Subjective craving and event-related brain response to olfactory and visual chocolate cues in binge-eating and healthy individuals.

High-sugar/high-fat foods are related to binge-eating behaviour and especially people with low inhibitory control may encounter elevated difficulties to resist their intake. Incentive sensitization to food-related cues might lead to increased motivated attention towards these stimuli and to cue-induced craving. To investigate the combined influence of olfactory and visual stimuli on craving, inhibitory control and motivated attention, 20 healthy controls and 19 individuals with binge-eating viewed chocolate and neutral pictures, primed by chocolate or neutral odours. Subjective craving and electroencephalogram activity were recorded during the task. N2 and Late Positive Potential (LPP) amplitudes were analysed. Patients reported higher craving than controls. Subjective craving, N2 and LPP amplitudes were higher for chocolate versus neutral pictures. Patients showed a higher relative increase in N2 amplitudes to chocolate versus neutral pictures than controls. Chocolate images induced significant increases in craving, motivated attention and measures of cognitive control. Chocolate odour might potentiate the craving response to visual stimuli, especially in patients with binge-eating.

Cognitive behavioral therapy for compulsive buying behavior: Predictors of treatment outcome.

BACKGROUND: Compulsive buying behavior (CBB) is receiving increasing consideration in both consumer and psychiatric-epidemiological research, yet empirical evidence on treatment interventions is scarce and mostly from small homogeneous clinical samples. OBJECTIVES: To estimate the short-term effectiveness of a standardized, individual cognitive behavioral therapy intervention (CBT) in a sample of n=97 treatment-seeking patients diagnosed with CBB, and to identify the most relevant predictors of therapy outcome. METHOD: The intervention consisted of 12 individual CBT weekly sessions, lasting approximately 45minutes each. Data on patients' personality traits, psychopathology, sociodemographic factors, and compulsive buying behavior were used in our analysis. RESULTS: The risk (cumulative incidence) of poor adherence to the CBT program was 27.8%. The presence of relapses during the CBT program was 47.4% and the dropout rate was 46.4%. Significant predictors of poor therapy adherence were being male, high levels of depression and obsessive-compulsive symptoms, low anxiety levels, high persistence, high harm avoidance and low self-transcendence. CONCLUSION: Cognitive behavioral models show promise in treating CBB, however future interventions for CBB should be designed via a multidimensional approach in which patients' sex, comorbid symptom levels and the personality-trait profiles play a central role.

Amyloid plaques arise from zinc-enriched cortical layers in APP/PS1 transgenic mice and are paradoxically enlarged with dietary zinc deficiency.

The ZnT3 zinc transporter is uniquely expressed in cortical glutamatergic synapses where it organizes zinc release into the synaptic cleft and mediates beta-amyloid deposition in transgenic mice. We studied the association of zinc in plaques in relation to cytoarchitectural zinc localization in the APP/PS1 transgenic mouse model of Alzheimer's disease. The effects of low dietary zinc for 3 months upon brain pathology were also studied. We determined that synaptic zinc distribution within cortical layers is paralleled by amyloid burden, which is heaviest for both in layers 2-3 and 5. ZnT3 immunoreactivity is prominent in dystrophic neurites within amyloid plaques. Low dietary zinc caused a significant 25% increase in total plaque volume in Alzheimer's mice using stereological measures. The level of oxidized proteins in brain tissue did not changed in animals on a zinc-deficient diet compared with controls. No obvious changes were observed in the autometallographic pattern of zinc-enriched terminals in the neocortex or in the expression levels of zinc transporters, zinc importers or metallothioneins. A small decrease in plasma zinc induced by the low-zinc diet was consistent with the subclinical zinc deficiency that is common in older human populations. While the mechanism remains uncertain, our findings indicate that subclinical zinc deficiency may be a risk factor for Alzheimer's pathology.

Bioactive hydroxyphenylpyrrole-dicarboxylic acids from a new marine Halomonas sp.: Production and structure elucidation.

