Liver cirrhosis reversion is improved in hamsters with a neurointermediate pituitary lobectomy.

Regulating mechanisms of fibrosis is an important goal in the treatment of fibrosis and liver cirrhosis. The role of arginine vasopressin (AVP) in promoting fibrosis in several organs has been well documented. However, the result of an AVP deficiency during liver fibrosis has not been reported. We herein study the effects of an AVP deficiency, which was induced by neurointermediate pituitary lobectomy (NIL), on liver cirrhosis and liver cirrhosis reversion. Hamsters were intact (control) or underwent CCl4-induced cirrhosis, the latter animals divided into four groups: Cirrhotic, NIL-cirrhotic, Cirrhotic-reversion (R) and NIL-cirrhotic-R. Liver function, liver histopathology (including the fibrosis area and collagen types) and liver expression of MMP-13 and TIMP-2 were assessed. Results show that the AVP deficiency decreased the levels of alkaline phosphatase in serum and the expression of type I collagen and TIMP-2, and increased type III collagen deposition, MMP-13 expression and the size of regeneration nodules in NIL-cirrhotic and NIL-cirrhotic-R animals. A significantly greater recovery was found in the NIL-cirrhotic-R than the Cirrhotic-R group. We conclude that an AVP deficiency participates importantly in hamster liver regeneration by: 1) prompting the fibroblasts to produce type III collagen deposit, 2) influencing the activity of AP from bile duct cells, and 3) inhibiting TIMP-2 expression while favoring the fibrolytic activity of MMP-13.

Modulation of amoebic hepatic abscess by the parasympathetic system.

The neuro-immune network, in which the vagus nerve is involved, provides feedback between its afferent branches for signalling central nervous system from sites of injury through cytokines and its efferent branches, which release acetylcholine, an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic mechanisms participating in the inflammatory response in the liver, we studied the effects of a vagotomy on the innate immune response in hamsters with amoebic liver abscess. At 7 days post-infection, compared to the control, liver parasympathectomy resulted in a larger abscess size, a greater production of collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN-γ and increased numbers of IL-10 and IFN-γ-positive cells in situ, with no change in the number of macrophages and NK cells. Data indicate that the vagotomy disrupted the inflammatory response, causing an increase in the response against infection, then could favour the innervation of the liver by the sympathetic nervous system and would then take the control of the immune response by stimulating the conversion of macrophages to epithelioid cells; and through increased IL-10 production would induce the hepatic stellar cells to become myofibroblast collagen producer cells, thus forming a barrier of collagen and blocking trophozoite migration.

Hypophysectomy and neurointermediate pituitary lobectomy decrease humoral immune responses to T-independent and T-dependent antigens.

In rats, hypophysectomy (HYPOX) or neurointermediate pituitary lobectomy (NIL) reduce humoral and cell-mediated immune responses. However, to our knowledge, the differences in the effects of anterior versus posterior pituitary hormones on the immune responses have not been studied to date. We compared in rats, the effects of sham surgery (SHAM), HYPOX, and NIL on humoral immune responses to T cell-independent (TI) type 1 antigen DNP-LPS and to TI type 2 antigen DNP-FICOLL, as well as to T cell-dependent (TD) antigens ovalbumin (OVA) and bovine serum albumin (BSA). The results showed that: (1) both HYPOX and NIL induced a similar and significant decrease in IgM responses towards TI-1 antigens, (2) NIL but not HYPOX induced a decreased IgM response to TI-2 antigens, and (3) both HYPOX and NIL induced similar and significant decrease in IgG responses to TI-2 antigens. Compared with the SHAM group, IgM responses to both TD antigens did not change in HYPOX and NIL animals, whereas the IgG responses to OVA and BSA significantly decreased in HYPOX and NIL animals. These results indicate that hormones of the anterior and posterior pituitary play their own role in the regulation of humoral immune responses.

