Toxicokinetic of flumethrin in rabbits.

In this study, the toxicokinetic of flumethrin after single oral and intravenous applications were studied. For this aim, 14 male New Zealand rabbits were used. The animals were divided into two groups of seven each. While 10 mg/kg.bw of flumethrin was intravenously injected into the first group, the same dose was administered orally with the second group. Serial blood samples were also collected at certain periods. Flumethrin concentrations were measured using a gas chromatography with a micro electron capture detector. The serum flumethrin concentration-time curve was determined to fit a two-compartment open model. Among the parameters calculated following intravenous application of flumethrin, the half-life at ß phase (t1/2ß), mean residence time (MRT) and area under the concentration time curve in 0-∞ (AUC0→∞) values were respectively found to be 34.0 ± 4.2 h, 48.0 ± 5.8 h and 36.1 ± 5.3. On the other hand, the maximal concentration in serum (Cmax), time needed to reach Cmax (tmax), t1/2ß, MRT and AUC0→∞ values of flumethrin after oral administration were determined to be 0.54 ± 0.09 µg/ml, 5.42 ± 0.97 h, 43.3 ± 8.6 h, 59.7 ± 10.5 h and 22.0 ± 2.0 mg.h/L, respectively. The bioavailability of flumethrin was found to be 60.9%. In conclusion, these results were considered to be important in terms of the toxication risk of flumethrin and its safe use.

A population model-based linear-quadratic Gaussian compensator for the control of intravenously infused alcohol studies and withdrawal symptom prophylaxis using transdermal sensing.

An output feedback LQG compensator (combined controller and state estimator) for the regulation of intravenous-infused alcohol studies and treatment using a noninvasive transdermal alcohol biosensor is developed. The design is based on a population model involving an abstract semi-linear parabolic hybrid reaction-diffusion system involving coupled partial and ordinary differential equations with random parameters known only up to their distributions. The scheme developed is based on a weak formulation of the model equations in an appropriately constructed Gelfand triple of Bochner spaces wherein the unknown random parameters are treated as additional spatial variables. Implementation relies on a Galerkin-based approximation and convergence theory and an abstract formulation involving linear semigroups of operators. The model is fit and validated using laboratory collected human subject data and the method of moments. The results of numerical simulations of controlled intravenous alcohol infusion are presented and discussed.

Anti-interferon alpha treatment in SLE.

Several studies in the last decade have highlighted the role of the type I interferon (IFN-I) pathway, and particularly interferon alpha (IFNα) in SLE pathogenesis. As a result, a multitude of potential treatments targeting IFNα have emerged in the last few years, a few of which have already completed phase II clinical trials. Some of the treatment strategies have focused on blocking IFNα or its receptor and others the plasmacytoid dendritic cell (pDC), which is the principal IFNα producing cell. In this review, we will discuss the evidence supporting a pathogenic role of IFNα and pDC in SLE, provide an update on the current status of these therapeutic strategies, and discuss the potential advantages and disadvantages of each therapeutic approach.

Enhancing Techniques for Determining Inflammatory Edema Formation and Neutrophil Accumulation in Murine Skin.

Inflammatory edema formation and polymorphonuclear leukocyte (neutrophil) accumulation are common components of cutaneous vascular inflammation, and their assessment is a powerful investigative and drug development tool but typically requires independent cohorts of animals to assess each. We have established the use of a mathematical formula to estimate the ellipsoidal-shaped volume of the edematous wheal or bleb after intradermal injections of substances in mice pretreated intravenously with Evans blue dye (which binds to plasma albumin) to act as an edema marker. Whereas previous extraction of Evans blue dye with formamide is suitable for all strains of mice, we report this quicker and more reliable assessment of edema volume in situ. This therefore allows neutrophil accumulation to be assessed from the same mouse using the myeloperoxidase assay. Importantly, we examined the influence of Evans blue dye on the spectrometry readout at the wavelength at which myeloperoxidase activity is measured. The results indicate that it is feasible to quantify edema formation and neutrophil accumulation in the same mouse skin site. Thus, we show techniques that can assess edema formation and neutrophil accumulation at the same site in the same mouse, allowing paired measurements and reducing the total use of mice by 50%.

