Periodontal attachment loss in patients after head and neck radiation therapy

Objective. The purpose of this study was to determine the potential impact of head and neck radiation therapy on the progression of periodontal attachment loss.Study design. Ten patients who received unilateral radiation fields that included the dentition were assessed before radiation treatment and after irradiation at a mean age of 6.01 years. Complete oral, dental, and periodontal examinations were completed by one examiner. The results were assessed through use of paired t tests.Results. More teeth were extracted because of periodontal disease in the field of radiation after irradiation. Remaining teeth in the radiated volume showed an increase in probing depth of 0.82 mm in comparison with 0.40 mm for teeth in the nonradiated region (P = .05). Recession on the facial aspects was 1.88 mm for teeth in the radiated volume and 1.16 mm for teeth in the nonradiated region (P = .001), and recession on the lingual aspects was 2.10 for teeth in the radiated volume and 0.91 for teeth in the nonradiated region (P = .05). Mean total attachment loss was 2.81 mm for teeth in the radiated sites; this compared with 1.43 mm for teeth in the nonradiated sites (P = .003). Increased mobility of teeth in the high-dose fields was seen (P = .02).Conclusions. This study showed that tooth loss and greater periodontal attachment loss occur in teeth that are included within high-dose radiated sites of patients treated with irradiation therapy for cancer. These findings should be considered in preradiation treatment planning.     

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy.     

The structural origin of second harmonic generation in fascia

Fascia tissue is rich in collagen type I proteins and can be imaged by second harmonic generation (SHG) microscopy. While identifying the overall alignment of the collagen fibrils is evident from those images, the tridimensional structural origin for the observation of SHG signal is more complex than it apparently seems. Those images reveal that the noncentrosymmetric (piezoelectric) structures are distributed heterogeneously on spatial dimensions inferior to the resolution provided by the nonlinear optical microscope (sub-micron). Using piezoresponse force microscopy (PFM), we show that an individual collagen fibril has a noncentrosymmetric structural organization. Fibrils are found to be arranged in nano-domains where the anisotropic axis is preserved along the fibrillar axis, while across the collagen sheets, the phase of the second order nonlinear susceptibility is changing by 180 degrees between adjacent nano-domains. This complex architecture of noncentrosymmetric nano-domains governs the coherent addition of 2ω light within the focal volume and the observed features in the SHG images taken in fascia.     

The spectrum of mutations in UBE3A causing Angelman syndrome

Angelman syndrome (AS) is characterized by mental retardation, absence of speech, seizures and motor dysfunction. AS is caused by maternal deletions for chromosome 15q11-q13, paternal uniparental disomy (UPD), imprinting defects or loss-of-function mutations in the UBE3A locus which encodes E6-AP ubiquitin-protein ligase. The UBE3A gene is imprinted with paternal silencing in human brain and similar silencing of the Ube3a locus in Purkinje cells and hippocampal neurons in the mouse. We have sequenced the major coding exons for UBE3A in 56 index patients with a clinical diagnosis of AS and a normal DNA methylation pattern. The analysis identified disease-causing mutations in 17 of 56 patients (30%) including 13 truncating mutations, two missense mutations, one single amino acid deletion and one stop codon mutation predicting an elongated protein. Mutations were identified in six of eight families (75%) with more than one affected case, and in 11 of 47 isolated cases (23%); no mutation was found in one family with two siblings, one with a typical and one with an atypical phenotype. Mutations were de novo in nine of the 11 isolated cases. An amino acid polymorphism of threonine substituted for alanine at codon 178 was identified, and a 3 bp length polymorphism was found in the intron upstream of exon 8. In all informative cases, phenotypic expression was consistent with imprinting with a normal phenotype when a mutation was on the paternal chromosome and an AS phenotype when a mutation was on the maternal chromosome. Laboratory diagnosis and genetic counseling for AS are complex, and mutation analysis is valuable in clinically typical AS patients with a normal methylation analysis.      

Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. results of a multicenter randomized,double-blind,placebo-controlled trial

Objective. To determine whether the side effects of methotrexate can be decreased by the concurrent use of leucovorin, without affecting the efficacy of the methotrexate. Methods. We conducted a multicenter randomized, double-blind, placebo-controlled trial of leucovorin administration, 2.5–5.0 mg orally, to be given 24 hours after the single, weekly, oral dose of methotrexate. Every 3 weeks for 52 weeks, patients were evaluated for rheumatic disease activity and side effects. Dosage adjustments for both methotrexate and leucovorin were made as needed, according to a defined protocol. The primary outcome evaluated was the frequency of study withdrawals because of side effects and/or inefficacy. Secondary outcomes evaluated included the frequency of side effects and the relative efficacy of methotrexate in the leucovorin and placebo treatment groups. Results. Ninety-two evaluable patients were analyzed (44 took leucovorin and 48 placebo). Twenty-two patients withdrew early because of side effects unresponsive to our protocol, and 1 because of inefficacy; 17 had been taking placebo and 6 had been taking leucovorin (35% versus 14%,P < 0.02). The number of visits during which side effects were reported was reduced by almost 50% in the leucovorin treatment group (P < 0.001). There were significant reductions in the frequencies of all common side effects. At 52 weeks, disease activity was similar in both patient groups. Conclusion. The methotrexate–leucovorin protocol used significantly reduces common side effects of methotrexate therapy without significantly altering efficacy.     

Influence of gut bacteria on development and progression of non-alcoholic fatty liver disease

The intestine of the human contains a dynamic population of microbes that have a symbiotic relationship with the host. In addition, there is an effect of the intestinal microbiota on metabolism and digestion. Non-alcoholic fatty liver disease (NAFLD) is a common cause worldwide of hepatic pathology and is thought to be the hepatic manifestation of the metabolic syndrome. In this review we examine the effect of the human microbiome on the components and pathogenesis of the metabolic syndrome. We are now on the threshold of therapeutic interventions on the human microbiome in order to effect human disease including NAFLD.