Search

Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. The impact of MO on fetal myocardium development has received little attention. Fibrogenesis is regulated by the transforming growth factor-[beta] (TGF-[beta])/p38 signaling pathway. Using the well-established model of MO in pregnant sheep, we evaluated the effect of MO on TGF-[beta]/p38 and collagen accumulation in fetal myocardium. Nonpregnant ewes were assigned to a control diet [Con, fed 100% of National Research Council (NRC) nutrient recommendations] or obesogenic diet (OB, fed 150% of NRC recommendations) from 60 days before conception. Fetal ventricular muscle was sampled at 75 and 135 days of gestation (dG). At 75 dG, the expression of precursor TGF-[beta] was 39.9 [+ or -] 9.9% higher (P < 0.05) in OB than Confetal myocardium, consistent with the higher content of phosphorylated Smad3 in OB myocardium. The phosphorylation of p38 tended to be higher in OB myocardium (P = 0.08). In addition, enhanced Smad complexes were bound to Smad-binding elements in 75 dG OB fetal myocardium measured by DNA mobility shift assay (130.2 [+ or -] 26.0% higher, P < 0.05). Similar elevation of TGF-[beta] signaling was observed in OB fetal myocardium at 135 dG. Total collagen concentration in OB was greater than Con fetal myocardium (2.42 [+ or -] 0.16 vs. 1.87 [+ or -] 0.04%, P < 0.05). Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 were higher in the Con group compared with OB sheep (43.86 [+ or -] 16.01 and 37.23 [+ or -] 7.97% respectively, P < 0.05). In summary, MO results in greater fetal heart connective tissue accumulation associated with an upregulated TGF-[beta]/p38 signaling pathway at late gestation; such changes would be expected to negatively impact offspring heart function. collagen; fibrogenesis; transforming growth factor-[beta]; maternal obesity; fetus; myocardium doi: 10.1152/ajpendo.00434.2010.

Maternal obesity (MO) is increasing at an alarming rate. The objective of this study was to evaluate the effect of MO on fibrogenesis in fetal skeletal muscle during maturation in late gestation. Nonpregnant ewes were assigned to a control diet (Con; fed 100% of NRC nutrient recommendations, n = 6) or obesogenic diet (OB; fed 150% of NRC recommendations, n = 6) from 60 days before conception, and fetal semitendenosus (St) muscle was sampled at 135 days of gestation (term 148 days). Total concentration and area of collagen in cross-sections of muscle increased by 27.0 [+ or -] 6.0 (P < 0.05) and 105.1 [+ or -] 5.9% (P = 0.05) in OB compared with Con fetuses. The expression of precursor TGF-[beta] was 177.3 [+ or -] 47.6% higher, and concentration of phospho-p38 74.7 [+ or -] 23.6% was higher (P < 0.05) in OB than in CON fetal muscle. Increases of 327.9 [+ or -] 168.0 (P < 0.05) and 188.9 [+ or -] 82.1% (P < 0.05), respectively, were observed for mRNA expression of Smad7 and fibronectin in OB compared with Con muscles. In addition, enzymes involved in collagen synthesis, including lysyl oxidase, lysyl hydroxylase 2b, and prolyl 4-hydroxylase-[alpha]1, were increased by 350.2 [+ or -] 90.0 (P < 0.05), 236.5 [+ or -] 25.2 (P < 0.05), and 82.0 [+ or -] 36.2% (P = 0.05), respectively, in OB muscle. In conclusion, MO-enhanced fibrogenesis in fetal muscle in late gestation was associated with upregulation of the TGF-[beta]/p38 signaling pathway. Enhanced fibrogenesis at such an early stage of development is expected to negatively affect the properties of offspring muscle because muscle fibrosis is a hallmark of aging. collagen; maternal obesity; fetus doi: 10.1152/ajpendo.00015.2010.

The Unexpected President: The Life and Times of Chester A. Arthur. By Scott S. Greenberger. (New York, NY: Da Capo Press, 2017. Pp. x, 304. S28.00.) Civil service reform does [...]

Collagen accumulates disproportionately in cardiac remodeling induced by hypertension and associated with advancing age. Spironolactone (Spiro), an aldosterone antagonist, attenuates the accumulation of collagen induced by hypertension. It was hypothesized that Spiro would attenuate the age-associated increase in percent collagen in the heart. Female Fisher 344 rats at 3 months (Y), 12 months (M), and 21 months (O) of age were treated with Spiro (30 mg/kg/d) or vehicle (Veh) for 2 months, yielding six groups: Y-Veh, Y-Spiro, M-Veh, M-Spiro, O-Veh, and O-Spiro. Hearts were harvested for immunoblotting, RNA blotting, and biochemical analysis. Percent collagen in the left ventricle and septum was greatest in the oldest rats. Spiro did not significantly attenuate the age-associated increase in collagen fraction or the age-associated increases in expression of atrial natriuretic factor and [beta]-myosin heavy chain messenger RNA. Chronic aldosterone antagonism does not attenuate the age-associated increase in collagen fraction in the female Fisher 344 rat heart.

