Prevention of overweight and obesity in a Norwegian public health care context: a mixed-methods study.

BACKGROUND: Greater understanding about the prevention and treatment of overweight and obesity in preschool children within public health care is needed. This study assessed the impact of The First Steps module in routine primary health care including mapping of height/weight and diet followed by parental counselling of healthy habits on overweight and obesity in children aged 2 to 7 years. Further, we explored the experiences of public health nurses (PHNs) with the module. METHODS: Body weight and height obtained in 2014 and 2016 were extracted retrospectively for 676 children from the health records of children at 2, 4, or 6 years of age in five child health centers in Southern Norway. Sex- and age-adjusted body mass index (BMI) z-scores and weight status classifications were calculated according to the International Obesity Task Force reference values. Impact was assessed as change in mean BMI z-scores for children with under-, normal-, and overweight, respectively, and as proportion of children with overweight and obesity. In focus groups, PHNs described their experiences with the practical application of the module. Focus group transcripts were analyzed using Braun and Clarke's thematic analysis. RESULTS: Mean BMI z-scores decreased from 2014 to 2016 in overweight children (- 0.26) and increased in children with under- (0.63) and normal weight (0.06), whereas the proportion of children with overweight and obesity was stable. PHNs believed that the module provides them with new tools that are useful for addressing the intricacies of childhood obesity. They described counseling sessions with families as "moving upstream in a river" and that overweight and obesity may be one of many complex challenges for these families. CONCLUSIONS: Mean BMI z-score decreased in children with overweight during the 2 years after initiation of The First Steps module. PHNs considered the module as useful for addressing children's overweight and obesity, which was perceived as one of several complex challenges for most of these families. Specialist and evidence-based support is needed to address overweight and obesity in children in primary care. Further research should focus on integrating the issues relating to overweight and obesity within other family problems.

Bacterial adherence in otitis media: determination of N-acetylgalactosamine (GalNAc) residues in the submucosal glands and surface epithelium of the normal and diseased Eustachian tube.

BACKGROUND: Acute otitis media (AOM) is the most common childhood infection caused by bacteria. The pathogenesis of AOM implicates initial adherence of a pathogen to the nasopharyngeal epithelium, which is followed by bacterial colonization of the middle ear cavity through the Eustachian tube. N-acetylgalactosamine (GalNAc) is an important constituent of mucins and GalNAc containing sugar residues seem to be essential for initial adherence of respiratory bacteria to the surface of epithelial cells. OBJECTIVE: To explore the localization of GalNAc residues, we incubated Eustachian tube sections from Streptococcus pneumoniae infected and normal control rats with seven biotinylated, GalNAc recognizing lectins: Bauhinia purpurea lectin (BPA), Psophocarpus tetragonolobus lectin (PTA), Helix aspersa lectin (HAA), Helix pomatia lectin (HPA), Phaseolus lunatus lectin (PLA), Sophora japonica lectin (SJA) and Vicia Villosa isolectin B4 (VVA-B4). RESULTS: The mucin producing epithelium and submucosal glands of the normal Eustachian tube contained GalNAc residues, as evidenced by binding of several of the lectins. Lectin binding specificity and intensity changed following acute middle ear infection. BPA was the only lectin that exclusively stained the surface epithelium and the serous acini of the submucosal glands in the infected animals, whereas no binding was detected in the normal controls. HPA, HAA, PTA and VVA-B4 binding to surface epithelial cells increased after infection, indicating an active secretion of GalNAc containing glycans. Quantitative analysis of submucosal gland staining intensity showed significantly more GalNAc residues in the normal Eustachian tube, compared to infected animals. CONCLUSION: We conclude that the mucous producing elements of the normal rat Eustachian tube contain GalNAc residues essential for respiratory pathogen adherence. In addition, the GalNAc residue specificity and reacting intensity change in relation to acute infection, which may be important in relation to subsequent development of secretory otitis media or formation of a bacterial biofilm in the middle ear. The results show that GalNAc residues increased in both the submucosal serous glands and in the surface epithelium of the Eustachian tube after middle ear infection with S. pneumoniae.

