Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats

OBJECTIVE: To assess whether the variable impact of quantitative changes in myocardial collagen on left ventricular (LV) diastolic myocardial stiffness (myocardial k) and remodelling (increased volume intercept of diastolic pressure-volume relations) in LV hypertrophy (LVH) is associated with alterations in myocardial collagen cross-linking. METHODS: We evaluated myocardial collagen content (hydroxyproline concentrations [HPRO]) and the degree of myocardial collagen cross-linking (solubility to cyanogen bromide digestion) in 14-15- and 21-22-month-old spontaneously hypertensive rats (SHRs), and in aortic-banded rats with pressure overload hypertrophy (POH). RESULTS: In rats with POH and in SHRs irrespective of age, increases in myocardial [HPRO] were noted. However, hypertensive rats differed in the material and geometric properties of the myocardium, and in qualitative aspects of fibrosis. In 14-15-month-old SHRs myocardial k (determined from diastolic stress-strain relations) and insoluble (cross-linked) [HPRO] were increased, but no LV remodelling or increases in myocardial soluble (non-cross-linked) [HPRO] were noted. In rats with POH, LV remodelling and increases in soluble myocardial [HPRO] occurred, but no increase in k or insoluble myocardial [HPRO] were observed. In 21-22-month-old SHRs, increases in k, soluble and insoluble myocardial [HPRO], as well as LV remodelling occurred. CONCLUSIONS: Collagen cross-linking may determine the diverse relation that exists between increases in myocardial collagen concentrations and either myocardial stiffness or chamber remodelling in hypertension. These findings support the notion that fibrosis contributes to myocardial stiffness as well as LV dilatation in LVH, albeit an effect that is modulated by collagen quality.     

Impact and mechanisms of action of neurotensin on cardiac contractility in the rat left ventricle

Using immunoassay measurements, neurotensin was identified in rat ventricular tissue and in coronary effluent samples. Exogenous neurotensin evoked contractile responses in isolated ventricular preparations, which were equivalent in magnitude to those of norepinephrine and histamine, but greater than those for serotonin and angiotensin II. EC₅₀ values revealed neurotensin to be as potent as serotonin, but more potent than norepinephrine, histamine and angiotensin II. Structure–activity studies indicated that the contractile effects are attributed to the C-terminal portion of neurotensin. Neurotensin-induced responses were decreased by SR 48692, a specific neurotensin receptor antagonist. Neurotensin elicited an increase in coronary effluent norepinephrine concentrations, and a strong relationship between the magnitude of neurotensin-induced contractile effects and increments in myocardial norepinephrine release were noted. Neurotensin-induced contractile responses were abolished by β-adrenoceptor antagonists, but not by histamine, serotonin or angiotensin II receptor antagonists. In conclusion, neurotensin increases ventricular contractility through stimulation of myocardial norepinephrine release.     

Sonographic appearance of callosal agenesis: correlation with radiologic and pathologic findings

Sonographic features are described in six infants in whom total or partial agenesis of the corpus callosum was confirmed by either computed tomographic or pathologic examination. The six patients demonstrated a range of abnormalities involving the neuraxis as well as other systems, notably cardiovascular, gastrointestinal, and genitourinary. Chromosomal abnormalities were present in two patients. The sonographic features of callosal agenesis seen in these patients included: lack of characteristic acoustic interfaces to define the corpus callosum on both coronal and sagittal sonograms; increased separation and parallelism of the bodies of the lateral ventricles; loss of the characteristic convexity of the medial border of the anterior horns of the lateral ventricles; variable prominence of the occipital horns of the lateral ventricles; variable degree of superior extension of the third ventricle; alteration or absence of the cavum septi pellucidi; and radial arrangement of cerebral sulci about the prominent third ventricle. Cases of partial agenesis may show the dysplastic features found in complete agenesis. However, only some of the callosal echoes are present. The sonographic features of partial agenesis in one infant had not been described before.     

