Neuronal circuit regulation of the hypothalamo-pituitary-adrenocortical stress axis

The hypothalamo-pituitary-adrenocortical (HPA) axis is the primary modulator of the adrenal glucocorticoid stress response. Activation of this axis occurs by way of a discrete set of neurons in the hypothalamic paraventricular nucleus (PVN). The PVN neuron appears to be affected by multiple sources, including (1) brainstem aminergic/peptidergic afferents; (2) blood-borne information; (3) indirect input from limbic system-associated regions, including the prefrontal cortex, hippocampus, and amygdala; and (4) local-circuit interactions with the preoptic-hypothalamic continuum. Analysis of the literature suggests that different classes of stressor employ different stress circuits. Severe physiologic ("systemic") stress appears to trigger brainstem/circumventricular organ systems that project directly to the paraventricular nucleus. In contrast, stressors requiring interpretation with respect to previous experience ("processive" stressors) reach the PVN by way of multisynaptic limbic pathways. Limbic regions mediating processive stress responses appear to have bisynaptic connections with the PVN, forming intervening connections with preoptic/hypothalamic GABAergic neurons. Stressors of the latter category may thus require interaction with homeostatic information prior to promoting an HPA response. The HPA stress response thus appears to be a product of both the physiologic importance of the stimulus and the specific pathways a given stimulus excites.     

Diameter of the mammalian porin channel in open and "closed" states: direct measurement at the single channel level in planar lipid bilayer

Porin isolated from bovine skeletal muscle was reconstitute in planar lipid bilayers under voltage clamp conditions. A set of non-electrolytes were used as molecular probes for determining the pore diameter. The maximal diameter of the open channel was estimated to be 3.02 +/- 0.26 nm. As observed for other porin channels, a large transmembrane potential drove the channel into a "closed" state. The channel transition to the low conductance (closed) state was followed by a decrease in the maximal diameter of the channel to 2.4 +/- 0.08 nm.     

L-2-Hydroxyglutaric aciduria: neuropathological correlations and first report of severe neurodegenerative disease and neonatal death

Chromolaena odorata (formerly Eupatorium odoratum) is used as a traditional medicine in Vietnam (Nghiem, 1992), where its Vietnamese common name is "co hoi." While it has been widely considered a weed by agriculturalists (Holm et al., 1991), the aqueous extract and the decoction from the leaves of this plant have been used throughout Vietnam for the treatment of soft tissue wounds, burn wounds, and skin infections. A number of clinical studies done by Vietnamese as well as foreign medical workers has demonstrated the efficacy of this extract on the wound-healing process. In this article, the effect of the Eupolin extract on hydrated collagen lattice contraction by human dermal fibroblasts, an in vitro model of wound contraction, is described. The significant inhibition of collagen gel contraction by Eupolin extract at 50 to 200 micrograms/ml is demonstrated in various concentrations of collagen. When the extract at 50 to 150 micrograms/ml was washed out of the lattices and replaced by fresh medium without Eupolin, the contraction of collagen by cells was resumed. The visualization of cells in the lattices by incubation in a tetrazolium salt for 2 h showed live cells at 50 to 150 micrograms/ml of extract. In contrast, all cells were killed in the higher extract doses of 300 or 400 micrograms/ml. These preliminary results showing the inhibitory effect of Eupolin extract on collagen contraction suggest that a clinical evaluation of its effect on wound contraction and scar quality should be made. This work illustrates that traditional remedies that are used by folk practitioners to improve healing can be examined in a scientific manner using in vitro wound-healing models. It could be that the synergistic properties of components of the natural extract contribute to the positive effects demonstrated on various wound-healing mechanisms.     