Tenacibaculum sp. associated with winter ulcers in sea-reared Atlantic salmon Salmo salar.

Coldwater-associated ulcers, i.e. winter ulcers, in seawater-reared Atlantic salmon Salmo salar L. have been reported in Norway since the late 1980s, and Moritella viscosa has been established as an important factor in the pathogenesis of this condition. As routine histopathological examination of winter ulcer cases in our laboratory revealed frequent presence in ulcers of long, slender rods clearly different from M. viscosa, a closer study focusing on these bacteria was conducted. Field cases of winter ulcers during 2 sampling periods, 1996 and 2004-2005, were investigated and long, slender rods were observed by histopathological examination in 70 and 62.5% of the ulcers examined, respectively, whereas cultivation on marine agar resulted in the isolation of yellow-pigmented colonies with long rods from 3 and 13% of the ulcers only. The isolates could be separated into 2 groups, both identified as belonging to the genus Tenacibaculum based on phenotypic characterization and 16S rRNA sequencing. Bath challenge for 7 h confirmed the ability of Group 1 bacterium to produce skin and cornea ulcers. In fish already suffering from M. viscosa-induced ulcers, co-infection with the Group 1 bacterium was established within 1 h. Ulcers from field cases of winter ulcers and from the transmission experiments tested positive by immunohistochemistry with polyclonal antiserum against the Group 1 bacterium but not the Group 2 bacterium. Our results strongly indicate the importance of the Group 1 bacterium in the pathogenesis of winter ulcers in Norway. The bacterium is difficult to isolate and is therefore likely to be underdiagnosed based on cultivation only.

Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon.

The colon of Ws/Ws mutant rats shows impairment of pacemaker activity and altered inhibitory neurotransmission. The present study set out to find structural correlates to these findings to resolve mechanisms. In the colon of Ws/Ws rats, interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP) were significantly decreased and ICC located at the submuscular plexus and intramuscular ICC were rarely observed based on immunohistochemistry and electron microscopy. Ultrastructural investigations revealed that there was no overall loss of all types of interstitial cells combined. Where loss of ICC was observed, a marked increase in fibroblast-like ICC (FL-ICC) was found at the level of AP. Immunoelectron microscopy proved FL-ICC to be c-Kit(-) but gap junction coupled to each other and to c-Kit(+) ICC; they were associated with enteric nerves and occupied space normally occupied by ICC in the wild-type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin-like growth factor 1 receptor (Igf1r) occurred, co-localized with CD34 but not with c-Kit. A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws/Ws compared to wild-type rat colons. These CD34(+)/Igf1r(+) cells in the Ws/Ws colon occupied the same space as FL-ICC. Hence we propose that a subset of immature ICC (FL-ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase. The functional capabilities of the immature ICC and the regenerative capabilities of the adult progenitor cells need further study. The morphological features described here show that the loss of pacemaker activity is not associated with failure to develop a network of interstitial cells around AP but a failure to develop this network into fully functional pacemaker cells. The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.

On the formation and role of reactive oxygen species in light-driven LPMO oxidation of phosphoric acid swollen cellulose.

Light-driven activation of lytic polysaccharide monooxygenases (LPMOs) has been attributed to the transfer of high redox potential electrons from excited photopigments to the enzyme. However, due to the formation of reactive oxygen species (ROS) in such a system, not only electrons from the pigments but also ROS could be part of the enzyme mechanism. This work investigates the role of ROS in the oxidation of phosphoric acid swollen cellulose (PASC) by a light-driven LPMO system. Our results clearly show that the addition of superoxide dismutase or catalase to remove ROS did not attenuate the capacity of the light-driven LPMO system to oxidize PASC, as measured by formation of oxidized oligosaccharides. We conclude that ROS are not part of the light-driven LPMO activation; hence, transfer of high redox potential electrons from the excited photopigment to the LPMO remains the most likely mechanism under the conditions tested in this study.

