Complexes of 2,4,6-trihydroxybenzoic acid: effects of intramolecular hydrogen bonding on ligand geometry and metal binding modes.

This article describes a series of more than 20 new compounds formed by the combination of 2,4,6-trihydroxybenzoic acid (H4thba) with metal ions in the presence of a base, with structures that include discrete molecular units, chains, and two- and three-dimensional networks. As a result of the presence of two ortho-hydroxy groups, H4thba is a relatively strong acid (pKa1 = 1.68). The carboxylate group in H3thba- is therefore considerably less basic than most carboxylates with intramolecular hydrogen bonds, conferring a rigid planar geometry upon the anion. These characteristics of H3thba- significantly impact upon the way it interacts with metal ions. In s-block metal compounds, where the interaction of the metal centres with the carboxylate O atoms is essentially ionic, the anion bonds to up to three metal centres via a variety of binding modes. In cases where the metal ion is able to form directional coordinate bonds, however, the carboxylate group tends to bond in a monodentate mode, interacting with just one metal centre in the syn mode. A dominant influence on the structures of the complexes seems to be the face-to-face stacking of the aromatic rings, which creates networks containing layers of metal-oxygen polyhedra that participate in hydrogen bonding. This investigation was undertaken, in part, by a group of secondary school students as an educational exercise designed to introduce school students to the technique of single-crystal X-ray diffraction and enhance their understanding of primary and secondary bonding.

MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort.

The well-studied C677T variant in the methylenetetrahydrofolate reductase (MTHFR) enzyme is a biologically plausible genetic risk factor for seizures or epilepsy. First, plasma/serum levels of homocysteine, a pro-convulsant, are moderately elevated in individuals with the homozygote TT genotype. Furthermore, the TT genotype has been previously linked with migraine with aura-a comorbid condition-and with alcohol withdrawal seizures. Finally, several small studies have suggested that the TT genotype may be overrepresented in epilepsy patients. In this study, we consider whether the MTHFR C677T or A1298C variants are associated with risk of epilepsy including post-traumatic epilepsy (PTE) in a representative military cohort. Study subjects were selected from the cohort of military personnel on active duty during the years 2003 through 2007 who had archived serum samples at the DoD Serum Repository, essentially all active duty personnel during this time frame. We randomly selected 800 epilepsy patients and 800 matched controls based on ICD-9-CM diagnostic codes. We were able to isolate sufficient genetic material from the archived sera to genotype approximately 85% of our study subjects. The odds of epilepsy were increased in subjects with the TT versus CC genotype (crude OR=1.52 [1.04-2.22], p=0.031; adjusted OR=1.57 [1.07-2.32], p=0.023). In our sensitivity analysis, risk was most evident for patients with repeated rather than single medical encounters for epilepsy (crude OR=1.85 [1.14-2.97], p=0.011, adjusted OR=1.95 [1.19-3.19], p=0.008), and particularly for PTE (crude OR=3.14 [1.41-6.99], p=0.005; adjusted OR=2.55 [1.12-5.80], p=0.026). Our early results suggest a role for the common MTHFR C677T variant as a predisposing factors for epilepsy including PTE. Further exploration of baseline homocysteine and folate levels as predictors of seizure risk following traumatic brain injury is warranted.

The relationship between the cardiometabolic syndrome and coronary artery calcium progression.

J Clin Hypertens (Greenwich). 2009;11:505-511. (c)2009 Wiley Periodicals, Inc.Cardiometabolic syndrome has been associated with increased likelihood and extent of coronary artery calcium (CAC). The authors examined the relationship of cardiometabolic syndrome to CAC progression in 200 healthy men who volunteered to undergo repeated electron beam tomography separated by 4.2+/-1.3 years. Prediction of clinically significant CAC progression (>/=15% per year) was evaluated using multivariable logistic regression models and principal component analysis. Clinically significant CAC progression was observed in 52.5% of the cohort, with the mean and median rate of annual progression 41.3% and 18.3%, respectively. The cardiometabolic syndrome in clinically significant CAC progression participants was significantly higher compared with those without CAC progression (24.8% vs 11.6%; P=.016). Cardiometabolic syndrome was a significant independent predictor of clinically significant CAC progression (odds ratio, 2.65; P=.022). Cardiometabolic syndrome is associated with the baseline CAC score, and independently associated with the progression of CAC over 4 years.

Comparison of coronary artery calcium progression in African American and white men.

BACKGROUND: Although African Americans have a lower prevalence and extent of coronary artery calcium (CAC) than whites, the relationship between ethnicity and CAC progression is unknown. In a prospective rescan substudy of the Prospective Army Coronary Calcium (PACC) Project, we evaluated ethnic differences in the rates of CAC progression over 4 years. METHODS: Two hundred healthy male PACC Project participants (age, 47.8 +/- 2.8 years) with CAC on their original scan volunteered to undergo a second electron beam tomography (EBT) scan and cardiovascular risk factor assessment (interscan interval, 4.3 +/- 1.2 y). All results were independently examined and blinded to baseline data. A change in CAC score >or=15%/y was defined as clinically significant progression. The relationship between race and CAC progression was evaluated with multivariable linear and logistic regression models controlling for age and other cardiovascular risk factors. RESULTS: African Americans had significantly lower baseline CAC scores (34.3 vs 101.5; P = 0.004); lower follow-up CAC scores (56.6 vs 180.6; P = 0.001); and worse cardiovascular risk profiles. The annualized CAC progression rate was not significantly related to race in the multivariable linear regression model controlling for age, the Framingham risk score, and other cardiovascular risk factors. Significant CAC progression occurred in 43.5% of all participants. The incidence of significant progression of CAC for African American and white men was similar (53.1% vs 52.4%; P = 0.94), even when controlling for age, the Framingham risk score, and other cardiovascular risk factors. CONCLUSION: Although African American men have less CAC than white men, CAC progression occurs at a comparable rate over 4 years.

Community-based provision of statin and aspirin after the detection of coronary artery calcium within a community-based screening cohort.

OBJECTIVES: We examined the association of coronary artery calcium (CAC) detected on a screening exam with subsequent statin and aspirin usage in a healthy male screening cohort. BACKGROUND: Whether the presence of CAC, an independent predictor of coronary heart disease outcomes, alters clinical management, such as the use of preventive medications, is unknown. METHODS: Men (n = 1,640) ages 40 to 50 years (mean 42 years) were screened for coronary heart disease risk factors and CAC. The CAC scores and risk factors were reported to patients, and results were made available in the electronic medical record; however, medications were not prescribed or recommended by the study. During up to 6 years of subsequent annual structured telephone follow-up, we observed the community-based initiation and persistence of aspirin and statin therapy. RESULTS: A progressive increase in the incidence of pharmacotherapy was noted over time such that those with CAC were 3 times more likely to receive a statin (48.5% vs. 15.5%, p < 0.001) and also significantly more likely to receive aspirin (53.0% vs. 32.3%; p < 0.001) than those without CAC. In multivariable models controlling for National Cholesterol Education Program risk variables and baseline medication use, CAC was strongly and independently associated with use of either statin (odds ratio [OR] 3.53; 95% confidence interval [CI] 2.66 to 4.69), aspirin (OR 3.05; 95% CI 2.30 to 4.05) or both (OR 6.97; 95% CI 4.81 to 10.10). CONCLUSIONS: In this prospective cohort, the presence of coronary calcification was associated with an independent 3-fold greater likelihood of statin and aspirin usage.