Parental alcohol misuse is a powerful predictor for the risk of traumatic brain injury in childhood

Background: Although the positive relationship between parental alcohol use and children's injuries is well established, it is not known whether parental alcohol misuse is a risk factor for traumatic brain injuries (TBIs) of their children and whether subjects with childhood TBI have hazardous drinking habits in adolescence.

Methods: The authors conducted a longitudinal cohort study at Oulu University Hospital. The cohort consisted of 12 058 subjects born in 1966, of which 207 had sustained TBI before the age of 14 years. Data on parental alcohol problems were obtained from the Finnish Hospital Discharge Register and the adolescents' drinking habits were analysed based on a postal inquiry at the age of 14 years.

Results: Parental alcohol misuse (RR 1.99, CI 1.19-3.33) and male gender (RR 1.53, CI 1.12-2.08) significantly predicted the risk of childhood TBI. Drinking to intoxication at the age of 14 was significantly associated with parental alcohol misuse (RR 1.62, CI 1.34-1.96), belonging to a one-parent family (RR 1.80, CI 1.61-2.02) and mild TBI (RR 1.67, CI 1.20-2.33).

Conclusions: It was observed that parental alcohol misuse is a major risk factor for TBI in children and drinking to intoxication is a common drinking pattern of adolescents who have sustained TBI in childhood.     

Sleep disturbances in aspartylglucosaminuria (AGU): A questionnaire study

Summary Sleep disturbances are common in many progressive metabolic encephalopathies. The possible presence of disturbed sleep–wake behaviour in the lysosomal storage disorder aspartylglucosaminuria, has not been previously studied, however. The sleep–wake behaviour of 81 patients with aspartylglucosaminuria (AGU, age 3–55 years, median 22 years; 42 female and 39 male) and 49 controls (age 2–57 years, median 18 years; 25 female and 24 male) was assessed through a postal survey. A slightly modified version of the validated Basic Nordic Sleep Questionnaire was used. Fifty-eight per cent of the AGU patients were reported to suffer daily from a sleep-related problem (controls 31%, p < 0.01). In AGU adults (age >17 years) and children (age ≤17 years), the corresponding figures were 52% and 61%, respectively (control children 22%, p < 0.05 and control adults 38%, p = 0.06). In AGU children, settling difficulties were reported to occur significantly more commonly than in control children. Children with AGU were also reported to snore more often than were the controls. Adults with this disorder were found to suffer from severely fragmented night-time sleep, which was experienced as highly distressing by the parents and other caregivers. A long night sleep period was reported to be common in the ageing AGU patients (AGU 9.5 ± 1.7 vs controls 7.2 ± 1.0 h, mean ± SD, p < 0.001). Parents and caregivers also often complained about disturbing movements during sleep in AGU patients. In conclusion, both children and adults with aspartylglucosaminuria were reported to display several types of sleep disturbances significantly more commonly than healthy controls. Competing interests: None declared     

Vesicular release of glutamate from hippocampal neurons in culture: an immunocytochemical assay

Glutamate, the main excitatory neurotransmitter in the brain, may cause excitotoxic damage through excessive release during a number of pathological conditions. We have developed an immunocytochemical assay to investigate the mechanisms and regulation of glutamate release from intact, cultured neurons. Our results indicate that cultured hippocampal neurons have a large surplus of glutamate available for release upon chemically induced depolarization. Long incubations with high K⁺-concentrations, and induction of repetitive action potentials with the K⁺-channel blocker 4-aminopyridine (4-AP), caused a significant reduction in glutamate labeling in a subset of boutons, demonstrating that transmitter release exceeded the capacity for replenishment. The number of boutons where release exceeded replenishment increased continuously with time of stimulation. This depletion was Ca²⁺-dependent and sensitive to bafilomycin A1 (baf), indicating that it was dominated by vesicular release mechanisms. The depletion of glutamate from cell bodies and dendrites was also Ca²⁺-dependent. Thus, under the present conditions, cytosolic glutamate is taken up in vesicles prior to release, and the main escape route for the amino acid is through vesicular exocytosis. Depolarization with lower concentrations of K⁺ caused sustainable release of glutamate, i.e., without full depletion.

