[The associations between God representations and suicidality among Christian patients with a major depressive disorder]. / De relatie tussen godsrepresentaties en suïcidaliteit bij christelijke patiënten met een depressieve stoornis.

BACKGROUND: Depression strongly increases the risk of suicide. Religion is described as a protective factor against suicide. Considering the emotional blunting associated with depression, it is important to investigate the affective dimension of religion. This dimension is conveyed in God representations.
AIM: To describe what types of God representation occur among Christian patients with major depressive disorder and to determine whether there is a relationship between types of God representation and suicide.
METHOD: Clinical and outpatients with a major depressive disorder (n=155) completed the Questionnaire God Representations and the Paykel Suicide Items. A k-means cluster analysis is applied to examine which types of God representations occur among depressed patients. Whether there is a relationship between the different God representations and suicide is examined by applying a linear regression analysis.
RESULTS: Depressed patients uphold two types of God representation: a positive type (n=82) with positive feelings towards God and where God was experienced as supportive, and a negative type (n=73) with anger and anxiety towards God and where God was experienced as passive. Patients with a negative type of God representation scored significantly higher on suicidality. The severity of depression was the main predictor of suicidality, but God representations were also related with a 4% increase in the explained variance.
CONCLUSION: In Christian patients with major depressive disorder a negative and a positive God representation emerged. Patients with a negative God representation mainly seem to feel abandoned by God. The suicidality is significantly increased in patients with a negative God representation, however, the increase in the proportion of the explained variance is small.

Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging Mouse Model.

BACKGROUND: Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. PURPOSE: We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. METHOD: Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. RESULTS: Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. CONCLUSIONS: Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.

Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-ß Signaling.

Aneurysm-osteoarthritis syndrome characterized by unpredictable aortic aneurysm formation, is caused by SMAD3 mutations. SMAD3 is part of the SMAD2/3/4 transcription factor, essential for TGF-ß-activated transcription. Although TGF-ß-related gene mutations result in aneurysms, the underlying mechanism is unknown. Here, we examined aneurysm formation and progression in Smad3-/- animals. Smad3-/- animals developed aortic aneurysms rapidly, resulting in premature death. Aortic wall immunohistochemistry showed no increase in extracellular matrix and collagen accumulation, nor loss of vascular smooth muscle cells (VSMCs) but instead revealed medial elastin disruption and adventitial inflammation. Remarkably, matrix metalloproteases (MMPs) were not activated in VSMCs, but rather specifically in inflammatory areas. Although Smad3-/- aortas showed increased nuclear pSmad2 and pErk, indicating TGF-ß receptor activation, downstream TGF-ß-activated target genes were not upregulated. Increased pSmad2 and pErk staining in pre-aneurysmal Smad3-/- aortas implied that aortic damage and TGF-ß receptor-activated signaling precede aortic inflammation. Finally, impaired downstream TGF-ß activated transcription resulted in increased Smad3-/- VSMC proliferation. Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-ß signaling, immune suppression may be more beneficial.

Synthetic approaches toward total synthesis of 12 beta-methyl- and 12-methylene-19-norpregnanes.

The effect of a substituent in the 12-position of progestagens was studied. To this end, various approaches toward the preparation of 12 beta-alkyl- and 12-alkylidenenorpregnanes were investigated. Eventually, the desired compounds 17 beta-hydroxy-12 beta-methyl-18a-homo-19-nor-17 alpha-pregn-4-en-20-yn-3-one (37) and 17 beta-hydroxy-12-methylene-18a-homo-19-nor-17 alpha-pregn-4-en-20-yn- 3-one (38) were obtained in racemic form by total synthesis; they were shown to lack progestagenic activity.

Urinary schistosomiasis in the Sichili Health Zone, Western Province, Zambia.