Effectiveness and Safety of Ultrasound-Guided Local Paricalcitol Injection in Treating Secondary Hyperparathyroidism in ESRD: A Retrospective Study.

PURPOSE: To compare the safety and efficacy of percutaneous paricalcitol injection with intravenously administered paricalcitol in treating parathyroid hyperplasia in patients with secondary hyperparathyroidism (SHPT). METHODS: This study was approved by the Ethics Committee of our institution. We retrospectively collected data on patients who received percutaneous paricalcitol injection (24 patients) and intravenously administered paricalcitol (22 patients) based on their intact parathyroid hormone (iPTH) level. Serum iPTH, calcium, phosphorus, and the volume of the parathyroid gland were measured at several indicated time points after treatment, and adverse events associated with the two treatments were evaluated. RESULTS: After 6 months of follow-up, we found that patients from the percutaneous injection group had significantly decreased levels of iPTH (from 1887.81 ± 726.81 pg/mL to 631.06 ± 393.06 pg/mL), phosphate (from 1.94 ± 0.36 mmol/L to 1.71 ± 0.34 mmol/L), and volume of the parathyroid gland (from 0.87 ± 0.50 cm3 to 0.60 ± 0.36 cm3), with relief from ostealgia within 48-72 h. In the intravenously administered group, the levels of iPTH decreased from 686.87 ± 260.44 pg/mL to 388.47 ± 167.36 pg/mL; while there was no significant change in phosphate levels, the volume of the parathyroid gland and ostealgia relief were observed at the end of follow-up. The serum calcium level did not significantly change, and no severe complications were observed in both groups. In vitro fluorescence-activated single cell sorting (FACS) analysis indicated that paricalcitol induced parathyroid cell apoptosis in a dose-dependent manner. CONCLUSIONS: Percutaneous paricalcitol injection is a selective treatment for SHPT in ESRD.

Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement.

T cell engaging bispecific antibody (TCB) is an effective immunotherapy for cancer treatment. Through co-targeting CD3 and tumor-associated antigen (TAA), TCB can redirect CD3+ T cells to eliminate tumor cells regardless of the specificity of T cell receptor. Tissue factor (TF) is a TAA that involved in tumor progression. Here, we designed and characterized a novel TCB targeting TF (TF-TCB) for the treatment of TF-positive tumors. In vitro, robust T cell activation, tumor cell lysis and T cell proliferation were induced by TF-TCB. The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB, and was related to TF expression level of tumor cells. In vivo, in both tumor cell/human peripheral blood mononuclear cells (PBMC) co-grafting model and established tumor models with poor T cell infiltration, tumor growth was strongly inhibited by TF-TCB. T cell infiltration into tumors was induced during the treatment. Furthermore, efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors. For the first time, our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.

The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond.

Ghrelin is a stomach-derived peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) and displays a plethora of neuroendocrine, metabolic, autonomic and behavioral actions. It has been proposed that some actions of ghrelin are exerted via the vagus nerve, which provides a bidirectional communication between the central nervous system and peripheral systems. The vagus nerve comprises sensory fibers, which originate from neurons of the nodose and jugular ganglia, and motor fibers, which originate from neurons of the medulla. Many anatomical studies have mapped GHSR expression in vagal sensory or motor neurons. Also, numerous functional studies investigated the role of the vagus nerve mediating specific actions of ghrelin. Here, we critically review the topic and discuss the available evidence supporting, or not, a role for the vagus nerve mediating some specific actions of ghrelin. We conclude that studies using rats have provided the most congruent evidence indicating that the vagus nerve mediates some actions of ghrelin on the digestive and cardiovascular systems, whereas studies in mice resulted in conflicting observations. Even considering exclusively studies performed in rats, the putative role of the vagus nerve in mediating the orexigenic and growth hormone (GH) secretagogue properties of ghrelin remains debated. In humans, studies are still insufficient to draw definitive conclusions regarding the role of the vagus nerve mediating most of the actions of ghrelin. Thus, the extent to which the vagus nerve mediates ghrelin actions, particularly in humans, is still uncertain and likely one of the most intriguing unsolved aspects of the field.

