An Investigation into the Role of Insulin in Pain Threshold

Pain is part of our life, existing throughout human development, from birth to death. It is a perception triggered in the nervous system and evoked as a result of external stimuli, disease or tissue damage. Pain is important for survival because it acts as protective and alarm mechanism. According to the International Association for the Study of Pain, it is an unpleasant sensory and emotional experience associated with potential or actual tissue damage.1It is associated with various diseases, inflammatory conditions, tissue damage and surgical interventions. Various factors such as physiological, pathological and psychological are involved in pain perception. In addition to these factors, various chemical substances are involved in the modulation and transduction of pain such as 5-hydroxytryptamine, gamma amino butyric acid, acetylcholine, histamine, bradykinin, substance P, opioid peptides etc. The present study investigated the relation between endogenous insulin level and pain threshold and its interaction with opioid system and diurnal rhythm in animal model using different nociceptive tests and pentazocine as a model drug. We observed significant relation between endogenous insulin level and pain threshold independent of the glycemic status in acetic acid, formalin and tail flick models except in the hot plate model where such a relation seems dependent on the glycemic status. Insulin appears interacting with opioid receptor (kappa receptor) based on the preliminary study by protein-protein docking method. Endogenous insulin positively correlate with pain threshold which was found to be influenced by diurnal rhythm. Endogenous insulin level showed peak in the dark cycle and trough in the light cycle in all the pain models investigated. The study reports for the first time on the involvement of endogenous insulin in pain threshold against different nociceptive tests in animal models. The above findings clearly delineate that there seems to be no direct relation between blood glucose levels and antinociception, however, a possible involvement of endogenous insulin in pain threshold through opioid pathway by binding with kappa receptor which is independent of the glycemic status. The association between endogenous insulin and pain threshold seems dependent on the type of nociceptive stimuli and the endogenous insulin level and pain intensities seems influenced by diurnal rhythm

Nanostructured thermoelectric generator for energy harvesting

This paper presents the development processes towards a new generation of nanostructured thermoelectric generators for power harvesting from small temperature gradients by using a combination of traditional silicon microfabrication techniques, electroplating and submicron ion-track nanolithography. Polyimide nanotemplates with pore diameters ranging from 30nm to 120 nm were fabricated. Preliminary results for Bi2Te3 nanowires (50 and 120 nm diameter) electroplated into polycarbonate ion-track commercial membranes are presented. Bi2Te3 nanowires of R ̄ 3m structure, with preferential orientation in the (015) and (110) crystallographic plans with nearly stoichiometric composition were electroplated. The fine-grained observed microstructure (6-10 nm) and (110) crystalline orientation appear extremely promising for improving thermoelectric material properties

Phosphorous-doped porous carbon derived from paste of newly growing Ficus benghalensis as hydrogen storage material

The synthesis of heteroatom (P)-doped porous carbon derived from the paste of newly growing Indian banyan tree (Ficus benghalensis) is described. The synthesis involves activation, carbonization and phosphorous-doping processes using H3PO4 as activating agent and as phosphorous source. The phosphorous-doped porous carbon material shows a wafer-like morphology with specific surface area of 1406 m²/g. This material exhibits hydrogen storage capacity of ~1.2 wt% at 298 K and 100 bar. This easily prepared carbon material is promising for realistic hydrogen storage

Effect of rifampicin & isoniazid on the steady state pharmacokinetics of moxifloxacin.

BACKGROUND & OBJECTIVES Moxifloxacin (MFX) is reported to have promising antimycobacterial activity, and has a potential to shorten tuberculosis (TB) treatment. We undertook this study to examine the influence of rifampicin (RMP) and isoniazid (INH) on the steady state pharmacokinetics of MFX individually in healthy individuals. METHODS A baseline pharmacokinetic study of MFX (400 mg once daily) was conducted in 36 healthy adults and repeated after one week of daily MFX with either RMP (450/600 mg) (n = 18) or INH (300 mg) (n = 18). Plasma MFX concentrations were determined by a validated HPLC method. RESULTS Plasma peak concentration and exposure of MFX was significantly lower and plasma clearance significantly higher when combined with RMP (P<0.001). The C max to MIC and AUC 0-12 to MIC ratios of MFX were significantly lower during concomitant RMP (P<0.001). INH had no significant effect on the pharmacokinetics of MFX. INTERPRETATION & CONCLUSIONS Concomitant RMP administration caused a significant decrease in C max and AUC 0-12 of MFX, the mean decreases being 26 and 29 per cent, respectively. It is uncertain whether this decrease would affect the treatment efficacy of MFX. Prospective studies in TB patients are needed to correlate MFX pharmacokinetics with treatment outcomes

HDAC inhibitor confers radiosensitivity to prostate stem-like cells

Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. Results: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. Interpretation: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe