Decreased interstitial glucose and transmural gradient in lactate during ischemia

Summary The purpose of this investigation was to assess the effects of ischemia and reperfusion on the transmural levels of glucose and lactate in the interstitium in 11 open-chest swine. Microdialysis probes were used to estimate changes in interstitial metabolities across the ventricular wall. Probes were placed in the subepicardium and the subendocardium of the left anterior descending (LAD) coronary artery perfusion bed and in the midmyocardium of the circumflex (CFX) perfusion bed. The LAD coronary artery was cannulated and perfused with blood from the femoral artery through an extracorporal perfusion circuit. Ischemia was induced in the LAD perfusion bed by reducing the flow of the LAD perfusion pump by 60% for 50 min, and was followed by 30 min of reperfusion. Regional myocardial blood flow was assessed with fluorescent microspheres. Ischemia resulted in a transmural gradient in blood flow, with the most severe reduction in flow occurring in the subendocardium (p<0.05). We found a significant reduction in interstitial glucose in both the LAD subepicardium (1.26±0.24 mM) (p=0.0009) and subendocardium (0.89±0.21 mM) (p=0.0001) during ischemia compared to the aerobic (non-ischemic) period (1.97±0.25 mM, 2.03±0.29 mM for the subepicardium and subendocardium, respectively). This coincided with a significant reduction in glucose delivery (LAD pump flow^* arterial glucose) to the LAD perfusion bed during ischemia (54.5±8.5 mol/min) compared to aerobic values (182.1±25.3 mol/min) (p<0.05). Interstitial lactate levels were significantly increased during ischemia in the LAD subendocardium (3.39±0.46 mM) compared to the aerobic values (1.73±0.46 mM) (p<0.0029). A transmural gradient in interstitial lactate levels was observed during ischemia: this gradient was not seen during the aerobic period and was negated upon reperfusion. In conclusion, ischemia resulted in a decrease in interstitial glucose in both the LAD subepicardium and subendocardium, and an increase in interstitial lactate in the LAD subendocardium. Further, a transmural gradient in interstitial lactate levels was observed during ischemia, with the highest lactate values appearing in the subendocardium.     

Induction of gene expression of amyloid precursor protein (APP) in activated human lymphoblastoid cells and lymphocytes

To understand the possible role of amyloid precursor protein (APP) in human lymphocytes, and the regulation of APP gene expression in this cell type, we determined levels of cellular APP protein and of mRNA in human T-cell-derived Jurkat cells that were treated with lectin, phorbol ester, and calcium ionophore. We also related these levels to cell aggregation and adhesion. Cell-cell aggregation and cell-plastic adhesion were observed over a 24-h period after incubating cells for 2 h with phytohemagglutinin or phorbol myristate acetate. Cells treated with a calcium ionophore showed no aggregation or adhesion. Western blots indicated no obvious alteration in the level of cellular APP with different treatments. Northern blots showed a significant transient increase of APP mRNA after incubation with the calcium ionophore, whereas phorbol ester treatment showed a slight increase of APP mRNA. We analyzed the level of APP mRNA in human peripheral T cells which had been separated from peripheral lymphocytes. The level increased transiently by up to threefold after treatment with calcium ionophore plus phorbol esters. These data suggest that cell-cell aggregation and cell-matrix adhesion by human lymphocytes are not associated with an increased level of cellular APP protein or of mRNA.     

Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin

Idiopathic crescentic glomerulonephritis is characterized by an absence of immunohistological evidence of immune deposits, often with evidence of segmental glomerular necrosis. Such pauciimmune crescentic glomerulonephritis is the most common renal manifestation seen in patients with Wegener's granulomatosis, polyarteritis nodosa, and glomerulonephritis associated with other systemic vasculitic disorders (i.e., Churg-Strauss syndrome). Recently, the idiopathic crescentic glomerulonephritides, either in renal-limited form or in association with other systemic vasculitic disorders, were found to have in common a serologic marker, antineutrophil cytoplasmic autoantibodies. These cytoplasmic and perinuclear antineutrophil cytoplasmic autoantibodies are specific for constituents of neutrophil primary granules and monocyte lysosomes. As serologic markers for vasculitic disorders, they are also felt to be directly involved in the pathogenesis of necrotizing vascular injury.In vitro, both perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies are capable of causing cytokineprimed neutrophils to undergo degranulation and respiratory burst, releasing toxic oxygen species and lytic enzymes. Antiidiotype antibodies which inhibit antineutrophil cytoplasmic autoantibodiesin vitro, in a V region-dependent manner, are found in pooled humanγ-globulin preparations. Intravenous immune globulin infusionsin vivo have produced dramatic improvements in the necrotizing vascular injury produced by antineutrophil cytoplasmic autoantibodies, and a rapid reduction in these autoantibody levels is seen post-intravenous immune globulin infusion in most patients. The proposed mechanisms of action of intravenous immune globulin in vasculitic disorders include Fc-dependent mechanisms, and F(ab′)₂-dependent mechanisms are likely important. Intravenous immune globulin infusions appear to have an important place in the management of the necrotizing vascular injury. Blinded, randomized, placebo-controlled trials will be necessary to establish definitively intravenous immune globulin as a therapeutic option in vasculitic disorders.     

