Oxidative modification of type II collagen differentially affects its arthritogenic and tolerogenic capacity in experimental arthritis

INTRODUCTION: Oxidative modification of proteins affects their biological properties. Previously we have shown that hypochlorite (HOCl), the product of activated neutrophils, enhances protein immunogenecity. Collagen type II, a primary component of cartilage, is commonly used in the induction of arthritis in animals (CIA). The aim of this study was to examine whether HOCl may affect immunogenic, tolerogenic, and arthritogenic properties of collagen. MATERIALS AND METHODS: DBA/J mice were injected with either native (CNAT) or chlorinated collagen (CHOCl) to induce arthritis. The effect of chlorination on collagen properties was measured by evaluation of incidence and severity of CIA. Moreover, the concentration of serum anti-collagen IgG antibodies and myeloperoxidase (MPO) activity in inflamed joints was determined. RESULTS: Mice immunized with CNAT in adjuvant developed arthritis (CIA) with an incidence of 69%. CNAT also exerted tolerogenic properties when injected intravenously either before or shortly after primary immunization, resulting in decreased incidence and severity of CIA, reduced MPO activity in inflamed joints, and lowered serum levels of anti-CNAT IgG anti-bodies. Chlorination of collagen significantly diminished its ability to induce CIA and to trigger generation of anti-CNAT IgG antibodies. Interestingly, chlorination did not affect tolerogenic properties of collagen administered prior to primary immunization with CNAT. CONCLUSIONS: These results suggest that chlorination of collagen may selectively affect functional epitopes of collagen. It is likely that in inflamed joints, neutrophil derived HOCl, in some circumstances, will destroy arthritogenic and immunogenic B cell epitopes, while regulatory T cell epitopes will be preserved.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Nutritional Support in Head and Neck Radiotherapy Patients Considering HPV Status

Malnutrition is a common problem in patients with head and neck cancer (HNC), including oropharyngeal cancer (OPC). It is caused by insufficient food intake due to dysphagia, odynophagia, and a lack of appetite caused by the tumor. It is also secondary to the oncological treatment of the basic disease, such as radiotherapy (RT) and chemoradiotherapy (CRT), as a consequence of mucositis with the dry mouth, loss of taste, and dysphagia. The severe dysphagia leads to a definitive total impossibility of eating through the mouth in 20–30% of patients. These patients usually require enteral nutritional support. Feeding tubes are a commonly used nutritional intervention during radiotherapy, most frequently percutaneous gastrostomy tube. Recently, a novel HPV-related type of OPC has been described. Patients with HPV-associated OPC are different from the HPV− ones. Typical HPV− OPC is associated with smoking and alcohol abuse. Patients with HPV+ OPC are younger and healthy (without comorbidities) at diagnosis compared to HPV− ones. Patients with OPC are at high nutritional risk, and therefore, they require nutritional support in order to improve the treatment results and quality of life. Some authors noted the high incidence of critical weight loss (CWL) in patients with HPV-related OPC. Other authors have observed the increased acute toxicities during oncological treatment in HPV+ OPC patients compared to HPV− ones. The aim of this paper is to review and discuss the indications for nutritional support and the kinds of nutrition, including immunonutrition (IN), in HNC, particularly OPC patients, undergoing RT/CRT, considering HPV status.     

Botanicals in Postmenopausal Osteoporosis

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.     

Comparing changes in transient-evoked otoacoustic emission and pure-tone audiometry following short exposure to industrial noise

It has been suggested that otoacoustic emissions, particularly transient-evoked otoacoustic emissions (TEOAE), might be more sensitive in assessment of changes to the cochlea caused by noise than pure-tone audiometry (PTA). The aim of the study was to compare temporary threshold shifts with the changes in TEOAE following a six-hour exposure to industrial noise at the intensity of 85-97 dB (A). Thirty two male employees of a metal factory were screened. TEOAE, PTA and tympanometry were included in the hearing test battery. Both, PTA and TEOAE showed significant reduction due to noise exposure, but no correlation between temporary threshold shifts and decreases in either the overall TOAE level or the level of otoacoustic emission in the frequency bands was found. Our results confirm the high sensitivity of TEOAE to short exposure to industrial noise. This study may recommend this measurement as a method of evaluation for TTS conditions for hearing conservation programme purposes, in addition to pure-tone audiometry.     

