Pain management in hemophilia: expert recommendations.

Introduction: As a typical consequence of bleeding into muscles and joints, patients with severe hemophilia suffer from acute and chronic pain. In spite of its high prevalence, pain in this patient group is not always sufficiently considered or treated in an effective manner.

Aim: The recommendations presented in this paper address possible improvements in pain management in hemophilia patients and particularities that have to be taken into account in this patient group.

[Pain treatment in old age: special features and recommendations].

Background: For geriatric patients with chronic pain, a comprehensive well-coordinated pain management is pivotal to ensure the best possible pain relief and to minimize as far as possible preventable negative side effects of treatment.

Objective: Description of the difficulties in pain management of geriatric patients with respect to general basic rules that are worth paying attention to and presentation of pharmacological and non-pharmacological treatment options.

Methods: This article describes the special features of pain management in older patients and gives recommendations on the use of analgesics and potential drug interactions in geriatric patients with organ dysfunction.

[Pain and pain management in old age: special features and recommendations].

Introduction: Pain is highly prevalent in older persons and has a variety of causes. In geriatric patients, especially in patients with dementia, pain is often not sufficiently recognized and therefore frequently remains untreated. For the affected patient group this can have far-reaching consequences for their functional and cognitive abilities and may consequently lead to loss of autonomy.

Forward Modeling of Coronal Mass Ejection Flux Ropes in the Inner Heliosphere with 3DCORE.

Forecasting the geomagnetic effects of solar storms, known as coronal mass ejections (CMEs), is currently severely limited by our inability to predict the magnetic field configuration in the CME magnetic core and by observational effects of a single spacecraft trajectory through its 3-D structure. CME magnetic flux ropes can lead to continuous forcing of the energy input to the Earth's magnetosphere by strong and steady southward-pointing magnetic fields. Here we demonstrate in a proof-of-concept way a new approach to predict the southward field B in a CME flux rope.

Effect of CB1 Ligands on Neurogenic and Myogenic Contractile Responses in the Guinea-Pig Ileum.

This study aimed at investigating whether the synthetic cannabinoid receptor agonist (+)-WIN 55212-2 has neurogenic and myogenic relaxant effects on the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. (+)-WIN 55212-2, 1-1,000 nmol/L, concentration-dependently inhibited both the electrical stimulation-induced cholinergic twitch responses as well as the myogenic smooth muscle contractions in the LMMP preparation. SR-141716A (rimonabant) 1-1,000 nmol/L, the cannabinoid CB1 receptor antagonist, being without effect on its own, antagonized the (+)-WIN 55212-2-induced effects.

Upregulation of BDNF and Interleukin-1ß in rat spinal cord following noxious hind paw stimulation.

The aim of the present study was to investigate the protein levels of BDNF and IL-1ß in the lumbar dorsal horn of the rat by Western blot analysis following a noxious thermal hind paw stimulation. Ten min, 1h and 3h after the combined chemical and thermal stimulation an up to 2-fold increase in BDNF and Il-1ß protein expression was observed in the lumbar dorsal spinal cord. A pretreatment with the opioid analgesic morphine or the glial cell activation inhibitor minocycline partly attenuated protein expression.

Effects of Allyl Isothiocyanate, Acetaminophen, and Dipyrone in the Guinea-Pig Ileum.

Allyl isothiocyanate (AITC, mustard oil, 50-200 µmol/l), depending on specific dosages, inhibited the cholinergic twitch response in the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. AITC also induced short-lasting contractile responses, and decreases of the basal tone of the LMMP strip at low concentrations and increases at high concentrations. Hexamethonium, a blocker of nicotinic ganglionic transmission, was able to prevent the AITC-evoked inhibitory effect, an effect that was also observed with the opioid antagonist naloxone.

Interaction of αβ-Methylene ATP with the Cholinergic Twitch Response in the Guinea-Pig Ileum.

In this study, direct effects of the P2X purinoceptor agonist αβ-methylene ATP (αβ-meATP) and effects on the cholinergic twitch response of the electrically stimulated longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum, were investigated. αβ-meATP (1, 3, and 10 µmol/l) induced short-lasting contractions on its own, followed by an inhibition of the twitch response during its presence in the organ bath. The inhibitor of small conductance Ca2+-activated K+ (SK) channels, apamin (100 nmol/l), prevented the inhibitory effect of αβ-meATP on the twitch response, whereas tetraethylammonium (300 µmol/l), a blocker of voltage-gated K+ channels and an inhibitor at nicotinic acetylcholine receptors, augmented the inhibitory effect of αβ-meATP on the twitch response.