Electrical synapses between AII amacrine cells: dynamic range and functional consequences of variation in junctional conductance

AII amacrine cells form a network of electrically coupled interneurons in the mammalian retina and tracer coupling studies suggest that the junctional conductance (G(j)) can be modulated. However, the dynamic range of G(j) and the functional consequences of varying G(j) over the dynamic range are unknown. Here we use whole cell recordings from pairs of coupled AII amacrine cells in rat retinal slices to provide direct evidence for physiological modulation of G(j), appearing as a time-dependent increase from about 500 pS to a maximum of about 3,000 pS after 30-90 min of recording. The increase occurred in recordings with low- but not high-resistance pipettes, suggesting that it was related to intracellular washout and perturbation of a modulatory system. Computer simulations of a network of electrically coupled cells verified that our recordings were able to detect and quantify changes in G(j) over a large range. Dynamic-clamp electrophysiology, with insertion of electrical synapses between AII amacrine cells, allowed us to finely and reversibly control G(j) within the same range observed for physiologically coupled cells and to examine the quantitative relationship between G(j) and steady-state coupling coefficient, synchronization of subthreshold membrane potential fluctuations, synchronization and transmission of action potentials, and low-pass filter characteristics. The range of G(j) values over which signal transmission was modulated depended strongly on the specific functional parameter examined, with the largest range observed for action potential transmission and synchronization, suggesting that the full range of G(j) values observed during spontaneous run-up of coupling could represent a physiologically relevant dynamic range.     

Serum retinol and risk of prostate cancer

Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041) and aggressive (n = 461) prostate cancer by quintiles of baseline and 3-year serum retinol concentrations and by change in serum retinol levels from baseline to 3 years. Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; P(trend) = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. Future studies may clarify the underlying biologic mechanisms of the retinol-prostate cancer association.     

Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine

Background: Acetaldehyde, associated with alcohol consumption, has recently been classified as a group 1 carcinogen in humans. Achlorhydric atrophic gastritis is a well‐known risk factor for gastric cancer. Achlorhydria leads to microbial colonization of the stomach. Several of these microbes are able to produce significant amounts of acetaldehyde by oxidation from alcohol. Acetaldehyde can be eliminated from saliva after alcohol intake and during smoking with a semi‐essential amino acid, l‐ cysteine. The aim of this study was to determine whether cysteine can be used to bind acetaldehyde in the achlorhydric stomach after ethanol ingestion. Methods: Seven volunteers with achlorhydric atrophic gastritis were given either slow‐release l‐ cysteine or placebo capsules in a double‐blinded randomized trial. Volunteers served as their own controls. A naso‐gastric tube was inserted to each volunteer. The volunteers ingested placebo or 200 mg of l‐ cysteine capsules, and ethanol 0.3 g/kg body weight (15 vol%) was infused intragastrically through a naso‐gastric tube. Five‐milliliter samples of gastric contents were aspirated at 5‐minute intervals. Results: During the follow‐up period, the mean acetaldehyde level of gastric juice was 2.6 times higher with placebo than with l‐ cysteine (13 vs. 4.7 μM, p < 0.05, n = 7). Conclusions: l‐ cysteine can be used to decrease acetaldehyde concentration in the achlorhydric stomach during alcohol exposure. Intervention studies with l‐ cysteine are needed on reducing acetaldehyde exposure in this important risk group for gastric cancer.     

Post‐trial costs,clinical outcomes,and dental service utilization after a randomized clinical trial for caries control among Finnish adolescents

Hietasalo P, Seppä L, Niinimaa A, Kallio J, Lahti S, Hausen H. Post‐trial costs, clinical outcomes, and dental service utilization after a randomized clinical trial for caries control among Finnish adolescents. Eur J Oral Sci 2010; 118: 265–269. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The aim of this study was to assess post‐trial treatment costs, clinical outcomes [decayed, missing or filled surfaces (DMFS) scores], and utilization of dental services among adolescents who had participated in a randomized clinical trial (RCT) in Pori, Finland, in 2001–2005. At baseline the children were 11–12 yr of age and had had at least one active initial caries lesion. The children in the experimental group (n = 250) had been exposed to multiple measures for caries control, while those in the control group (n = 247) had received standard dental care. During the post‐trial period (2005–2008), all participants received the standard dental care offered in public dental clinics in Pori. In both groups the costs of treatment procedures and outcomes for the post‐trial period were calculated for each adolescent. Information from patient records was available for 487 adolescents (former experimental n = 246, control n = 241). The mean total costs per adolescent were lower and the clinical outcome was better among the former experimental‐group participants. The differences in mean costs between the groups were statistically significant for preventive and restorative procedures. The utilization of dental services was significantly more regular among the former experimental‐group participants.