Vasoactive intestinal polypeptide (VIP)--immunoreactive nerve fibres in the mammary gland of the pig

Immunohistochemical studies have been performed to investigate the coexistence of VIP with dopamine-beta-hydroxylase (D(beta)H), vesicular acetylcholine transporter (VAChT), somatostatin (SOM) or neuropeptyd Y (NPY) within nerve fibres supplying the immature mammary gland in the pig. Generally, a moderate number of the VIP-immunoreactive (VIP-IR) nerve fibres were located in the nipple and parenchyma of the gland. VIP-IR fibres surrounded smooth muscle cells (SMC), blood vessels (BV) and lactiferous ducts (LD). Double-labelling immunohistochemistry revealed that some of VIP-IR nerve fibres also contained immunoreactivity to D(beta)H. VIP/D(beta)H-IR nerves were associated with BV and SMC and single fibres were observed around the LD in both nipple and parenchyma of the gland. VIP/VAChT-IR nerve fibres were not observed. The majority of VIP-IR fibres associated with SMC were also SOM-IR. Less numerous VIP/SOM-IR fibres supplied the BV and were located around the LD of the gland. A small number of VIP-IR nerves also displayed immunoreactivity to NPY. VIP/NPY-IR nerve fibres supplied the BV of the gland.     

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-alpha and IL-6

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) down-regulate cytokine production. Because human septic shock involves excessive cytokine production, the effect of VIP/PACAP was investigated in a high endotoxemia murine model. Both peptides protect against endotoxin-induced lethality and prevent septic shock-associated histopathological alterations. VIP/PACAP reduce serum and peritoneal TNF-alpha and IL-6, suggesting that the protective effect is exerted by inhibiting the production of endogenous TNF-alpha/IL-6. Consistent with this mechanism, VIP does not protect against septic shock induced by exogenous TNF-alpha. The immunomodulatory role of VIP in vivo is supported by the appearance of high levels of VIP in serum and peritoneal fluid following LPS administration. Thus, the neuropeptides VIP/PACAP protect from the lethal effect of high endotoxemia, presumably by down-regulating TNF-alpha and IL-6 production, and may offer an alternative in the treatment of human septic shock syndrome.     

High-dose interferon-gamma alters the distribution of B lymphocytes and macrophages in rat spleen and lymph nodes

Continuous intravenous infusion of rat interferon-gamma (IFN-gamma) for 3 days provokes profound alterations of splenic architecture in LEW rats. The marginal zone of the white pulp is almost totally depleted of B lymphocytes and the follicles are reduced to small remnants. IgM kappa + plasmablasts and plasma cells increase substantially in the outer periarteriolar lymphatic sheath (PALS) and in the splenic red pulp. In addition, marginal metallophilic and marginal zone macrophages are augmented, partially by proliferation. It is discussed whether the activation and proliferation of these macrophages prevent replenishment of the marginal zone and follicles with recirculating B cells. Changes in B lymphocyte and medullary macrophage distribution are also present in submandibular and mesenteric lymph nodes.     

Plasticity of innervation of the medulla of axillary lymph nodes in the rat after antigenic stimulation

The purpose of this investigation was to test the hypothesis that activation of the immune system in rats will lead to changes in the density of innervation in lymph nodes. In order to reduce the variability between animals, the rats were reared under sterile conditions and immunostimulation was effected by subcutaneous application of bovine albumin in a region draining to the axillary lymph nodes of both sides. Control animals received an equivalent application of sterile physiological saline. The animals were sacrificed 10 days and 27 days and 4 months after immunostimulation. The nerves in the axillary lymph nodes were quantified by light microscopy in silver impregnated sections and at the ultrastructural level on ultrathin sections. The survival times were chosen so that the first group was in the ascending phase of antibody production, the second group at the peak, and the third group in the declining phase. Both at the light and ultrastructural levels, there were statistically significant differences in the density of innervation of medulla between the groups, with a particularly pronounced increase in the group 4 months after immunostimulation. At the ultrastructural level, there was also an increase in the density of incompletely ensheathed axonal profiles in the parenchyma of the medulla, while the nerves associated with blood vessels were not increased. We conclude that immunostimulation leads to morphological changes in the innervation of the medulla of axillary lymph nodes, that are consistent with the concept of functional activation of the autonomic nervous system through the immune system.     