The new marine Halomonas sp. strain GWS-BW-H8hM (DSM 17996) was found to produce 3-(4'-hydroxyphenyl)-4-phenylpyrrole-2,5-dicarboxylic acid (HPPD-1) and 3,4-bis(4'-hydroxy- phenyl)pyrrole-2,5-dicarboxylic acid (HPPD-2). In initial cultivations using marine broth, only low contents of these compounds have been isolated. Improving the conditions and growing the strain on artificial seawater supplemented with tryptone 10 g l(-1), yeast extract 5 g l(-1), L-tyrosine 0.6 g l(-1), glycine 1 g l(-1), and glucose 6 g l(-1), the growth-associated HPPD-1 and HPPD-2 production of a 40-l batch cultivation reached the amounts of 47 mg l(-1) and 116 mg l(-1), respectively, after 65 h. Both compounds showed potent anti-tumor-promoting activities.

Mucolipidosis III type C: first-trimester biochemical and molecular prenatal diagnosis.

OBJECTIVES: Mucolipidosis IIIC (MLIIIC) is a rare autosomal recessive lysosomal storage disease resulting from defective mannose 6-phosphate-dependent lysosomal enzyme trafficking; mutations of the gamma subunit of N-acetylglucosamine-1 phosphotransferase (GINAcPT) were recently found to cause its pathogenesis. We report here for the first time prenatal diagnosis (PND) for MLIIIC by means of chorionic villous sampling (CVS). METHODS AND RESULTS: A fetus in a large Bedouin-Moslem family was found to be homozygous for the founder haplotype and the mutational SSCP pattern of MLIIIC. The diagnosis was confirmed by markedly reduced lysosomal enzyme activities in cultured chorionic villi. The molecular identification of the disease-causing mutation in this large Bedouin-Moslem kindred permitted, for the first time, identification of carriers and couples at risk. CONCLUSIONS: The feasibility of early PND for a progressive disabling disease is important for its prevention. Nevertheless, the feasibility of PND raises a serious dilemma since affected individuals might have a variable phenotype and the disease is progressive and non-lethal. In addition, religious and social constraints are important factors to be taken into consideration in the genetic counseling of couples at risk.

Mucolipidosis IV: novel mutation and diverse ultrastructural spectrum in the skin.

Mucolipidosis IV, a severe neurologic and ophthalmologic progressive disorder has a clinical range of onset between early childhood and adolescence entailing clinically severe, moderate, and mild forms, all of them majorly affecting Ashkenazi Jewish patients in an autosomal-recessive fashion owing to mutations in the MCOLN1 gene which encodes a transmembrane protein called mucolipin 1. We report on one of two affected siblings, the older brother having died of ML IV at the age of 33 years, the younger recently at the age of 37 years. Biopsied skin disclosed several types of lysosomal residual bodies, membrane-bound vacuoles, avacuolar lamellar bodies resembling membraneous cytoplasmic bodies, and a diverse spectrum of lipopigments which include curvilinear and fingerprint profiles. Contrary to earlier reports, disease-specific lysosomal residual bodies could not be identified in circulating lymphocytes of our patient. Mutation analysis revealed a homozygous novel mutation of a 34 bp deletion and 3 bp insertion in exon 2 of the MCOLN1 gene, perhaps the reason for this unusual clinical and morphological phenotype.

Mucolipidosis type IV.