Hypophysectomy and neurointermediate pituitary lobectomy decrease humoral immune responses to T-independent and T-dependent antigens

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In rats, hypophysectomy (HYPOX) or neurointermediate pituitary lobectomy (NIL) reduce humoral and cell-mediated immune responses. However, to our knowledge, the differences in the effects of anterior versus posterior pituitary hormones on the immune responses have not been studied to date. We compared in rats, the effects of sham surgery (SHAM), HYPOX, and NIL on humoral immune responses to T cell-independent (TI) type 1 antigen DNP-LPS and to TI type 2 antigen DNP-FICOLL, as well as to T cell-dependent (TD) antigens ovalbumin (OVA) and bovine serum albumin(BSA). The results showed that: (1) both HYPOX and NIL induced a similar and significant decrease in IgM responses towards TI-1 antigens, (2) NIL but not HYPOX induced a decreased IgM response to TI-2 antigens, and (3) both HYPOX and NIL induced similar and significant decrease in IgG responses to TI-2 antigens. Compared with the SHAM group, IgM responses to both TD antigens did not change in HYPOX and NIL animals, whereas the IgG responses to OVA and BSA significantly decreased in HYPOX and NIL animals. These results indicate that hormones of the anterior and posterior pituitary play their own role in the regulation of humoral immune responses (AU)

Effect of arsenic on regulatory T cells.

INTRODUCTION: Arsenic (As) affects the function and survival of lymphocytes, and some arsenic compounds exert a relevant antineoplastic effect. We have explored the effect of As on T regulatory cells. RESULTS AND DISCUSSION: In vitro experiments with peripheral blood mononuclear cells from healthy subjects showed that low concentrations of As tended to increase the number of natural T regulatory (nTreg) lymphocytes, whereas concentrations >5.0 muM had an opposite effect. Furthermore, rats exposed to As showed redistribution of nTreg cells, and As administration to rats with experimental allergic encephalomyelitis increased the levels of nTreg cells in spleen and diminished the severity of this condition. On the other hand, in 47 apparently healthy subjects chronically exposed to As, we found significant inverse correlation between urinary As levels and the number and function of nTreg lymphocytes. Although most of these individuals showed enhanced levels of apoptotic lymphocytes in peripheral blood, with a diminution of mitochondrial membrane potential, no significant correlation between these parameters and urinary As was detected. CONCLUSION: Our data indicate that As seems to have a relevant and complex effect on nTreg cells.

Delayed lung maturation of foetus of diabetic mother rats develop with a diminish, but without changes in the proportion of type I and II pneumocytes, and decreased expression of protein D-associated surfactant factor.

Newborn children of diabetic mothers have an increased morbidity and mortality because of respiratory distress syndrome. We study lung histogenesis during intrauterine development of offspring of diabetic Sprague-Dawley rats at 18, 19 and 21 days of gestation (DG). Pregnant rats were grouped into diabetic (streptozotocin-induced), citrate, and control groups; five female and five male offspring were selected randomly from each group at 18, 19 and 21 DG, and a biopsy of the lung was taken and processed in paraffin for histological examination. The biopsy for the transmission electron microscopy (TEM) analysis was taken at 21 days. A delay in alveolization of the offspring at 18, 19 and 21 days of the diabetic group was observed, which was confirmed at TEM level, and also less quantity of protein D associated to surfactant in diabetic group was detected (P < 0.001). The foetuses of the diabetic group presented a delay in lung histogenesis and in differentiation of the type II pneumocytes cells, but conserved the proportion with a decrease in 50% of pneumocytes, accompanied by a diminish of protein D associated to surfactant factor.

Allergen-sensitization increases mast-cell expression of the exocytotic proteins SNAP-23 and syntaxin 4, which are involved in histamine secretion.

