Increased in vitro uptake of the complement C3b in the serum of patients with Guillain-Barré syndrome, myasthenia gravis and dermatomyositis

To examine the role of complement in certain autoimmune neuromuscular diseases, we used an in-vitro quantitative complement uptake assay that allows measurement of the capacity of patients' sera to deposit fragments of the third complement component onto sensitized targets. C3 uptake was significantly higher in patients with active dermatomyositis, Guillain-Barré syndrome and myasthenia gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake assay supports the role of C3b neoantigen and Membranolytic Attack Complex deposition in the target tissues and may be a useful tool to monitor disease activity in patients with complement-mediated neurological disorders.     

Noise-induced cell death in the mouse medial geniculate body and primary auditory cortex

Noise-induced effects within the inner ear have been well investigated for several years. However, this peripheral damage cannot fully explain the audiological symptoms in noise-induced hearing loss (NIHL), e.g. tinnitus, recruitment, reduced speech intelligibility, hyperacusis. There are few reports on central noise effects. Noise can induce an apoptosis of neuronal tissue within the lower auditory pathway. Higher auditory structures (e.g. medial geniculate body, auditory cortex) are characterized by metabolic changes after noise exposure. However, little is known about the microstructural changes of the higher auditory pathway after noise exposure. The present paper was therefore aimed at investigating the cell density in the medial geniculate body (MGB) and the primary auditory cortex (AI) after noise exposure. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun, 10:1). After 1 week, auditory brainstem response recordings (ABR) were performed in noise exposed and normal hearing animals. After fixation, the brain was microdissected and stained (Kluever-Barrera). The cell density in the MGB subdivisions and the AI were determined by counting the cells within a grid. Noise-exposed animals showed a significant ABR threshold shift over the whole frequency range. Cell density was significantly reduced in all subdivisions of the MGB and in layers IV-VI of AI. The present findings demonstrate a significant noise-induced change of the neuronal cytoarchitecture in central key areas of auditory processing. These changes could contribute to the complex psychoacoustic symptoms after NIHL.     

Multifunctional microcapsules for pancreatic islet cell entrapment: design,preparation and in vitro characterization

Great advances in cell transplantation have been made, including the recent, remarkable success in pancreatic islet transplantation for the treatment of type 1 diabetes mellitus. Unfortunately, the transplanted cells are very susceptible to oxidative stress that cause severe damage to either allo- or xenogeneic islets upon graft in diabetic patients. Consequently, the transplanted islet functional life span is significantly shortened. The aim of this study was to examine the possible effects of antioxidants on in vitro cultured adult rat islets, and to evaluate the effects of a prolonged-release formulation, in form of cellulose acetate (CA) microspheres, on Vitamin D(3) activity. Isolated rat islets, both free and entrapped in microspheres were treated with Vitamin D(3). The effects of the vitamin were studied at 3, 6 and 9 days of in vitro cell culture. According to insulin secretory patterns, treatment with Vitamin D(3) of both free and CA entrapped microspheres, increased the insulin output as compared to untreated controls. Such positive effects were confirmed under islet static incubation with glucose at day 6. These results suggest that pancreatic islets can be advantageously treated with anti-oxidising vitamins before implantation, and speculatively, with the help of special delivery systems, throughout the islet cell life span, in the post-transplant time period.     

Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes

The formation of advanced glycation end products (AGEs) is an important biochemical abnormality that accompanies diabetes mellitus and, likely, inflammation in general. Here we summarize and discuss recent studies indicating that the effects of AGEs on vessel wall homeostasis may account for the rapidly progressive atherosclerosis associated with diabetes mellitus. Driven by hyperglycemia and oxidant stress, AGEs form to a greatly accelerated degree in diabetes. Within the vessel wall, collagen-linked AGEs may "trap" plasma proteins, quench nitric oxide (NO) activity and interact with specific receptors to modulate a large number of cellular properties. On plasma low density lipoproteins (LDL), AGEs initiate oxidative reactions that promote the formation of oxidized LDL. Interaction of AGEs with endothelial cells as well as with other cells accumulating within the atherosclerotic plaque, such as mononuclear phagocytes and smooth muscle cells (SMCs), provides a mechanism to augment vascular dysfunction. Specifically, the interaction of AGEs with vessel wall components increases vascular permeability, the expression of procoagulant activity and the generation of reactive oxygen species (ROS), resulting in increased endothelial expression of endothelial leukocyte adhesion molecules. AGEs potently modulate initiating steps in atherogenesis involving blood-vessel wall interactions, triggering an inflammatory-proliferative process and, furthermore, critically contribute to propagation of inflammation and vascular perturbation in established disease. Thus, a better understanding of the biochemical mechanisms by which AGEs contribute to such processes in the vessel wall could be relevant to devise preventive and therapeutic strategies for diabetic atherosclerosis.     

Chronic and Acute Prenatal and Postnatal Ethanol Exposure on Lymphocyte Subsets from Offspring Thymic, Splenic, and Intestinal Intraepithelial Sources

The overall objective of this study was to analyze the effects of a combined prenatal and postnatal (entire gestational human chronic drinking model) ethanol exposure on T-cell development in mice. Specifically, this study evaluated the effects of chronic exposure to prenatal ethanol on lymphocyte makeup and proliferative capabilities of postnatal offspring's (4 and 12 weeks) peripheral lymphoid tissues. Chronic exposure regimens were conducted over the entire gestational period and through postnatal day 14 or 21. Thymus, spleen, and intestinal intraepithelial lymphocytes were harvested and analyzed by flow cytometry for percentages of T-cell subsets. Splenic lymphocytes were also analyzed for their ability to proliferate in response to a T-cell mitogen. Limited effects of chronic ethanol exposure were seen.     

Termination of recurrent supraventricular tachycardia by right ventricular endocardial pacing but not by left ventricular epicardial pacing

Externally controlled ventricular pacing was employed in a patient with recurrent disabling supraventricular tachycardia and frequent sinus pauses between attacks of tachyarrhythmia. A permanent transthoracic demand pacemaker was inserted after electrophysiologic study demonstrated the effectiveness of ventricular stimulation in terminating induced supraventricular tachycardia. Subsequently, spontaneous recurrences of tachyarrhythmia failed to respond to fixed rate left ventricular stimulation accomplished by placing a magnet externally over the pacemaker pack. During an induced supraventricular tachycardia, repeat electrophysiologic study demonstrated that paced left ventricular beats failed to invade the A-V junctional area before it was depolarized previously by the corresponding tachycardia beat. Right ventricular stimulation from a transvenous pacemaker could depolarize the site of the reentrant circuit and terminate an induced supraventricular tachycardia. The addition of propranolol increased the ease by which spontaneous attacks of tachyarrhythmia could be terminated by right ventricular endocardial pacing.