Novel insights into the role of Clostridium novyi-NT related combination bacteriolytic therapy in solid tumors.

Several solid tumors (for example leiomyosarcoma, melanoma and hepatocellular carcinoma) possess areas of hypoxia, which underlies one of the primary reasons of failure of conventional anticancer therapies. The areas of poor vascularization are insensitive to radiotherapy and chemotherapeutic drugs. Conversely, the hypoxic regions of tumors provide an ideal environment for anaerobic bacteria. The attenuated anaerobic bacterium, Clostridium novyi-NT (C. novyi-NT), is highly sensitive to oxygen and can target the destruction of hypoxic and necrotic areas of tumors, inducing oncolysis and characteristics indicative of an immune response. Theoretically, chemotherapy, radiotherapy and immunotherapy combined with bacterial therapy can be used as a novel means of treating solid tumors, promoting tumor regression and inhibiting metastasis formation with a notable beneficial effect. The present review discusses the molecular mechanisms of combined bacteriolytic therapy, predominantly focusing on C. novyi-NT, and summarizes the findings of previous studies on experimental animal models, including its efficacy and safety via different drug delivery routes. This strategy has great potential to overcome the limitations of conventional cancer therapy, resulting in improved treatments, and thus potentially improved outcomes for patients.

Evaluation of the anti-diarrheal effects of the whole plant extracts of Cuscuta reflexa Roxb in pigeons.

BACKGROUND: Cuscuta reflexa (dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant. In the present study, the antidiarrheal activity of C. reflexa was evaluated in pigeons (Columba livia) using the juice (JCR), aqueous (CRAE), and methanol (CRME) extracts. METHODS: The antidiarrheal effect of C. reflexa was evaluated using different reported research models, with few modifications. In pigeons, diarrhea was induced by administration of castor oil (6 mL/kg, PO), ampicillin (250 mg/kg, IP), magnesium sulfate (2 gm/kg, PO), and cisplatin (6 mg/kg, IV). In these experiments, loperamide (2 mg/kg, IM) was used as a positive control, whereas JCR (1 mL/kg (1%) and 1 mL/kg (2%), CRAE (50, 100 and 200 mg/kg) and CRME (50, 100 and 200 mg/kg) were administered intramuscularly at different doses into each pigeon in the test groups. RESULTS: In addition to cisplatin-induced diarrhea, all paradigms tested gave significant results (P < 0.01). The JCR, at different doses, exhibited a significant (p < 0.01) a dose-dependent antidiarrheal effect on both the frequency and the onset of diarrhea. Similarly, CRAE and CRME, at doses of 100 and 200 mg/kg, showed considerable (p < 0.001) inhibition against the onset and frequency of diarrhea. On the other hand, JCR, CRAE, and CRME exerted significant effects (p < 0.001) on the percentage inhibition (PI) of diarrhea and gastrointestinal charcoal transit in a dose-dependent manner. In this respect, the maximum PI (p < 0.01) of JCR, CRAE, and CRME in different experimental paradigms was 43.13, 49.14, and 55.99 %, respectively. CONCLUSIONS: Taken all together, results from this study reveal that the juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of C. reflexa in folk medicine as an antidiarrheal medicinal plant.

A Potential Long-Acting LDL-Cholesterol-Lowering PCSK9 Monoclonal Antibody: Randomized, Placebo-Controlled Phase 1 Studies.

The aim of the studies was to evaluate the safety, tolerability, and efficacy of tafolecimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, in Chinese healthy volunteers and patients with hypercholesterolemia. Fifty-eight healthy volunteers (phase 1a) were randomized to receive a single dose of 25, 75, 150, 300, 450, or 600 mg tafolecimab subcutaneously, 75 or 450 mg intravenously, or placebo. Sixty patients with hypercholesterolemia (phase 1b) were randomized to receive 75 or 140 mg tafolecimab every 2 weeks, 300 or 420 mg every 4 weeks, or 450 or 600 mg every 6 weeks subcutaneously or placebo for 12 weeks. Tafolecimab was well tolerated. Adverse events in both studies were either mild or moderate. In the phase 1a study, a single dose of tafolecimab reduced low-density lipoprotein-cholesterol (LDL-C) levels up to 72% in healthy volunteers. In the phase 1b study, tafolecimab reduced LDL-C levels up to 71.6% and by more than 50% consistently to week 12 for all tafolecimab dose regimens. Tafolecimab is a safe PCSK9 monoclonal antibody with significant and potential long-acting LDL-C-lowering effect. (Single Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Healthy Subjects; NCT03366688) (Multiple Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Chinese Patients With Hypercholesterolemia; NCT03815812).

