105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Antihistamines Block Radiation-Induced Increased Intestinal Blood Flow in Canines

Antihistamines Block Radiation-Induced Increased IntestinalBlood Flow in Canines. COCK-ERHAM, L. G., DOYLE, T. F., DONLON,M. A., AND GOSSETT-HAGERMAN, C. J. (1985). Fundam. Appl. Toxicol.5, 597–604. Radiation-induced systemic hypotension isaccompanied by increased intestinal blood flow (IBF) and anincreased hematocrit (HCT) in dogs. Histamine infusion leadsto increased IBF and intestinal edema with consequent secretionof fluid into the intestinal lumen. This study was performedto determine whether these effects could be diminished by prioradministration of H₁ and H₂ histamine blockers. Dogs were givenan iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25mg/min) for 1 hr before and for 1 hr after radiation (H₁ andH₂ blockers, respectively). Mean systemic arterial blood pressure(MBP), IBF, and HCT were monitored for 2 hr. Systemic plasmahistamine levels were determined simultaneously. Data obtainedindicated that the H₁ and H₂ blockers, given simultaneously,were successful in blocking the increased IBF and the increasedHCT seen after 100 Gy, whole-body, radiation. However, thepostradiation hypotension was only somewhat affected, with theMBP falling to a level 28% below the preradiation level. Plasmahistamine levels reached a sharp peak, as much as 20% abovebaseline, at 4 min postradiation. These findings implicate histaminein the radiation-induced increase in IBF and HCT but not forthe gradual decrease in postradiation blood pressure     

ARE SLOW-ACTING ANTI-RHEUMATIC DRUGS MONITORED TOO OFTEN? AN AUDIT OF CURRENT CLINICAL PRATICE

Rheumatologists usually recommend monthly blood monitoring whenpatients with rheumatoid arthritis (RA) are treated with slow-actinganti-rheumatic drugs (SAARDs). Is monthly monitoring neededor could its frequency be reduced? We audited the opinions ofUK rheumatologists and reviewed clinical experience at threecentres. To ascertain the interval at which patients are monitoredand the determinants of monitoring policy we sent a questionnaireto 193 consultant rheumatologists; 143 (74%) replied. The majorityuse monthly monitoring for most SAARDs except sulphasalazine,chloroquine and hydroxychloroquine. There is extensive variation,which is not related to the type of rheumatology unit or whethera shared scheme with general practitioners is used. Reviewingexperience in 390 patients treated with SAARDs at three adjacentrheumatology units in London showed that haematological adversereactions were infrequent. During 1560 patient-years of treatmentinvolving 18 720 monthly monitoring visits there were 13 haematologicaladverse reactions (1 1 thrombocytopenias and two leucopenias).Five thrombocytopenias occurred in the first 6 months of therapy;two were gradual and three developed more rapidly over 1–2months. Six thrombocytopenias developed after 6 months of treatment;five occurred gradually over 5 months or more and one borderlinelow platelet count was seen once. The two leucopenias were borderlinelow white cell counts occurring gradually over 3–6 months.Such frequent monitoring is expensive. The total cost of monitoring390 patients for 1560 patient-years was $420 000. The cost ofdetecting each adverse reaction was $ 32 000. Three-monthlymonitoring when therapy is established after an initial stabilizingperiod would have identified seven out of eight late adversereactions. Monitoring policies are mainly based on clinicalconsensus with few prospective studies of their value; theyneed re-evaluation. KEY WORDS: Rheumatoid arthritis, Drug toxicity, Slow-acting anti-rheumatic drugs