Attentional bias for alcohol-related information in adolescents with alcohol-dependent parents

AIMS: to assess the attentional bias for alcohol-related information in adolescents with (n = 15), and without (n = 15), a parental history of alcohol dependence. METHODS: participants completed questionnaires assessing depression, weekly alcohol consumption, anxiety, and concerns about alcohol consumption and undertook subliminal and supraliminal computerized Stroop tasks using colour-words, alcohol-related words, and control words. RESULTS: adolescents with alcohol-dependent parents showed supraliminal interference for alcohol-related words. The magnitude of this interference was correlated with higher trait and state anxiety, and lower levels of weekly alcohol consumption. No interference was found on the subliminal alcohol Stroop task. CONCLUSIONS: while it is likely that this attentional bias for alcohol-related cues reflects the concerns regarding parental drinking, it is also possible that this might underlie the increased risk of future alcohol dependence in the children of alcohol-dependent parents.     

The utility of optical loupe magnification for testis sperm extraction in men with nonobstructive azoospermia

The testis of patients with nonobstructive azoospermia (NOA) harbors sperm in approximately 30% to 60% of cases. Use of an operating microscope has been shown to result in better sperm retrieval rates. This investigation was undertaken to evaluate the ability of a modified microsurgical approach using magnifying loupes (3.5x) to improve the rates of sperm retrieval during testis sperm extraction (TESE). The study group consisted of patients with NOA who underwent TESE. Before December 1998, TESE was conducted in a standard fashion, and from 1999 on, loupe magnification was used. Comparison was made between the 2 groups with regard to sperm retrieval rates, need for bilateral TESE, and number of tunical incisions. Overall sperm retrieval rates did not differ between the 2 groups (45% vs 50%). However, in patients with testicular volumes of 10 mL or less, patients who underwent standard TESE had a retrieval rate of 27% compared with 42% when using the optical loupe magnification (P = .025). The use of loupe magnification may permit surgeons without access to or experience using an operating microscope to obtain better rates of sperm retrieval in men with NOA who have testicular volumes of 10 mL or less.     

Leukotriene modifier therapy for mild sleep-disordered breathing in children

BACKGROUND: Children with mild sleep-disordered breathing (SDB), who may not be recommended for adenotonsillectomy, frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions, such as leukotriene modifier therapy. METHODS: Twenty-four children with SDB completed an open-label intervention study for 16 weeks with daily montelukast therapy. Sleep studies and adenoid size estimates from lateral X-ray films of the neck were obtained before and after treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea or recurrent throat infections were subjected to quantitative polymerase chain reaction, immunohistochemistry, and Western blotting for gene and protein expression of leukotriene receptors LT1-R and LT2-R, and for concentrations of LTB4 and LTC4/D4/E4. RESULTS: Montelukast treatment induced significant reductions in adenoid size and respiratory-related sleep disturbances, which were absent in 16 children with SDB who did not receive treatment. LT1-R and LT2-R mRNA was similarly abundant in adenoid tissues, but increased LT1-R and LT2-R protein expression and higher levels of LTB4 and LTC4/D4/E4 emerged in children with obstructive sleep apnea. CONCLUSIONS: Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep. Double-blind, placebo-controlled trials will be needed to corroborate current findings and solidly establish antiinflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for adenotonsillectomy.     

Intermittent hypoxia induces time-dependent changes in the protein kinase B signaling pathway in the hippocampal CA1 region of the rat

Intermittent hypoxia (IH) during sleep induces temporally defined increases in apoptosis within vulnerable brain regions such as the hippocampal CA1 region in rats. Protein kinase B (AKT) has emerged as major signal transduction protein underlying inhibition of apoptosis and consequent increases in cell survival. Sprague Dawley adult male rats were exposed during sleep to IH or to normoxia (RA) for periods ranging from 0 to 30 days, and expression of total and phosphorylated AKT, of forkhead family members FKHR and FKHRL1, and of glycogen synthase kinase 3beta (GSK3beta) was assessed. Decreases in phosphorylation occurred as early as 1 h IH exposure, reached a nadir at 6 h-3 days, and then progressively returned to baseline levels at 14-30 days. Phosphorylated AKT and GSK3beta were intensely expressed and highly colocalized within neuronal cells (Neu-N positive) in the CA1 region. Thus, IH induces time-dependent biphasic changes in AKT survival pathways within the CA1 region that are temporally correlated with the initial increases and subsequent decreases in neuronal apoptosis.     