ERK1/2 Phosphorylation in the Rat Supraoptic Nucleus, Dorsal Raphe Nucleus, and Locus Coeruleus Neurons Following Noxious Stimulation to the Hind Paw.

Phospho-ERK1/2 (pERK1/2) fluorescence-immunohistochemistry is specifically well suited to mirror neuronal activity in the pain pathway at the cellular level. This study employed this method to visualize neuronal activity in 3 rat CNS nuclei following an acute noxious stimulation. The rat hind paw was stimulated either by heat or by a sequence of mustard oil and heat.

Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig.

In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own.

pERK1/2 immunofluorescence in rat dorsal horn and paraventricular nucleus neurons as a marker for sensitization and inhibition in the pain pathway.

The aim of the present study was to investigate whether the phosphorylation of ERK1/2 in the rat lumbar dorsal horn and in the parvocellularis part of the paraventricular nucleus can be used to visualize neuronal activity. pERK1/2 fluorescence-immunohistochemistry is specifically suited to mirror neuronal activity in the pain pathway following an acute noxious stimulation. The rat hind paw was either stimulated by noxious heat or by a sequence of mustard oil and noxious heat.

Drug fever due to a single dose of pantoprazole.

Although proton pump inhibitors (PPI) are generally well tolerated, with most adverse effects being minor and self-limiting, there are singular reports on hypersensitivity immune reactions triggered by a PPI or its metabolites. Here we report a case of acute drug-induced fever with leukocytosis and a transient increase in CRP due to pantoprazole. This was apparently an idiosyncratic reaction (inflammatory fever), showing no cross-sensitivity towards esomeprazole.

Hexamethonium-induced augmentation of the electrical twitch response in the guinea-pig ileum longitudinal muscle-myenteric plexus strip.

Longitudinal muscle-myenteric plexus strips of the guinea-pig ileum were used to investigate the nature of the hexamethonium-induced augmentation of the twitch response. All preparations were set up in Tyrode solution and intermittent longitudinal twitch contractions were evoked by single pulse electrical field stimulation. Hexamethonium, a blocker of nicotinic ganglionic transmission, at 300 μmol/l and 1 mmol/l augmented the twitch contractions by 21% and 35%, respectively.

Amphotericin B transfer to CSF following intravenous administration of liposomal amphotericin B.

Objectives: Although amphotericin B (AmB) and its lipid formulations are used for the treatment of fungal infections of the CNS, the kinetics of AmB in the CSF after intravenous administration of liposomal amphotericin B (LAmB) are not well characterized.

Patients And Methods: From 14 paediatric haemato-oncological patients (aged 0.4-19.

The pain pathway in the rat following noxious thermal stimulation: effect of morphine on pERK1/2 and TRPV1 at the dorsal horn level, and on hyperalgesia.

The aim of the present study was to investigate the phosphorylation of ERK1/2 in the lumbar dorsal horn of the rat by fluorescence immunohistochemistry following a noxious thermal stimulation of the hind paw. The protein level of TRPV1 in the dorsal spinal cord and the development of a heat hyperalgesia after the acute noxious thermal stimulation were also measured. The protein content of TRPV1 was determined by Western blot and heat hyperalgesia by the plantar test.

Thermal stimulation of primary sensory neurons in the rat hind paw: effect of morphine on ERK1/2 phosphorylation, TRPV1 and TRPA1 channel expression.

Temperature-sensitive transient receptor potential (TRP) channels or 'thermo-TRP' were stimulated on rat sensory afferents, and the effects on the phosphorylation of ERK1/2, on the regulation of TRPV1 and TRPA1, as well as the pharmacological modulation by the opioid analgesic morphine were investigated. The thermal stimuli were applied to the rat hind paw by immersion into either hot or cold water. Phospho-ERK1/2 (p-ERK1/2) was measured by fluorescence-immunohistochemistry in the lumbar dorsal root ganglion (DRG) neurons.

Phosphorylation of ERK1/2 in dorsal root ganglia following sequential mustard oil and thermal stimulation of the rat hind paw.

