Reductions in clinical inflammation and oral neutrophils with improving oral hygiene

Clinical Oral Investigations - This study compared the effects of oral hygiene with a toothpaste formulated with zinc (test) to a fluoride dentifrice (control) for effects on oral polymorphonuclear...     

Prion-Like Propagation of Post-Translationally Modified Tau in Alzheimer’s Disease: A Hypothesis

The microtubule-associated protein Tau plays a key role in the neuropathology of Alzheimer’s disease by forming intracellular neurofibrillary tangles. Tau in the normal physiological condition helps stabilize microtubules and transport. Tau aggregates due to various gene mutations, intracellular insults and abnormal post-translational modifications, phosphorylation being the most important one. Other modifications which alter the function of Tau protein are glycation, nitration, acetylation, methylation, oxidation, etc. In addition to forming intracellular aggregates, Tau pathology might spread in a prion-like manner as revealed by several in vitro and in vivo studies. The possible mechanism of Tau spread can be via bulk endocytosis of misfolded Tau species. The recent studies elucidating this mechanism have mainly focussed on the aggregation and spread of repeat domain of Tau in the cell culture models. Further studies are needed to elucidate the prion-like propagation property of full-length Tau and its aggregates in a more intense manner in vitro as well as in vivo conditions. Varied post-translational modifications can have discrete effects on aggregation propensity of Tau as well as its propagation. Here, we review the prion-like properties of Tau and hypothesize the role of glycation in prion-like properties of Tau. This post-translationally modified Tau might have an enhanced propagation property due to differential properties conferred by the modifications.     

Measurement of Novel Biomarkers to Predict Chronic Heart Failure Outcomes and Left Ventricular Remodeling

Myocardial remodeling is pivotal in the progression and complication of chronic heart failure (HF). We assessed serial measurement of five biomarkers with biologic links to remodeling (biglycan, secreted frizzled-related protein 3, endostatin, insulin-like growth factor binding protein 7 [IGFBP7], mimecan) in 142 patients with HF followed through 882 office visits. IGFBP7 and mimecan were most associated with events; in fully adjusted models, lower IGFBP7 concentrations across visits independently predicted fewer events (odds ratio [OR]?=?0.83; 95 % confidence interval [CI]?=?0.73–0.95, p?=?0.01). Subjects with rising mimecan had greater decrease in left ventricular end diastolic (p?=?0.07) and systolic (p?=?0.01) volumes, greater increase in ejection fraction (p?=?0.02), and had lowest event rates. Statistical models suggested several HF medications might lead to changes in both IGFBP7 and mimecan values. The results suggest serial measurement of IGFBP7 provides prognostic information, while changes in mimecan provide unique information regarding myocardial remodeling.     

Hemophilia A: role of FVIIIC/vWF Ag in assisting linkage analysis for carrier detection.

Carrier detection for hemophilia A was carried out in 52 females from 30 families presenting to the Haematology Department AIIMS, using linkage analysis and factor VIIIC (FVIIIC)-von Willebrand factor (vWF) antigen assay. The allelic frequency for the marker Bcl 1 and Xba 1 was 0.58 and 0.54, respectively, for the positive alleles and 0.42 and 0.46, respectively, for the negative alleles. The heterozygosity frequency of Bcl I and Xba 1 was 0.65 and 0.55, respectively. Of the 52 females, 30 were mothers of hemophilic patients and 22 were sisters of hemophilic patients. Of the 30 mothers, positive family history was present in 14. In these patients, the defective X chromosome was tracked in 10, and in four the defective X chromosome could not be tracked because the mothers were homozygous for the marker used. Of the 16 mothers without a family history of disease, three were observed to be carriers based on linkage analysis and reduced factor VIII levels in mother/sister. Possible defective X chromosome was tracked in 11 mothers and five were noninformative because they did not show heterozygosity for the markers used. Using linkage analysis, nine of the 22 sisters were found to be definite carriers, 10 noncarriers, and three were noninformative. It is thus concluded that using Bcl 1 and Xba 1 linkage analysis, carrier status can be definitely ascertained in 50% females and this level of information can be increased to 61.5% by measuring FVIIIC/vWF antigen levels in them.