Objective: This study examined the effect of motivation for change, measured by the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), on alcohol use severity among alcoholic patients with severe and persistent mental illness. Method: At a Veterans Affairs hospital, 390 dually diagnosed patients were recruited and assessed for motivation for change, alcohol use severity, psychotic symptoms and global functioning at baseline and 9-month follow-up. Results: Regression analyses showed that patients who were highly ambivalent about their alcohol use at baseline consumed significantly more alcohol 9 months later, on the basis of Addiction Severity Index ratings (p ≤ .01), than patients who felt less ambivalent. Conclusions: The findings suggest that increased awareness of alcohol-related problems is essential to reducing alcohol use severity for alcoholic patients with severe and persistent mental illness. The implications and limitations of the findings are discussed., SUBSTANCE USE DISORDERS are prevalent among patients with severe and persistent mental illness. The Epidemiologic Catchment Area (ECA) study reports that 47% of patients with a lifetime diagnosis of schizophrenia [...]

To date, no study has assessed the degree of similarity between left ventricular (LV) reverse remodeling and atrophic remodeling. Stable LV hypertrophy was induced by creation of an arteriovenous fistula (AVF) in Lewis rats (32 days). LV unloading was induced by heterotopic transplantation of normal (NL-HT) and/or hypertrophic (AVF-HT) hearts (7 days). We compared indexes of remodeling in AVF, NL-HT, and AVF-HT groups with those of normal controls. LV unloading induced decreases in cardiomyocyte size in NL-HT and AVF-HT hearts. NL-HT and AVF-HT LV were both characterized by relative increases in collagen concentration that were largely a reflection of decreases in myocyte volume. NL-HT and AVF-HT LV were associated with similar increases in matrix metalloproteinase (MMP-2 and -9) zymographic activity, without change in the abundance of the tissue inhibitors of the MMPs. In contrast, AVF-HT, but not NL-HT, was associated with a dramatic increase in collagen cross-linking. Our findings suggest an overall similarity in the response of the normal and hypertrophic LV to surgical unloading. However, the dramatic increase in collagen cross-linking after just 1 wk of unloading suggests a potential difference in the dynamics of collagen metabolism between the two models. Further studies will be required to determine the precise molecular mechanisms responsible for these differences in extracellular matrix regulation. However, with respect to these and related issues, heterotopic transplantation of hypertrophied hearts will be a useful small animal model for defining mechanisms of myocyte-matrix interactions during decreased loading conditions. myocardial atrophy; reverse remodeling; extracellular matrix; volume overload

Completed suicides over a one year period of time were reported from a nationwide survey of Department of Veteran Affairs medical centers. Of a total of 248 completed suicides, 11 occurred in outpatient substance abuse programs, and an additional 5 occurred among patients receiving combined outpatient substance abuse and psychiatric treatment. There were no inpatient suicides. During this time, there were 7 suicide attempts on inpatient units and 37 suicide attempts in outpatient chemical dependency treatment. The majority of suicides were committed by males who had a primary alcohol addiction (63%). Thirty-eight percent of the sample had a comorbid mood disorder and 38% had a comorbid personality disorder. Risk factors relating to the potential for suicide in chemical dependency programs are discussed. Keywords: Suicide; Chemical dependency treatment; Assessing suicide risk; Suicide in treatment programs; Suicide attempts

This is the first study to test concurrently the effectiveness of four treatment programs for patients with serious mental illness. Three-year outcome data on utilization and functioning demonstrated important positive changes for seriously mentally ill veterans enrolled in specialized, enhanced inpatient and community case management treatment programs, when compared to patients in an enhanced day treatment program or traditional standard care.

