The effects of harman and norharman on the metabolism of benzo(a)pyrene in isolated perfused rat lung and in rat lung microsomes.

The effects of harman and norharman, nitrogen-containing pyrolysis products of amino acids present in cigarette smoke, on the metabolism of benzo(a)pyrene in rat lung microsomes in vitro and in isolated perfused rat lung were studied. In rat lung microsomes, both harman and norharman inhibited the metabolism of benzo(a)pyrene (BP) to dihydrodiols, phenols and quinones at concentrations over approximately 0.05 mM. The formation of BP-7, 8-dihydrodiol and BP-9, 10-dihydrodiol was inhibited more than that of BP-4, 5-dihydrodiol. No appreciable differences in inhibition were seen between microsomes from control or 3-methylcholanthrene-pretreated rats. In isolated perfused rat lung, 1 mM of harman in the perfusion fluid inhibited the formation of ethyl acetate-soluble metabolites of benzo(a)pyrene except BP-9, 10-dihydrodiol, and inhibited the total covalent binding of benzo(a)pyrene metabolites to lung tissue macromolecules. 0.03 mM of harman seemed to increase other metabolites than BP-7,8-dihydrodiol without changing the total covalent binding. These results suggest that at most concentrations both β-carboline derivatives, harman and norharman, inhibit benzo(a)pyrene metabolism and covalent binding both in lung microsomes in vitro and in isolated perfused rat lung.     

The relation of the Xbal and Pvull polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene to peak bone mass and bone turnover rate among young healthy men

The genes coding for estrogen receptor- (ER-) and androgen receptors (AR) are potential candidates for the regulation of bone mass and turnover, which may contribute to both the achievement of peak bone mass and bone loss after completion of growth. The present study was aimed at elucidating the role of two restriction fragment lengths (XbaI and PvuII) polymorphisms of the ER gene and the CAG repeat polymorphism of the AR gene as determinants of peak bone mass in men; special attention was paid to the interaction between serum free estradiol (E₂) levels and the XbaI and PvuII genotypes. A cross-sectional study, with data on lifestyle factors collected retrospectively, was performed in 234 young men, aged 18.3 to 20.6 years. Of the men, 184 were recruits of the Finnish Army and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content (BMC), density (BMD) and scan area were measured in the lumbar spine and upper femur by dual-energy X-ray absorptiometry (DXA). The bone turnover rate was assessed by measuring serum type I procollagen aminoterminal propeptide (PINP) and tartrate-resistant acid phosphatase 5b (TRACP5b) as well as urinary excretion of type I collagen aminoterminal telopeptide (NTX). After adjusting for age, height, weight, exercise, smoking, calcium and alcohol intake, BMC, scan area and BMD at all measurement sites were similar for the different XbaI and PvuII genotypes of the ER and independent of the number of the CAG repeats of the AR gene. No association was found between free E₂ levels and bone parameters among any genotype group of the XbaI and PvuII polymorphisms. Except for urinary NTX, which showed a tendency to higher values for the xx ( P =0.08) and pp ( P =0.10) genotypes of the ER, bone turnover markers were not related to the genotypes studied. Our study does not support the view that the XbaI and PvuII polymorphisms of the ER gene and the CAG polymorphism of the AR gene would have a substantial impact on the development of peak bone mass in young Finnish men.     

Characterization of breast milk received by infants with gross blood in stools

OBJECTIVE: The aim of this study was to ascertain factors that might be protective of the appearance of gross blood in the stools of breast-fed infants. METHODS: Logistic regression models were formed to search for variables possibly explaining the condition. In addition to the analyzed breast milk factors, mother's allergic disease was introduced into the models to control for its possible confounding effect. The breast milk samples, collected from mothers of infants with gross blood in stools (n = 23) and from mothers of healthy age-matched infants (n = 71), were analyzed for concentrations of transforming growth factor-beta2, tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, prostaglandin (PG)E2, cysteinyl leukotrienes (Cys-LTs) and fatty acid composition. RESULTS AND CONCLUSIONS: Increase in the concentrations of PGE2 and Cys-LTs in the breast milk together with mother's allergic disease reduced the likelihood of gross blood in stools in the breast-fed infant. The results suggest that no single factor, but a combination of immunomodulatory factors may protect the child from gross blood in the stools of breast-fed infants. Allergic disease was not a risk factor as mother's allergic disease appeared to counterbalance the gross blood in stools. Due to the preliminary nature of the study, the results need to be verified in a larger setting. The challenge for the future lies in identifying of such active compounds for dietary modification to enforce particularly the properties of the breast milk which are immunoprotective for the infant and to reduce the likelihood of intestinal disorders in at risk infants.     