Motility patterns and distribution of interstitial cells of Cajal and nitrergic neurons in the proximal, mid- and distal-colon of the rat.

The aim of this work was to study the patterns of spontaneous motility in the circular and longitudinal muscle strips and to characterize the distribution of c-kit positive interstitial cells of Cajal (ICCs) and nitrergic neurons (nNOS) in the proximal, mid- and distal-colon of Sprague-Dawley rats. We described two types of spontaneous contractions: high frequency (HF) and low frequency (LF) contractions, which were recorded in the presence of tetrodotoxin, suggesting a non-neurogenic origin. Regional differences were found in the motility patterns depending on the muscle layer and on the part of the colon studied. Muscle strips without submuscular plexus (SMP) showed only LF contractions. The density of ICCs was of the same magnitude along the extent of the colon: about 90-120 cells mm(-2) at Auerbach's plexus (AP) and 50-60 cells mm(-2) at the SMP. nNOS positive cells were found at the level of the AP and the major density was found in the mid-colon. Electrical field stimulation abolished LF but did not affect HF contractions. Our results indicate that HF contractions are due to the ICC network found associated with the submuscular plexus (ICC-SMP). The origin of LF contractions is still unknown.

4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogues of THIP. Synthesis and biological activity.

The thio analogues of the GABA (gamma-aminobutyric acid) agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), the GABA uptake inhibitor THPO (4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol), and the glycine antagonist THAZ (5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol) have been synthesized and tested biologically on single neurons in the cat spinal cord and in vitro by using synaptic membrane preparations obtained from rat brains. In contrast to THIP, thio-THIP (4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridin-3-ol, 5) was only a weak GABA agonist. Thio-THPO (4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol, 10) was slightly weaker than THPO as an inhibitor of GABA uptake in vitro, and these two compounds were approximately equipotent in enhancing the inhibition of the firing of cat spinal neurons by GABA. Like THAZ and structurally related bicyclic isoxazole zwitterions, thio-THAZ (5,6,7,8-tetrahydro-4H-isothiazolo[4,5-d]azepin-3-ol, 15) was an antagonist at glycine receptors on cat spinal neurons. The I/U ratios, which reflect the ability of neutral amino acids to penetrate the blood-brain barrier (BBB), were calculated for 5 (I/U = 16), 10 (63), and 15 (200). These low I/U ratios, compared with the findings that THIP (I/U = 500 or 1500) and THPO (I/U = 2500) enter the brain after systemic administration, suggest that the thio analogues may penetrate the BBB very easily.

Efficacy and tolerability of moclobemide compared with fluvoxamine in depressive disorder (DSM III). A French/Swiss double-blind trial.

The efficacy and tolerability of moclobemide and fluvoxamine, two new types of antidepressant agents, were compared in a multicentre, double-blind prospective study of patients with a diagnosis of major depressive episode (DSM III). Patients were randomized to receive either moclobemide (150 mg) or fluvoxamine (50 mg) twice daily for 7 days, immediately following a washout period of at least 1 week. Dosages were increased where necessary on day 8, to a maximum of moclobemide 450 mg or fluvoxamine 200 mg and in most cases were maintained at these levels for the remainder of the study period (4-6 weeks). Both treatment groups showed a marked antidepressant effect. While both treatments were well tolerated, moclobemide showed a more favourable side-effect profile than fluvoxamine. Of the 126 patients eligible for evaluation, 34 withdrew from therapy, 22% in the moclobemide group and 30% in the fluvoxamine group. Adverse events were reported in 41.8% of patients treated with moclobemide compared to 60.3% of patients in the fluvoxamine group. Reports of dry mouth and other anticholinergic effects were more frequent among those treated with fluvoxamine. A greater number of gastrointestinal complaints, especially nausea, also occurred in the fluvoxamine-treated patients.

Theoretical considerations and perspectives on the onset of action of moclobemide.