Nuclear Pedigree Criteria for the Identification of Individuals Suspected to Be at Risk of an Inherited Predisposition to Gastric Cancer

Gastric cancer is the second most frequently diagnosed malignancy worldwide and therefore represents a significant healthcare burden. Environmental and genetic factors are involved in the development of gastric cancer. To date only one clear genetic predisposition has been identified involving mutations in the E-cadherin gene. The disease phenotype in patients harbouring E-cadherin mutations appears to be specifically related to diffuse gastric cancer. Little is known genetically about the other forms of gastric cancer. Since there is a growing awareness about the necessity of early intervention criteria have been developed that aid the identification of hereditary forms of gastric cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be provided with risk assessment and/or genetic testing.The results reveal that inclusion features described herein such as (a) gastric cancer diagnosed before 46 years of age; (b) two gastric cancers among first degree relatives diagnosed over the age of 50 are useful in identifying suspected hereditary gastric cancer patients.     

Fly agaric (Amanita muscaria) poisoning, case report and review.

Gathering and eating mushrooms and other plants containing psychoactive substances has become increasingly popular among young people experimenting with drugs. Dried fly agaric Amanita muscaria fruiting bodies were eaten by five young persons (18-21 years of age) at a party in order to evoke hallucinations. Visual and auditory hallucinations occurred in four of them, whereas a 18-year-old girl lost consciousness. The following morning, she went to the Clinic of Toxicology. Due to the fact that not all the active substances present in the fly agaric have been identified, and some of them have an effect after a period of latency, the patient was admitted for several days of observation during which check-up examinations were performed. After four days without any problems, she was discharged. The poisoning regressed with no organ complications. The remaining persons who had eaten the fly agaric were free from any complaints.     

Effect of Transmural Extent of the Simulated Infarction in a Left Ventricular Model on Displacement and Strain Distribution Estimated from Synthetic Ultrasonic Data

The identification of a sub-endocardial infarction is of major interest in cardiology. This study evaluates the sensitivity of selected measures to the thickness of such an infarction. Synthetic ultrasonic data (long-axis view) of left ventricular models with inclusions were generated using Field II and meshes obtained from finite-element simulations, which also provided the reference for the estimates obtained from ultrasonic data. The displacements, the first and second component of the principal strain (ε₁ and ε₂), and several measures derived from these quantities were estimated. All estimates, except for the poorly estimated ε₂, exhibited sensitivity to the presence and transmurality of the inclusion. The most sensitive was the gradient of the averaged transmural profiles of ε₁, and ε₁ averaged over the area corresponding to the transmural inclusion. The inflection point of the ε₁ profile shifted toward the outer wall with increasing thickness of the non-transmural inclusion.     

Observations on Degenerative Changes Within the Optic Nerve in Patients With Primary Open Glaucoma and Arterial Hypertension: 6-Month Follow-Up

J Clin Hypertens (Greenwich). 2012;14:701–710. ©2012 Wiley Periodicals, Inc. The authors aimed to determine the effect of the time of hypotensive drug administration on the progress of degenerative changes within the optic nerve in patients with hypertension and glaucoma. Two groups were included in the study: group A comprised patients-dippers taking drugs in the mornings, and group B comprised patients-nondippers taking drugs both in the mornings and in the evenings. After 6 months, group B showed significant drops in nocturnal diastolic blood pressure (BP) (month 1=73.27 mm Hg vs month 6=67.50 mm Hg), nocturnal mean BP (89.34 vs 84.65 mm Hg), and minimum diastolic BP (50.74 vs 44.03 mm Hg). Group B also showed significant reductions in nocturnal ocular perfusion pressure (43.0 vs 39.73), retinal nerve fiber layer thickness (131.31 vs 113.12 μm), and flow in the eye vessels. Taking hypotensive drugs in the evening may significantly decrease blood flow in the eye arteries, cause degenerative changes within the optic nerves, and result in greater loss in the field of vision.