Impact of early dietary gamma-linolenic acid supplementation on atopic eczema in infancy

Polyunsaturated fatty acids (PUFAs) are components of cell membranes and may play an immunomodulating role in the pathogenesis of atopic dermatitis (AD). The goal was to determine the impact of PUFAs on AD by dietary supplementation of infants. Based on the parents' decision on their babies' primary feeding, mothers and newborns were randomized to the supplementation with gamma-linolenic acid (GLA) or placebo for up to 6 months. Breastfed infants received GLA by supplementing their mothers. Formula diet was commercial whey hydrolysate unsupplemented with PUFAs. Of 131 eligible infants, 24 developed AD within the first year of life. Of these, nine belonged to the exclusively breastfed group (n = 58), 14 to the combined-fed group (n = 53), and one to the never breastfed group (n = 20). We could not find an influence of GLA on the development of AD. In subjects with AD, at 1 yr of age the serum-immunoglobulin E (IgE) was the lowest in the GLA-supplemented group A-subjects. In the GLA-supplemented group, GLA-levels in breast milk were similar in atopic and non-atopic infants. In the non-supplemented group the GLA-content of breast milk was 0.07% of total fatty acids in atopic infants vs. 0.17% in non-atopic infants (p < 0.01). Dietary GLA-supplementation could not prevent AD. Interestingly, the number of infants developing AD was the lowest in never breastfed children. In infants suffering from AD, GLA-supplementation seemed to reduce total IgE in the first year of life.     

Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain.

The 2-deoxy-D-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n. basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticulata. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.     

A critical assessment of allergen component-based in vitro diagnosis in cherry allergy across Europe

BACKGROUND: Food allergy to cherry occurs throughout Europe, typically with restricted oral reactions in the central and northern parts but with frequent systemic reactions in the Mediterranean region. Previous studies have demonstrated insufficient sensitivity of commercially available cherry extract reagents in the diagnosis of cherry allergy. OBJECTIVE: To assess the diagnostic performance of specific IgE tests based on recombinant cherry allergens in comparison with an extract-based assay and to skin prick test (SPT). A secondary objective was to analyse the frequency of systemic reactions in cherry-allergic subjects across Europe, including the largest population of LTP-sensitized subjects from central Europe studied to date. METHODS: A total of 186 subjects from central Europe and Spain were studied. Serum IgE was analysed with ImmunoCAP tests carrying rPru av 1, 3 and 4, combined and separately, and cherry extract. RESULTS: Among the central European cherry allergics, the mix of rPru av 1, 3 and 4 had a sensitivity of 95%, compared with 65% for cherry extract, and the IgE binding capacity of the recombinant mix was considerably higher. The sensitivity of the two tests was more comparable in the Spanish population, 95% and 86%, respectively. The recombinant allergen ImmunoCAP equalled SPT in terms of sensitivity and specificity. Consistent with previous reports, major geographic differences in sensitization pattern and prevalence of systemic reactions were found. A significantly higher rate of systemic reactions was found in Spanish patients sensitized to Pru av 3 whereas German patients sensitized to LTP only had oral allergy syndrome. CONCLUSIONS: The recombinant cherry allergen ImmunoCAP is a highly sensitive diagnostic tool, clearly superior to any diagnostic method based on cherry extract. Three cherry allergens are sufficient for detecting sensitization in 95% of cherry-allergic subjects. Systemic reactions are common in LTP-sensitized individuals but seem to require at least one additional causative factor.     

Lymphocytic and collagenous colitis: the emerging entity of microscopic colitis. An update on pathophysiology, diagnosis and management.

Microscopic colitis (MC) encompasses the two morphologically distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). MC was first described less than 30 years ago but is presently recognized as a relatively common cause of chronic diarrhea in the adult population. Remarkably, up to 10% of adults who have a colonoscopy for the investigation of chronic diarrhea, and have endoscopically normal appearing mucosa, may have MC. Patients with MC generally present with chronic diarrhea, which can be associated with cramping and bloating. Endoscopic and radiological examinations are usually normal. Histological assessment reveals inflammation consisting predominantly of lymphocytic infiltration, and a thickened subepithelial collagen band is diagnostic of CC. Both LC and CC can be associated with autoimmune diseases such as celiac disease, diabetes, arthritis and thyroiditis, yet the mechanisms involved in the pathogenesis remain unclear. Emerging studies suggest that a stepwise approach be taken in the medical management of MC. This approach includes antidiarrheal agents and stopping of any offending agents; budesonide or bismuth subsalicylate; and cholestyramine or 5-acetylsalicylic acid agents. In resistant cases, oral corticosteroids and other immune modulatory therapy have been used.     