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP-27, but not PACAP-38) degradation by the neutral endopeptidase EC 3.4.24.11

VIP (vasoactive intestinal polypeptide) and PACAP (pituitary adenylate cyclase-activating polypeptide), which are potent relaxing agents in the airways, were submitted to in vitro degradation by the neutral endopeptidase EC 3.4.24.11 (NEP), one of the most active peptidase in the lung, to test their relative resistance to proteolysis. Both VIP and PACAP(1-27) were cleaved by NEP, but PACAP(1-38) was not. The main fragments produced were VIP(1-22) and VIP(1-25), and PACAP(1-22) and PACAP(1-25), respectively. The degradation of VIP(1-27), PACAP(6-27), and PACAP(13-27) was also hindered by extending their C-terminal ends with the (28-38) sequence of PACAP(1-38). The sensitivity to enzyme degradation was gradually reduced when the C-terminal extension was increased from PACAP(1-27) to PACAP(1-29), PACAP(1-32) and PACAP(1-38). The biological activities of the degradation products were evaluated on the three classes of PACAP/VIP receptors, with VIP(1-25) and PACAP(1-25) retaining an important part of their activities on the VIP1 receptor. Thus, the degradation of VIP and PACAP(1-27) by the neutral endopeptidase 24.11 might produce a VIP1 receptor-selective active metabolite, provided that very high VIP or PACAP(1-27) concentrations are achieved in the receptor vicinity.     

Twenty-four-hour rhythms in immune responses in rat submaxillary lymph nodes and spleen: effect of cyclosporine

Twenty-four-hour variations in cellularity, lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation, and natural killer (NK) activity were examined in submaxillary lymph nodes and spleen of rats injected with Freund's complete adjuvant or its vehicle and kept under light from 08:00 to 20:00 h daily. A significant daily variation in cellularity was detected, exhibiting maxima at 09:00 h in submaxillary lymph nodes (nonimmunized and immunized rats) and at 13:00 h in spleen (immunized rats only). Submaxillary lymph node LPS- and Con A-mitogenic effect displayed maximal activity during daytime (peak at 13:00-17:00 h). In spleen, the maxima for 24-h rhythm in LPS-induced cell proliferation and NK activity occurred at midnight and at early morning (09:00 h), respectively. Con A-induced spleen cell proliferation peaked at midday in nonimmunized rats only. Injection of the immunosuppressive drug cyclosporine decreased Freund's adjuvant-induced augmentation of LPS and Con A mitogenic effect in both tissues and diminished spleen cell number. Cyclosporine blunted circadian rhythms in submaxillary lymph node Con A response and cell number, while it shifted the maximum in LPS effect to peak at 01:00 h. Cyclosporine also suppressed the circadian changes in LPS- and Con A-induced spleen cell proliferation, but not those found in NK activity. The results indicate the existence of 24-h rhythms in immune responses of rat submaxillary lymph nodes and spleen with maxima at different times of the day and that were significantly affected by cyclosporine injection.     

Neurogenic relaxation mediated by vasoactive intestinal polypeptide (VIP) in the isthmus of the human fallopian tube

The smooth musculature of the Fallopian tube is important for normal ovum transport, fertilization and implantation. Little is known about the factors controlling the motor activity of the isthmic sphincter. Studies were performed on smooth muscle preparations from the human tube in vitro. Electrical field stimulation of the nerves in the isthmic region reduced the motor activity, particularly in the circular muscle. The response was unaffected by adrenergic and cholinergic antagonists, but blocked by tetrodotoxin, suggesting a neural involvement. Vasoactive intestinal polypeptide (VIP) was considered a likely candidate for the neural mediation of this response in view of the high density of VIP-containing nerve fibres in this region, and in view of the fact that exogenous VIP causes a marked reduction of the tubal motor activity. To test whether VIP might be the endogenous mediator of this effect, nerve stimulation was carried out in the presence of large amounts of exogenous VIP in order to occupy all VIP receptors; the motor inhibitory action of VIP was counteracted by vasopressin. Under these conditions, nerve stimulation failed to reduce isthmic motor activity. This was not due to vasopressin since reduction occurred in the presence of this peptide alone. The results suggest that VIP is responsible for the neurogenic inhibition of motor activity in the isthmus region of the human Fallopian tube.     