The aim of this paper is to focus on methodological problems related to clinical studies on the onset of action of antidepressants, especially moclobemide. The methodological discussion proposed focuses on: --global efficacy as a function of time; --proposals for a specific approach to the study of the onset of action; --quality of the response and onset of action; --the dimensional level and the onset of action.

Macrophages in the external muscle layers of mammalian intestines.

The literature on macrophages in the muscularis externa of mouse, rat, guinea pig, cat, dog and human gut is reviewed. In smaller mammals macrophages are regularly situated in two locations: in the serosa and at the level of Auerbach's plexus between the longitudinal and circular muscle layers. In addition a few solitary cells are present at the level of the deep muscular plexus. At the level of Auerbach's plexus the macrophages occur as a constant and regularly distributed cell population with intimate associations between macrophages and interstitial cells of Cajal. Morphologically they differ from most resident macrophages in being irregular in shape with 4-6 primary cytoplasmic processes, which branch and give a stellate appearance. They have been demonstrated with endocytotic markers (trypan red, FITC-dextran, cholera toxin), immunocytochemically with macrophage antibodies (F4/80, M1/70) and antibodies against MHC class-II antigen, GABA and cGMP. In muscularis externa of the human gut a regularly distributed cell population of macrophages is not obvious. However, a phenotypically distinct subgroup is identified by light microscopy with the pan macrophage antibodies (EBM11, C3b1 and partly by p150.95), and shows MHC class-II antigen. By electron microscopy muscularis externa macrophages, in all species investigated, appear to be endocytically downregulated, and since they are lysozyme, prostaglandine H synthase (both constitutive and activated) and acid phosphatase negative, they appear to be inactivated cells. Both origin and function of these cells are unknown. They may be immuno-competent, participate in a neuroimmune axis, tissue growth and modulation or other regulations of specific cell functions.

Moclobemide versus fluoxetine for double depression: a randomized double-blind study.

The efficacy and tolerability of the selective reversible monoamine oxidase A inhibitor, moclobemide (300 mg/day) and the selective serotonin uptake inhibitor, fluoxetine (200 mg/day), were compared in a six-week single-centre double-blind fixed-dose study in patients (n = 42) with double depression (DSM-III-R: dysthymia with superimposed major depressive episode) using weekly assessment on the Hamilton depression rating scale (HDRS-17 items) and clinical global impression (CGI) scale. The primary efficacy outcome measure was a decrease > or = 50% in end of treatment HDRS score, secondary measures were the mean total endpoint HDRS scores and percentages of CGI very good and good responses. Tolerability was measured by the frequency and severity of volunteered adverse events. There were no significant differences in secondary efficacy outcome measures, but more patients achieved a > or = 50% decrease in HDRS score on moclobemide (71% vs 38%, p < 0.05). The only adverse event was mild transient anxiety (n = 1) with moclobemide. The results suggest that moclobemide and fluoxetine are equally well tolerated and at least similar in efficacy in double depression. Evidence that moclobemide may be more effective requires confirmation in a larger comparative study incorporating a placebo control group.

Course of obsessive-compulsive disorder in children and adolescents: a prospective follow-up study of 23 Danish cases.

OBJECTIVE: The course of obsessive-compulsive disorder (OCD) in childhood and adolescence was analyzed. METHOD: Twenty-three (88%) of 26 children and adolescents with OCD, all referred to a county child psychiatric clinic as inpatients or outpatients, were longitudinally evaluated every 6 months for obsessive-compulsive symptomatology. At follow-up, 1 1/2 to 5 years after referral (mean follow-up time 3.2 years, SD 1.1), obsessive-compulsive as well as comorbid symptomatology was assessed and compared with that of an age- and sex-matched child psychiatric control group. RESULTS: Approximately one half of the children and adolescents retained an OCD diagnosis at follow-up. One third of these had an episodic course of the illness, and two thirds had chronic OCD. None in the control group had clinical OCD at follow-up, but three had subclinical obsessive-compulsive symptoms. Thirteen of the probands with OCD received medication (either clomipramine or citalopram) for a period of 1/2 to 2 years (mean 1.4 years). Medication seemed to reduce the severity of OCD in most cases. CONCLUSIONS: This short-term but intensive study supported theories of OCD as an illness with fluctuating severity. Previous findings, that OCD seems to be chronic in approximately half of the cases, were supported by this study.

