Clinical efficacy of mesalamine in the treatment of the spondyloarthropathies

OBJECTIVE: Sulfasalazine (SSZ) has been found to have beneficial effects in the treatment of patients with spondyloarthropathy (SpA) with active disease. The effectiveness of SSZ is limited by both idiosyncratic and dose related side effects when treating SpA. Mesalamine is a drug used to treat inflammatory bowel disease. Case reports have suggested potential efficacy in SpA. We investigated the efficacy and safety of the Pentasa formulation of mesalamine in treating SpA. METHODS: Thirty patients with SpA as defined by the European Spondylarthropathy Study Group were recruited from a rheumatology specialty clinic. All subjects began 16 week open label therapy with mesalamine 1500 mg/day. Dose escalation for lack of efficacy was permitted after 8 weeks of therapy. Clinical, physical, and laboratory data were collected at baseline, at 8 weeks, and at the conclusion of the study at 16 weeks. RESULTS: Twenty-nine of the 30 patients completed the study. There was clinically and statistically significant improvement in all clinical measures (morning stiffness, night awakenings, quality of sleep, severity of stiffness, severity of pain, Dougados functional index, patient and physician global indices). Joint counts and enthesitis counts improved, but measures of axial flexibility did not. Erythrocyte sedimentation rate and C-reactive protein also improved over the duration of the study. CONCLUSION: In this population of patients with SpA, mesalamine was well tolerated in the dose range 1500 to 4000 mg/day. Improvements in clinical, physical, and laboratory measures indicate the efficacy of mesalamine in treating SpA.     

Acute pain and pain control: state of the art

Recognition and treatment of pain in the emergency department has undergone an evolution in the past decade. Emergency clinicians, educators, and researchers have begun to address the undertreatment of pain as well as challenge the long-standing dogmas concerning pain treatment. Well-described barriers, both psychological and educational, contribute to our providing inadequate pain relief. This state-of-the-art update describes the current perception of our practice with regard to pain relief and how it can be modified. Pain and pain control is such a broad and complex topic that only new advances and important principles relevant to the practice of emergency medicine are presented. Headache, pediatric pain, and procedural sedation and analgesia are not covered in this article as they will be addressed in future state-of-the-art articles.     

Effects of maternal alcohol intoxication on fetal circulation and myocardial function: an experimental study in the ovine fetus

To determine whether acute alcohol ingestion during pregnancy could affect fetal myocardial function, studies were carried in six chronically catheterized fetal sheep during maternal alcohol infusion. Absolute ethyl alcohol (0.8 ml/kg) was administered to the mother over 10 minutes via the jugular vein. These infusions were repeated every 30 minutes during 3 hours, and peak maternal and fetal blood concentrations close to 200 mg/dl alcohol were reached. Fetal PCO2 decreased from a baseline of 43.15 +/- 3.75 to 36.13 +/- 2.6 torr 1 hour after the start of alcohol infusion (P less than 0.05). Similarly, pH rose from 7.37 +/- 0.027 to 7.44 +/- 0.015 (P less than 0.05). Both values returned to baseline level at the end of alcohol infusion. PO2 remained within physiologic limits. The systolic time intervals of the fetal heart showed a rapid and prolonged modification. The pre-ejection period from 58 +/- 8 to 66 +/- 4 msec (P less than 0.05) during the infusion; this change was related to an increase in the isometric contraction period. The ratio of the pre-ejection period over the ejection time was also significantly increased (P less than 0.01), and remained elevated until the end of the experiment (12 hours). A rise in fetal systolic and diastolic pressures was observed at about 2 hours after the start of the alcohol infusion, and lasted 4 hours. This study suggests that an episode of maternal alcohol intoxication causes rapid depression of fetal myocardial contractility that is maintained several hours after cessation of alcohol ingestion.     