Posttraumatic stress disorder (PTSD) patients with histories of cocaine and alcohol abuse (CA-PTSD) were compared with normal volunteers. Positron emission tomography (PET) scans with (super 15)O-butanol were used to compare regional cerebral blood flow (rCBF) between the groups during rest and during an auditory continuous performance task (ACPT). CA-PTSD patients had significantly higher rCBF in right amygdala and left parahippocampal gyrus than normals during the ACPT. Normals had higher rCBF at frontal cortex during the resting scan and during the ACPT. The role of the amygdala in attention and fear conditioning suggests that increased amygdala rCBF may be related to clinical features of PTSD. Cocaine use may be associated with increased amygdala rCBF in PTSD patients. Amygdala and frontal cortex attention system components may be reciprocally related and their relative contributions to processing of neutral stimuli perturbed in CA-PTSD.

NEO Personality Inventory (NEO-PI) data from male substance abusers undergoing treatment were analyzed to elucidate the relationship of neo-pi performance to coping mechanisms, patterns of abuse, and triggers for use. The results were then compared to the scores on measures of psychopathology that evaluate characteristics related to those incorporated in the NEO-PI. Extroversion, agreebleness and conscientiousness were found to be related to the greater confidence in the capability to avoid usage, while neuroticism was more related to the absence of confidence in self-control.

Numerous proteins bend DNA upon binding, a phenomenon of potential significance for regulation of gene expression and chromatin. DNA bending is commonly predicted from the presence of electrophoretic mobility anomalies in protein-DNA complexes. However, as compared with electrophoretic methods, several DNA binding oncoprotein families do not display comparable evidence of DNA bends in x-ray structural studies. Herein, circularization kinetics and affinity measurements with prebent DNA templates were employed to assess bending and DNA structural preferences for Max and other basic helix-loop-helix/leucine zipper proteins. In this way, proteins in the Myc/Max basic helix-loop-helix/leucine zipper family were found not to bend DNA in solution but to actually stabilize DNA in an unbent configuration that resists circularization. The mobility anomaly was found to be induced by the leucine zipper protein motif, rather than structural distortions of DNA. Thus rigid protein domain structures may induce anomalous electrophoretic mobility. Moreover, the energetic preference of non-DNA bending proteins for unbent templates suggests mechanisms whereby chromatin structure may regulate transcription.

Examination of the hostile and aggressive attitudes using the NEO Personality Inventory Hostility Scale of 3,367 substance abusers undergoing treatment revealed that multiple substance abusers scored substantially high on all the measures with frequent inclinations for escape avoidance, distancing and confrontational coping styles. Highly hostile and aggressive patients experienced more episodes that triggered substance use and reported lower confidence in resisting use during adverse situations.

A tripartite model enables the grouping of depression symptoms to three types, namely, the indications of somatic tension and arousal that are specific to anxiety, nonspecific symptoms of general stress and symptoms of anhedonia and low Positive Affect unique to depression. The results from this model are consistent with the MASQ Anxious Arousal and Anhedonic Depression scales. Thus, an understanding of the several symptoms enables a comprehension of the depression phenomena.

A study of a tripartite model of depression and anxiety by separate factor analysis of three students, one adult and a patient revealed symptom structures to be similar for diverse groups of people. The three symptom groups proposed by the model are non-specific general distress, somatic arousal related to anxiety and symptoms of anhedonia pertaining to depression.

VERITATIS SPLENDOR has elicited a broad range of reactions, both favorable and unfavorable. In this article, I shall first review comments on, responses to, and studies of the papal letter, [...]

Experiments on the rat left ventricular free wall reveal that extracellular matrix (ECM) response and constituent collagen changes are essential components of post-myocardial infarction (MI) myocardium. The left ventricular wall scar exhibits elevated collagen and hydroxylsylpyridinoline (HP) levels after MI. THe HP concentration indicates that covalent cross-linking of collagen fibrils varies regionally in the ECM.

A diet deficient in copper results in altered connective tissue metabolism responsible for lesions in cardiovascular and other organ systems, and affects the structural and functional features of collagen and elastin by causing abnormal collagen and elastin cross-linking. Extensive restructuring of collagen fraction of cardiac interstitium occurs due to Cu deficiency. Cardiac hypertrophy arises due to impaired left ventricular collagen cross-linking, resulting in enhanced compliance of the ventricular wall.

The 'Ordinance' of 1784 is examined as a form of legislation in order to determine how the Confederation Congress defined the scope of its authority and how it chose to frame its decisions. It is contended that the 'Ordinance' of 1784 is not an ordinance because it does not fulfill the requirements of an ordinance based on the rules adopted by Congress on May 4, 178l. This lack of adherence to the legislative rules implies that Congress did not sanction the plan prepared by the Jefferson committee as an ordinance.

On August 12, 1996, the late Cardinal Joseph Bernardin announced what is now known as the Common Ground Initiative. There were many initial responses, both critical and supportive. Bernardin reflected [...]