BACKGROUND: Activation of mast cells (MCs) via aggregation of immunoglobulin E (IgE) bound to its high affinity receptor (FcepsilonRI) results in release of inflammatory mediators from secretory granules. Histamine is one of the critical biological mediators released in the allergic response. Synaptosomal-associated protein of 23 kDa (SNAP-23) and syntaxin 4 are plasma membrane proteins that have been associated with exocytosis in MCs. Studies with monoclonal IgEs indicate that binding of IgE to FcepsilonRI induces molecular and biological changes in OBJECTIVES: The aim of this study was to investigate changes in the expression of SNAP-23 and syntaxin 4 by MCs following rat sensitization with ovalbumin (OVA). In addition, we assessed whether these proteins were involved in histamine secretion. METHODS: SNAP-23 and syntaxin 4 expression was analyzed by Western blot using MCs from control and sensitized animals. Successful sensitization was confirmed based on the passive cutaneous anaphylaxis reaction. To test the role of these exocytotic proteins in histamine secretion, permeabilized MCs were incubated with SNAP-23 and syntaxin 4 antibodies. RESULTS: Expression of SNAP-23 and syntaxin 4 was significantly higher in MCs from OVA-sensitized rats than in cells from control animals. In addition, incubation of permabilized cells with antibodies to SNAP-23 and syntaxin 4 led to a marked reduction of histamine secretion in stimulated cells. CONCLUSIONS: Sensitization with OVA increases the expression of SNAP-23 and syntaxin 4 in MCs. Furthermore, our data suggest that these exocytotic proteins participate in histamine secretion.

Cysts in the rat adenohypophysis: incidence and histology.

The incidence and histology of cysts in the adenohypophysis of adult male Wistar rats are reported. Of sixty pituitaries studied 13 of them (21.6%) presented a single cyst located in the pars distalis. The cysts varied in shape and size and were usually multilocular. Two of them were connected with the subdural space at the ventral surface of the adenohypophysis. Histology demonstrated that the cysts were filled with mucinous material and foamy macrophages and were lined by flat and cuboidal ciliated and nonciliated epithelial cells, goblet cells as well as several adenohypophysial endocrine cells such as somatotrophs, thyrotrophs, and gonadotrophs. The ciliated cells were the most numerous. Histologic and immunohistochemical studies of the uninvolved areas of the adenohypophysis showed no abnormalities and the weights and histology of the adenohypophyses and peripheral endocrine glands were within normal range, suggesting that the cysts did not impair the adenohypophysial endocrine activity. Although the morphogenesis of the cysts remained obscure, the histological and immunohistochemical findings support the hypothesis that during embryonic development, the future cysts coming from the pharyngeal epithelium is fused with the stomodeum before or during the formation of the Rathke's pouch.

Mitogenic effects of thyroxine and TRH on thyrotrophs and somatotrophs of the anterior pituitary gland in thyroidectomized rats.

The question of whether thyroxine (T4) and TRH have a mitogenic effect on pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated. Mitoses were counted in hematoxylin-eosin-stained or periodic acid-Schiff-hematoxylin-stained pituitary slides or immunostained for TSH or GH using male rats thyroidectomized for 5 months. Ten days before they were killed groups of rats were injected with different doses of T4 (0.5, 3 or 10 micrograms i.m. every second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days), or T4 plus TRH (same doses as above). Mitoses (stopped with colchicine) were counted in 1 mm2 areas at a magnification of x1000. In thyroidectomized rats, mitoses were not significantly increased and treatment with TRH or 0.5 microgram T4 alone in thyroidectomized rats did not affect mitotic counts. In thyroidectomized rats treated with higher doses of T4, mitoses were increased in a dose-dependent fashion. Simultaneous administration of TRH and T4 had a significant synergistic effect on pituitary mitoses in a T4 dose-dependent manner. The treatments also had differential effects on the relative percentages of cellular types in mitosis. Thus, 60% somatotrophs and 12.5% thyrotrophs were found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28.5% and 33.3% respectively. In thyroidectomized rats treated with low doses of T4, somatotrophs and thyrotrophs in mitosis increased to 38.4% and 80% respectively and, with simultaneous administration of a low dose of T4 plus TRH, although less effective than T4 alone, mitosis increased in somatotrophs and thyrotrophs to 11.1% and 54.5% respectively. A high dose of T4 alone did not increase the mitotic figures in somatotrophs (38.8%), while it diminished the percentage of thyrotrophs to 25%. The administration of high doses of T4 plus TRH had an opposite effect on the mitotic figures of somatotrophs and thyrotrophs and thus the percentage of somatotrophs increased to 50% while thyrotrophs decreased to 5.5%. Ten days of treatment with T4 were insufficient to reverse the histology to euthyroidism. It can be concluded that in long-standing hypothyroidism: (1) thyroid hormone replacement elicits a dose-dependent and differential proliferative response on pituitary thyrotrophs and somatotrophs, (2) TRH is devoid of mitogenic effects when administered alone and (3) the proliferative response of somatotrophs to T4 is enhanced by its co-administration with TRH, suggesting a permissive and/or synergistic effect of the thyroid hormone and TRH.