PERCEPTION OF ELIGIBLE BLACK MEN AS A CONTEXT FOR HIV‐RELATED RISK BEHAVIOR AMONG BLACK WOMEN

African American women are leading in number of newly diagnosed HIV cases, which is a cause for alarm and has a deleterious effect on families and communities. Research suggests the gender‐ratio imbalance as a contextual factor leading to increases in high‐risk sexual behavior and subsequent increases in the rates of HIV infection among African American women. The current study examines correlates of consistent condom use among 213 single, heterosexual, African American women in the community, on probation, and incarcerated who believe it is difficult to find an eligible Black man. Results of this study reveal that drug‐using women and incarcerated women were less likely to use condoms consistently. In addition, after controlling for drug use and criminal justice status, age emerged as significant. Specifically, older African American women were less likely to use condoms consistently. Community‐level implications and targeted prevention efforts are discussed.     

Relationship Between Children’s Sleep and Mental Health in Mothers of Children with and Without Autism

The study employed 90 children with autism spectrum disorders (ASDs) who were matched to 90 typically developing children on age, gender, and ethnicity. Using structural equation modeling, maternal sleep and maternal stress mediated the relationship between children’s sleep and mothers’ mental health for mothers of children with and without ASDs. Mothers of children with ASDs reported more problems related to children’s sleep, their own sleep, greater stress, and poorer mental health; however, children’s sleep and maternal sleep were more closely related to maternal stress for mothers of typically developing children. Implications of these findings and future directions for research are discussed.     

Moxifloxacin population pharmacokinetics in patients with pulmonary tuberculosis and the effect of intermittent high-dose rifapentine

We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure.     

B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia

Mice bearing a v-Myc myelocytomatosis viral oncogene homolog (c-Myc) transgene controlled by an Ig-alpha heavy-chain enhancer (iMyc(Cα) mice) rarely develop lymphomas but instead have increased rates of memory B-cell turnover and impaired antibody responses to antigen. We found that male progeny of iMyc(Cα) mice mated with mice transgenic (Tg) for CD257 (B-cell activating factor, BAFF) developed CD5(+) B-cell leukemia resembling human chronic lymphocytic leukemia (CLL), which also displays a male gender bias. Surprisingly, leukemic cells of Myc/Baff Tg mice expressed higher levels of c-Myc than did B cells of iMyc(Cα) mice. We found that CLL cells of many patients with progressive disease also expressed high amounts of c-MYC, particularly CLL cells whose survival depends on nurse-like cells (NLC), which express high-levels of BAFF. We find that BAFF could enhance CLL-cell expression of c-MYC via activation the canonical IκB kinase (IKK)/NF-κB pathway. Inhibition of the IKK/NF-κB pathway in mouse or human leukemia cells blocked the capacity of BAFF to induce c-MYC or promote leukemia-cell survival and significantly impaired disease progression in Myc/Baff Tg mice. This study reveals an important relationship between BAFF and c-MYC in CLL which may affect disease development and progression, and suggests that inhibitors of the canonical NF-κB pathway may be effective in treatment of patients with this disease.     

Utility of recent studies to assess the National Research Council 2001 estimates of cancer risk from ingested arsenic

OBJECTIVE: The purpose of this review is to evaluate the impact of recent epidemiologic literature on the National Research Council (NRC) assessment of the lung and bladder cancer risks from ingesting low concentrations (< 100 μg/L) of arsenic-contaminated water. DATA SOURCES, EXTRACTION, AND SYNTHESIS: PubMed was searched for epidemiologic studies pertinent to the lung and bladder cancer risk estimates from low-dose arsenic exposure. Articles published from 2001, the date of the NRC assessment, through September 2010 were included. Fourteen epidemiologic studies on lung and bladder cancer risk were identified as potentially useful for the analysis. CONCLUSIONS: Recent epidemiologic studies that have investigated the risk of lung and bladder cancer from low arsenic exposure are limited in their ability to detect the NRC estimates of excess risk because of sample size and less than lifetime exposure. Although the ecologic nature of the Taiwanese studies on which the NRC estimates are based present certain limitations, the data from these studies have particular strengths in that they describe lung and bladder cancer risks resulting from lifetime exposure in a large population and remain the best data on which to conduct quantitative risk assessment. Continued follow-up of a population in northeastern Taiwan, however, offers the best opportunity to improve the cancer risk assessment for arsenic in drinking water. Future studies of arsenic < 100 μg/L in drinking water and lung and bladder cancer should consider adequacy of the sample size, the synergistic relationship of arsenic and smoking, duration of arsenic exposure, age when exposure began and ended, and histologic subtype.