The distribution of Schistosoma haematobium in the Sichili Health Zone in the Western Province of Zambia was studied by performing cross-sectional surveys in Mwanalulenga (n = 493), a cluster of rural settlements along the Namakala stream and the Machili river, Mulobezi (n = 114), a semi-urban settlement along the Mulobezi river; and school-based surveys in Mulauli (n = 85), a small rural settlement along the Machili river, and in Sichili (n = 199), along the Namakala stream. The S. haematobium infection was assessed by the urine filtration technique. Prevalences ranged from 20.6 to 87.1%, 23.8% of all people were heavily infected (greater than or equal to 50 eggs per 10 ml of urine).

A new focus of Schistosoma mansoni in the western province of Zambia.

A new focus of Schistosoma mansoni in the Western Province of Zambia is described. Four study groups were investigated using the Kato faecal smear method. Prevalence ranged form 2-38%, intensity of infection ranged from 0-4920 eggs per gram faeces.

Presence of the schistosome circulating anodic antigen (CAA) in urine of patients with Schistosoma mansoni or S. haematobium infections.

We investigated the presence of the circulating anodic antigen (CAA) in the urine of schistosomiasis patients. This genus specific antigen was hitherto demonstrated only in the serum of schistosomiasis patients. The urine of 80 patients with Schistosoma mansoni infections, 33 patients with S. haematobium infections, and 2 patients with mixed S. haematobium and S. mansoni infections were screened by a quantitative enzyme-linked immunosorbent assay (ELISA). CAA was demonstrated in 81% of those with intestinal schistosomiasis and in 97% of those with urinary schistosomiasis. CAA titers were less than 1:0.2-1:51.2. Results were compared with circulating cathodic antigen (CCA) titers in urine obtained in an indirect hemagglutination assay (IHA). CCA was generally not detectable in the urine of patients with S. haematobium infection, but was demonstrated in the urine of 85% of the patients with S. mansoni infection. Both CAA titers and CCA titers correlated positively with the number of S. mansoni eggs excreted in the feces, but CAA titers did not show a significant correlation with the number of S. haematobium eggs in urine. Both antigen titers showed a moderate correlation with the serum CAA level in schistosomiasis mansoni. The discovery of CAA in the urine of the majority of schistosomiasis patients tested suggests the use of urine samples for non-invasive immunodiagnosis of the disease.

Structure and progestational activity of 13-substituted-18-norpregn-4-ene-3, 20-diones, a pilot study.

13-Ethyl-18-norpregn-4-ene-3, 20-dione (7) and 13-acetyl-18-norpregn-4-ene-3, 20-dione (4) were synthesized and tested in the s.c. Clauberg assay. The potencies of these compounds (1X and 1/3 X progesterone, respectively) are compared with those reported for 13-vinyl- and 13-cyanomethyl-18-norpregn-4-ene-3, 20-dione. A comparable activity (1/3 X progesterone) was found for 13-acetyl-18-norpregn-4-en-3-one (10) which lacks the 20-carbonyl group.

Strategy in drug research. Synthesis and study of the progestational and ovulation inhibitory activity of a series of 11beta-substituted-17alpha-ethynyl-4-estren-17beta-ols.

Using the strategy based on the Hansch method which analyses effects of substituents on biological activity in terms of their hydrophobic, electronic and steric effects we selectively synthesised a series of 11beta-substituted-17alpha-ethynyl-4-estren-17beta-ols that combine ease of synthesis with good discrimination between these factors aiming at finding the compounds with optimum biological activity in that series. The compounds were tested quantitatively in the Clauberg test (rabbit) and the ovulation inhibition test (rat). The differences in biological activity could reasonably be correlated with two steric effects introduced by the 11beta-substituent. These were a change in the overall shape of the 11beta-substituent and the angular methyl group, and direct steric hindrance of the steroid-receptor protein binding. Some exceptions were found possibly due to metabolic conversion of these compounds to the corresponding 11beta-substituted-17alpha-ethynyl-1,3,5(10)-estra-triene-3,17beta-diols.