Pediatrics COVID-19 and neurological manifestations: Single tertiary centre experience.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome that is caused by a novel coronavirus 2 (SARS-CoV-2). It originated in China late December 2019 and was declared a global pandemic on March 12, 2020. Most reports of COVID-19 cases either presented with neurological manifestations or complications involve adults. Only few cases were reported in pediatric patients. OBJECTIVE: To report COVID-19 pediatric cases with neurological manifestations and identify the wide spectrum of its manifestations. DESIGN SETTING AND PARTICIPANTS: This was a retrospective, observational case series. Data of pediatric patients infected by SARS-CoV-2 presenting with neurological manifestations at King Abdullah Specialized Children Hospital in King Abdulaziz Medical City in Riyadh were collected from May 23 to June 30, 2020. RESULTS: We encountered 5 COVID-19 cases with neurological manifestations. Three patients who were previously healthy had new-onset neurological symptoms. Symptoms and signs included encephalopathy, ataxia, headache, seizure, papilledema, ophthalmoplegia, hyporeflexia, and different clinical spectra, such as Miller Fisher syndrome, meningoencephalitis, and idiopathic intracranial hypertension. Other patients attending our center were incidentally found to be SARS-CoV-2-positive, which caused a delay in the investigations required to reach diagnosis. CONCLUSIONS AND RELEVANCE: Our cases highlight the wide clinical spectrum of neurological manifestations in COVID-19 patients. Given the paucity of information about pediatric COVID-19 cases with neurological symptoms, we here reported these cases to shed light on the association between SARS-CoV-2 and neurological presentation. Moreover, our study indicates that many investigations are being delayed and could affect diagnosis and treatment.

Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway.

Epilepsy is identified as a brain disorder and characterized by unpredictable disruption of normal brain function. Due to adverse side effect associated with antiepileptic drugs and also resistance profile, improvement of antiepileptic medications with more beneficial anticonvulsant activity is essential. Natural products have demonstrated their therapeutic properties such as anxiolytic, antidepressant and anticonvulsant activities and a source for identification of novel lead compounds. Therefore, the purpose of this study was to evaluate the effects of Onopordon acanthium secondary metabolite, onopordia, on pentylenetetrazole (PTZ)-induced seizure in male mice and investigate the possible role of nitric oxide pathway. Different doses of onopordia (0.1, 1 and 10 mg/kg) and phenobarbital (20 mg/kg) were administered intraperitoneally (i.p., 30, 60 and 120 min) prior to induction of epileptic seizure and compared to control groups. Onopordia demonstrated anticonvulsant effects when administrated at dose of 10 mg/kg, i.p. and optimum time 60 min prior to induction of seizure. Anticonvulsant effect of onopordia was blocked by applying a single dose of a non-selective nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; 10 mg/kg, i.p.), and also a single dose of a selective neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI; 30 mg/kg, i.p.). Administration of ketamine as a N-Methyl-d-aspartic acid (NMDA) receptor antagonist (0.5 mg/kg; i.p.) with onopordia did not change the anticonvulsant effect of onopordia. The results of the present study demonstrated the anticonvulsant effect of onopordia as a new lead compound and also contribution of NO/nNOS pathway on PTZ-induced seizure in mice.

Efficacy and Safety of Intravenously Administered Tramadol in Patients with Moderate to Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.