Urinary 5-Hydroxytryptophol: A Possible Marker of Recent Alcohol Consumption

Urinary 5-hydroxytryptophol (5-HTOL) is currently being evaluated as a marker of recent alcohol consumption. To compensate for urinary dilution, the molar ratio between 5-HTOL and 5-hydroxyindole-3-acetic acid (5-HIAA) is used. The 5-HTOL/5-HIAA ratio showed a satisfactory degree of individual stability when it was followed in a group of teetotallers for 1 month. The mean value of 5-HTOL/5-HIAA in a group of 69 persons abstaining from alcohol was 7.6 (pmoles 5-HTOL/nmoles 5-HIAA). Ninety-seven percent had values ranging from 4 to 17, with no value exceeding 20. A group of healthy volunteers were tested 12 hr after alcohol consumption and showed a dose-dependent and statistically significant elevation in the 5-HTOL/5-HIAA ratio. Four regular alcohol consumers who were followed during a period of 3 months of drinking had elevated values of the 5-HTOL/5-HIAA ratio in 60% of their urine samples. The present study indicates that urinary 5-HTOL/5-HIAA is a sensitive and reliable marker of recent alcohol consumption. We propose that a 5-HTOL/5-HIAA ratio greater than 20 (pmoles/nmoles) can be used to indicate recent alcohol consumption. This limit gives a low frequency of false positives; the statistical probability of having a value greater than 20 during abstinence from alcohol was calculated to be less than 0.001.     

The therapeutic use of botulinum toxin in cervical and maxillofacial conditions: an evidence-based review.

INTRODUCTION: The role of botulinum toxin as a therapeutic agent for several conditions is expanding. We sought to determine if botulinum toxin is safe and effective in treating patients with cervical dystonia and maxillofacial conditions. Our purpose was to establish a safety and efficacy profile to determine whether or not this treatment may be used prophylactically in patients undergoing dental implant therapy. METHODS: We performed a systematic search of the literature to identify randomized clinical trials evaluating patients treated with botulinum toxin as an adjunct to dental implant therapy, maxillofacial conditions including temporomandibular disorders (TMD), and cervical dystonia. RESULTS: Four randomized controlled trials (RCTs) met our search criteria in the area of cervical dystonia and chronic facial pain. No RCTs were identified evaluating dental implant therapy. Patients with cervical dystonia exhibited significant improvements in baseline functional, pain, and global assessments compared to placebo. Adverse events were mild and transient with numbers needed to harm (NNH) ranging from 12 to 17. Patients with chronic facial pain improved significantly from baseline in terms of pain compared to placebo. Rates of adverse events were less than 1%. CONCLUSION: Botulinum toxin appears relatively safe and effective in treating cervical dystonia and chronic facial pain associated with masticatory hyperactivity. No literature exists evaluating its use in dental implantology. Randomized clinical trials are warranted to determine its safety and efficacy in dental implantology and other maxillofacial conditions such as bruxism.     

Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists.

The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications.     

An efficient, robust and fast method for the offline detection of epileptic seizures in long-term scalp EEG recordings.

OBJECTIVE: A robust and fast algorithm for the offline detection of epileptic seizures in scalp EEG is described. It is aimed for seizure detection with high sensitivity and low number of false detections in long-term EEG data without a priori information. METHODS: To capture the characteristic electrographic changes of seizures, we developed an efficient method based on power spectral analysis techniques. The integrated power is calculated in two frequency bands for three multi-channel seizure detection montages (referenced against the average of Fz-Cz-Pz, common average, bipolar) using the same parameters for all montages and all patients taking into account an appropriate artifact rejection. RESULTS: A total of 3248 h of scalp recordings containing 148 seizures from 19 patients were examined. The averaged sensitivity was 90.9% and selectivity (false-positive errors/h, FPH) was 0.29/h of the Fz-Cz-Pz montage; the other montages yielded lower sensitivities but even better selectivity values. CONCLUSIONS: Taking into account that the method has been performed in a standardized way with fixed parameters for all patients and montages the obtained values for sensitivity are quite high while the selectivity is acceptably low. The parameters can additionally be tuned to patient specific seizures. It is assumed that this may further improve the seizure detection performance. SIGNIFICANCE: The proposed method may enhance the clinical use for the detection of seizures in scalp EEG long-term monitoring during presurgical evaluation.     

Sensitivity-encoded (SENSE) proton echo-planar spectroscopic imaging (PEPSI) in the human brain.

Magnetic resonance spectroscopic imaging (MRSI) provides spatially resolved metabolite information that is invaluable for both neuroscience studies and clinical applications. However, lengthy data acquisition times, which are a result of time-consuming phase encoding, represent a major challenge for MRSI. Fast MRSI pulse sequences that use echo-planar readout gradients, such as proton echo-planar spectroscopic imaging (PEPSI), are capable of fast spectral-spatial encoding and thus enable acceleration of image acquisition times. Combining PEPSI with recent advances in parallel MRI utilizing RF coil arrays can further accelerate MRSI data acquisition. Here we investigate the feasibility of ultrafast spectroscopic imaging at high field (3T and 4T) by combining PEPSI with sensitivity-encoded (SENSE) MRI using eight-channel head coil arrays. We show that the acquisition of single-average SENSE-PEPSI data at a short TE (15 ms) can be accelerated to 32 s or less, depending on the field strength, to obtain metabolic images of choline (Cho), creatine (Cre), N-acetyl-aspartate (NAA), and J-coupled metabolites (e.g., glutamate (Glu) and inositol (Ino)) with acceptable spectral quality and localization. The experimentally measured reductions in signal-to-noise ratio (SNR) and Cramer-Rao lower bounds (CRLBs) of metabolite resonances were well explained by both the g-factor and reduced measurement times. Thus, this technology is a promising means of reducing the scan times of 3D acquisitions and time-resolved 2D measurements.