Inflamed Group Research Articles

Comparison of synovial PO2 and sympathetic vasoconstrictor responses in normal and acutely inflamed rabbit knee joints

Experiments were performed to assess the effect of acute inflammation of the rabbit knee joint on the partial pressure of oxygen in synovial fluid (Ps,O2) and nerve-mediated vasoconstrictor responses of articular blood vessels. With the hypodermic needle oxygen electrode sited within the synovial cavity in the posterior region of the knee joint, mean (+/- S.E.M.). Ps,O2 was 37.4 +/- 3.6 mmHg (n = 10) in the inflamed group, which differed significantly (P < 0.05) from that occurring in the normal group from a different series (48.2 +/- 3.1 mmHg; n = 18). Ps,O2 was found to decrease with increasing depth of penetration of the oxygen electrode into the joint cavity of the inflamed knee, as in the normal knee. The lowest values were observed close to articular cartilage. Absolute blood flow was measured using radiolabelled microspheres whilst relative changes in blood flow were assessed using laser Doppler flowmetry. The former technique showed that the inflamed joints had a significantly higher blood flow. Electrical stimulation of the posterior articular nerve (PAN) of the knee resulted in vasoconstriction of knee joint blood vessels, which was accompanied by a reduction in Ps,O2. The frequency-response and voltage-response profiles to electrical stimulation of the PAN, although differing in magnitude, showed a high degree of correlation between blood flow and Ps,O2. The frequency-response profile to electrical stimulation of the PAN shifted to the right in inflamed joints compared with normal joints, suggesting a reduction in the efficacy of the sympathetic nervous system in regulating blood flow to the inflamed joints. Although the inflamed joint had a higher blood flow, Ps,O2 was lower compared with the normal joint. The results of this study show significantly altered blood flow, Ps,O2 and nerve-mediated constrictor responses in the acutely inflamed joint. These are related to the inflammatory response and may contribute to the pathogenesis of arthritis.

Conditioned place preference paradigm: a novel approach for analgesic drug assessment against chronic pain

In response to concerns over the clinical relevance of analgesic testing paradigms which involve acute nociceptive stimuli, the present research examined the utility of the conditioned place preference (CPP) paradigm as a novel approach for determination of analgesic drug efficacy against chronic nociception. Rats display preferences for environments that have been previously paired with positively reinforcing drugs; whether place preference to the negatively reinforcing effects of analgesic drugs in an animal model of chronic pain occurs is yet unknown. The present research sought to determine whether animals experiencing chronic pain would display a place preference for an environment paired with analgesic drug treatment. Persistent inflammatory nociception was induced by unilateral injections of complete Freund's adjuvant (0.1 ml) into the rat hind paw. Place preference to the opiate agonist morphine, the N- methyl- d-aspartate (NMDA) receptor antagonist MK-801 and the non-steroidal anti-inflammatory drug (NSAID) indomethacin was examined in 3 separate experiments. Rats received 8 counterbalanced conditioning trials (4 drug, 4 no-drug) of 60 min each with various drug doses (morphine: 3.0 and 10.0 mg/kg; indomethacin: 2.5 and 5.0 mg/kg; MK-801: 0.03, 0.1 and 0.3 mg/kg i.p.) or vehicle serving as the reinforcing stimuli in a 3 compartment (2 stimuli, 1 neutral) place preference apparatus. In general, morphine place preference was observed in both inflamed and non-inflamed groups; inflamed groups exhibited enhanced morphine place preference than non-inflamed groups. MK-801 produced a low-dose place preference in inflamed animals; higher doses of MK-801 produced a place aversion in both inflamed and non-inflamed groups. Indomethacin failed to produced place preference in either inflamed or non-inflamed groups. These data demonstrate that the negatively reinforcing properties of analgesic drugs can be assessed via the CPP paradigm. In addition, this paradigm offers greater clinical relevance as animals determine drug efficacy without the involvement of high-intensity, phasic nociceptive stimulation.