INTRODUCTION: This study is part of the registrational program for intravenously administered (IV) tramadol in the USA and compared the analgesic benefit and tolerability of two doses of IV tramadol (50 mg and 25 mg) to placebo in adult patients undergoing bunionectomy, an orthopedic surgical model. METHODS: This was a phase 3, multicenter, double-blind, three-arm, randomized, placebo-controlled, multiple-dose, parallel-group trial to evaluate IV tramadol in the management of postoperative pain following bunionectomy. Eligible patients were randomized (1:1:1 ratio) to IV tramadol 50 mg, 25 mg, or placebo. Primary endpoint was summary of pain intensity differences over 48 h (SPID48). Key secondary endpoints included SPID24, total consumption of rescue analgesia, and patient global assessment of efficacy (PGA). Safety assessments included treatment emergent adverse events (TEAEs), clinical laboratory tests, vital signs, and electrocardiograms (ECGs). Assessment of the dose-response was an important objective of the study. RESULTS: The study established a dose response, with IV tramadol 50 mg demonstrating statistically significant benefit (p < 0.05) over placebo for primary and all key secondary efficacy endpoints, whereas tramadol 25 mg demonstrated intermediate results between the 50 mg and placebo arms. IV tramadol 50 mg was well tolerated; most common TEAEs were nausea and vomiting; and there were no meaningful differences among treatments for vital signs, ECG, and laboratory assessments. The largest proportion of patients completed tramadol 50 mg (98.6%) compared to tramadol 25 mg (91.8%) and placebo (88.2%). CONCLUSION: IV tramadol 50 mg was effective and well tolerated as treatment for postoperative pain following bunionectomy surgery, while IV tramadol 25 mg, although well tolerated, was judged an ineffective dose for the treatment of pain in this setting. IV tramadol 50 mg was further developed in the registrational program for the USA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03290378.

Efficacy of a Novel Mitochondrial-Derived Peptide in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac ischemia.

Lysophosphatidic acid LPA1 and LPA3 receptors play roles in the maintenance of late tissue plasminogen activator-induced central poststroke pain in mice.

We developed a mouse model for central post-stroke pain (CPSP), a centrally-originated neuropathic pain (NeuP). In this mode, mice were first injected with Rose Bengal, followed by photo-irradiation of left middle cerebral artery (MCA) to generate thrombosis. Although the MCA thrombosis was soon dissolved, the reduced blood flow remained for more than 24 h due to subsequent occlusion of microvessels. This photochemically induced thrombosis (PIT) model showed a hypersensitivity to the electrical stimulation of both sides of paw, but did not show any abnormal pain in popular thermal or mechanical nociception tests. When tissue-type plasminogen activator (tPA) was injected 6 h after the PIT stress, tPA-dependent hypersensitivity to the electrical paw stimulation and stable thermal and mechanical hyperalgesia on both sides for more than 17 or 18 days after the PIT treatment. These hyperalgesic effects were abolished in lysophosphatidic acid receptor 1 (LPA1)- and lysophosphatidic acid receptor 3 (LPA3)-deficient mice. When Ki-16425, an LPA1 and LPA3 antagonist was treated twice daily for 6 days consecutively, the thermal and mechanical hyperalgesia at day 17 and 18 were significantly reversed. The liquid chromatography-mass spectrometry (LC-MS/MS) analysis revealed that there is a significant increase in several species of LPA molecules in somatosensory S-I and medial dorsal thalamus (MD), but not in striatum or ventroposterior thalamus. All these results suggest that LPA1 and LPA3 signaling play key roles in the development and maintenance of CPSP.

Intratumoral delivery of bortezomib: impact on survival in an intracranial glioma tumor model.