Experience with New World cutaneous leishmaniasis in travelers

In recent years, New World cutaneous leishmaniasis has been seen at a higher incidence among returning Israeli travelers. Leishmania braziliensis and related species cause unsightly cutaneous lesions possibly complicated with a mucosal disease. A total of 12 patients with New World cutaneous leishmaniasis were treated in our clinic, 11 of whom (92%) acquired the disease in the Bolivian Amazon Basin. Five (42%) had regional lymphadenopathy in addition to cutaneous lesions. Polymerase chain reaction was performed for 8 patients to identify the causative Leishmania species. In all, 9 patients (75%) were cured by a single course, and 3 (25%) after an additional course of intravenous sodium stibogluconate. The treatment was well tolerated clinically. Laboratory abnormalities, mainly elevation of liver enzymes (58%), were reversible. We concluded that polymerase chain reaction is a useful tool in establishing the species diagnosis of leishmaniasis and that sodium stibogluconate appears to be a safe and effective treatment for L braziliensis infection.     

Nitric oxide-induced motility in aortic smooth muscle cells: role of protein tyrosine phosphatase SHP-2 and GTP-binding protein Rho

We have previously reported that SHP-2 upregulation is necessary for NO-stimulated motility in differentiated rat aortic smooth muscle cells. We now test the hypothesis that upregulation of SHP-2 is necessary and sufficient to stimulate cell motility. Overexpression of SHP-2 via recombinant adenoviral vector stimulated motility to the same extent as NO, whereas the expression of C463S-SHP-2, the dominant-negative SHP-2 allele, blocked the motogenic effect of NO. On the basis of previous studies, we next tested the hypothesis that NO decreases RhoA activity and that this event is necessary and sufficient to explain NO-induced motogenesis. We found that NO decreased RhoA activity in a concentration-dependent manner. Moreover, a dominant-negative SHP-2 allele, DSH2, blocked the NO-induced inhibition of RhoA activity, indicating that upregulation of SHP-2 is necessary for this event. Expression of G14V-RhoA, the constitutively active RhoA allele, decreased cell motility and blocked the motogenic effect of NO, whereas the expression of T19N-RhoA, the dominant-negative RhoA allele, increased cell motility to an extent similar to that induced by NO. Dominant-negative RhoA reversed the effect of dominant-negative SHP-2, indicating that RhoA functions downstream from SHP-2. To investigate events downstream from RhoA, we treated cells with fasudil, a selective Rho kinase inhibitor, and found that it increased cell motility. These results indicate that upregulation of SHP-2, leading to downregulation of RhoA, which is followed by decreased Rho kinase activity, is a sequence of events necessary and sufficient to explain NO-induced cell motility in differentiated aortic smooth muscle cells. The results may be of relevance to in vivo events such as neointimal formation, angiogenesis, and vasculogenesis.     

Loss of chromosome 16 from renal epithelial cells in humans

This work explores the notion that low-frequency, acquired aneuploidy may play a role in complex genetic traits such as essential hypertension. To this end, renal epithelial cells in urinary sediments and in renal cysts were examined by fluorescent in situ hybridization with DNA probes specific for the heterochromatic and centromere regions of chromosomes 16 and 1. Chromosome 16 was probed because it harbors variant genes causing monogenic hypertension. These genes have also been investigated for their role in essential hypertension. Chromosome 1 was also probed as an internal control. Higher proportions of renal epithelial cells in the urinary sediments showed monosomy of chromosome 16 than monosomy of chromosome 1 (P<0.001). We also observed in epithelial cells of renal cysts a preponderance of monosomy for chromosome 16 over monosomy for chromosome 1 (P<0.024). Low-frequency loss of heterozygosity that results from acquired monosomy of chromosome 16 and perhaps other chromosomes may contribute to expression of complex genetic traits such as essential hypertension, in which the diverse phenotypic manifestations are poorly understood.     

Telomere length in the newborn

Telomere length is similar in different organs of the human fetus but variable among fetuses. During extrauterine life telomere length is highly variable among individuals and longer in women than men. In the present work we addressed the following questions: 1) Are there sex-related differences in telomere length at birth? 2) Is there synchrony (i.e. correlation in length) of telomeres in tissues within the newborn? 3) Is the variability in telomere length among newborns as large as that in adults? We studied normal male and female newborns who donated DNA samples from three sources: white blood cells, umbilical artery, and foreskin. Telomere length was measured by the mean length of the terminal restriction fragments (TRF). TRF length was not different between male and female newborns. It was highly synchronized among the DNA samples from white blood cells, umbilical artery and skin within individual donors but exhibited a high variability among donors. We conclude that there is no evidence for the effect of sex on telomere length at birth, suggesting that longer telomeres in women than men arise from a slower rate of telomeric attrition in women. The variability in telomere length among newborns and synchrony in telomere length within organs of the newborn are consistent with the concept that variations in telomere length among adults are in large part attributed to determinants (genetic and environmental) that start exerting their effect in utero.