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P V Andrews

Publications and source records attributed to P V Andrews.

17 recordsLinked to original sources
PubMed1993

In vivo inhibition of the rat primary antibody response to antigenic stimulation by somatostatin.

Somatostatin inhibits in vitro lymphocyte proliferative responses from a variety of species including human, mouse and rat. The immunoinhibitory effects of somatostatin are thought to involve binding to specific cell surface somatostatin receptors on immunocompetent cells. This report describes an in vivo immunoinhibitory effect of somatostatin on the rat popliteal lymph node lymphocyte primary antibody response to sheep red blood cell (SRBC) stimulation. Infusion of somatostatin immediately following SRBC injection into the hind feet of rats had a dose-related inhibitory effect. At the highest concentration used, 10 mumol/L, the level of inhibition was similar to that previously described following neonatal capsaicin treatment of rats. This suggests that neonatal capsaicin treatment may lead to decreased primary antibody responses to SRBC by a selective effect on tachykinin containing nerves and a lesser effect on somatostatin containing nerves. The immunoinhibitory effect of somatostatin was reversed by co-infusion of neurokinin A but not substance P, both of which have been shown to stimulate this response. This suggests the possibility that multiple tachykinin receptors are involved in the modulation of the SRBC primary antibody response in vivo. These results present evidence for an in vivo immunomodulatory role of somatostatin.

Adjuvants, Immunologic↗
PubMed1992

Students can learn medicine with computers. Evaluation of an interactive computer learning package in geriatric medicine.

OBJECTIVE: To assess the effectiveness of a computer-aided learning program on dementia. DESIGN: Fourth year medical students were arbitrarily assigned to groups that used a computer-aided learning program (65) or had a tutorial covering similar material (73). These sessions were in addition to a base curriculum in a two-week course in geriatric medicine. MAIN OUTCOME MEASURES: The effectiveness of the teaching sessions was judged by the performance on a multiple choice questionnaire about dementia, given to the students on two occasions, one at the beginning and one at the end of the two-week course. RESULTS: Both groups of students scored significantly better on the second test (computer group, 66% [95% confidence interval, 64-69] to 81% [79-83] and tutorial group, 66% [63-67] to 74% [73-77]). The difference between the groups at the start of the course was not significant (F1,136 = 0.61, P = 0.61); however, there was a significant difference between the groups at the end of the course (F1,136 = 21.83, P < 0.001). CONCLUSION: Both groups improved their knowledge of dementia during the two-week course. Students who used the computer-aided learning programs showed a greater improvement in score. Computer learning programs are effective learning tools and are a useful addition to traditional teaching methods. Further study is required to assess the effects of computer-aided learning programs in long-term studies of dementia knowledge.

Computer Literacy↗
PubMed1991

Tachykinin-mediated modulation of the primary antibody response in rats: evidence for mediation by an NK-2 receptor.

Evidence for the involvement of primary afferent nerves and their associated neuropeptides in in vivo immunologic responses has been based on experiments in rats in which destruction of primary afferent nerves by the sensory neurotoxin capsaicin results in a diminished ability of the animal to mount a primary antibody response to sheep red blood cell (SRBC) antigen. This effect was shown to be reversed by substance P infusion immediately following antigenic stimulation. In this report we show that neurokinin A (NKA) is 12 times more potent than substance P in its capacity to reverse the effects of neonatal capsaicin pretreatment on the antibody response. Neurokinin A has a pD2 of 6.65 compared to 5.98 for substance P. In addition, NKA was more potent than substance P in reversing the effects of surgical lesions 2 days prior to antigenic stimulation. The effects of the D- and L-Pro9 analogues of [Glp6, Pro9]-SP6-11 on the plaque-forming cell response in capsaicin-treated rats provide further support for the hypothesis that the tachykinin receptor modulating the primary antibody response is an NK-2 receptor. These results demonstrate, for the first time, a role for NKA in in vivo immunomodulation.

Animals↗
PubMed1991

Modulation of the immune response by tachykinins.