Novel approaches to the nutritional management of the allergic infant

The increased prevalence of atopic diseases, i.e. atopic eczema, allergic rhinitis and asthma, has been described as the epidemic of the 21st century in Western societies. New approaches in the fight against allergic diseases are clearly called for, the target being the persistence of the allergic responder pattern beyond infancy. The advantage afforded by elimination diets lies in the silencing of specific allergic inflammation induced by an offending food. Novel nutritional approaches, beyond the treatment of food allergies, have recently attracted research interest subsequent to the identification of the immunomodulatory potential of specific dietary compounds. Dietary lipids as immunomodulators may prevent allergic sensitization by down-regulating inflammatory response whilst protecting the epithelial barrier. Probiotic bacteria have been shown to reinforce the different lines of gut defence: immune exclusion, immune elimination and immune regulation. On this basis, the strategy against allergic disease proposed here is based on the administration of tolerogenic gut-processed peptide fragments of a specific protein, in addition to the use of specific dietary compounds such as fatty acids and antioxidants, and introducing a microbial stimulus for the immature immune system by means of cultures of beneficial live micro-organisms characteristic of the healthy infant gut microbiota.     

Effect of cholinergic medication, before and after focal photothrombotic ischemic cortical injury, on histological and functional outcome in aged and young adult rats

The present study evaluated the effect of galanthamine, a selective competitive cholinesterase inhibitor, on histological and functional outcome after experimental stroke in rats. Cholinesterase inhibitors are commonly used as cognitive enhancers for dementia in aged people, including those who may sustain ischemic attacks. Young adult (5 months) and aged (24 months) rats were treated with saline or galanthamine at a dose of 2.5 mg/kg (i.p., once a day). Drug treatment started 4 days before focal cortical photothrombosis (Rose Bengal, 20 mg/kg) and continued for 21 days thereafter. Sensorimotor recovery was assessed by a new beam-walking test and spatial learning by the Morris water-maze over a 3-week follow-up period. Infarct volumes were measured from nitroblue tetrazolium-stained sections at the end of follow-up. Infarct volumes in the cortex were similar in ischemic controls and ischemic rats treated with galanthamine. In the beam-walking test, there was a transient impairment forelimb function and a permanent impairment in hindlimb after cortical infarct both in young adult and aged rats. Galanthamine treatment did not affect the sensorimotor recovery rate. Analysis of water-maze data did not reveal significant differences in length of path, escape latency, or swim speed between sham-operated, ischemic controls and ischemic rats treated with galanthamine. In conclusion, present findings suggest that the aging brain has considerable plastic capacity to maintain functioning after focal cerebral insults restricted to the motor cortex. Galanthamine is not beneficial with respect to the histological or functional outcome in rats subjected to cortical photothrombosis.     

Self-inflicted burns: an eight year retrospective study in Finland

The aim of this study was to investigate differences in characteristics of burn patients who had attempted suicide, as compared with other burn patients admitted to the Helsinki Burn Centre during 1989-97. Burn patients were first drawn from a computerised register, after which a psychiatrist examined their medical records and ascertained the suicide attempters. Of the total of 811 burn patients, 46 (5.7%) had attempted suicide. The median total body surface area (TBSA) of suicide attempters (24.0%) was markedly higher than in the other patients (6.0%, P < 0.001). Flame was a much more common cause of burns among suicide attempters (82.1%) than among the remainder (44.5%, P < 0.001). Suicide attempters were also more often unemployed (28.2 versus 12.9%) or on disability pension (30.8 versus 7.1%) before the injury (P < 0.001). Although the proportion with self-inflicted burns among all burn patients was not high, the markedly higher severity of their burns makes them an important clinical subgroup for further study.     

CHEK2 1100delC is not a risk factor for male breast cancer population

Genetic risk factors for male breast cancer (MBC) are poorly understood. High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of the disease. A 1100delC mutation in CHEK2 (previously known as CHK2), a cell-cycle checkpoint kinase, has been implicated in predisposition of Li-Fraumeni syndrome (LFS) and breast cancer in families suggestive of LFS. This 1100delC mutation has also been shown to confer a 2-fold increase of breast cancer risk in women and a 10-fold increase of risk in men. It was estimated to account for 1% of breast cancers in women and as much as 9% of breast cancers in men at the population level based on analysis of breast cancer families without BRCA1 or BRCA2 mutations. We wanted to evaluate the significance of CHEK2 1100delC in predisposition to MBC by assessing its frequency in a population-based material of 114 Finnish MBC patients. Two patients (1.8%) carried the 1100delC mutation. The mutation frequency among MBC cases was similar to that seen in population controls (26/1885, 1.4%). Our results indicate that CHEK2 1100delC variant does not substantially increase the risk of male breast cancer at the population level. We cannot exclude the fact that a small fraction of hereditary, family-positive male breast cancers could be attributable to CHEK2 mutations.     