Order writing for parenteral nutrition by registered dietitians

OBJECTIVES: The purpose of the study was to describe the involvement of registered dietitians in parenteral nutrition (PN) orders, to identify characteristics of those who write orders; and to rank education, training, and support elements that dietitians believe facilitate PN order-writing skills. DESIGN: Mail survey method. SUBJECTS: Usable returned questionnaires (n = 266) represented randomly sampled membership of the Dietitians in Nutrition Support (a dietetic practice group of The American Dietetic Association) and registered dietitian membership of the American Society of Parenteral and Enteral Nutrition. STATISTICAL ANALYSIS: Data were analyzed using basic frequency displays on all questionnaire items, Pearson correlations between the quantitative variables, and one-way analysis of variance with each of the categorical variables and the quantitative variables. Detail exploration among variables was done by chi(2) analyses and two-tailed t tests. RESULTS: "Recommend" was the most frequent response to a query about participation in PN orders. An average of 37% of respondents sometimes or always wrote orders for nutrients. Specialists were more likely to write orders than clinicians and managers. No relationship was found between those who wrote orders and educational level, and writers had been registered for a shorter length of time. Agreement on the training and support needed for order-writing skills was nearly unanimous. APPLICATIONS: The PN skills of respondents who were specialists distinguished them from managers and clinicians. Specialists did not fit criteria for advanced practice, and specialty practice in metabolic nutrition care may be too broad to define their practice. Educators must recognize the importance of including PN training in didactic and clinical training programs. Registered dietitians with PN skills will be well positioned to play an active role in the evolving health care system.     

Uterine allergy: a cause of preterm birth?

OBJECTIVE: To identify the origin of eosinophils in cases of eosinophil-associated preterm delivery. METHODS: From an established set of 465 consecutive non-anomalous singleton infants delivered at 22-32 weeks' gestation, we retrieved 161 cases of preterm delivery following spontaneous onset of preterm labor, 78 cases with maternal preeclampsia, 33 cases of abruption, and 193 cases of premature rupture of membranes (PROM). Charts were reviewed, and the placenta, umbilical cord, and membranes were examined histologically. In cases with extravascular eosinophils showing evident gradient toward the amniotic cavity, the origin of the eosinophils (fetal or maternal) was determined by the proximity to fetal or maternal vessels. RESULTS: Histologic evidence of an eosinophilic gradient toward the amniotic cavity was present only in the fetal (including umbilical cord and chorion) compartments. This eosinophilic gradient was present in 19% (90 of 465) of preterm delivery cases and was significantly more common in cases of PROM (54 of 193, 28%) and preterm labor (34 of 161, 21%) than abruption (two of 33, 6%) and preeclampsia (none of 78) (P < .001). In 84 of 90 cases (93%), the eosinophilic gradient was present along with multiple histologic indicators of acute intrauterine inflammation. CONCLUSION: An eosinophilic gradient toward the amniotic cavity, present in nearly a fifth of cases of preterm delivery, is probably of fetal origin, making it unlikely that a maternal "allergy-like" mechanism is a cause of preterm delivery.     

Signalling by TGF-beta family members: short-range effects of Xnr-2 and BMP-4 contrast with the long-range effects of activin

BACKGROUND: One way of establishing a morphogen gradient in a developing embryo involves the localized synthesis of an inducing molecule followed by its diffusion into surrounding tissues. The morphogen-like effects of the mesoderm-inducing factor activin provide support for this idea in amphibian development. The questions remain, however, of how activin exerts its long-range effects, and whether long-range signalling is a property of all transforming growth factor beta (TGF-beta) family members. RESULTS: We compare the signalling ranges of activin and two other TGF-beta family members, Xnr-2 and BMP-4. Unlike activin, Xnr-2 and BMP-4 act over short distances. Furthermore, the effects of constitutively active activin receptors are strictly cell-autonomous. These observations suggest that the long-range effects of activin occur through protein diffusion and that "relay' mechanisms are not initiated by any of these TGF-beta family members. Mechanisms limiting the signalling range of Xnr-2 were addressed by studying Xnr-2 processing and secretion. An activin-Xnr-2 fusion protein signals over many cell diameters, suggesting that regulated processing or secretion is one limiting factor. Disaggregation and reaggregation of Xnr-2-producing tissues also extends the range of Xnr-2, suggesting that components of intact tissue restrict spread of the protein. CONCLUSIONS: The long-range effects of activin are likely to occur through the diffusion of activin protein. The short-range effects of Xnr-2 and BMP-4 emphasize that long-range diffusion is not a general property of TGF-beta-related molecules. Finally, signalling ranges may be regulated by constraints on processing or secretion and by interactions with extracellular components of embryonic tissues.     

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part IV

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part IV of this six-part series focuses on morphologic correlates of coronary angiographic patterns of remodeling after balloon angioplasty and discusses effects of angioplasty on adjacent, nondilated vessels.     