High-voltage-activated calcium channel messenger RNA expression in the 140-3 neuroblastoma-glioma cell line

Expression of calcium channel alpha1 subunits in oocytes or cell lines has proven to be a powerful method in the analysis of structure-function relations, but these experimental systems are of limited value in the examination of neuron-specific functions such as transmitter release. Cell lines derived from neurons are often capable of these functions, but their intrinsic calcium channel alpha1 subunits are complicating factors in experimental design. We have examined the biophysical and molecular properties of calcium channels in a little studied neuroblastoma-glioma hybrid cell line, 140-3, a close relative of the NG108-15 cell line, to test whether this cell line might serve a role as an expression system for neural mechanisms. This cell was selected as it contains an intact transmitter release mechanism yet secretes little in response to depolarization. Patch-clamp recording revealed only a prominent low-threshold, rapidly inactivating calcium current with a single-channel conductance of approximately 7 pS that was identified as T type. A search for calcium channel alpha1 subunit messenger RNA in the 140-3 cells with three different tests only revealed alpha1C, whereas alpha1A-alpha1C were present in the parent NG108-15 line. We made a particular effort to search for alpha1E, since this subunit has been associated with a low-voltage-activated current. Our findings suggest that, since the principal nerve terminal-associated calcium channels (alpha1A, alpha1B, alpha1E) are absent in the 140-3 cell, this cell line may prove a particularly useful model for the analysis of the role of high-voltage-activated calcium channels in complex functions of neuronal cells.     

The use of delayed computerized tomography in the evaluation of blunt abdominal trauma: a preliminary report

This purpose of this study was to analyze the use of abdominal computed tomography (CT) imaging in patients with possible blunt abdominal trauma. A retrospective analysis of all trauma patients over a 1-year period (1993-1994) was conducted, with prospective study protocol in 52 patients using serial abdominal exam and hematocrits (Hcts) instead of abdominal CT for evaluation of blunt abdominal trauma. Urgent abdominal CT was used as the initial diagnostic test for evaluation of blunt abdominal trauma in 813 patients over this 1-year period. CT was obtained in 379 (46.6%) of these patients who arrived hemodynamically stable (admission systolic blood pressure > or = 90), had a Glasgow Coma Scale > 13, and had admission Hct > or = 35 because of distracting injuries, possible traumatic brain injury, or alcohol/drug use, which might render the abdominal physical exam unreliable. Only 47 CT scans (12.4%) were positive, and three patients (0.8%) required laparotomy. In an effort to more efficiently use abdominal CT, we performed a prospective study in 52 patients with possible blunt abdominal trauma, admission systolic blood pressure > or = 90, Hct > or = 35, Glasgow Coma Scale > 13, and a normal abdominal exam on admission. These patients were followed with serial abdominal examinations and Hcts every 6 hours for 24 hours, and delayed CT, when applicable. CT was obtained in seven patients (13.5%) for evaluation of fall in Hct or abnormal abdominal examination; all were negative for abdominal injury. A protocol using serial abdominal exams, Hcts, and delayed abdominal CT imaging may be useful in select patients to decrease the high number of negative routine abdominal CTs that are obtained in the evaluation of blunt abdominal trauma.     

Transcutaneous cranial electrical stimulation (TCES): a review 1998

The Transcutaneous Cranial Electrical Stimulation (TCES) technique appeared at the beginning of the 1960s and is aimed to act at the level of the central nervous system. The current, composed of high frequency pulses interrupted with a repetitive low frequency, is delivered through three electrodes (a negative electrode placed between the eyebrows while two positive electrodes are located in the retro-mastoid region). Due to the characteristics of the current delivered, shortcomings encountered with previous electrical stimulation techniques are avoided. The main property of TCES is to potentiate some drug effects, especially opiates and neuroleptics, during anesthetic clinical procedures. This potentiation effect permits drastic reduction of pharmacological anesthetic agent and reduces post-operative complications. Animal studies performed with TCES demonstrated that this stimulation releases 5-hydroxy-indol-acetic acid and enkephalins. Despite numerous clinical and animal studies performed with this technique for several decades, TCES mechanisms are not completely elucidated but results obtained without undesirable effect are encouraging signs to continue investigations of this particular technique.     

