Depression embodied: an ambiguous striving against fading

Although depression is associated to physical discomfort, meanings of the body in depression are rarely addressed in clinical research. Drawing on the concept of the lived body, this study explores depression as an embodied phenomenon. Using a hermeneutic phenomenological approach, the analysis of narrative‐based interviews with 11 depressed adults discloses a thematic structure of an embodied process of an ambiguous striving against fading. Five subthemes elicit different dimensions of this process, interpreted as disabling or enabling: feeling estranged, feeling confined, feeling burdensome, sensing life and seeking belongingness. In relation to clinical practice, we suggest that the interdisciplinary team can focus on enhancing the enabling dimensions, for example through guided physical activities to support the patient to feel more alive, capable and connected. Moreover, we suggest that the treatment process benefits from an increased awareness of the ambiguity in the patient's struggle, acknowledging both destructive and recharging elements of the withdrawing, and the perceived conflict in‐between.     

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.     

Variations in attachment ofNeisseria gonorrhoeae to vaginal epithelial cells during the menstrual cycle and early pregnancy

An in vitro system was used to study the ability of virulent gonococci to adhere to vaginal epithelial cells obtained from healthy donors during the pre- and postmenstrual phases, and from those in early pregnancy. It was found that more gonococci adhered to the cells from donors in the postmenstrual phase than to cells from those in the premenstrual one. This difference was statistically highly significant. The attachment rate of gonococci to vaginal epithelial cells was similar in early pragnancy and in the premenstrual phase.     

Co-expression in Helicobacter pylori of cagA and non-opsonic neutrophil activation enhances the association with peptic ulcer disease

AIMS: To investigate the association of cagA positivity and non-opsonic neutrophil activation capacity in wild-type Helicobacter pylori strains with peptic ulcer disease or chronic gastritis only. METHODS: Helicobacter pylori were isolated from antral biopsies of 53 consecutive patients with chronic antral gastritis, of whom 24 had peptic ulcer disease endoscopically. The presence of cagA, a marker for the cag pathogenicity island, was determined by polymerase chain reaction with specific oligonucleotide primers, and non-opsonic neutrophil activation capacity by luminol enhanced chemiluminescence. RESULTS: The cagA gene was present in 39 of 53 (73.6%) strains, 20 of which (83.3%) were from the 24 patients with peptic ulcer disease and 19 (65.5%) from the 29 patients with chronic gastritis only. Non-opsonic neutrophil activation was found in 29 (54.7%) strains, 16 of which (66.7%) were from patients with peptic ulcer disease, and 13 (44.8%) from those with chronic gastritis. Non-opsonic neutrophil activation was found more frequently in cagA+ than cagA- strains (59% v 42.9%). Whereas four of the 14 cagA- strains and eight of the 24 non-opsonic neutrophil activation negative strains were from patients with peptic ulcer disease, only two of 24 (8.3%) peptic ulcer disease strains expressed neither cagA nor non-opsonic neutrophil activation. The cagA gene and non-opsonic neutrophil activation capacity were co-expressed in 14 of 24 (58.3%) strains from patients with peptic ulcer disease, and in nine of 29 (31%) strains from individuals with chronic gastritis. CONCLUSIONS: Positivity for cagA and non-opsonic neutrophil activation occur independently in wild-type H pylori strains. However, co-expression of the two markers enhanced the prediction of peptic ulcer disease.     

VIP-sensitive adenylate cyclase, guanylate cyclase, muscarinic receptors, choline acetyltransferase and acetylcholinesterase, in brain tissue afflicted by Alzheimer's disease/senile dementia of the Alzheimer type

Biochemical parameters were determined in autopsy material from several brain regions of thirteen patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) (mean age 75 years) and from brains of ten age-matched controls (mean age 76 years). Choline acetyltransferase specific activity was significantly lower in the nucleus caudatus, putamen, left thalamus, hippocampus and the cortex from gyrus hippocampus and the temporal lobe in AD/SDAT, acetylcholinesterase specific activity was significantly lower in the hippocampus, parietal and left frontal lobe in AD/SDAT samples than in corresponding samples from aged-matched controls. A compensatory increase of muscarinic receptors was found in the nucleus caudatus and left frontal lobe samples in AD/SDAT. Guanylate cyclase activity was not significantly altered in AD/SDAT in the brain regions examined. The basal, non-stimulated activity of adenylate cyclase was significantly (p less than 0.05) elevated in hippocampus samples from AD/SDAT patients and the enzyme activity stimulated by the vasoactive intestinal polypeptide VIP (2 microM) or forskolin (10 microM) was also elevated in AD/SDAT although not significantly.     