Detection of Cellular Adhesion Molecules in Inflamed Human Corneas

The expression of cellular adhesion molecules in 31 penetrating keratoplasty specimens from a broad range of corneal inflammatory diseases was studied using monoclonal antibodies and an immunoperoxidase technique. Corneas were divided into noninflamed, mild to moderately inflamed, and severely inflamed groups based on histologic findings. The panel of adhesion molecules studied included HLA-ABC, HLA-DR, CD3, LFA-1, MAC-1, ICAM-1, PECAM-1, VCAM-1, and E-selectin-1. The adhesion molecules ICAM-1, HLA-DR, PECAM-1, CD3, VCAM-1, LFA-1, and MAC-1 were selectively expressed in areas of corneal inflammation. In general, HLA-DR and intercellular adhesion molecule ICAM-1 were co-expressed in similar regions. PECAM-1 was restricted to zones of marked inflammation and vascularization. E-selectin-1 was detected only in the stroma of a graft melt in a patient with active ocular cicatricial pemphigoid, and may reflect a primary regulatory dysfunction in this disorder. The ICAM-1 ligand was, in general, more diffusely distributed than its receptor LFA-1, a beta-2 integrin found on leukocyte cell membranes. The localization of the integrin MAC-1, present on macrophages, neutrophils, and some lymphocytes, did not always parallel the staining pattern of ICAM-1, suggesting promiscuity in its binding to other ligands besides ICAM-1. Adhesion molecules are detected readily at sites of corneal inflammation and may play a critical role in facilitating the recruitment of immune regulatory cells to these areas. Future efforts to block or modulate the expression of intercellular adhesion molecules may provide new therapeutic options in the treatment of corneal inflammatory diseases.

Evidence of impaired acidification in vitro by human gall bladder mucosa in patients with gallstone disease

Objective: To study the capacity of the human gall bladder with and without gallstones to secrete H + ions. Design: Human gall bladders were studied in vitro which permitted the measurement of the electrical potential difference and secretion of H + ions. Results: Thirty-three gall bladders were studied (five normal, 20 with cholesterol and eight with pigment gallstones). The normal gall bladder group secreted 14.53 ± 1.04 nmol (mean ± SEM), the mildly inflamed group 8.27 ± 1.71 nmol and the moderately inflamed group 4.03 ± 0.94 H + over 60 min in the mucosal bathing fluid. H + secretion was significantly different when the mildly and moderately inflamed groups were compared with the normal group (P < 0.002 and P < 0.009, respectively)

Effect of peripheral nerve stimulation on the dorsal horn cell activity in cats with cutaneous inflammation.

There are some reports showing that an experience of long-enduring pain causes a change in the pain transmission system, suggesting a plastic nature of the nociceptive system. However, most of the studies concerning the analgesic effect of peripheral nerve stimulation dealt with normal animal or human subjects. So, the present study was undertaken to investigate the effect of peripheral nerve stimulation on the dorsal horn cell activity using a tonic pain model, which was made by producing a cutaneous inflammation. The main results are summarized as follows. 1) The evoked activity by electrical or natural stimulation as well as spontaneous activity was enhanced, and the receptive field size was also expanded by the inflammation. 2) Peripheral nerve conditioning stimulation reduced the C-response of the dorsal horn cell in the normal and inflamed group, and the degree of inhibition between the two groups showed no significant difference. 3) Inhibition of the C-response of the dorsal horn cells by peripheral conditioning stimulation was completely reversed by naloxone in the inflamed group whereas there was a partial block in the normal group.

Abnormalities of differentiation and maturation in the oesophageal squamous epithelium of patients with tylosis: morphological features

Tylosis is an autosomal dominant inherited defect of keratinization, associated in two Liverpool families with a high risk of developing oesophageal squamous carcinoma. In 29 individuals, followed by regular endoscopy and biopsy, we have noted several morphological abnormalities of the epithelium in this pre-cancerous condition. A control group of 43 non-tylotic patients with normal oesophageal histology and a further 26 patients with acute oesophagitis was used for comparison. Recognizable dysplasia was confined to the older age range in the tylotic group and was present in four patients. Almost half of the patients showed acute inflammation. Abnormalities of maturation were common, the most frequent being the presence of prominent basophilic inclusions and clear cell acanthosis, with parakeratosis and frank surface keratinization present in smaller numbers. There was, however, no statistically significant difference between the tylotic and inflamed control groups for any of these features. The only feature to show a significant difference between these groups was the presence of individual cell keratinization. The results suggest that in the oesophageal epithelium of the patients with tylosis, inflammation is the predominant abnormality, together with individual cell keratinization, and that these lesions appear in a much younger age group than dysplasia.

Demonstration of tissue collagenase activity in vivo and its relationship to inflammation severity in human gingiva.