Effect of protein malnutrition on the glycolytic and glutaminolytic enzyme activity of rat thymus and mesenteric lymph nodes

Genotyping of hepatitis C virus (HCV) of liver disease patients in the Dominican Republic was performed. Eighty-four samples positive for HCV antibody, which were confirmed by ELISA, particle agglutination, and recombinant immunoblot assay III tests, were subjected to HCV genotyping by polymerase chain reaction using type-specific primers located in the nonstructural protein 5 region. Of the 84 samples tested, 50 (59%) were found to have genotype 1a/I and this genotype was the most frequent type detected in the present study. The numbers of isolates of genotypes 1b/II, 2a/III, 2b/IV, and 3a/V were three (3.6%) six (7.1%), two (2.4%), and two 2.4%), respectively. The number of samples having mixed genotype populations was 16 (19%). The possible causes of the high prevalence of genotype 1a/I in the Dominican Republic compared with other countries and of the high detection ratio of samples having mixed genotypes are discussed.     

Vasoactive intestinal polypeptide induces analgesia and impairs the antinociceptive effect of morphine in mice

OBJECTIVE: To explore the use of sun protection behaviours and the experience of sunburn in a sample of parents and their children in New Zealand. METHODOLOGY: Information was collected from 887 parents using postal questionnaires at the beginning of and during the summer. RESULTS: Thirty per cent of the parents believed their child looked healthier with a suntan, and 40% intended to let their child get a suntan during the summer. Predictors of intention to tan included level of parental education, the child's age, the child's sensitivity to burning and experience of sunburn in the parent. At the end of the summer period, 29% of the children were reported as being sunburned. Predictors of sunburn in the child were the age of the child, experience of sunburn in the parent and use of sunscreen SPF15+ by the parent. CONCLUSION: Despite intense media coverage of the dangers of overexposure to the sun, it is clear that a significant proportion of children are still getting sunburned.     

Different effects of visual deprivation on vasoactive intestinal polypeptide (VIP)-containing cells in the retinas of juvenile and adult rats

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide that has been shown to be present in a distinct subset of retinal amacrine cells (VIP+ cells). Previous work has suggested that the expression of retinal VIP might depend on the lighting conditions prevailing. Reasoning that a careful analysis of the exact conditions of this interaction and its time course might offer clues to the functional role of retinal VIP, we performed a quantitative immunohistochemical analysis of the effects of visual deprivation on the retinal VIP+ system in adult and in visually inexperienced neonatal rats. In adult rats visual deprivation caused a marked suppression of VIP-like immunoreactivity (IR) in both somata and processes of VIP+ cells which increased linearly over time, reducing the number of VIP+ cells to about 30% of the control value after approximately 50 days of deprivation. The observed changes were specific for VIP and were independent of the form of deprivation used (monocular lid suture versus keeping rats in constant darkness). However, the effects of visual deprivation were dependent on the developmental state of the rats, since juvenile rats without previous visual experience exhibited a decrease in VIP+ cells and fibers which was much smaller and occurred significantly slower than in adult rats. The suppression of VIP-like IR was completely reversible in both juvenile and adult rats when previously deprived rats were returned to a normal visual environment.     

Tuberculosis of peripheral lymph nodes (author's transl)

The diagnosis and therapy of tuberculosis involving peripheral lymph nodes is discussed in a series of thirthy patients. Diagnosis is best made by both bacteriological and histologic study. Therapy is best effected by combining medical tuberculostatics with operative intervention. Epithelioid cell or proliferative forms of lymph node tuberculosis best respond to medical management.     

