Altered cannabinoid receptor expression in pancreatic islets in experimental model of uraemia

Background: Uraemia leads to a number of metabolic and hormonal disorders including defective carbohydrate metabolism. Endocannabinoids exert their effect on insulin and glucagon secretion via activation of specific receptors named CB1 and CB2. For this reason and the absence of reports on location and immunoreactivity of CB1, CB2 receptors compared to immunoreactivity of insulin- and glucagon-secreting cells in experimental uraemia, the author decided to investigate this issue. The aim of the present study was the immunohistochemical localisation and evaluation of cannabinoid receptors (CB1, CB2), insulin and glucagon in the pancreatic islets of uraemic rats. Materials and methods: Fragments of the rat’s pancreas were collected 28 days after surgical resection of one kidney and removal of 70% of the other kidney cortex. Paraffin-embedded sections were stained with haematoxylin-eosin and immunohistochemical reactions were performed with the use of a specific antibody against CB1-, CB2-receptors, insulin and glucagon. Results: It was revealed the decreased immunoreactivity of the CB1 receptor and higher intensity of the immunohistochemical reaction against CB2 receptor as compared to the value in the control animals. Significantly higher immunoreactivity of glucagon-positive cells and weaker immunoreactivity of insulin-positive cells were observed in pancreatic islets of uraemic rats. Conclusions: The obtained results indicate the involvement of cannabinoid receptors in the pathomechanism of carbohydrate metabolism disorders, associated with abnormal secretion of hormones by the α and β cells in uraemia

Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Gastrointestinal neuroendocrine cells in various types of hypertension – a review

Recent years have witnessed a progressive increase in the number of people suffering from hypertension, which is one of the most serious health problems in the world. Hypertension results in changes leading to function disorders, not only of the organs and tissues, but also changes leading to the activation of many defense mechanisms in the cells in order to prevent damage. One of them is the expression of neuroendocrine (NE) hormones and biologically active substances, which has been the focus of extensive research for a number of years. Active involvement of NE cells and the biological and therapeutic properties of various substances synthesized by them have been confirmed in clinical trials and in various experimental models. Results obtained in many research studies indicate intense activity of enteroendocrine cells in the gastrointestinal tract in various pathological conditions, including hypertension. In the present review, we discuss the morphological and functional changes of gastrointestinal neuroendocrine cells under conditions of different types of hypertension

Liquid Crystalline Polymorphism of Methyl and Ethyl trans-4-{[4'-(alkanoyloxy)phenyl]diazenyl}benzoates

uthors present two new homologous series of liquid-crystalline compounds, methyl and ethyl 4-{[4-(alkanoyloxy)phenyl]diazenyl}benzoates, synthesis and investigation of their mesogenic properties. In the methyl series only nematic phase was detected and in the ethyl series nematic and smectic mesophases. Influence of the alkyl chain length on the phase transition temperatures and their entropic values are discussed and compared with literature data

Liquid Crystalline Polymorphism of Methyl and Ethyl trans-4-{[4'-(alkanoyloxy)phenyl]diazenyl}benzoates

uthors present two new homologous series of liquid-crystalline compounds, methyl and ethyl 4-{[4-(alkanoyloxy)phenyl]diazenyl}benzoates, synthesis and investigation of their mesogenic properties. In the methyl series only nematic phase was detected and in the ethyl series nematic and smectic mesophases. Influence of the alkyl chain length on the phase transition temperatures and their entropic values are discussed and compared with literature data

Gastrointestinal neuroendocrine cells in various types of hypertension – a review

Recent years have witnessed a progressive increase in the number of people suffering from hypertension, which is one of the most serious health problems in the world. Hypertension results in changes leading to function disorders, not only of the organs and tissues, but also changes leading to the activation of many defense mechanisms in the cells in order to prevent damage. One of them is the expression of neuroendocrine (NE) hormones and biologically active substances, which has been the focus of extensive research for a number of years. Active involvement of NE cells and the biological and therapeutic properties of various substances synthesized by them have been confirmed in clinical trials and in various experimental models. Results obtained in many research studies indicate intense activity of enteroendocrine cells in the gastrointestinal tract in various pathological conditions, including hypertension. In the present review, we discuss the morphological and functional changes of gastrointestinal neuroendocrine cells under conditions of different types of hypertension