Action potential generation, Kit receptor immunohistochemistry and morphology of steel-Dickie (Sl/Sld) mutant mouse small intestine.

In contrast to wild-type mice, homozygotes with mutations of the W locus do not express the functional Kit receptor and are severely deficient in the Auerbach's plexus (AP)-associated subtype of interstitial cells of Cajal (ICC-AP). With a morphologically intact neural and muscular structure, the absence in these mutants of both small-intestinal slow waves and ICC-AP constitutes strong evidence for a key role of ICC-AP as pacemaker cells. In steel-Dickie mutant mice (Sl/Sld), the gene coding for the Kit ligand (stem cell factor) is defective. We examined Sl/Sld mutants and controls with intracellular microelectrode techniques, combined with light and electron microscopy. The absence of the normal Kit ligand (Sl/Sld mice) had very similar effects as the absence of the Kit receptor in viable mice, mutated at the White spotting, W, locus (W/Wv mice), in that neither slow waves, nor Kit receptor immunoreactivity in the region of Auerbach's plexus nor ICC-AP were present in the small intestine. In the Sl/Sld mouse, the smooth muscle cells generated action potentials at variable frequencies from a depolarized cell membrane of -40 to -55 mV. Increasing excitability by K channel blockers created many different patterns of action potential generation and the frequency increased from approximately 16 cpm to 66 cpm. This was in sharp contrast to control mice where action potentials were always restricted to the plateau phase of the slow waves and the slow wave frequency remained constant at approximately 39 cpm. Our data provide further strong support for the identification of ICC-AP as small-intestinal pacemaker cells. In addition, they provide a basis for the understanding of intestinal motor function without pacemaker activity.

Acquired zinc deficiency dermatosis in man.

We encountered two cases of acquired zinc deficiency. In one of the patients the state was due to alcoholism with liver cirrhosis and pancreatitis, and in the other patient it was attributed to a small intestine bypass operation for obesity. The skin symptoms included hair loss, acrodermatitis, and widespread eczema craquelé (asteatosis). The cutaneous manifestations of zinc deficiency seem to constitute a characteristic syndrome that might be helpful in recognizing manifest zinc-deficient states in man.

Determination of minute amounts of ATP by flow injection analysis using enzyme amplification reactions and fluorescence detection.

A flow-injection system for assay of trace levels of ATP is described that incorporates a small column reactor containing co-immobilized hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase. In the presence of appropriate cofactors, ATP is by the synergistic operation of the enzymes repeatedly recycled, resulting in substrate amplification. The ultimately generated NADH is measured fluorometrically. By this approach, where the enzymatic degradation step and the detection step are completely separated, it is possible to operate them individually under optimal conditions. The amplification factor is directly proportional to the residence time of the sample zone within the enzyme reactor, which time might be manipulated by altering the flow-rate and in the extreme by performing stopped-flow experiments. Amplification factors between 15 and 1000 were obtained, but it was found that increased amplifications did not lead to significantly lower detection limits; thus, it appears that a practical lower limit of detection is of the order of 1-5 nM. An investigation of this paradoxical feature, and a possible explanation for it, is given.

Therapeutic efficacy of antidepressants in agitated anxious depression--a meta-analysis of moclobemide studies.