Heterosexually acquired CRF01_AE/B recombinant HIV type 1 found in Thailand

CRF01_AE and subtype B are circulating in Thailand and the strains have become intermixed in some high-risk groups, establishing the possibility of intersubtype recombination. The first such recombinant, mostly B with gp120 from CRF01_AE, was recently identified. Here we report a heterosexually acquired recombinant of different structure, with most of the genome from CRF01_AE but almost the entire envelope from subtype B. Surveillance by V3 serotype and genotype in multiple regions, followed by full-genome sequencing, was used to identify this strain. Pending vaccine trials in Thailand require knowledge of the presence of such strains in the population, and these recombinants provide valuable reagents for the laboratory evaluation of cross-subtype immunity. Studies are underway to determine whether either recombinant is circulating widely.     

Inhibition of proliferation of PC-3 human prostate cancer by antagonists of growth hormone-releasing hormone: lack of correlation with the levels of serum IGF-I and expression of tumoral IGF-II and vascular endothelial growth factor

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) such as JV-1-38 can inhibit androgen-independent prostate cancer directly by several mechanisms and/or indirectly by suppressing growth hormone/insulin-like growth factor-I (GH/IGF-I) axis. To shed more light on the mechanisms involved, the effects of JV-1-38 on PC-3 human prostate cancer were compared with those of somatostatin analog RC-160 in vivo and in vitro. METHODS: Nude mice bearing PC-3 tumors received JV-1-38 (20 microg), RC-160 (50 microg) or a combination of JV-1-38 and RC-160. The concentration of IGF-I in serum and the expression of mRNA for IGF-II and vascular endothelial growth factor (VEGF) in tumor tissue were investigated. RESULTS: In vivo, the final volume of PC-3 tumors treated with JV-1-38 was significantly lowered by 49% (P < 0.01), whereas RC-160 exerted only 30% inhibition (NS), compared with controls. Combined use of both compounds augmented tumor inhibition to 63% (P < 0.001). Serum IGF-I levels were decreased only in mice treated with RC-160. JV-1-38 suppressed mRNA for IGF-II in PC-3 tumors by 42%, whereas RC-160 alone or in combination with JV-1-38 caused a 65% reduction. JV-1-38 and RC-160 used as single drugs decreased the expression of VEGF by 50%, and their combination caused a 63% reduction. In vitro, JV-1-38 inhibited the proliferation of PC-3 cells by 39%. This effect could be partially reversed by addition of IGF-I to the serum-free medium. RC-160 alone did not affect the PC-3 cell growth in vitro, but in combination with JV-1-38 it augmented the antiproliferative effect of the GH-RH antagonist to 72%. Exposure to JV-1-38 in vitro reduced the expression of mRNA for IGF-II in PC-3 cells by 55% but did not change VEGF mRNA levels, whereas RC-160 had no effect. CONCLUSIONS: The antiproliferative effect of JV-1-38 was not associated with the suppression of serum IGF-I and was only partially correlated with the expression of IGF-II and VEGF in PC-3 tumors, suggesting that other mechanisms play a role in the antitumor action of GHRH antagonists. Nevertheless, the stronger inhibition of tumor growth after combined treatment with JV-1-38 and RC-160 indicates that the interference with multiple local stimulatory factors leads to an enhanced inhibition of prostate cancer.     

Fatty acid esters of triterpenoids and steroid glycosides from Gambeya africana

Chemical studies of the CH2 Cl2 -MeOH extract of the seeds of Gambeya africana (Baker) Pierre led to the isolation of 15 compounds. Their structures were established on the basis of spectroscopic methods and chemical reactions. They comprised five new fatty acid esters of erythrodiol, [3 beta-octacosanoyloxy-12-oleanen-28-ol, 3 beta-triacontanoyloxy-12-oleanen-28-ol, 3 beta-dotriacontanoyloxy-12-oleanen-28-ol, 3 beta-tetratriacontanoyloxy-12-oleanen-28-ol and 3 beta-hexatriacontanoyloxy-12-oleanen-28-ol], one new steroidal glycoside, [3 beta-O-beta-xylopyranosylchondrillasterol] and nine known compounds, (3 beta-octadecanoyloxy-12-oleanene, 3 beta-eicosanoyloxy-12-oleanene, 3 beta-docosanoyloxy-12-oleanene, 3 beta-acetoxy-12-oleanene, erythrodiol, 28-hydroxy-beta-amyrone, chondrillasterol, chondrillasterone and 3 beta-O-beta-glucopyranosylchondrillasterol).     