Mucolipidosis type IV (MLIV) is a neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmological abnormalities, including corneal opacities, retinal degeneration, and strabismus. Severely affected as well as milder patients have been described. Over 80% of the MLIV patients are Ashkenazi Jews; the estimated heterozygote frequency in this population is 1/100. The disease is classified as a mucolipidosis due to the simultaneous lysosomal storage of lipids together with water-soluble substances. A broad spectrum of lipids and acid mucopolysaccharides were identified as the storage substances. Kinetic studies demonstrated that this heterogeneous storage stems from an abnormal endocytosis process in cells from MLIV patients of membrane components from late endosomes to the lysosomes and/or delayed efflux to the Golgi apparatus. The MLIV gene was mapped to chromosome 19p13.2--13.3 where a novel gene, MCOLN1, with MLIV-causing mutations, was identified. Two mutations were found among 95% of the Ashkenazi MLIV alleles, including an intronic acceptor splice-site mutation in 72% of the alleles and a partial gene deletion in 23%. Each of these mutations was associated with a defined haplotype in this chromosomal region. Other mutations were mostly identified in single, Ashkenazi and non-Ashkanazi patients, including missense, nonsense nucleotide deletions, and insertions. All mutations but one were identified in patients exhibiting the severe phenotype, an in-frame amino acid deletion was identified in a mild patient. MCOLN1 encodes a 580 aa protein, mucolipin 1, which is a member of a new protein family of unknown function at present, the mucolipins. Mucolipin 1 is a membrane protein with 6 transmembrane domains, a serine lipase, and nuclear localization signal motives. The protein shows homology to a group of calcium channels of the TRP/TRPL family. The involvement of this protein in the endocytosis process of membrane components is currently studied. A population screening operation among the Ashkenazi population for the detection of heterozygotes has been started in Israel as a prevention program.

Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population.

The gene MCOLN1 is mutated in Mucolipidosis type IV (MLIV), a neurodegenerative, recessive, lysosomal storage disorder. The disease is found in relatively high frequency among Ashkenazi Jews due to two founder mutations that comprise 95% of the MLIV alleles in this population [Bargal et al., 2000]. In this report we complete the mutation analysis of Jewish and non-Jewish MLIV patients whose DNA were available to us. Four novel mutations were identified in the MCOLN1 gene of severely affected patients: two missense, T232P and F465L; a nonsense, R322X; and an 11-bp insertion in exon 12. The nonsense mutation (R322X) was identified in two unrelated patients with different haplotypes in the MCOLN1 chromosomal region, indicating a mutation hotspot in this CpG site. An in-frame deletion (F408del) was identified in a patient with unusual mild psychomotor retardation. The frequency of MLIV in the general Jewish Ashkenazi population was estimated in a sample of 2,000 anonymous, unrelated individuals assayed for the two founder mutations. This analysis indicated a heterozygotes frequency of about 1/100. A preferred nucleotide numbering system for MCOLN1 mutations is presented and the issue of a screening program for the detection of high-risk families in the Jewish Ashkenazi population is discussed.

Tay-Sachs screening in the Jewish Ashkenazi population: DNA testing is the preferred procedure.

A unique screening program for the identification of Tay-Sachs Disease (TSD) heterozygotes has been performed in the tradi- tional Orthodox Ashkenazi Jewish (AJ) community since 1983. In recent years the program has utilized the biochemical assay for the determination of hexosaminidase A levels by the heat inactivation technique as well as by direct DNA analysis. The three mutations which were analyzed were those that have been shown to be prevalent among AJ TSD patients and carriers, namely the four nucleotide insertion mutation in exon 11 (1278+TATC), the splice mutation at the 5' end of intron 12 (1421+1g-->c), and the adult mutation, a Gly(269)-->Ser substitution in exon 5 (G269S). A total of 103,133 individuals were tested by biochemical analysis, and 38,197 of them were also assayed by DNA testing. Furthermore, 151 chromosomes from TSD patients or obligate heterozygotes were subjected to DNA analysis for one of the three mutations. DNA testing of the latter identified one of the three AJ mutations in every case, predicting a very high detection rate of heterozygotes in this community by this method. By contrast, the sensitivity of the enzyme assay ranged from 93.1% to 99.1% depending on the exclusion (inclusion) of inconclusive results as positive, while the specificity ranged from 88.1% to 98.8% depending on the inclusion (exclusion) of inconclusive results as positive. Our results strongly support the use of DNA testing alone as the most cost-effective and efficient approach to carrier screening for TSD in individuals of confirmed Ashkenazi Jewish ancestry.

