Prenatal exposure to alcohol impairs responses of cerebral arterioles to activation of potassium channels: Role of oxidative stress.

BACKGROUND: Potassium channels play an important role in the basal tone and dilation of cerebral resistance arterioles in response to many stimuli. However, the effect of prenatal alcohol exposure (PAE) on specific potassium channel function remains unknown. The first goal of this study was to determine the influence of PAE on the reactivity of cerebral arterioles to activation of ATP-sensitive potassium (KATP ) and BK channels. Our second goal was to determine whether oxidative stress contributed to potassium channel dysfunction of cerebral arterioles following PAE. METHODS: We fed Sprague-Dawley dams a liquid diet with or without alcohol (3% EtOH) for the duration of their pregnancy (21 to 23 days). We examined in vivo responses of cerebral arterioles in control and PAE male and female offspring (14 to 16 weeks after birth) to activators of potassium channels (Iloprost [BK channels] and pinacidil [KATP channels]), before and following inhibition of oxidative stress with apocynin. RESULTS: We found that PAE impaired dilation of cerebral arterioles in response to activation of potassium channels with iloprost and pinacidil, and this impairment was similar in male and female rats. In addition, treatment with apocynin reversed the impaired vasodilation to iloprost and pinacidil in PAE rats to levels observed in control rats. This effect of apocynin also was similar in male and female rats. CONCLUSIONS: PAE induces dysfunction in the ability of specific potassium channels to dilate cerebral arterioles which appears to be mediated by an increase in oxidative stress. We suggest that these alterations in potassium channel function may contribute to the pathogenesis of cerebral vascular abnormalities and/or behavioral/cognitive deficits observed in fetal alcohol spectrum disorders.

Prenatal exposure to alcohol: mechanisms of cerebral vascular damage and lifelong consequences.

Alcohol is a well-known teratogen, and prenatal alcohol exposure (PAE) leads to a greater incidence of many cardiovascular-related pathologies. Alcohol negatively impacts vasculogenesis and angiogenesis in the developing fetal brain, resulting in fetal alcohol spectrum disorders (FASD). Ample preclinical evidence indicates that the normal reactivity of cerebral resistance arterioles, which regulate blood flow distribution in response to metabolic demand (neurovascular coupling), is impaired by PAE. This impairment of dilation of cerebral arteries may carry implications for the susceptibility of the brain to cerebral ischemic damage well into adulthood. The focus of this review is to consolidate findings from studies examining the influence of PAE on vascular development, give insights into relevant pathological mechanisms at the vascular level, evaluate the risks of ethanol-driven alterations of cerebrovascular reactivity, and revisit different preventive interventions that may have promise in reversing vascular changes in preclinical FASD models.

Constrictor responses of cerebral resistance arterioles in male and female rats exposed to prenatal alcohol.

While it is known that dilation of cerebral arterioles to NOS-dependent agonists is impaired in rats exposed to prenatal alcohol, no studies have examined the influence of prenatal alcohol on constrictor response of cerebral arterioles. Our goal was to determine whether constrictor responses of cerebral resistance arterioles are altered by prenatal exposure to alcohol and if any changes differed as a function of age or sex. We fed Sprague-Dawley rat dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy. We then examined reactivity of cerebral arterioles to thromboxane (U-46619; 0.01 and 0.1 µM), arginine vasopressin (0.1 and 1 nM), and angiotensin II (1 and 10 µM) in four groups of offspring: control male and female, and prenatal alcohol male and female at two different ages (adolescent: 4-6 weeks old and adult: 14-16 weeks old). Constriction of cerebral arterioles to U-46619 and AVP were similar in male and female rats regardless of exposure to prenatal alcohol and age. Similarly, adolescent male and female rats showed no difference to angiotensin II following prenatal exposure to alcohol. However, alcohol-exposed females exhibited an unexpected dilation to the high concentration of angiotensin II in adulthood, which was absent in males. We suggest that the findings from these studies may have implications regarding the susceptibility of the brain to cerebral ischemic damage. We speculate that impaired vasodilation, coupled with preserved vasoconstriction, can lead to a scenario favoring a decrease in cerebral blood flow during times of increased metabolic demand.

Rosiglitazone restores nitric oxide synthase-dependent reactivity of cerebral arterioles in rats exposed to prenatal alcohol.