Endonucleolysis of chromatin in rat thymus and spleen lymphocytes after irradiation

The level of soluble DNA fragments (polydesoxynucleotides) in thymus and spleen lymphocytes is enhanced 12 h after the whole-body X-ray irradiation in dose of 0.5 and 1 Gy. The level of Ca2+, Mg(2+)-DNAase activity in lysed cells extracts, measured with calf spleen DNA, was enhanced in the region of 0.1-0.5 mM CaCl2 in incubation medium and decreased at 5 mM CaCl2. Monitoring of DNA fragmentation by electrophoresis in agarose gels showed the presence of fragments with approximately 200, 400, 800 bp length. X-ray induced DNA fragmentation is supposed to be associated with Ca2+, Mg(2+)-endonuclease activation.     

Ischemic-reperfused rat skeletal muscle: the effect of vasoactive intestinal peptide (VIP) on contractile force, oxygenation and antioxidant enzyme systems

The effect of vasoactive intestinal peptide (VIP) on the nerve-stimulated contraction, tissue oxygenation, lipid peroxidation and antioxidant enzymes activities-superoxide dismutase and catalase was investigated in the rat gastrocnemius muscle exposed to 4 h ischemia-4hr reperfusion. Ischemia caused significant decrease in muscle contractile force, oxygenation and superoxide dismutase enzyme activity. Reperfusion of ischemic muscle increased the muscle contractile force and restored the tissue oxygenation to the baseline level. Superoxide dismutase and catalase activities of reperfused muscle increased significantly. However neither ischemia nor reperfusion affected gastrocnemius muscle malondialdehide (MDA) levels. VIP administration at the onset of reperfusion significantly increased skeletal muscle contractile force and tissue oxygenation even higher than baseline and reperfusion values. VIP also normalized the increased superoxide dismutase and catalase activities of reperfused skeletal muscle. In conclusion, VIP, acting as a powerful antioxidant and preserving contractile machinery seems to be a promising endogenous peptide that can salvage the skeletal muscle from severe ischemia-reperfusion injury.     

Human adrenocortical NCI-H295 cells express VIP receptors. Steroidogenic effect of vasoactive intestinal peptide (VIP)

VIP receptors are frequently overexpressed by various endocrine tumors. In this study the expression of VIP receptors in the human adrenocortical carcinoma cell line NCI-H295 and their involvement in the regulation of steroidogenesis was investigated. NCI-H295 cells express VIP1 and VIP2 receptors as demonstrated by RT-PCR, whereas they do not express VIP itself. The receptors are functionally coupled to steroidogenesis since VIP (10(-9) M to 10(-6) M) exerted a dose-dependent stimulatory effect on the release of aldosterone, cortisol, and DHEA. VIP increased ACTH-stimulated releases of aldosterone and cortisol. The proliferation rate of NCI-H295 cells was not affected by VIP. These data show that NCI-H295 cells express both forms of the VIP receptor and that VIP is involved in an ACTH-independent regulation of steroidogenesis in the adrenal tumor cells.     

Aberrant retropharyngeal lymph nodes of a horse (Equus caballus)

The occurrence of aberrant lymph nodes, on both sides of the head of a horse, belonging to the retropharyngeal lymphocenter has been reported.     

An electrophysiological study on the vagal innervation of the thymus in the rat

Vagal innervation of the thymus was studied by means of electrophysiological technique in the rat. Under urethane anesthesia, evoked action potentials originated from cervical vagus by electrical stimulations were recorded from the central cut end of the thymic branch of the vagus nerve after averaging for 32 times. It was observed that the conduction velocities are distributed in the range of 0.56-6.84 m/s, and the majority of vagal fibers in the thymic branch of the vagus nerve belong to a nonmyelinated C-fiber group. Further, it was confirmed that the right and left lobes of the thymus are innervated by cervical vagi bilaterally. The results suggest that the thymic branch of the vagus nerve plays a role in modulation of thymic function.