Crown-root ratio of permanent teeth in cleft lip and palate patients

Objectives:To determine root lengths of fully developed permanent teeth of cleft lip and palate (CLP) patients and to define their crown-root (C/R) ratios.Method:Crown height and root length of permanent teeth were measured from panoramic radiographs of 44 CLP patients and 37 controls. A total of 1397 teeth were measured, and C/R ratios were calculated.Results:Higher C/R ratios were found in CLP patients; this was statistically significant for both maxillary and mandibular incisors and canines. Bilateral CLP subjects showed higher C/R ratios in general than unilateral CLP subjects. Roots of maxillary incisors, canines, and some other teeth were significantly shorter in CLP patients than in controls.Conclusions:CLP patients should be considered to have unfavorable C/R ratios, which could be the result of short root lengths for some teeth.     

The α7-nAChR/heme oxygenase-1/carbon monoxide pathway mediates the nicotine counteraction of renal inflammation and vasoconstrictor hyporeactivity in endotoxic male rats

Inflammation Research - The objective of the study was to test the hypothesis that nicotine guards against endotoxemia-associated renal inflammation and vasoconstrictor dysfunction via the...     

Morphometry and epidermal fas expression of unexposed aged versus young skin

Background:

Identifying the molecular mechanisms of intrinsic aging is critical in developing modalities for reversal of cutaneous aging.

Objective:

The objective was to evaluate the expression of epidermal Fas, epidermal thickness, collagen, and elastic fibers degeneration in unexposed skin of aged individuals compared with young ones.

Materials and Methods:

Skin biopsies were taken from normal skin of the back of 22 old subjects (age range: 48-75 years) and 15 young subjects (age range: 18-28 years). Skin sections were stained with hematoxylin and eosin, Masson trichrome, orcein. Epidermal thickness was measured with image analyzer and scoring was done for collagen and elastic fiber degeneration. Fas immunostaining was done. Quantitative and qualitative data were compared statistically between the old and young subjects.

Results:

A statistically significant decreased epidermal thickness was found in old compared with young skin (P<0.05). A statistically significant number of patients showed decreased epidermal thickness, density, and fragmentation of both collagen and elastic fibers in old compared with young skin (P<0.001). Epidermal Fas expression was detected in 19 of 22 old subjects (86.4%) compared with 2 of 15 young subjects (13.3%) (P<0.001). There was no statistically significant correlation between age of old subjects and each of epidermal thickness, collagen, and elastic fiber degeneration.

Conclusion:

The decreased epidermal thickness and morphological alteration of collagen and elastic fibers are not correlated with aging and Fas-mediated apoptosis could be involved in thinning of the epidermis in unexposed aged skin.     

The antiprotozoal activity of methylated flavonoids from Ageratum conyzoides L.

Aim of the study

The dichloromethane extract prepared from aerial parts of Ageratum conyzoides L. (Asteraceae), a plant commonly used in folk medicine for a number of illnesses including sleeping sickness, was recently found to exhibit a prominent activity (IC₅₀ = 0.78 μg/mL) against bloodstream forms of Trypanosoma brucei rhodesiense, the etiologic agent of East African Human Trypanosomiasis (East African Sleeping Sickness). This extract also exhibited noticeable activities against Leishmania donovani (Kala-Azar, IC₅₀ = 3.4 μg/mL) as well as Plasmodium falciparum (Malaria tropica, IC₅₀ = 8.0 μg/mL). In the current study, we sought for potentially active constituents of Ageratum conyzoides.

Materials and methods

Extracts prepared with solvents of different polarity were tested for activity against the above mentioned parasites as well as against Trypanosoma cruzi (Chagas’ disease) and for cytotoxicity using established protocols. The dicholoromethane extract showed the highest level of activity and was chosen for phytochemical studies aimed at the isolation of potential active constituents.

Results and conclusion

Five highly methoxylated flavonoids along with the chromene derivative encecalol methyl ether were isolated. All isolated compounds were previously reported from Ageratum conyzoides. While the chromene turned out to be inactive against the tested parasites, the flavonoids showed activity against the protozoan pathogens, some in the lower micromolar range. However, none of these isolated compounds was as active as the crude extract. This is the first report on antiprotozoal activity of this plant species and some of its constituents. The chemical principle accounting for the high activity of the crude extract, however, remains to be identified.     

Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project

Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci (CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6. The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci (CYP4F2, EPHX1, ABCB1, HLAB, KIF6, CYP3A4, CYP3A5, TPMT, and DPD) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research.     

Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder caused by mutations in Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes. We performed molecular characterization in clinically affected probands of 31 HHT families and detected a total of 28 different mutations in the two genes, including four shared by more than one family. Twelve mutations were identified in the ENG gene, six of which were novel and comprised two nonsense mutations in exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and intron 8. Eleven of sixteen mutations identified in the ALK1 gene were novel single base pair substitutions in exons 4, 7, 8, and 9. We also describe the first de novo ALK1 mutation that causes a previously unreported c.1133C>A substitution of a highly conserved residue (p.P378H). The proband and his two daughters, who also carried the familial mutation, all suffered from gastrointestinal (GI) bleeding. In addition, we report seven newly identified polymorphisms and summarize all known ones in both genes.     

Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1

Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic oxidative stress and exacerbate injury caused by other toxins such as ethanol that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1 (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and immunoreactive protein. Prooxidant production, as determined by cellular oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by expression of HCV core protein in the presence or absence of CYP2E1. Depletion of glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant production in both C34 and E47 cells. In addition, prooxidant production was greater in BSO-treated cells expressing HCV core protein, and this effect was further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1 inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed significantly decreased viability following GSH depletion. These studies show simultaneous expression of HCV core protein and CYP2E1 increases parameters indicative of oxidative stress as well as sensitization to cell injury induced by GSH depletion. These results support the hypothesis that enhanced injury in hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by increases in oxidative stress.     

Macroscopic placental changes associated with fetal and maternal events in diabetes mellitus

OBJECTIVES:

The current study sought to identify macroscopic placental changes associated with clinical conditions in women with or without diabetes and their newborns.

METHODS:

The study population consisted of 62 pregnant women clinically diagnosed with diabetes and 62 healthy women (control group).

RESULTS:

Among the subjects with diabetes, 43 women (69.3%) were diagnosed with gestational diabetes mellitus, 15 had diabetes mellitus I (24.2%), and four had diabetes mellitus II (6.5%). The mean age of the women studied was 28.5±5.71 years, and the mean gestational age of the diabetic women was 38.51 weeks. Of the 62 placentas from diabetic pregnancies, 49 (79%) maternal surfaces and 59 (95.2%) fetal surfaces showed abnormalities, including calcium and fibrin deposits, placental infarction, hematoma, and fibrosis. A statistical association was found between newborn gender and fetal and maternal placental changes (p = 0.002). The mean weight of the newborns studied was 3,287±563 g for women with diabetes mellitus, 3,205±544 g for those with gestational diabetes mellitus, 3,563±696 g for those with diabetes mellitus II, and 3,095±451 g for those with diabetes mellitus I.

CONCLUSIONS:

Infarction, hematoma, calcification, and fibrin were found on the maternal and fetal placental surfaces in women with diabetes. Women with gestational diabetes and post-term infants had more calcium deposits on the maternal placental surface as compared to those with type I and type II diabetes.