BACKGROUND: Prenatal exposure to alcohol leads to a greater incidence of many cardiovascular-related diseases, presumably via a mechanism that may involve increased oxidative stress. An agonist of peroxisome proliferator-activated receptor gamma (PPARγ; rosiglitazone) has been shown to suppress alcohol-induced neuroinflammation and oxidative stress. The goal of this study was to determine whether acute and chronic treatment with rosiglitazone could restore or prevent impaired nitric oxide synthase (NOS)-dependent responses of cerebral arterioles in male and female adult (14-16 weeks old) rats exposed to alcohol in utero. METHODS: We fed Sprague-Dawley dams a liquid diet with or without 3% ethanol for the duration of their pregnancy (21-23 days). In the first series of studies, we examined the reactivity of cerebral arterioles to eNOS- (ADP), nNOS-dependent (NMDA), and NOS-independent agonists in male and female adult rats before and during acute (1 hour) topical application of rosiglitazone (1 µM). In a second series of studies, we examined the influence of chronic treatment with rosiglitazone (3 mg/kg/day in drinking water for 2-3 weeks) on the responses of cerebral arterioles in male and female adult rats exposed to alcohol in utero. RESULTS: We found that in utero exposure to alcohol similarly reduced responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in male and female adult rats. In addition, acute treatment of the male and female adult rats with rosiglitazone similarly restored this impairment in cerebral vascular function to that observed in controls. We also found that chronic treatment with rosiglitazone prevented impaired vascular function in male and female adult rats that were exposed to alcohol in utero. CONCLUSIONS: PPARγ activation may be an effective and relevant treatment to reverse or prevent cerebral vascular abnormalities associated with prenatal exposure to alcohol.

Monomer release from direct and indirect adhesive restorations: A comparative in vitro study.

OBJECTIVES: Indirect dental restorations produced by computer-aided design and computer-aided manufacturing (CAD/CAM) are relatively new in daily dental practice. The aim of the present study was to compare the monomer release between direct composite restorations and indirect CAD/CAM produced restorations (composite, ceramic and hybrid). METHODS: Identical crown restorations were prepared from three indirect materials (Cerasmart, Vitablocs Mark II and Vita Enamic) and one composite material (Clearfil AP-X). For each restoration, eight crown restorations were luted onto tooth samples and immersed into 2.5mL of an aqueous extraction solvent. Additionally, three nonluted crowns of each restoration type were also immersed in the extraction solvent, and served as controls. Every week, the extraction solvent was collected and refreshed, during a period of 8 weeks. The released monomers were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Indirect restorations release significantly lower quantities of residual monomers than direct restorations, and the monomers released by the luted indirect restorations are mainly derived from the composite material used for cementation. The quantity of monomers released by direct restorations greatly depended on the time of light polymerization. SIGNIFICANCE: In terms of monomer release, indirect restorations are a good alternative to direct restorations to limit patient exposure to residual monomers. It is important to ideally design the fit of indirect restoration so that the cement layer is as thin as possible and the monomer release from this cement layer remains as low as possible.

A molecular phylogeny of the genus Drimia (Asparagaceae: Scilloideae: Urgineeae) in India inferred from non-coding chloroplast and nuclear ribosomal DNA sequences.

The evolutionary history of the medicinally important bulbous geophyte Drimia (subfamily: Scilloideae) has long been considered as a matter of debate in the monocot systematics. In India the genus is represented by a species complex, however, the taxonomic delimitation among them is ill-defined till date. In the present study, a comprehensive phylogenetic relationship among Indian species of this genus has been inferred for the first time based on chloroplast DNA trnL intron, rps16-trnK intergenic spacer, atpB-rbcL intergenic spacer and ribosomal DNA ITS1-5.8S-ITS2 sequences, leaf morphology, anatomy, stomatal characteristics and pollen exine ornamentations. The present findings revealed the monophyletic origin of the Indian members of Drimia and grouped them into two possible lineages (clade- I and II). The phylogenetic tree based on cpDNA concatenated sequences further resolved the clade-I into two distinct subclades (I and II) and clarified the intraspecies relationship among the studied members. The present study suggested a strong relationship between the molecular phylogeny and the morphological characteristics of the species studied. A possible trend of evolution of two important traits: 'type of palisade cells' in leaf and 'pollen exine patterns' among the members of Drimia in India was also suggested.