Unenhanced helical CT of ureterolithiasis: value of the tissue rim sign

OBJECTIVE: The tissue rim sign-a rim or halo of soft-tissue attenuation seen around the circumference of an intraureteral calculus on unenhanced axial CT-has been described as useful in differentiating ureteral calculi from extraurinary abdominal or pelvic calcifications. The purpose of this study was to determine the prevalence of the tissue rim sign in patients with ureterolithiasis and extraurinary calcifications and to determine the relationship between the tissue rim sign, the size of a calculus, and the degree of urinary obstruction. MATERIALS AND METHODS: Unenhanced helical CT studies followed by excretory urography were obtained in 59 patients with suspected acute ureterolithiasis. Each calcification along the expected course of the ureter seen on axial CT scans was categorized as a ureteral calculus or as an extraurinary calcification. Each categorization was based on CT, urographic, and clinical findings and the presence or absence of a tissue rim sign. When the outer wall of the ureter could not be seen because there was no clear fat plane at the level of the calcification on CT, the sign was categorized as "indeterminate." The size of the calculus was measured on CT, and the degree of urinary obstruction was estimated on the basis of the urograms. RESULTS: Thirty-two patients each had a single ureteral calculus. Of these patients, CT revealed a positive tissue rim sign in 16 patients (50%), was negative in five patients (16%), and was indeterminate in 11 patients (34%). In addition, we saw 57 extraurinary calcifications in 18 patients (11 patients with ureteral calculi and seven patients without ureteral calculi). None of the 57 extraurinary calcifications was associated with a positive tissue rim sign. The tissue rim sign was negative in 39 (68%) of the 57 extraurinary calcifications and indeterminate in the remaining 18 (32%). Ureteral calculi with a negative tissue rim sign were larger than ureteral calculi with a positive tissue rim sign (p < .01). A high degree of obstruction was present in four of five patients with ureteral calculi for which CT showed a negative tissue rim sign. Conversely, six of 16 patients in whom CT revealed a positive tissue rim sign also had a high degree of obstruction. Therefore, no clear relationship was found between the degree of obstruction and the presence of a positive tissue rim sign. CONCLUSION: A positive tissue rim sign is specific for the diagnosis of ureterolithiasis. However, a negative tissue rim sign does not preclude such a diagnosis. The presence or absence of this tissue rim sign correlates with the size of a calculus but not with the degree of urinary obstruction. When CT reveals an indeterminate tissue rim sign, careful inspection for other CT findings, such as ipsilateral ureteral dilatation, perinephric edema, dilatation of the intrarenal collecting system, and renal swelling, is necessary.     

High-yield expression, purification, and characterization of active, soluble Bacteroides fragilis metallo-beta-lactamase, CcrA

Two new areas of anchor development are biodegradable anchors and "mini" anchors. The group of biodegradable anchors tested include the Bio-Anchor, LactoSorb, Biofix, Bio-Statak, Mini Screw suture anchor, DePuy 4.5 molded, DePuy 4.5 machined, DePuy 3.5 machined, TAG Wedge 4, TAG Rod 2, TAG Wedge 3, TAG Wedge 2, and Stealth. "Mini anchors" have drill holes or minor diameters of < 2.2 mm. Those tested include the Mini Revo and Bio-Anchor, miniHarpoon, mini Mitek and Fast in 3, Statak 1.5 and 2.5, SB 2 and PeBA 3, Corkscrew 5, Corkscrew 3.5, and Fastak A2, Ogden 2.5, TAG Wedge 2, ROC 1.9, and Questus 2.5. Additional anchors tested that fit neither category include the Anspach, Questus 3.5 and 5.0, SB 3 and PeBA-C, Ogden 3.5, Fast in 4, Ultrafix, and the ROC 3.5, ROC 2.8, ROC 2.3, and ROC XS. An anchor comparison, using an established protocol in fresh porcine femurs, recorded failure strength, failure mode, eyelet size, minor and major diameters, and drill hole sizes. Except for the Bio-Anchor and TAG Wedge 2, biodegradable anchors tend to be larger to compensate for their lower strength relative to metal. Biodegradable screw anchors' predominant failure mode was eyelet cutout, whereas biodegradable nonscrew anchors failed to predominantly by anchor pullout. From an initial mechanical perspective, these biodegradable anchors perform acceptably. Both biodegradable and "mini" anchors include screw and nonscrew designs. As expected, screw designs perform well and generally fail at higher loads than nonscrew anchors. Although biodegradable anchors, as a group, are not as strong as metal anchors, they are stronger than the sutures for which they are designed. The move to smaller ("mini") and biodegradable anchors is supported by these data. Whether an anchor fails at twice the suture breaking strength or 10 times the suture breaking strength should make no difference.