Neuro-immunology is becoming an increasingly important discipline of immunology. This review has examined the immunomodulatory function of one group of neuropeptides, the TK, particularly SP and NKA. These peptides are localized in primary afferent nerves which have been shown to innervate several immune organs. In addition, binding sites for the TK have been demonstrated in thymus, spleen and lymph node. Several immune cell types also express neurokinin receptors including human circulating lymphocytes with binding to the Th/i class predominating, murine T and B cells, a human T lymphoblastoid cell line, human monocytes, rabbit polymorphonuclear leucocytes and guinea-pig macrophages. The apposition of nerves with immune cells and receptors for neuropeptides thus produces an environment for interaction between the nervous and immune systems. Studies in vitro and, more recently, in vivo have examined how the TK regulate immune cell responses. The TK stimulate proliferation of T cells, enhance mitogen-induced release of cytokines including IFN-gamma, TNF-alpha, IL-1 and IL-6 from mononuclear cells and macrophages, enhance immunoglobulin secretion and affect cellular chemotaxis and phagocytosis. Studies in vivo have shown a role for TK in lymphocyte recirculation of sheep lymph nodes, reversal of stress-induced thymic involution and Ig production in both rat and mouse. Many of these effects appear to be mediated via NK-2 type receptors. To date, most of the work has involved studies in vitro, but the results from these are now being validated by studies in vivo where both the immune system and neuropeptides are able to interact at many anatomical sites. The complexities of the immune and the nervous systems mean that only a small number of potential interactions has been examined. Future studies can be expected to amplify these observations, especially with respect to the understanding of inflammatory and immune diseases in humans.

Amino Acid Sequence↗
PubMed1990

Effects of capsaicin treatment on immunoglobulin secretion in the rat: further evidence for involvement of tachykinin-containing afferent nerves.

Neonatal capsaicin treatment has previously been shown to diminish the primary antibody response of adult rats to the subcutaneously administered T-dependent antigen, sheep red blood cells, as measured using a modification of the Cunningham plaque-forming cell assay technique. We have now studied the kinetics of this response in adult normal, neonatally capsaicin-pretreated and neonatally capsaicin-pretreated substance P-infused rats, and examined the effects of the tachykinin antagonist Spantide, on the plaque-forming cell response. Capsaicin pretreatment did not affect the antigen-specific plaque-forming cell response over the first 4 days following antigen injection. At days 5, 6 and 7 of the response, there was a statistically significant decrease in the number of plaque-forming cells secreting antigen-specific IgM, an effect not observed in capsaicin-pretreated rats which were given a subcutaneous infusion of substance P at the time of antigen injection. The tachykinin antagonist Spantide inhibited the plaque-forming cell response in normal rats after in vivo infusion at the time of antigen injection by more than 70%. This effect of Spantide was dose dependent, occurred with maximal effect at 10 microM, and appeared to be independent of any histamine-mediated action. The results of this study provide further evidence for a receptor-mediated immunomodulatory role of tachykinin-containing primary afferent nerves.

Animals↗
PubMed1989

Photoperiodic variation in substance P induced plasma extravasation in the rat.

Photoperiodic variation in plasma extravasation was examined following exogenous perfusion of substance P over a vacuum-induced blister base on the rat hind footpad. The results showed a generalised suppression of plasma extravasation during the dark or active phase of the light/dark cycle which appears to be independent of the circadian fluctuations in endogenous corticosterone. These findings emphasise the need to consider photoperiodic conditions as a possible source of variability in neurogenic inflammatory responses.

Animals↗
PubMed1989

Substance P induced hydrolysis of inositol phospholipids in rat skin in an in vivo model of inflammation.

The present study was undertaken to study the ability of substance P (SP) to induce inositol phospholipid (IP) hydrolysis measured as inositol mono-phosphate (IP1) accumulation, in an in vivo blister model of neurogenic inflammation in the rat hind footpad. SP was found to induce IP1 accumulation in a concentration dependent manner. The use of SP analogues (SP5-11 and SP1-7) indicated that the response is mainly mediated by the C-terminal sequence of the peptide. The response was significantly reduced by the SP antagonist spantide, suggesting that the response is mostly due to activation of the SP receptor on small diameter vessels. Capsaicin pretreatment did not have an effect on the ability of SP to induce the response. Experiments with mepyramine suggest that the response is also partly mediated by SP induced histamine release from mast cells. This is the first study to provide direct evidence for phosphoinositide mediated SP effects in the skin.

Animals↗
PubMed1989

NK-1 receptor mediation of neurogenic plasma extravasation in rat skin.

1. Plasma extravasation was induced by electrical nerve stimulation and by perfusion of tachykinins over a vacuum-induced blister base on rat footpad. 2. Stimulation of the sciatic nerve (18 V, 15 Hz, 0.5 ms) for 20 min produced a significant increase in the protein content of the perfusate. The response in capsaicin pretreated rats was only 4% of the control response. This indicates that the electrically-induced plasma extravasation response was mediated by capsaicin-sensitive sensory fibres. 3. Exogenous perfusion of the mammalian tachykinins substance P, neurokinin A and neurokinin B and the non-mammalian tachykinins physalaemin, kassinin and eledoisin was used to determine the tachykinin receptor type mediating the plasma extravasation response. Dose-response curves of the tachykinins (10(-9) M-10(-4) M) gave a rank order of potency of substance P = physalaemin greater than eledoisin greater than or equal to kassinin greater than neurokinin B = neurokinin A. 4. In addition, specific agonists of neurokinin receptors were perfused. Perfusion of [Glp6, D-Pro9] SP6-11 and [Glp6, L-Pro9]SP6-11 demonstrated that the L-Pro isomer was much more potent than the D-Pro isomer. 5. The rank order of potency and the greater potency of [Glp6, L-Pro9]SP6-11 over its D-isomer indicate an NK-1 neurokinin receptor mediates plasma extravasation in rat footpad skin.