Identification of the gene causing mucolipidosis type IV.

Mucolipidosis type IV (MLIV) is an autosomal recessive, neurodegenerative, lysosomal storage disorder characterized by psychomotor retardation and ophthalmological abnormalities including corneal opacities, retinal degeneration and strabismus. Most patients reach a maximal developmental level of 12?15 months. The disease was classified as a mucolipidosis following observations by electron microscopy indicating the lysosomal storage of lipids together with water-soluble, granulated substances. Over 80% of the MLIV patients diagnosed are Ashkenazi Jews, including severely affected and mildly affected patients. The gene causing MLIV was previously mapped to human chromosome 19p13.2-13.3 in a region of approximately 1 cM (ref. 7). Haplotype analysis in the MLIV gene region of over 70 MLIV Ashkenazi chromosomes indicated the existence of two founder chromosomes among 95% of the Ashkenazi MLIV families: a major haplotype in 72% and a minor haplotype in 23% of the MLIV chromosomes (ref. 7, and G.B., unpublished data). The remaining 5% are distinct haplotypes found only in single patients. The basic metabolic defect causing the lysosomal storage in MLIV has not yet been identified. Thus, positional cloning was an alternative to identify the MLIV gene. We report here the identification of a new gene in this human chromosomal region in which MLIV-specific mutations were identified.

Electrical Conductivity and Dielectric Dispersion Phenomena of Concentrated TiO(2) Suspensions.

The complex conductivity of concentrated TiO(2) suspensions (up to 50 vol%) was measured over a large frequency range (1 MHz-1.8 GHz), as a function of grain volume content. These measurements highlight relaxation phenomena in the intermediate frequency range, which are associated with the dispersed powder. These phenomena were previously noted in O'Brien's theoretical developments. A quantitative data analysis was made, in terms of time constant distribution, using the CONTIN software, from Provencher. As a result, a complex process is highlighted, including two main mechanisms in different ranges of time constants. Particularly, we showed good agreement between the higher frequency mechanism and the O'Brien theory. From Dukhin's lambda ratios, which are ratios of grain surface to bulk electrolyte conductances, we calculated the electrolyte conductivity as a function of powder concentrations. At higher powder concentrations, these values are different from those measured with centrifuged liquids. Copyright 2000 Academic Press.

Uptake of lactate by the liver: effect of red blood cell carriage.

Multiple-indicator dilution experiments with labeled lactate were performed in the livers of anesthetized dogs. A mixture of (51)Cr-labeled erythrocytes, [(3)H]sucrose, and L-[1-(14)C]lactate or a mixture of (51)Cr-labeled erythrocytes, [(14)C]sucrose, and L-[2-(3)H]lactate was injected into the portal vein, and samples were obtained from the hepatic vein. Data were evaluated using a model comprising flow along sinusoids, exchange of lactate between plasma and erythrocytes and between plasma and hepatocytes, and, in the case of L-[1-(14)C]lactate, metabolism to H[(14)C]O(-)(3) within hepatocytes. The coefficient for lactate efflux from erythrocytes was 0.62 +/- 0.24 s(-1), and those for influx into and efflux from hepatocytes were 0.44 +/- 0.13 and 0.14 +/- 0.07 s(-1), respectively. The influx permeability-surface area product of the hepatocyte membrane for lactate (P(in)S, in ml x s(-1) x g(-1)) varied with total flow rate (F, in ml s(-1) x g(-1)) according to P(in)S = (3.1 +/- 0.5)F + (0.021 +/- 0.014). Lactate in plasma, erythrocytes, and hepatocytes was close to equilibrium, whereas lactate metabolism was rate limiting.

Conventional versus laser-assisted therapy of periimplantitis: a five-year comparative study.