Trophic effect of the sympathetic nervous system on the early development of the rat parotid gland: A quantitative ultrastructural study

Rats were sympathetically denervated on one side by avulsion of the superior cervical ganglion either immediately after birth (within 4 hr) or when the salivary glands were fully developed. Nine weeks after ganglionectomy the parotid glands were subjected to microscopical studies. As shown by the lack of specific fluorescence, sympathetic denervation caused an almost total depletion of catecholamines in the acini. This was further substantiated at the electron microscopic level using KMnO⁴ as fixative. No alterations in either gland weight or in acinar cell size were noticeable after adult sympathectomy. On the other hand, neonatal denervation caused a decrease in gland weight as well as acinar cell hypotrophy. The mean volume of individual acinar cells was reduced by roughly 25% and the granule volume density by about 50%. Also the mean volume of individual granules was decreased. These findings indicate an important role for the sympathetic nerve system in the maturation of the rat parotid gland.     

Neuroendocrine changes in colon of mice with a disrupted IL-2 gene

Neuroendocrine peptides have a variety of physiological functions in the gastrointestinal tract. This study was carried out to investigate the impact of IL-2 deficiency on the neuroendocrine system in normal colon, and the neuroendocrine changes during colonic inflammation. Mice with homozygous disrupted IL-2 gene (IL-2-/-) spontaneously developed a bowel disease with similarities to human ulcerative colitis. Different types of colonic endocrine cells and myenteric nerves were analysed in the IL-2-/- mice using immunomorphometry. The neuropeptide contents in the colonic tissues were determined by radioimmunoassay. Age-matched healthy IL-2+/- and IL-2+/+ mice served as controls and the colonic IL-2 levels were compared between these two groups of mice by ELISA. Our data showed that less than half the amount of IL-2 was synthesized in the colon of IL-2+/- mice compared with the IL-2+/+ wild-type mice. Two major differences in the neuroendocrine colon were found between the mice with an intact and disrupted IL-2 gene. One was age-related. The frequencies of various endocrine cells and myenteric nerves increased with age in the IL-2+/+ mice. However, no such increases were seen in the mice with a disrupted IL-2 gene. Instead, the volume densities of enteroglucagon, serotonin cells and substance P (SP), vasoactive intestinal polypeptide (VIP) and total myenteric nerves were lower in the older IL-2+/- and IL-2-/- mice compared with the wild type. The other was disease-related. Polypeptide YY (PYY) cells and tissue levels of PYY, SP and VIP were significantly decreased in the IL-2-/- mice during the course of bowel inflammation compared with the healthy IL-2+/- and IL-2+/+ controls. These findings indicate that colonic neuroendocrine alterations did occur in the mice with a disrupted IL-2 gene and diminished local IL-2 level, suggesting a role of IL-2 in the regulation of the neuroendocrine system and a prevalent interaction between the immune and neuroendocrine systems in normal colon. On the other hand, there were some changes that seemed to correlate with the bowel inflammatory process. They might be associated with the impaired function in inflamed gut and contribute to the development and/or prolongation of disease.     

Placental transfer and fetal distribution of cadmium and mercury after treatment with dithiocarbamates

The distribution in pregnant C57BL mice (day 18 of gestation) of intravenously administered cadmium (Cd) chloride and mercury (Hg) chloride (0.75 mol/kg b.w.) was studied, with or without previous dithiocarbamate pretreatment. Diethyldithiocarbamate (DEDTC), disulfiram, or thiram (2×1 mmol/kg b.w.) or vehicle (gelatine) alone, were given by gavage 2 h before and immediately after injection of the metals. The mice were sacrificed 4 and 24 h later and subjected to autoradiography or impulse counting of excised organs.All the dithiocarbamates increased the concentration of both Cd and Hg in brain and most other maternal organs. While DEDTC and thiram, in that order, strongly increased Cd concentrations in whole fetuses (around 17-fold at 4 h) and all fetal organs measured, disulfiram caused a decrease in fetal Cd concentrations. For Hg, all the dithiocarbamates substantially decreased fetal levels. Disulfiram, for example, decreased Hg levels by a factor of 5. The 24 h values confirmed those at 4 h both elements, although the differences between control and treatment groups were less pronounced.Although the results suggest the formation of lipid-soluble metal-dithiocarbamate complexes in vivo (e.g., increased concentration in brain), this does not necessarily lead to increased fetal levels of the metals. The increased levels of Cd after thiram and DEDTC pretreatment, however, indicate a risk for higher Cd fetotoxicity. It is likely that Cd is released in fetal cells following metabolism of the dithiocarbamate moiety of the complex.