Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA

Hyperhomocysteinemia is an emerging risk factor for cardiovascular disease and stroke. The mechanisms underlying the pathophysiology of hyperhomocysteinemia are not completely defined, but endothelial dysfunction resulting from impaired bioavailability of nitric oxide is a consistent finding in experimental models. One potential mechanism for decreased nitric oxide bioavailability is inhibition of endothelial nitric oxide synthase by its endogenous inhibitor, asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA have been found in association with hyperhomocysteinemia and endothelial dysfunction in both animals and humans. Additional studies are required to determine the mechanisms by which ADMA accumulates in hyperhomocysteinemia and to define the importance of ADMA in the endothelial dysfunction of hyperhomocysteinemia in vivo.     

Usefulness of the assessment of the appropriateness of left ventricular mass to detect left ventricular systolic and diastolic abnormalities in absence of echocardiographic left ventricular hypertrophy: the LIFE study

Conventional definitions of left ventricular (LV) hypertrophy do not account for interindividual differences in loading conditions. We may define LV mass as inappropriately high when exceeding 128% of theoretical values predicted by gender, height(2.7), and stroke work, which explain up to 82% of the variability of LV mass in normal reference subjects. In 652 participants in the Losartan Intervention For Endpoint reduction in hypertension study without clinically overt cardiovascular disease or diabetes, we investigated whether inappropriately high LV mass is associated with relevant LV abnormalities independent of traditional definition of LV hypertrophy (ie, LV mass index >116 g/m(2) in men and >104 g/m(2) in women). The study sample was divided into three groups: patients with inappropriately high LV mass but without LV hypertrophy were compared to patients with LV hypertrophy and to patients with appropriate LV mass and without LV hypertrophy. Patients with inappropriately high but nonhypertrophic LV mass had higher body mass index and relative wall thickness, and lower LV myocardial systolic function, than patients with appropriate LV mass or patients with LV hypertrophy. In multivariate analyses, inappropriately high LV mass was independently associated with lower myocardial systolic function independent of LV hypertrophy and other covariates. Inappropriately high LV mass was also associated with prolonged isovolumic relaxation time and lower mitral E/A ratio independent of covariates. In conclusion, inappropriately high LV mass was associated with relevant, often preclinical, manifestations of cardiac disease in the absence of traditionally defined echocardiographic LV hypertrophy and concentric geometry.     

A population-based assessment of left ventricular systolic dysfunction in middle-aged and older adults: the Strong Heart Study

BACKGROUND: Although clinical congestive heart failure (CHF) is increasingly common, few data document the prevalence and correlates of underlying left ventricular (LV) systolic dysfunction (D) in population-based samples. METHODS: Echocardiography was used in the second Strong Heart Study (SHS) examination to identify mild and severe LVD (LV ejection fraction [EF] 40%-54% and <40%, respectively) in 3184 American Indians. RESULTS: Mild and severe LVD were more common in men than women (17.4% vs 7.2% and 4.7% vs 1.8%) and in diabetic than nondiabetic participants (12.7% vs 9.1% and 3.5% vs 1.6%). Stepwise increases were observed from participants with normal EF to those with mild and severe LVD in age (mean 60 vs 61 and 63 years, P <.001), prevalence of overt CHF (2% vs 6% and 28%) and definite coronary heart disease (3% vs 11% and 32%), systolic pressure (129 vs 135 and 136 mm Hg), serum creatinine level (0.98 vs 1.34 and 2.16 mg/dL), and log urinary albumin/creatinine level (3.2 vs 3.7 and 4.7); a negative relation was seen with body mass index (31.1 vs 31.0 and 28.4 kg/m(2)) (all P <.001). In multivariate analyses lower LVEFs were independently associated with clinical CHF and coronary heart disease, lower myocardial contractility, male sex, hypertension, overweight, arterial stiffening (higher pulse pressure/stroke volume) and renal dysfunction (higher serum creatinine level), higher LV mass, and lower relative wall thickness. CONCLUSIONS: LVD, present in approximately 14% of middle-aged to elderly adults, is independently associated with overt heart failure and coronary heart disease, male sex, hypertension, overweight, arterial stiffening, and renal target organ damage and, less consistently, with older age and diabetes.     

Early stage of adjuvant arthritis alters behavioral responses in male but not female rats

Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known about how inflammatory disease in its early stage, before any clinical manifestation, may affect general activity. The aim of this study was to compare the anxiety-like behaviour in the early stage of adjuvant arthritis (AA), and the paw edema, and corticosterone (CORT) levels in the developed stage of AA among male and female Long Evans rats. The behavioural activity was evaluated by elevated plus maze tests. These revealed significantly reduced number of entries into the open arm of the maze in arthritic males compared to controls or to females 4 days after AA induction. Arthrihtic and control females did not differ. The number of entries into the closed arm of the maze was the same across the genders and studied intervals. Time spent in the open arm was significantly lower in arthritic males against controls or arthitic females. Time spent in the closed arm showed inverse picture to the time spent in the open arm. Hind paw swelling measured on day 23 of AA was the same in males and females, as was the elevation of CORT levels in plasma. Male rats showed anxiety-like behaviour on day 4 of AA, while female rats did not show any change, indicating different brain sensitivity to early inflammation among the genders.     

Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans

Azoles (imidazoles and triazoles) are used as antifungal agents in agriculture and in medicine, and also for antiestrogen therapy, e.g., for breast cancer treatment. Antifungal activity is based on inhibition of fungal CYP51 (lanosterol 14alpha-demethylase), and estrogen biosynthesis reduction is due to azole inhibition of CYP19 (aromatase). Inhibition of aromatase by antifungal agents is usually an unwanted side effect and may cause endocrine disruption. A fluorimetric assay based on human recombinant CYP19 enzyme with dibenzylfluorescein as a substrate was used to compare the inhibitory potency of 22 azole compounds. Dose responses were established and duplicate datasets were analyzed with a nonlinear mixed-effects model with cumulative normal distribution for the logarithm of concentration. IC50 values (50% inhibitory concentration) of 13 fungicides used in agriculture ranged more than 700-fold, starting from 0.047 microM. The potency of seven human drugs spanned more than 7000-fold, starting from 0.019 microM. Most potent fungicides included prochloraz, flusilazole, and imazalil, and most potent medicinal antifungals were bifonazole, miconazole, and clotrimazole. These in vitro data indicate that the top-ranking azoles used as antifungal agents or drugs are as potent inhibitors of aromatase as are antiestrogen therapeutics used to treat breast cancer. These putative effects of azole agents and drugs on steroid biosynthesis and sex hormone balance should be considered when used in human subjects and also in wildlife exposed to azole fungicides used in agriculture.     

Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight.

OBJECTIVES. This study was designed to determine the most appropriate method to normalize left ventricular mass for body size. BACKGROUND. Left ventricular mass has been normalized for body weight, surface area or height in experimental and clinical studies, but it is uncertain which of these approaches is most appropriate. METHODS. Three normotensive population samples--in New York City (127 adults), Naples, Italy (114 adults) and Cincinnati, Ohio (444 infants to young adults)--were studied by echocardiography. Relations of left ventricular mass to body size were similar in all normal weight groups, as assessed by linear and nonlinear regression analysis, and results were pooled (n = 611). RESULTS. Left ventricular mass was related to body weight to the first power (r = 0.88), to body surface area to the 1.5 power (r = 0.88) and to height to the 2.7 power (r = 0.84), consistent with expected allometric (growth) relations between variables with linear (height), second-power (body surface area) and volumetric (left ventricular mass and body weight) dimensions. Strong residual relations of left ventricular mass/body surface area to body surface area (r = 0.54) and of ventricular mass/height to height (r = 0.72) were markedly reduced by normalization of ventricular mass for height2.7 and body surface area1.5. The variability among subjects of ventricular mass was also reduced (p < 0.01 to p < 0.002) by normalization for body weight, body surface area, body surface area1.5 or height2.7 but not for height. In 20% of adults who were overweight, ventricular mass was 14% higher (p < 0.001) than ideal mass predicted from observed height and ideal weight; this increase was identified as 14% by left ventricular mass/height2.7 and 9% by ventricular mass/height, whereas indexation for body surface area, body surface area1.5 and body weight erroneously identified left ventricular mass as reduced in overweight adults. CONCLUSIONS. Normalizations of left ventricular mass for height or body surface area introduce artifactual relations of indexed ventricular mass to body size and errors in estimating the impact of overweight. These problems are avoided and variability among normal subjects is reduced by using left ventricular mass/height2.7. Simple nomograms of the normal relation between height and left ventricular mass allow detection of ventricular hypertrophy in children and adults.     

The role of diabetes mellitus on the formation of severe odontogenic abscesses—a retrospective study

Objectives

To analyze the correlation of diabetes mellitus and hyperglycemia with severe odontogenic abscesses.

Materials and methods

Records of all patients in the Department of Oral and Maxillofacial Surgery of the Medical Center of the Johannes Gutenberg-University who underwent inpatient treatment for severe odontogenic abscesses between 2010 and 2016 were evaluated retrospectively regarding diabetes anamnesis, maximum and fasting blood sugar count, and duration until discharge. In order to compare the numbers to a general maxillofacial group, all patients who received inpatient treatment in 2013 for any diagnosis other than an abscess of the head and neck region were analyzed as well, and the numbers were correlated.

Results

In total, 977 abscess patients were found in the analyzed period. 7.0% of the patients had a known diagnosis of diabetes mellitus type II and 0.6% of type I. Correlation with the general group showed that abscesses were significantly more likely in diabetics as well as patients with abnormal maximum and fasting blood sugar counts. These patients also needed significantly longer inpatient treatment.

Conclusions

Diabetics and patients with abnormal glucose tolerance show significantly higher numbers of severe odontogenic abscesses and might therefore benefit from earlier escalation of antibiotic medication.

Clinical relevance

Severe odontogenic abscesses are one of the most frequent diagnoses in maxillofacial practice. Adjusting the therapeutic approach for diabetics or patients with abnormal blood sugar counts might help to prevent the development of abscesses.