The results of the meta-analysis of studies comparing the efficacy of moclobemide, imipramine and so-called sedative antidepressants (amitriptyline, mianserin and maprotiline) in 2416 patients are described. The results demonstrated that in agitated-anxious depressive patients (defined by HAMD factor score or HAMD item 9) a nonsedative, reversible MAO-A inhibitor moclobemide has about equal efficacy as imipramine or sedative antidepressants. All antidepressants were clearly superior to placebo, irrespective of the outcome measures applied (> 50% HAMD decrease, CGI improvement). The efficacy of antidepressants in agitated patients was unrelated to the severity of agitation and did not appear to be inferior to the efficacy in nonagitated patients. Comedication with benzodiazepines had no impact on overall efficacy of either moclobemide or other antidepressants in this patient population. Previous treatment with antidepressants, however, always negatively influenced the outcome with trial drugs, e.g., reduced their efficacy. Placebo response in agitated depressives appeared generally to be low (20-30%) and was clearly reduced with increased severity of agitation, irrespectively of how the agitation was defined.

Osmotic lysis of erythrocytes in relation to the zinc concentration of the medium.

The influence of various zinc concentrations on the osmotic resistance of erythrocytes was studied in six normal adults. Sodium chloride solutions ranging from 0.1% to 0.7% were prepared, each containing 0 microgram % zinc, 50 microgram % zinc, 100 microgram % zinc, 500 microgram %, and 1000 microgram % zinc. Heparin-stabilized venous blood was added to the various solutions at 25 degrees C, and the degree of haemolysis (erythrolysis) after 1 h was determined by measurement of the absorbance at 540 nm. Neither the absence, nor the presence of relatively high zinc concentrations were found to influence the degree of haemolysis. The results indicate that haemolytic anaemia which was observed in zinc-deficient patients is not due to a zinc-dependent change in the osmotic resistance of erythrocytes.

Identification and characterization of Carnobacteria isolated from fish intestine.

Eleven bacterial strains were isolated from the gastrointestinal tract of four fish species, Atlantic salmon (Salmo salar L.), Arctic charr (Salvelinus alpinus L.), Atlantic cod (Gadus morhua L.) and wolffish (Anarhichas lupus L.). All the strains were Gram-positive rods, non-sporing, catalase and oxidase-negative, able to grow at pH 9.0 but not on acetate containing media (pH < or = 5.4), and were fermentative. They had a high content of oleic acid (18:1 n-9) in cellular lipid, and were found to belong to the genus Carnobacterium by phenotypic criteria. The eleven carnobacteria strains were further identified on the basis of 16S rDNA sequence analysis and AFLP(TM) fingerprinting.

Dimensional assessment of onset of action of antidepressants: a comparative study of moclobemide vs. clomipramine in depressed patients with blunted affect and psychomotor retardation.

The onset of action (during the first 2 weeks of treatment) of moclobemide (450 mg/day), a reversible MAO-A inhibitor, was compared in a double-blind, multi-center trial with clomipramine (150 mg/day) on dimensional and global depressive symptoms in 124 hospitalized patients suffering from a major depressive episode according to DSM-III-R criteria and with blunted affect and retardation. An earlier efficacy was found for moclobemide with significant treatment differences in favor of moclobemide, which were detected on negative symptoms (anhedonia, blunted affect and retardation) on days 7 and 10. The overall effect on depression at the end of the 4-week trial period was similar in both groups. However, a higher termination rate due to lack of efficacy was found with moclobemide (10 vs. 3). The tolerability was significantly better for moclobemide, as shown by the lower frequency of adverse events.

Selective double staining of interstitial cells of Cajal and macrophage-like cells in small intestine by an improved supravital methylene blue technique combined with FITC-dextran uptake.

By a brief exposure of small intestine (mouse, rat, guinea pig) to lysolecithin prior to vital methylene blue staining we were able to demonstrate in a selective way the complete network of interstitial cells of Cajal, located in the space between the longitudinal and circular muscle layers. A combination with fluorescence labeling (FITC-dextran uptake) of macrophage-like cells, allowed us to demonstrate 1) the complete, regular distribution of both cell populations along the entire small intestine, and 2) the constant, intimate associations between interstitial cells of Cajal and macrophage-like cells. In relation to current hypotheses concerning a role of interstitial cells of Cajal in motility regulation, our results call attention to the possible involvement of another cell type, the macrophage-like cell.