Mechanisms underlying lipopolysaccharide-induced kinin B1 receptor up-regulation in the pig iris sphincter in vitro

Kinin B1 receptors are known to be highly induced after inflammatory stimuli in several biological systems. We report that incubation of pig iris sphincter with lipopolysaccharide from Escherichia coli caused a marked and time-related up-regulation of B1, accompanied by a reduction of B2 receptor-mediated contractile responses. The up-regulation of B1 receptors by lipopolysaccharide stimulation was decreased by the inhibitors of protein synthesis, cycloheximide and actinomycin D, and by dexamethasone and the nuclear factor-kappaB (NF-kappaB) inhibitor pyrrolidinedithiocarbamate (PDTC). In addition, lipopolysaccharide-induced up-regulation of B1 receptors in the pig iris sphincter was significantly reduced by the p38 inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) and to a lesser extent by the extracellular signal-regulated kinases 1 and 2 (ERK1/2) blocker 2'-amino-3'-methoxyflavone (PD98059). Molecular biology experiments demonstrated that in vitro incubation with lipopolysaccharide resulted in a time-dependent and remarkable activation of NF-kappaB and of p38 and ERK1/2 mitogen-activated protein (MAP) kinases, in pig iris sphincter preparations. While attempting to verify how MAP kinases are part of the B1 receptor-activated signaling transduction pathways, we observed that PD98059 was able to markedly reduce the contraction induced by B1 receptor activation in lipopolysaccharide-pretreated pig iris sphincter muscle but that this response was only partially decreased by SB203580. Our results extend the previous evidence on the mechanisms underlying the B1 receptor upregulation processes and demonstrate for the first time how this takes place in an ocular tissue, the pig iris sphincter. It is therefore possible to define B1 receptors as therapeutic targets for the treatment of infectious and inflammatory alterations of the eye.     

Mortality of patients with heatstroke admitted to intensive care units during the 2003 heat wave in France: a national multiple-center risk-factor study

OBJECTIVE: Heatstroke requires active body cooling and organ failure supportive care. Although heat waves are expected to recur over the next decades, little is known about the risk factors for mortality in heatstroke patients. We examined the prognosis and risk factors for hospital mortality in patients with heatstroke admitted to an intensive care unit (ICU) during the heat wave in France in August 2003. DESIGN: A questionnaire was sent to the physicians leading an ICU in France to identify the patients admitted with heatstroke during August 2003. Data included demographics, factors predisposing to heatstroke, severity during the first day in the ICU, air conditioning in the ICU, and hospital mortality. Risk factors for mortality were determined in multivariate Cox proportional hazards analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were obtained for 345 patients. Hospital mortality was 62.6%. Occurrence of heatstroke at home or in a healthcare facility rather than in a public location, high Simplified Acute Physiology Score II, high body temperature, prolonged prothrombin time, use of vasoactive drugs within the first day in the ICU, and patient management in an ICU without air conditioning were independently associated with an increased risk of death. CONCLUSIONS: Mortality of patients admitted to the ICU with heatstroke is high. Predictors of mortality are available within the first 24 hrs after admission. Furthermore, in this study, air conditioning in the ICU was associated with improved outcome.     

A case of preserved fertility in an hemodialyzed patient with systemic lupus erythematosus

BACKGROUND: Pregnancy and child birth in haemodialysis remains a rare event, even more, when pregnancy occurs in patient with systemic lupus erythematosus (SLE). AIM: We report a case of a patient with end stage renal failure secondary to SLE and who carried out 3 pregnancies. CASE REPORT: She was a woman with proliferative and diffuse lupus glomerulonephritis since 1985 treated by corticosteroids and cyclophosphamide. In 1995, she developed chronic renal failure. In 1996, she underwent a 1st full term spontaneous pregnancy with normal birth weight. In 2001, she underwent a second spontaneous pregnancy while she was on periodic haemodialysis. She had a full term baby birth with a birth weight at 1 Kg 700 and who died 4 days later. In 2002, she had a third pregnancy with voluntary abortion at 8 weeks. CONCLUSION: Our patient had conserved fertility despite treatment by cyclophosphamide, chronic renal failure and haemodialysis. The two successful deliveries may be attributed to the control of SLE activity and to the adequacy of haemodialysis.     

Fat necrosis: A neglected side effect of intramuscular injections

Panniculitis has various etiologies. One of the less common causes is trauma and hence traumatic fat necrosis (FN). These soft tissue injuries usually appear on the shins, thighs, breasts, arms, and buttocks. FN is mainly caused by trauma and may be associated with other conditions such as pancreatic disease. FN arising after intramuscular injections is uncommon and usually appears as firm, encapsulated, mobile, nontender, and solitary or multiple subcutaneous nodules. We report an interesting case of FN caused by intramuscular injections of cefazolin and meglumine antimoniate (MA) in a 38‐year‐old female patient. MA is regarded as the first‐line systemic treatment for cutaneous leishmaniasis (CL). However, these drugs are not devoid of various potentially adverse reactions.