. They were graded from 1–3 based on necrosis, mitosis, cellularity, and pleomor-phism. Mean age of occurrence was 42 years, with a range of 12–70 years. Male preponderance was noted (M:F = 3.5:1). The most common site of involvement was the neck (44.6%). The main presenting symptom was an enlarging mass. The nerve of origin could be identified in 33% of patients. Treatment consisted of wide excision. The 5-year observed survival was 33%. Fifty-two percent of patients developed local recurrence of disease. Fifteen percent of patients died due to advanced local disease within 18 months of treatment. Distant metastasis was seen in 18.5% of patients. Lymph node metastasis was not seen. At the end of 5 years 15% of patients remained disease free. Large tumor size (>5 cm) adversely affected the prognosis (P = < 0.1). No significant correlation was noted between the grade of tumor and survival. © Wiley-Liss, Inc.     

The future lies in chiral purity: a perspective

Racemates are fixed-dose combinations of stereoisomers. Each isomer may have different pharmacokinetic or pharmacodynamic properties. Recent research has allowed appreciation of the need to purify racemates and develop useful unichiral molecules. Some examples are: S-amlodipine besylate, S-atenolol, S-metoprolol succinate, S-pantoprazole sodium and R-ondansetron hydrochloride.     

Utility of subsequent conventional dose chemotherapy in relapsed/refractory transplant-eligible patients with diffuse large B-cell lymphoma failing platinum-based salvage chemotherapy

Up to 60% of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) do not respond to second-line (salvage) chemotherapy and hence are not offered autologous hematopoietic cell transplantation (AHCT). The utility of further salvage chemotherapy in an attempt to proceed with AHCT remains undefined. The authors reviewed 201 patients with DLBCL relapsed/refractory to anthracycline-based chemotherapy who received first-line salvage chemotherapy containing cis-platinum. Of the 120 non-responders to first-line platinum-based salvage chemotherapy, 73 received second-line salvage chemotherapy. The response rate to second-line salvage chemotherapy was 14%. Factors predicting lack of response were progression on primary therapy (p = 0.007), abnormal lactate dehydrogenase findings (p = 0.0027) and tumor bulk (p = 0.013) at second progression. Eight patients who responded received AHCT and appeared to have comparable survival to those transplanted after one salvage regimen. The authors conclude that the utility of second-line salvage chemotherapy is low, and that it is best reserved for patients demonstrating initial anthracycline sensitivity and low tumor burden.