Fibrovascular ingrowth in porous ocular implants: the effect of material composition, porosity, growth factors, and coatings.

PURPOSE: Fibrovascular ingrowth into various porous ocular implants as a function of implant material composition, porosity, growth factors, and coatings was investigated in a pilot study in an animal model. METHODS: Eighty-one New Zealand white rabbits underwent unilateral enucleation and implantation with ocular implants composed of the following materials: coralline hydroxyapatite (HA) with 200-microm pores (HA200) or 500-microm pores (HA500), synthetic HA (synHA), and high-density porous polyethylene (PP). The HA200, HA500, and PP implants were implanted untreated or after treatment with recombinant human basic fibroblast growth factor (Rh-bFGF). Nine HA500 implants were implanted after coating with calcium sulfate (plaster of Paris) to provide a smooth outer surface. Implants were harvested at 1-, 2-, 4-, or 8-week intervals and were examined histologically. RESULTS: A significant difference was found between untreated HA500 and PP, with PP showing better ingrowth. There was no significant difference between untreated HA and PP, nor between untreated HA500 and synHA. Significant increases in ingrowth were found in HA200 compared with HA500, and in Rh-bFGF-treated implants compared with untreated controls. The calcium sulfate-coated implants showed less vascularization compared with the uncoated implants, although the difference was not significant. CONCLUSIONS: Fibrovascular ingrowth occurred earlier in HA200 implants than in HA500 implants, and was enhanced when implants were treated with Rh-bFGF.     

Activity-based anorexia: relationship to gender and activity-stress ulcers.

The phenomena of activity-based anorexia (ABA) and the activity-stress ulcer (ASU) both involve paradigms in which the food intake of rats is restricted and the animals are allowed voluntary exercise in a running wheel. This study determined the susceptibility of male and female rats to ABA and ASU following 25- and 30-percent losses of their original body weights. Male rats reached both weight loss criteria in a fewer number of days than did female rats. None of the male and female rats sacrificed at the 25% weight loss criterion evidenced gastric lesions; 52% of the animals sacrificed at the 30% weight loss criterion had one or more lesions. No gender differences with respect to gastric lesions were observed at the 30% weight loss criterion; however, at both weight loss criteria, females ate and ran more than males. It is concluded that ASUs are a consequence rather than a cause of ABA, and that there is a sexually "dimorphic" susceptibility to ABA but not ASUs. The utility of using a 25% weight loss criterion for defining ABA is also discussed.     

A video-based information system for patients

This paper describes a video-based information system (VISP) for general practice waiting areas, and considers its potential for broadening the range of information which might be made available to patients.     

Association of aggressive behavior with altered serotonergic function in patients who are not suicidal

OBJECTIVE: The purpose of this study was to determine whether aggression and serotonergic dysfunction are related in the absence of a history of suicidal behavior. Although serotonergic dysfunction has been implicated in aggressive and impulsive behavior, most studies of such behavior have included individuals with a history of suicide attempts. Low concentrations of CSF 5-hydroxyindoleacetic acid (5-HIAA) have been consistently associated with suicidal behavior, presenting a potential confound in the link between aggression and serotonergic dysfunction. METHOD: The authors examined the association between aggression and CSF 5-HIAA concentrations in a group of 64 patients who had different DSM-III-R axis I diagnoses and no past suicidal behavior. Aggressive (N=35) and nonaggressive (N=29) groups were defined by a median split on a six-item history of adulthood aggressive behavior. RESULTS: The aggressive group had significantly lower CSF 5-HIAA concentrations than the nonaggressive group. Aggressive individuals also scored significantly higher on self-report measures of hostility, impulsiveness, and sensation seeking. CSF 5-HIAA concentrations, however, did not correlate with self-reported hostility and impulsivity. CONCLUSIONS: There is an association between aggressive behavior and serotonergic dysfunction independent of suicidal behavior in patients with axis I disorders who exhibit relatively milder forms of aggressive behavior. Analogous to findings with suicidal behavior, a low concentration of CSF 5-HIAA is related to aggressive behavior but does not show the same relationship to the continuum of aggressive feelings and thoughts.