To directly demonstrate both the presence and in vivo activity of tissue collagenase (EC 3.4.24.7) during gingival inflammation, tissue extracts from 54 specimens of variously inflamed human gingiva were analyzed individually for: a) collagenase‐specific collagen degradation products, and b) collagen‐bound collagenase. The TCA collagen degradation product, identified using SDS‐PAGE, was shown in 13/19 (68.4%) of insoluble tissue‐residue fractions extracted from moderate‐to‐severely inflamed gingiva, but in only 2/21 (9.6%) slight‐to‐mildly inflamed gingival specimens, suggesting differences in the in vivo collagenase activity between the two groups. Using in vitro collagenase assays, gingival collagenase (as bound to insoluble collagen) was demonstrated in 92.8% of the moderate‐to‐severely inflamed gingival specimens and in 50% of the slight‐to‐mildly inflamed gingival specimens. A relationship was established between the active and latent forms of the enzyme and the degree of inflammation. Active enzyme was present in 78% of the moderate‐to‐severely inflamed specimens and in 14% of the slight‐to‐mildly inflamed gingiva. In contrast, latent collagenase was predominant in the slight‐to‐mildly inflamed group (86% of coliagenase‐positive samples) compared with 46% of coliagenase‐positive moderate‐to‐severely inflamed gingival samples. The collagen‐bound gingival collagenase was inhibited by metal ion chelators, sulphydryl reagents and 10% FBS, but not by serine nor thiol‐proteinase inhibitors and is therefore a neutral metalloproteinase.

Effect of inflammation upon human gingival cyclic AMP metabolism.

The effect of the increasing degree of human gingival inflammation on adenylate cyclase (basal, fluoride stimulated) and low Km and high Km cAMP phosphodiesterase activities were evaluated in separate studies. Human gingival biopsies were classified by the Löe Bleeding Index as mildly, moderately, and markedly inflamed. Basal and F- stimulated adenylate cyclase (cAMP synthesis) activities were found to be unaltered by the increasing degree of inflammation when the data were expressed on either a mg wet wt, or mg protein basis. A significant loss of F- stimulated adenylate cyclase (mg protein) activity was observed in the moderately inflamed group when the data were compared with either the mildly or markedly inflamed groups of tissue. The low Km, and high Km cAMP phosphodiesterase activities (cAMP degradation) were found to be unaffected by gingival inflammation. This suggests that neither cAMP synthesis, nor degradation are stimulated in human gingiva by inflammation.

Discharge characteristics of fine medial articular afferents at rest and during passive movements of inflamed knee joints

After induction of an experimental knee joint inflammation, the activity of single Group III and IV afferent units in the medial articular nerve of the cat was recorded at rest and during passive movements. the properties of these units were compared to those sampled from normal knee joints. The proportion of units displaying resting discharges was higher in the inflamed group. The frequency of discharges was also higher. The receptive fields were larger than those in the control units. Passive movements in the normal working range of the joint activated many more units in the inflamed joint than in the control sample. We conclude that joint inflammation sensitizes articular nociceptors to be active not only at rest, but also during normally innocuous joint movements.

Quantitative and functional aspects of T-cell populations in human gut mucosa

Lymphocytes were isolated from rectal biopsies and resected gut specimens through a simple mechanical technique, and assayed for T-cell quantitation and mitogenic response to PHA and PPD. T-cells were found in considerable numbers in gut mucosa of all groups, but in each case their percentage was lower than that of the autologous peripheral blood. The mitogenic response to PHA was found in general to be lower in the mucosal lymphocytes compared to those in blood, with the exception of the polyposis group which responded highly. No response of mucosal cells to PPD was seen. Inhibition studies done by means of mixed cultures revealed the presence of a suppressor activity in many mucosal lymphocytes, especially in the inflamed mucosa group, which may partly account for some low responses observed with mucosal lymphocytes. Further studies are under way to better define these quantitative and functional differences seen in gut mucosal cells, and to correlate differences with disease states.

An examination of the cytology of uninflammed and inflammed gingiva using a filter imprint technique.

Filter imprint cytologic specimens were obtained from the gingiva of 41 male dental students following clinical assessment of gingival health using a modification of the Loe gingival index. Nineteen of the specimens were from inflamed, and 22 from uninflamed gingiva. The imprints were fixed and stained by a modification of the Papanicolaou method and macroscopic and microscopic examinations showed that: 1. With increasing severity of clinically detectable gingival inflammation,, there appears to be an increase in the width of the bands of inflammatory cells and epithelial cells adjacent to the gingival margin. 2. An inverse relationship is found between keratinization and inflammation in that the percentages of anucleated epithelial cells was reduced at the gingival margin and significantly reduced midway in the attached gingiva of the inflamed groups. 3. No changes associated with inflammation were noted in cell cytology at the mucogingival junction.