Usefulness of the Pain-induced Functional Impairment Model to Relate Plasma Levels of Analgesics to Their Efficacy in Rats

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.     

Cutaneous facial sinus tract of dental origin

Abstract: Cutaneous sinus tract on the head and neck area in a child may originate from dental disease. A high degree of clinical suspicion and complementary tests are often needed, as the diagnosis is usually not straight forward. Anatomical correlation is also useful in tracing the affected tooth or teeth. We present the case of a boy with a facial sinus tract that originated from periapical abscesses of maxillary molars.     

Different Th1/Th2 responses to Anisakis simplex are related to distinct clinical manifestations in sensitized patients

Anisakis simplex is a fish parasite capable of inducing inflammatory and allergic reactions in humans who eat raw or undercooked fish. The aim of this study was to characterize the T helper type 1 (Th1)/Th2 immune response to parasite crude (CE) and thermostable (TsE) extracts in A. simplex-sensitized patients. Cytokines were quantified by a multiplex flow cytometric method in short-term whole blood cultures. Higher concentrations of IL-2, IL-4 and IL-5, measured with the CE and TsE, were found in patients than in controls. Patients showing urticaria-angio-oedema or anaphylaxis (UA/A) had higher total and specific IgE levels than those with gastrointestinal symptoms (GI). The UA/A group showed high levels of IL-5 and IL-4 and low expression of IFN-γ than the GI group. The GI group had significantly higher IFN-γ/IL4 ratio than the UA/A group. Four patients with severe GI symptoms reporting a delayed skin test reaction had very low values of specific IgE to A. simplex and higher IFN-γ/IL4 ratios than that observed in other patients belonging to the GI group. This short-term whole blood test can be useful for immune response characterization in Anisakis infection and showed that heated parasite antigens are still capable of inducing cellular immune response in sensitized patients.     

The incidence and causes of erectile dysfunction after pelvic fractures associated with posterior urethral disruption

PURPOSE: Erectile dysfunction is a common sequel of pelvic fractures, particularly those associated with posterior urethral injury when it can be neurogenic or arteriogenic due to damage to the cavernous nerves or branches of the pudendal arteries. We studied erectile function of patients with posterior urethral injuries due to pelvic fractures. MATERIALS AND METHODS: Patients referred for posterior urethral reconstruction and strictures due to pelvic fractures were evaluated before reconstruction. All patients underwent nocturnal penile tumescence testing, and if those results were abnormal, penile duplex ultrasound with intracavernous injection was performed. Patients with normal vascular function on duplex ultrasound were diagnosed with neurogenic erectile dysfunction. Those patients with abnormal arterial function on duplex ultrasound underwent arteriography to further define the extent and location of arterial damage. RESULTS: The study included 25 consecutive patients with posterior urethral strictures and a mean age of 28.6 years. Of the patients 18 (72%) had erectile dysfunction as demonstrated by nocturnal penile tumescence and all underwent penile duplex ultrasound. Ultrasound confirmed normal vascular response in 13 of the 18 patients and they were diagnosed with probable neurogenic erectile dysfunction. The remaining 5 patients (28%) with erectile dysfunction had an abnormal arterial response, and significant arterial pathology was confirmed by arteriography. CONCLUSIONS: Erectile dysfunction is common in patients with pelvic fractures associated with urethral injury. We believe that erectile function should be assessed and documented in such patients before attempting urethroplasty. In the majority of these patients erectile dysfunction is caused by disruption of the cavernous nerves with sparing of arterial inflow.     

Efficacy of lasalocid against murine Pneumocystis carinii pneumonitis.

The efficacy of the ionophore lasalocid against Pneumocystis carinii pneumonitis in corticosteroid-immunosuppressed Sprague-Dawley rats was investigated. Lasalocid was effective in the prevention of the pneumonitis in a dose-dependent manner. At dosages of 0, 5, 10, and 20 mg/kg/day, P. carinii infection rates were 92, 60, 20, and 0%, respectively, during dexamethasone immunosuppression. Also, lasalocid compared favorably with other drugs known to have anti-P. carinii activity, including trimethoprim-sulfamethoxazole, atovaquone, and dapsone-trimethoprim.     

Drug-related behavior change for HIV transmission among American injection drug users

While high risk drug-related behaviors for human immunodeficiency virus (HIV) transmission among injection drug users (IDUs) are asserted to have declined over time in response to the AIDS epidemic, evidence from longitudinal cohorts has been sparse. In a cohort of 810 IDUs (442 seronegatives and 368 seropositives) in Baltimore, we identified drug-related risk behaviors at four consecutive semi-annual visits. Using robust methods for repeated measurements and multiple logistic regression, we estimated the probabilities of maintaining and reducing risk behaviors according to HIV serostatus and time in the study. Seropositive participants were more likely to maintain lower risk behaviors, and behavior maintenance increased with time in study for both seronegative and seropositive IDUs. Greater risk reduction (towards non-use and not sharing injection equipment) was seen among seropositive IDUs, with behavior change occurring soon after enrollment in the study. While behavior changes have been reported, many active IDUs, especially those still at risk for acquiring HIV infection, have not adequately reduced their risk. Continuing prevention programs and efforts in vaccine development are imperative to reduce the risk of HIV infection among IDUs.