Immunoregulators in the nervous system

The nervous system, through the production of neuroregulators (neurotransmitters, neuromodulators and neuropeptides) can regulate specific immune system functions, while the immune system, through the production of immunoregulators (immunomodulators and immunopeptides) can regulate specific nervous system functions. This indicates a reciprocal communication between the nervous and immune systems. The presence of immunoregulators in the brain and cerebrospinal fluid is the result of local synthesis--by intrinsic and blood-derived macrophages, activated T-lymphocytes that cross the blood-brain barrier, endothelial cells of the cerebrovasculature, microglia, astrocytes, and neuronal components--and/or uptake from the peripheral blood through the blood-brain barrier (in specific cases) and circumventricular organs. Acute and chronic pathological processes (infection, inflammation, immunological reactions, malignancy, necrosis) stimulate the synthesis and release of immunoregulators in various cell systems. These immunoregulators have pivotal roles in the coordination of the host defense mechanisms and repair, and induce a series of immunological, endocrinological, metabolical and neurological responses. This review summarizes studies concerning immunoregulators--such as interleukins, tumor necrosis factor, interferons, transforming growth factors, thymic peptides, tuftsin, platelet activating factor, neuro-immunoregulators--in the nervous system. It also describes the monitoring of immunoregulators by the central nervous system (CNS) as part of the regulatory factors that induce neurological manifestations (e.g., fever, somnolence, appetite suppression, neuroendocrine alterations) frequently accompanying acute and chronic pathological processes.     

Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat

Synaptic contacts between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurons were demonstrated in the rat hypothalamus by a double-staining immunocytochemical method at the electron microscopic level. Somatostatin-immunoreactive nerve terminals synapse on GHRH-positive dendrites and cell bodies in the arcuate nucleus. A fine network of GHRH-immunopositive nerve terminals was observed at the light microscopic level in the rostral part of the periventricular nucleus and in the dorsal part of the arcuate nucleus around somatostatin-containing neuronal elements. With the electron microscope synaptic contact between GHRH-containing nerve terminals and somatostatin-containing dendrites are demonstrated. The reciprocal innervation between GHRH- and somatostatin-containing neurons that project to the median eminence and regulate growth hormone secretion must allow them to coordinate their activities.     

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.     

Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

Maximized combined modality treatment of an unselected population of oral and oropharyngeal cancer patients. Final results of a pilot study compared with a treatment-dependent prognosis index.

BACKGROUND: In an attempt to raise the survival of an unselected and representative population of oral and oropharyngeal squamous cell cancer patients, a pilot study of an integrated four-modality treatment was conceived. Final endpoints were compliance, loco-regional control, survival (after complete 5-year follow-up), and a concept of trial assessment using the treatment-dependent prognostic index TPI. PATIENTS: Eighty-seven consecutive patients with histologically proven untreated stages I-IV disease presented in the period between 1997 and 1999 of whom 14 had to be considered uncurable and 73 were fit to be treated with the intention of achieving a cure. METHODS: All patients received one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin (systemically neutralized with sodium thiosulphate), and, if possible, by consecutive treatment applying both surgery of the primary tumour and the neck lymphatics, as well as by adjuvant radiation over 5 weeks (51.3 Gy) plus concurrent chemotherapy (weekly systemic docetaxel 25 mg/m(2)). RESULTS: Ninety per cent of all cases and 96% of the patients treated with curative intention received more than one modality due to study design. Patient non-compliance in the group treated with curative intention has been 18/73 (=25%), and protocol compliance has been 32/73 (=44%). The locoregional control rate for all cases was 71% (62/87 patients) and for the patients treated with curative intention 83.5% (61/73 patients). Thirteen/fourteen non-curable patients died after a mean period of 4 months. After a median observation time of 5 years, the final absolute survival of the unselected population was 53%, and of the patients treated with curative intention 62% (especially, 70% and 50% for patients with operable stages III and IV, respectively). CONCLUSION: The multimodality regimen as presented proved feasible and showed high objective and relative survival rates in comparison with known data from tumour registries of unselected populations. Intra-arterial chemotherapy should be considered a valuable addition to treatment. The potential of survival benefit from this multimodality regimen in comparison with the prognosis index TPI should be investigated in further studies.