Differential effects of sera from normotensive and hypertensive pregnant women on Ca(2+) metabolism in normal vasular smooth muscle cells

The clinical features of preeclampsia have been traditionally ascribed to a generalized vascular endothelial cell dysfunction. The present study investigates the effect of sera from preeclamptic women and normal pregnancy on the metabolism of intracellular Ca(2+) concentration ([Ca(2+)](i)) in normal cultured vascular smooth muscle cells (VSMC). Sera were obtained from normotensive pregnant women (NTP) (n = 17), preeclamptic women (PE) (n = 15), pregnant women with chronic (essential) hypertension (pregnant EHT) (n = 8), non-pregnant women with essential hypertension (non-pregnant EHT) (n = 12), and age-matched non-pregnant normotensive women (NNP) (n = 18). Serum (10%) was applied to both primary cultures of rat aortic smooth muscle cells and to the A-10 vascular muscle cell line. Levels of [Ca(2+)](i) were determined fluorometrically. After a 4-h incubation with serum, basal [Ca(2+)](i) was not significantly altered. However, compared with normal pregnant sera, PE sera markedly reduced hormonally induced Ca(2+) transients. Thus, following acute stimulation of rat VSMC (primary cultures) with 10(-8)M angiotensin II, peak [Ca(2+)](i) responses (% increment over baseline) were 443 +/- 22, 184 +/- 18, 259 +/- 12, 274 +/- 23, and 255 +/- 15% in NTP, PE, pregnant EHT, non-pregnant EHT, and NNP, respectively (P <0.01 PE versus NTP, P <0.05 PE versus NNP and pregnant and non-pregnant EHT). These effects of sera on [Ca(2+)](i) were qualitatively reproduced in platelets obtained from healthy volunteers. Also, depolarization-activated Ca(2+) influx in VSMC was affected by the different sera groups in a manner similar to that seen with hormonally induced [Ca(2+)](i) responses. The altered [Ca(2+)](i) changes by PE sera disappeared 5 wk after delivery. The effect of the different sera groups on hormonally triggered Ca(2+) transients in normal VSMC, as well as the normalization of [Ca(2+)](i) responses after delivery, suggest the presence of a circulating serum factor in PE. Inasmuch as [Ca(2+)](i) is the major determinant of VSMC tone, it is possible that consequent to the attenuation of [Ca(2+)](i) responses, this putative circulating factor counterbalances the intense vasoconstriction in PE.     

Chronic daily ethanol and withdrawal: 2. Behavioral changes during prolonged abstinence

BACKGROUND: Our previous investigations have suggested that alcohol abuse may induce persistently compromised hypothalamo-pituitary-adrenal (HPA) function, which could increase risk for subsequent alcohol abuse. The apparent similarity of chronic alcohol abuse-induced HPA defects to the compromised HPA functions associated with posttraumatic stress disorder and atypical depression also suggest potential common mechanisms shared with varied neurobehavioral disorders. Accordingly, we have investigated persistent behavioral effects of previous repetitive daily ethanol consumption and withdrawal. METHODS: Male Sprague-Dawley rats received either daily ad libitum chow, ad libitum liquid diet containing ethanol, or pair-fed isocaloric control liquid diet. The ethanol was gradually introduced over 4 weeks, maintained at 5% w/v for four subsequent weeks, and then gradually removed over 1 week. RESULTS: Four weeks after removal of ethanol from the diet, the previously ethanol-consuming rats exhibited greater (p < 0.05) evidence of anxiety in the elevated plus-maze test and in the novel cork-gnawing test, as well as greater (p < 0.05) locomotor response to a novel environment, compared with controls. CONCLUSIONS: These results suggest that repetitive daily alcohol consumption and withdrawal can induce not only persistent defects in HPA function, but also persistent increases in anxiety and behavioral responsiveness to novelty, all consistent with characteristics of abstinent alcoholics as well as with rats that self-administer increased amounts of alcohol and other drugs of abuse. This suggests that alcohol abuse can induce persistent common or interacting changes in neuroendocrine and behavioral responses that may increase risk for subsequent abuse.     