The effect of a sequential stimulation by mustard oil and noxious heat or cold on the phosphorylation of ERK1/2 in sensory afferents was investigated. The stimuli were applied to the rat hind paw and phospho-ERK1/2 (p-ERK1/2) was measured by fluorescence-immunohistochemistry in the lumbar dorsal root ganglia (DRGs) neurons. All stimuli lead to a significant increase in the number of small size DRG cells displaying cytoplasmic staining for p-ERK1/2.

A fluorescence-immunohistochemical study on phosphorylation of ERK1/2, p38, and STAT3 in rat dorsal root ganglia following noxious stimulation of hind paw sensory neurons.

A fluorescence-immunohistochemical investigation was performed in lumbar dorsal root ganglia (DRGs) neurons of the rat with regard to ERK1/2-, p38- and STAT3-phosphorylation in response to nociceptor activation in the rat. The stimuli applied were perineural capsaicin treatment of the sciatic nerve, mustard oil application to the hind paw and heat or cold stimulation of the hind paw. The time points of investigations were 15 min/30 min after perineural capsaicin, 30 min/2 h/4 h for mustard oil, 10 min/4 h for cold and 30 min/2 h/8 h for the heat stimulus.

Antidepressants: clinically relevant drug interactions to be considered.

Drug interactions in clinical practice are common and have developed into an increasing challenge for the medical profession. Specifically antidepressant drugs (ADs), which are among the 5 most frequently prescribed drugs, are predestined for adverse drug interactions because of their multiple mechanisms of action and/or their influence on drug-metabolizing cytochrome P450 (CYP) enzymes. Although selective serotonin reuptake inhibitors (SSRIs) and other new-generation ADs have an overall improved safety profile, their potential for drug interactions is to be considered.

Seminal fluid ribavirin level and functional semen parameters in patients with chronic hepatitis C on antiviral combination therapy.

Background & Aims: Due to the possible teratogenic effect of ribavirin, effective contraception is mandatory during antiviral therapy in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate seminal parameters and ribavirin and HCV-RNA concentrations in seminal fluid and serum prior to and during antiviral treatment.

Patients And Methods: Fifteen male patients (age: 42+/-9 (years+/-SD)) with CHC treated with pegylated interferon-alpha-2a and ribavirin were investigated.

Dorsal root ganglion neurons respond with prolonged extracellular signal-regulated protein kinase phosphorylation following noxious heat and cold stimulation.

In the present study the time course of extracellular signal-regulated protein kinase phosphorylation (pERK1/2 appearance) in lumbar sensory dorsal root ganglia (DRG) was determined following a 5-min noxious heat or a noxious cold stimulus to the hind paw of the rat. The thermal stimuli were chosen to activate transient receptor potential (TRP) channels, but not to induce tissue damage. A quantitative analysis of phospho-ERK1/2 was performed by protein extraction and Western blot analysis.

Evidence for opioid-induced release of glutamate in guinea pig longitudinal muscle-myenteric plexus strip.

By the use of longitudinal muscle-myenteric plexus (LMMP) strips of the guinea pig ileum it should be investigated whether opioids can contribute to an excitatory component of the intestinal smooth muscle contractions. LMMP preparations were set up in Tyrode solution with 1 micromol/l naloxone present or without naloxone from the beginning of tissue preparation. After a 30-min equilibration period the twitch contractions evoked by the first and the fifth electrical 3-s-stimulus in an 80-s-sequence were significantly higher in the tissues prepared and tested without naloxone present.

Capsaicin- and mustard oil-induced extracellular signal-regulated protein kinase phosphorylation in sensory neurons in vivo: effects of neurokinins 1 and 2 receptor antagonists and of a nitric oxide synthase inhibitor.

Stimulation of primary sensory neurons with capsaicin or mustard oil leads to phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) via activation of transient receptor potential V1 (TRPV1) or TRPA1, respectively. p-ERK1/2 was determined by Western immunoblotting in the dorsal root ganglia and in the sciatic nerve of rats following either systemic or perineural capsaicin treatment, or mustard oil application to the hind paw skin. To investigate the possible involvement of neurokinin 1 (NK(1)) and NK(2) receptors as well as of nitric oxide, the selective antagonists, SR140333 for NK(1) and SR48968 for NK(2), and the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), were employed.