Axonal swellings and spheroids: a new insight into the pathology of neurocysticercosis.

Neurocysticercosis is a parasitic brain disease caused by the larval form (Cysticercus cellulosae) of Taenia solium and is the leading cause of preventable epilepsy worldwide. However, the pathophysiology and relation to the wide range of clinical features remains poorly understood. Axonal swelling is emerging as an important early pathological finding in multiple neurodegenerative diseases and as a cause of brain injury, but has not been well described in neurocysticercosis.

The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?

Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age.

Intravesical nanocrystalline silver decreases experimental bladder inflammation.

Purpose: Interstitial cystitis is a sterile bladder inflammatory disease characterized by pelvic pain, urinary urgency and frequency. Nanocrystalline silver has anti-inflammatory properties, prompting us to investigate its effect in experimental bladder inflammation.

Materials And Methods: Nanocrystalline silver (0.

Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine.

The kinetic and dynamic interaction of caffeine and zolpidem was evaluated in a double-blind, single-dose, six-way crossover study of 7.5 mg zolpidem (Z) or placebo (P) combined with low-dose caffeine (250 mg), high-dose caffeine (500 mg), or placebo. Caffeine coadministration modestly increased maximum plasma concentration (C(max)) and area under the plasma concentration-time curve of zolpidem by 30-40%, whereas zolpidem did not significantly affect the pharmacokinetics of caffeine or its metabolites.

Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2.

Effects of age and gender on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic acting via binding to melatonin MT(1) and MT(2) receptors, were evaluated in healthy young (18-34 years) and elderly (63-79 years) volunteers. Part 1 evaluated the pharmacokinetics of open-label oral ramelteon, 16 mg. Part 2 was a double-blind, randomized, 2-trial crossover pharmacodynamic study of 16-mg ramelteon and matching placebo.

Intravesical suplatast tosilate (IPD-1151T) inhibits experimental bladder inflammation.

Purpose: Interstitial cystitis is a painful bladder disease characterized by urgency, frequency and variable inflammation but there is no curative therapy. Suplatast tosilate (IPD-1151T) is an immunoregulatory compound that decreases interstitial cystitis symptoms but to our knowledge its mechanism of action is unknown. We investigated the effect of intravesical IPD-1151T on mediator release from bladder explants in experimental cystitis.

Skin biopsy: a useful tool in the diagnosis of lysosomal storage diseases.

In this report, the authors summarize their 19-year experience with over 200 biochemically proven cases of lysosomal storage diseases using electron microscopic screening of more than 950 skin biopsies. They found that electron microscopy (EM) is a highly sensitive, efficient, cost-effective, and rapid diagnostic screening tool for evaluation of lysosomal storage diseases in skin biopsies. Although EM is more expensive than a single enzyme assay, it can exclude more than 90% of cases in which lysosomal storage disease is being considered.

Corticotropin-releasing hormone and the blood-brain-barrier.

Increased blood-brain-barrier (BBB) permeability precedes any clinical or pathologic signs and is critical in the pathogenesis of multiple sclerosis (MS) and brain metastases. CD4+ TH1 cells mediate demyelination in MS, but how they get sensitized and enter the brain to induce brain inflammation remains obscure. TH2 cytokines associated with allergic disorders have recently been implicated in MS, while genes upregulated in MS plaques include the mast cell-specific tryptase, the IgE receptor (Fc-epsilon-RI) and the histamine-1 receptor.

Lessons learned combining N-of-1 trials to assess fibromyalgia therapies.

Objective: Applying population research to individual treatment requires understanding the connections between patient-specific characteristics, population-based studies, and treatment responses. Conducting practice-based research using individual-focused (N-of-1) trials may aid this process. We combined N-of-1 trials to compare fibromyalgia therapies and to assess the feasibility and outcomes of this approach for practice-based effectiveness research.

Regulation of IL-1-induced selective IL-6 release from human mast cells and inhibition by quercetin.

Mast cells are involved in allergic reactions, but also in innate immunity and inflammation. Crosslinkage of mast cell Fc immunoglobulin E receptors (FcvarepsilonRI) by multivalent antigen triggers secretion of granule-stored mediators, as well as de novo synthesis of cytokines, including interleukin (IL)-6. We showed recently that the proinflammatory cytokine IL-1 stimulates human leukemic mast cells (HMC-1) and human umbilical cord blood-derived cultured mast cells (hCBMCs) to release newly synthesized IL-6 without tryptase in the absence of degranulation.

In vitro interactions of water-soluble garlic components with human cytochromes p450.

Eight water-soluble components of aged garlic extract were evaluated to assess their potential to inhibit the activity of human cytochrome-P450 (CYP) enzymes. The in vitro model consisted of human liver microsomes with index reactions chosen to profile the activity of the following six CYP isoforms: CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. With only 2 exceptions, none of the 8 garlic components produced >50% inhibition even at high concentrations (100 micromol/L).

Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies.

Objectives: Recent anecdotal, unvalidated case reports have suggested potentiation of warfarin-induced anticoagulation by cranberry juice, possibly through inhibition of human cytochrome P450 (CYP) 2C9, the enzyme responsible for the clearance of the active S-enantiomer of warfarin. To address this question, the effect of cranberry juice and other beverages on CYP2C9 activity was evaluated in vitro and in vivo.

Methods: The effects of 4 beverages on CYP2C9 activity were studied in human liver microsomes, by use of flurbiprofen hydroxylation as the index reaction.

Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics.

Background: Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established.

Aim: To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine.

Pharmocokinetics and pharmacodynamics of single-dose triazolam: electroencephalography compared with the Digit-Symbol Substitution Test.

Aims: To investigate whether the electroencephalogram (EEG) directly reflects the CNS effects of benzodiazepines by evaluating the relation of the EEG to plasma drug concentrations and to Digit-Symbol Substitution Test (DSST) scores after a single dose of triazolam, a representative benzodiazepine agonist.

Methods: Thirteen healthy male subjects were given 0.375 mg triazolam or placebo in a double-blind crossover study.

The role of mast cells in migraine pathophysiology.

Mast cells are critical players in allergic reactions, but they have also been shown to be important in immunity and recently also in inflammatory diseases, especially asthma. Migraines are episodic, typically unilateral, throbbing headaches that occur more frequently in patients with allergy and asthma implying involvement of meningeal and/or brain mast cells. These mast cells are located perivascularly, in close association with neurons especially in the dura, where they can be activated following trigeminal nerve, as well as cervical or sphenopalatine ganglion stimulation.

Rhabdomyoma of the head and neck demonstrated by prenatal magnetic resonance imaging.

A case of fetal rhabdomyoma (myxoid type) of the head and neck demonstrated on prenatal magnetic resonance imaging (MRI) is presented. This benign tumor of skeletal muscle is uncommon and should not be confused with its malignant counterpart-rhabdomyosarcoma. With the increasing use of ultrafast MRI, the radiologist is more likely to encounter head and neck masses in the fetus.

Prophylactic antibiotics for non-laboring patients with intact membranes undergoing cesarean delivery: an economic analysis.

Objective: We conducted an economic analysis of prophylactic antibiotic administration for elective cesarean delivery.

Study Design: We created a decision tree comparing the use of prophylactic antibiotics (cefazolin 1 gm intravenous) with no antibiotic use. We modeled the potential for anaphylaxis, and included outcomes of fever and endometritis.

Increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin.

Problem: Mast cells are critical in allergic and inflammatory diseases such as interstitial cystitis, which is often clinically associated with or mistaken as endometriosis. Mast cells had previously been reported to be increased at sites of endometriosis, and tryptase may contribute to the fibrosis and inflammation characterizing endometriosis.

Method Of Study: This is a pilot study of mast cell numbers and its activation in endometriosis biopsies (n = 10) by immunostaining for mast cell tryptase, corticotropin-releasing hormone (CRH) and urocortin (Ucn).

Mast cells and mast cell mediators as targets of dietary supplements.

Objective: To review the increasing amount of data that support or dispel the use of dietary supplements in the treatment of inflammatory conditions that involve mast cells, such as allergies, arthritis, and chronic pelvic pain syndrome.

Data Sources: A search was conducted in MEDLINE for natural substances, dietary supplements, flavonoids, and proteoglycans for their in vitro or in vivo effects on allergic and inflammatory conditions.

Study Selection: Studies were selected for inclusion because of the impact factor of the journal, the definitive nature of the findings, the soundness of the study design, and the expert opinion of the authors.

Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis.

Objective: To define the role of suture closure of the subcutaneous dead space in preventing wound complications after cesarean delivery.

Data Sources: We searched MEDLINE, the Cochrane Database of Systematic Reviews, and the bibliographies of major texts and review articles.

Methods Of Study Selection: Only studies in which patients undergoing cesarean delivery were randomly assigned to closure of the subcutaneous space or to no closure were included.

Azelastine inhibits secretion of IL-6, TNF-alpha and IL-8 as well as NF-kappaB activation and intracellular calcium ion levels in normal human mast cells.

Background: Mast cells are involved in allergic inflammation by secreting histamine, proteases and several cytokines, including interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8. Certain histamine-1 receptor antagonists, such as azelastine present in the ophthalmic solution Optivar, have been reported to inhibit histamine and tryptase secretion, but its effect on inflammatory cytokine release from normal human umbilical cord blood-derived cultured mast cells (hCBMC) are not well known.

Methods: We investigated the effect of azelastine on the secretion of IL-6, TNF-alpha and IL-8 from hCBMC, as well as its possible mechanism of action.

Women experience more pain and require more morphine than men to achieve a similar degree of analgesia.

Unlabelled: Sex differences in pain perception and in response to opioids have been described, but the findings are inconsistent. We sought to determine the effect of sex on pain perception, morphine consumption, and morphine analgesia after surgery. We designed a prospective cohort study and included 423 women and 277 men who emerged from general anesthesia after surgical procedures and who reported pain intensity of >or=5 on the 0-10 numeric rating scale (NRS).