Animals↗
PubMed1988

VIP modulates substance P-induced plasma extravasation in vivo.

Substance P (SP), a putative mediator of neurogenic inflammation, has previously been shown to induce plasma extravasation when exogenously perfused over a blister base induced on the rat hind foot pad. Using the same animal model, we have studied the role of vasoactive intestinal polypeptide (VIP), one of the neuromodulators in primary afferent neurons, on SP-induced plasma extravasation. At all concentrations tested (2.5, 5 and 10 microM), VIP did not cause plasma extravasation by itself, however, it increased that due to 1 microM SP, in a dose-related manner. We have also studied the effect of VIP on the local blood flow in the blister base using a laser doppler-flowmeter. VIP was also found to increase the local blood flow in a dose-dependent manner. The present results provide evidence for the first time in vivo of a role for VIP in modulating a neurogenic inflammatory response induced by SP. The mechanism underlying this action is probably related to the vasodilator activity of VIP.

Animals↗
PubMed1987

The effect of substance P on the regional lymph node antibody response to antigenic stimulation in capsaicin-pretreated rats.

The undecapeptide substance P (SP) contained in primary afferent nerves is thought to mediate that part of the neurogenic inflammatory response consisting of vasodilation and plasma extravasation. This response is diminished in rats pretreated as neonates with the neurotoxin capsaicin. It is not known whether primary afferent nerves influence cellular responses of the immune response to antigenic stimulation. Using 6- to 12-wk-old Sprague-Dawley rats pretreated as neonates with capsaicin, we examined the regional lymph node response to a s.c. antigenic stimulus of sheep red blood cells. The number of cells secreting antigen-specific antibody in these animals was reduced by more than 80% using direct and indirect plaque assay methods. The reduced antibody response in capsaicin-pretreated animals was reversed by a s.c. infusion of SP given over a 4-hr period at the injection site immediately after antigen stimulation. This response had a threshold at approximately 1.0 X 10(-5) M SP. SP1-7 (1.0 X 10(-5) M) was without effect but an infusion of SP5-11 (1.0 X 10(-5) M) reversed the effects of capsaicin treatment indicating a carboxyl-terminal effect of SP. The results suggest that the reduced response of capsaicin-treated animals to an antigenic stimulus is due to an effect of capsaicin on the SP-containing primary afferent nerves rather than a toxic effect of capsaicin on the immune system.

Animals↗
PubMed1987

Neurogenic plasma extravasation in response to mechanical, chemical and thermal stimuli.

Nociceptors at distal terminals of unmyelinated primary afferent nerve fibres mediate neurogenic inflammation. Most studies have examined only the neurogenic inflammatory response to non-physiological antidromic electrical nerve stimulation. It has not been possible to determine whether polymodal nociceptors mediate the response to physiological stimulation with mechanical, chemical and thermal stimuli. In this study we have induced plasma protein extravasation to stimulation with wool fabric (81 +/- 9 micrograms/mL), bradykinin (86 +/- 8 micrograms/mL) and heat (111 +/- 16 micrograms/mL) in perfused vacuum-induced blisters on the rat hind footpad. These values represent significant increases over the protein concentration of 30 micrograms/mL (p less than 0.005; p less than 0.001; p less than 0.001, respectively; n = 6 to 8 for each group). Plasma extravasation was significantly reduced for each stimulus modality (p less than 0.001; p less than 0.05; p less than 0.01, respectively) in animals pretreated as neonates with capsaicin, demonstrating that part of the response is neurogenically mediated. It is concluded that neurogenic inflammation to polymodal physiological stimuli occurs in the rat through capsaicin-sensitive primary afferent nerve fibres.

Animals↗
PubMed1987

The effects of capsaicin denervation on leucocyte and complement components of the inflammatory response.