OBJECTIVE Glioblastoma (GBM) is the most prevalent and the most aggressive of primary brain tumors. There is currently no effective treatment for this tumor. The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. The authors' goal was to demonstrate that bortezomib can be effective in the orthotopic GBM murine model if the appropriate method of drug delivery is used. In this study the Alzet mini-osmotic pump was used to bring the drug directly to the tumor in the brain, circumventing the blood-brain barrier; thus making bortezomib an effective treatment for GBM. METHODS The 2 human glioma cell lines, U87 and U251, were labeled with luciferase and used in the subcutaneous and intracranial in vivo tumor models. Glioma cells were implanted subcutaneously into the right flank, or intracranially into the frontal cortex of athymic nude mice. Mice bearing intracranial glioma tumors were implanted with an Alzet mini-osmotic pump containing different doses of bortezomib. The Alzet pumps were introduced directly into the tumor bed in the brain. Survival was documented for mice with intracranial tumors. RESULTS Glioma cells were sensitive to bortezomib at nanomolar quantities in vitro. In the subcutaneous in vivo xenograft tumor model, bortezomib given intravenously was effective in reducing tumor progression. However, in the intracranial glioma model, bortezomib given systemically did not affect survival. By sharp contrast, animals treated with bortezomib intracranially at the tumor site exhibited significantly increased survival. CONCLUSIONS Bypassing the blood-brain barrier by using the osmotic pump resulted in an increase in the efficacy of bortezomib for the treatment of intracranial tumors. Thus, the intratumoral administration of bortezomib into the cranial cavity is an effective approach for glioma therapy.

Uso de la vía intraósea en emergencias extrahospitalarias / Use of the intraosseous route in outpatient emergencies

En situaciones de emergencia, la canalización de un acceso venoso puede complicarse. En esos casos se utiliza la vía intraósea, al tratarse de un sistema de inserción rápido y seguro y de fácil ejecución. A través de la vía intraósea se consigue el paso de sustancias a la circulación sistémica con la misma rapidez que un acceso venoso periférico. Además, no se colapsa en situaciones de shock. Para su inserción existen distintos dispositivos según la situación clínica del paciente. Con este manuscrito se pretende dar a conocer las ventajas de la punción intraósea en emergencias extrahospitalarias, así como la necesidad de adquirir ciertos conocimientos y el adiestramiento necesario para el uso de esta vía de perfusión. Es una técnica que presenta muchas ventajas en situaciones de emergencia, cada vez más utilizada, pero aún desconocida por gran parte de los profesionales de Enfermería.(AU)

In emergency situations, the insertion of a venous IV line might get complicated. In these cases, the intraosseous route is used, because it is a fast and safe insertion system, and easy to conduct. Through the intraosseous route, the transit of substances to the systemic circulation is achieved with the same speed than with a peripheral venous access. Besides, there is no collapsing in shock situations. There are different devices for its insertion, according to the clinical situation of the patient. The objective of this text is to make public the advantages of intraosseous puncture in outpatient emergencies, as well as the need to acquire certain skills and the training necessary for the use of this perfusion route. This is a technique which offers many advantages in emergency situations and which is increasingly used, but still unknown by a great part of Nursing professionals.(AU)

Spontaneous Bilateral Adrenal Haemorrhage after Duodenopancreatectomy: a case report.

it is difficult to diagnose because of its nonspecific presentation. This condition frequently occurs in association with an extreme physical stress and may lead to acute adrenal insufficiency or death if not promptly and properly treated. We report a rare case of acute bilateral adrenal hemorrhage with adrenal insufficiency following duodenopancreatectomy for ampulloma in absence of surgical complications. Early diagnosis and corticosteroid replacement with aggressive management of the precipitating pathology are essential to enable a successful outcome.

[Effect of intraoperative intravenous lidocaine on pain and plasma interleukin-6 in patients undergoing hysterectomy]. / Efeito da lidocaína venosa intraoperatória sobre dor e interleucina-6 plasmática em pacientes submetidas a histerectomia.

BACKGROUND AND OBJECTIVES: Interleukin-6 (IL-6) is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma IL-6 after hysterectomy. METHOD: A prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2mg.kg(-1).h(-1)) or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24hours), first analgesic request, and dose of morphine in 24hours were evaluated. IL-6 was measured before starting surgery (T0), five hours after the start (T5), and 24hours after the end of surgery (T24). RESULTS: There was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0±104.4min) than in G1 (26.7±23.3min). There was no difference in supplemental dose of morphine between G1 (23.5±12.6mg) and G2 (18.7±11.3mg). There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5±364.1 ng.mL(-1) in T5 and 30.1±14.2 ng.mL(-1) in T24. CONCLUSION: Intravenous lidocaine (2mg.kg(-1).h(-1)) did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy.