Mig chemokine in primary biliary cirrhosis.

Different studies investigated about the role of T-helper 1 cytokines and chemokines in primary biliary cirrhosis (PBC). Animal models with autoimmune cholangitis have been used to investigate the involvement of (C-X-C motif) receptor (CXCR)3 and its ligand (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) in the pathogenesis of PBC, suggesting a contribution of MIG in the development of PBC. In patients with PBC, in particular at the level of the portal areas of diseased livers, MIG expression and CXCR3+ cells have been found. MIG is positively associated with the severity of liver fibrosis. In PBC, circulating MIG levels and CXCR3+ cells are related with the progression of the disease; in fact, their expression increases significantly in PBC patients with respect to controls. Furthermore, it has been shown a significant reduction of these chemokines in the serum of PBC patients after treatment with ursodeoxycholic acid.

Allergic rhinitis and CXCR3 chemokines.

The underlying mechanism of allergic rhinitis involves IgE antibodies attaching to the allergen and causing the release of inflammatory chemicals such as histamine from mast cells. Cytokines are very important in this process. Many data suggest a systemic shift to more intensely type 1-dominated immune responses in non-allergic individuals and, conversely, to more type 2-dominated responses in allergic individuals upon natural re-exposure to grass pollen. However other studies have found that chemokine (C-X-C motif) ligand (CXCL)10/ interferon (IFN)-γ-induced protein 10 (IP-10) and CXCL9/monokine induced by IFN-γ (MIG) concentrations are elevated in nasal lavages from allergic patients suggesting that these chemokines may play a role in chronic allergic inflammation. Several studies have also evaluated the effect of different immune-modulating drugs in allergic rhinitis showing local and peripheral increase of IFN-γ and IP-10, associated with a reduction of symptoms. Further studies are needed to clarify the role of T helper (Th)1 chemokines in the pathogenesis of allergic rhinitis, and to evaluate their role as biomarkers of disease and of response to treatments.

Cytokines and chemokines in multiple sclerosis.

Chemokine (C-X-C motif) receptor 3 (CXCR3) and its ligands (MIG, IP-10) play an important role in multiple sclerosis (MS). The CXCR3 receptor is expressed on the majority of T cells in the cerebrospinal fluid (CSF) of patients with MS, suggesting that the CXCR3 receptor may mediate the trafficking of T cells into the central nervous system. IP-10, and MIG were found to be elevated in the CSF of patients with MS during relapse. These chemokines were also detected in actively demyelinating lesions, and upregulation of CXCR3 expression on peripheral blood CD4+ lymphocytes was associated with MS relapses.Treatment with Interferon (IFN)-ß-1a or IFN-ß-1b was associated with increased IP-10. Natalizumab that exerts impressive therapeutic effects in patients with MS induces a marked decline of Th1 chemokines (MIG, IP-10, I-TAC) in CSF.

[Cryoglobulinemia and the α-chemokine IP-10]. / Crioglobulinemia e l'α-chemochina IP-10.

IFN-γ-induced protein 10 (IP-10) and its receptor, CXCR3 chemokine (C-X-C motif) receptor 3 (CXCR3), appear to contribute to the pathogenesis of HCV related mixed cryoglobulinemia (HCV+MC). The secretion of IP-10 by CD4+, CD8+ and natural killer (NK)-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin (IL)-12 cytokine family. Under the influence of IFN-γ, IP-10 is secreted by several cell types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In tissues, recruited T helper (Th) 1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor (TNF)-α production, which in turn stimulates IP-10 secretion from the cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. High levels circulation of IP-10 have been found in HCV+MC, especially in patients with clinically active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT), have higher levels than those without AT. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis, and to evaluate whether IP-10 is a novel therapeutic target in HCV+MC.

Hepatitis C virus and type 1 diabetes.

Hepatitis C virus infection and diabetes mellitus are two worldwide, major public health problems with increasing complication and mortality rates. Type 1 diabetes mellitus (T1D) is characterized by an autoimmune process leading to pancreatic beta cell destruction; only when the major part of pancreatic beta cells have been destroyed the diabetes become clinically manifest. At the basis of the development of the T1D there is an interplay among environmental factors, pancreatic beta cells, the innate and adaptive immune system, the genetic background and the comorbidities of the patient. Viral infections, including hepatitis C virus infection, may be one of the factors that can almost accelerate progression to diabetes, through different mechanisms.

Connections of the posterior pallium in the crested newt, Triturus carnifex.

The connections of the posterior pallial regions were studied in the crested newt, Triturus carnifex, by means of the horseradish peroxidase technique. The tracer was injected into the lateral and medial pallia, caudal to the interventricular foramen. In addition, the connections between the posterior pallium and the infundibular hypothalamus were investigated with both horseradish peroxidase and the fluorescent dye DiI. The results show important differences between the connection patterns of the medial and lateral pallia. The lateral pallium receives inputs from the main olfactory bulb and send fibers to the contralateral hemisphere through the anterior commissure. It also shows modes extra-telencephalic connections. Conversely, the medial pallium receives direct afferent inputs from the amygdala (pars medialis) and the anterior dorsal thalamus. It is reciprocally connected to the contralateral homologue region through the hippocampal commissure, and its main efferent system is the medial forebrain bundle, which reaches the infundibular hypothalamus. The infundibulum also receives a prominent projection from the amygdala (pars lateralis). The connectivity of the posterior pallium is comparable to that reported previously for the anterior pallium, although a few differences are noted. These differences in the connectivity of the lateral pallium and the medial pallium may reflect different functional properties of these telencephalic regions.

Dihydronicotinamide adenine dinucleotide diaphorase in the central nervous system of the crested newt.

By using a histochemical procedure, the distribution of neurons containing dihydronicotinamide adenine dinucleotide diaphorase (NADPHd) was examined in the brain, retina and olfactory epithelium of the urodele amphibian Triturus carnifex. Positive nerve fibers and terminals were observed throughout the brain and cell bodies were seen within the telencephalon, optic tectum, brain stem, cerebellum and spinal cord. In the retina, NADPHd labeling was localized in the outer segment of photoreceptors and in some amacrine cells as well as in the outer and inner plexiform layers. In the olfactory epithelium, NADPHd labeling was found in the olfactory neurons. By comparing NADPHd distribution with nitric oxide synthase (NOS) immunoreactivity (using a polyclonal antiserum raised against mouse cerebellar NOS) it was found that NADPHd labeling and NOS immunoreaction patterns generally matched. The organization of NADPHd and NOS containing neurons in the central nervous system of the crested newt, which is simpler than in other vertebrates investigated, shows some peculiarities, such as the occurrence of NADPHD in the pinealocytes of the epiphysis, nucleus rubber of the brain stem and eminentia cerebellaris ventralis of the cerebellum.

Immunolocalization of aromatic L-amino acid decarboxylase in goldfish (Carassius auratus) brain.

The distribution of monoamines (catecholamines and serotonin) in fishes has been previously studied by immunohistochemistry of both the monoamines themselves and their biosynthetic enzymes. But the distribution of neurons containing aromatic L-amino acid decarboxylase, an enzyme involved in the biosynthesis of both catecholamines and serotonin, has up to now not been investigated. In order to improve knowledge about the localization of aromatic L-amino acid decarboxylase, neurons containing this enzyme were mapped immunohistochemically in the goldfish brain. Furthermore, neurons bearing aromatic L-amino acid decarboxylase immunoreactivity have been compared with those containing tyrosine hydroxylase and serotonin immunoreactivities. Our results show that distribution of aromatic L-amino acid decarboxylase immunoreactivity generally coincides with that of tyrosine hydroxylase and serotonin. Nevertheless, the presence of nine D cell groups (containing aromatic L-amino acid decarboxylase but lacking both catecholamines and serotonin) and six groups of neurons which are aromatic L-amino acid decarboxylase-immunonegative but contain tyrosine hydroxylase, and might produce L-DOPA, have been revealed. The occurrence of both D cell groups and presumptive L-DOPA neurons in goldfish brain is discussed in relation to similar findings in fish and mammalian brain.