Primary afferent unmyelinated nerves containing substance P modulate the inflammatory response to injury through a process known as neurogenic inflammation. Rats treated as neonates with capsaicin, to destroy these nerves permanently, have a reduced capacity to mount an inflammatory response as measured by swelling or plasma extravasation. In this study we examined some aspects of the immunological response to injury in capsaicin-treated rats. One question addressed was whether changes in the inflammatory response are due to abnormal innervation or to a direct toxic effect of capsaicin. It was observed that the histological appearance of thymus, splenic white pulp and popliteal lymph nodes was unaltered in capsaicin-treated rats. However, there was an increase in leucocyte number in splenic red pulp. There was also an increase in the white cell numbers in the peripheral circulation (7 +/- 1 X 10(6)/mL for normal rats and 14 +/- 2 X 10(6)/mL in capsaicin-treated rats, p less than 0.001, Student's t-test). This affected all white cell subgroups. Complement levels in capsaicin-treated rats were not different from normals and both groups showed a similar depletion 6 days following antigenic stimulation with sheep red cells. These data support the view that the reduced cellular response to injury in the capsaicin-treated rat is secondary to the effect of the chemical on afferent nerves and not to a primary toxic effect on cells of the inflammatory response.

Animals↗
PubMed1986

Neurogenic inflammation caused by wool fabric in the rat; possible mediation by substance P.

We have measured plasma extravasation in response to stimulation of the rat hind footpad with wool fabric. The stimulus was delivered using a constantly weighted disc of wool rotating at 4 revolutions per minute for 30 min on the base of blisters induced by vacuum. The protein content of prestimulated blister base perfusate was 38 +/- 2 micrograms/ml in a 30-min collection. With stimulation this increased to 80 +/- 10 micrograms/ml (P less than 0.001; Student's paired t-test). No increase in plasma extravasation was observed in adult animals pretreated as neonates with capsaicin indicating that the plasma extravasation observed was neurogenically mediated. Plasma extravasation was also observed with substance P added to the perfusate. The threshold for substance P-induced plasma extravasation was 2 X 10(-11) mol/30 min. These results suggest that neurogenic inflammation induced by the mechanical stimulus of wool fabric may be mediated by substance P. This reaction may be involved in wool-induced prickle and itch noted in some individuals.

Animals↗
PubMed1985

The effect of nerve lesions on the inflammatory response to injury.

The effects of surgical denervation, capsaicin, and 6-Hydroxydopamine pretreatment on the inflammatory response to thermal injury have been investigated in the rat. Surgical denervation and capsaicin pretreatment reduced the cellular and exudative reactions to the injury. 6-Hydroxydopamine appeared to have a selective effect on the exudative reaction only. The effects of surgical denervation are partly explained by local and systemic effects of the procedure.

Animals↗
PubMed1985

Neurogenic inflammation in skin blisters.

The histology of blisters induced in rats using dry-ice or vacuum applied to the hind limb footpad has been examined by light microscopy and indirect fluorescence immunohistochemistry for substance P like immunoreactivity. The effects of sciatic nerve stimulation on plasma extravasation as determined by estimation of Evans Blue content of blister fluid has been examined. Plasma extravasation occurs in both blister types following nerve stimulation. Plasma extravasation may be induced by substance P released from nerve terminals in the blister wall. Vacuum induced blisters have less tissue and nerve damage and therefore less of an inflammatory response, but plasma extravasation is greater in thermal blisters. Blisters serve as a useful model for the study of neurogenic inflammation.

Animals↗
PubMedDate not supplied

Tachykinin-induced vasodilatation in rat skin measured with a laser-Doppler flowmeter: evidence for receptor-mediated effects.

Vasodilatation was induced by perfusion of the tachykinins substance P (SP), neurokinin A and neurokinin B and the analogues [Glp6, D-Pro9]SP-(6-11) and [Glp6, L-Pro9]SP-(6-11) over the base of vacuum-induced blisters on the rat footpad. Vasodilatation was measured as change in blood flow using a laser-Doppler flowmeter. The tachykinins induced vasodilatation in a dose-response manner with a threshold of approximately 3 pmol and pD2's of 6.48, 6.13 and 6.21 for SP, neurokinin A and neurokinin B respectively. The D- and L-Pro analogues of [Glp6, Pro9]SP-(6-11) also induced vasodilatation in a dose-dependent manner. The L-Pro analogue was more potent than the D-Pro analogue (D/L ratio of the EC50's = 21) which suggests the involvement of an NK-1 type receptor in the mediation of small vessel vasodilatation. The vasodilatation to SP was reduced by 64% and 59% in capsaicin- and antihistamine-pretreated animals respectively, demonstrating the involvement of capsaicin-sensitive primary afferent nerves and mast cells in the vasodilatation component of the neurogenic inflammatory response.

Animals↗