Effect of Equine Hypothalamic Extract on hormone secretion by the adenohypophysis of rats.

The effect of Equine Hypothalamic Extract (EHE) on pituitary weight and secretion of TSH, FSH-LH and ACTH was studied in the rat. The pituitary response to EHE was assessed by measuring 131I uptake by the thyroid and by weight changes of the pituitary glands, thyroids, adrenals, ovaries and uteri. 131I uptake of the thyroid and weights of the pituitary, thyroid, adrenal and uterus increased in the treated rats, whereas ovarian weights were similar to control groups. These findings indicate that the EHE containes hypophysiotropic peptides which can stimulate the secretion of pituitary hormones in the rat.

Effect of posterior pituitary lobectomy on in vivo and in vitro secretion of prolactin in lactating rats.

The effect of removing the posterior and neuro-intermediate lobes (PLX) of the pituitary gland of lactating rats was determined on both suckling-induced release and transformation of prolactin (PRL), and on regionalization of PRL release. Sixteen hours, or 1 or 4 d after either PLX or sham surgery, acute (15-min) suckling was applied. Also, regionalization of PRL release was analyzed by incubating the central and peripheral regions of APs from nonsuckled rats. Plasma PRL was analyzed by radioimmunoanalysis (RIA), whereas anterior pituitary (AP) PRL content and in vitro released PRL were determined by polyacrylamide gel electrophoresis. Plasma PRL increased 25- to 30-fold after suckling in intact and sham, and 10- to 15-fold in 1- and 4-d PLX rats, but no change occurred on either 16-h PLX nonsuckled and suckled rats. Also, PRL transformation occurred in intact, sham, and 4-d PLX suckled rats, but not in 16-h sham, or in 16-h and 1-d PLX suckled rats. Finally, the higher secretion of PRL shown in vitro by the central region of APs from intact and sham was not observed in APs from PLX rats. These results show that PLX transiently depresses the suckling-regulated PRL transformation and release. Likewise, influences from the posterior and/or neuro-intermediate lobes may determine regionalization of PRL release.

Effect of the exposure to chronic-intermittent cold on the thyrotropin and thyroid hormones in the rat.

Rats exposed to acute cold (4 degrees C for 2 h), chronic cold (4 degrees C), and chronic-intermittent cold (4 degrees C for 2 h daily) were killed after 1, 2, 3, 4, and 10 days of cold exposure. The control group was maintained at 25 degrees C. In each animal, the plasma concentration of thyrotropine (THS), triiodothyronine (T3), and thyroxine (T4) was determined by radioimmunoassay. At the initial time of exposure, elevations in TSH, T3, and T4 were observed in the rats in each experimental group. However, on the 10th day, in rats exposed to chronic-intermittent cold, TSH, T3, and T4 decreased to values lower than the control values. In animals exposed to acute cold as well as to chronic cold no differences were found, with respect to the controls, in TSH and T4. In rats exposed to acute cold for 10 days, the T3 value was lower than the control value; however, in animals exposed to chronic cold, T3 was same as that in the controls. The results indicate that, in the rat, exposure to chronic-intermittent cold produces an inhibition in the secretion of TSH and thyroid hormones.

Technical note: removal of the unfragmented pituitary gland (hypophysectomy) in the rat.

A technique to excise the pituitary gland (hypophysis) in rats is described. The basisphenoid bone is reached from the ventral neck and is perforated to expose the pituitary gland and its stalk. An aspirator allows the removal of the hypophysis and the stalk, including pars tuberalis, in one piece. The advantages of this new technique include: 1) immediate verification of the entirety of hypophysectomy; 2) broad operating field which exposes the pituitary stalk up to the hypothalamus; 3) the use of tracheal intubation and artificial respiration to improve postoperative recovery and to allow expanded operation field even during prolonged surgery. Pre- and postoperative care are described. The mean survival rate after this type of operation was 79% in rats weighing 50 to 130 g and 90% in rats larger than 130 g.