Effects of permanent deafferentation of the anterior preoptic area on serum aldosterone levels in the crested newt (Triturus cristatus carnifex Laur.).

By cutting off the fiber systems running along the medial forebrain bundle of the urodele amphibian Triturus cristatus, a wide deafferentation of the preoptic area was evoked. This operation elicited a decrease in aldosterone serum level, probably through a reduction of ACTH secretion. At present we are not able to ascertain whether such reduction was prompted by changes in the hypothalamic production of the neurohypophysial hormones or the corticotropin-releasing factor (CRF).

Enhanced triiodothyronine production in crested newts bearing permanent lesions to the anterior preoptic area.

In the crested newt, permanent lesions to the anterior preoptic area brought about an enhancement of triiodothyronine (T3) production. This was not mediated by prolactin, since the effect was demonstrable also in ergocryptine (CB 154)-treated animals. The observed rise in circulating T3 levels in the ergocryptine-treated surgical animals confirms that lesions to the anterior preoptic area stimulate pituitary thyrotrophic activity, resulting in the activation of the thyroid gland.

A Golgi study of the hypothalamus of Actinopterygii. II. The posterior hypothalamus.

The posterior hypothalami of the polypteriform, Calamoichthys, and of the teleost, Anguilla, were studied by means of the Golgi technique. In Calamoichthys, the lateral lobes are not developed and the median lobe is simple. In Anguilla, the median (tuberal) lobe shows lophodendritic, CSF-contacting cells and horizontal cells in the periventricular grey and some reticular elements directed toward the cell-poor lateral areas. In the lateral lobes the periventricular grey is formed by multipolar neurons and a diffuse population of multipolar cells of uncertain identity. The nucleus diffusus lobi lateralis is formed by scarce multipolar neurons, often placed next to the external surface of the brain. The organization of the lateral lobes in Actinopterygii is reminiscent of highly developed integrative regions.

A Golgi study of the hypothalamus of actinopterygii.

The preoptic area of a primitive actinopterygian, the polypteriform, Calamoichthys calabaricus Smithi, and of the teleost, Anguilla anguilla L., have been studied by Golgi and other neurohistological and histochemical methods. In the preoptic area two regions can be recognized: a cell rich median region and a lateral one, composed mostly of fiber systems. After Golgi staining a varied population of neurons is seen, including: (1) magnocellular neurons, endowed with a number of dendrites and an axon emerging from the main dendritic shaft; (2) lophodendritic tufted or pyriform neurons of variable morphology (often of the midget type); (3) cerebrospinal fluid contacting neurons; (4) bipolar and horizontal neurons. Of relevant interest is also the observation of commissural neurons, of a distinct precommissural necleus, and of bipolar neurons, the axons of which course toward the ventral hypopallium.

The optic tectum of calamoichthys calabaricus Smithi. A Golgi study.

The optic tectum of Calamoichthys calabaricus (Polypteriformes) shows a relatively complex vertical stratification, with six main layers and a varied neuronal typology. In particular, pyriform neurons in the well developed stratum griseum periventriculare and some multipolar neurons in the stratum griseum profundum represent the efferent elements of the tectum, while the optic and lemniscal inputs to the tectum converge in the plexiform sublayers of the stratum fibrosum et griseum superficiale. In the circuitry of the tectum some modulation is achieved by some of the polymorphic cells of the stratum griseum internum and by the horizontal cells of the outer layers. Notwithstanding some differences with respect to the teleost optic lobe (i.e., the absence of a torus longitudinalis; the lack of a stratum fibrosum marginale; the modest size of the stratum fibrosum profundum; the paucity of neurons in the stratum fibrosum et griseum fibrosum profundum; the paucity of neurons in the stratum fibrosum et griseum superficiale; and the ill-defined separation of the layers of the afferent and efferent fibers), the optic tectum of Calamoichthys resembles the mesotectal type chracteristic of teleost, anurans and reptiles. It exhibits higher degree of organization than the optic tectum of the Chondrostei.