Therapeutic effects of environmental enrichment on cognitive function and tissue integrity following severe traumatic brain injury in rats

Postinjury environmental enrichment (EE) has been shown to alter functional and anatomical outcomes in a number of injury paradigms, including traumatic brain injury (TBI). The question of whether EE alters functional outcome following TBI in a model which produces overt histopathological consequences has not been addressed. We investigated this question using the severe, parasagittal fluid percussion injury (FPI) model. Rats (n = 7 per group, enriched and standard for behavior; n = 15 per group for histology) underwent severe (2.2-2.6 atm) FPI, with sham-operated rats (n = 7 per group, enriched and standard for behavior; n = 6 enriched, n = 3 standard for histology) serving as controls. Animals were allowed to recover for 11 days either in standard single housing or together (injured and sham) in an enriched environment consisting of a 92 x 61 x 77-cm ferret cage filled with various stimulatory objects. Consistent with earlier reports, injured animals recovering in the enriched environment showed significantly (P < 0.05) shorter latencies to find the platform in a Morris Water Maze task versus injured/standard animals on day 12 post-TBI. However, both injured groups showed significant deficits versus sham groups (P < 0.05). There were no differences between the sham/enriched and sham/standard groups. No significant group differences in swim speed were observed. At 14 days post-TBI, enriched animals had approximately twofold smaller lesion areas in regions of the cerebral cortex posterior to the injury epicenter (-4.5, -5.8, -6.8 mm relative to bregma; P < 0.05) compared to injured/standard animals. In addition, overall lesion volume for the entire injured cortical hemisphere was significantly smaller in animals recovering in the enriched environment. These results indicate that noninvasive environmental stimulation is beneficial in attenuating cognitive deficits and preserving tissue integrity in a TBI model which causes cerebral contusion and cell death.     

Working in a flawed mental health care system: an ethical challenge

OBJECTIVE: Psychiatrists are under immense ethical pressure when practicing in circumstances that reasonable, informed colleagues would regard as not "good enough" in that they do not adequately meet the needs of patients and patients' families. This article is an examination of the ethical quandaries that ensue and options for response. METHOD: The authors explore the ways in which mental health systems may become flawed and compare philosophical arguments that deal with the predicament of working in such systems. RESULTS: The principle of fidelity to the patient is compromised in flawed systems, thus threatening professional integrity. Arguments for efficiency or the greater good in the provision of mental health care fail as remedies since they both lead to harms for particular clinical groups, as well as downgrading of a psychiatrist's integrity. CONCLUSIONS: Psychiatrists should submit to the principle of fidelity in working with patients. Since flawed systems undermine fidelity, threatening the patient's interests, psychiatrists are morally responsible for working to improve such systems.     

Quality of life in treated and never-treated schizophrenic patients

OBJECTIVE: To evaluate quality of life (QOL) among treated and never-treated schizophrenic patients. METHOD: QOL ratings were obtained for (a) 112 Moroccan participants with schizophrenia who had never received neuroleptic medications, (b) matched samples of chronically-medicated schizophrenic patients in Morocco and the United States and (c) matched community controls in both countries. RESULTS: QOL ratings were generally higher for US groups, although Moroccan controls obtained higher ratings than US controls for some domains. QOL ratings were higher for controls compared to patients within each country, although US patients' scores were similar to controls on some dimensions. We found no differences between treated and untreated Moroccan patients for any QOL domain, although relationships among predictors were different. CONCLUSION: Within the context of Moroccan culture, benefits of medications alone are not evident in QOL scores. QOL appears to be a complex construct influenced by different factors within each of the groups studied.     

Behavioral, electrophysiological, and histopathological consequences of mild fluid-percussion injury in the rat

We investigated in rats the effect N(G)-nitro-L-arginine methyl ester (L-NAME) on retention of a passive avoidance response, and cortical ACh release monitored using the microdialysis technique. Post-training administration of L-NAME impaired 24 h retention of a passive avoidance and decreased cortical ACh release. Both effects of L-NAME were reversed by L-Arg. These results suggest that nitric oxide is involved in retention of the passive avoidance response through the modulation of the forebrain cholinergic system.     

Subscapularis tendon tear: primary and associated signs on MRI

PURPOSE: The purpose of this work was to investigate signs of subscapularis tendon tear on MRI. METHOD: Preoperative written interpretations of high field (n = 9) and low field (n = 7) MRI of 16 patients with tears confirmed at surgery or arthroscopy were reviewed, followed by retrospective review of these studies. RESULTS: A preoperative diagnosis of subscapularis tear was made in five (31%) cases. On retrospective review, primary signs of tear were present in 15 (94%) cases and in two-thirds were limited to the cranial third of the tendon. Supraspinatus tears were present in 69% of cases. Associated findings included medial dislocation (n = 4) or subluxation (n = 3) of biceps tendon, biceps tendinopathy (n = 2), superior labral tear (n = 5), and effusions of superior subscapularis recess (n = 6), subcoracoid bursa (n = 2), or both (n = 5). One or more associated signs were present in 94% of cases. CONCLUSION: Subscapularis tear is frequently missed on MRI. Recognizing that primary signs of tear may be limited to the cranial third of the subscapularis tendon and identifying associated signs should facilitate diagnosis.