Between 1994 and 1999, 50 patients were treated with either profound parodontopathy (30) or periimplantitis (20). Half of each of the two groups of patients was treated conventionally, and the other half was treated with laser support. Before the operation, microbiological examinations were carried out, in addition to registering the clinical findings and taking x-rays. These procedures were repeated after the operation, and again after 6, 12, 24, 36, 48, and 60 months. The surgical part of therapy for each half of the patient groups included surface decontamination with diode laser light (1-watt output, maximum of 20 seconds) in addition to conventional procedures. The values of the laser-supported therapy were lower than those specified in the relevant literature. The relapse rate of the two diseases (13% for the periimplantitis and 23% for the parodontopathy group) after 5 years was lower than the comparative values of researched literature where decontamination was not included in the therapy. We think that integrating diode laser light decontamination in the approved treatment schemes for periimplantitis and parodontitis contributes considerably to the success of this therapy.

The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan.

The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan.

Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.

Mucolipidosis type IV (MLIV) is a lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. It is a rare autosomal recessive disease, and the majority of patients diagnosed, to date, are of Ashkenazi Jewish descent. We have mapped the MLIV gene to chromosome 19p13.2-13.3 by linkage analysis with 15 markers in 13 families. A maximum LOD score of 5.51 with no recombinants was observed with marker D19S873. Several markers in the linked interval also displayed significant linkage disequilibrium with the disorder. We constructed haplotypes in 26 Ashkenazi Jewish families and demonstrate the existence of two founder chromosomes in this population. The localization of MLIV to chromosome 19 will permit genetic prenatal diagnosis in affected families and will aid in the isolation of the disease gene.

Mucolipidosis type IV: the origin of the disease in the Ashkenazi Jewish population.

Mucolipidosis type IV (MLIV) is a neurodegenerative lysosomal storage disease in which most of the patients diagnosed hitherto are Ashkenazi Jews. The basic metabolic defect causing this disease is still unknown and the relevant gene has not yet been mapped or cloned. Seventeen Israel Ashkenazi families with MLIV patients had been interviewed to study their family origin. Although the families immigrated to Israel from various European countries they all could trace their roots three to four generations back to northern Poland or the immediate neighbouring country, Lithuania. Furthermore, there are only one or two ultraorthodox families among the 70-80 Ashkenazi families with MLIV patients worldwide, a marked under-representation of this group which constitutes at least 10% of the Ashkenazi population. This data indicate that MLIV mutation occurred only around the 18th and 19th centuries, after the major expansion of this population, in a founder in this defined European region belonging to a more modern, secular family.

Elevated lysosomal pH in Mucolipidosis type IV cells.

The lysosomal pH in Mucolipidosis type IV (ML-IV) and several other storage disease fibroblasts (Niemann Pick, type A; Niemann Pick, type C; Hunter (MPS II); and Farber) and in normal human skin fibroblasts was determined in situ. Cells were pulse labeled with a fluorescein-conjugated dextran to label the lysosomes. Quantitative fluorescence microscopy was then carried out on living cells to measure the ratio of fluorescence at two different excitation wavelengths. An image processing routine was used to quantify fluorescence from individual lysosomes. Ratiometric data were converted to an absolute value of pH using an appropriate standard curve. Lysosomal pH varied between 4.3 and 4.5 for all the cell types examined except ML-IV cells which was almost one pH unit higher (pH approximately 5.2). Qualitatively similar results were obtained using acridine orange, another fluorophore whose fluorescence emission is pH dependent, ruling out the possibility that the stored molecules in ML-IV cells might induce an artifact in the fluorescein-based pH measurements. We conclude that elevated lysosomal pH is unique to ML-IV cells. This property may be an important factor, if not the cause, for the accumulation of the broad spectrum of substances, including sphingolipids, phospholipids, and acid mucopolysaccharides, even though the lysosomal hydrolases participating in the catabolism of these molecules appear to be normal.