Assessing the estrogenic potential of organochlorine pesticides in primary cultures of male rainbow trout (Oncorhynchus mykiss) hepatocytes using vitellogenin as a biomarker

Many organochlorine pesticides are suspected of impairing natural hormonal function in organisms by mimicking endogenous estrogen. The aim of this study was to assess the estrogenic activity of the organochlorine pesticides o,p'-DDT, dieldrin, aldrin, heptachlor, mirex and DDT in rainbow trout hepatocyte cultures using vitellogenin (Vtg) as the biomarker. A wide range of pesticide concentrations (0.0001-100 microM) was evaluated. Among the pesticides tested, o,p'-DDT was the most potent inducer of Vtg. The lower potency of technical grade DDT relative to o,p'-DDT could be explained by the fact that this pesticide is a mixture of two different pesticides (18% o,p'-DDT and 77% p,p'-DDT). This suggests that o,p'-DDT is a stronger inducer of Vtg than p,p'-DDT. A simple hypothesis could be that pesticides mixed together competed for the same receptor to favor the formation of a complex with reduced activity towards EREs. If these compounds are classified according to the level of Vtg secreted, we observed the following decreasing order: 17beta-estradiol (E(2))>o,p'-DDT>dieldrin>aldrin>DDT. Non-toxic levels of these compounds competed with E(2) for binding to the estrogen receptor. Heptachlor and mirex did not induce Vtg. Since the latter compounds failed to stimulate Vtg production, the possibility that they could interfere with the estrogenic response by inhibiting E(2) action was tested. In the presence of heptachlor, Vtg production triggered by E(2) significantly decreased. The EC50 value for inhibition of ER binding by heptachlor was cytotoxic for hepatocytes in culture, and this could in part explain the lack of Vtg response observed with this compound at the concentrations tested. Our results indicate that organochlorine pesticides can act as positive or negative modulators of estrogenic function in rainbow trout.     

Acute asthma in children and adolescents: should inhaled anticholinergics be added to beta(2)-agonists?

Children and adolescents experiencing acute exacerbations of asthma benefit from the use of beta(2)-adrenoceptor agonists (beta(2)-agonists) and systemic corticosteroids. However, there have been conflicting reports regarding the efficacy of inhaled anticholinergic agents. This article summarizes the evidence provided by randomized controlled trials studying the efficacy of adding inhaled anticholinergic agents to beta(2)-agonists in nonhospitalized children and adolescents with acute exacerbations of asthma. This systematic review of randomized controlled trials suggests that the addition of inhaled anticholinergic agents to beta(2)-agonists is beneficial in children and adolescents, particularly those with severe exacerbations of asthma. When given in repeated doses, the addition of inhaled anticholinergic agents to beta(2)-agonists improves lung function and reduces the risk of hospital admission by 25%. Several treatment regimens, namely ipratropium bromide (250 or 500 microg per dose) every 20-60 minutes for two to three doses have been tested with similar beneficial effects. The addition of a single dose of an inhaled anticholinergic agent to beta(2)-agonists improves lung function but does not prevent hospital admission. The review did not identify any beneficial effects of anticholinergic agents in children with nonsevere asthma. Use of anticholinergic agents was not associated with increase in the incidence of nausea, vomiting or tremor. In conclusion, the addition of repeated doses of an inhaled anticholinergic agent to inhaled beta(2)-agonist is indicated in the emergency room management of children and adolescents with acute asthma, particularly those with severe exacerbations.