Do stressful life-events or sociodemographic variables associate with depression and alexithymia among a general population?--A 3-year follow-up study

This 3-year follow-up study examined background factors, stressful life-events, and changes in alexithymia and depression scores in four groups of subjects from a general population (N = 1,339): alexithymic (A), depressed (D), simultaneously alexithymic/depressed (AD), and non-alexithymic/non-depressed (O). Alexithymia was assessed using the 20-item version of the Toronto Alexithymia Scale (TAS) and depression using the 21-item Beck Depression Inventory (BDI). A questionnaire screening sociodemography and stressful life-events was also used. The results showed that alexithymia was associated with male gender and blue-collar working, whereas depressive symptoms associated with female gender, older age, poor subjective health, poor financial situation, and low life satisfaction. During the follow-up the sum of stressful life-events was higher among groups AD and D than in groups A and O. The most common stressful life-events were the death of a close relative or friend, a negative change in the health of a family member, and financial problems. The TAS scores decreased only in groups A and AD. The BDI scores decreased in group AD but remained relatively unchanged in group D. Interestingly, if only those without depressive symptoms are considered, alexithymia appears to be a rarer phenomenon than has been reported previously. Furthermore, it seems that depressive symptoms were chronic and long-lasting among the general population.     

Alexithymia and suicidal ideation: a 12-month follow-up study in a general population

Alexithymic features are often associated with depression, which is the most important risk factor for suicidal behaviors. Nevertheless, little is known about the associations between alexithymia and suicidality. In this 12-month follow-up study we investigated the relationship between alexithymia and suicidal ideation in a sample of the general population (N = 1,563) using the 20-item Toronto Alexithymia Scale (TAS-20) and the 21-item Beck Depression Inventory (BDI). Suicidal ideation was more common among subjects with alexithymia than among nonalexithymic subjects (32% v 9% at baseline and 36% v 9% after 12 months). In cross-sectional analyses, alexithymia associated with the presence of suicidal ideation even after adjustment for sex, age, and several psychosocial and socioeconomic factors and the presence of depression. Moreover, after adjustment for depression at baseline, the decrease and increase in alexithymic features during the study period associated independently with recovery from and the occurrence of suicidal ideation, respectively. Nevertheless, these associations were no longer independent when adjusted for concomitant changes in the level of depressive symptoms. In conclusion, if depression presents alexithymic features the subject has an additive impact on the risk of suicidal ideation.     

Evaluation of exposure to man-made vitreous fibers by nasal lavage

The objectives of this study were to develop a biomonitoring method for the assessment of exposure to man-made vitreous fibers (MMVF), to examine the level of exposure to MMVF in the prefabricated house industry, and to study nasal inflammatory reactions and respiratory symptoms associated with MMVF among workers. Nasal lavage was performed on workers from two factories, and concentrations of MMVF were measured by electron microscopy. Cytokines (IL-6, IL-8, TNF-alpha, and IFN-gamma) were also assayed and inflammatory cells (lymphocytes, eosinophils, neutrophils, and macrophages) were counted microscopically. Concentrations of airborne fibers (longer than 5 microm) were measured for comparison. Moreover, the exposure to MMVF and the related symptoms were studied with a structured questionnaire. In nasal lavage samples, the mean concentration of MMVF (length >1.5 microm) was 3260 f/ mL in Factory 1, 1680 f/mL in Factory 2, and below 500 f/mL in the control group. About 52% of the retained fibers were longer than 100 microm. The group-specific mean concentrations of MMVF in nasal lavage samples correlated with production rates and airborne fiber levels in both plants. The airborne concentrations of MMVF both in the breathing zone and fixed-point samples were low (below 0.1 f/cm(3)). No significant differences in the biological response (inflammatory cells, cytokines) were found between the groups exposed and the control group. The workers complained of some irritation of the skin, eyes, and upper respiratory tract, which could be reduced by appropriate protective equipment. It is concluded that nasal lavage can be used as a biomonitoring method in the assessment of MMVF exposure.